Summary Background Hand, foot, and mouth disease is a common childhood illness caused by enteroviruses. Increasingly, the disease has a substantial burden throughout east and southeast Asia. To better inform vaccine and other interventions, we characterised the epidemiology of hand, foot, and mouth disease in China on the basis of enhanced surveillance. Methods We extracted epidemiological, clinical, and laboratory data from cases of hand, foot, and mouth disease reported to the Chinese Center for Disease Control and Prevention between Jan 1, 2008, and Dec 31, 2012. We then compiled climatic, geographical, and demographic information. All analyses were stratified by age, disease severity, laboratory confirmation status, and enterovirus serotype. Findings The surveillance registry included 7 200 092 probable cases of hand, foot, and mouth disease (annual incidence, 1·2 per 1000 person-years from 2010–12), of which 267 942 (3·7%) were laboratory confirmed and 2457 (0·03%) were fatal. Incidence and mortality were highest in children aged 12–23 months (38·2 cases per 1000 person-years and 1·5 deaths per 100 000 person-years in 2012). Median duration from onset to diagnosis was 1·5 days (IQR 0·5–2·5) and median duration from onset to death was 3·5 days (2·5–4·5). The absolute number of patients with cardiopulmonary or neurological complications was 82  486 (case-severity rate 1·1%), and 2457 of 82486 patients with severe disease died (fatality rate 3·0%); 1617 of 1737 laboratory confirmed deaths (93%) were associated with enterovirus 71. Every year in June, hand, foot, and mouth disease peaked in north China, whereas southern China had semiannual outbreaks in May and September–October. Geographical differences in seasonal patterns were weakly associated with climate and demographic factors (variance explained 8–23% and 3–19%, respectively). Interpretation This is the largest population-based study up to now of the epidemiology of hand, foot, and mouth disease. Future mitigation policies should take into account the heterogeneities of disease burden identified. Additional epidemiological and serological studies are warranted to elucidate the dynamics and immunity patterns of local hand, foot, and mouth disease and to optimise interventions. Funding China–US Collaborative Program on Emerging and Re-emerging Infectious Diseases, WHO, The Li Ka Shing Oxford Global Health Programme and Wellcome Trust, Harvard Center for Communicable Disease Dynamics, and Health and Medical Research Fund, Government of Hong Kong Special Administrative Region.

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Hand, foot, and mouth disease in China, 2008–12: an epidemiological study

Hand, foot and mouth disease (HFMD), a common contagious disease that usually affects children, is normally mild but can have life-threatening manifestations. It can be caused by enteroviruses, particularly Coxsackieviruses and human enterovirus 71 (HEV71) with highly variable clinical manifestations. In the spring of 2008, a large, unprecedented HFMD outbreak in Fuyang city of Anhui province in the central part of southeastern China resulted in a high aggregation of fatal cases. In this study, epidemiologic and clinical investigations, laboratory testing, and genetic analyses were performed to identify the causal pathogen of the outbreak. Of the 6,049 cases reported between 1 March and 9 May of 2008, 3023 (50%) were hospitalized, 353 (5.8%) were severe and 22 (0.36%) were fatal. HEV71 was confirmed as the etiological pathogen of the outbreak. Phylogenetic analyses of entire VP1 capsid protein sequence of 45 Fuyang HEV71 isolates showed that they belong to C4a cluster of the C4 subgenotype. In addition, genetic recombinations were found in the 3D region (RNA-dependent RNA polymerase, a major component of the viral replication complex of the genome) between the Fuyang HEV71 strain and Coxsackievirus A16 (CV-A16), resulting in a recombination virus. In conclusion, an emerging recombinant HEV71 was responsible for the HFMD outbreak in Fuyang City of China, 2008.

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An emerging recombinant human enterovirus 71 responsible for the 2008 outbreak of hand foot and mouth disease in Fuyang city of China.

Background Enterovirus 71 (EV71) is a major cause of hand, foot, and mouth disease in children and may be fatal. A vaccine against EV71 is needed. Methods We conducted a randomized, double-blind, placebo-controlled phase 3 trial involving healthy children 6 to 71 months of age in Guangxi Zhuang Autonomous Region, China. Two doses of an inactivated EV71 vaccine or placebo were administered intramuscularly, with a 4-week interval between doses, and children were monitored for up to 11 months. The primary end point was protection against hand, foot, and mouth disease caused by EV71. Results A total of 12,000 children were randomly assigned to receive vaccine or placebo. Serum neutralizing antibodies were assessed in 549 children who received the vaccine. The seroconversion rate was 100% 4 weeks after the two vaccinations, with a geometric mean titer of 170.6. Over the course of two epidemic seasons, the vaccine efficacy was 97.4% (95% confidence interval [CI], 92.9 to 99.0) according to the intention-to-trea...

https://www.nejm.org/doi/pdf/10.1056/NEJMoa1303224

An Inactivated Enterovirus 71 Vaccine in Healthy Children

We investigated an outbreak of severe fever with thrombocytopenia syndrome (SFTS) that occurred during May and June 2010, to identify the mode of transmission. Contact with the index patient's blood was significantly associated with development of SFTS (P = .01, by the χ(2) test for linear trend); the frequency of contact with the index patient's blood increased the risk of SFTS in a dose-response manner (P = .03, by the χ(2) test for linear trend). We concluded that human-to-human transmission caused this cluster of cases.

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Human-to-Human Transmission of Severe Fever With Thrombocytopenia Syndrome Bunyavirus Through Contact With Infectious Blood

Background Glucocorticoids increase the risk of developing critical disease from viral infections. However, primary care practitioners in China use them as antipyretics, potentially exposing hundreds of millions to this risk. Methods We enrolled all patients with confirmed pandemic influenza A (pH1N1) virus infection aged ≥3 years with available medical records at 4 Shenyang City hospitals from 20 October to 30 November 2009. A critical patient was any confirmed, hospitalized pH1N1 patient who developed ≥1 of the following: death, respiratory failure, septic shock, failure or insufficiency of ≥2 nonpulmonary organs, mechanical ventilation, or ICU admission. In a retrospective cohort study, we evaluated the risk of developing critical illness in relation to early (≤72 hours of influenza-like illness [ILI] onset) glucocorticoids treatment. Results Of the 83 hospitalized case-patients, 46% developed critical illness, 17% died, and 37% recovered and were discharged. Critically ill and other patients did not differ by underlying conditions and severity, median temperature at first clinic visit, and other measured risk factors. Of 17 patients who received early glucocorticoid treatment, 71% subsequently developed critical disease compared with 39% of 66 patients who received late (>72 hours) or no glucocorticoid treatment (RR(M-H) = 1.8, 95% CI = 1.2-2.8, after adjusting for 2 summary variables; ie, presence of underlying diseases and presence of underlying risk factors). Proportional hazards modeling showed that use of glucocorticoids tripled the hazard of developing critical disease (hazard ratio [HR] = 2.9, 95% CI = 1.3-6.2, after adjusting for the same summary variables). Conclusions Early use of parenteral glucocorticoids therapy for fever reduction and pneumonia prevention increases the risk for critical disease or death from pH1N1 infection. We recommend that guidelines on glucocorticoid use be established and enforced.

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Early Use of Glucocorticoids Was a Risk Factor for Critical Disease and Death From pH1N1 Infection

BACKGROUND Human enterovirus 71 (HEV71) causes outbreaks of life-threatening diseases throughout the world. The genesis of these severe diseases is unknown. METHODS During an outbreak of HEV71 infection, we investigated risk factors for critical illness. We developed a modified pediatric index of mortality (mPIM) incorporating heart rate, temperature, white blood cell count, respiratory rate, chest infiltrates, skin color, reflexes, responsiveness, and mobility. We calculated the mPIM for 103 patients (22 deaths) using complete scoring criteria in the medical record. In a case-control study, we compared cases (mPIM > or =10 or death) with controls (mPIM = 0-9) by drugs received within 96 hours after onset of fever, initial temperature, age, and nutritional anthropometry. RESULTS About 66% (68/103) of the patients with an mPIM score (28 cases and 40 controls) had data on initial exposures. About 50% of the 28 cases and 18% of the 40 controls received an injection to treat fever during the first 96 hours after onset (Odds ratio [OR] = 7.0, 95% confidence interval [CI]: 1.8-28). Injections containing exclusively glucocorticoids (OR = 4.8, 95% CI: 1.2-21) or pyrazolones (OR = 4.1, 95% CI: 0.91-19, P = 0.047) were risk factors for severe HEV71 infection. About 25% of cases and 5% of controls received both drugs parenterally while 7% of cases and 30% of controls received neither (OR = 21, 95% CI: 1.8-305). Conversely, cases and controls had identical average initial temperature, and did not differ significantly by age, sex, nutritional measurements, use of other drugs, or timeliness of medical care received. CONCLUSION Fever treatment with glucocorticoids and/or pyrazolones is a risk factor for life-threatening HEV71 infection.

Glucocorticoid and pyrazolone treatment of acute fever is a risk factor for critical and life-threatening human enterovirus 71 infection during an outbreak in China, 2008.

Network pharmacology was rapidly developed based on multidisciplinary holistic analysis of biological systems, which has become a popular tool in traditional Chinese medicine (TCM) research in recent years. Its characteristics of integrity and systematization provide a new approach for the study on complex TCM systems, which has many similarities with the holistic concept of TCM. It has been widely used to explain the mechanism of TCM treatment of diseases, drug repositioning, and interpretation of compatibility of TCM prescriptions, to promote the modernization of TCM. The use of TCM have provided crucial support on prevention and treatment of diseases such as the famous “three medicines and three prescriptions”. Furthermore, TCM has become an important part of the treatment of COVID-19 and is one of the main contents of the “Chinese plan” to fight the epidemic. The current review demonstrated the role of TCM in treating diseases with multiple components, multiple targets, and multiple pathways, interprets the connotation of TCM treatment method selection based on pathogenesis and also discusses the application of network pharmacology in the study of COVID-19 treatment in TCM including single drug and prescription. However, there are still some shortcomings such as the lack of experimental verification and regular upgrading of the TCM pharmacology network. Therefore, we must pay attention to the characteristics of TCM and develop a network pharmacology method suitable for TCM system research when applying network pharmacology to TCM research.

Application of network pharmacology in the study of the mechanism of action of traditional chinese medicine in the treatment of COVID-19

Network pharmacology is a research method based on a multidisciplinary holistic analysis of biological systems, which coincides with the idea of the holistic view of traditional Chinese medicine. In this review, we summarized the use of network pharmacology technology through studying Chinese medicine single medicine or Chinese medicine compound research ideas and methods for the treatment of ulcerative colitis, based on the application of the current network pharmacology in Chinese medicine research, including the important role in the mechanism of the prediction and verification, to search for new ideas for disease diagnosis and treatment, this study summarizes the application of network pharmacology in the treatment of ulcerative colitis in traditional Chinese medicine, including monotherapy and compound therapy, and considers that relevant research studies have fully demonstrated the function characteristics of the multi-component, multi-target, and multi-pathway of traditional Chinese medicine, and can also explain the connotation of “selecting appropriate treatment methods according to the differences and similarities of pathogenesis” of traditional Chinese medicine. Finally, we raised important questions about the prospects and limitations of network pharmacology, such as differences caused by different data collection methods, a considerable lag, and so on.

Application of network pharmacology in the study of mechanism of Chinese medicine in the treatment of ulcerative colitis: A review

Ulcerative colitis (UC) is a common clinical inflammatory bowel disease characterized by repeated attacks, difficult treatment, and great harm to the physical and mental health of the patients. The occurrence and development of UC were closely related to the physiological and pathological processes, such as intestinal inflammatory reaction, oxidizing reaction, and immune response. Treatment of ulcerative colitis using Western medicine is often associated with a number of limitations and adverse events. There is a long history of using traditional Chinese medicine in dealing with this medical condition. Commonly used traditional Chinese medicines for the treatment of UC include Caulis Sargentodoxae, Flos Lonicerae, Fructus Cnidii, etc. Additionally, classic prescriptions such as Gegen Qinlian Formulae and Zuojin Pills can also be used to treat UC. To enrich the traditional Chinese medicine theory, the cognitive theory and perspective of network pharmacology and bioinformatics research of cell signal transduction mechanism of UC are emerging rapidly. Modern pharmacological studies focus on underlying mechanisms for the management of UC with Chinese medicine monomers, single Chinese medicines, and traditional Chinese medicine formulations, alleviating the symptoms of UC, controlling the development of intestinal inflammation, and restoring intestinal function through the regulation of key molecular signaling pathways, including PI3K/Akt, NF-[Formula: see text]B, JAK/STAT, MAPK and Notch. By summarizing current research progressions, this review provides key references for the in-depth exploration of the mechanisms focused on signaling pathways for the clinical management of UC using traditional Chinese medicine.

Chinese Medicine in the Treatment of Ulcerative Colitis: The Mechanisms of Signaling Pathway Regulations.

Determining the prognosis of gastric cancer is the most crucial step in the treatment process. Cytokeratins are intermediate filaments found in the intracellular structure of epithelial tissues. Recent researches have focused on determining the relationship between the expression of cytokeratins and the degree and prognosis of tumors. This study aimed to investigate the relationship between the incidence of cytokeratin-20 and cytokeratin-7 in patients with gastric carcinoma with factors influencing the prognosis. In this regard, the study was conducted cross-sectional. The expression of cytokeratin-20 and cytokeratin-7 was evaluated on 50 gastric adenocarcinoma specimens with different degrees of differentiation by the immunohistochemical method. We determined the relationship between the incidence of cytokeratin-20 and cytokeratin-7 with factors affecting the prognosis of patients, including the degree of differentiation of gastric cancer tissue, lymph node involvement, and the depth of tumor invasion. Data were statistically analyzed by Chi-square and Spearman tests. The results showed a statistically inverse relationship between the incidence of cytokeratin-20 and cytokeratin-7 with the degree of tissue differentiation and lymph node involvement in gastric cancer. Although there was a statistically significant relationship between the incidence of tissue invasion in gastric cancer and the incidence of cytokeratin-7, there was no association between the incidence of cytokeratin-20 and tissue invasion. In general, decreased cytokeratin-20 and cytokeratin-7 are associated with decreased tissue differentiation and increased lymph node involvement.

QiQuan Liu

Papers

Glucocorticoid and pyrazolone treatment of acute fever is a risk factor for critical and life-threatening human enterovirus 71 infection during an outbreak in China, 2008.

Application of network pharmacology in the study of the mechanism of action of traditional chinese medicine in the treatment of COVID-19

Application of network pharmacology in the study of mechanism of Chinese medicine in the treatment of ulcerative colitis: A review

Chinese Medicine in the Treatment of Ulcerative Colitis: The Mechanisms of Signaling Pathway Regulations.

Determining the relationship between cytokeratin expression and prognostic factors in human gastric cancer.