Objective:To evaluate the effect and causality of serum metabolites on the pathogenesis of ulcerative colitis (UC), so as to provide reference for nutritional programs for patients with UC.Methods:Two-sample Mendelian randomization (MR) analysis was performed to estimate the causal relationship between serum metabolites and UC. Genome-wide association studies (GWAS) of 1 400 metabolites were performed, with the metabolites as exposure and UC as outcome. Inverse-variance weighted (IVW) was used to calculate causal estimates. Four other MR methods with different modeling assumptions including MR-Egger, weighted median, weighted mode, and simple mode were used as additional analyses to improve the stability of the results. The results were validated through heterogeneity and pleiotropy tests. Finally, the possible causal metabolites were analyzed by metabolic pathway analysis.Results:MR analysis revealed that 85 metabolites had a possible causal relationship with UC. Among them, phosphatidylglycerol 1,2-dipalmitoyl-gpc (DPPC) ( P=2.75×10 -6) and isovaleryl carnitine (C5) ( P=1.84×10 -5) were significant risk factors for UC. Metabolic pathway analysis identified 5 metabolic pathways that might be affected by these metabolites (all P<0.05), among which the porphyrin ( P=0.004) and pyrimidine metabolic pathways ( P=0.008) had higher confidence in impacting UC. Conclusions:There are causal relationships between some serum metabolites (in particular 1,2-dipalmitoyl-GPC and isovalerylcarnitine) and the risk of UC. The porphyrin and pyrimidine metabolic pathways may impact the pathogenesis of UC.

Objective To investigate the association of Chinese visceral adiposity index(CVAI)and high-sensitivity C-reactive protein(hs-CRP)with the risk of digestive malignancies in the Kailuan study population,and to provide a basis for the prevention and control of digestive malignancies in the population.Methods A prospective cohort study was conducted,and a total of 94 377 Kailuan workers who participated in the 2006 health examination,had no history of cancer,and had complete data on CVAI,CRP,and related covariates were selected as the observation cohort.According to the levels of CVAI and CRP,the subjects were divided into low CVAI+CRP≤3 mg/L group[CVAI(-)CRP(-)group],low CVAI+CRP>3 mg/L group[CVAI(-)CRP(+)group],high CVAI+CRP≤3 mg/L group[CVAI(+)CRP(-)group],and high CVAI+CRP>3 mg/L group[CVAI(+)CRP(+)group].An analysis of variance was used for comparison of normally distributed continuous data between groups,and the non-parametric Kruskal-Wallis H test was used for comparison of continuous data with skewed distribution between groups;the chi-square test was used for comparison of categorical data between groups.The Cox proportional-hazards regression model was used to assess the impact of CVAI and CRP alone or in combination on the risk of digestive malignancies.Results There were significant differences between the four groups in age,male/female ratio,total cholesterol,triglycerides,high-density lipoprotein cholesterol,systolic blood pressure,diastolic blood pressure,fasting blood glucose,high-sensitivity C-reactive protein,waist circumference,body mass index,marital status,alcohol consumption,smoking,reported income,and physical exercise(all P<0.05).During a mean follow-up time of 14.08±2.76 years,2 043 new-onset cases of digestive malignancies were identified by the end of follow-up on December 31,2021.The Cox proportional-hazards regression model showed that after adjustment for CRP and other factors,compared with the low CVAI group,the high CVAI group had a hazard ratio(HR)of 1.34(95%confidence interval[CI]:1.23-1.47)for the risk of digestive malignancies.After adjustment for CVAI and other factors,compared with the CRP≤3 mg/L group,the CRP>3 mg/L group had an HR of 1.14(95%CI:1.02-1.28)for the risk of digestive malignancies.Compared with the CVAI(-)CRP(-)group(n=40 978),the CVAI(-)CRP(+)group(n=6 210),the CVAI(+)CRP(-)group(n=36 502),and the CVAI(+)CRP(+)group(n=10 687)had an HR of 1.05(95%CI:1.01-1.09,P<0.05),1.32(95%CI:1.20-1.45,P<0.05),and 1.48(95%CI:1.28-1.70,P<0.05),respectively,for the risk of digestive malignancies.As for digestive malignancies at specific locations,the CVAI(+)CRP(+)group had an increased risk of liver cancer,gastric cancer,pancreatic cancer,colorectal cancer,and small intestinal cancer with an HR of 1.35(95%CI:1.05-1.81,P<0.05),1.48(95%CI:1.09-2.00,P<0.05),1.60(95%CI:1.07-2.41,P<0.05),1.76(1.40-2.21,P<0.05),and 3.85(95%CI:1.43-10.33,P<0.05),respectively.Conclusion A high level of CVAI,a high level of CRP,and high levels of CVAI and CRP in combination can all increase the risk of digestive malignancies,among which the high levels of CVAI and CRP in combination may lead to a higher risk.

Objective To investigate the association of Chinese visceral adiposity index(CVAI)and high-sensitivity C-reactive protein(hs-CRP)with the risk of digestive malignancies in the Kailuan study population,and to provide a basis for the prevention and control of digestive malignancies in the population.Methods A prospective cohort study was conducted,and a total of 94 377 Kailuan workers who participated in the 2006 health examination,had no history of cancer,and had complete data on CVAI,CRP,and related covariates were selected as the observation cohort.According to the levels of CVAI and CRP,the subjects were divided into low CVAI+CRP≤3 mg/L group[CVAI(-)CRP(-)group],low CVAI+CRP>3 mg/L group[CVAI(-)CRP(+)group],high CVAI+CRP≤3 mg/L group[CVAI(+)CRP(-)group],and high CVAI+CRP>3 mg/L group[CVAI(+)CRP(+)group].An analysis of variance was used for comparison of normally distributed continuous data between groups,and the non-parametric Kruskal-Wallis H test was used for comparison of continuous data with skewed distribution between groups;the chi-square test was used for comparison of categorical data between groups.The Cox proportional-hazards regression model was used to assess the impact of CVAI and CRP alone or in combination on the risk of digestive malignancies.Results There were significant differences between the four groups in age,male/female ratio,total cholesterol,triglycerides,high-density lipoprotein cholesterol,systolic blood pressure,diastolic blood pressure,fasting blood glucose,high-sensitivity C-reactive protein,waist circumference,body mass index,marital status,alcohol consumption,smoking,reported income,and physical exercise(all P<0.05).During a mean follow-up time of 14.08±2.76 years,2 043 new-onset cases of digestive malignancies were identified by the end of follow-up on December 31,2021.The Cox proportional-hazards regression model showed that after adjustment for CRP and other factors,compared with the low CVAI group,the high CVAI group had a hazard ratio(HR)of 1.34(95%confidence interval[CI]:1.23-1.47)for the risk of digestive malignancies.After adjustment for CVAI and other factors,compared with the CRP≤3 mg/L group,the CRP>3 mg/L group had an HR of 1.14(95%CI:1.02-1.28)for the risk of digestive malignancies.Compared with the CVAI(-)CRP(-)group(n=40 978),the CVAI(-)CRP(+)group(n=6 210),the CVAI(+)CRP(-)group(n=36 502),and the CVAI(+)CRP(+)group(n=10 687)had an HR of 1.05(95%CI:1.01-1.09,P<0.05),1.32(95%CI:1.20-1.45,P<0.05),and 1.48(95%CI:1.28-1.70,P<0.05),respectively,for the risk of digestive malignancies.As for digestive malignancies at specific locations,the CVAI(+)CRP(+)group had an increased risk of liver cancer,gastric cancer,pancreatic cancer,colorectal cancer,and small intestinal cancer with an HR of 1.35(95%CI:1.05-1.81,P<0.05),1.48(95%CI:1.09-2.00,P<0.05),1.60(95%CI:1.07-2.41,P<0.05),1.76(1.40-2.21,P<0.05),and 3.85(95%CI:1.43-10.33,P<0.05),respectively.Conclusion A high level of CVAI,a high level of CRP,and high levels of CVAI and CRP in combination can all increase the risk of digestive malignancies,among which the high levels of CVAI and CRP in combination may lead to a higher risk.

Objective:To evaluate the effect and causality of serum metabolites on the pathogenesis of ulcerative colitis (UC), so as to provide reference for nutritional programs for patients with UC.Methods:Two-sample Mendelian randomization (MR) analysis was performed to estimate the causal relationship between serum metabolites and UC. Genome-wide association studies (GWAS) of 1 400 metabolites were performed, with the metabolites as exposure and UC as outcome. Inverse-variance weighted (IVW) was used to calculate causal estimates. Four other MR methods with different modeling assumptions including MR-Egger, weighted median, weighted mode, and simple mode were used as additional analyses to improve the stability of the results. The results were validated through heterogeneity and pleiotropy tests. Finally, the possible causal metabolites were analyzed by metabolic pathway analysis.Results:MR analysis revealed that 85 metabolites had a possible causal relationship with UC. Among them, phosphatidylglycerol 1,2-dipalmitoyl-gpc (DPPC) ( P=2.75×10 -6) and isovaleryl carnitine (C5) ( P=1.84×10 -5) were significant risk factors for UC. Metabolic pathway analysis identified 5 metabolic pathways that might be affected by these metabolites (all P<0.05), among which the porphyrin ( P=0.004) and pyrimidine metabolic pathways ( P=0.008) had higher confidence in impacting UC. Conclusions:There are causal relationships between some serum metabolites (in particular 1,2-dipalmitoyl-GPC and isovalerylcarnitine) and the risk of UC. The porphyrin and pyrimidine metabolic pathways may impact the pathogenesis of UC.

Objective:To investigate the role of survivin in the regulation of leptin expression and its sensitivity.Methods:Survivin was overexpressed in adipocytes via lentivirus, and the RNA-sequencing(RNA-seq) was used to explore the effect of survivin on the regulation of adipocyte secretory proteins. Survivin was overexpressed in the inguinal adipose tissue(iWAT) of mice by targeted injection of adeno-associated virus(AAV). The transcription levels of leptin and adiponectin were detected by realtime quantitative PCR(RT-qPCR), and the secretion levels of leptin and adiponectin in cellular supernatants and mice serum were detected by enzyme-linked immunosorbent assay(ELISA). The protein level of phosphorylated signal transducer and activator of transcription 3(STAT3) in hypothalamus was detected by Western blotting to investigate the effect of survivin on central leptin sensitivity.Results:Survivin overexpression in both 3T3-L1 and primary white adipocyte significantly down-regulated the leptin transcriptional expression without affecting the adipocyte differentiation( P<0.01). Overexpression of survivin significantly decreased leptin level without affecting the adiponectin levels in the cellular supernatant( P<0.001). Overexpression of survivin in iWAT via AAV injection, not only specifically down-regulated leptin transcriptional level in a dose dependent manner in local adipose tissue, but also led to a decrease in serum leptin level( P<0.05). In mice fed short-term high-fat diet, STAT3 phosphorylation level in hypothalamus significantly increased, suggesting improved central leptin sensitivity. Conclusion:Survivin could downregulate leptin expression and improve leptin sensitivity in high-fat diet induced obese mice.

In 2009,the World Health Organization included snakebite on the list of neglected tropical diseases,acknowledging it as a common occupational hazard for farmers,plantation workers,and others,causing tens of thousands of deaths and chronic physical disabilities every year.This guideline aims to provide practical information to help clinical professionals evaluate and treat snakebite victims.These recommendations are based on clinical experience and clinical research evidence.This guideline focuses on the following topics:snake venom,clinical manifestations,auxiliary examination,diagnosis,treatments,and prevention.

Network Meta-analysis was used to compare the efficacy and safety of Chinese patent medicines in the treatment of unstable angina pectoris. PubMed, Cochrane Library, CNKI, Wanfang, VIP and other databases were retrieved by computers from the establishment of the databases to June 2020. Randomized controlled trials(RCTs) of Chinese patent medicines for the treatment of unstable angina pectoris were collected. Two investigators independently screened out the literatures, and extracted data according to the inclusion and exclusion criteria. The quality of the included RCTs was evaluated according to the bias risk assessment tool recommended by the Cochrane System Reviewer Manual, and the Stata 13.0 software was used for data analysis and mapping. Through screening, 28 eligible studies were finally included, with the sample size of 2 885 cases, involving 8 Chinese patent medicines. The results of the network Meta-analysis showed that in terms of total effective rate for angina symptom improvement, the order was as follows: Shenshao Capsules > Naoxintong Capsules > Ginkgo Ketone Ester Dripping Pills > Compound Danshen Dripping Pills > Ginkgo Leaf Tablets > Shexiang Baoxin Pills > Tongxinluo Capsules > Yindan Xinnaotong Soft Capsules; in terms of total effective rate for ECG curative effect, the order was as follows: Ginkgo Ketone Ester Dripping Pills>Compound Danshen Dripping Pills > Tongxinluo Capsules > Shenshao Capsules > Shexiang Baoxin Pills > Yindan Xinnaotong Soft Capsules; in terms of hypersensitivity-C-reactive protein curative effect, the order was as follows: Tongxinluo Capsules > Shenshao Capsules > Ginkgo Leaf Tablets>Compound Danshen Dropping Pills> Shexiang Baoxin Pills > Naoxintong Capsules > Yindan Xinnaotong Soft Capsules > Ginkgo Ketone Ester Dropping Pills. Chinese patent medicine combined with conventional therapy can improve the clinical efficacy of unstable angina pectoris. Due to the differences in the quantity and quality of the included studies, the order results of Chinese patent medicines need to be further verified.
Angina, Unstable/drug therapy* ; China ; Drugs, Chinese Herbal ; Humans ; Medicine, East Asian Traditional ; Network Meta-Analysis ; Nonprescription Drugs

Objective To establish the key question list for the development of evidencebased guideline in China according to the content and limitation of current evidence-based guidelines around the world.Methods First,we introduced the evidence-based guidelines in detail which met the criteria based on World Health Organization guideline development handbook and then formulated the draft list of key questions for the development of evidence-based guidelines.At last,the Delphi method was used to determine the list of key questions in developing evidence-based guidelines of colorectal cancer screening.Results Totally,34 questionnaires were collected,with experts from clinical and epidemiological fields.The average experts' authority coefficient was 0.81,indicating a high degree of authority.The concentration of opinions on all items in the questionnaire was relatively high,with the full score ratio greater than 75％ and the coefficient of variation less than 0.3.The list of key questions on evidence-based guidelines for colorectal cancer screening has been divided into six parts:epidemiological problems,risk classification,screening age,screening tools,implementation and selection of steering group members,which covers the issues that need to be considered in the development of evidence-based colorectal cancer screening guidelines in China.Conclusion The key question list for evidence-based guideline development in our study can be applied to the development of evidence-based guidelines for colorectal cancer screening in the future,as well as the development of evidence-based guidelines for other cancer screening in China.

Objective: To determine the hemoglobin level and blood pressure and the factors that influence their recovery in relocated workers who were unfit for duties at high altitude. Methods: The physical examination data of 693 relocated workers who previously worked at high altitude were dynamically monitored from January 2006 to June 2015 in order to examine the recovery of hemoglobin level and blood pressure. Results: The rate of hemoglobin recovery was 81.37% among the 161 relocated workers with abnormal hemoglobin levels, and the rate of blood pressure recovery was 69.51% among the 164 relocated workers with abnormal blood pressure. The rates of hemoglobin and blood pressure recovery were decreased in individuals aged 40 years and older. The peak recovery time of hemoglobin was 11-15 months following relocation, and that of blood pressure was 5-7 months and 11-13 months following relocation. The half-year blood pressure recovery rate and 2-year hemoglobin recovery rate following relocation were significantly higher in workers who worked at 2500-3000 m altitude than in those at ≥3000 m (P<0.05) . Total cholesterol and educational level were factors that influence the half-year blood pressure recovery in relocated workers (P<0.05) . Conclusion The rate of hemoglobin and blood pressure recovery are high among relocated workers who previously worked at high altitude. Factors that influence blood pressure, such as total cholesterol, should be closely monitored so that high-altitude workers with abnormal blood pressure and hemoglobin level can be relocated as early as possible.

Amiloride ; analogs & derivatives ; chemistry ; metabolism ; Binding Sites ; Genotype ; Hepacivirus ; genetics ; metabolism ; Humans ; Magnetic Resonance Spectroscopy ; Molecular Dynamics Simulation ; Protein Structure, Tertiary ; Viral Proteins ; antagonists & inhibitors ; metabolism