Mechanism of action of the Banxia-Xiakucao herb pair in sleep deprivation: New comprehensive evidence from network pharmacology, transcriptomics and molecular biology experiments.

ETHNOPHARMACOLOGICAL RELEVANCE: Chinese herb pairs are the most basic and compressed examples of Chinese herbal combinations and can be used to effectively explain the fundamental concepts of traditional Chinese medicine prescriptions. These pairings have gained significant interest due to their subtle therapeutic benefits, minimal side effects, and efficacy in treating complicated chronic conditions. The Banxia-Xiakucao Chinese herb pair (BXHP) consists of Pinellia ternata (Thunb.) Breit. (Banxia) and Prunella vulgaris L. (Xiakucao). This formula was documented in The Medical Classic of the Yellow Emperor approximately 2000 years ago，and clinical research has demonstrated that BXHP effectively treats insomnia. AIM OF THE STUDY: This study aimed to evaluate the efficacy and therapeutic mechanism of the BXHP through a comprehensive strategy involving network pharmacology, molecular docking, transcriptomics, and molecular biology experimental validation. MATERIALS AND METHODS: The composition of BXHP was characterized using the UPLC-Q-TOF-MS. The active compounds were screened to find drug-likeness compounds by analyzing the ADME data. To predict the molecular mechanism of BXHP in sleep deprivation (SD) by network pharmacology and molecular docking. We established a rat model of SD and the in vivo efficacy of BXHP was verified through the pentobarbital sodium righting reflex test, behavioral assays, enzyme-linked immunosorbent assay, transmission electron microscopy, HE staining, and Nissl staining, and the underlying molecular mechanism of BXHP in SD was revealed through transcriptomic and bioinformatic analyses in conjunction with quantitative real-time PCR, Western blot, and immunofluorescence staining. RESULTS: In the present study, we showed for the first time that BXHP reduced sleep latency, prolongs sleep duration, and improves anxiety; lowered serum CORT, IL6, TNF-α and MDA levels; decreased hypothalamic Glu levels; and elevated hypothalamic GABA and 5-HT levels in SD rats. We found 16 active compounds that acted on 583 targets, 145 of which are related to SD. By modularly dissecting the PPI network, we discovered three critical targets, Akt1, CREB1, and PRKACA, all of which play important roles in the effects of BXHP on SD. Molecular docking resulted in the identification of 16 active compounds that strongly bind to key targets. The results of GO and KEGG enrichment analyses of network pharmacology and transcriptomics focused on both the regulation of circadian rhythm and the cAMP signaling pathway, which strongly demonstrated that BXHP affects SD via the cAMP-PKA-CREB-Circadian rhythm pathway. Molecular biology experiments verified this hypothesis. Following BXHP administration, PKA and CREB phosphorylation levels were elevated in SD rats, the cAMP-PKA-CREB signaling pathway was activated, the expression levels of the biological clock genes CLOCK, p-BMAL1/BMAL1, and PER3 were increased, and the rhythmicity of the biological clock was improved. CONCLUSIONS: The active compounds in BXHP can activate the cAMP-PKA-CREB-Circadian rhythm pathway, improve the rhythmicity of the biological clock, promote sleep and ameliorate anxiety, which suggests that BXHP improves SD through a multicomponent, multitarget, multipathway mechanism. This study is important for the development of herbal medicines and clinical therapies for improving sleep deprivation.

Longitudinal Relationship Between Psychological Capital and Anxiety in College Students: The Mediating Effect of Emotion Reregulation Strategy and Moderating Effect of Parent-Child Relationship.

Objective: Based on Conservation of resources theory, process model of emotion regulation and attachment theory, the present study examined how psychological capital affects anxiety through the mediation of emotion regulation strategies and explored the moderating role of parent-child relationship. Methods: Using a longitudinal study method, 962 college students were surveyed twice at one-year intervals. Results: (1) College students' emotion regulation strategies (including cognitive reappraisal and expressive suppression) partially mediated psychological capital and anxiety mood; (2) parent-child relationship moderated the pathways of psychological capital and expressive suppression on anxiety, respectively. Conclusion: College students with higher levels of parent-child relationship had stronger predictive effects of psychological capital and weaker predictive effects of expressive suppression on anxiety mood. The research findings clarify the combined effects of emotion regulation and parent-child relationships on anxiety among college students, providing valuable reference for the design and implementation of interventions to promote individual psychological well-being.

Effects of major air pollutants on angina hospitalizations: a correlation study.

BACKGROUND: Angina is a crucial risk signal for cardiovascular disease. However, few studies have evaluated the effects of ambient air pollution exposure on angina. OBJECTIVE: We aimed to explore the short-term effects of air pollution on hospitalization for angina and its lag effects. METHODS: We collected data on air pollutant concentrations and angina hospitalizations from 2013 to 2020. Distributed lag nonlinear model (DLNM) was used to evaluate the short-term effects of air pollutants on angina hospitalization under different lag structures. Stratified analysis by sex, age and season was obtained. RESULTS: A total of 39,110 cases of angina hospitalization were included in the study. The results showed a significant positive correlation between PM2.5, SO2, NO2, and CO and angina hospitalization. Their maximum harmful effects were observed at lag0-7 (RR = 1.042; 95% CI: 1.017, 1.068), lag0-3 (RR = 1.067; 95% CI: 1.005, 1.133), lag0-6 (RR = 1.078; 95% CI: 1.041, 1.117), and lag0-6 (RR = 1.244; 95% CI: 1.109, 1.397), respectively. PM10 did not have an overall risk effect on angina hospitalization, but it did have a risk effect on women and the elderly. O3 was significantly negatively correlated with angina hospitalization, with the most pronounced effect observed at lag0-6 (RR = 0.960; 95% CI: 0.940, 0.982). Stratified analysis results showed that women and the elderly were more susceptible to pollutants, and the adverse effects of pollutants were stronger in the cold season. CONCLUSION: Short-term exposure to PM2.5, SO2, NO2, and CO increases the risk of hospitalization for angina.

Effect of social participation on the trajectories of activities of daily living disability among community-dwelling older adults: a 7-year community-based cohort.

INTRODUCTION: Studies examining the effects of social participation on activities of daily living (ADL) disability are still scarce. AIM: To assess the reciprocal relationship between ADL disability trajectories and social participation among older Chinese people aged ≥ 60 years. METHODS: This study included 2976 participants aged ≥ 60 years in six waves of a community-based survey from 2015 to 2022. Basic activities of daily living (BADL) and instrumental activities of daily living (IADL) were used to assess the ADL disability in each survey. Social participation was assessed by involvement in four social activities and an extensive social participation score. Group-based trajectory modeling was used to identify potential heterogeneity in longitudinal changes over 7 years and explore associations between baseline predictors of group membership and these trajectories. RESULTS: Two BADL disability trajectories were identified: stable (94.8%) and increase (5.2%). Additionally, three IADL disability trajectories were distinguished: stable (73.2%), moderate (20.2%), and increase (6.6%). After controlling for the potential covariates, each point increase in the extensive social participation score correlated with a 17% decrease in the odds of older individuals belonging to the increase BADL trajectory group (OR = 0.83, 95% CI = 0.68-1.00). For IADL, it decreased the odds of being assigned to the moderate trajectory group by 16% (OR = 0.84, 95% CI = 0.75-0.95) and to the increase trajectory group by 23% (OR = 0.77, 95% CI = 0.64-0.93). CONCLUSIONS: Higher levels of social participation among older individuals were more likely to be classified as stable trajectories in both BADL and IADL. Increased participation in social activities by community-dwelling elderly adults may promote healthy aging.

Short-term effects of nitrogen dioxide on inpatient acute myocardial infarction in Lanzhou, China.

Nitrogen dioxide (NO2) represents a deleterious effect on acute myocardial infarction (AMI), but few relevant studies have been conducted in China. We aim to evaluate the acute effects of NO2 exposure on hospitalization for AMI in Lanzhou, China. In this study, we applied a distributional lag nonlinear model (DLNM) to assess the association between NO2 exposure and AMI hospitalization. We explored the sensitivity of various groups through stratified analysis by gender, age, and season. The daily average concentration of NO2 is 47.50 ± 17.38 µg/m3. We observed a significant exposure-response relationship between NO2 concentration and AMI hospitalization. The single pollutant model analysis shows that NO2 is positively correlated with AMI hospitalization at lag1, lag01, lag02, and lag03. The greatest lag effect estimate occurs at lag01, where a 10 µg/m3 increase in NO2 concentrations is significantly associated with a relative risk (RR) of hospitalization due to AMI of 1.027 [95% confidence interval (CI): 1.013, 1.042]. The results of the stratified analysis by gender, age, and season indicate that males, those aged ≥65 years, and the cold season are more sensitive to the deleterious effects caused by NO2 exposure. Short-term exposure to NO2 can enhance the risk of AMI hospitalization in urban Lanzhou.Implications: Exposure to particulate matter can lead to an increased incidence of AMI. Our study once again shows that NO2 exposure increases the risk of AMI hospital admission. AMI is a common and expensive fatal condition. Reducing NO2 exposure will benefit cardiovascular health and save on healthcare costs.

Effects of a Multicomponent Intervention With Cognitive Training and Lifestyle Guidance for Older Adults at Risk of Dementia: A Randomized Controlled Trial.

Objective: This study examined the effects of a multicomponent intervention program on cognitive function in community-dwelling older adults with mild cognitive impairment (MCI) and subjective cognitive decline (SCD).Methods: This was a 2-arm, randomized controlled trial in which a multicomponent intervention was applied. Participants were recruited from June 2020 to August 2020, randomization and intervention began in August 2020, and the entire program ended in January 2021. It included cognitive training (mnemonic strategy training) and lifestyle guidance (diet, sleep, and exercise guidance) for 7 weeks. A total of 123 Chinese community-dwelling older adults experiencing MCI or SCD were randomly divided into a multicomponent intervention group (n = 62) and a health education group (n = 61). The global cognitive function was measured using the Mini-Mental State Examination (MMSE). The cognitive domains outcomes included memory functions measured using the immediate and delayed tests of the Auditory Verbal Learning Test (AVLT) and Logical Memory Test (LMT), and executive function and attention measured using the Digital Symbol Substitution Test (DSST) and Digit Span Test (DST). Data were collected at baseline and postintervention.Results: For cognitive outcome, the results of linear mixed-effect model showed significant time × group effects in the MMSE (Cohen d =0.63 [95% CI, 0.27 to 1.00], F = 10.25, P = .002). This study found significant time × group effects in AVLT-immediate (Cohen d = 0.47 [95% CI, 0.11 to 0.83], F = 8.18, P = .005), AVLT delayed (Cohen d = 0.45 [95% CI, 0.10 to 0.81], F = 4.59, P = .034), LMT-delayed (Cohen d = 0.71 [95% CI, 0.34 to 1.07], F = 4.59, P = .034), DSST (Cohen d = 0.27 [95% CI, -0.08 to 0.63], F = 4.83, P = .030), and DST (Cohen d =0.69 [95% CI, 0.33 to 1.05], F = 8.58, P = .004).Conclusions and Implications: The results support the feasibility and effectiveness of the multicomponent intervention program in improving cognitive function in community dwelling older adults at risk of dementia. The high adherence of this program shows its potential for promotion in the community and supports a larger and longer trial.Trial Registration: Chinese Clinical Trial Registry (ChiCTR2200061420).

Chronic kidney disease: a contraindication for using biodegradable magnesium or its alloys as potential orthopedic implants?

Magnesium (Mg) has gained widespread recognition as a potential revolutionary orthopedic biomaterial. However, whether the biodegradation of the Mg-based orthopedic implants would pose a risk to patients with chronic kidney disease (CKD) remains undetermined as the kidney is a key organ regulating mineral homeostasis. A rat CKD model was established by a 5/6 subtotal nephrectomy approach, followed by intramedullary implantation of three types of pins: stainless steel, high pure Mg with high corrosion resistance, and the Mg-Sr-Zn alloy with a fast degradation rate. The long-term biosafety of the biodegradable Mg or its alloys as orthopedic implants were systematically evaluated. During an experimental period of 12 weeks, the implantation did not result in a substantial rise of Mg ion concentration in serum or major organs such as hearts, livers, spleens, lungs, or kidneys. No pathological changes were observed in organs using various histological techniques. No significantly increased iNOS-positive cells or apoptotic cells in these organs were identified. The biodegradable Mg or its alloys as orthopedic implants did not pose an extra health risk to CKD rats at long-term follow-up, suggesting that these biodegradable orthopedic devices might be suitable for most target populations, including patients with CKD.

Sagittal balance parameters measurement on cervical spine MR images based on superpixel segmentation.

Introduction: Magnetic Resonance Imaging (MRI) is essential in diagnosing cervical spondylosis, providing detailed visualization of osseous and soft tissue structures in the cervical spine. However, manual measurements hinder the assessment of cervical spine sagittal balance, leading to time-consuming and error-prone processes. This study presents the Pyramid DBSCAN Simple Linear Iterative Cluster (PDB-SLIC), an automated segmentation algorithm for vertebral bodies in T2-weighted MR images, aiming to streamline sagittal balance assessment for spinal surgeons. Method: PDB-SLIC combines the SLIC superpixel segmentation algorithm with DBSCAN clustering and underwent rigorous testing using an extensive dataset of T2-weighted mid-sagittal MR images from 4,258 patients across ten hospitals in China. The efficacy of PDB-SLIC was compared against other algorithms and networks in terms of superpixel segmentation quality and vertebral body segmentation accuracy. Validation included a comparative analysis of manual and automated measurements of cervical sagittal parameters and scrutiny of PDB-SLIC's measurement stability across diverse hospital settings and MR scanning machines. Result: PDB-SLIC outperforms other algorithms in vertebral body segmentation quality, with high accuracy, recall, and Jaccard index. Minimal error deviation was observed compared to manual measurements, with correlation coefficients exceeding 95%. PDB-SLIC demonstrated commendable performance in processing cervical spine T2-weighted MR images from various hospital settings, MRI machines, and patient demographics. Discussion: The PDB-SLIC algorithm emerges as an accurate, objective, and efficient tool for evaluating cervical spine sagittal balance, providing valuable assistance to spinal surgeons in preoperative assessment, surgical strategy formulation, and prognostic inference. Additionally, it facilitates comprehensive measurement of sagittal balance parameters across diverse patient cohorts, contributing to the establishment of normative standards for cervical spine MR imaging.

Small-molecule caspase-1 inhibitor CZL80 terminates refractory status epilepticus via inhibition of glutamatergic transmission.

Status epilepticus (SE), a serious and often life-threatening medical emergency, is characterized by abnormally prolonged seizures. It is not effectively managed by present first-line anti-seizure medications and could readily develop into drug resistance without timely treatment. In this study, we highlight the therapeutic potential of CZL80, a small molecule that inhibits caspase-1, in SE termination and its related mechanisms. We found that delayed treatment of diazepam (0.5 h) easily induces resistance in kainic acid (KA)-induced SE. CZL80 dose-dependently terminated diazepam-resistant SE, extending the therapeutic time window to 3 h following SE, and also protected against neuronal damage. Interestingly, the effect of CZL80 on SE termination was model-dependent, as evidenced by ineffectiveness in the pilocarpine-induced SE. Further, we found that CZL80 did not terminate KA-induced SE in Caspase-1-/- mice but partially terminated SE in IL1R1-/- mice, suggesting the SE termination effect of CZL80 was dependent on the caspase-1, but not entirely through the downstream IL-1ß pathway. Furthermore, in vivo calcium fiber photometry revealed that CZL80 completely reversed the neuroinflammation-augmented glutamatergic transmission in SE. Together, our results demonstrate that caspase-1 inhibitor CZL80 terminates diazepam-resistant SE by blocking glutamatergic transmission. This may be of great therapeutic significance for the clinical treatment of refractory SE.

Online mindfulness-based stress reduction improves anxiety and depression status and quality of life in caregivers of patients with severe mental disorders. / ç½‘ç»œæ­£å¿µå‡åŽ‹ç–—æ³•å¯æ”¹å–„ä¸¥é‡ç²¾ç¥žéšœç¢æ‚£è€ ç §æ–™è€ ç„¦è™‘æŠ‘éƒçŠ¶æ€åŠå ¶ç”Ÿæ´»è´¨é‡.

OBJECTIVES: To explore the effects of online mindfulness-based stress reduction (MBSR) on the anxiety and depression status, and quality of life in the caregivers of patients with severe mental disorders. METHODS: Ninety-three caregivers for patients with schizophrenia or bipolar disorder, who were hospitalized in Yunnan Provincial Mental Hospital in March 2021, were enrolled and randomly divided into control group (n=47) and MBSR intervention group (n=46). Both groups received basic health education and rehabilitation skill training, while the intervention group received additional online MBSR for 8 weeks. The anxiety and depression status, and the quality of life of the caregivers were evaluated by Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS) and the 36-item Short Form Health Survey (SF-36) before and 8 weeks after intervention, respectively. RESULTS: Thirteen caregivers dropped out of the study, and 80 subjects (40 in each group) were included in the final analysis. At the baseline, there were no significant differences in SAS, SDS and SF-36 scores between two groups (all P>0.05). Compared with the baseline, SAS and SDS scores in the intervention group significantly decreased after 8 weeks of intervention (both P<0.01) and were significantly lower than those in the control group (both P<0.01). There were no significant changes in the control group (all P>0.05). Except the physiological function dimension, the total score and the scores of each dimension of SF-36 in the intervention group were significantly increased after 8-week intervention (all P<0.05), and were significantly higher than those in the control group (all P<0.01). There were no significant changes in the control group before and after intervention (all P>0.05). CONCLUSIONS: Online MBSR can reduce the anxiety and depression levels, improve the quality of life in the caregivers of patients with severe mental disorders.

Short-term association between air pollution and daily genitourinary disorder admissions in Lanzhou, China.

The aim of this study was to determine the relationship between short-term exposure to ambient air pollution and the number of daily hospital admissions for genitourinary disorders in Lanzhou. Hospital admission data and air pollutants, including PM2.5, PM10, SO2, NO2, O38h and CO, were obtained from the period 2013 to 2020. A generalized additive model (GAM) combined with distribution lag nonlinear model (DLNM) based on quasi-Poisson distribution was used by the controlling for trends, weather, weekdays and holidays. Short-term exposure to PM2.5, NO2 and CO increased the risk of genitourinary disorder admissions with RR of 1.0096 (95% CI 1.0002-1.0190), 1.0255 (95% CI 1.0123-1.0389) and 1.0686 (95% CI 1.0083-1.1326), respectively. PM10, O38h and SO2 have no significant effect on genitourinary disorders. PM2.5 and NO2 are more strongly correlated in female and ≥ 65 years patients. CO is more strongly correlated in male and < 65 years patients. PM2.5, NO2 and CO are risk factors for genitourinary morbidity, and public health interventions should be strengthened to protect vulnerable populations.

A Prognostic Model for Survival in Patients with Gastric Signet Ring Cell Carcinoma.

INTRODUCTION: The objective of our study was to develop a nomogram to predict overall survival (OS) and cancer-specific survival (CSS) in patients with gastric signet ring cell carcinoma (GSRCC). METHODS: A total of 3,408 GSRCC patients between 1975 and 2017 were screened from the Surveillance, Epidemiology, and End Results (SEER) database and randomly divided into training and validation cohorts. Univariate and multivariate Cox analyses were conducted to identify independent prognostic factors for the construction of a nomogram. The performance of the model was then assessed by the concordance index (C-index), calibration plot, and area under the receiver operating characteristic curve (AUC). Then, the novel nomogram was further assessed by 64 GSRCC patients from our hospital as the external cohort. RESULTS: We identified age, tumor lymph node metastasis (TNM) staging system, surgery, and chemotherapy as significant independent elements of prognosis. On this basis, a nomogram was constructed, with a C-index of OS in the training and validation cohorts of 0.763 (95% CI: 0.751-0.774) and 0.766 (95% CI: 0.748-0.784) and a C-index of CSS of 0.765 (95% CI: 0.753-0.777) and 0.773 (95% CI: 0.755-0.791), respectively. The AUCs of the nomogram for predicting 2- and 5-year OS were 0.848 and 0.885, respectively, and those for predicting CSS were 0.854 and 0.899, respectively, demonstrating the excellent predictive value of the constructed nomogram compared to the traditional AJCC staging system. Similar results were also observed in both the internal and external validation sets. CONCLUSION: The nomogram provided an accurate tool to predict OS and CSS in patients with GSRCC, which can assist clinicians in making predictions about individual patient survival.

Association Between Air Pollution and Cardiovascular Disease Hospitalizations in Lanzhou City, 2013-2020: A Time Series Analysis.

Extensive evidence has shown that air pollution increases the risk of cardiovascular disease (CVD) admissions. We aimed to explore the short-term effect of air pollution on CVD admissions in Lanzhou residents and their lag effects. Meteorological data, air pollution data, and a total of 309,561 daily hospitalizations for CVD among urban residents in Lanzhou were collected from 2013 to 2020. Distributed lag non-linear model was used to analyze the relationship between air pollutants and CVD admissions, stratified by gender, age, and season. PM2.5, NO2, and CO have the strongest harmful effects at lag03, while SO2 at lag3. The relative risks of CVD admissions were 1.0013(95% CI: 1.0003, 1.0023), 1.0032(95% CI: 1.0008, 1.0056), and 1.0040(95% CI: 1.0024, 1.0057) when PM2.5, SO2, and NO2 concentrations were increased by 10 µg/m³, respectively. Each 1 mg/m3 increase in CO concentration was associated with a relative risk of cardiovascular hospitalization of risk was 1.0909(95% CI: 1.0367, 1.1479). We observed a relative risk of 0.9981(95% CI: 0.9972, 0.9991) for each 10 µg/m³ increase in O3 for CVD admissions at lag06. We found a significant lag effects of air pollutants on CVD admissions. NO2 and CO pose a greater risk of hospitalization for women, while PM2.5 and SO2 have a greater impact on men. PM2.5, NO2, and CO have a greater impact on CVD admissions in individuals aged <65 years, whereas SO2 affects those aged ≥65 years. Our research indicates a possible short-term impact of air pollution on CVD. Local public health and environmental policies should take these preliminary findings into account.

Long-term MNNG exposure promotes gastric carcinogenesis by activating METTL3/m6A/miR1184 axis-mediated epithelial-mesenchymal transition.

As the representative item of environmental chemical carcinogen, MNNG was closely associated with the onset of Gastric cancer (GC), while the underlying mechanisms remain largely unknown. Here, we comprehensively analyzed the potential clinical significance of METTL3 in multiple GC patient cohorts. Additionally, we demonstrated that long-term exposure to MNNG elevated METTL3 and EMT marker expression by in vitro and in vivo models. Furthermore, the depletion of METTL3 impacted the proliferation, migration, invasion, and tumorigenesis of MNNG malignant transformation cells and GC cells. By me-RIP sequencing, we identified a panel of vital miRNAs potentially regulated by METTL3 that aberrantly expressed in MNNG-induced GC cells. Mechanistically, we showed that METTL3 meditated miR-1184/TRPM2 axis by regulating the process of miRNA-118. Our results provide novel insights into critical epigenetic molecular events vital to MNNG-induced gastric carcinogenesis. These findings suggest the potential therapeutic targets of METTL3 for GC treatment.

New cassane-type alkaloids and diterpenoids from the pericarps of Caesalpinia bonduc.

The phytochemical investigation of the pericarps of Caesalpinia bonduc led to the isolation and identification of five new cassane-type alkaloids: caesalminines C - G (1-5) and six new diterpenoids: caesalbonducin K - P (6-11), along with seven known compounds (12-18). Compounds 1-5 were identified as a group of rare alkaloids possessing a tetracyclic cassane-type diterpenoid skeleton with a lactam D-ring instead of a typical furan or lactone moiety. The structures of 1-11 were elucidated on the basis of 1D and 2D NMR including HSQC, HMBC, COSY and NOESY, and other spectroscopic analyses. The cytotoxic activities of the isolated compounds were evaluated in the A431, A549 and U87MG cancer cell lines.

Androgen-induced upregulation of CFTR in pancreatic ß-cell contributes to hyperinsulinemia in PCOS model.

PURPOSE: Polycystic ovarian syndrome (PCOS) is an endocrine-metabolic condition affecting 5-10% of reproductive-aged women and characterized by hyperandrogenism, insulin resistance (IR), and hyperinsulinemia. CFTR is known to be regulated by steroid hormones, and our previous study has demonstrated an essential role of CFTR in ß-cell function. This study aims to investigate the contribution of androgen and CFTR to hypersecretion of insulin in PCOS and the underlying mechanism. METHODS: We established a rat PCOS model by subcutaneously implanting silicon tubing containing Dihydrotestosterone (DHT). Glucose tolerance test with insulin levels was performed at 9 weeks after implantation. A rat ß-cell line RINm5F, a mouse ß-cell line ß-TC-6, and mouse islets were treated with DHT, and with or without the androgen antagonist flutamide for CFTR and insulin secretion-related functional assays or mRNA/protein expression measurement. The effect of CFTR inhibitors on DHT-promoted membrane depolarization, glucose-stimulated intracellular Ca2+ oscillation and insulin secretion were examined by membrane potential imaging, calcium imaging and ELISA, respectively. RESULTS: The DHT-induced PCOS model showed increased body weight, impaired glucose tolerance, and higher blood glucose and insulin levels after glucose stimulation. CFTR was upregulated in islets of PCOS model and DHT-treated cells, which was reversed by flutamide. The androgen receptor (AR) could bind to the CFTR promoter region, which was enhanced by DHT. Furthermore, DHT-induced membrane depolarization, enhanced glucose-stimulated Ca2+ oscillations and insulin secretion, which could be abolished by CFTR inhibitors. CONCLUSIONS: Excessive androgen enhances glucose-stimulating insulin secretion through upregulation of CFTR, which may contribute to hyperinsulinemia in PCOS.

Heavy metal contamination impacts the structure and co-occurrence patterns of bacterial communities in agricultural soils.

Heavy metal (HM) contamination caused by mining and smelting activities can be harmful to soil microbiota, which are highly sensitive to HM stress. Here, we explore the effects of HM contamination on the taxonomic composition, predicted function, and co-occurrence patterns of soil bacterial communities in two agricultural fields with contrasting levels of soil HMs (i.e., contaminated and uncontaminated natural areas). Our results indicate that HM contamination does not significantly influence soil bacterial α diversity but changes the bacterial community composition by enriching the phyla Gemmatimonadetes, Planctomycetes, and Parcubacteria and reducing the relative abundance of Actinobacteria. Our results further demonstrate that HM contamination can strengthen the complexity and modularity of the bacterial co-occurrence network but weaken positive interactions between keystone taxa, leading to the gradual disappearance of some taxa that originally played an important role in healthy soil, thereby possibly reducing the resistance of bacterial communities to HM toxicity. The predicted functions of bacterial communities are related to membrane transport, amino acid metabolism, energy metabolism, and carbohydrate metabolism. Among these, functions related to HM detoxification and antioxidation are enriched in uncontaminated soils, while HM contamination enriches functions related to metal resistance. This study demonstrated that microorganisms adapt to the stress of HM pollution by adjusting their composition and enhancing their network complexity and potential ecological functions.

Biliary hemorrhage caused by a malignant small round cell tumor in the common bile duct: A case report.

BACKGROUND: Malignant small round cell tumor (MSRCT) metastasis to the common bile duct associated with recurrent biliary hemorrhage is extremely rare. Thus far, there have been no reports of metastatic small round cell tumors of the common bile duct. CASE SUMMARY: Herein, we report the case of a 77-year-old female patient with an MSRCT in the common bile duct. The patient was admitted to hospital due to gastrointestinal hemorrhage and abdominal pain. We found a neoplasm in the common bile duct with active bleeding through a spyglass. We performed biopsy through the spyglass and placed a metal stent to stop bleeding. The pathological result suggested that it was an MSRCT metastasized from the back to the common bile duct. Later, we found using fluorescence in situ hybridization that the SS18 gene break test was negative, ruling out the diagnosis of synovial sarcoma. CONCLUSION: MSRCT is a group of tumors with similar cell morphology and diffuse histological structure. Complete tumor resection results in improved survival in patients with MSRCT. Roux-en-Y cholangiojejunostomy was performed. After excision of the common bile duct tumor, the patient felt that the abdominal pain improved and hemorrhage disappeared. The patient underwent routine fecal examination one month after surgery, indicating a negative fecal occult blood test. On May 22, 2023, the patient was reexamined by abdominal computed tomography, and no abdominal space occupying lesions or abdominal lymphadenopathy was found.