BackgroundErectile dysfunction (ED) is the leading cause of sexual dysfunction in hundreds of millions of men worldwide, with serious negative consequences for the quality of life of both men and their partners. Whereas antihypertensive drugs may play a role in the progression of ED, evidence of causality is limited. We aimed to investigate the causal effect of antihypertensive drugs on ED risk using Mendelian randomization (MR).MethodsPooled data based on genome-wide association studies (GWASs) were included in relation to five antihypertensive drugs including: renin-angiotensin, calcium channel blockers, beta-blockers, diuretics, and overall antihypertensive medication use. We performed MR analyses to estimate the causal effect of antihypertensive medications on ED risk. We also performed some sensitivity analyses to assess the validity of the MR hypothesis.ResultsGenetically predicted drug use of drugs acting on the renin-angiotensin system (RAS), calcium channel blockers, beta-blockers, and antihypertensive medications were all found to be significantly and positively associated with ED (agents acting on the RAS: odds ratio [OR] = 1.136; 95% CI = 1.049-1.230; p = 0.002; beta blocking agents: OR = 1.120; 95% CI = 1.001-1.252; p = 0.048; calcium channel blockers: OR = 1.103; 95% CI = 1.017-1.196; p = 0.018; blood pressure medication: OR = 1.867; 95% CI = 1.175-2.965; p = 0.008). In contrast, there was a lack of association between diuretic use and ED (diuretics: OR = 1.083; 95% CI = 0.994-1.180; p = 0.067). Sensitivity analyses showed more robust results.ConclusionsOur study supports the idea that medication use of drugs acting on the RAS, calcium channel blockers, beta-blockers, and antihypertensive medications may have a negative effect on ED, whereas diuretic use had no effect on ED.

Background Chronic liver disease (CLD) and Mental health disorders (MHDs) represent two escalating public health challenges in the United States. Although their bidirectional relationship is increasingly recognized, comprehensive national-level assessments of long-term mortality trends among individuals with coexisting CLD and MHDs remain limited. Methods Using CDC WONDER Multiple Cause-of-Death data from 1999 to 2023, we examined age-adjusted mortality rates (AAMRs) among adults aged ≥ 35 years with coexisting CLD and MHDs. Mortality trends were stratified by gender, age group, race, census region, and urban-rural classification. Join-point regression was applied to estimate annual percent changes (APCs) and identify temporal inflection points. Future trends were projected through 2030 using ETS model. Results A total of 148,757 deaths with coexisting CLD and MHDs were recorded during the study period. The overall AAMR rose from 2.67 per 100,000 in 1999 to 4.26 in 2023. Substantial demographic disparities were observed. Males exhibited consistently higher mortality than females. Non-Hispanic Whites showed the steepest long-term increases, whereas the Northeast maintained the lowest rates. Non-metropolitan areas demonstrated persistently higher mortality than metropolitan regions. Mortality was highest among adults aged 55–64 and 65–74 years. Forecasting models projected AAMRs to 4.71 per 100,000 by 2030. Conclusions Mortality related to coexisting CLD and MHDs has accelerated markedly in the United States over the past two decades, with widening disparities across gender, age group, race, census region, and urban-rural classification. Have the necessity of systemic reforms in healthcare delivery and public health policy to address structural inequities and improve outcomes for high-risk groups.

ObjectiveTo observe the effect of electroacupuncture （EA） at “Tianshu” （ST26） and “Shangjuxu” （ST37） acupoints on the expressions of mitochondrial unfolded protein response （UPRmt） - related proteins in the colon tissue of functional constipation （FC） model mice， so as to explore its potential mechanisms underlying improvement of FC.MethodsEighteen male C57BL/6J mice were randomly divided into 3 groups： normal control （NC）， FC model （M）， and EA （n=6 per group）. The FC model was established by gavage of loperamide suspension （1 mg/mL， 0.1 mL/10 g）， twice daily for 14 d. The EA group received alternating unilateral EA stimulation of ST26 and ST37（3 Hz/15 Hz， an electric current intensity being able to induce slight tremor of the mouse’s limbs） for 20 min， once daily， 5 d a week for 2 weeks. The mice in the NC and M groups underwent equivalent restraint. Gastrointestinal transit function was assessed by measuring the first blue stool discharge time， 6-hour fecal pellet count， stool character score， rate of water content， and intestinal propulsion rate. Histopathological changes of the colon tissue were examined by H.E. staining， and the mitochondrial ultrastructure of colonic smooth muscle cells （SMCs） was observed by using a transmission electron microscopy （TEM）. The mitochondrial function was comprehensively evaluated by measuring the mitochondrial membrane potential （MMP） and the mitochondrial reactive oxygen species （mtROS） levels were assayed using flow cytometry， and the mitochondrial ATP content in the colon tissue was measured using colorimetric assay. The immunohistochemistry stain was employed to detect the expressions of key UPRmt markers heat shock protein-60 （HSP60） and LON protease 1 （LONP1） in the colon tissue.ResultsCompared with the NC group， the M group exhibited a significant increase in the first blue stool discharge time and average immunofluorescence intensity of mtROS （P<0.01）， and a considerable reduction in the 6-hour fecal pellet count， stool character score， rate of water content， small intestine propulsion rate， MMP level， ATP content， and the expressions of HSP60 and LONP1 proteins in the colon tissue （P<0.01， P<0.05）. Following EA intervention， compared to the M group， the EA group showed a marked decrease in the first blue stool discharge time and average immunofluorescence intensity of mtROS （P<0.01）， and a notable increase in the 6-hour fecal pellet count， stool character score， rate of water content， intestine propulsion rate， MMP， ATP content， and the expression of HSP60 and LONP1 proteins in the colon tissue （P<0.01， P<0.05）. The results of morphological structure showed that the mitochondria in the colon tissue were significantly swollen， with membrane damage and severe cristae rupture in the model group， while in the EA group， the mitochondrial swelling was mild， with significant improvement in the membrane and cristae integrity of the SMCs.ConclusionEA at ST26 and ST37 can effectively ameliorate gastrointestinal dysfunction and restore mitochondrial integrity in colonic SMCs of FC mice， which may be associated with its functions in up-regulating the expressions of HSP60 and LONP1 proteins to activate UPRmt.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a clinicopathological syndrome characterized by abnormal accumulation of fat within hepatocytes, and there is currently no standardized clinical treatment available. Consequently, there is an urgent need to discover new pharmacological interventions and to investigate novel therapeutic targets for MASLD. Melatonin, known for its multifaceted biological functions, has shown therapeutic potential for the treatment of MASLD. However, the underlying mechanisms remain unclear, particularly since the direct targets of melatonin remain poorly understood. In our study, we found that melatonin significantly improved various indicators in a mouse MASLD model and protected palmitic acid-induced mouse hepatocytes from lipid accumulation. We successfully identified and validated the mitochondrial trifunctional enzyme α-subunit HADHA as a binding target for melatonin using the cellular thermal shift assay (CETSA). This interaction enhanced the expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), which subsequently promotes mitochondrial biogenesis and accelerates lipid metabolism. In addition, melatonin reduced lipid accumulation and ameliorated MASLD through its regulatory effect on key proteins involved in fatty acid metabolism, including acyl coenzyme A oxidase 1 (ACOX1), cluster of differentiation 36 (CD36), and fatty acid synthase (FASN). Importantly, these beneficial effects were diminished when HADHA was knocked down. In conclusion, our study suggests that melatonin ameliorates MASLD through HADHA-mediated regulation of mitochondrial biogenesis and lipid oxidation, highlighting its potential as a promising therapeutic agent for MASLD. These results offer novel insights into the role of melatonin in the treatment of MASLD.

CDC25B, as an important member of the CDC25 family, plays a vital role in cell regulation. Recent studies have identified it as a potential oncogene implicated in tumorigenesis and cancer progression. The goal of our research was to shed light on the usefulness and significance of CDC25B as a reliable marker for predicting cancer outcomes. The databases PubMed, Web of Science, China National Knowledge Infrastructure (CNKI) and Wanfang data were used to find relevant articles published prior to May 30, 2025. The correlation between CDC25B expression and tumor prognosis or clinical features by calculating the overall hazard ratio or odds ratio and 95

Type 2 diabetes mellitus (T2DM) affects the patient's quality of life. Currently, hypoglycemic drugs are mainly used for the standard care for T2DM, but they appear to cause many adverse reactions. As a traditional therapy, acupuncture has been gradually applied to the treatment of T2DM. However, the best acupuncture regimen is still uncertain. Therefore, we evaluated the clinical efficacy of various acupuncture therapies in the treatment of T2DM. Up to December 2nd, 2024, eight databases were searched. The data were analyzed using Stata 15.1 and R 4.2.1 software. The included studies were assessed for bias using the Cochrane risk of bias tool (RoB2.0). A total of 139 randomized controlled trials were included, involving 12,231 patients with T2DM. The results showed that compared with conventional treatment (CT), body acupuncture + CT had the best effect on improving fasting blood glucose (FBG) (MD = -0.84, 95% CI: -1.01, -0.67; SUCRA = 84.44%) and HbA1c (MD = -1.08, 95% CI: -1.42, -0.76; SUCRA = 87.44%); auricular acupuncture + CT had the best effect on improving 2 h postprandial blood glucose (2hBG) (MD = -1.56, 95% CI: -2.05, -1.06: SUCRA = 82.10%), and laser acupuncture + CT had the best effect on improving homeostasis model assessment for insulin resistance (HOMA-IR) (MD = -2.46, 95% CI: -5.85, 0.96; SUCRA = 83.95%), fasting insulin (FINS) (MD = -7.21, 95% CI: -19, 4.54; SUCRA = 82.00%) and overall response rate (RR = 1.45, 95% CI: 0.97, 2.31; SUCRA = 84.00%) Acupuncture can effectively improve diabetes related indicators. Body acupuncture, auricular acupuncture, and laser acupuncture appear to be the most advantageous options for managing T2DM. However, due to the low quality of the included studies, more evidence may be needed to verify the conclusions.

Introduction Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder worldwide. Although not life-threatening, its chronic and recurrent nature greatly impacts patients’ quality of life. There is strong evidence that gut-directed psychotherapies (GDPs) help improve IBS symptoms. With technological advances, digital GDP is increasingly used as an alternative to traditional face-to-face GDP. This study will compare the clinical effectiveness of digital versus face-to-face GDP for IBS through network meta-analysis.Methods and analysis We will search English databases (PubMed, Cochrane Library, EMBASE and Web of Science) and Chinese databases (China National Knowledge Infrastructure, Wanfang, VIP and Chinese Biomedical Database) for randomised controlled trials (RCTs) of digital or face-to-face GDP for IBS. The search will cover the period from database inception to May 2025. We will perform multivariate network meta-analyses within a frequentist framework, using the mvmeta command in STATA V.16 software, and traditional pairwise meta-analysis using the DerSimonian-Laird random-effects model. The Cochrane Risk of Bias (RoB) tool (V.2) will be used to assess the RoB of each RCT, and the Confidence in Network Meta-Analysis (CINeMA) tool will be used to evaluate the certainty of the evidence.Ethics and dissemination Ethical approval is not required for this systematic review, as it involves the collection and synthesis of data from previously published primary studies.OSF registration Open Science Framework (OSF) registration: DOI 10.17605/OSF.IO/87463.

OBJECTIVES:To investigate the effect of electroacupuncture (EA) on intestinal motility and visceral sensitivity in functional constipation (FC) mice and its regulatory mechanism on Piezo1/2 channels in enterochromaffin (EC) cell. METHODS:Twenty-four male C57BL/6J mice were randomly divided into normal control, model, and EA groups (n=8 in each group). The FC model was established by gavage of loperamide hydrochloride. EA (1 mA, 3 Hz/15 Hz) was applied to unilateral "Tianshu" (ST25) and "Shangjuxu" (ST37) for 20 min per session, once daily for 5 consecutive days per week, two weeks altogether. Fecal parameters (number of stool particles in 6 h, characters, and fecal water content), intestinal motility (the time of the first blue stool excretion after gavage of Evans blue solution and small intestinal transit rate), and visceral sensitivity (assessed by abdominal withdrawal reflex [AWR] in responding to colorectal dilation) were observed. A transmission electron microscopy (TEM) was used to observe EC cells' ultrastructure. Triple immunofluorescence, Western blot and real-time qPCR were used to detect the expressions of Piezo1/2 in the EC cells and colon, and ELISA was employed to detect the contents of serum and colonic 5-HT and colonic Ca2+. RESULTS:Compared with the normal group, the model group showed a significant reduction in the number of stool particles, fecal character score, and fecal water content, small intestinal transit rate, AWR scores at 0.25 mL, 0.35 mL and 0.65 mL, contents of serum and colonic 5-HT and colonic Ca2+, expression levels of colonic Piezol1 and Piezol 2 proteins and mRNAs, and the positive areas of Piezol1 and Piezol2, EC, Piezol1/EC and Piezol2/EC (P<0.01, P<0.001, P<0.05), and an evident increase in the time of the first blue stool particle excretion (decrease of intestinal propulsion) and AWR 3-points threshold (P<0.01). Following EA treatment, both the decrease and increase of the indexes mentioned above were reversed completely (P<0.05, P<0.001, P<0.01). TEM showed mitochondrial swelling and a reduction in the secretory granules of EC cells in the model group, which was partially restored following EA treatment. CONCLUSIONS:EA of ST25 and ST37 can alleviate FC-related intestinal dysmotility and visceral hypersensitivity in FC mice, which may be associated with its functions in up-regulating Piezo1/2 channels of EC cell, promoting Ca2+ influx and 5-HT secretion.

ObjectiveTo explore the mechanism of electroacupuncture （EA） at “Zusanli” （ST36） in combination with omeprazole in treating gastrointestinal injury induced by indomethacin in mice.MethodsThirty C57BL/6J mice were randomly divided into normal control， model， omeprazole， EA combined with omeprazole （combination）， and combination + nuclear factor E2-related factor 2 （Nrf2） inhibitor （inhibitor） groups， with 6 mice in each group. The gastrointestinal injury mouse model was established by intragastric administration of indomethacin （30 mg/kg）. EA was applied to bilateral ST36 for 20 min， a total of 2 times. The omeprazole （10 mg/kg） was given by gavage. Mice in the inhibitor group were intraperitoneally injected with the Nrf2 inhibitor ML385 （30 mg/kg）. HE staining was used to observe the morphological changes of the gastrointestinal mucosa. The contents of glutathione （GSH）， malondialdehyde （MDA） and the activity of superoxide dismutase （SOD） in gastric tissue and the activities of SOD and glutathione peroxidase （GSH-Px） in colon tissue were detected by colorimetric method. The level of reactive oxygen species （ROS） in colon tissue was detected by flow cytometry. The mRNA and protein expressions of Nrf2/heme oxygenase-1 （HO-1） signaling pathway-related factors Kelch-like epichlorohydrin-related protein factor 1 （Keap1）， Nrf2， HO-1 and NADPH oxidase 1 （NOX1） in colon tissue were detected by qPCR and Western blot， respectively.ResultsAfter modeling and compared with the normal control group， the mice of model group showed severe gastrointestinal mucosal damage， with decreased GSH content and SOD activity in gastric tissue （P<0.01）， increased MDA content （P<0.01）， elevated ROS levels， and increased Keap1 and NOX1 mRNA and protein expressions in colon tissue （P<0.01）， reduced SOD and GSH-Px activities （P<0.01， P<0.05）， decreased Nrf2 and HO-1 mRNA and protein levels in colon tissue （P<0.01）. Compared with the model group， the gastric mucosal injury was improved， the content of GSH and the activity of SOD in the gastric tissue were increased （P<0.01， P<0.05）， while the content of MDA was decreased （P<0.05， P<0.01） in both omeprazole and combination groups. In comparison with the model and the omeprazole groups， the combination group showed improved colonic mucosal injury， decreased ROS level （P<0.01）， increased SOD and GSH-Px activities （P<0.05）， up-regulated mRNA and protein expressions of Nrf2 and HO-1 （P<0.01）， and down-regulated mRNA and protein expressions of Keap1 and NOX1 （P<0.01， P<0.05） in colon tissue. However， the improvement of gastrointestinal oxidative stress of combination treatment was reversed after the injection of Nrf2 inhibitor in the inhibitor group （P<0.01， P<0.05）.ConclusionThe integration of acupuncture and medication can effectively ameliorate indomethacin-induced gastrointestinal oxidative stress injury， which may be related to its function in activating the Nrf2/HO-1 signaling pathway.

To compare the effectiveness of electroacupuncture (EA) combined with omeprazole (Ome) and Ome alone on indomethacin-induced gastric injury mice and reveal the underlying mechanism of this combination. Fourty-eight male C57BL/6J mice were randomly divided into 6 groups by a simple random method (n=8), including control, model, Ome, Ome + EA, Ome + sham EA, and Ome + EA + ML385 groups. A gastric ulcer mouse model was constructed by intragastrically administering indomethacin at a dose of 30 mg/kg. EA and Ome treatment were performed twice daily with each session of EA treatment lasting 20 min. Gastric injury severity was determined by measuring the ulcer index. Sixteen mice with gastric ulcers underwent left cervical vagotomy (CV) were further divided into model + CV and Ome + EA + CV groups. Eight mice with gastric ulcers underwent sham vagotomy and EA combined with Ome treatment were included in the Ome + EA + SCV group. Following respective treatments, the gastric mucosal ulcer tissues were collected and pathologic scores were evaluated by HE staining. Oxygenase-1/tumor necrosis factor-α levels in gastric tissue were measured using ELISA. Colorimetric assay was conducted to measure oxidative stress levels. Real-time polymerase chain reaction was applied to detect the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) in gastric tissue. Immunofluorescence staining was performed to observe the locations and expressions of F4-80 and Nrf2 in the gastric mucosa. CV was conducted to evaluate the role of the vagus nerve in EA-mediated gastric injury improvement. EA combined with Ome alleviated gastric ulcers and decreased gastric pathologic scores (both P<0.01). Furthermore, it decreased gastric oxidative stress levels and inhibited macrophages activation (all P<0.01). However, vagotomy abolished the antioxidant function of EA. Meanwhile, we observed that Nrf2 plays a critical role in inducing the therapeutic effect of EA combined with Ome on gastric injury. In mice with gastric ulcers, EA combined with Ome can better repair indomethacin-induced gastric injury via inactivation of macrophages and Nrf2-mediated antioxidant signaling pathway, which is primarily mediated by vagus nerve.

OBJECTIVES: To examine the effectiveness of sandplay therapy in reducing emotional problems and enhancing quality of life in children with central nervous system (CNS) tumors. SAMPLE & SETTING: This randomized controlled trial was conducted in a tertiary hospital in China from January to August 2024, involving 56 children aged 6-14 years with CNS tumors. METHODS & VARIABLES: The intervention and control groups received regulartreatment, and the intervention group received an additional four sessions of sandplay therapy. Data were collected at baseline and at 5 weeks and 12 weeks after baseline. The children's scores on three assessments before and after the intervention were analyzed using a mixed-effects model. RESULTS: Participants in the intervention group reported statistically significant lower depression and anxiety scores and higher quality-of-life scores than the control group at 5-and 12-week follow-up. IMPLICATIONS FOR NURSING: Sandplay therapy can reduce depression and anxiety and enhance quality of life in children with CNStumors. Sandplay therapy is feasible and effective in developing psychological support interventions for children.

Mitochondrial dysfunction in colonic smooth muscle cells (SMCs) is closely associated with impaired gut motility in functional constipation (FC), but the underlying molecular mechanisms remain incompletely understood. The mitochondrial unfolded protein response (UPRmt) is a critical pathway for maintaining mitochondrial proteostasis, and heat shock factor 1 (HSF1) acts as an important upstream regulator of this response. In the present study, we employed a loperamide-induced FC mouse model, combined with single-cell transcriptomic, molecular, and functional analyses to characterize the HSF1-UPRmt pathway in colonic SMCs and to investigate its role in FC. Single-cell transcriptomic analysis of colon tissue from FC mice revealed marked downregulation of UPRmt-associated genes in colonic SMCs. Immunofluorescence, Western blotting, and RT-qPCR analyses of colonic tissue confirmed that HSF1 expression was reduced in colonic SMCs, along with the downregulation of the UPRmt components, including HSP60, mtHSP70, and LONP1. These molecular changes were accompanied by mitochondrial structural damage, seen by transmission electron microscopy, and by functional impairments, including reduced mitochondrial membrane potential, elevated mtROS production, decreased ATP levels, and diminished activities of respiratory chain complexes I-V. AAV9-mediated overexpression of HSF1 reactivated the UPRmt pathway, improved mitochondrial function, and ameliorated constipation, whereas shRNA-mediated knockdown of HSF1 further suppressed UPRmt activity and aggravated mitochondrial damage, indicating that HSF1 bidirectionally regulates this pathway. Complementary experiments in primary colonic SMCs confirmed that this regulatory mechanism operates in a cell-autonomous manner, as modulation of HSF1 expression produced corresponding changes in the UPRmt pathway, in the expression of mitochondrial respiratory chain complex subunits (ATP5A, NDUFA9, COX1, SDHA, UQCRC1), and in ATP production, mirroring the in vivo findings. Collectively, these results demonstrate that HSF1 plays a pivotal role in maintaining mitochondrial homeostasis in colonic SMCs through regulation of the UPRmt pathway and that HSF1 dysfunction is closely associated with slowed gut motility in FC. These findings offer a new mechanistic perspective on FC and point to the HSF1-UPRmt axis as a potential therapeutic target.

Intestinal stem cells (ISCs) are essential for maintaining intestinal homeostasis and repairing injury, and have garnered extensive attention in recent years. ISC research has not only advanced our understanding of intestinal physiology but also revealed pathological roles of ISCs in diseases and facilitated the identification of potential targeted therapies. This review aims to comprehensively present the current state of ISC research. It elaborates on the multi-level regulatory mechanisms governing ISCs, including niche cells, signaling pathways, gut microbiota, extracellular matrix, and epigenetic regulation. It further summarizes the involvement of ISCs in colorectal cancer, inflammatory bowel disease, radiation-induced intestinal injury, and short bowel syndrome, as well as their application in organoid technology. Finally, this review highlights future directions, including dissecting how distinct cellular states and microenvironments dynamically regulate ISC function, and the integration of cutting-edge technologies like microfluidic organ-on-a-chip and gene editing technologies to accelerate the translation of basic discoveries into clinical practice, thereby providing a valuable reference for researchers in the field.

Paralytic ileus and intestinal obstruction (PIAIO) severely strain healthcare systems, yet the long-term mortality trends and demographic disparities among U.S. adults aged 55 and older are insufficiently examined. This study aimed to investigate temporal variations in PIAIO-related mortalities across subgroups categorized by sex, age, ethnicity, and geographic region. We conducted a retrospective study using death certificate data from the CDC WONDER database (1999–2023), including U.S. adults aged 55 years and older for whom an ICD-10 code within K56 was recorded as the underlying cause of death. Age-adjusted mortality rates (AAMRs) were computed based on the 2000 U.S. census population. We utilized joinpoint regression modeling to quantify annual fluctuations in mortality trends, calculating both annual percentage changes (APCs) and average annual percentage changes (AAPCs). A total of 147,214 deaths related to PIAIO were documented (89,594 females; 57,620 males). Joinpoint analysis revealed that although the overall AAMR remained statistically stable from 1999 to 2023 (AAPC 0.14, 95

Currently, chemotherapy remains the primary treatment for acute myeloid leukemia (AML). Drug resistance in AML cells is a critical factor contributing to the failure of chemotherapy remission and subsequent relapse. Iron overload frequently occurs in AML patients because of hematopoietic suppression or supportive blood transfusion therapy. Previous studies have indicated that iron overload may promote the progression of AML; however, the underlying mechanisms remain unclear. Our results demonstrate that, compared with TP53-wild-type AML cells, TP53-mutant AML cells exhibit increased resistance to cytarabine-induced cytotoxicity. Moreover, reducing TP53 expression in wild-type AML cells diminishes their sensitivity to cytarabine. The TP53 signaling pathway is essential for mediating cytarabine-induced apoptosis in AML cells. In this study, an iron overload model in AML cells via the use of ferric citrate is constructed. Our data indicate that iron overload can suppress the TP53/BCL2/BAX signaling pathway, counteracting cytarabine-induced apoptosis. In TP53 wild-type AML cells, TFR1 participates in iron-mediated resistance to cytarabine by regulating the entry of iron into the cells. These findings provide a foundation for further exploration of the molecular mechanisms involved in AML resistance to cytarabine.

Accumulating evidence indicates that microbial infections and their elicited immune responses may contribute to allergic disease pathogenesis, but the causal relationships remain unclear. We performed a bidirectional 2-sample Mendelian randomization (MR) study utilizing genome-wide association study summary statistics. We analyzed causal relationships between 46 antibody-mediated immune responses and 5 allergic diseases: allergic asthma (AA), allergic conjunctivitis, atopic dermatitis (AD), allergic rhinitis (AR), and allergic urticaria (AU). The primary analysis method was inverse-variance weighted, supplemented by MR-Egger, weighted median, and weighted mode methods. Robustness was assessed through tests for heterogeneity, pleiotropy, and leave-one-out sensitivity analysis. As an observational genetic methodology, MR estimates are subject to potential biases from pleiotropy. Thus, our findings suggest associations rather than definitive causation. Polyomavirus 2 JC VP1 antibody levels and Antihuman herpes virus 7 IgG seropositivity may influence the risk of AA disease. Toxoplasma gondii p22 antibody levels may confer protection against allergic conjunctivitis. Epstein–Barr virus EBNA-1 antibody levels are positively associated with AD, while Chlamydia trachomatis momp A antibody levels are negatively associated with AD. H pylori CagA antibody levels are positively linked to AR. Epstein–Barr virus EBNA-1 antibody levels are inversely related to AR. The positivity of H pylori Catalase antibody levels and herpes simplex virus 2 mgG-1 antibody levels are potential risk factors for AU. Antihuman herpes virus 6 IE1B IgG seropositivity may be a protective factor for AU. Reverse MR indicated that AA may elevate anti- H pylori IgG seropositivity. Sensitivity analyses confirmed robustness ( P > .05). Our findings unveil potential causal links between antibody-mediated immune responses and allergic diseases, which may inform future mechanistic research and therapeutic strategies, highlighting the role of pathogen-immune interactions.

Tuina therapy is a promising treatment for spinal diseases, but its therapeutic mechanism remains poorly understood. Nucleus pulposus (NP) cell apoptosis is an important pathologic mechanism of intervertebral disc degeneration (IDD). We evaluated the intervention effect of sham-controlled placebo therapy on NP apoptosis in rabbit model of IDD and dissected the molecular mechanism by transcriptome analysis. IDD rabbit model was established by using intervertebral disc fibrous annulus puncture, and the intervention was carried out for 4 weeks in the Tuina group and the Placebo group. The intervention effects of the two therapies were assessed by H E staining, MRI scanning, Tunel staining and flow cytometry. Transcriptome analysis was performed to detect key differentially expressed genes (DEGs) and related signaling pathways. The mRNA expression levels of key differentially expressed genes were verified by RT-qPCR. Compared with the Placebo therapy, the Tuina intervention was superior in inhibiting nucleus pulposus cell apoptosis and maintenance of disc morphology and structure. Protein–Protein Interaction (PPI) analysis showed that there were common differentially expressed genes among the Tuina, Placebo and Model groups. The mRNA expression of core signaling factors RPL17, LOC100354980 and LOC100339314 was consistent with the transcriptome sequencing results after the Tuina intervention, as verified by RT-qPCR. Our results suggest that compared to Placebo therapy, Tuina intervention showed improved effects on tissue structural morphology and NP cell apoptosis. Tuina slowed down NP cell apoptosis in the rabbit model of IDD, which may be related to pathways such as Wnt, and the RPL17 gene may be a promising therapeutic target, and further studies are needed to elucidate their functional profile in IDD.

Intestinal stem cell (ISC) regeneration is the key to maintaining intestinal homeostasis. The proliferation and differentiation of ISCs are regulated by the specific cells in the stem cell niche, and these cells mainly regulate ISC activity through secreting related ligands of various pathways, among which the Wnt pathway is the primary pathway regulating ISC regeneration, and the Hippo pathway plays an important role in controlling organ size and repairing injury. Accumulating evidence has identified that these two pathways closely cooperate to regulate the self-renewal and regeneration of ISCs, which has important significance in the maintenance of intestinal homeostasis and the treatment of intestinal disorders. Therefore, we provide an overview of the interaction of the Wnt and Hippo pathways in ISC regeneration and intestinal diseases, which not only sheds light on the mechanisms of maintaining intestinal homeostasis but also paves the way for novel therapeutic strategies for intestinal diseases.

BACKGROUND:Acupuncture is an effective adjunctive therapy for stroke and has been suggested for the treatment for acute cerebral infarction (ACI). However, there is a lack of high-quality data from randomized clinical trials. Thus, this study aims to reach a consensus to guide the clinical research and practice. METHODS:The initial project list was based on a systematic review of research evidence and a clinical problem survey conducted by a multidisciplinary team. After discussion with experts and a two-round Delphi consensus survey, the final list was optimized. Then, Likert scale of 9 points was used to measure the degree of expert consensus (1 = strongly disagree, 9 = strongly agree) and 80% of scores between 7 and 9 were defined as "agreement." RESULTS:A total of 30 professionals (response rate: 100%) confirmed their participation in the voting group. After two rounds of Delphi voting, a consensus was achieved including 34 items that can be broadly categorized into six aspects. According to expert consensus, acupuncture should be initiated within 6 h and the main acupoints are Shuigou (GV26), Neiguan (PC6), Hegu (LI4), and Taichong (LR3), while the auxiliary acupoints include Quchi (LI11), Waiguan (SJ5), Huantiao (GB30), Weizhong (BL40), etc. Furthermore, the adverse events of acupuncture are generally considered to be few, only subcutaneous hematoma is commonly reported. CONCLUSION:This expert consensus provides recommendations for clinical research and practice in treating ACI with acupuncture. However, due to the limited clinical evidence, further exploration is needed through rigorous clinical trials.

Objective Shuangxia Decoction is a traditional Chinese medicine classic formula used clinically to treat insomnia, consisting of Pinellia ternata (Banxia) and Prunella vulgaris (Xiakucao). The aim of this study is to explore the pharmacokinetic characteristics of the main core components in Shuangxia Decoction based on Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) analysis, as well as to preliminarily investigate its mechanisms of action in treating insomnia using quantitative targeted network pharmacology. Methods In this research, an LC-MS/MS method was established to analyze four main core components in Shuangxia Decoction: rosmarinic acid, 4-hydroxy-3-methoxyphenyllactic acid (HMLA), danshensu, and liquiritigenin. The pharmacokinetic characteristics of these phenolic compounds were investigated after oral administration of Shuangxia Decoction in rats. Network pharmacology and molecular docking were used to identify the underlying mechanism of Shuangxia Decoction in treating insomnia. Results The results showed that the analysis of the four components was completed within 6 ​min. The Tmax for rosmarinic acid, HMLA, danshensu, and liquiritigenin were 0.79 ​± ​0.09, 0.63 ​± ​0.12, 0.51 ​± ​0.21, and 0.38 ​± ​0.19 ​h, respectively; their Cmax were 110.83 ​± ​10.98, 25.20 ​± ​4.13, 37.57 ​± ​7.70, and 22.27 ​± ​8.75 ​μg/L, respectively; and their T1/2 were 1.20 ​± ​0.24, 0.79 ​± ​0.26, 4.93 ​± ​1.08, and 2.85 ​± ​0.11 ​h, respectively. Danshensu exhibited the highest peak concentration (Cmax: 110.83 ​± ​10.98 ​μg/L), while rosmarinic acid showed the lowest Cmax (37.57 ​± ​7.70 ​μg/L), likely due to hydrolysis by intestinal carboxylesterases. Network pharmacology results indicated that the main active components of Shuangxia Decoction exert their effects primarily through neuro-signaling pathways such as the dopaminergic synapse and glutamatergic synapse. Conclusion This study is the first to explore the pharmacokinetic characteristics of the four core components in Shuangxia Decoction and to provide preliminary predictions of its mechanisms in treating insomnia, laying a foundation for further exploration of its pharmacological mechanisms.