Showing papers in "Chinese Medical Journal in 2021"

Changing profiles of cancer burden worldwide and in China: a secondary analysis of the global cancer statistics 2020.

Abstract: Background Cancer is one of the leading causes of death globally, but its burden is not uniform. GLOBOCAN 2020 has newly updated the estimates of cancer burden. This study summarizes the most recent changing profiles of cancer burden worldwide and in China and compares the cancer data of China with those of other regions. Methods We conducted a descriptive secondary analysis of the GLOBOCAN 2020 data. To depict the changing global profile of the leading cancer types in 2020 compared with 2018, we extracted the numbers of cases and deaths in 2018 from GLOBOCAN 2018. We also obtained cancer incidence and mortality from the 2015 National Cancer Registry Report in China when sorting the leading cancer types by new cases and deaths. For the leading cancer types according to sex in China, we summarized the estimated numbers of incidence and mortality, and calculated China's percentage of the global new cases and deaths. Results Breast cancer displaced lung cancer to become the most leading diagnosed cancer worldwide in 2020. Lung, liver, stomach, breast, and colon cancers were the top five leading causes of cancer-related death, among which liver cancer changed from the third-highest cancer mortality in 2018 to the second-highest in 2020. China accounted for 24% of newly diagnosed cases and 30% of the cancer-related deaths worldwide in 2020. Among the 185 countries included in the database, China's age-standardized incidence rate (204.8 per 100,000) ranked 65th and the age-standardized mortality rate (129.4 per 100,000) ranked 13th. The two rates were above the global average. Lung cancer remained the most common cancer type and the leading cause of cancer death in China. However, breast cancer became the most frequent cancer type among women if the incidence was stratified by sex. Incidences of colorectal cancer and breast cancer increased rapidly. The leading causes of cancer death varied minimally in ranking from 2015 to 2020 in China. Gastrointestinal cancers, including stomach, colorectal, liver, and esophageal cancers, contributed to a massive burden of cancer for both sexes. Conclusions The burden of breast cancer is increasing globally. China is undergoing cancer transition with an increasing burden of lung cancer, gastrointestinal cancer, and breast cancers. The mortality rate of cancer in China is high. Comprehensive strategies are urgently needed to target China's changing profiles of the cancer burden.

MAFLD vs. NAFLD: shared features and potential changes in epidemiology, pathophysiology, diagnosis, and pharmacotherapy

Abstract: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, placing an increasing burden on human health. NAFLD is a complex multifactorial disease involving genetic, metabolic, and environmental factors. It is closely associated with metabolic syndrome, obesity, and type 2 diabetes, of which insulin resistance is the main pathophysiological mechanism. Over the past few decades, investigation of the pathogenesis, diagnosis, and treatments has revealed different aspects of NAFLD, challenging the accuracy of definition and therapeutic strategy for the clinical practice. Recently, experts reach a consensus that NAFLD does not reflect the current knowledge, and metabolic (dysfunction) associated fatty liver disease (MAFLD) is suggested as a more appropriate term. The new definition puts increased emphasis on the important role of metabolic dysfunction in it. Herein, the shared features and potential changes in epidemiology, pathophysiology, diagnosis, and pharmacotherapy of the newly defined MAFLD, as compared with the formerly defined NAFLD, are reviewed for updating our understanding.

Immunogenicity and safety of a severe acute respiratory syndrome coronavirus 2 inactivated vaccine in healthy adults: randomized, double-blind, and placebo-controlled phase 1 and phase 2 clinical trials.

Abstract: BACKGROUND: The significant morbidity and mortality resulted from the infection of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) call for urgent development of effective and safe vaccines. We report the immunogenicity and safety of an inactivated SARS-CoV-2 vaccine, KCONVAC, in healthy adults. METHODS: Phase 1 and phase 2 randomized, double-blind, and placebo-controlled trials of KCONVAC were conducted in healthy Chinese adults aged 18 to 59 years. The participants in the phase 1 trial were randomized to receive two doses, one each on Days 0 and 14, of either KCONVAC (5 or 10 µg/dose) or placebo. The participants in the phase 2 trial were randomized to receive either KCONVAC (at 5 or 10 µg/dose) or placebo on Days 0 and 14 (0/14 regimen) or Days 0 and 28 (0/28 regimen). In the phase 1 trial, the primary safety endpoint was the proportion of participants experiencing adverse reactions/events within 28 days following the administration of each dose. In the phase 2 trial, the primary immunogenicity endpoints were neutralization antibody seroconversion and titer and anti-receptor-binding domain immunoglobulin G seroconversion at 28 days after the second dose. RESULTS: In the phase 1 trial, 60 participants were enrolled and received at least one dose of 5-µg vaccine (n = 24), 10-µg vaccine (n = 24), or placebo (n = 12). In the phase 2 trial, 500 participants were enrolled and received at least one dose of 5-µg vaccine (n = 100 for 0/14 or 0/28 regimens), 10-µg vaccine (n = 100 for each regimen), or placebo (n = 50 for each regimen). In the phase 1 trial, 13 (54%), 11 (46%), and seven (7/12) participants reported at least one adverse event (AE) after receiving 5-, 10-µg vaccine, or placebo, respectively. In the phase 2 trial, 16 (16%), 19 (19%), and nine (18%) 0/14-regimen participants reported at least one AE after receiving 5-, 10-µg vaccine, or placebo, respectively. Similar AE incidences were observed in the three 0/28-regimen treatment groups. No AEs with an intensity of grade 3+ were reported, expect for one vaccine-unrelated serious AE (foot fracture) reported in the phase 1 trial. KCONVAC induced significant antibody responses; 0/28 regimen showed a higher immune responses than that did 0/14 regimen after receiving two vaccine doses. CONCLUSIONS: Both doses of KCONVAC are well tolerated and able to induce robust immune responses in healthy adults. These results support testing 5-µg vaccine in the 0/28 regimen in an upcoming phase 3 efficacy trial. TRIAL REGISTRATION: http://www.chictr.org.cn/index.aspx (No. ChiCTR2000038804, http://www.chictr.org.cn/showproj.aspx?proj=62350; No. ChiCTR2000039462, http://www.chictr.org.cn/showproj.aspx?proj=63353).

Pneumoconiosis: current status and future prospects.

Abstract: Pneumoconiosis refers to a spectrum of pulmonary diseases caused by inhalation of mineral dust, usually as the result of certain occupations. The main pathological features include chronic pulmonary inflammation and progressive pulmonary fibrosis, which can eventually lead to death caused by respiratory and/or heart failure. Pneumoconiosis is widespread globally, seriously threatening global public health. Its high incidence and mortality lie in improper occupational protection, and in the lack of early diagnostic methods and effective treatments. This article reviews the epidemiology, safeguard procedures, diagnosis, and treatment of pneumoconiosis, and summarizes recent research advances and future research prospects.

Cerebral amyloid angiopathy-related inflammation: current status and future implications.

Abstract: Cerebral amyloid angiopathy-related inflammation (CAA-RI) is a rare but increasingly recognized subtype of CAA. CAA-RI consists of two subtypes: inflammatory cerebral amyloid angiopathy and amyloid β (Aβ)-related angiitis. Acute or subacute onset of cognitive decline or behavioral changes is the most common symptom of CAA-RI. Rapid progressive dementia, headache, seizures, or focal neurological deficits, with patchy or confluent hyperintensity on T2 or fluid-attenuated inversion recovery sequences and evidence of strictly lobar microbleeds or cortical superficial siderosis on susceptibility-weighted imaging imply CAA-RI. The gold standard for diagnosis is autopsy or brain biopsy. However, biopsy is invasive; consequently, most clinically diagnosed cases have been based on clinical and radiological data. Other diagnostic indexes include the apolipoprotein E e4 allele, Aβ and anti-Aβ antibodies in cerebral spinal fluid and amyloid positron emission tomography. Many diseases with similar clinical manifestations should be carefully ruled out. Immunosuppressive therapy is effective both during initial presentation and in relapses. The use of glucocorticoids and immunosuppressants improves prognosis. This article reviews the pathology and pathogenesis, clinical and imaging manifestations, diagnostic criteria, treatment, and prognosis of CAA-RI, and highlights unsolved problems in the existing research.

Colorectal cancer incidence and mortality: the current status, temporal trends and their attributable risk factors in 60 countries in 2000-2019.

Abstract: BACKGROUND Globally, colorectal cancer (CRC) imposes a substantial burden on healthcare systems and confers considerable medical expenditures. We aimed to evaluate the global and regional burden in epidemiological trends and factors associated with the incidence and mortality of CRC. METHODS We used data from the GLOBOCAN database to estimate CRC incidence and mortality worldwide in 2020 and their association with the human development index (HDI). Trends of age-standardized rates of incidence and mortality in 60 countries (2000-2019) were evaluated by Joinpoint regression analysis using data of Global Burden of Disease 2019. The association between exposure to country-level lifestyle, metabolic and socioeconomic factors obtained from the World Health Organization Global Health Observatory and World Bank DataBank data and CRC incidence and mortality was determined by multivariable linear regression. RESULTS CRC incidence and mortality varied greatly in the 60 selected countries, and much higher incidence and mortality were observed in countries with higher HDIs, and vice versa. From 2000 to 2019, significant increases of incidence and mortality were observed for 33 countries (average annual percent changes [AAPCs], 0.24-3.82) and 18 countries (AAPCs, 0.41-2.22), respectively. A stronger increase in incidence was observed among males (AAPCs, 0.36-4.54) and individuals <50 years (AAPCs, 0.56-3.86). Notably, 15 countries showed significant decreases in both incidence (AAPCs, -0.24 to -2.19) and mortality (AAPCs, -0.84 to -2.74). A significant increase of incidence among individuals <50 years was observed in 30 countries (AAPCs, 0.28-3.62). Countries with higher incidence were more likely to have a higher prevalence of alcohol drinking, higher level of cholesterol level, higher level of unemployment, and a poorer healthcare system. CONCLUSIONS Some high-HDI countries showed decreasing trends in CRC incidence and mortality, whereas developing countries that previously had low disease burden showed significantly increased incidence and mortality trends, especially in males and populations ≥50 years, which require targeted preventive health programs.

Arginine metabolism: a potential target in pancreatic cancer therapy.

Abstract: Pancreatic ductal adenocarcinoma (PDAC) is an extremely malignant disease, which has an extremely low survival rate of <9% in the United States. As a new hallmark of cancer, metabolism reprogramming exerts crucial impacts on PDAC development and progression. Notably, arginine metabolism is altered in PDAC cells and participates in vital signaling pathways. In addition, arginine and its metabolites including polyamine, creatine, agmatine, and nitric oxide regulate the proliferation, growth, autophagy, apoptosis, and metastasis of cancer cells. Due to the loss of argininosuccinate synthetase 1 (ASS1) expression, the key enzyme in arginine biosynthesis, arginine deprivation is regarded as a potential strategy for PDAC therapy. However, drug resistance develops during arginine depletion treatment, along with the re-expression of ASS1, metabolic dysfunction, and the appearance of anti-drug antibody. Additionally, arginase 1 exerts crucial roles in myeloid-derived suppressor cells, indicating its potential targeting by cancer immunotherapy. In this review, we introduce arginine metabolism and its impacts on PDAC cells. Also, we discuss the role of arginine metabolism in arginine deprivation therapy and immunotherapy for cancer.

Cardiovascular and renal burdens of metabolic associated fatty liver disease from serial US national surveys, 1999-2016.

Abstract: Background Non-communicable chronic diseases have become the leading causes of disease burden worldwide. The trends and burden of "metabolic associated fatty liver disease" (MAFLD) are unknown. We aimed to investigate the cardiovascular and renal burdens in adults with MAFLD and non-alcoholic fatty liver disease (NAFLD). Methods Nationally representative data were analyzed including data from 19,617 non-pregnant adults aged ≥20 years from the cross-sectional US National Health and Nutrition Examination Survey periods, 1999 to 2002, 2003 to 2006, 2007 to 2010, and 2011 to 2016. MAFLD was defined by the presence of hepatic steatosis plus general overweight/obesity, type 2 diabetes mellitus, or evidence of metabolic dysregulation. Results The prevalence of MAFLD increased from 28.4% (95% confidence interval 26.3-30.6) in 1999 to 2002 to 35.8% (33.8-37.9) in 2011 to 2016. In 2011 to 2016, among adults with MAFLD, 49.0% (45.8-52.2) had hypertension, 57.8% (55.2-60.4) had dyslipidemia, 26.4% (23.9-28.9) had diabetes mellitus, 88.7% (87.0-80.1) had central obesity, and 18.5% (16.3-20.8) were current smokers. The 10-year cardiovascular risk ranged from 10.5% to 13.1%; 19.7% (17.6-21.9) had chronic kidney diseases (CKDs). Through the four periods, adults with MAFLD showed an increase in obesity; increase in treatment to lower blood pressure (BP), lipids, and hemoglobin A1c; and increase in goal achievements for BP and lipids but not in goal achievement for glycemic control in diabetes mellitus. Patients showed a decreasing 10-year cardiovascular risk over time but no change in the prevalence of CKDs, myocardial infarction, or stroke. Generally, although participants with NAFLD and those with MAFLD had a comparable prevalence of cardiovascular disease and CKD, the prevalence of MAFLD was significantly higher than that of NAFLD. Conclusions From 1999 to 2016, cardiovascular and renal risks and diseases have become highly prevalent in adults with MAFLD. The absolute cardiorenal burden may be greater for MAFLD than for NAFLD. These data call for early identification and risk stratification of MAFLD and close collaboration between endocrinologists and hepatologists.

Population diversity of cardiovascular outcome trials and real-world patients with diabetes in a Chinese tertiary hospital.

Abstract: Background Recent cardiovascular outcome trials (CVOTs) changed the therapeutic strategy of guidelines for type 2 diabetes. We compared the characteristics of patients from real-world hospital settings with those of participants in recent pragmatic randomized trials. Methods This electronic medical record (EMR)-based retrospective observational study investigated the data of patients with diabetes from inpatient and outpatient settings in West China Hospital of Sichuan University from January 1, 2011, to June 30, 2019. We identified patients meeting the inclusion criteria of a pragmatic randomized trial (EMPA-REG OUTCOME) based on EMRs and compared their baseline characteristics with those of the trial participants. The cutoff for the clinical significance of each characteristic was set as its minimal clinically important difference based on expert consultation. Results We included 48,257 inpatients and 36,857 outpatients with diabetes and found that 8389 (17.4%) inpatients and 2646 (7.2%) outpatients met the inclusion criteria for the EMPA-REG OUTCOME trial. Compared with the trial population, the real-world inpatients meeting the eligibility criteria of the EMPA-REG OUTCOME had similar age, blood pressure, and lipid profiles but comprised of fewer males, metformin users, anti-hypertensive drug users, and aspirin users, and had a lower body mass index. The group of outpatients meeting the eligibility criteria had fewer males, similar age, fewer metformin users, fewer insulin users, fewer anti-hypertensive drug users, and fewer aspirin users compared with the trial population. Conclusions The trial population in EMPA-REG OUTCOME represents only a small portion of patients with diabetes from the inpatient and outpatient departments of a Chinese tertiary medical center. Evidence localization in different clinical settings and validation are essential to enabling extrapolation of the results from CVOTs in patients with diabetes to Chinese clinical practice.

Cancer incidence and mortality in Zhejiang Province, Southeast China, 2016: a population-based study.

Abstract: Backgrounds Cancer is one of the main causes of death worldwide, seriously threatening human health and life expectancy. We aimed to analyze the cancer incidence and mortality rates during 2016 in Zhejiang Province, Southeast China. Methods Data were collected from 14 population-based cancer registries across Zhejiang Province of China. Cancer incidence and mortality rates stratified by sex and region were analyzed. The crude rate, age-standardized rate, age-specific and region-specific rate, and cumulative rate were calculated. The proportions of 10 common cancers in different groups and the incidence and mortality rates of the top five cancers in different age groups were also calculated. The Chinese national census of 2000 and the world Segi population was used for calculating the age-standardized incidence and mortality rates. Results The 14 cancer registries covered a population of 14,250,844 individuals, accounting for 29.13% of the population of Zhejiang Province. The total reported cancer cases and deaths were 55,835 and 27,013, respectively. The proportion of morphological verification (MV%) was 78.95% of the population, and percentage of incident cases identified through death certificates only (DCO%) was 1.23% with a mortality-to-incidence ratio (M/I ratio) of 0.48. The crude incidence rate in Zhejiang cancer registration areas was 391.80/105; the age-standardized incidence rate of the Chinese standard population (ASIRC) and the age-standardized incidence rate of the world standard population (ASIRW) were 229.76/105 and 220.96/105, respectively. The incidence rate in men was higher than that in women. The incidence rate increased rapidly after 45 years of age and peaked in individuals aged 80 to 84 years. The top 10 incidence rates of cancers were lung cancer, female breast cancer, thyroid cancer, colorectal cancer, stomach cancer, liver cancer, prostate cancer, cervical cancer, esophageal cancer, and pancreatic cancer (from highest to lowest). The crude mortality rate in Zhejiang cancer registration areas was 189.55/105; the age-standardized mortality rate of the Chinese standard population (ASMRC) and the age-standardized mortality rate of the world standard population (ASMRW) were 94.46/105 and 93.42/105, respectively. The mortality rate in men was higher than that in women, and the male population in rural areas was higher than that in urban areas. The cancer mortality rate increased rapidly after 50 years of age and peaked in individuals aged 85+ years. The top 10 mortality rates of cancers were lung cancer, liver cancer, stomach cancer, colorectal cancer, pancreatic cancer, esophageal cancer, female breast cancer, prostate cancer, lymphoma, and leukemia (from highest to lowest). Conclusions Lung cancer, female breast cancer, thyroid cancer, colorectal cancer, prostate cancer, liver cancer, and stomach cancer were the most common cancers in Zhejiang Province. Effective prevention and control measures should be established after considering the different characteristics of cancers in urban and rural areas.

Single-cell analysis of angiotensin-converting enzyme II expression in human kidneys and bladders reveals a potential route of 2019 novel coronavirus infection.

Abstract: Background Since 2019, a novel coronavirus named 2019 novel coronavirus (2019-nCoV) has emerged worldwide. Apart from fever and respiratory complications, acute kidney injury has been observed in a few patients with coronavirus disease 2019. Furthermore, according to recent findings, the virus has been detected in urine. Angiotensin-converting enzyme II (ACE2) has been proposed to serve as the receptor for the entry of 2019-nCoV, which is the same as that for the severe acute respiratory syndrome. This study aimed to investigate the possible cause of kidney damage and the potential route of 2019-nCoV infection in the urinary system. Methods We used both published kidney and bladder cell atlas data and new independent kidney single-cell RNA sequencing data generated in-house to evaluate ACE2 gene expression in all cell types in healthy kidneys and bladders. The Pearson correlation coefficients between ACE2 and all other genes were first generated. Then, genes with r values larger than 0.1 and P values smaller than 0.01 were deemed significant co-expression genes with ACE2. Results Our results showed the enriched expression of ACE2 in all subtypes of proximal tubule (PT) cells of the kidney. ACE2 expression was found in 5.12%, 5.80%, and 14.38% of the proximal convoluted tubule cells, PT cells, and proximal straight tubule cells, respectively, in three published kidney cell atlas datasets. In addition, ACE2 expression was also confirmed in 12.05%, 6.80%, and 10.20% of cells of the proximal convoluted tubule, PT, and proximal straight tubule, respectively, in our own two healthy kidney samples. For the analysis of public data from three bladder samples, ACE2 expression was low but detectable in bladder epithelial cells. Only 0.25% and 1.28% of intermediate cells and umbrella cells, respectively, had ACE2 expression. Conclusion This study has provided bioinformatics evidence of the potential route of 2019-nCoV infection in the urinary system.

Immunogenicity and safety of a recombinant fusion protein vaccine (V-01) against coronavirus disease 2019 in healthy adults: a randomized, double-blind, placebo-controlled, phase II trial.

Abstract: BACKGROUND: Innovative coronavirus disease 2019 (COVID-19) vaccines, with elevated global manufacturing capacity, enhanced safety and efficacy, simplified dosing regimens, and distribution that is less cold chain-dependent, are still global imperatives for tackling the ongoing pandemic. A previous phase I trial indicated that the recombinant COVID-19 vaccine (V-01), which contains a fusion protein (IFN-PADRE-RBD-Fc dimer) as its antigen, is safe and well tolerated, capable of inducing rapid and robust immune responses, and warranted further testing in additional clinical trials. Herein, we aimed to assess the immunogenicity and safety of V-01, providing rationales of appropriate dose regimen for further efficacy study. METHODS: A randomized, double-blind, placebo-controlled phase II clinical trial was initiated at the Gaozhou Municipal Centre for Disease Control and Prevention (Guangdong, China) in March 2021. Both younger (n = 440; 18-59 years of age) and older (n = 440; ≥60 years of age) adult participants in this trial were sequentially recruited into two distinct groups: two-dose regimen group in which participants were randomized either to follow a 10 or 25 µg of V-01 or placebo given intramuscularly 21 days apart (allocation ratio, 3:3:1, n = 120, 120, 40 for each regimen, respectively), or one-dose regimen groups in which participants were randomized either to receive a single injection of 50 µg of V-01 or placebo (allocation ratio, 3:1, n = 120, 40, respectively). The primary immunogenicity endpoints were the geometric mean titers of neutralizing antibodies against live severe acute respiratory syndrome coronavirus 2, and specific binding antibodies to the receptor binding domain (RBD). The primary safety endpoint evaluation was the frequencies and percentages of overall adverse events (AEs) within 30 days after full immunization. RESULTS: V-01 provoked substantial immune responses in the two-dose group, achieving encouragingly high titers of neutralizing antibody and anti-RBD immunoglobulin, which peaked at day 35 (161.9 [95% confidence interval [CI]: 133.3-196.7] and 149.3 [95%CI: 123.9-179.9] in 10 and 25 µg V-01 group of younger adults, respectively; 111.6 [95%CI: 89.6-139.1] and 111.1 [95%CI: 89.2-138.4] in 10 and 25 µg V-01 group of older adults, respectively), and remained high at day 49 after a day-21 second dose; these levels significantly exceed those in convalescent serum from symptomatic COVID-19 patients (53.6, 95%CI: 31.3-91.7). Our preliminary data show that V-01 is safe and well tolerated, with reactogenicity predominantly being absent or mild in severity and only one vaccine-related grade 3 or worse AE being observed within 30 days. The older adult participants demonstrated a more favorable safety profile compared with those in the younger adult group: with AEs percentages of 19.2%, 25.8%, 17.5% in older adults vs. 34.2%, 23.3%, 26.7% in younger adults at the 10, 25 µg V-01 two-dose group, and 50 µg V-01 one-dose group, respectively. CONCLUSIONS: The vaccine candidate V-01 appears to be safe and immunogenic. The preliminary findings support the advancement of the two-dose, 10 µg V-01 regimen to a phase III trial for a large-scale population-based evaluation of safety and efficacy. TRIAL REGISTRATION: http://www.chictr.org.cn/index.aspx (No. ChiCTR2100045107, http://www.chictr.org.cn/showproj.aspx?proj=124702).

NLRP3 inflammasome: a new therapeutic target for high-risk reproductive disorders?

Abstract: The NOD-like receptor protein 3 (NLRP3) inflammasome is a key regulator of the host's immune response, and many immune and metabolic disorders are linked to its activation. This review aimed to investigate and clarify the relationship between this inflammasome and high-risk reproductive disorders. Papers cited here were retrieved from PubMed up to August 2020 using the keywords "NLRP3" or "NALP3", "caspase-1", "endometriosis", "gestational diabetes", "interleukin (IL)-18", "IL-1β", "pre-eclampsia (PE)", "preterm birth", "polycystic ovarian syndrome (PCOS)", "recurrent spontaneous abortion (RSA)", and combinations of these terms. The results show that NLRP3 inflammasome is associated with various high-risk reproductive disorders and many inflammatory factors are secreted during its activation, such as IL-1β induced during the development of endometriosis. PCOS is also associated with activation of the NLRP3 inflammasome, especially in overweight patients. It also participates in the pathogenesis of RSA and is activated in fetal membranes before preterm birth. The placentas of pregnant women with PE show higher expression of the NLRP3 inflammasome, and gestational diabetes mellitus occurs simultaneously with its activation. Current evidence suggest that the NLRP3 inflammasome plays an important role in female reproductive disorders. New treatment and management methods targeting it might help reduce the incidence of such disorders and improve neonatal outcomes.

Efficacy and safety of Shexiang Baoxin pill (MUSKARDIA) in patients with stable coronary artery disease: a multicenter, double-blind, placebo-controlled phase IV randomized clinical trial.

Abstract: Background The Shexiang Baoxin Pill (MUSKARDIA) has been used for treating coronary artery disease (CAD) and angina for more than 30 years in China. Nevertheless, methodologically sound trials on the use of MUSKARDIA in CAD patients are scarce. The aim of the study is to determine the effects of MUSKARDIA as an add-on to optimal medical therapy (OMT) in patients with stable CAD. Methods A total of 2674 participants with stable CAD from 97 hospitals in China were randomized 1:1 to a MUSKARDIA or placebo group for 24 months. Both groups received OMT according to local tertiary hospital protocols. The primary outcome was the occurrence of a major adverse cardiovascular event (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction (MI), or non-fatal stroke. Secondary outcomes included all-cause mortality, non-fatal MI, non-fatal stroke, hospitalization for unstable angina or heart failure, peripheral revascularization, angina stability and angina frequency. Results In all, 99.7% of the patients were treated with aspirin and 93.0% with statin. After 2 years of treatment, the occurrence of MACEs was reduced by 26.9% in the MUSKARDIA group (MUSKARDIA: 1.9% vs. placebo: 2.6%; odds ratio = 0.80; 95% confidence interval: 0.45-1.07; P = 0.2869). Angina frequency was significantly reduced in the MUSKARDIA group at 18 months (P = 0.0362). Other secondary endpoints were similar between the two groups. The rates of adverse events were also similar between the two groups (MUSKARDIA: 17.7% vs. placebo: 17.4%, P = 0.8785). Conclusions As an add-on to OMT, MUSKARDIA is safe and significantly reduces angina frequency in patients with stable CAD. Moreover, the use of MUSKARDIA is associated with a trend toward reduced MACEs in patients with stable CAD. The results suggest that MUSKARDIA can be used to manage patients with CAD. Trial registration chictr.org.cn, No. ChiCTR-TRC-12003513.

Clinical features and risk factors associated with severe COVID-19 patients in China.

Abstract: BACKGROUND: Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread throughout the world. In this study, we aimed to identify the risk factors for severe COVID-19 to improve treatment guidelines. METHODS: A multicenter, cross-sectional study was conducted on 313 patients hospitalized with COVID-19. Patients were classified into two groups based on disease severity (nonsevere and severe) according to initial clinical presentation. Laboratory test results and epidemiological and clinical characteristics were analyzed using descriptive statistics. Univariate and multivariate logistic regression models were used to detect potential risk factors associated with severe COVID-19. RESULTS: A total of 289 patients (197 nonsevere and 92 severe cases) with a median age of 45.0 (33.0, 61.0) years were included in this study, and 53.3% (154/289) were male. Fever (192/286, 67.1%) and cough (170/289, 58.8%) were commonly observed, followed by sore throat (49/289, 17.0%). Multivariate logistic regression analysis suggested that patients who were aged ≥ 65 years (OR: 2.725, 95% confidence interval [CI]: 1.317-5.636; P = 0.007), were male (OR: 1.878, 95% CI: 1.002-3.520, P = 0.049), had comorbid diabetes (OR: 3.314, 95% CI: 1.126-9.758, P = 0.030), cough (OR: 3.427, 95% CI: 1.752-6.706, P < 0.001), and/or diarrhea (OR: 2.629, 95% CI: 1.109-6.231, P = 0.028) on admission had a higher risk of severe disease. Moreover, stratification analysis indicated that male patients with diabetes were more likely to have severe COVID-19 (71.4% vs. 28.6%, χ2 = 8.183, P = 0.004). CONCLUSIONS: The clinical characteristics of those with severe and nonsevere COVID-19 were significantly different. The elderly, male patients with COVID-19, diabetes, and presenting with cough and/or diarrhea on admission may require close monitoring to prevent deterioration.

Mortality and years of life lost of colorectal cancer in China, 2005-2020: findings from the national mortality surveillance system.

Abstract: Background Colorectal cancer (CRC) is the fourth cause of cancer death in China. We aimed to provide national and subnational estimates and changes of CRC premature mortality burden during 2005-2020. Methods Data from multi-source on the basis of the national surveillance mortality system were used to estimate mortality and years of life lost (YLL) of CRC in the Chinese population during 2005-2020. Estimates were generated and compared for 31 provincial-level administrative divisions in China. Results Estimated CRC deaths increased from 111.41 thousand in 2005 to 178.02 thousand in 2020; age-standardized mortality rate decreased from 10.01 per 100,000 in 2005 to 9.68 per 100,000 in 2020. Substantial reduction in CRC premature mortality burden, as measured by age-standardized YLL rate, was observed with a reduction of 10.20% nationwide. Marked differences were observed in the geographical patterns of provincial units, and they appeared to be obvious in areas with higher economic development. Population aging was the dominant driver which contributed to the increase in CRC deaths, followed by population growth and age-specific mortality change. Conclusions Substantial discrepancies were observed in the premature mortality burden of CRC across China. Targeted considerations were needed to promote a healthy lifestyle, expand cost-effective CRC early screening and diagnosis, and improve medical treatment to reduce CRC mortality among high-risk populations and regions with inadequate healthcare resources.

UBE2C affects breast cancer proliferation through the AKT/mTOR signaling pathway.

Abstract: BACKGROUND Ubiquitin-conjugating enzyme E2C (UBE2C) has been shown to be associated with the occurrence of various cancers and involved in many tumorigenic processes. This study aimed to investigate the specific molecular mechanism through which UBE2C affects breast cancer (BC) proliferation. METHODS BC-related datasets were screened according to filter criteria in the Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA) database. Then differentially expressed genes (DEGs) were identified using Venn diagram analysis. By using DEGs, we conducted the following analyses including Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), protein-protein interaction (PPI), and survival analysis, and then validated the function of the hub gene UBE2C using quantitative reverse transcription-polymerase chain reaction (RT-qPCR), cell counting kit-8 (CCK-8) assay, transwell assay, and Western blot assay. RESULTS In total, 151 DEGs were identified from the GEO and TCGA databases. The results of GO analysis demonstrated that the DEGs were significantly enriched with mitotic nuclear division, lipid droplet, and organic acid-binding. KEGG analysis showed that the peroxisome proliferators-activated receptor (PPAR) signaling pathway, regulation of lipolysis in adipocytes, and proximal tubule bicarbonate reclamation were significantly enriched in the signal transduction pathway category. The top three hub genes that resulted from the PPI network were FOXM1, UBE2C, and CDKN3. The results of survival analysis showed a close relationship between UBE2C and BC. The results of CCK-8 and transwell assays suggested that the proliferation and invasion of UBE2C knockdown cells were significantly inhibited (P < 0.050). The results of Western blot assay showed that the level of phosphorylated phosphatase and tensin homology deleted on chromosome 10 (p-PTEN) was obviously increased (P < 0.050), whereas the levels of phosphorylated protein kinase B (p-AKT), phosphorylated mammalian target of rapamycin (p-mTOR), and hypoxia-inducible factor-1 alpha (HIF-1α) were dramatically decreased (P < 0.050) in the UBE2C knockdown cell. CONCLUSION UBE2C can promote BC proliferation by activating the AKT/mTOR signaling pathway.

Establishment and clinical application value of an automatic diagnosis platform for rectal cancer T-staging based on a deep neural network.

Abstract: Background Colorectal cancer is harmful to the patient's life. The treatment of patients is determined by accurate preoperative staging. Magnetic resonance imaging (MRI) played an important role in the preoperative examination of patients with rectal cancer, and artificial intelligence (AI) in the learning of images made significant achievements in recent years. Introducing AI into MRI recognition, a stable platform for image recognition and judgment can be established in a short period. This study aimed to establish an automatic diagnostic platform for predicting preoperative T staging of rectal cancer through a deep neural network. Methods A total of 183 rectal cancer patients' data were collected retrospectively as research objects. Faster region-based convolutional neural networks (Faster R-CNN) were used to build the platform. And the platform was evaluated according to the receiver operating characteristic (ROC) curve. Results An automatic diagnosis platform for T staging of rectal cancer was established through the study of MRI. The areas under the ROC curve (AUC) were 0.99 in the horizontal plane, 0.97 in the sagittal plane, and 0.98 in the coronal plane. In the horizontal plane, the AUC of T1 stage was 1, AUC of T2 stage was 1, AUC of T3 stage was 1, AUC of T4 stage was 1. In the coronal plane, AUC of T1 stage was 0.96, AUC of T2 stage was 0.97, AUC of T3 stage was 0.97, AUC of T4 stage was 0.97. In the sagittal plane, AUC of T1 stage was 0.95, AUC of T2 stage was 0.99, AUC of T3 stage was 0.96, and AUC of T4 stage was 1.00. Conclusion Faster R-CNN AI might be an effective and objective method to build the platform for predicting rectal cancer T-staging. Trial registration chictr.org.cn: ChiCTR1900023575; http://www.chictr.org.cn/showproj.aspx?proj=39665.

HTRA1-related autosomal dominant cerebral small vessel disease

Abstract: BACKGROUND Homozygous or compound heterozygous mutations in high temperature requirement serine peptidase A1 (HTRA1) gene are responsible for cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL). Recently, increasing evidence has shown that heterozygous HTRA1 mutations are also associated with cerebral small vessel disease (CSVD) with an autosomal dominant pattern of inheritance. This study was aimed to analyze the genetic and clinical characteristics of HTRA1-related autosomal dominant CSVD. METHODS We presented three new Chinese cases of familial CSVD with heterozygous HTRA1 mutations and reviewed all clinical case reports and articles on HTRA1-related autosomal dominant CSVD included in PUBMED by the end of March 1, 2020. CARASIL probands with genetic diagnosis reported to date were also reviewed. The genetic and clinical characteristics of HTRA1-related autosomal dominant CSVD were summarized and analyzed by comparing with CARASIL. RESULTS Forty-four HTRA1-related autosomal dominant CSVD probands and 22 CARASIL probands were included. Compared with typical CARASIL, HTRA1-related autosomal dominant probands has a higher proportion of vascular risk factors (P < 0.001), a later onset age (P < 0.001), and a relatively slower clinical progression. Alopecia and spondylosis can be observed, but less than those in the typical CARASIL. Thirty-five heterozygous mutations in HTRA1 were reported, most of which were missense mutations. Amino acids located close to amino acids 250-300 were most frequently affected, followed by these located near 150∼200. While amino acids 250∼300 were also the most frequently affected region in CARASIL patients, fewer mutations precede the 200th amino acids were detected, especially in the Kazal-type serine protease domain. CONCLUSIONS HTRA1-related autosomal dominant CSVD is present as a mild phenotype of CARASIL. The trend of regional concentration of mutation sites may be related to the concentration of key sites in these regions which are responsible for pathogenesis of HTRA1-related autosomal dominant CSVD.

R-CHOP resistance in diffuse large B-cell lymphoma: biological and molecular mechanisms.

Abstract: Although the first-line rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone regimen (R-CHOP) substantially improved outcomes for patients with diffuse large B-cell lymphoma (DLBCL), 40% of the patients suffered from relapsed/refractory disease and had poor survival outcomes. The detailed mechanism underlying R-CHOP resistance has not been well defined. For this review, we conducted a thorough search for literature and clinical trials involving DLBCL resistance. We discussed DLBCL biology, epigenetics, and aberrant signaling of the B-cell receptor (BCR), phosphatidylinositol 3-kinase (PI3K)/Akt, nuclear factor kappa light chain enhancer of activated B-cells (NF-κB), and the Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) pathways as defining mechanisms of DLBCL heterogeneity and R-CHOP resistance. The cell of origin, double- or triple-hit lymphoma and double-protein-expression, clonal evolution, tumor microenvironment, and multi-drug resistance help to contextualize DLBCL resistance in an (epi)genetically and biologically comparative manner. With better understanding of the biological and molecular landscape of DLBCL, a more detailed classification system and tailored treatments will ideally become available to further improve the prognosis of DLBCL patients.

Hyperbaric oxygen treatment on keloid tumor immune gene expression.

Abstract: Background Hyperbaric oxygen treatment (HBOT) has been demonstrated to influence the keloid recurrence rate after surgery and to relieve keloid symptoms and other pathological processes in keloids. To explore the mechanism of the effect of HBOT on keloids, tumor immune gene expression and immune cell infiltration were studied in this work. Methods From February 2021 to April 2021, HBOT was carried out on keloid patients four times before surgery. Keloid tissue samples were collected and divided into an HBOT group (keloid with HBOT before surgery [HK] group, n = 6) and a non-HBOT group (K group, n = 6). Tumor gene expression was analyzed with an Oncomine Immune Response Research Assay kit. Data were mined with R package. The differentially expressed genes between the groups were compared. Hub genes between the groups were determined and verified with Quantitative Real-time PCR. Immune cell infiltration was analyzed based on CIBERSORT deconvolution algorithm analysis of gene expression and verified with immunohistochemistry (IHC). Results Inflammatory cell infiltration was reduced in the HK group. There were 178 upregulated genes and 217 downregulated genes. Ten hub genes were identified, including Integrin Subunit Alpha M (ITGAM), interleukin (IL)-4, IL-6, IL-2, Protein Tyrosine Phosphatase Receptor Type C (PTPRC), CD86, transforming growth factor (TGF), CD80, CTLA4, and IL-10. CD80, ITGAM, IL-4, and PTPRC with significantly downregulated expression were identified. IL-10 and IL-2 were upregulated in the HK group but without a significant difference. Infiltration differences of CD8 lymphocyte T cells, CD4 lymphocyte T-activated memory cells, and dendritic resting cells were identified with gene CIBERSORT deconvolution algorithm analysis. Infiltration levels of CD4 lymphocyte T cell in the HK group were significantly higher than those of the K group in IHC verification. Conclusion HBOT affected tumor gene expression and immune cell infiltration in keloids. CD4 lymphocyte T cell, especially activated memory CD4+T, might be the key regulatory immune cell, and its related gene expression needs further study.

Relationship of serum vitamin D levels with diabetic microvascular complications in patients with type 2 diabetes mellitus.

Abstract: BACKGROUND Vitamin D deficiency has been reported to be associated with diabetic microvascular complications, but previous studies have only focused on the relationship between vitamin D and specific complications. Therefore, we aimed to explore the relationship between vitamin D level and diabetic microvascular complications in general, including diabetic retinopathy (DR), diabetic nephropathy (DN), and diabetic peripheral neuropathy (DPN). METHODS This was a cross-sectional study of 815 patients with type 2 diabetes mellitus (T2DM). Clinical information and laboratory results were collected from the medical records. The relationship between vitamin D and the three diabetic microvascular complications was investigated. RESULTS The serum 25-hydroxyvitamin D (25 [OH] D) level of patients with DPN and/or DN was significantly lower than that of T2DM patients without any microvascular complications (P < 0.01). Univariate analysis showed that the 25 (OH) D level was related to DPN and DN, but not DR. After adjustment, the 25 (OH) D level was confirmed to be an independent protective factor for DPN (odds ratio [OR]: 0.968, P = 0.004]) and DN (OR: 0.962, P = 0.006). The prevalence of DPN and DN increased significantly as the serum 25 (OH) D levels decreased. Furthermore, patients with both DPN and DN had the lowest concentration of serum 25 (OH) D (P < 0.001), and the prevalence of macroalbuminuria increased more abruptly than that of microalbuminuria across the 25 (OH) D tertiles. Among the patients with vitamin D insufficiency, those with DPN presented more comorbid macroalbuminuria than those without DPN (15.32% vs. 4.91%; P = 0.001). CONCLUSIONS Vitamin D deficiency is independently associated with higher risk of DPN and DN, but not DR, in T2DM patients. Further, it may be a potential predictor for both the occurrence and severity of DPN and DN.

Irritable bowel syndrome in China: a review on the epidemiology, diagnosis, and management.

Abstract: Irritable bowel syndrome (IBS) is a common functional gastrointestinal disease worldwide. Current guidelines of IBS are mostly based on the western populations and expected to vary in different communities. China has a large population and a vast literature is available on IBS. Due to linguistic variations in the literature, the studies are not widely known and their conclusions thus remain largely obscured to the western medical literature. In this article, we reviewed the published literatures on the investigations of IBS epidemiology, diagnosis, and management in the Chinese population and emphasized the different findings gleaned from the western publications. The detailed literature review will benefit understanding of and promote future study on IBS.

Expert consensus on the use of human serum albumin in critically ill patients.

Abstract: Human serum albumin (HSA) is a non-glycosylated, negatively charged, single-chain polypeptide composed of 585 amino acid residues with a relative molecular mass of 66.438 kD. It is synthesized by the liver at a rate of approximately 200 mg·kg−1·day−1, with a half-life of 21 days, and subjected to catabolism in the muscles, liver, and kidneys at a rate of 4% per day.[1] Albumin, accounting for 60% of the total plasma protein, has various physiological functions,[2] such as maintaining 70% to 80% of effective plasma colloid osmotic pressure, coordinating vascular endothelial integrity, anti-oxidant and anti-inflammatory activities, maintaining the acid-base balance, and participating in the transport, distribution, and metabolism of a variety of endogenous and exogenous substances. The normal concentration of plasma albumin is 35 to 50 g/L. In clinical practice, hypoalbuminemia often occurs because of reduced albumin synthesis due to liver dysfunction, redistribution of serum albumin due to capillary leakage, or increased loss via the intestinal and renal routes. Hypoalbuminemia (defined as a serum albumin concentration less than 35 g/L) reportedly has an incidence of 24% to 87% in critically ill patients,[3] while severe hypoalbuminemia (a serum albumin concentration less than 25 g/L) has an incidence of 5.0–9.6%.[4] Hypoalbuminemia is an independent risk factor for increased short- and long-term mortality and an increased incidence of acute kidney injury (AKI) in patients with acute conditions such as trauma, cardiogenic shock, and sepsis.[5] A meta-analysis showed that for every 10 g/L decrease in the serum albumin concentration in critically ill patients, there was a 137% increase in in-hospital mortality, an 89% increase in the incidence of comorbidities, and a 72% increase in the length of hospital stay.[6] Hypoalbuminemia can also alter the pharmacokinetics of antibiotics, leading to either insufficient or excessively high blood concentrations, thereby resulting in treatment failure or excessive toxicity.[7] HSA is mainly used for fluid resuscitation and the treatment of hypoproteinemia in critically ill patients.[2] Existing studies have shown controversial results regarding whether the use of albumin in critically ill patients improves their clinical prognosis.[8] Albumin consumption varies greatly among countries,[9] and its inappropriate use is frequently seen, with 40% to 90% of reported HSA applications failing to follow clinical guidelines.[10] A tertiary hospital in China reported that hypoproteinemia was the most common indication for the use of HSA (35.6%); however, it was also used in 11.8% of patients with serum albumin concentrations more than 40 g/L. The reason for its use was not documented in 22% of cases.[11] In clinical practice, guidelines and consensus are lacking regarding the selection of HSA concentration, the timing of administration, dosage, and target concentration. Inappropriate use of HSA will cause adverse effects and increase medical costs inevitably, whereas guidance from clinical pharmacists or hospital standards can help reduce inappropriate HSA use by 30% and decrease medical costs without affecting patient prognosis.[12] To further strengthen the standardized application of HSA in critically ill patients and achieve optimal clinical outcomes, the Chinese Society of Critical Care Medicine convened a panel of relevant experts who reviewed and summarized data on the clinical use of HSA, outlined 11 relevant clinical problems, and formulated the “Expert Consensus on the Use of Human Serum Albumin in Critically Ill Patients” using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology.

Neutrophil to lymphocyte ratio is a prognosis factor for post-operative pneumonia in aneurysmal subarachnoid hemorrhage patients.

Abstract: Background Although a variety of risk factors of pneumonia after clipping or coiling of the aneurysm (post-operative pneumonia [POP]) in patients with aneurysmal subarachnoid hemorrhage (aSAH) have been studied, the predictive model of POP after aSAH has still not been well established. Thus, the aim of this study was to assess the feasibility of using admission neutrophil to lymphocyte ratio (NLR) to predict the occurrence of POP in aSAH patients. Methods We evaluated 711 aSAH patients who were enrolled in a prospective observational study and collected admission blood cell counts data. We analyzed available demographics and baseline variables for these patients and analyzed the correlation of these factors with POP using Cox regression. After screening out the prognosis-related factors, the predictive value of these factors for POP was further assessed. Results POP occurred in 219 patients (30.4%) in this cohort. Patients with POP had significantly higher NLR than those without (14.11 ± 8.90 vs. 8.80 ± 5.82, P Conclusions Regardless of good or poor WNFS grade, patients having NLR >10 had significantly worse POP survival rate than patients having NLR ≤10. NLR at admission might be helpful as a predictor of POP in aSAH patients.

Oxidative stress in leukemia and antioxidant treatment.

Abstract: Oxidative stress is caused by the imbalance between the generation of free radicals/reactive oxygen species (ROS) and the antioxidant defense systems, which can activate various transcription factors and affect their transcriptional pathways. Oxidative stress plays an important role in the occurrence and development of leukemia and is closely related to the treatment and prognosis of leukemia. The standard chemotherapy strategies for the pre-treatment of leukemia have many drawbacks. Hence, the usage of antioxidants and oxidants in the treatment of leukemia is being explored and has been preliminarily applied. This article reviews the research progress of oxidative stress and leukemia. In addition, the application of antioxidants treatment in leukemia has been summarized.