Jin-Kui Yang

Bio: Jin-Kui Yang is an academic researcher from Capital Medical University. The author has contributed to research in topics: Diabetes mellitus & Type 2 diabetes. The author has an hindex of 25, co-authored 125 publications receiving 3705 citations. Previous affiliations of Jin-Kui Yang include Beijing Tongren Hospital.

Gender Differences in Patients With COVID-19: Focus on Severity and Mortality

Abstract: Objective: The recent outbreak of Novel Coronavirus Disease (COVID-19) is reminiscent of the SARS outbreak in 2003. We aim to compare the severity and mortality between male and female patients with COVID-19 or SARS. Study Design and Setting: We extracted the data from: (1) a case series of 43 hospitalized patients we treated, (2) a public data set of the first 37 cases of patients who died of COVID-19 and 1,019 patients who survived in China, and (3) data of 524 patients with SARS, including 139 deaths, from Beijing in early 2003. Results: Older age and a high number of comorbidities were associated with higher severity and mortality in patients with both COVID-19 and SARS. Age was comparable between men and women in all data sets. In the case series, however, men's cases tended to be more serious than women's (P = 0.035). In the public data set, the number of men who died from COVID-19 is 2.4 times that of women (70.3 vs. 29.7%, P = 0.016). In SARS patients, the gender role in mortality was also observed. The percentage of males were higher in the deceased group than in the survived group (P = 0.015). Conclusion: While men and women have the same prevalence, men with COVID-19 are more at risk for worse outcomes and death, independent of age.

Binding of SARS coronavirus to its receptor damages islets and causes acute diabetes.

Abstract: Multiple organ damage in severe acute respiratory syndrome (SARS) patients is common; however, the pathogenesis remains controversial. This study was to determine whether the damage was correlated with expression of the SARS coronavirus receptor, angiotensin converting enzyme 2 (ACE2), in different organs, especially in the endocrine tissues of the pancreas, and to elucidate the pathogenesis of glucose intolerance in SARS patients. The effect of clinical variables on survival was estimated in 135 SARS patients who died, 385 hospitalized SARS patients who survived, and 19 patients with non-SARS pneumonia. A total of 39 SARS patients who had no previous diabetes and received no steroid treatment were compared to 39 matched healthy siblings during a 3-year follow-up period. The pattern of SARS coronavirus receptor-ACE2 proteins in different human organs was also studied. Significant elevations in oxygen saturation, serum creatinine, lactate dehydrogenase, creatine kinase MB isoenzyme, and fasting plasma glucose (FPG), but not in alanine transaminase were predictors for death. Abundant ACE2 immunostaining was found in lung, kidney, heart, and islets of pancreas, but not in hepatocytes. Twenty of the 39 followed-up patients were diabetic during hospitalization. After 3 years, only two of these patients had diabetes. Compared with their non-SARS siblings, these patients exhibited no significant differences in FPG, postprandial glucose (PPG), and insulin levels. The organ involvements of SARS correlated with organ expression of ACE2. The localization of ACE2 expression in the endocrine part of the pancreas suggests that SARS coronavirus enters islets using ACE2 as its receptor and damages islets causing acute diabetes.

Plasma glucose levels and diabetes are independent predictors for mortality and morbidity in patients with SARS

Abstract: Aims To investigate the relationships between a known history of diabetes and ambient fasting plasma glucose (FPG) levels with death and morbidity rates in patients with severe acute respiratory syndrome (SARS). Methods In this retrospective analysis, the clinical and biochemical characteristics of 135 patients who had died from SARS, 385 survivors of SARS and 19 patients with non-SARS pneumonia were compared. Results All patients were treated according to a predefined protocol. Before steroid treatment, the mean FPG level was significantly higher in the SARS group (deceased vs. survivors vs. non-SARS pneumonia group: 9.7 ± 5.2 vs. 6.5 ± 3.0 vs. 5.1 ± 1.0 mmol/l, P < 0.01). In the SARS group, the percentage of patients with a known history of diabetes was significantly higher in the deceased patients than in the survivors (21.5% vs. 3.9%, P < 0.01). Among patients with no known history of diabetes and before commencement of steroid therapy, those who had hypoxaemia (SaO2 < 93%) had higher FPG levels than those who did not have hypoxia in both the survivor (8.7 ± 4.9 vs. 6.3 ± 2.1 mmol/l, P < 0.001) and deceased (9.8 ± 4.8 vs. 7.2 ± 1.5 mmol/l, P < 0.001) groups. A known history of diabetes [odds ratio (OR) 3.0, 95% confidence interval (CI) 1.4, 6.3; P = 0.005] and FPG ≥ 7.0 mmol/l before steroid treatment (OR 3.3, 95% CI 1.4, 7.7, P = 0.006) were independent predictors of death. During the course of the illness, FPG levels were negatively associated with SaO2 (β =−0.682 ± 0.305, P = 0.025, general estimation equation model) in SARS patients. Survival analysis showed that FPG was independently associated with an increased hazard ratio (HR) of mortality (HR = 1.1, 95% CI 1.0, 1.1, P = 0.001) and hypoxia (HR = 1.1, 95% CI 1.0, 1.1, P = 0.002) after controlling for age and gender. Conclusions A known history of diabetes and ambient hyperglycaemia were independent predictors for death and morbidity in SARS patients. Metabolic control may improve the prognosis of SARS patients.

Gender differences in patients with COVID-19: Focus on severity and mortality

Abstract: Importance The recent outbreak of Novel Coronavirus (SARS-CoV-2) Disease (COVID-19) has put the world on alert, that is reminiscent of the SARS outbreak seventeen years ago. Objective We aim to compare the severity and mortality between male and female patients with both COVID-19 and SARS, to explore the most useful prognostic factors for individualized assessment. Design, Setting, and Participants We extracted the data from a case series of 43 hospitalized patients we treated, a public data set of the first 37 cases died of COVID-19 in Wuhan city and 1019 survived patients from six cities in China. We also analyzed the data of 524 patients with SARS, including 139 deaths, from Beijing city in early 2003. Main Outcomes and Measures Severity and mortality. Results Older age and high number of comorbidities were associated with higher severity and mortality in patients with both COVID-19 and SARS. The percentages of older age (≥65 years) were much higher in the deceased group than in the survived group in patients with both COVID-19 (83.8 vs. 13.2, P Conclusions and Relevance Older age and male gender are risk factors for worse outcome in patients with COVID. While men and women have the same susceptibility to both SARS-CoV-2 and SARS-CoV, men may be more prone to have higher severity and mortality independent of age and susceptibility. Key Points Question Are men more susceptible to getting and dying from COVID-19? Findings In the case series, men tend to be more serious than women. In the public data set, the percentage of men were higher in the deceased group than in the survived group, although age was comparable between men and women. Meaning Male gender is a risk factor for worse outcome in patients with COVID independent of age and susceptibility.

Cathepsin L plays a key role in SARS-CoV-2 infection in humans and humanized mice and is a promising target for new drug development.

Abstract: To discover new drugs to combat COVID-19, an understanding of the molecular basis of SARS-CoV-2 infection is urgently needed. Here, for the first time, we report the crucial role of cathepsin L (CTSL) in patients with COVID-19. The circulating level of CTSL was elevated after SARS-CoV-2 infection and was positively correlated with disease course and severity. Correspondingly, SARS-CoV-2 pseudovirus infection increased CTSL expression in human cells in vitro and human ACE2 transgenic mice in vivo, while CTSL overexpression, in turn, enhanced pseudovirus infection in human cells. CTSL functionally cleaved the SARS-CoV-2 spike protein and enhanced virus entry, as evidenced by CTSL overexpression and knockdown in vitro and application of CTSL inhibitor drugs in vivo. Furthermore, amantadine, a licensed anti-influenza drug, significantly inhibited CTSL activity after SARS-CoV-2 pseudovirus infection and prevented infection both in vitro and in vivo. Therefore, CTSL is a promising target for new anti-COVID-19 drug development.

Standards of Medical Care in Diabetes

Abstract: XI. STRATEGIES FOR IMPROVING DIABETES CARE D iabetes is a chronic illness that requires continuing medical care and patient self-management education to prevent acute complications and to reduce the risk of long-term complications. Diabetes care is complex and requires that many issues, beyond glycemic control, be addressed. A large body of evidence exists that supports a range of interventions to improve diabetes outcomes. These standards of care are intended to provide clinicians, patients, researchers, payors, and other interested individuals with the components of diabetes care, treatment goals, and tools to evaluate the quality of care. While individual preferences, comorbidities, and other patient factors may require modification of goals, targets that are desirable for most patients with diabetes are provided. These standards are not intended to preclude more extensive evaluation and management of the patient by other specialists as needed. For more detailed information, refer to Bode (Ed.): Medical Management of Type 1 Diabetes (1), Burant (Ed): Medical Management of Type 2 Diabetes (2), and Klingensmith (Ed): Intensive Diabetes Management (3). The recommendations included are diagnostic and therapeutic actions that are known or believed to favorably affect health outcomes of patients with diabetes. A grading system (Table 1), developed by the American Diabetes Association (ADA) and modeled after existing methods, was utilized to clarify and codify the evidence that forms the basis for the recommendations. The level of evidence that supports each recommendation is listed after each recommendation using the letters A, B, C, or E.

Natural Products as Sources of New Drugs over the Nearly Four Decades from 01/1981 to 09/2019.

Abstract: This review is an updated and expanded version of the five prior reviews that were published in this journal in 1997, 2003, 2007, 2012, and 2016. For all approved therapeutic agents, the time frame has been extended to cover the almost 39 years from the first of January 1981 to the 30th of September 2019 for all diseases worldwide and from ∼1946 (earliest so far identified) to the 30th of September 2019 for all approved antitumor drugs worldwide. As in earlier reviews, only the first approval of any drug is counted, irrespective of how many "biosimilars" or added approvals were subsequently identified. As in the 2012 and 2016 reviews, we have continued to utilize our secondary subdivision of a "natural product mimic", or "NM", to join the original primary divisions, and the designation "natural product botanical", or "NB", to cover those botanical "defined mixtures" now recognized as drug entities by the FDA (and similar organizations). From the data presented in this review, the utilization of natural products and/or synthetic variations using their novel structures, in order to discover and develop the final drug entity, is still alive and well. For example, in the area of cancer, over the time frame from 1946 to 1980, of the 75 small molecules, 40, or 53.3%, are N or ND. In the 1981 to date time frame the equivalent figures for the N* compounds of the 185 small molecules are 62, or 33.5%, though to these can be added the 58 S* and S*/NMs, bringing the figure to 64.9%. In other areas, the influence of natural product structures is quite marked with, as expected from prior information, the anti-infective area being dependent on natural products and their structures, though as can be seen in the review there are still disease areas (shown in Table 2) for which there are no drugs derived from natural products. Although combinatorial chemistry techniques have succeeded as methods of optimizing structures and have been used very successfully in the optimization of many recently approved agents, we are still able to identify only two de novo combinatorial compounds (one of which is a little speculative) approved as drugs in this 39-year time frame, though there is also one drug that was developed using the "fragment-binding methodology" and approved in 2012. We have also added a discussion of candidate drug entities currently in clinical trials as "warheads" and some very interesting preliminary reports on sources of novel antibiotics from Nature due to the absolute requirement for new agents to combat plasmid-borne resistance genes now in the general populace. We continue to draw the attention of readers to the recognition that a significant number of natural product drugs/leads are actually produced by microbes and/or microbial interactions with the "host from whence it was isolated"; thus we consider that this area of natural product research should be expanded significantly.

Post-acute COVID-19 syndrome.

Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen responsible for the coronavirus disease 2019 (COVID-19) pandemic, which has resulted in global healthcare crises and strained health resources. As the population of patients recovering from COVID-19 grows, it is paramount to establish an understanding of the healthcare issues surrounding them. COVID-19 is now recognized as a multi-organ disease with a broad spectrum of manifestations. Similarly to post-acute viral syndromes described in survivors of other virulent coronavirus epidemics, there are increasing reports of persistent and prolonged effects after acute COVID-19. Patient advocacy groups, many members of which identify themselves as long haulers, have helped contribute to the recognition of post-acute COVID-19, a syndrome characterized by persistent symptoms and/or delayed or long-term complications beyond 4 weeks from the onset of symptoms. Here, we provide a comprehensive review of the current literature on post-acute COVID-19, its pathophysiology and its organ-specific sequelae. Finally, we discuss relevant considerations for the multidisciplinary care of COVID-19 survivors and propose a framework for the identification of those at high risk for post-acute COVID-19 and their coordinated management through dedicated COVID-19 clinics.

Features, Evaluation and Treatment Coronavirus (COVID-19)

Abstract: According to the World Health Organization (WHO), viral diseases continue to emerge and represent a serious issue to public health In the last twenty years, several viral epidemics such as the severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002 to 2003, and H1N1 influenza in 2009, have been recorded Most recently, the Middle East respiratory syndrome coronavirus (MERS-CoV) was first identified in Saudi Arabia in 2012 In a timeline that reaches the present day, an epidemic of cases with unexplained low respiratory infections detected in Wuhan, the largest metropolitan area in China's Hubei province, was first reported to the WHO Country Office in China, on December 31, 2019 Published literature can trace the beginning of symptomatic individuals back to the beginning of December 2019 As they were unable to identify the causative agent, these first cases were classified as "pneumonia of unknown etiology " The Chinese Center for Disease Control and Prevention (CDC) and local CDCs organized an intensive outbreak investigation program The etiology of this illness is now attributed to a novel virus belonging to the coronavirus (CoV) family, COVID-19 On February 11, 2020, the WHO Director-General, Dr Tedros Adhanom Ghebreyesus, announced that the disease caused by this new CoV was a "COVID-19," which is the acronym of "coronavirus disease 2019" In the past twenty years, two additional coronavirus epidemics have occurred SARS-CoV provoked a large-scale epidemic beginning in China and involving two dozen countries with approximately 8000 cases and 800 deaths, and the MERS-CoV that began in Saudi Arabia and has approximately 2,500 cases and 800 deaths and still causes as sporadic cases This new virus seems to be very contagious and has quickly spread globally In a meeting on January 30, 2020, per the International Health Regulations (IHR, 2005), the outbreak was declared by the WHO a Public Health Emergency of International Concern (PHEIC) as it had spread to 18 countries with four countries reporting human-to-human transmission An additional landmark occurred on February 26, 2020, as the first case of the disease, not imported from China, was recorded in the United States Initially, the new virus was called 2019-nCoV Subsequently, the task of experts of the International Committee on Taxonomy of Viruses (ICTV) termed it the SARS-CoV-2 virus as it is very similar to the one that caused the SARS outbreak (SARS-CoVs) The CoVs have become the major pathogens of emerging respiratory disease outbreaks They are a large family of single-stranded RNA viruses (+ssRNA) that can be isolated in different animal species For reasons yet to be explained, these viruses can cross species barriers and can cause, in humans, illness ranging from the common cold to more severe diseases such as MERS and SARS Interestingly, these latter viruses have probably originated from bats and then moving into other mammalian hosts — the Himalayan palm civet for SARS-CoV, and the dromedary camel for MERS-CoV — before jumping to humans The dynamics of SARS-Cov-2 are currently unknown, but there is speculation that it also has an animal origin The potential for these viruses to grow to become a pandemic worldwide seems to be a serious public health risk Concerning COVID-19, the WHO raised the threat to the CoV epidemic to the "very high" level, on February 28, 2020 Probably, the effects of the epidemic caused by the new CoV has yet to emerge as the situation is quickly evolving World governments are at work to establish countermeasures to stem possible devastating effects Health organizations coordinate information flows and issues directives and guidelines to best mitigate the impact of the threat At the same time, scientists around the world work tirelessly, and information about the transmission mechanisms, the clinical spectrum of disease, new diagnostics, and prevention and therapeutic strategies are rapidly developing Many uncertainties remain with regard to both the virus-host interac ion and the evolution of the epidemic, with specific reference to the times when the epidemic will reach its peak At the moment, the therapeutic strategies to deal with the infection are only supportive, and prevention aimed at reducing transmission in the community is our best weapon Aggressive isolation measures in China have led to a progressive reduction of cases in the last few days In Italy, in geographic regions of the north of the peninsula, political and health authorities are making incredible efforts to contain a shock wave that is severely testing the health system In the midst of the crisis, the authors have chosen to use the "Statpearls" platform because, within the PubMed scenario, it represents a unique tool that may allow them to make updates in real-time The aim, therefore, is to collect information and scientific evidence and to provide an overview of the topic that will be continuously updated

Extrapulmonary manifestations of COVID-19.

Abstract: Although COVID-19 is most well known for causing substantial respiratory pathology, it can also result in several extrapulmonary manifestations. These conditions include thrombotic complications, myocardial dysfunction and arrhythmia, acute coronary syndromes, acute kidney injury, gastrointestinal symptoms, hepatocellular injury, hyperglycemia and ketosis, neurologic illnesses, ocular symptoms, and dermatologic complications. Given that ACE2, the entry receptor for the causative coronavirus SARS-CoV-2, is expressed in multiple extrapulmonary tissues, direct viral tissue damage is a plausible mechanism of injury. In addition, endothelial damage and thromboinflammation, dysregulation of immune responses, and maladaptation of ACE2-related pathways might all contribute to these extrapulmonary manifestations of COVID-19. Here we review the extrapulmonary organ-specific pathophysiology, presentations and management considerations for patients with COVID-19 to aid clinicians and scientists in recognizing and monitoring the spectrum of manifestations, and in developing research priorities and therapeutic strategies for all organ systems involved.