Lower urinary tract dysfunction is multifactorial, yet the role of environmental exposure remains poorly investigated. Developmental exposure to polychlorinated biphenyls (PCBs) has been linked to altered voiding in mice; however, the disposition of PCBs in the bladder, their bioactivation, and their effects on cytochrome P450 (CYP) expression remain unclear. We exposed mice to an environmentally relevant PCB mixture via maternal diet during gestation and lactation (vehicle, 0.1, 1, or 6 mg/kg/day). Offspring were euthanized at 6 to 7 weeks of age. PCB and hydroxylated PCB (OH-PCB) levels were quantified in the bladder, liver, blood, and urine. CYP expression was measured in the bladder and liver. PCBs and OH-PCBs accumulated in all tissues in dose- and sex-dependent manners, with higher-chlorinated congeners (e.g., PCB118, PCB138, PCB153, and PCB180) preferentially retained. Females exhibited greater hepatic accumulation, reduced urinary elimination, and distinct CYP regulation characterized by increased hepatic and decreased bladder expression. These findings, for the first time, define the signature of PCBs and OH-PCBs in the bladder and reveal a sex-specific PCB disposition and CYP responses. Our results provide new mechanistic insights into developmental PCB exposure and its potential contribution to voiding dysfunction in wildlife, domestic animals, and humans.

Many women suffer from symptoms associated with dysfunction of the lower urinary tract, including incontinence and overactive bladder, especially during pregnancy. While causes are likely multifactorial, environmental factors, such as exposure to polychlorinated biphenyls (PCBs), have been shown to alter voiding in adult female mice. However, the distribution of PCBs and their metabolites to the bladder and urine, as well as their effects on bladder drug-metabolizing enzyme expression after dosing with PCB mixtures, remains largely unexplored. Female C57BL/6J mice were exposed to MARBLES PCB mixture (0, 0.1, 1, and 6 mg/kg/d) through gestation and lactation, and post-weaning bladder, urine, blood, adipose, and liver were collected for measurement of PCBs and OH-PCBs, and for abundance of cytochrome P450 (Cyp) transcripts in liver and bladder. PCBs and OH-PCBs were detected in all tissues in a dose-dependent manner. Bladder, adipose, and liver retained parent PCBs while OH-PCBs were predominant in urine and blood. Cyp1a2 mRNA abundance was elevated in the liver of the high dose PCB group versus the vehicle, and the same trend was observed in the bladder. These results define the signatures of PCBs and OH-PCBs in the bladders and urine of post-weaning dams exposed to the MARBLES mixture of PCBs and provide a reference for comparison with accumulation in more commonly studied tissues. Our results also provide new insights into the regulation of Cyp1a2 in the liver and bladder, changes that may play a role in how environmental exposures in adulthood alter voiding function.

Polychlorinated biphenyls (PCBs) are highly stable synthetic organic compounds that are present in air, water, and soil. PCBs have been identified in post-mortem human brains, indicating a possible link between environmental factors and disease risk. Research has revealed an association between PCB exposure and cognitive decline. Therefore, it is crucial to evaluate how PCB mixtures relevant to humans affect brain function and cognition. To investigate the effects of PCBs on memory and transcriptomic profiles, we exposed male C57BL/6 J mice orally to a synthetic PCB mixture daily. After seven weeks of exposure, the adult mice were assessed in a spatial object recognition task (SOR) to evaluate long-term spatial memory. Our findings showed that mice exposed to PCBs exhibited deficits in long-term spatial memory. To examine the molecular effects of PCB on the brain, we used a spatial transcriptomics technique to analyze gene expression changes in five brain regions: the hippocampus, neocortex, thalamus, caudal putamen, and fiber tracts. Our analysis of spatial gene expression revealed the molecular signatures influenced by PCB in these susceptible brain regions of mice. Network analysis suggests that these changes are associated with higher chlorinated PCBs present in the brain. Additionally, we show that PCB exposure disrupts the expression of tight junction proteins, which are crucial for maintaining the integrity of the blood-brain barrier (BBB). Thus, our results offer mechanistic insights into how PCB exposure affects brain function and cognition.

OBJECTIVES:Given the variable eradication efficacy of bismuth-containing quadruple therapies (BcQT), comparator choice is critical in randomised controlled trials (RCTs) of Helicobacter pylori (H. pylori) eradication. This study compared the efficacy and safety of tegoprazan-amoxicillin dual therapy (TADT) versus esomeprazole-amoxicillin-tetracycline bismuth-containing quadruple therapy (EBQT) as first-line treatment. METHODS:In this non-inferiority RCT conducted at Qilu Hospital of Shandong University from March 2023 to January 2024, treatment-naïve H. pylori-infected patients were randomised to receive TADT or EBQT for 14 days. The primary outcome was eradication rate in the intention-to-treat (ITT), modified ITT (mITT) and per-protocol (PP) analyses. Secondary outcomes were adverse events and compliance. A meta-analysis of RCTs comparing TADT with BcQT for first-line eradication was also performed. RESULTS:A total of 258 patients were randomised. Eradication rates were 82.95% vs 90.70% (P = 0.066) in ITT, 84.25% vs 91.41% (P = 0.080) in mITT, and 89.17% vs 95.80% (P = 0.052) in PP analysis for TADT and EBQT, respectively. Although eradication rates were comparable, TADT failed to demonstrate non-inferiority to EBQT. Adverse events (20.16% vs 26.36%, P = 0.238), and compliance (96.12% vs 95.35%, P = 0.758) were similar. Seven groups were included in the meta-analysis. In the ITT subgroup analysis by antibiotic combination, TADT showed a significantly lower eradication rate than amoxicillin- and tetracycline/metronidazole-containing BcQT (RR = 0.90, 95% CI: 0.84-0.97; P = 0.006). CONCLUSIONS:TADT showed comparable eradication rates to EBQT but was not non-inferior, with similar safety and compliance. Comparator choice is critical in RCTs.

Polychlorinated biphenyls (PCBs) are environmental pollutants linked to neurological impairments by mechanisms involving the gut microbiome. This study examines the effects of maternal exposure to a PCB mixture on the gut microbiome of post-weaning mouse dams. Female C57BL/6 J mice were exposed daily to PCBs at different doses (0, 0.1, 1, or 6 mg/kg body weight/day) before mating, and throughout gestation and lactation. Post-weaning intestinal contents from dams were analyzed to assess microbiome abundance and quantify PCBs and their metabolites. PCB exposure affected the composition of microbial taxa, though not significantly. However, topic modeling analysis identified a distinct microbial community that was significantly more prevalent in the control group compared to post-weaning mouse dams exposed to the MARBLES mixture at medium and high doses. Complex PCBs and metabolite mixtures were detected in the intestinal contents. Certain PCBs and their metabolites were associated with changes in bacterial abundance, as determined by network analysis. These findings show that individual PCBs and their metabolites can affect gut microbial communities, potentially contributing to neurological impairments in mice exposed to PCBs during gestation and lactation.

BACKGROUND:Accurate determination of postmortem interval (PMI) and cause of death (COD) is a critical challenge in forensic pathology, with significant implications for criminal investigations. Traditional PMI estimation methods are based on macroscopic changes and are influenced by environmental factors and investigator subjectivity. Recent advances in molecular biology have shown that certain cellular structures, such as mitochondria, retain functionality after death, making them potential biomarkers for forensic assessment. As mitochondria play a central role in cellular metabolism and respond dynamically to post-mortem hypoxia, investigation of mitochondrial membrane potential (ΔΨm) may provide a quantifiable and objective method for estimating PMI. RESULTS:We successfully isolated mitochondria from post-mortem tissues and cultured cells, confirming their purity and membrane integrity. Regression analysis showed a strong linear correlation between ΔΨm and PMI in brain, myocardium and skeletal muscle within the first 15-18 h postmortem, with skeletal muscle showing the highest correlation coefficient. ΔΨm values remained stable at different temperatures, suggesting that it is a robust biomarker for estimating PMI. In vitro experiments under hypoxic conditions revealed a transient increase in ΔΨm at 24 h, accompanied by ATP depletion, ROS accumulation and shifts in mitochondrial fission and fusion dynamics, indicating mitochondrial adaptation to oxygen deprivation. CONCLUSIONS:These findings highlight ΔΨm as a promising temperature stable biomarker for early assessment of PMI. The observed mitochondrial adaptations suggest that ΔΨm-based models may improve forensic accuracy and provide insights into postmortem metabolic processes. Further validation with human postmortem samples is essential to refine these models and explore their applicability to COD determination.

BACKGROUND:Penicillin allergy significantly restricts therapeutic options for Helicobacter pylori eradication. This multicenter randomized controlled study was designed to evaluate the efficacy and safety of a novel cefuroxime-tetracycline-containing bismuth quadruple therapy (Cef-Tet BQT) as first-line treatment in this population. MATERIALS AND METHODS:Penicillin-allergic treatment-naïve patients with confirmed H. pylori infection (N = 248) were randomized to two 14-day regimens: one received Cef-Tet BQT (Tegoprazan 50 mg twice a day, bismuth potassium citrate 220 mg twice daily, cefuroxime 500 mg twice daily, tetracycline 500 mg three times daily), and the other received cefuroxime-levofloxacin-containing bismuth quadruple therapy (Cef-Lev BQT: cefuroxime 500 mg twice daily, levofloxacin 500 mg once daily). The primary endpoint assessed noninferiority of eradication rates, with secondary endpoints including safety profiles and adherence. RESULTS:In total, 248 patients underwent randomization. The intention-to-treat (ITT) eradication rates were 90.32% (112/124, 95% confidence interval [CI]: 85.12%-95.52%) and 81.45% (101/124, 95% CI: 74.61%-88.29%) (p = 0.045); the modified intention-to-treat (MITT) eradication rates were 91.80% (112/122, 95% CI: 86.93%-96.67%) and 83.47% (101/121, 95% CI: 76.85%-90.09%) (p = 0.048); and the per-protocol (PP) eradication rates were 92.37% (109/118, 95% CI: 87.58%-97.16%) and 85.34% (99/116, 95% CI: 78.90%-91.78%) (p = 0.087) in the Cef-Tet BQT group and Cef-Lev BQT group, respectively. Noninferiority of the Cef-Tet BQT group was demonstrated in all three analyses (p < 0.0001). The incidence of adverse events (21.77% vs. 24.19%) and compliance (96.77% vs. 95.97%) were comparable between the two groups. CONCLUSIONS:BQT containing cefuroxime and tetracycline is efficacious and safe for the first-line eradication of H. pylori in penicillin-allergic patients. This regimen provides a viable alternative to circumvent the antimicrobial resistance concerns associated with levofloxacin-based regimens. TRIAL REGISTRATION:ClinicalTrials.gov ID: NCT06351891.

Toxicities of lower-chlorinated biphenyls (LC-PCBs) have drawn increasing attention due to growing evidence of their presence in school indoor air, with 2,4,4'-trichlorobiphenyl (PCB28) being a prevalent congener. The tissue levels and characteristics of individual PCB congeners determine the PCB toxicity. Yet, the tissue disposition time course of individual LC-PCBs following pulmonary exposure is largely unknown. To address this data gap, we investigated the whole-body disposition, metabolism, and elimination kinetics of PCB28 in rats following intratracheal lung dosing of radiolabeled [14C]-PCB28. Blood, 36 tissue types, 6 digestive matters, and excreta were sampled at specific intervals (12, 25, 50, 100, 200, 400, 720, and 1440 min) postexposure. The pulmonary uptake of PCB28 was nearly complete at 99.9 ± 3.5%. PCB28 rapidly distributed across multiple tissues, initially accumulating in lung and liver, followed by redistribution to the adipose and skin. PCB28 exhibited linear toxicokinetics (TK) in highly perfused tissues, resulting in dose-proportional increases in the area under the concentration-time curves. In contrast, adipose tissue, skin, and prostate displayed nonlinear TK. The elimination half-life of [14C]-PCB28 was 12 h, with elimination primarily via the fecal route. This study provides new data on the toxicokinetics of PCB28 following pulmonary exposure to support the development of TK models for evaluating the health risks posed by this persistent environmental pollutant.

Polychlorinated biphenyls (PCBs) remain an environmental health concern due to their persistence and ongoing release from legacy and emerging sources. 2,2',5,5'-Tetrachlorobiphenyl (PCB52), a PCB congener frequently detected in the environment and human blood, is oxidized to 2,2',5,5'-tetrachlorobiphenyl-4-ol (4-52). The neurotoxicity of this hydroxylated (OH-PCB) metabolite remains poorly characterized. In this study, we exposed 4-week-old male Sprague Dawley rats to 4-52 via a polymeric implant drug delivery system grafted in the subcutaneous cavity at 4-52 concentrations of 0 %, 1 %, 5 %, and 10 % in the implant (w/w) for 28 days. Metabolomic analyses were performed in the serum. RNA sequencing, immunofluorescence, and dopamine (DA) measurement with electrochemical detection were used to characterize the effects of 4-52 on the striatum and cerebellum, brain regions implicated in PCB neurotoxicity. Serum metabolomic analysis revealed disruptions in the "arginine biosynthesis" pathway following 4-52 exposure. Exposure to 4-52 caused moderate transcriptomic changes in pathways related to "oxidative phosphorylation" and "neuroactive ligand-receptor interactions." Immunofluorescence showed no significant alterations in microglial, astrocytic, or apoptotic biomarkers. In the medium dose group, the levels of the DA metabolite DOPAL (3,4-dihydroxyphenylacetaldehyde) were significantly reduced in the striatum. Subsequent multi-omics network analysis identified interactions among OH-PCBs, endogenous metabolites, and the transcriptome. For example, levels of glutamic acid, aspartic acid, choline, and glycerophosphocholine negatively correlated with 4-52 in the striatum. Expression levels of heat shock protein (HSP) family genes, Hsp90b1, Hspa8, and Hspa5, positively correlated with serum metabolites, including proline, 1-methylguanidine, and methionine sulfoxide. These findings identify novel biomarkers and targets of 4-52-induced neurotoxicity.

Environmental toxicants, such as polychlorinated biphenyls (PCBs), are highly stable synthetic organic compounds that are present in air, water, and soil. PCBs have been identified in post-mortem human brains of individuals with neurodegenerative diseases, indicating a possible link between environmental factors and disease risk. Research has revealed an association between PCB exposure and cognitive decline. Therefore, it is crucial to evaluate how PCB mixtures relevant to humans affect brain function and cognition. To investigate the effects of PCBs on memory and transcriptomic profiles, we exposed adult male C57BL/6J mice orally to a synthetic PCB mixture daily. After seven weeks of exposure, the mice were assessed in a spatial object recognition task (SOR) to evaluate long-term spatial memory. Our findings showed that mice exposed to PCBs exhibited deficits in long-term spatial memory. To examine the molecular effects of PCB on the brain, we used a spatial transcriptomics technique to analyze gene expression changes in five brain regions: the hippocampus, neocortex, thalamus, caudal putamen, and fiber tracts. Our analysis of spatial gene expression revealed the molecular signatures influenced by PCB in these susceptible brain regions of mice. Network analysis suggests that these changes are associated with higher chlorinated PCBs present in the brain. Additionally, we show that PCB exposure disrupts the expression of tight junction proteins, which are crucial for maintaining the integrity of the blood-brain barrier (BBB). Thus, our results offer mechanistic insights into how PCB exposure affects brain function and cognition.

Polychlorinated biphenyls (PCBs) are neurotoxic hazardous materials that may cause toxicity via the gut-liver-brain axis. This study investigated PCB × microbiome interactions in adult female mice exposed orally to an environmental PCB mixture. Female mice (6-week-old) were exposed daily for 7 weeks to peanut butter containing 0, 0.1, 1, or 6 mg/kg/day of PCBs. Twenty hours after the final exposure, the cecal content was collected to characterize the microbiome composition and predicted function. PCB and its metabolites in feces were analyzed using gas chromatography-tandem mass spectrometry (GC-MS/MS), while cecal content was assessed with liquid chromatography-high resolution mass spectrometry (LC-HRMS). PCB exposure influenced the abundance of microbial taxa and predicted functions within the cecal content. Complex PCB and metabolite mixtures were detected in the gastrointestinal tract. Network analysis revealed associations between specific parent PCBs and metabolites with changes in the abundance of bacteria in the gastrointestinal tract. These findings demonstrate that individual PCBs and their metabolites significantly influence the abundance of specific bacteria in the gastrointestinal tract following oral PCB exposure. These findings inform further research targeting the microbiome to attenuate the adverse health outcomes of PCB exposure.

Over the past few decades, many studies assessing the effect of thiazide diuretics showed controversial results. Additionally, recent guidelines fail to address the optimal dosage and treatment duration of thiazide diuretics. Therefore, we conducted a meta-analysis to evaluate the efficacy, optimal dosage, and treatment duration of thiazide diuretics in preventing recurrent urolithiasis. We conducted a comprehensive search of three electronic databases (PubMed, Embase and Cochrane Library) up to January 2024, utilizing specific keywords to identify eligible studies. Subsequently, we performed an overall meta-analysis. Subgroup analysis was also performed to evaluate the efficacy, optimal dosage, and treatment duration of thiazide diuretics. Twelve eligible studies were included, with a total of 1217 patients. Overall, our findings demonstrated the efficacy of thiazide diuretics in preventing recurrent urolithiasis (RR = 0.55, 95

This protocol aims to determine the levels of dopamine (DA) and its metabolites 3,4-dihydroxyphenylacetaldehyde (DOPAL) and 3,4-dihydroxyphenylacetic acid (DOPAC) in brain tissue samples. The measurement was performed by a high-performance liquid chromatography (HPLC)with electrochemical detection (ECD). The levels of DA, DOPAL, and DOPAC were quantified using a 5-point calibration curve prepared in 0.3 M perchloric acid and were expressed as pmol of analyte per mg of protein. Protein content in the sample pellet was determined using a bicinchoninic acid (BCA) protein assay kit following the manufacturer's instructions.

ObjectiveTo update evidence‐based data comparing the efficacy and safety of high‐dose dual therapy (HDDT) and bismuth‐containing quadruple therapy (BQT) in eradicating Helicobacter pylori infection through meta‐analysis.MethodsMultiple databases were systematically searched for randomized controlled trials (RCTs) published up to May 18, 2023. Dichotomous data were evaluated using risk ratio (RR) and 95% confidence interval (CI). Subgroup analysis, sensitivity analysis, risk of bias assessment, and quality of evidence evaluation were performed.ResultsTwenty RCTs containing 7891 subjects were included in the analysis. There was no statistically significant difference in H. pylori eradication rate between HDDT and BQT in the intention‐to‐treat (ITT) analysis (86.31% vs 84.88%; RR 1.02, 95% CI 1.00–1.04, P = 0.12). In the per‐protocol (PP) analysis, the eradication rates for HDDT and BQT were 90.27% and 89.94%, respectively (RR 1.01, 95% CI 0.99–1.03, P = 0.44). Adverse events were significantly lower with HDDT than with BQT (RR 0.44, 95% CI 0.38–0.51, P < 0.00001). Patient adherence was significantly different between the two groups (RR 1.01, 95% CI 1.00–1.03, P = 0.02). Subgroup analysis based on antibiotic combinations within the BQT group showed a significantly higher eradication rate for HDDT than for BQT only when BQT used amoxicillin combined with clarithromycin (P = 0.0009).ConclusionsHDDT showed comparable efficacy with BQT for H. pylori eradication, with fewer adverse effects and higher compliance. Due to regional differences, antibiotic resistance rates, and combined BQT antibiotics, more studies are needed for further validation and optimization of HDDT.

Polychlorinated biphenyls (PCBs) are persistent organic pollutants that pose a current ecosystem and human health concern. PCB exposure impacts the gut microbiome in animal models, suggesting a mechanistic link between PCB exposure and adverse health outcomes. The presence and absence of the microbiome and exposure to PCBs independently affect the lipid composition in the liver, which in turn affects the PCB disposition in target tissues, such as the liver. Here, we investigated microbiome × subacute PCB effects on the hepatic lipid composition of conventional and germ-free female mice exposed to 0, 6, or 30mg/kg body weight of an environmental PCB mixture in sterile corn oil once daily for 3 consecutive days. Hepatic triacylglyceride and polar lipid levels were quantified using mass spectrometric methods following the subacute PCB exposure. The lipidomic analysis revealed no PCB effect on the hepatic levels. No microbiome effect was observed on levels of triacylglyceride and most polar lipid classes. The total hepatic levels of phosphatidylcholine (PC) and ether-phosphatidylcholine (ePC) lipids were lower in germ-free mice than the conventional mice from the same exposure group. Moreover, levels of several unsaturated PCs, such as PC(36:5) and PC(42:10), and ePCs, such as ePC(36:2) and ePC(4:2), were lower in germ-free than conventional female mice. Based on a KEGG pathway meta-analysis of RNA sequencing data, the ether lipid metabolism pathway is altered in the germ-free mouse liver. In contrast to the liver, extractable lipid levels, determined gravimetrically, differed in several tissues from naïve conventional vs. germ-free mice. Overall, microbiome × subacute PCB exposure effects on hepatic lipid composition are unlikely to affect PCB distribution into the mouse liver. Further studies are needed to assess how the different extractable lipid levels in other tissues alter PCB distribution in conventional vs. germ-free mice.

Bismuth-containing quadruple therapy is the first-line treatment for eradicating Helicobacter pylori (H. pylori). The optimal duration for H. pylori eradication using bismuth-containing quadruple therapy remains controversial. Therefore, we aimed to compare the clinical effects of the 10- and 14-day bismuth-containing quadruple treatment regimen to eradicate H. pylori. Treatment-naïve patients with H. pylori infection (n = 1300) were enrolled in this multicenter randomized controlled study across five hospitals in China. They were randomized into 10- or 14-day treatment groups to receive bismuth-containing quadruple therapy as follows: vonoprazan 20 mg twice daily; bismuth 220 mg twice daily; amoxicillin 1000 mg twice daily; and either clarithromycin 500 mg twice daily or tetracycline 500 mg four times daily. At least 6 weeks after treatment, we performed a 13C-urea breath test to evaluate H. pylori eradication. The per-protocol eradication rates were 93.22

ABSTRACT Background Current guidelines recommend bismuth‐containing quadruple therapy for patients newly diagnosed with Helicobacter pylori ( H. pylori ) infection. We aimed to compare the efficacy and safety of tetracycline administered three times daily versus four times daily in bismuth‐containing quadruple therapy for first‐line treatment of H. pylori infection. Methods This multicenter, noninferiority, randomized controlled study, conducted in China, recruited treatment‐naïve adults with H. pylori infection, randomized 1:1 into two treatment groups to receive either of the following bismuth‐containing quadruple therapies: esomeprazole 20 mg twice‐daily; bismuth 220 mg twice‐daily; amoxicillin 1000 mg twice‐daily; and tetracycline 500 mg three times daily (TET‐T) versus 500 mg four times daily (TET‐F). At least 6 weeks post‐treatment, a 13 C‐urea breath test was performed to evaluate H. pylori eradication. Results In total, 406 patients were randomly assigned to the two treatment groups. Intention‐to‐treat eradication rates were 91.63% (186/203; 95% confidence interval [CI] 87.82%–95.44%) versus 90.15% (183/203; 95% CI 86.05%–94.25%) ( p = 0.0005) and per‐protocol eradication rates were 95.34% (184/193; 95% CI 92.36%–98.31%) versus 95.72% (179/187; 95% CI 92.82%–98.62%) ( p = 0.0002) for the TET‐T and TET‐F group, respectively. TET‐T‐treated patients had a lower incidence of adverse effects than TET‐F‐treated patients (21.61% vs. 31.63%, p = 0.024), with no significant differences in compliance to treatment between the groups. Conclusion As a first‐line therapy for H. pylori infection, the eradication rate of the TET‐T therapy was noninferior to that of the TET‐F therapy while significantly reducing the incidence of adverse reactions. Trial Registration ClinicalTrials.gov identifier: NCT05431075

BACKGROUND:The eradication of Helicobacter pylori (H. pylori) is crucial due to its rising prevalence and increasing resistance. Bismuth-containing quadruple therapies (BcQTs) have been proposed as a viable treatment option; however, the optimal duration for it remains contentious. This systematic review and meta-analysis aimed to compare the clinical efficacy of short-term BcQT (defined as 7 or 10 days) with a standard 14-day course. METHODS:A systematic search of PubMed, Embase, Web of Science, and the Cochrane Library was conducted for randomized controlled trials published in English until June 20, 2024. Eligibility criteria were applied to identify relevant studies. Summary risk ratios (RRs) and 95% confidence intervals (CIs) were calculated for the included studies regarding eradication rates, adverse effects, and compliance. This systematic review and meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and was previously registered in PROSPERO under registration number CRD42024547773. RESULTS:This meta-analysis finally included 15 trials involving a total of 4505 patients. The eradication rates for short courses of BcQT were lower than those for the 14-day course (RR 0.96, 95% CI 0.93-0.99). However, the eradication rate for the 10-day therapy was comparable to that of the 14-day therapy (RR 0.98, 95% CI 0.95-1.00). Subgroup analyses of antibiotic combinations indicated that tetracycline and metronidazole combinations yielded similar H. pylori eradication rates in the 7-day versus the 14-day BcQT (RR 0.93, 95% CI 0.84-1.02). In the potassium-competitive acid blocker subgroup, the eradication rates remained similar across the 14-day group and the short-course treatment groups, whether evaluating the short-term treatment groups as a whole or the 7- and 10-day subgroups separately. Additionally, the adverse effects and compliance associated with the short course of BcQT were comparable to those of the 14-day therapy. CONCLUSION:A 10-day course of BcQT may represent the optimal treatment duration. Nevertheless, the choice of antibiotic combination should be guided by the regional antibiotic resistance patterns of H. pylori, as combinations with lower resistance rates are more effective. TRIAL REGISTRATION:PROSPERO number: CRD42024547773.

Elevated airborne PCB levels in older schools are concerning due to their health impacts, including cancer, metabolic dysfunction-associated steatotic liver disease (MASLD), cardiovascular issues, neurodevelopmental diseases, and diabetes. During a four-week inhalation exposure to PCB52, an air pollutant commonly found in school environments, adolescent rats exhibited notable presence of PCB52 and its hydroxylated forms in their livers, alongside changes in gene expression. Female rats exhibited more pronounced changes in gene expression compared to males, particularly in fatty acid synthesis genes regulated by the transcription factor SREBP1. In vitro studies with human liver cells showed that the hydroxylated metabolite of PCB52, 4-OH-PCB52, but not the parent compound, upregulated genes involved in fatty acid biosynthesis similar to in vivo exposure. These findings highlight the sex-specific effects of PCB52 exposure on livers, particularly in females, suggesting a potential pathway for increased MASLD susceptibility.

ObjectivePrevious studies reported possible connections between inflammatory bowel disease (IBD) and several neurodegenerative disorders. However, the comprehensive relationships between IBD and various neurodegenerative disorders were not summarized. We executed a meta-analysis of longitudinal studies to provide an estimate of the strength of the two-directional prospective association between IBD and neurodegenerative disorders.MethodsWe accomplished a thorough bibliographic search of PubMed, Web of Science, Embase, PsycINFO, and Cochrane Library databases until June 2023 to locate relevant longitudinal studies. The extracted data were then analyzed via meta-analysis using either a fixed or random effects model.ResultsThe final analysis encompassed 27 studies. Individuals with IBD faced an increased risk of developing four neurodegenerative disorders than the general public, namely, Alzheimer’s disease (hazard ratio[HR] = 1.35, 95% confidence interval [CI]: 1.03–1.77, P=0.031), dementia (HR =1.24, 95% CI: 1.13–1.36, P<0.001), multiple sclerosis (HR =2.07, 95% CI:1.42–3.02, P<0.001) and Parkinson’s disease (HR =1.23, 95% CI:1.10–1.38, P<0.001). Two articles reported an increased incidence of amyotrophic lateral sclerosis or multiple system atrophy in IBD patients. Three studies investigated the prospective association between multiple sclerosis and IBD, revealing an elevated risk of the latter in patients with the former. (HR=1.87, 95% CI:1.66–2.10, P<0.001).InterpretationThese findings verified the two-directional relationship between the brain-gut axis, specifically demonstrating a heightened risk of various neurodegenerative diseases among IBD patients. It may be profitable to prepare screening strategies for IBD patients to find neurodegenerative diseases during the long-term course of treatment for IBD with a view to potential earlier diagnosis and treatment of neurodegenerative diseases, reducing public health and social burden.Systematic Review RegistrationPROSPERO (CRD42023437553).