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 elucidate the molecular mechanism by which prohibitin 2(PHB2) mediates periodontitis-induced bone tissue inflammation through regulating the nuclear factor kappa B(NF-κB) signaling pathway and its role in irreversible alveolar bone resorption. Methods: Quantitative real-time reverse transcription polymerase chain reaction(qRT-PCR) and immunohistochemistry(IHC) were used to detect the expression differences of inflammatory factors and PHB2 in healthy and inflamed alveolar bone tissues of mice in vivo. In vitro, an inflammatory model was established using lipopolysaccharide(LPS)-induced a mouse calvaria-derived preosteoblastic cell line, subclone E1(MC3T3-E1) cells. Western blot and qRT-PCR were used to clarify the regulatory relationship between PHB2 and inflammatory factors, and immunofluorescence staining was performed to observe changes in PHB2 subcellular localization. PHB2 overexpression plasmids were constructed using molecular cloning, and RNA interference was employed to knock down PHB2 expression to assess its regulatory role in inflammation. Based on RNA-seq data, differential expression analysis based on the negative binomial distribution, version 2(DESeq2) was used for differential expression analysis, and kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment along with gene ontology(GO) functional annotation were performed to identify key signaling pathways and differentially expressed genes. Results: In the mouse periodontitis model, PHB2 expression was significantly upregulated in alveolar bone tissues. In the in vitro inflammatory cell model, PHB2 levels positively correlated with interleukin(IL)-6, IL-1β, and tumor necrosis factor-alpha(TNF-α) levels, and its subcellular localization shifted during inflammation. RNA-seq data and the detection of the level of phosphorylation of p65 protein(p-p65) demonstrated that PHB2 exacerbated inflammatory responses through the NF-κB signaling pathway and was mechanistically linked to upregulation of the upstream chemokine C-X-C motif chemokine ligand 10(CXCL10). Conclusion PHB2 aggravates LPS-induced periodontitis inflammation via the NF-κB signaling pathway, providing new insights into the molecular mechanisms underlying the development of periodontitis.

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.

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.

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.

Sex difference has shown in the arthritis diseases in human population and animal models. We investigate how the sex and symmetry vary among mouse models with different genomic backgrounds. Disease data of sex and limbs accumulated in the past more than two decades from four unique populations of murine arthritis models were analyzed. They are (1) interleukin-1 receptor antagonist (IL-1ra) deficient mice under Balb/c background (Balb/c KO); (2) Mice with collagen II induced arthritis under DBA/1 background; (3) Mice with collagen II induced arthritis under C57BL/6 (B6) background and (4) A F2 generation population created by Balb/c KO X DBA/1 KO.Our data shows that there is a great variation in sexual dimorphism for arthritis incidence and severity of arthritis in mice harboring specific genetic modifications. For a F2 population, the incidence of arthritis was 57.1% in female mice and 75.6% in male mice. There was a difference in severity related to sex in two populations: B6.DR1/ B6.DR4 (P < 0.001) and F2 (P = 0.023) There was no difference Balb/c parental strain or in collagen-induced arthritis (CIA) in DBA/1 mice. Among these populations, the right hindlimbs are significantly higher than the scores for the left hindlimbs in males (P < 0.05). However, when examining disease expression using the collagen induced arthritis model with DBA/1 mice, sex-dimorphism did not reach statistical significance, while left hindlimbs showed a tendency toward greater disease expression over the right. Sexual dimorphism in disease expression in mouse models is strain and genomic background dependent. It sets an alarm that potential variation in sexual dimorphism among different racial and ethnic groups in human populations may exist. It is important to not only include both sexes and but also pay attention to possible variations caused by disease expression and response to treatment in all the studies of arthritis in animal models and human populations.