ObjectiveThis paper aims to investigate the effects of Xixintang on aquaporin-4 （AQP4） polarity distribution， blood-brain barrier （BBB） function， and neuroinflammationin rats with Alzheimer's disease （AD）， thereby revealing the potential mechanism through which this formula protects the BBB by regulating AQP4 polarization. The aim is to provide a scientific basis for clinical treatment. MethodsSixty Sprague-Dawley （SD） rats were randomly divided into a normal group， a model group， a probiotic group， a donepezil group， and an Xixintang group. The model was established by intraperitoneal injection of D-galactose （D-Gal） combined with bilateral intracerebroventricular injection of amyloid-β_25-35 （Aβ_25-35）. The probiotic group （30.85 mg·kg^-1）， donepezil group （0.88 mg·kg^-1）， and Xixintang group （1.174 g·kg^-1） received daily gavage administration， while the normal and model groups received intragastric administration with an equal volume of normal saline for one month. Cognitive ability was assessed by using the Morris water maze. BBB permeability was detected via Evans blue extravasation. The contents of interleukin-6 （IL-6）， amyloid-β_1-42 （Aβ_1-42）， and tumor necrosis factor-α （TNF-α） in the hippocampal tissues were measured by enzyme-linked immunosorbent assay （ELISA）. The protein expressions of zonula occludens-1 （ZO-1）， occludin， tissue inhibitor of metalloproteinase-1 （TIMP-1）， matrix metalloproteinase-9 （MMP-9）， and AQP4 in the hippocampal tissues were detected by western blot. The expression and co-localization levels of Aβ_1-42， ionized calcium-binding adapter molecule 1 （IBA1）， and AQP4/platelet endothelial cell adhesion molecule 31 （CD31） in the hippocampal region were examined by immunofluorescence. ResultsCompared with the normal group， the model group exhibited a significant decline in cognitive ability （P<0.01） and a marked increase in Evans blue extravasation in the brain （P<0.01）. The expressions of ZO-1， occludin， and TIMP-1 were significantly decreased （P<0.01）， while the expressions of AQP4 and MMP-9 were significantly increased （P<0.01）. The co-localization level of AQP4/CD31 was significantly reduced （P<0.01）， and the expressions of Aβ_1-42， IL-6， TNF-α， and IBA1 were significantly elevated （P<0.01）. Compared with the model group， the Xixintang group showed significant improvement in cognitive ability （P<0.01） and a significant reduction in Evans blue extravasation in the brain （P<0.01）. The expressions of occludin， TIMP-1， and ZO-1 were significantly increased （P<0.05， P<0.01）， while the expressions of AQP4 and MMP-9 were significantly decreased （P<0.05）. The co-localization level of AQP4/CD31 was significantly enhanced （P<0.01）， and the expressions of Aβ_1-42， IL-6， TNF-α， and IBA1 were significantly reduced （P<0.05， P<0.01）. ConclusionXixintang may improve cognitive function and alleviate AD pathology in AD model rats by regulating AQP4 polarity distribution， thereby breaking the vicious cycle of "Aβ deposition-neuroinflammation-BBB damage" and restoring the homeostasis of the microenvironment in the brain.

ObjectiveThis study aims to investigate whether Xixintang could ameliorate cognitive dysfunction in an Alzheimer's disease （AD） rat model induced by D-galactose and β-amyloid （Aβ_25-35）， by means of repairing the colonic mucosal barrier， regulating the Toll-like receptor 4 （TLR4）/nuclear factor-κB p65 （NF-κB p65） signaling pathway， and intervening in the pathological process mediated by the gut-brain axis. MethodsSixty specific pathogen-free （SPF） male Sprague-Dawley （SD） rats were randomly divided to five groups （n=12）： A control group， a model group， a donepezil group， an Xixintang group， and a probiotic group. Except for those in the control group， rats in all other groups received daily intraperitoneal injections of D-galactose for six consecutive weeks. Subsequently， aggregated Aβ_25-35 was injected stereotactically into the bilateral ventricles to establish the AD model. During the intervention periods， the rats in all groups were administered their respective drugs and normal saline by gavage. The Morris water maze test was used to assess the capacity for spatial learning and memory. Hematoxylin-eosin （HE） staining was employed to observe the histopathological changes in the colon tissues. Immunofluorescence was used to detect Aβ_1-41 deposition in the hippocampal region and Mucin 2 （MUC2） expression in the colonic mucosa. Western blot was performed to measure the protein expression levels of FFAR2，TLR4， NF-κB p65， occludin （OCLN）， zonula occludens-1 （ZO-1）， and MUC2 in the colonic tissues. Enzyme-linked immunosorbent assay （ELISA） was used to determine the contents of interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， serum amyloid A （SAA）， and Aβ_1-42 in the hippocampal region from the colonic tissues. The lipopolysaccharide （LPS） concentrations in colon tissues of rats were measured by using a dynamic chromogenic limulus assay. ResultsCompared with those in the control group， the rats in the model group exhibited a significantly prolonged escape latency and a markedly shorter duration in the target quadrant （P<0.01）. The integrity of the colonic mucosal structure was compromised， with disordered gland arrangement and a reduced number of goblet cells. The Aβ_1-42 deposition in the hippocampal region was significantly increased （P<0.01）. The protein expression levels of TLR4 and NF-κB p65 in colonic tissues were significantly upregulated （P<0.01）， while those of occludin and ZO-1 were downregulated （P<0.01）. The contents of inflammatory factors such as IL-6， TNF-α， and SAA were significantly elevated （P<0.01）， and the LPS level in the serum was markedly increased （P<0.01）. In comparison to those in the model group， the rats in the Xixintang group showed a significantly shortened escape latency and a prolonged duration in the target quadrant （P<0.01）. The colonic mucosal structure was ameliorated， with neat gland arrangement and an increased number of goblet cells. The Aβ_1-42 deposition in the hippocampal region was reduced （P<0.01）. The protein expressions of TLR4 and NF-κB p65 in the colon tissues were decreased （P<0.05，P<0.01）， while the protein levels of occludin and ZO-1 were increased （P<0.01）. The contents of IL-6， TNF-α， and serum amyloid A （SAA） were decreased （P<0.01）， and the LPS level was reduced （P<0.01）. ConclusionXixintang can significantly ameliorate cognitive dysfunction of AD model rats， by means of restoring the colonic mucosal barrier structure， reducing cerebral Aβ deposition， and suppressing peripheral and central inflammatory response. Its mechanism of action may be closely associated with the suppression of the TLR4/NF-κB signaling pathway activation， reduction of endotoxin levels， and regulation of the gut-brain axis.

ObjectiveThis study aims to investigate whether Xixintang could ameliorate cognitive dysfunction in an Alzheimer's disease （AD） rat model induced by D-galactose and β-amyloid （Aβ_25-35）， by means of repairing the colonic mucosal barrier， regulating the Toll-like receptor 4 （TLR4）/nuclear factor-κB p65 （NF-κB p65） signaling pathway， and intervening in the pathological process mediated by the gut-brain axis. MethodsSixty specific pathogen-free （SPF） male Sprague-Dawley （SD） rats were randomly divided to five groups （n=12）： A control group， a model group， a donepezil group， an Xixintang group， and a probiotic group. Except for those in the control group， rats in all other groups received daily intraperitoneal injections of D-galactose for six consecutive weeks. Subsequently， aggregated Aβ_25-35 was injected stereotactically into the bilateral ventricles to establish the AD model. During the intervention periods， the rats in all groups were administered their respective drugs and normal saline by gavage. The Morris water maze test was used to assess the capacity for spatial learning and memory. Hematoxylin-eosin （HE） staining was employed to observe the histopathological changes in the colon tissues. Immunofluorescence was used to detect Aβ_1-41 deposition in the hippocampal region and Mucin 2 （MUC2） expression in the colonic mucosa. Western blot was performed to measure the protein expression levels of FFAR2，TLR4， NF-κB p65， occludin （OCLN）， zonula occludens-1 （ZO-1）， and MUC2 in the colonic tissues. Enzyme-linked immunosorbent assay （ELISA） was used to determine the contents of interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， serum amyloid A （SAA）， and Aβ_1-42 in the hippocampal region from the colonic tissues. The lipopolysaccharide （LPS） concentrations in colon tissues of rats were measured by using a dynamic chromogenic limulus assay. ResultsCompared with those in the control group， the rats in the model group exhibited a significantly prolonged escape latency and a markedly shorter duration in the target quadrant （P<0.01）. The integrity of the colonic mucosal structure was compromised， with disordered gland arrangement and a reduced number of goblet cells. The Aβ_1-42 deposition in the hippocampal region was significantly increased （P<0.01）. The protein expression levels of TLR4 and NF-κB p65 in colonic tissues were significantly upregulated （P<0.01）， while those of occludin and ZO-1 were downregulated （P<0.01）. The contents of inflammatory factors such as IL-6， TNF-α， and SAA were significantly elevated （P<0.01）， and the LPS level in the serum was markedly increased （P<0.01）. In comparison to those in the model group， the rats in the Xixintang group showed a significantly shortened escape latency and a prolonged duration in the target quadrant （P<0.01）. The colonic mucosal structure was ameliorated， with neat gland arrangement and an increased number of goblet cells. The Aβ_1-42 deposition in the hippocampal region was reduced （P<0.01）. The protein expressions of TLR4 and NF-κB p65 in the colon tissues were decreased （P<0.05，P<0.01）， while the protein levels of occludin and ZO-1 were increased （P<0.01）. The contents of IL-6， TNF-α， and serum amyloid A （SAA） were decreased （P<0.01）， and the LPS level was reduced （P<0.01）. ConclusionXixintang can significantly ameliorate cognitive dysfunction of AD model rats， by means of restoring the colonic mucosal barrier structure， reducing cerebral Aβ deposition， and suppressing peripheral and central inflammatory response. Its mechanism of action may be closely associated with the suppression of the TLR4/NF-κB signaling pathway activation， reduction of endotoxin levels， and regulation of the gut-brain axis.

After two decades of development, transcatheter left atrial appendage closure has emerged as a safe and effective intervention for stroke prevention in patients with atrial fibrillation. In 2024, significant advancements were made in the field of left atrial appendage closure in terms of evidence-based medicine, device research and development, and guideline consensus. The annual report on transcatheter left atrial appendage closure systematically reviews global academic progress in 2024, encompassing newly published clinical evidence, recently developed occlusion devices, and updated international guidelines/consensus statements. In the future, the development direction of transcatheter left atrial appendage closure mainly includes expanding surgical indications, optimizing imaging assistance technology, improving closure device design, and exploring individualized strategies for postoperative antithrombotic therapy.

ObjectiveTo investigate and analyze an outbreak of rotavirus infectious diarrhea in a prison in Chongqing Municipality, to provide a basis for adult rotavirus surveillance and prevention, and to explore the public health problems in special settings. MethodsA retrospective survey was conducted to collect and analyze data on individual cases with diarrheal disease on-site. The clinical characteristics, as well as the temporal, spatial and geographical distribution patterns of the epidemic were described. Multi-pathogen detection tests were conducted both on diarrhea cases and environmental samples, with viral genotyping performed on positive samples. A case-control analysis was performed to identify the causes of the outbreak, and an SEIR model was adopted to predict the outbreak trend and evaluate the effectiveness of interventions. ResultsA total of 65 cases were found among the inmates, with an attack rate of 2.03%. The predominant clinical manifestations included diarrhea (89.23%), watery stool (73.85%), and dehydration (18.46%). The epidemic curve indicated a “human-to-human” transmission pattern, with an average incubation period of 5‒6 days. The attack rates among chefs in the main canteen (80.00%, 8/10) and caterers (28.33%, 17/60) were significantly higher than those of other inmates （P<0.05）. Multi-pathogen polymerase chain reaction (PCR) testing detected positive for group A rotavirus, with the viral genotyping identified as G9P [8] strain. Factors such as unprotected "bare-handed" food distribution among cases with diarrhea (OR=9.512, 95%CI: 4.261‒21.234) and close contact with diarrhea cases (OR=3.656, 95%CI: 1.719‒7.778) were the possible cause of the outbreak. The SEIR model (r₀=5, α=0.3, β₁=0.08, β₂=0.04) was constructed using prison inmates as susceptible population, aiming at fitting the initial transmission trend of the outbreak, and the epidemic rate declined rapidly after intervention measures were implemented (r_t≈0). ConclusionThis rare rotavirus infection diarrhea outbreak among adults in confined settings suggests that the construction of public health prevention and control systems in prison may be overlooked. Cross infection during meal processing and distribution in the canteens of such settings is likely to be the cause of the outbreak. Given the potential neglect of public heath system construction in special settings, it is imperative to enhance the surveillance and monitoring of rotavirus and other intestinal multi-pathogens among adults, as well as the construction of public health prevention and control systems in these special settings.

OBJECTIVE: Glucocorticoid-induced osteoporosis (GIOP) is a common complication of prolonged glucocorticoid therapy. Chlorogenic acid (CGA), a polyphenol with antioxidant properties that is extracted from traditional Chinese medicines such as Eucommiae Cortex, has potential anti-osteoporotic activity. This study aimed to investigate the possible effects of CGA on GIOP in mice and murine long bone osteocyte Y4 (MLO-Y4) cells and explore the underlying molecular mechanisms. METHODS: The protective effects of CGA were initially evaluated in the GIOP mouse model induced by dexamethasone (Dex). The micro-computed tomography, hematoxylin-eosin staining, silver nitrate staining, and serum detection were used to assess the efficacy of CGA for improving bone formation in vivo. Then, network pharmacology analysis was used to predict the potential targets and molecular mechanisms underlying the therapeutic efficacy of CGA against GIOP. After that, 2',7'-dichlorofluorescein diacetate staining, flow cytometry, real-time quantitative reverse transcription polymerase chain reaction, and Western blotting were used to verify the mechanisms of CGA against GIOP in vitro. RESULTS: Animal experiments showed that CGA treatment effectively attenuated Dex-induced decreases in bone mass and strength and improved disrupted osteocyte morphology in mice. The protein-protein interaction analysis highlighted erb-b2 receptor tyrosine kinase (ERBB2), which is also known as human epidermal growth factor receptor 2 (HER2), caspase-3, kinase insert domain receptor, matrix metallopeptidase 9, matrix metallopeptidase 2, proto-oncogene tyrosine-protein kinase Src, and epidermal growth factor receptor as core targets. The Kyoto Encyclopedia of Genes and Genomes analysis revealed several significantly enriched pathways (P < 0.05), including the ERBB, phosphoinositide 3 kinase-AKT serine/threonine kinase 1 (AKT), and mechanistic target of rapamycin kinase (mTOR) pathways. Cellular experiments verified that CGA enhanced bone formation and promoted autophagy while inhibiting apoptosis in MLO-Y4 cells exposed to Dex, which was associated with the upregulated expression of HER2 and activation of the HER2/AKT/mTOR signaling pathway. CONCLUSION CGA exerted anti-osteoporotic effects against GIOP, partially through targeting osteocytes and modulating the HER2/AKT/mTOR signaling pathway. Please cite this article as: Xie AN, Zhang SZY, Zhang Y, Cao JL, Wang CL, Wang LB, Wu HJ, Zhang J, Dai WW. Chlorogenic acid mitigates glucocorticoid-induced osteoporosis via modulation of HER2/AKT/mTOR signaling pathway. J Integr Med. 2025; 23(6):670-682.
Animals ; Chlorogenic Acid/therapeutic use* ; Osteoporosis/metabolism* ; Signal Transduction/drug effects* ; Proto-Oncogene Proteins c-akt/metabolism* ; TOR Serine-Threonine Kinases/metabolism* ; Mice ; Glucocorticoids/adverse effects* ; Receptor, ErbB-2/metabolism* ; Proto-Oncogene Mas ; Dexamethasone/adverse effects* ; Osteocytes/drug effects* ; Osteogenesis/drug effects* ; Male ; Cell Line ; Mice, Inbred C57BL ; Humans

OBJECTIVE: Observational studies have found associations between inflammatory bowel disease (IBD) and the risk of dementia, including Alzheimer's dementia (AD) and vascular dementia (VD); however, these findings are inconsistent. It remains unclear whether these associations are causal. METHODS: We conducted a meta-analysis by systematically searching for observational studies on the association between IBD and dementia. Mendelian randomization (MR) analysis based on summary genome-wide association studies (GWASs) was performed. Genetic correlation and Bayesian co-localization analyses were used to provide robust genetic evidence. RESULTS: Ten observational studies involving 80,565,688 participants were included in this meta-analysis. IBD was significantly associated with dementia (risk ratio [ RR] =1.36, 95% CI = 1.04-1.78; I ² = 84.8%) and VD ( RR = 2.60, 95% CI = 1.18-5.70; only one study), but not with AD ( RR = 2.00, 95% CI = 0.96-4.13; I ² = 99.8%). MR analyses did not supported significant causal associations of IBD with dementia (dementia: odds ratio [ OR] = 1.01, 95% CI = 0.98-1.03; AD: OR = 0.98, 95% CI = 0.95-1.01; VD: OR = 1.02, 95% CI = 0.97-1.07). In addition, genetic correlation and co-localization analyses did not reveal any genetic associations between IBD and dementia. CONCLUSION Our study did not provide genetic evidence for a causal association between IBD and dementia risk. The increased risk of dementia observed in observational studies may be attributed to unobserved confounding factors or detection bias.
Humans ; Mendelian Randomization Analysis ; Inflammatory Bowel Diseases/complications* ; Dementia/etiology* ; Observational Studies as Topic ; Genome-Wide Association Study

Objective:To investigate the feasibility of improving quality of life through outcome self-reporting and clinical intervention based on the Ureteral Stent Symptom Questionnaire(USSQ)for patients with upper tract urolithiasis.Methods:We enrolled 106 patients with upper urinary tract calculi from June 2023 to June 2024 who underwent ureteral stent placement at The First Affiliated Hospital of Chongqing Medical University.We applied the USSQ to monitor the patients'outcomes through their self-reports,and used the data to inform clinical interventions.The feasibility of this USSQ-based approach for improving patients'quality of life was evalu-ated.Results:The main symptoms after ureteral stent placement were pain and hematuria,while frequency,urgency,fever,and sexual problems were less common.The USSQ score was highest on the third day after operation,and thereafter declined in all the dimensions.except the additional problem.After intervention,the total USSQ score(57.5±10.1 vs.51.6±8.9,t=2.981,P=0.004)and urinary symptom score(30.8±5.3 vs.26.7±5.6,t=3.478,P<0.001)were significantly decreased.USSQ-based outcome self-reporting and clinical intervention could reduce symptom scores and improve patients'quality of life.Conclusion:USSQ-based outcome monitoring and management are feasible and effective for improving the quality of life of patients with upper tract urolithiasis.

Surgical methods for varicocele remain controversial. This study intends to evaluate the efficacy and safety of different surgical approaches for treating varicocele through a network meta-analysis (NMA). PubMed, Embase, Cochrane, and Web of Science databases were thoroughly searched. In total, 13 randomized controlled trials (RCTs) and 24 cohort studies were included, covering 9 different surgical methods. Pairwise meta-analysis and NMA were performed by means of random-effects models, and interventions were ranked based on the surface under the cumulative ranking curve (SUCRA). According to the SUCRA, microsurgical subinguinal varicocelectomy (MSV; 91.6%), microsurgical retroperitoneal varicocelectomy (MRV; 78.2%), and microsurgical inguinal varicocelectomy (MIV; 76.7%) demonstrated the highest effectiveness in reducing postoperative recurrence rates. In this study, sclerotherapy embolization (SE; 87.2%), MSV (77.9%), and MIV (67.7%) showed the best results in lowering the risk of hydrocele occurrence. MIV (82.9%), MSV (75.9%), and coil embolization (CE; 58.7%) were notably effective in increasing sperm motility. Moreover, CE (76.7%), subinguinal approach varicocelectomy (SV; 69.2%), and SE (55.7%) were the most effective in increasing sperm count. SE (82.5%), transabdominal laparoscopic varicocelectomy (TLV; 76.5%), and MRV (52.7%) were superior in shortening the length of hospital stay. The incidence rates of adverse events for MRV (0), SE (3.3%), and MIV (4.1%) were notably low. Cluster analyses indicated that MSV was the most effective in the treatment of varicocele. Based on the existing evidence, MSV may represent the optimal choice for varicocele surgery. However, selecting clinical surgical strategies requires consideration of various factors, including patient needs, surgeon experience, and the learning curve.
Humans ; Male ; Embolization, Therapeutic/methods* ; Microsurgery/methods* ; Randomized Controlled Trials as Topic ; Sclerotherapy/methods* ; Treatment Outcome ; Urologic Surgical Procedures, Male/methods* ; Varicocele/surgery*

OBJECTIVE: To explore the therapeutic effects and underlying mechanisms of Dendrobium officinale (Tiepi Shihu) extract (DOE) on insomnia. METHODS: Forty-two male Sprague-Dawley rats were randomly divided into 6 groups (n=7 per group): normal control, model control, melatonin (MT, 40 mg/kg), and 3-dose DOE (0.25, 0.50, and 1.00 g/kg) groups. Rats were raised in a strong-light (10,000 LUX) and -noise (>80 db) environment (12 h/d) for 16 weeks to induce insomnia, and from week 10 to week 16, MT and DOE were correspondingly administered to rats. The behavior tests including sodium pentobarbital-induced sleep experiment, sucrose preference test, and autonomous activity test were used to evaluate changes in sleep and emotions of rats. The metabolic-related indicators such as blood pressure, blood viscosity, blood glucose, and uric acid in rats were measured. The pathological changes in the cornu ammonis 1 (CA1) region of rat brain were evaluated using hematoxylin and eosin staining and Nissl staining. Additionally, the sleep-related factors gamma-aminobutyric acid (GABA), glutamate (GA), 5-hydroxytryptamine (5-HT), and interleukin-6 (IL-6) were measured using enzyme linked immunosorbent assay. Finally, we screened potential sleep-improving receptors of DOE using polymerase chain reaction (PCR) array and validated the results with quantitative PCR and immunohistochemistry. RESULTS: DOE significantly improved rats' sleep and mood, increased the sodium pentobarbital-induced sleep time and sucrose preference index, and reduced autonomic activity times (P<0.05 or P<0.01). DOE also had a good effect on metabolic abnormalities, significantly reducing triglyceride, blood glucose, blood pressure, and blood viscosity indicators (P<0.05 or P<0.01). DOE significantly increased the GABA content in hippocampus and reduced the GA/GABA ratio and IL-6 level (P<0.05 or P<0.01). In addition, DOE improved the pathological changes such as the disorder of cell arrangement in the hippocampus and the decrease of Nissel bodies. Seven differential genes were screened by PCR array, and the GABA_A receptors (Gabra5, Gabra6, Gabrq) were selected for verification. The results showed that DOE could up-regulate their expressions (P<0.05 or P<0.01). CONCLUSION DOE demonstrated remarkable potential for improving insomnia, which may be through regulating GABA_A receptors expressions and GA/GABA ratio.
Animals ; Dendrobium/chemistry* ; Rats, Sprague-Dawley ; Male ; Sleep Initiation and Maintenance Disorders/blood* ; Plant Extracts/therapeutic use* ; Receptors, GABA-A/metabolism* ; Noise/adverse effects* ; Light/adverse effects* ; gamma-Aminobutyric Acid/metabolism* ; Sleep/drug effects* ; Rats ; Receptors, GABA/metabolism*