BACKGROUND: To date, results on relationship between CYP3A4 gene polymorphism were limited and inconclusive, and no study focused on the influence of CYP3A4 gene-obesity interaction on breast cancer risk, especially in Chinese women. The purpose of this study was to evaluate the impact of four single nucleotide polymorphisms (SNPs) of CYP3A4 gene, the SNP-SNP and gene-environment interactions on the susceptibility to breast cancer in Chinese women. METHODS: Logistic regression was used to explore the relationship between four SNPs of CYP3A4 gene and the risk of breast cancer. Generalized multifactor dimensionality reduction (GMDR) was used to screen the best SNP-SNP and gene-abdominal obesity interaction combinations among four SNPs and abdominal obesity. Haplotype examination among 4 SNPs was conducted using the SHEsis web-based platform. RESULTS: Logistic regression analysis showed that carriers of rs2242480- T allele have significantly higher breast cancer risk, than those with rs2242480- CC genotype, adjusted OR (95%CI) was 1.68 (1.23-2.16) and 2.03 (1.53-2.58) for participants with CT genotype and TT genotype under additive model. We did not find any notable interactions between the four SNPs within the CYP3A4 gene. GMDR model found a significant association in a two-locus model involving rs2242480 and obesity, with a p-value of 0.018. Stratified analysis found that breast cancer risk was the highest in obese participants with rs2242480- CT or TT genotype, compared to those non-obese participants with rs2242480- CC genotype, OR (95%CI) was 3.02 (1.83-4.25). We found that all haplotype combinations were not correlated with breast cancer risk. CONCLUSIONS We found that the T allele of rs2242480 within the CYP3A4 gene and interaction between rs2242480 and obesity were associated with an increased risk of breast cancer. However, the results of this study were only applicable to the Han ethnic group and cannot be generalized to other ethnic groups in China, and more SNPs of CYP3A4 gene should been enrolled in the analysis in the future, to verify the results obtained in this study.
Adult ; Aged ; Female ; Humans ; Middle Aged ; Breast Neoplasms/etiology* ; China/epidemiology* ; Cytochrome P-450 CYP3A/metabolism* ; Gene-Environment Interaction ; Genetic Predisposition to Disease ; Haplotypes ; Obesity/epidemiology* ; Polymorphism, Single Nucleotide ; Risk Factors ; East Asian People

Postoperative stress symptoms are caused by surgical trauma,and now still lack active intervention methods to promote the recovery of body function in the field of western medicine.Professor Cai Bingqin analyzed the etiology and pathogenesis of stress symptoms after abdominal surgery,which usually manifested as abnormal sweating,sleep disorders,emotional disorders,and gastrointestinal dysfunction,and then put forward the concept of postoperative stress syndrome for the perioperative period.Professor Cai Bingqin believes that surgical stimulation,as the important etiological factor responsible for postoperative stress symptoms,can cause excessive stress in the body,which results in a series of symptoms affecting the recovery of patients.Liver plays a defensive and adaptive role in postoperative stress by regulating qi movement,blood circulation and emotions.The symptoms of abnormal sweating,sleep disorders and emotional disorders are related with the function of the liver in governing emotions,housing the ethereal soul,and ensuring the free movement of qi,while the gastrointestinal dysfunction manifestations of poor appetite,abdominal distention and constipation are due to the disharmony of liver and spleen.For the treatment of postoperative stress syndrome,Professor Cai proposes the principle of treating disease from the perspective of liver,and the methods of soothing liver and alleviating depression,and warming and activating qi movement are adopted.Sini San(Sini Powder for Soothing Liver and Regulating Qi)is commonly used as the basic prescription to ensure the normal function of liver and to ensure the free movement of qi,and then the harmony of qi and blood and the unobstruction of blood vessels will be achieved.Additionally,the assistance of therapy for invigorating spleen to dissolve dampness,and replenishing qi to consolidate superficies can adjust zang-fu organs'dysfunction,and will restore the balance of qi-blood and yin-yang.The proposal of"postoperative stress syndrome"will provide an approach to the management of perioperative period with traditional Chinese medicine,and will become the beneficial supplement to the existing fast-track surgery system.

Objective:To examine the burden and trends of acute viral hepatitis in Guangdong Province from 1990 to 2019, and provide reference evidences for hepatitis prevention and control in the province.Methods:Data on acute viral hepatitis (hepatitis A, B, C, and E) in Guangdong from 1990 to 2019 were extracted from the Global Burden of Disease Study 2019 database. The incidence, prevalence, mortality, and disability-adjusted life years (DALY) data were analyzed by age and gender, and the estimated annual percentage change (EAPC) was calculated to describe the changing trends in disease burden.Results:From 1999 to 2019, the standardized incidence, prevalence, mortality, and DALY of acute viral hepatitis in Guangdong were higher than the national averages. In 2019, 51.43% (2 245 087/4 365 221) of acute viral hepatitis cases in Guangdong Province were mainly attributed to hepatitis B, and 77.18% (106/138) of deaths were due to acute hepatitis B. In different age groups, except for acute hepatitis B, which was more common in adults, the incidence rates of other types of viral hepatitis such as hepatitis A, B, and E showed an overall decreasing trend with age. The mortality rates of different types of acute viral hepatitis, except for the <5 age group, increased with age. The overall incidence and mortality rates of acute viral hepatitis were higher in men than in women.Conclusions:The overall burden of acute viral hepatitis in Guangdong declined in 2019, but remained higher than the national level. Further efforts are needed to strengthen hepatitis prevention and screening in different population in Guangdong Province, especially in children and the elderly.

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Hepatocellular carcinoma(HCC)and biliary tract cancer(BTC)are significant health challenges in China because of their high prevalence and mortality rates.Advances in molecular diagnostics have opened new avenues for personalized treatment strategies.This consensus provides a comprehensive update on the clinical applications of molecular diagnostics in HCC and BTC and addresses the urgent need for personalized treatment strategies tailored to the Chinese population,emphasizing the importance of molecular markers in guiding targeted therapies and immunotherapies.By employing the Delphi method and the Grading of Recommendations Assessment,Development,and Evaluation system,the expert panel formulated evidence-based recommendations for the use of molecular diagnostics in the clinical management of HCC and BTC.Key molecular markers,such as isocitrate dehydrogenase(IDH)1 and 2,fibroblast growth factor receptor 2(FGFR2),BRAF V600E,human epidermal growth factor receptor 2(HER2),rearranged during transfection(RET),and neurotrophic tyrosine receptor kinase(NTRK),are highlighted for their roles in optimizing treatment regimens.The consensus also explores the signifi-cance of emerging biomarkers,such as tumor mutation burden and microsatellite instability,in pre-dicting responses to immune checkpoint inhibitors.The recommendations aim to enhance precision medicine approaches,improve patient outcomes,and foster the integration of molecular diagnostics into routine clinical practice.

T cell immunoglobulin and mucin domain-containing protein 3(Tim-3)is a member of the Tim family,which is widely expressed on the surface of various cells and can be involved in the occurrence and development of diseases such as autoimmune,infection and cancer.Clinical trials have found that a combination of blocking Tim-3 and programmed cell death 1(PD-1)can improve the anti-cancer immune response and regression of tumors in patients with advanced cancer.This arti-cle reviewed the basic biological structure of Tim-3,corresponding ligand and its role in tumor micro-environment,and summarized the ongoing clinical trials of TIM-3.These data suggested that Tim-3 could be used as a potentially significant checkpoint receptor for future anti-tumor therapy,and sum-marized the ongoing clinical trials of drugs,indicating that Tim-3 can be used as a potential check-point receptor for future anti-tumor therapy.

T cell immunoglobulin and mucin domain-containing protein 3(Tim-3)is a member of the Tim family,which is widely expressed on the surface of various cells and can be involved in the occurrence and development of diseases such as autoimmune,infection and cancer.Clinical trials have found that a combination of blocking Tim-3 and programmed cell death 1(PD-1)can improve the anti-cancer immune response and regression of tumors in patients with advanced cancer.This arti-cle reviewed the basic biological structure of Tim-3,corresponding ligand and its role in tumor micro-environment,and summarized the ongoing clinical trials of TIM-3.These data suggested that Tim-3 could be used as a potentially significant checkpoint receptor for future anti-tumor therapy,and sum-marized the ongoing clinical trials of drugs,indicating that Tim-3 can be used as a potential check-point receptor for future anti-tumor therapy.

Objective:To investigate the predictive value of preoperative lymphocyte-to-monocyte ratio (LMR) combined with platelet-to-lymphocyte ratio (PLR) (LMR-PLR) scoring model for prognosis of pancreatic ductal adenocarcinoma (PDAC) after radical resection.Methods:The retrospective cohort study was conducted. The clinicopathological data of 116 patients with PDAC who were admitted to the Second Hospital of Lanzhou University from January 2015 to December 2019 were collected. There were 73 males and 43 females, aged 61.5(range, 29.0-75.0)years. All patients underwent radical resection for PDAC. Observation indicators: (1) optimal cut-off value of LMR and PLR; (2) clinicopathological features of patients with different scores of preoperative LMR-PLR scoring model; (3) follow-up and survival; (4) influencing factors for prognosis of PDAC patients; (5) construction and verification of nomogram prediction model. Measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data was conducted using the Mann-Whitney U test. The Graphpad prism 8 was used to draw survival curve, the Kaplan-Meier method was used to calculate survival rate, and the Log-Rank test was used for survival analysis. The COX proportional hazard regression model was used for univariate and multivariate analyses. The X-tile software was used to determine the optimal cut-off values of LMR and PLR. The nomogram prediction model was conducted based on the results of multivariate analysis, and the receiver operating characteristic (ROC) curve was drawn. The area under curve (AUC) was used to evaluate the discrimination of nomogram prediction model. The calibration curve was used to evaluate the consistency of nomogram prediction model and the decision curve was used to evaluate the clinical benefits. Results:(1) Optimal cut-off value of LMR and PLR. The optimal cut-off values of LMR and PLR were 1.9 and 156.3. (2) Clinicopathological features of patients with different scores of preoperative LMR-PLR scoring model. Cases with LMR-PLR scoring as 0, 1, 2 were 11, 42, 63. Cases with CA125 <12.4 U/mL, cases postoperative with vascular invasion, cases with postoperative chemotherapy in patients with 0, 1, 2 of LMR-PLR scoring were 1, 8, 24, 9, 27, 27, 3, 26, 43, showing significant differences among them ( χ2=6.73, 8.37, 6.68, P<0.05). (3) Follow-up and survival. All 116 patients were followed up for 39(range, 2-86)months. The 1-, 2-, 3-year survival rate of 116 PDAC patients was 50.9%, 37.9%, 19.3%, respectively, with a survival time of 13(range, 1-85)months. The survival time of patients with LMR-PLR scoring as 0, 1, 2 was 3(range, 1-9)months, 7(range, 2-56)months, 26(range, 2-85)months, respectively, showing a significant difference among them ( χ2=48.78, P<0.05). (4) Influencing factors for prognosis of PDAC patients. Results of multivariate analysis showed that carcinoembryonic antigen (CEA), CA19-9, LMR-PLR score, tumor diameter were independent factors affecting prognosis of patients ( hazard ratio=1.61, 1.88, 0.27, 1.87, 95% confidence interval as 1.02-2.54, 1.18-3.00, 0.19-0.39, 1.13-3.09, P<0.05). (5) Construction and verification of nomogram prediction model. The nomogram prediction model was constructed based on CEA, CA19-9, LMR-PLR score and tumor diameter. The AUC of ROC curve in predicting 1-, 2-, 3-year survival rate of patients was 0.86 (95% confidence interval as 0.79-0.93, P<0.05), 0.86 (95% confidence interval as 0.79-0.92, P<0.05), 0.87 (95% confidence interval as 0.78-0.95, P<0.05), respectively. Results of calibration curve showed that the predicted survival rate of nomogram prediction model was consistent with the actual survival rate, with the consistency index as 0.74. Results of decision curve showed that the predictive performance of nomogram prediction model was superior to that of a single factor at a risk threshold of 0.12-0.85. Conclusions:CEA, CA19-9, LMR-PLR score, tumor diameter are independent factors affecting prognosis of patients undergoing radical resection for PDAC, and the nomogram prediction model can predict postoperative survival rate. The predicted survival rate of nomogram prediction model is consistent with the actual survival rate, and the predictive performance of nomogram prediction model is superior to that of a single factor at a risk threshold of 0.12-0.85.

Objective:To analyze the specific reasons for journal articles being retracted due to biomedical research-related ethical issues after publication and propose corresponding preventive measures.Methods:Journal articles that were retracted between January 1, 2021, and January 1, 2023, were retrieved from PubMed, a literature database in the biomedical field. The retraction statements of those articles that were retracted due to ethical-related issues were analyzed with a summarization of detailed reasons and types.Results:A total of 77 and 128 articles were retracted due to ethical issues in 2021 and 2022 respectively, accounting for 3.9% and 5.4% of all retracted articles in the same period. The major ethical issue was the lack of valid ethical approval. Among articles retracted for ethical issues related to human trials, the proportion of articles retracted due to lack of valid ethical approval increased from 45.9% in 2021 to 57.0% in 2022, which also increased from 50.0% in 2021 to 67.3% in 2022 among retracted articles related to animal experiments. Other ethical issues included problems in the informed consent process, delay in obtaining ethical approval, inconsistency between ethical approvals and the content of the article, and violation of the principles of laboratory animal welfare.Conclusions:The ethical review of medical research involving humans and laboratory animal welfare needs to be strengthened. By promoting the construction of an institutional ethical review system, encouraging researchers to study ethics-related knowledge, standardizing ethical applications and approvals, improving the informed consent process, and attaching importance to the welfare of laboratory animals, the retraction due to ethical issues can be prevented.

Objective To investigate the predictive value of preoperative fibrinogen/albumin ratio (FAR) and systemic immune inflammation index (SII) on the postoperative prognosis of patients with pancreatic ductal adenocarcinoma. Methods An ROC curve was used in determining the best cutoff values of FAR and SII and then grouped. The Cox proportional hazards model was used in analyzing the prognostic factors of radical pancreatic cancer surgery, and then a Nomogram prognostic model was established. C-index, AUC, and calibration curve were used in evaluating the discrimination and calibration ability of the Nomogram. DCA curves were used in assessing the clinical validity of the Nomograms. Results The optimal cutoff values for preoperative FAR and SII were 0.095 and 532.945, respectively. FAR≥ 0.095, SII≥ 532.945, CA199≥ 450.9 U/ml, maximum tumor diameter≥ 4 cm, and the absence of postoperative chemotherapy were independent risk factors for the poor prognosis of pancreatic cancer (P<0.05). The discrimination ability, calibration ability, and clinical effectiveness of Nomogram prognostic model were better than those of the TNM staging system. Conclusion The constructed Nomogram prognostic model has higher accuracy and level of discrimination and more clinical benefits than the TNM staging prognostic model.