ObjectiveThis study aimed to provide a scientific basis for the safety management of drinking water by assessing the contamination levels of 21 per- and polyfluoroalkyl substances (PFASs) in water samples collected from the Yangtze River Delta region. MethodsSolid-phase extraction coupled with ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was employed to determine 21 PFASs in 6 source water samples, 20 treated water samples, and 60 tap water samples collected from 5 administrative districts in the Yangtze River Delta region across four seasons in 2023. The Kruskal-Wallis H test was used to compare differences in PFAS concentrations among the three types of water samples, followed by post hoc pairwise comparisons with Bonferroni correction. Removal efficiencies of target compounds were also calculated. ResultsAmong the 86 samples, 14 PFASs were detected, with 7 compounds detected in 100% of samples. The total concentrations of PFASs in source water, treated water, and tap water ranged from 63.85 to 190.54 ng·L^-¹, 55.75 to 774.36 ng·L^-¹, and 40.72 to 689.80 ng·L^-¹, respectively. The compounds with the highest median concentrations were perfluorobutanoic acid (PFBA) (40.19, 15.20, and 14.05 ng·L^-¹), perfluorohexanoic acid (PFHxA) (29.69, 32.62, and 34.24 ng·L^-¹), perfluorooctanoic acid (PFOA) (17.65, 39.45, and 36.83 ng·L^-¹), and potassium perfluorobutanesulfonic acid (PFBS) (16.99, 24.38, and 23.89 ng·L^-¹). Notably, concentrations of PFOA (7.71‒71.63 ng·L^-¹) and PFOS (-¹) in tap water were below the regulatory limits specified in GB 5749‒2022 Standards for Drinking Water Quality (PFOA: 0.000 08 mg·L^-1, PFOS: 0.000 04 mg·L^-1). Significant seasonal variations in PFAS concentrations were observed, with total PFAS levels in March being higher than those in September and November (adjusted P<0.001, and P=0.006), and levels in May being higher than those in September (adjusted P=0.037). The removal efficiencies of PFASs in the water treatment plants ranged from -14% to 34%. ConclusionPFAS contamination is widespread in source water, treated water, and tap water in the Yangtze River Delta region, and concentrations of PFOA and PFOS in all tested water samples comply with the Chinese national standards for drinking water quality (GB 5749‒2022). The use of PFASs should be continuously regulated to ensure water safety.

Objective:To investigate the completion rate of tumor evaluation at initial assessment and after neoadjuvant therapy for mid and low rectal cancer patients in the national multicenter real-world database.Methods:The prospective real-world study was conducted. The clinicopathological data of 1 074 patients who underwent surgical treatment for mid and low rectal cancer in 47 national medical institutions, including Peking Union Medical College Hospital et al, from May 12,2023 to May 11,2024 were collected. Observation indicators: (1) clinical characteristics of patients with mid and low rectal cancer; (2) initial colonoscopy and pathologic evaluation of tumors in patients with mid and low rectal cancer; (3) initial imaging evaluation of patients with mid and low rectal cancer; (4) imaging evaluation after neoadjuvant therapy for patients with mid and low rectal cancer. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M( Q1, Q3). Count data were described as absoluter numbers and/or percentages. Results:(1) Clinical characteristics of patients with mid and low rectal cancer. Of the 1 074 patients, there were 713 males and 361 females, aged 63(56,70)years. The body mass index of 1 074 patients was 24(21,26)kg/m 2.For American Society of Anesthesiologists classification, there were 147 cases of stage Ⅰ, 641 cases of stage Ⅱ, 157 cases of stage Ⅲ, 2 cases of stage Ⅳ, and there were 127 cases missing data. (2) Initial colonoscopy and pathologic evaluation of tumors in patients with mid and low rectal cancer. Of the 1 074 patients, there were 787 cases (73.28%) undergoing complete colonoscopy, and there were only 197 cases (18.34%) undergoing immunohistochemical evaluation of all four mismatch repair proteins. (3) Initial imaging evaluation of patients with mid and low rectal cancer. Of the 1 074 patients, there were 842(78.40%) patients completing magnetic resonance imaging (MRI) or ultrasound evaluation, and there were 914(85.10%) patients completing chest, abdomen, and pelvis enhanced computed tomography (CT) evaluation. In the 149 patients completing rectal ultrasound evaluation, there were 122 cases (81.88%) comple-ting T staging evaluation, and there were 81 cases (54.36%) completing N staging evaluation. In the 808 patients completing rectal MRI evaluation, there were 708 cases (87.62%) completing T staging evaluation, and there were 590 cases (73.02%) completing N staging evaluation. (4) Imaging evalua-tion after neoadjuvant therapy for patients with mid and low rectal cancer. Of the 388 patients with neoadjuvant therapy, there were 332 patients (85.57%) completing MRI or ultrasound evaluation, and there were 327 patients (84.28%) completing chest, abdomen, and pelvis enhanced CT evalua-tion. In the 70 patients completing rectal ultrasound evaluation, there were 65 cases (92.86%) com-pleting T staging evaluation, and there were 49 cases (70.00%) completing N staging evaluation. In the 327 patients completing rectal MRI evaluation, there were 246 cases (75.23%) completing T staging, and there were 228 cases (69.72%) completing N staging evaluation. Conclusion:The com-pletion rate of tumor imaging evaluation at initial assessment and after neoadjuvant therapy for mid and low rectal cancer patients on a national scale is relatively good.

Early-onset colorectal cancer (EOCRC) shows a different epidemiological trend compared to later-onset colorectal cancer, with its incidence rising in most regions and countries worldwide. However, the reasons behind this trend remain unclear. The etiology of EOCRC is complex and could involve both genetic and environmental factors. Apart from Lynch syndrome and Familial Adenomatous Polyposis, sporadic EOCRC exhibits a broad spectrum of pathogenic germline mutations, genetic polymorphisms, methylation changes, and chromosomal instability. Early-life exposures and environmental risk factors, including lifestyle and dietary risk factors, have been found to be associated with EOCRC risk. Meanwhile, specific chronic diseases, such as inflammatory bowel disease, diabetes, and metabolic syndrome, have been associated with EOCRC. Interactions between genetic and environmental risk factors in EOCRC have also been explored. Here we present findings from a narrative review of epidemiological studies on the assessment of early-life exposures, of EOCRC-specific environmental factors, and their interactions with susceptible loci. We also present results from EOCRC-specific genome-wide association studies that could be used to perform Mendelian randomization analyses to ascertain potential causal links between environmental factors and EOCRC.
Humans ; Colorectal Neoplasms/etiology* ; Risk Factors ; Genome-Wide Association Study ; Genetic Predisposition to Disease/genetics*

Hepatocellular carcinoma(HCC), the third leading cause of cancer-related death worldwide, is characterized by high mortality and recurrence rates. Common treatments include hepatectomy, liver transplantation, ablation therapy, interventional therapy, radiotherapy, systemic therapy, and traditional Chinese medicine(TCM). While exhibiting specific advantages, these approaches are associated with varying degrees of adverse effects. To alleviate patients' suffering and burdens, it is crucial to explore additional treatments and elucidate the pathogenesis of HCC, laying a foundation for the development of new TCM-based drugs. With emerging research on gut microbiota, it has been revealed that microbiota plays a vital role in the development of HCC by influencing intestinal barrier function, microbial metabolites, and immune regulation. TCM, with its multi-component, multi-target, and multi-pathway characteristics, has been increasingly recognized as a vital therapeutic treatment for HCC, particularly in patients at intermediate or advanced stages, by prolonging survival and improving quality of life. Recent global studies demonstrate that TCM exerts anti-HCC effects by modulating gut microbiota, restoring intestinal barrier function, regulating microbial composition and its metabolites, suppressing inflammation, and enhancing immune responses, thereby inhibiting the malignant phenotype of HCC. This review aims to elucidate the mechanisms by which gut microbiota contributes to the development and progression of HCC and highlight the regulatory effects of TCM, addressing the current gap in systematic understanding of the "TCM-gut microbiota-HCC" axis. The findings provide theoretical support for integrating TCM with western medicine in HCC treatment and promote the transition from basic research to precision clinical therapy through microbiota-targeted drug development and TCM-based interventions.
Humans ; Gastrointestinal Microbiome/drug effects* ; Carcinoma, Hepatocellular/microbiology* ; Liver Neoplasms/microbiology* ; Drugs, Chinese Herbal/administration & dosage* ; Animals ; Medicine, Chinese Traditional

Researchers commonly use cyclization recombination enzyme/locus of X-over P1 (Cre/loxP) technology-based conditional gene knockouts of model mice to investigate the functional roles of genes of interest in Sertoli and Leydig cells within the testis. However, the shortcomings of these genetic tools include high costs, lengthy experimental periods, and limited accessibility for researchers. Therefore, exploring alternative gene silencing techniques is of great practical value. In this study, we employed adeno-associated virus (AAV) as a vector for gene silencing in Sertoli and Leydig cells. Our findings demonstrated that AAV serotypes 1, 8, and 9 exhibited high infection efficiency in both types of testis cells. Importantly, we discovered that all three AAV serotypes exhibited exquisite specificity in targeting Sertoli cells via tubular injection while demonstrating remarkable selectivity in targeting Leydig cells via interstitial injection. We achieved cell-specific knockouts of the steroidogenic acute regulatory ( Star ) and luteinizing hormone/human chorionic gonadotropin receptor (Lhcgr) genes in Leydig cells, but not in Sertoli cells, using AAV9-single guide RNA (sgRNA)-mediated gene editing in Rosa26-LSL-Cas9 mice. Knockdown of androgen receptor ( Ar ) gene expression in Sertoli cells of wild-type mice was achieved via tubular injection of AAV9-short hairpin RNA (shRNA)-mediated targeting. Our findings offer technical approaches for investigating gene function in Sertoli and Leydig cells through AAV9-mediated gene silencing.
Animals ; Male ; Leydig Cells/metabolism* ; Mice ; Dependovirus/genetics* ; Sertoli Cells/metabolism* ; Gene Silencing ; Genetic Vectors ; Testis/cytology*

OBJECTIVE: To investigate the predictive value of the prognostic nutritional index (PNI) and systemic inflammatory response index (SIRI) for short-term efficacy and prognosis in newly treated patients with peripheral T-cell lymphoma (PTCL). METHODS: The general data, laboratory indicators, disease stage and other clinical data of 91 newly treated PTCL patients admitted to the Affiliated Hospital of Xuzhou Medical University from January 2015 to December 2023 were retrospectively analyzed. The optimal cutoff values for PNI and SIRI were determined using receiver operating characteristic (ROC) curves, and the patients were stratified into groups based on these cutoffs to compare clinical features and short-term efficacy between the different groups. Kaplan-Meier method was used to plot survival curves, and univariate and multivariate analyses were performed to identify the factors affecting overall survival (OS). RESULTS: The optimal cutoff values for PNI and SIRI were 45.30 and 1.74×10⁹/L, respectively. Patients in different PNI groups showed statistically significant differences in age, Ann Arbor stage, lactate dehydrogenase (LDH) level, international prognostic index (IPI), prognostic index for PTCL-not otherwise specified (PIT), pathological subtypes, and complete response (CR) rate (P < 0.05). PTCL patients in different SIRI groups exhibited significant differences in Ann Arbor stage, LDH level, IPI score, PIT score, and CR rate (P < 0.05). Logistic regression analysis showed that age ≥60 years old (OR =2.750), Ann Arbor stage Ⅲ-Ⅳ (OR =5.200), IPI score ≥2 (OR =7.650), low PNI (OR =3.296), and high SIRI (OR =3.130) were independent risk factors affecting treatment efficacy in PTCL patients (P < 0.05). Cox proportional hazards regression model analysis showed that low PNI and elevated β₂-microglobulin (β₂-MG) levels were independent risk factors affecting OS (P < 0.05). CONCLUSION PNI and SIRI have certain application value in evaluating short-term efficacy and prognosis in patients with PTCL. Compared with SIRI, PNI demonstrates greater predictive value for patient prognosis.
Humans ; Prognosis ; Lymphoma, T-Cell, Peripheral/therapy* ; Retrospective Studies ; Nutrition Assessment ; Male ; Female ; Middle Aged ; ROC Curve ; Inflammation

OBJECTIVE: To explore the efficacy and safety of Juan Bi Pill (JBP) in treatment of active rheumatoid arthritis (RA). METHODS: From February 2017 to May 2018, 115 participants from 4 centers were randomly divided into JBP group (57 cases) and placebo group (58 cases) in a 1:1 ratio using a random number table method. Participants received a dose of JBP (4 g, twice a day, orally) combined with methotrexate (MTX, 10 mg per week) or placebo (4 g, twice a day, orally) combined with MTX for 12 weeks. Participants were required with follow-up visits at 24 and 48 weeks, attending 7 assessment visits. Participants were undergo disease activity assessment 7 times (at baseline and 2, 4, 8, 12, 24, 48 weeks) and safety assessments 6 times (at baseline and 4, 8, 12, 24, 48 weeks). The primary endpoint was 28-joint Disease Activity Score (DAS28-ESR and DAS28-CRP). The secondary endpoints included American College of Rheumatology (ACR) criteria for 20% and 50% improvement (ACR20/50), Health Assessment Questionnaire Disability Index (HAQ-DI), clinical disease activity index (CDAI), visual analog scale (VAS), Short Form-36 (SF-36) score, Medial Outcomes Study (MOS) sleep scale score, serum erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), tender joint count, swollen joint count, and morning stiffness. The adverse reactions were observed during the treatment. RESULTS: After 12 weeks of treatment, DAS28-ESR and DAS28-CRP scores in both groups were lower than before treatment (both P<0.01), while the remission rate of DAS28-ESR and DAS28-CRP and low disease activity of JBP group were higher than those in the placebo group (both P<0.01). JBP demonstrated better efficacy on ACR20 and ACR50 compliance rate at 12 and 48 weeks comparing to placebo (all P<0.05). The CDAI and HAQ-DI score, pain VAS and global VAS change of RA patients and physicians, the serum ESR and CRP levels, and the number of tenderness and swelling joints were lower than before treatment at 4, 8, 12, 24, 48 weeks in both groups (P<0.05 or P<0.01), while the reduction of above indices in the JBP group was more obvious than those in the placebo group at 12 weeks (ESR and CRP, both P<0.05) or at 12 and 48 weeks (all P<0.01). There was no difference in adverse reactions between the 2 groups during treatment (P=0.75). CONCLUSION JBP combined with MTX could effectively reduce disease activity in patients with RA in active stage, reduce the symptoms of arthritis, and improve the quality of life, while ensuring safety, reliability, and fewer adverse effects. (Trial Registration: ClinicalTrials.gov, No. NCT02885597).
Humans ; Arthritis, Rheumatoid/drug therapy* ; Methotrexate/adverse effects* ; Female ; Double-Blind Method ; Male ; Middle Aged ; Treatment Outcome ; Drugs, Chinese Herbal/adverse effects* ; Drug Therapy, Combination ; Adult ; Antirheumatic Agents/adverse effects* ; Aged

Objective To explore the effect of management model of clinical pharmacists participating in multidisciplinary collaborative diagnosis and treatment(MDT)for new anti-tumor drugs in the national medical insurance drug negotiation(hereinafter referred to as"national negotiation"),including efficacy,safe-ty,economy and rationality.Methods The medical records of 326 cases using novel anti-tumor drugs by na-tional negotiation and conforming to the including and excluding standards in this hospital from July 2018 to June 2023 were retrospectively analyzed.The patients were divided into the MDT group(n=122)and non-MDT group(n=204).The patients diagnosed as non-small cell lung cancer(NSCLC)in the two groups were extracted and defined as the MDT-NSCLC subgroup(n=41)and non-MDT-NSCLC subgroup(n=77).The progression-free survival(PFS),overall survival(OS),disease control rate(DCR)and the indexes such as survival quality and medical quality control were compared between the groups.Results The median PFS in the two groups was 12.7 months and 8.0 months,the median OS was 75.2 months and 56.3 months,DCR was 96.72％and 81.86％respectively,and the differences were statistically significant(P＜0.05).The COX multivariate regression analysis indicated that the HR value of clinical pharmacists participating in MDT was higher than the other influencing factors.The median PFS time in the MDT-NSCLC subgroup and non-MDT-NSCLC subgroup was 10.5 months and 6.7 months,DCR was 97.30％and 75.64％respectively,and the differences were statistically significant(P＜0.05),the median OS time was 55.1 months and 40.3 months respectively,and the difference was statistically significant(P＞0.05).The COX multivariate regression anal-ysis indicated that the HR value with clinical pharmacists participating in MDT was higher than the other in-fluencing factors;The adverse reaction occurrence rate in the MDT group and non-MDT group was 45.9％and 58.3％respectively,and the difference was statistically significant(P＜0.05).The KPS score after treatment in the MDT group was higher than that in the non-MDT group,and the difference was statistically significant;in the aspect of medical quality control,the average drug proportion in the MDT group and non-MDT group was 63.93％and 64.54％respectively,the rational drug rate of comments on prescription was 98.36％and 88.73％respectively,the patient satisfaction average value was 90.69 points and 87.36 points respectively and the differences were statistically significant(P＜0.05).Conclusion Clinical pharmacists participating in MDT related to novel anti-tumor drugs by national negotiation is beneficial to improve the therapeutic effects,living quality and patient satisfaction,also benefit to management and control of off-label drug use and medical quality control indexes.