Background Benzothiazoles and benzotriazoles are ubiquitously detected in drinking water, posing potential health risks. Developing a reliable and sensitive analytical method is critical for assessing their exposure levels and associated risks. Objective To establish an automated solid-phase extraction (SPE) coupled with liquid chromatography-tandem mass spectrometry method for the simultaneous determination of benzothiazole, 2-aminobenzothiazole, benzotriazole, and 5-chlorobenzotriazole in drinking water. Methods Key parameters were systematically optimized. Three mobile phase systems were compared to evaluate their effects on chromatographic peak shape and separation; three SPE cartridges were tested for extraction efficiency; the influences of water pH on extraction recoveries and matrix effects were investigated; the contributions of pretreatment steps to benzothiazole blank were analyzed, and control measures were established; nitrogen evaporation temperatures were tested to ensure analyte stability. The optimized parameters were used to develop the method, validate its performance, and analyze drinking water samples. Results Drinking water samples were first adjusted to pH 6.0 with formic acid, and then extracted using HLB cartridges. After elution with 6 mL methanol, the eluate was concentrated under nitrogen evaporation at 45 °C, followed by separation on a C18 column using a gradient elution of acetonitrile-0.1% formic acid solution, and tandem mass spectrometry detection. Avoiding nitrogen blow-drying during SPE and eliminating the use of polypropylene materials during nitrogen evaporation can effectively minimize benzothiazole contamination. Good calibration linearity was obtained for the target analytes in the concentration range of 5.0-250 μg·L⁻¹, with a correlation coefficient of r > 0.995. The method detection limits were in the range of 1.0-5.0 ng·L⁻¹. The recoveries of the target analytes in pure water and tap water were 80.2%-119.5% and 72.2%-115.6%, respectively, with relative standard deviations of were 3.2%-12.8% and 2.3%-11.6%, respectively. When applying this method to actual water samples, benzotriazole was detected in 100% of treated and tap water samples, with median concentrations of 79.4 ng·L⁻¹ and 114 ng·L⁻¹, respectively. Benzothiazole was detected in 83.3% of treated water samples and 100% of tap water samples, with median concentrations of 48.3 ng·L⁻¹ and 65.4 ng·L⁻¹, respectively. In addition, 5-chloro-benzotriazole exhibited low detection rates and concentrations, while 2-amino-benzothiazole was undetected. Conclusion The developed method demonstrates high accuracy, reliability, and sensitivity, making it suitable for the analysis of trace levels of benzothiazoles and benzotriazoles in drinking water.

Several types of arthritis share the common feature that the generation of inflammatory mediators leads to joint cartilage degradation. However, the shared mechanism is largely unknown. H2BK120ub1 was reportedly involved in various inflammatory diseases but its role in the shared mechanism in inflammatory joint conditions remains elusive. The present study demonstrated that levels of cartilage degradation, H2BK120ub1, and its regulator WW domain-containing adapter protein with coiled-coil (WAC) were increased in cartilage in human rheumatoid arthritis (RA) and osteoarthritis (OA) patients as well as in experimental RA and OA mice. By regulating H2BK120ub1 and H3K27me3, WAC regulated the secretion of inflammatory and cartilage-degrading factors. WAC influenced the level of H3K27me3 by regulating nuclear entry of the H3K27 demethylase KDM6B, and acted as a key factor of the crosstalk between H2BK120ub1 and H3K27me3. The cartilage-specific knockout of WAC demonstrated the ability to alleviate cartilage degradation in collagen-induced arthritis (CIA) and collagenase-induced osteoarthritis (CIOA) mice. Through molecular docking and dynamic simulation, doxercalciferol was found to inhibit WAC and the development of cartilage degradation in the CIA and CIOA models. Our study demonstrated that WAC is a key factor of cartilage degradation in arthritis, and targeting WAC by doxercalciferol could be a viable therapeutic strategy for treating cartilage destruction in several types of arthritis.

Glutamine provides carbon and nitrogen to support the proliferation of cancer cells. However, the precise reason why cancer cells are particularly dependent on glutamine remains unclear. In this study, we report that glutamine modulates the tumor suppressor F-box and WD repeat domain-containing 7 (FBW7) to promote cancer cell proliferation and survival. Specifically, lysine 604 (K604) in the sixth of the 7 substrate-recruiting WD repeats of FBW7 undergoes glutaminylation (Gln-K604) by glutaminyl tRNA synthetase. Gln-K604 inhibits SCFFBW7-mediated degradation of c-Myc and Mcl-1, enhances glutamine utilization, and stimulates nucleotide and DNA biosynthesis through the activation of c-Myc. Additionally, Gln-K604 promotes resistance to apoptosis by activating Mcl-1. In contrast, SIRT1 deglutaminylates Gln-K604, thereby reversing its effects. Cancer cells lacking Gln-K604 exhibit overexpression of c-Myc and Mcl-1 and display resistance to chemotherapy-induced apoptosis. Silencing both c-MYC and MCL-1 in these cells sensitizes them to chemotherapy. These findings indicate that the glutamine-mediated signal via Gln-K604 is a key driver of cancer progression and suggest potential strategies for targeted cancer therapies based on varying Gln-K604 status.
Glutamine/metabolism* ; Myeloid Cell Leukemia Sequence 1 Protein/genetics* ; Humans ; Proto-Oncogene Proteins c-myc/genetics* ; Cell Proliferation ; Signal Transduction ; Neoplasms/pathology* ; F-Box-WD Repeat-Containing Protein 7/genetics* ; Cell Survival ; Cell Line, Tumor ; Apoptosis

Functional dyspepsia (FD), characterized by persistent or recurrent dyspeptic symptoms without identifiable organic, systemic or metabolic causes, is an increasingly recognized global health issue. The objective of this guideline is to equip clinicians and nursing professionals with evidence-based strategies for the management and treatment of adult patients with FD using traditional Chinese medicine (TCM). The Guideline Development Group consulted existing TCM consensus documents on FD and convened a panel of 35 clinicians to generate initial clinical queries. To address these queries, a systematic literature search was conducted across PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, China Biology Medicine (SinoMed) Database, Wanfang Database, Traditional Medicine Research Data Expanded (TMRDE), and the Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS). The evidence from the literature was critically appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The strength of the recommendations was ascertained through a consensus-building process involving TCM and allopathic medicine experts, methodologists, pharmacologists, nursing specialists, and health economists, leveraging their collective expertise and empirical knowledge. The guideline comprises a total of 43 evidence-informed recommendations that span a range of clinical aspects, including the pathogenesis according to TCM, diagnostic approaches, therapeutic interventions, efficacy assessments, and prognostic considerations. Please cite this article as: Zhang SS, Zhao LQ, Hou XH, Bian ZX, Zheng JH, Tian HH, Yang GH, Hong WS, He YY, Liu L, Shen H, Li YP, Xie S, Shu J, Zeng BF, Li JX, Liu Z, Xiao ZH, Xiao JD, Zheng PY, Huang SG, Chen SL, Fei GJ. International clinical practice guideline on the use of traditional Chinese medicine for functional dyspepsia (2025). J Integr Med. 2025; 23(5):502-518.
Dyspepsia/drug therapy* ; Humans ; Medicine, Chinese Traditional/methods* ; Practice Guidelines as Topic ; Drugs, Chinese Herbal/therapeutic use*

OBJECTIVE: To investigate the relationship between physical activity and genetic risk and their combined effects on the risk of developing chronic obstructive pulmonary disease. METHODS: This prospective cohort study included 318,085 biobank participants from the UK. Physical activity was assessed using the short form of the International Physical Activity Questionnaire. The participants were stratified into low-, intermediate-, and high-genetic-risk groups based on their polygenic risk scores. Multivariate Cox regression models and multiplicative interaction analyses were used. RESULTS: During a median follow-up period of 13 years, 9,209 participants were diagnosed with chronic obstructive pulmonary disease. For low genetic risk, compared to low physical activity, the hazard ratios ( HRs) for moderate and high physical activity were 0.853 (95% confidence interval [ CI]: 0.748-0.972) and 0.831 (95% CI: 0.727-0.950), respectively. For intermediate genetic risk, the HRs were 0.829 (95% CI: 0.758-0.905) and 0.835 (95% CI: 0.764-0.914), respectively. For participants with high genetic risk, the HRs were 0.809 (95% CI: 0.746-0.877) and 0.818 (95% CI: 0.754-0.888), respectively. A significant interaction was observed between genetic risk and physical activity. CONCLUSION Moderate or high levels of physical activity were associated with a lower risk of developing chronic obstructive pulmonary disease across all genetic risk groups, highlighting the need to tailor activity interventions for genetically susceptible individuals.
Humans ; Pulmonary Disease, Chronic Obstructive/epidemiology* ; Exercise ; Male ; Female ; Middle Aged ; Prospective Studies ; Aged ; Genetic Predisposition to Disease ; Risk Factors ; United Kingdom/epidemiology* ; Incidence ; Adult

Objective: To analyze the status and trends of physical fitness test data among college freshmen with different body mass index (BMI) groups from 2014 to 2024, providing the scientific evidence for monitoring and intervening in college students physical health. Methods: A census was conducted on all 67 949 freshmen at Civil Aviation University of China from 2014 to 2024. Physical tests included vital capacity, sit and reach, sit ups, 50 m sprint, standing long jump, pull ups, and 800 m/1 000 m run. Freshmen were divided into underweight, normal weight, overweight and obese groups according to WHO BMI standards. The Kruskal-Wallis H test was used to compare differences in physical fitness indicators across gender and BMI groups, while the Mann-Kendall trend test was employed to detect upward or downward trends in physical indicators over time. Results: From 2014 to 2024, statistically significant differences were observed in vital capacity, 50 m sprint, standing long jump, and sit and reach among different BMI groups for both genders (boy: Z =2 396.40, 4 160.33, 4 662.23, 531.85; girl: Z =593.37, 308.86, 499.37, 128.70). Significant differences were also found in 1 000 m run and pull ups for boys, and 800 m run and sit ups for girls across BMI groups (boy: Z =6 574.80, 6 880.48; girl: Z =528.56, 146.18) ( P <0.01). Overall physical test scores showed a declining trend during 2014-2024, particularly pronounced in overweight and obese groups. Male vital capacity in 2014 exceeded national survey data( d =320 mL), with the gap widening to 734 mL by 2019, while the female vital capacity difference increased from 271 mL in 2014 to 576 mL in 2019. Male 1 000 m run times were 23.0 s and 17.5 s faster than national data in 2014 and 2019 respectively, while female 800 m run times were 22.3 s and 21.5 s faster than corresponding national data. Conclusions Physical health status among freshmen at this university varies across BMI groups and changes over time. Although overall test scores remain higher than national levels, the declining trend in physical fitness performance requires attention.

Objective:To investigate the association between the triglyceride-glucose(TyG)index and the incidence and mortality of cardiovascular disease(CVD)in a large population-based cohort.Methods:Participants aged 40-79 years without a history of CVD at baseline were drawn from the CHi-nese Electronic health Records Research in Yinzhou(CHERRY)study between January 1,2010,and May 31,2020.The TyG index was calculated using baseline triglyceride and fasting blood glucose.Cox proportional hazards models were used to assess the association between the TyG index and the composite outcome of CVD(incidence and mortality),adjusting for age,gender,education,region,smoking sta-tus,body mass index,systolic blood pressure,and total cholesterol.Hazard ratios(HR)and 95％confi-dence intervals(CI)were calculated.Nonlinear associations between the TyG index and CVD were fur-ther evaluated using restricted cubic splines,and subgroup analyses by gender and age were conducted to explore potential differences.Results:A total of 226 406 individuals were included,with a mean age of(55.0±9.7)years at baseline,46.8％of whom were men,and a median TyG index of 8.68.Over a median follow-up of 7.99 years,9 815(4.34％)participants experienced CVD incidence or mortality.After adjusting for age,gender,education,region,smoking status,body mass index,systolic blood pressure and total cholesterol,the risk of CVD increased with higher TyG index levels(P＜0.001).The risk in the highest TyG quartile(TyG＞9.10)was 42％higher than in the lowest quartile(TyG ≤8.32)(HR=1.42,95％CI:1.34-1.51).Individuals under 60 years had a higher HR for CVD compared with those aged 60 years and above(HR:1.71 vs.1.27,P＜0.05).Restricted cubic spline analysis revealed a reverse L-shaped association between the TyG index and CVD risk in the overall population(P＜0.001 for nonlinear trend),with risk increasing after the TyG index exceeded 8.67.However,the threshold varied by gender,with a lower threshold in women(8.51)than in men(8.67).Conclusion:A significant nonlinear relationship was revealed between the TyG index and CVD risk,with a threshold effect.The risk of CVD increased once the TyG index surpassed a certain threshold,with a lower threshold in women than in men.These findings suggest that cardiovascular risk prediction and interven-tions based on the TyG index should be gender-stratified,and early intervention for individuals under 60 years old might have important public health implications.

BACKGROUND:D1-3-n-butylphthalide has antioxidant and anti-inflammatory effects and has been explored to have protective role in Parkinson's disease,but the underlying mechanisms are unknown.OBJECTIVE:To investigate the protective effect of D1-3-n-butylphthalide by the approach of network pharmacology,molecular docking,and cellular experimental validation.METHODS:(1)Network pharmacology and molecular docking:The database was used to screen the targets of D1-3-n-butylphthalide and Parkinson's disease.The intersection was taken from the construction of the target protein interaction network,and then screen the core targets.The GO and KEGG pathway enrichment was used to further analyze the core targets.The interaction between the target proteins and D1-3-n-butylphthalide was verified by molecular docking.(2)Cell validation:The passage 6 PC12 cells were divided into six groups for culture.The control group was cultured with conventional culture medium.The model group was cultured with N-methyl-4-phenylpyridinium iodide to induce Parkinson's disease model.The ML385 inhibitor group was added with nuclear factor E2-related factor 2 inhibitor ML385 on the basis of inducing Parkinson's disease model.The D1-3-n-butylphthalide treatment group was added with butylphthalide on the basis of inducing Parkinson's disease model.The D1-3-n-butylphthalide combined with ML385 treatment group was added with D1-3-n-butylphthalide and ML385 on the basis of inducing Parkinson's disease model.The D1-3-n-butylphthalide group was cultured with conventional culture medium containing butylphthalide alone.Cell proliferation,intracellular reduced glutathione and malondialdehyde levels,and protein expression of protein kinase B/glycogen synthase kinase 3β/nuclear factor E2-related factor 2(AKT/GSK-3β/Nrf2)signaling pathway were detected.RESULTS AND CONCLUSION:(1)A total of 52 targets were screened for the intersection of drugs and disease targets,and the core targets including the matrix metalloproteinase 9 and GSK-3β were involved the phosphatidylinositol 3-kinase(PI3K)/AKT and oxidative stress-related signaling pathways.The molecular docking binding energy of D1-3-n-butylphthalide and GSK-3β was-18.27 kJ/mol,which indicated that D1-3-n-butylphthalide had a good binding ability with GSK-3β.(2)Compared with the model group,the PC12 cell activity and reduced glutathione level in the D1-3-n-butylphthalide treatment group were increased(P＜0.05),the malondialdehyde level was decreased(P＜0.05),and the expression of p-AKT,p-GSK-3β,Nu-Nrf2,and T-Nrf2 proteins was increased(P＜0.05).Compared with the D1-3-n-butylphthalide group,the PC12 cell activity and reduced glutathione level in the D1-3-n-butylphthalide combined with ML385 treatment group were decreased(P＜0.05),the malondialdehyde level was increased(P＜0.05),and the expression of Nu-Nrf2 and T-Nrf2 proteins was decreased(P＜0.05).(3)These results demonstrate that D1-3-n-butylphthalide can inhibit oxidative stress and improve cell activity through the AKT/GSK-3β/Nrf2 signaling pathway,and has a protective effect on the Parkinson's cell model induced by N-methyl-4-phenylpyridinium iodide.

In this report, the protective effect and molecular mechanism of Chaihu Shugan San-containing serum on corticosterone(CORT)-induced mitochondrial damage in pheochromocytoma(PC12) cells was studied based on CORT-induced rat PC12 cell model. The cultured cells were divided into five groups: blank control group, CORT group(400 μmol·L~(-1) CORT), Chaihu Shugan San-containing serum group(400 μmol·L~(-1) CORT + 10% Chaihu Shugan San-containing serum), control serum group(400 μmol·L~(-1) CORT + 10% control serum), and fluoxetine group(400 μmol·L~(-1) CORT + 10% fluoxetine-containing serum). The study was carried out by cell activity detection, mitochondrial morphology observation, membrane potential measurement, energy metabolism analysis, and mitochondrial dynamics-related protein detection. The results showed that CORT treatment significantly reduced the survival rate of PC12 cells, altered mitochondrial morphology, and decreased mitochondrial membrane potential and adenosine triphosphate(ATP) synthetic rate. Both Chaihu Shugan San-and fluoxetine-containing serum significantly increased the survival rate of CORT-treated PC12 cells and the ATP synthetic rate in the mitochondria. Unlike fluoxetine, Chaihu Shugan San-containing serum significantly inhibited the decrease in mitochondrial membrane potential caused by CORT and increased the oxygen consumption rate(OCR) values of both mitochondrial maximum respiration and reserve respiration capacity. Western blot analysis showed that CORT induced upregulated protein expressions of dynamin-related protein 1(Drp1) and peroxisome proliferator-activated receptor gamma co-activator 1α(PGC-1α) in PC12 cells and specific protein expression of optic atrophy protein 1(OPA1), yet it repressed the protein expressions of silent information regulator 1(SIRT1) and mitochondrial fusion protein 1(Mfn1) in PC12 cells. Both Chaihu Shugan San-and fluoxetine-containing serum significantly inhibited the protein expression of Drp1. However, only Chaihu Shugan San-containing serum could significantly inhibit the CORT-induced upregulation protein of PGC-1α. RESULTS:: herein suggest that Chaihu Shugan San-containing serum can alleviate CORT-induced damage in PC12 cells, which may be related to the mitochondrial fragmentation/lipid peroxidation protection by Drp1 inhibition, as well as mitochondrial dynamics and energy metabolism mediated by PGC-1α/SIRT1 signaling pathway.
Animals ; PC12 Cells ; Rats ; Mitochondrial Dynamics/drug effects* ; Mitochondria/metabolism* ; Corticosterone/adverse effects* ; Membrane Potential, Mitochondrial/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Protective Agents/pharmacology* ; Cell Survival/drug effects*

OBJECTIVES: To investigate the characteristics and clinical significance of anorectal manometry measurements in children with tethered cord syndrome (TCS) before and after surgery. METHODS: A retrospective study was conducted on 44 children with TCS treated at the Children's Hospital of Zhejiang University School of Medicine from January 2022 to September 2023. These patients were divided into effective subgroup (n=34) and non-effective subgroup (n=10) based on postoperative symptom improvement. Additionally, 34 children with functional constipation were selected as a control group. Baseline data and manometry measurements were compared between the preoperative TCS group and the control group, as well as between the non-effective and effective subgroups. RESULTS: The TCS group had lower short contraction time and defecation relaxation rate compared to the control group (P<0.05), while defecation residual pressure and maximum rectal tolerable threshold were higher than the control group (P<0.05). The length of the anal canal in the high-pressure zone in the effective subgroup was greater postoperatively than preoperatively (P<0.05), and the initial rectal sensation threshold decreased postoperatively (P<0.05). The non-effective subgroup had lower preoperative maximum rectal expulsion pressure compared to the effective subgroup (P<0.05). Postoperative rectal anal inhibition reflex values in the effective subgroup were higher than those in the non-effective subgroup (P<0.05). CONCLUSIONS There are some differences in anorectal dynamics between children with TCS and those with functional constipation. Maximum rectal expulsion pressure may be a key predictor of surgical outcomes. Surgery can alter certain defecation functions in some children.
Humans ; Male ; Anal Canal/physiopathology* ; Female ; Rectum/physiopathology* ; Child ; Child, Preschool ; Retrospective Studies ; Manometry ; Neural Tube Defects/physiopathology* ; Infant ; Defecation ; Adolescent ; Constipation/physiopathology* ; Clinical Relevance