Effectiveness of antibiotic prophylaxis for acute esophageal variceal bleeding in patients with band ligation: A large observational study

BACKGROUND Esophageal variceal bleeding is a severe complication associated with liver cirrhosis and typically necessitates endoscopic hemostasis.The current standard treatment is endoscopic variceal ligation(EVL),and Western guidelines recom-mend antibiotic prophylaxis following hemostasis.However,given the impro-vements in prognosis for variceal bleeding due to advancements in the management of bleeding and treatments of liver cirrhosis and the global concerns regarding the emergence of multidrug-resistant bacteria,there is a need to reassess the use of routine antibiotic prophylaxis after hemostasis.AIM To evaluate the effectiveness of antibiotic prophylaxis in patients treated for EVL.METHODS We conducted a 13-year observational study using the Tokushukai medical database across 46 hospitals.Patients were divided into the prophylaxis group(received antibiotics on admission or the next day)and the non-prophylaxis group(did not receive antibiotics within one day of admission).The primary outcome was composed of 6-wk mortality,4-wk rebleeding,and 4-wk spontaneous bacterial peritonitis(SBP).The secondary outcomes were each individual result and in-hospital mortality.A logistic regression with inverse probability of treatment weighting was used.A subgroup analysis was conducted based on the Child-Pugh classification to determine its influence on the primary outcome measures,while sensitivity analyses for antibiotic type and duration were also performed.RESULTS Among 980 patients,790 were included(prophylaxis:232,non-prophylaxis:558).Most patients were males under the age of 65 years with a median Child-Pugh score of 8.The composite primary outcomes occurred in 11.2%of patients in the prophylaxis group and 9.5%in the non-prophylaxis group.No significant differences in outcomes were observed between the groups(adjusted odds ratio,1.11;95%confidence interval,0.61-1.99;P=0.74).Individual outcomes such as 6-wk mortality,4-wk rebleeding,4-wk onset of SBP,and in-hospital mortality were not significantly different between the groups.The primary outcome did not differ between the Child-Pugh subgroups.Similar results were observed in the sensitivity analyses.CONCLUSION No significant benefit to antibiotic prophylaxis for esophageal variceal bleeding treated with EVL was detected in this study.Global reassessment of routine antibiotic prophylaxis is imperative.

Uncovering the impact of alcohol on internal organs and reproductive health:Exploring TLR4/NF-kB and CYP2E1/ROS/Nrf2 pathways

This review delves into the detrimental impact of alcohol consumption on internal organs and reproductive health,elucidating the underlying mechanisms involving the Toll-like receptor 4(TLR4)/Nuclear factor kappa light chain enhancer of activated B cells(NF-kB)pathway and the Cytochrome P4502E1(CYP2E1)/reactive oxygen spe-cies(ROS)/nuclear factor erythroid 2-related factor 2(Nrf2)pathways.The TLR4/NF-kB pathway,crucial for inflammatory and immune responses,triggers the production of pro-inflammatory agents and type-1 interferon,disrupting the balance between inflammatory and antioxidant responses when tissues are chronically exposed to al-cohol.Alcohol-induced dysbiosis in gut microbes heightens gut wall permeability to pathogen-associated molecular patterns(PAMPs),leading to liver cell infection and subsequent inflammation.Concurrently,CYP2E1-mediated alcohol metabolism gen-erates ROS,causing oxidative stress and damaging cells,lipids,proteins,and deoxy-ribonucleic acid(DNA).To counteract this inflammatory imbalance,Nrf2 regulates gene expression,inhibiting inflammatory progression and promoting antioxidant re-sponses.Excessive alcohol intake results in elevated liver enzymes(ADH,CYP2E1,and catalase),ROS,NADH,acetaldehyde,and acetate,leading to damage in vital organs such as the heart,brain,and lungs.Moreover,alcohol negatively affects reproduc-tive health by inhibiting the hypothalamic-pituitary-gonadal axis,causing infertility in both men and women.These findings underscore the profound health concerns associated with alcohol-induced damage,emphasizing the need for public awareness regarding the intricate interplay between immune responses and the multi-organ im-pacts of alcohol consumption.

Metabolomics in liver diseases: A novel alternative for liver biopsy?

Hepatitis C virus(HCV)remains a significant public health problem as it can cause acute and chronic hepatitis.Chronic HCV infection is a major cause of liver fibrosis,and evaluation of liver fibrosis is essential because the prognosis of patients with chronic HCV infection is closely related to the stage of fibrosis.Liver fibrosis is traditionally evaluated based on pathological analysis of biopsy specimens,which is considered the gold standard.Nevertheless,liver biopsy is invasive and susceptible to sampling error and inter-and intraobserver variation in pathological interpretation;it is also costly.Therefore,noninvasive diagnostic investigations have been developed,including the use of fibrotic markers,scoring systems based on routine blood tests,and transient elastography with magnetic resonance imaging or ultrasonography.Recently,metabolomics,an emerging technology,has been used to detect the fibrosis stage.In this editorial,I comment on the article titled“Metabolomics in chronic hepatitis C:Decoding fibrosis grading and underlying pathways”by Ferrasi et al published in the recent issue of the World Journal of Hepatology.I discuss previous studies on the use of metabolome analysis for the diagnosis of HCV-related liver fibrosis and the potential development of biopsy-free diagnostic techniques.

Estimated Average Glandular Dose for 1,828 Mammography Procedures in China: A Multicenter Study

Objective To understand the distribution of the average glandular dose(AGD) in mammography by investigating 1,828 exposure parameters of 8 mammography machines in three cities, by using random sampling. Methods A survey of 8 mammography machines in three different cities, sampled using stratified random sampling methods, was performed, and 1,828 mammography exposure parameters were recorded. Incident air kerma(k) was measured by Quality-Assurance(QA) dosimeters, and AGD was calculated by series conversion coefficients based on a 3D detailed Monte Carlo breast model, published by Wang et al. Results The distribution of compressed breast thickness(CBT) fitted a normal distribution, while that of AGD fitted a skewed distribution. The mean value of CBT in a medio-lateral oblique(MLO) view was about 5.6% higher than that in the craniocaudal(CC) view, with significant statistical difference; mean value of AGD and CBT in the sample was 1.3 mGy and 4.6 cm, respectively. The AGD trended upward with increasing CBT, similar to the results of other researches. Conclusion The mean AGD and CBT levels in our study for mammography practice in China were 1.3 mGy and 4.6 cm, respectively. AGD is influenced by manufacturer-specific variation as machine response to CBT changes and target/filter combination. The present study can provide evidence for establishing a diagnostic reference level in China.

Nanobody-based immunosensing methods for safeguarding public health

Immunosensing methods are biosensing techniques based on specific recognition of an antigen-antibody immunocomplex,which have become commonly used in safeguarding public health.Taking advantage of antibody-related biotechnological advances,the utilization of an antigen-binding fragment of a heavy-chain-only antibody termed as'nanobody'holds significant biomedical potential.Compared with the conventional full-length antibody,a single-domain nanobody retaining cognate antigen specificity possesses remarkable physicochemical stability and structural adaptability,which enables a flexible and efficient molecular design of the immunosensing strategy.This minireview aims to summarize the recent progress in immunosensing methods using nanobody targeting tumor markers,environmental pollutants,and foodborne microbes.

Climate Change and Temperature-related Mortality:Implications for Health-related Climate Policy

It is widely recognized that climate change is one of the greatest challenges humanity faces in the 21st century[1,2].As the leading authority for the assessment of climate change,the Intergovernmental Panel on Climate Change (IPCC),in its special report on global warming of 1.5℃,has concluded that human activities have caused approximately 1.0℃ of global warming above preindustrial levels,with a likely increase of 1.5℃ between 2030 and 2052[3].Climate-related risks for natural and human systems are projected to increase with global warming of 1.5℃,and increase further with 2℃ or above.These risks depend on the magnitude and rate of warming,geographic location,levels of development and vulnerability,and on the choices and implementation of adaptation and mitigation options.

Estimation of economic burden throughout course of cervical squamous intraepithelial lesion and cervical cancer in China:A nationwide multicenter cross-sectional study

Objective: Cervical squamous intraepithelial lesion(SIL) and cervical cancer are major threats to females' health and life in China, and we aimed to estimate the economic burden associated with their diagnosis and treatment.Methods: A nationwide multicenter, cross-sectional, hospital-based survey was conducted in 26 qualified hospitals across seven administrative regions of China. We investigated females who had been pathologically diagnosed with SIL and cervical cancer, and included five disease courses(“diagnosis”, “initial treatment”,“chemoradiotherapy”, “follow-up” and “recurrence/progression/metastasis”) to estimate the total costs. The median and interquartile range(IQR) of total costs(including direct medical, direct non-medical, and indirect costs), reimbursement rate by medical insurance, and catastrophic health expenditures in every clinical stage were calculated.Results: A total of 3,471 patients in different clinical stages were analyzed, including low-grade SIL(LSIL)(n=549), high-grade SIL(HSIL)(n=803), cervical cancer stage ⅠA(n=226), ⅠB(n=610), ⅡA(n=487), ⅡB(n=282), Ⅲ(n=452) and Ⅳ(n=62). In urban areas, the estimated total costs of LSIL and HSIL were $1,637.7(IQR:$956.4-$2,669.2) and $2,467.1(IQR:$1,579.1-$3,762.3), while in rural areas the costs were $459.0(IQR:$167.7-$1,330.3) and $1,230.5(IQR:$560.6-$2,104.5), respectively. For patients with cervical cancer stage ⅠA,ⅠB, ⅡA, ⅡB, and Ⅲ-Ⅳ, the total costs were $15,034.9(IQR:$11,083.4-$21,632.4), $19,438.6(IQR:$14,060.0-$26,505.9), $22,968.8(IQR:$16,068.8-$34,615.9), $26,936.0(IQR:$18,176.6-$41,386.0) and $27,332.6(IQR:$17,538.7-$44,897.0), respectively. Medical insurance covered 43%-55% of direct medical costs for cervical cancer patients, while the coverage for SIL patients was 19%-43%. For most cervical cancer patients, the expense was catastrophic, and the extent of catastrophic health expenditure was about twice large for rural patients than that for urban patients in each stage.Conclusions: The economic burden of SIL and cervical cancer in China is substantial, with a significant proportion of the costs being avoidable for patients with LSIL. Even for those with medical insurance, catastrophic health expenditures are also a major concern for patients with cervical cancer, particularly for those living in rural areas.

Food insecurity: How to orchestrate a global health crisis

In 2007-2008, the world experienced over 1 billion people going hungry. This complex food security and public health crisis have many levels, actors and stakeholders. There lacks equity in access food markets, unbalanced consumption of nutrients and poor state institutions that, all negatively impact food security. Global financial products and regimes can greatly influence food prices, and if not properly regulated, this can lead to whole market manipulation and starvation. This paper discusses the basics of food security in a public health framework and describes the legal and financial mechanisms that lead to food insecurity.

Evaluating the Quality of Malaria-Related Health Information in the Nigerian Internet Context

Background: Patients and public are increasingly relying on Internet for health information. Health care providers are using internet for dissemination of health information. However, health information available on internet is not well regulated, and information quality varies greatly. Malaria is the leading cause of death and disease in many developing countries and has serious health burden around the world. The Internet could become a major resource for malaria education and information in Africa. This may potentially save millions of lives. The purpose of this study is to evaluate the quality of malaria health and treatment information available on the internet provided by the Nigerian context. Methods: Two key terms (malaria & treatment) were entered into three search engines: Google, Yahoo! and Bing. In order to retrieve articles as if the searches were conducted in Nigeria, the Local Area Network (LAN) settings were changed to a Nigerian proxy server, with a local Internet Protocol address. Three raters evaluated the quality of information using the DISCERN [9] instrument criteria. Kendall’s concordance coefficient (W) was calculated to determine the level of agreement among the three raters. Results: Thirty-eight websites evaluated, and the highest inter-rater average score was attributed to the Patient.co.uk website, followed by Wikipedia web site and Malaria Site. The “Home Remedies for You” website received the lowest score. Most evaluated websites were .com domains. The highest average score was given to .co.uk domains while .int had the lowest score. Conclusions: Improving the quality of malaria-related health information could lead to empowering communities, engaging and assisting them to strengthen their health and social information sharing and support.

Current state of practice for colonic diverticular bleeding in 37 hospitals in Japan:A multicenter questionnaire study

AIMTo clarify the current state of practice for colonic diverticular bleeding(CDB)in Japan.METHODSWe conducted multicenter questionnaire surveys of the practice for CDB including clinical settings(8 questions),diagnoses(8 questions),treatments(7 questions),and outcomes(4 questions)in 37 hospitals across Japan.The answers were compared between hospitals with high and low number of inpatient beds to investigate which factor influenced the answers.RESULTSEndoscopists at all 37 hospitals answered the questions,and the mean number of endoscopists at these hospitals was 12.7.Of all the hospitals,computed tomography was performed before colonoscopy in 67%of the hospitals.The rate of bowel preparation was 46.0%.Early colonoscopy was performed within 24 h in 43.2%of the hospitals.Of the hospitals,83.8%performed clipping as first-line endoscopic therapy.More than half of the hospitals experienced less than 20%rebleeding events after endoscopic hemostasis.No significant difference was observed in the annual number of patients hospitalized for CDB between high-(≥700 beds)and low-volume hospitals.More emergency visits(P=0.012)and endoscopists(P=0.015),and less frequent participation of nursing staff in early colonoscopy(P=0.045)were observed in the high-volume hospitals.CONCLUSIONSome practices unique to Japan were found,such as performing computed tomography before colonoscopy,no bowel preparation,and clipping as first-line therapy.Although,the number of staff differed,the practices for CDB were common irrespective of hospital size.

Moving Epidemic Method for Surveillance and Early Warning of Hand, Foot, and Mouth Disease in Beijing, China

Hand,foot,and mouth disease (HFMD) is an acute infection caused by enteroviruses that is commonly seen in children^([1]).High infectivity,large number of asymptomatic infections,complex transmission routes,and rapid spread make it difficult to control HFMD.Since 2008,China has reported> 23 million HFMD cases,including>0.15million severe cases^([2]).HFMD tops the list of notifiable infectious diseases in terms of case number and incidence rate,leading to a huge disease burden^([3]).Timely and accurate assessment of HFMD epidemics is essential for a holistic understanding of the outbreaks and for effective prevention and control strategies.Currently,there are no quantitative indicators to determine the duration and intensity of HFMD epidemics in Beijing.

Barriers in the Transition of Care for Heart Failure Patients Attending Clinics in Mwanza City, Tanzania

Introduction: Transition of care strategies have shown to improve quality of lives of heart failure patients, but it has little implemented in clinical settings. Objective: To evaluate context-specific perceived barriers and experiences of heart failure patients during their admission and after they were discharged from hospital. Methods: A cross-sectional qualitative study was conducted among 13 heart failure patients at two large referral hospitals in northwestern Tanzania. In-depth interviews among heart failure patients, in line with the Consolidated Criteria for Reporting Qualitative research checklist, were used to collect data. Interviews were audio recorded, transcribed, and translated into English. Results: Three key barriers were identified, as well as possible solutions that could improve the transition of care for heart failure patients. These include strengthening healthcare provider communications, organizing medication management, and assisting with follow-up appointments. Conclusion: The barriers identified are real and challenging in clinical resource- limited settings. Findings suggest they can be overcome when realistic and tailor-made interventions are in place.

Downregulation of Serum PTEN Expression in Mercury-Exposed Population and PI3K/AKT Pathway-Induced Inflammation

Objective This study investigated the impact of occupational mercury(Hg) exposure on human gene transcription and expression, and its potential biological mechanisms.Methods Differentially expressed genes related to Hg exposure were identified and validated using gene expression microarray analysis and extended validation. Hg-exposed cell models and PTEN lowexpression models were established in vitro using 293T cells. PTEN gene expression was assessed using qRT-PCR, and Western blotting was used to measure PTEN, AKT, and PI3K protein levels. IL-6 expression was determined by ELISA.Results Combined findings from gene expression microarray analysis, bioinformatics, and population expansion validation indicated significant downregulation of the PTEN gene in the high-concentration Hg exposure group. In the Hg-exposed cell model(25 and 10 μmol/L), a significant decrease in PTEN expression was observed, accompanied by a significant increase in PI3K, AKT, and IL-6 expression.Similarly, a low-expression cell model demonstrated that PTEN gene knockdown led to a significant decrease in PTEN protein expression and a substantial increase in PI3K, AKT, and IL-6 levels.Conclusion This is the first study to report that Hg exposure downregulates the PTEN gene, activates the PI3K/AKT regulatory pathway, and increases the expression of inflammatory factors, ultimately resulting in kidney inflammation.

Genetic variants in C1GALT1 are associated with gastric cancer risk by influencing immune infiltration

Core 1 synthase glycoprotein-N-acetylgalactosamine 3-β-galactosyltransferase 1(C1GALT1)is known to play a critical role in the development of gastric cancer,but few studies have elucidated associations between genetic variants in C1GALT1 and gastric cancer risk.By using the genome-wide association study data from the database of Genotype and Phenotype(dbGAP),we evaluated such associations with a multivariable logistic regression model and identified that the rs35999583 G>C in C1GALT1 was associated with gastric cancer risk(odds ratio,0.83;95% confidence interval[CI],0.75-0.92;P=3.95×10^(-4)).C1GALT1 mRNA expression levels were significantly higher in gastric tumor tissues than in normal tissues,and gastric cancer patients with higher C1GALT1 mRNA levels had worse overall survival rates(hazards ratio,1.33;95%CI,1.05-1.68;P_(log-rank)=1.90×10^(-2)).Furthermore,we found that C1GALT1 copy number differed in various immune cells and that C1GALT1 mRNA expression levels were positively correlated with the infiltrating levels of CD4^(+)T cells and macrophages.These results suggest that genetic variants of C1GALT1 may play an important role in gastric cancer risk and provide a new insight for C1GALT1 into a promising predictor of gastric cancer susceptibility and immune status.

The neutrophil–osteogenic cell axis promotes bone destruction in periodontitis

The immune-stromal cell interactions play a key role in health and diseases. In periodontitis, the most prevalent infectious disease in humans, immune cells accumulate in the oral mucosa and promote bone destruction by inducing receptor activator of nuclear factor-κB ligand (RANKL) expression in osteogenic cells such as osteoblasts and periodontal ligament cells. However, the detailed mechanism underlying immune–bone cell interactions in periodontitis is not fully understood. Here, we performed single-cell RNAsequencing analysis on mouse periodontal lesions and showed that neutrophil–osteogenic cell crosstalk is involved in periodontitis-induced bone loss. The periodontal lesions displayed marked infiltration of neutrophils, and in silico analyses suggested that the neutrophils interacted with osteogenic cells through cytokine production. Among the cytokines expressed in the periodontal neutrophils, oncostatin M (OSM) potently induced RANKL expression in the primary osteoblasts, and deletion of the OSM receptor in osteogenic cells significantly ameliorated periodontitis-induced bone loss. Epigenomic data analyses identified the OSM-regulated RANKL enhancer region in osteogenic cells, and mice lacking this enhancer showed decreased periodontal bone loss while maintaining physiological bone metabolism. These findings shed light on the role of neutrophils in bone regulation during bacterial infection, highlighting the novel mechanism underlying osteoimmune crosstalk.

Causal genetic regulation of DNA replication on immune microenvironment in colorectal tumorigenesis: Evidenced by an integrated approach of trans-omics and GWAS

The interplay between DNA replication stress and immune microenvironment alterations is known to play a crucial role in colorectal tumorigenesis,but a comprehensive understanding of their association with and relevant biomarkers involved in colorectal tumorigenesis is lacking.To address this gap,we conducted a study aiming to investigate this association and identify relevant biomarkers.We analyzed transcriptomic and proteomic profiles of 904 colorectal tumor tissues and 342 normal tissues to examine pathway enrichment,biological activity,and the immune microenvironment.Additionally,we evaluated genetic effects of single variants and genes on colorectal cancer susceptibility using data from genome-wide association studies(GWASs)involving both East Asian(7062 cases and 195745 controls)and European(24476 cases and 23073 controls)populations.We employed mediation analysis to infer the causal pathway,and applied multiplex immunofluorescence to visualize colocalized biomarkers in colorectal tumors and immune cells.Our findings revealed that both DNA replication activity and the flap structure-specific endonuclease 1(FEN1)gene were significantly enriched in colorectal tumor tissues,compared with normal tissues.Moreover,a genetic variant rs4246215 G>T in FEN1 was associated with a decreased risk of colorectal cancer(odds ratio=0.94,95%confidence interval:0.90–0.97,P_(meta)=4.70×10^(-9)).Importantly,we identified basophils and eosinophils that both exhibited a significantly decreased infiltration in colorectal tumors,and were regulated by rs4246215 through causal pathways involving both FEN1 and DNA replication.In conclusion,this trans-omics incorporating GWAS data provides insights into a plausible pathway connecting DNA replication and immunity,expanding biological knowledge of colorectal tumorigenesis and therapeutic targets.

Functional aspects of the brain lymphatic drainage system in aging and neurodegenerative diseases

The phenomenon of an aging population is advancing at a precipitous rate.Alzheimer's disease(AD)and Parkinson's disease(PD)are two of the most common age-associated neurodegenerative diseases,both of which are primarily characterized by the accumulation of toxic proteins and the progressive demise of neuronal structures.Recent discoveries about the brain lymphatic drainage system have precipitated a growing body of investigations substantiating its novel roles,including the clearance of macromolecular waste and the trafficking of immune cells.Notably,aquaporin 4-mediated glymphatic transport,crucial for maintaining neural homeostasis,becomes disrupted during the aging process and is further compromised in the pathogenesis of AD and PD.Functional meningeal lymphatic vessels,which facilitate the drainage of cerebrospinal fluid into the deep cervical lymph nodes,are integral in bridging the central nervous system with peripheral immune responses.Dysfunction in these meningeal lymphatic vessels exacerbates pathological trajectory of the age-related neurodegenerative disease.This review explores modulatory influence of the glymphatic system and meningeal lymphatic vessels on the aging brain and its associated neurodegenerative disorders.It also encapsulates the insights of potential mechanisms and prospects of the targeted non-pharmacological interventions.

circPVT1 promotes silica-induced epithelial-mesenchymal transition by modulating the miR-497-5p/TCF3 axis

Epithelial-mesenchymal transition(EMT)is a vital pathological feature of silica-induced pulmonary fibrosis.However,whether circRNA is involved in the process remains unclear.The present study aimed to investigate the role of circPVT1 in the silica-induced EMT and the underlying mechanisms.We found that an elevated expression of circPVT1 promoted EMT and enhanced the migratory capacity of silica-treated epithelial cells.The isolation of cytoplasmic and nuclear separation assay showed that circPVT1 was predominantly expressed in the cytoplasm.RNA immunoprecipitation assay and RNA pull-down experiment indicated that cytoplasmic-localized circPVT1 was capable of binding to miR-497-5p.Furthermore,we found that miR-497-5p attenuated the silica-induced EMT process by targeting transcription factor 3(TCF3),an E-cadherin transcriptional repressor,in the silica-treated epithelial cells.Collectively,these results reveal a novel role of the circPVT1/miR-497-5p/TCF3 axis in the silica-induced EMT process in lung epithelial cells.Once validated,this finding may provide a potential theoretical basis for the development of interventions and treatments for pulmonary fibrosis.

Evaluating short-term and long-term liver fibrosis improvement in hepatitis C patients after DAA treatment

Despite achieving a high cure rate with the direct-acting antivirals(DAAs)in hepatitis C treatment,further research is needed to identify additional benefits of the DAA therapy.The current study evaluated liver fibrosis improvement in 848 hepatitis C patients treated with DAAs,who also achieved sustained virologic response.By the fibrosis-4(FIB-4)index,patients were categorized based on their baseline fibrosis levels,and the improvement in fibrosis was analyzed in both short-term(9-26 weeks)and long-term(≥36 weeks)follow-up.The results showed a significant decrease in the FIB-4 index,indicating an improvement in liver fibrosis,in 63.0%and 67.6%of the patients during the short-term and long-term follow-up,respectively.Short-term improvement was associated with factors including ribavirin usage,blood cholinesterase levels,alanine transaminase levels,albumin levels,and the baseline FIB-4 index,while long-term improvement was associated with factors such as aspartate transaminase levels,total protein level,and the baseline FIB-4 index.The current study emphasizes the importance of continuous assessment and post-treatment monitoring of liver fibrosis,which will provide crucial insights for enhancing patient care in hepatitis C management.

Genetic variant in a BaP-activated super-enhancer increases prostate cancer risk by promoting AhR-mediated FAM227A expression

Genetic variants in super-enhancers(SEs)are increasingly implicated as a disease risk-driving mechanism.Previous studies have reported an associations between benzo[a]pyrene(BaP)exposure and some malignant tumor risk.Currently,it is unclear whether BaP is involved in the effect of genetic variants in SEs on prostate cancer risk,nor the associated intrinsic molecular mechanisms.In the current study,by using logistic regression analysis,we found that rs5750581T>C in 22q-SE was significantly associated with prostate cancer risk(odds ratio=1.26,P=7.61×10^(-5)).We also have found that the rs6001092T>G,in a high linkage disequilibrium with rs5750581T>C(r^(2)=0.98),is located in a regulatory aryl hydrocarbon receptor(AhR)motif and may interact with the FAM227A promoter in further bioinformatics analysis.We then performed a series of functional and BaP acute exposure experiments to assess biological function of the genetic variant and the target gene.Biologically,the rs6001092-G allele strengthened the transcription factor binding affinity to AhR,thereby upregulating FAM227A,especially upon exposure to BaP,which induced the malignant phenotypes of prostate cancer.The current study highlights that AhR acts as an environmental sensor of BaP and is involved in the SE-mediated prostate cancer risk,which may provide new insights into the etiology of prostate cancer associated with the inherited SE variants under environmental carcinogen stressors.