Objective Based on the theory of"stomach disharmony leads to restlessness",the causal relationship between gastroesophageal reflux disease and insomnia was discussed by Mendel randomization method with two samples.Methods The data were collected from genome-wide association studies,the exposure factor was gastroesophageal reflux disease,and the outcome variable was insomnia.Mendel randomization analysis is realized by inverse variance weighted method,MR-Egger method,simple model method,weighted model method and weighted median method.Sensitivity analysis includes pleiotropic test,heterogeneity test and one-by-one elimination test,and is calculated by MR-Egger method,Cochran Q test and one-out-of-one method in turn.Results A total of 75 single nucleotide polymorphisms(SNPs)were screened.The inverse variance weighted method showed that gastroesophageal reflux disease increased the risk of insomnia(OR=1.255,95%CI:1.071-1.470,P<0.05).The weighted median method also confirmed that there was a positive causal relationship between gastroesophageal reflux disease and insomnia(OR=1.403,95%CI:1.117-1.762,P<0.05).Multiple sensitivity analysis indicated that there was no pleiotropy and heterogeneity in the results of Mendelian randomized analysis,which verified the stability of the research results.Conclusion There is a positive causal relationship between gastroesophageal reflux disease and insomnia,which enriches the theoretical connotation of"stomach disharmony leads to restlessness"from the genetic point of view and lays a foundation for further study.

Objective Based on the theory of"stomach disharmony leads to restlessness",the causal relationship between gastroesophageal reflux disease and insomnia was discussed by Mendel randomization method with two samples.Methods The data were collected from genome-wide association studies,the exposure factor was gastroesophageal reflux disease,and the outcome variable was insomnia.Mendel randomization analysis is realized by inverse variance weighted method,MR-Egger method,simple model method,weighted model method and weighted median method.Sensitivity analysis includes pleiotropic test,heterogeneity test and one-by-one elimination test,and is calculated by MR-Egger method,Cochran Q test and one-out-of-one method in turn.Results A total of 75 single nucleotide polymorphisms(SNPs)were screened.The inverse variance weighted method showed that gastroesophageal reflux disease increased the risk of insomnia(OR=1.255,95%CI:1.071-1.470,P<0.05).The weighted median method also confirmed that there was a positive causal relationship between gastroesophageal reflux disease and insomnia(OR=1.403,95%CI:1.117-1.762,P<0.05).Multiple sensitivity analysis indicated that there was no pleiotropy and heterogeneity in the results of Mendelian randomized analysis,which verified the stability of the research results.Conclusion There is a positive causal relationship between gastroesophageal reflux disease and insomnia,which enriches the theoretical connotation of"stomach disharmony leads to restlessness"from the genetic point of view and lays a foundation for further study.

BackgroundInsomnia， a common sleep disorder， is robustly associated with cardiovascular diseases， diabetes， and psychiatric disorders， substantially impairing quality of life. Although clinically commonly used medications are effective， long-term use may lead to drug resistance and dependence. While the efficacy of Ganmai Dazao Decoction in improving insomnia is definite， its underlying molecular mechanisms remain unclear. ObjectiveTo explore the active ingredients and core targets of Ganmai Dazao Decoction in the treatment of insomnia， systematically reveal its potential molecular pharmacological mechanism， and to provide references for clinical application. MethodsIn November 2024， the active ingredients and related targets of Ganmai Dazao Decoction were screened from the INPUT database. Insomnia-related datasets were acquired from the Gene Expression Omnibus （GEO） database， followed by differential expression analysis using GEO2R to identify differentially expressed genes （DEGs） associated with insomnia. The shared targets were obtained through Venn diagrams， and the protein-protein interaction （PPI） network was constructed using the STRING database and Cytoscape 3.9.1. Enrichment analyses were conducted on the shared targets using Gene Ontology （GO） and the Kyoto Encyclopedia of Genes and Genomes （KEGG）. The top 3 key active ingredients and the top 10 core targets in terms of node degree values were selected. Molecular docking and molecular dynamics simulation of receptors and ligands were performed using AutoDock 4.4.6， and the results were visualized using Pymol 3.0.3 to further verify the stability of the receptor-ligand complex system. ResultsA total of 337 active ingredients and 5 265 drug-related targets in Ganmai Dazao Decoction were retrieved， along with 1 061 insomnia-related DEGs. 287 shared targets were identified between Ganmai Dazao Decoction and insomnia. The traditional Chinese medicine-active ingredients-shared targets-disease network showed that quercetin， catechins and kaempferol were the key components of Ganmai Dazao Decoction in treating insomnia. These three components alleviate insomnia by acting on ten core targets， including nuclear factor kappa B inhibitor alpha （NFKBIA）， fibronectin 1 （FN1）， interleukin-6 （IL6）， protein c-Fos （FOS）， histone acetyltransferase p300 （EP300）， histone deacetylase 1 （HDAC1）， transcription factor Jun （JUN）， heat shock protein HSP 90-alpha 1 （HSP90AA1）， glyceraldehyde 3-phosphate dehydrogenase （GAPDH）， and interleukin-1 beta （IL1β）. GO and KEGG enrichment analyses indicated that Ganmai Dazao Decoction may alleviate insomnia through the IL17 signaling pathways， lipid and atherosclerosis signaling pathways， and other mechanisms. The results of molecular docking demonstrated strong binding affinity between the 3 key components and the 10 core targets of Ganmai Dazao Decoction. Molecular dynamics simulations further confirmed the stability of the quercetin-GAPDH， catechin-HDAC1 and kaempferol-EP300 complexes. ConclusionThe key components of Ganmai Dazao Decoction， namely quercetin， catechin， and kaempferol， exert therapeutic effects on insomnia by targeting 10 core proteins and modulating multiple pathways， including the IL17 signaling pathway， lipids and atherosclerotic-related pathways. ［Funded by Chengdu Medical College Level Scientific Research Project （number， CYZYB23-01）］

The evolving stratified treatment approach based on molecular genetic alterations and minimal residual disease (MRD) monitoring has established a strong foundation for clinically managing Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL). However, with the growing use of immune-targeted therapies and the increased sensitivity of detection technologies, discrepancies in MRD assessment have emerged in some patients with Ph + ALL, particularly where BCR:: ABL1-based MRD levels remain consistently elevated compared to those detected by alternative methods. Research suggests that this persistent BCR:: ABL1 positivity may not solely reflect residual lymphoblasts but may also indicate the involvement of multilineage hematopoietic cells. This distinct biological feature has been termed Ph + ALL with multilineage involvement. Currently, the absence of standardized diagnostic criteria and prognostic frameworks for this subtype poses significant challenges in clinical decision-making. Therefore, this article offers a comprehensive review of its molecular and pathological characteristics, potential prognostic biomarkers, patterns of disease evolution, and clinical implications, with the goal of informing more accurate diagnostic and therapeutic strategies.

Objective:To investigate the safety and feasibility of one-stage flexible ureteroscopic lithotripsy without ureteral access sheath or ureteral stent in the treatment of upper ureteral calculi and renal calculi with a long diameter of≤10 mm.Methods:A total of 70 patients with upper ureteral calculi or renal calculi with a long diameter of≤10 mm who were admitted to Guang'an Hospital,West China Hospital of Sichuan University,from January 2023 to June 2024 were enrolled and randomly divided into experimental group(without ureteral access sheath or ureteral stent)and control group(with ureteral access sheath and ureteral stent),with 35 patients in each group.The patients in the experimental group did not use a ureteral access sheath or a ureteral stent,while those in the control group used the ureteral access sheath and the ureteral stent.The two groups were compared in terms of preoperative data,intraoperative complications,stone clearance rate,length of hospital stay,hospital costs,and postoperative complications.Results:There were no sig-nificant differences between the two groups in preoperative data such as age,body mass index,sex,previous history of stone surgery,af-fected side,maximum stone diameter,C-reactive protein,aggregation system separation,preoperative CT value of stones,and stone lo-cation.The experimental group had a significantly shorter time of operation than the control group[(44.94±52.60)minutes vs.(52.60±14.22)minutes,t=2.240,P=0.030].There were no significant differences between the two groups in intraoperative data such as ureteral injury,intraoperative leukocyte changes,and intraopera-tive blood loss.The experimental group had significantly lower hos-pital costs than the control group[(8041.89±1287.57)yuan vs.(13 011.63±1 780.21)yuan,t=13.450,P=0.000].There were no significant differences between the experimental group and the con-trol group in the postoperative data such as the length of hospital stay,the recurrence of calculi on CT at 1 and 3 months after sur-gery,stone clearance rate,postoperative urinary tract irritation,post-operative ureteral injury,postoperative hematuria,and postoperative hydronephrosis(P>0.05).Conclusion:One-stage flexible uretero-scopic lithotripsy without ureteral access sheath or ureteral stent is safe and feasible in the treatment of upper ureteral calculi and renal calculi with a long diameter of≤10 mm and can effectively reduce hospital costs and time of operation.

Objective:To explore the expression of transmembrane protein 9(TMEM9)as an oncogene in prostate cancer(PCa),and to examine its effect on the proliferation and invasion of PCa cells as well as on the Wnt/β-catenin signaling pathway and autophagy of PCa cells by intervening with its expression.Methods:The Cancer Genome Atlas was used for pan-cancer analysis of TMEM9 expres-sion levels in different tumors,and TMEM9 protein and messenger ribonucleic acid(mRNA)levels in clinical PCa and prostatic hyper-plasia specimens were analyzed.Real-time quantitative polymerase chain reaction and western blotting were used to analyze TMEM9 expression levels in different PCa cell lines.Cell counting,terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL),and Transwell assay were used to analyze cell proliferation,apoptosis,and PCa cell invasion,respectively.Subcutaneous tu-morigenesis in nude mice was used to analyze tumor proliferation in vivo.Western blotting was used to analyze the expression of autophagy-related pathway proteins,and transmission electron microscopy and immunofluorescence colocalization were used to deter-mine the colocalization of autophagosomes and lysosomes.Results:TMEM9 was highly expressed in PCa.The mRNA and protein ex-pression levels of TMEM9 were higher in PCa tissues than in prostatic hyperplasia tissues.The expression of TMEM9 was highest in PC3 cells(human PCa cells)(t=17.150,P<0.01).In TMEM9-knocked down PC3 cells,the proliferation(t=3.165,P<0.05)and inva-sion(F=76.620,P<0.01)significantly decreased,and apoptosis(t=13.530,P=0.010)significantly increased.After knockdown of TMEM9,the volume(F=1 699.000,P<0.01)and weight(t=9.057,P<0.01)of subcutaneous tumors in nude mice were reduced,and tu-mor growth was inhibited.TMEM9 regulated the Wnt/β-catenin signaling pathway and inhibited the AKT-mTOR signaling pathway to promote autophagy in PCa cells.Conclusion:TMEM9 inhibits the AKT-mTOR signaling pathway and promotes the proliferation and invasion of PCa cells through autophagy.

The evolving stratified treatment approach based on molecular genetic alterations and minimal residual disease (MRD) monitoring has established a strong foundation for clinically managing Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL). However, with the growing use of immune-targeted therapies and the increased sensitivity of detection technologies, discrepancies in MRD assessment have emerged in some patients with Ph + ALL, particularly where BCR:: ABL1-based MRD levels remain consistently elevated compared to those detected by alternative methods. Research suggests that this persistent BCR:: ABL1 positivity may not solely reflect residual lymphoblasts but may also indicate the involvement of multilineage hematopoietic cells. This distinct biological feature has been termed Ph + ALL with multilineage involvement. Currently, the absence of standardized diagnostic criteria and prognostic frameworks for this subtype poses significant challenges in clinical decision-making. Therefore, this article offers a comprehensive review of its molecular and pathological characteristics, potential prognostic biomarkers, patterns of disease evolution, and clinical implications, with the goal of informing more accurate diagnostic and therapeutic strategies.

Neuropathic pain is a chronic pain condition caused by damage or dysfunction of the nervous sys-tem.Symptoms of neuropathic pain include spontaneous pain,hyperalgesia,and sensory abnormalities.AMP-activated protein kinase(AMPK)is a key energy regulator that maintains cellular homeostasis by modulating carbohydrate and lipid metabolism.Recent studies have highlighted its role in synaptic plasticity and glial cell function,suggesting that AMPK signaling pathways contribute to the onset and progression of neurological disorders.Investigations using animal models of neuropathic pain as well as clinical research have illustrated aberrations in AMPK expression and activity at various sites along sensory conduction pathways.Treatment with AMPK agonists has been shown to alleviate pain symptoms,suggesting that dysregulation of AMPK expression/function contributes to the development and persistence of neuropathic pain.There-fore,the development of analgesics targeting AMPK has garnered considerable attention worldwide.This article provides a comprehensive review of the mechanisms by which AMPK participates in neuropathic pain,with the aim of guiding the de-velopment of related analgesic drugs.

Objective:To evaluate the clinical efficacy of acupuncture combined with extracorporeal shock wave therapy in the treatment of piriformis syndrome.Methods:Eighty patients with piriformis syndrome who received treatment in Huaihe Energy Occupational Disease Prevention Hospital Rehabilitation Medicine Center from February 2021 to December 2022 were included in this study. They were divided into a treatment group ( n = 40) and a control group ( n = 40) according to different treatment methods using a retrospective cohort study design. The treatment group was treated with acupuncture combined with extracorporeal shock wave therapy, once every 7 days for 3 consecutive weeks. The control group was treated with extracorporeal shock wave therapy alone once every 7 days for 3 consecutive weeks.Pre- and post-treatment visual analogue scale scores and clinical efficacy were compared between the two groups. Results:There was no significant difference in baseline data between the two groups (all P > 0.05). After treatment, the visual analogue scale score decreased in each group. After adjusting for covariates, there was no significant difference in visual analogue scale score between the two groups ( F = 112.38, P < 0.001). After adjusting the pre-treatment visual analogue scale score, the post-treatment visual analogue scale score in the treatment group was lower than that in the control group [1.417 (95% CI: 1.151-1.683)]. The total response rate in the treatment group was 97.5% (39/40), which was significantly higher than 82.5% (33/40) in the control group ( Z = -2.03, P = 0.042). Conclusion:Acupuncture combined with extracorporeal shock wave therapy is highly effective on piriformis syndrome.

Objective: To investigate the influencing factors of depressive symptoms among rural elderly patients with chronic diseases in China, so as to provide insights into depression prevention and control among the rural elderly patients with chronic diseases. Methods: The basic demographics, health status, and lifestyle of rural residents at ages of 65 years and older who had at least one chronic disease were retrieved from The Chinese Longitudinal Healthy Longevity Survey (CLHLS) database in 2018, and participants' depressive symptoms were assessed with The Center for Epidemiological Studies Depression-10 (CES-D-10) scale. Factors affecting the depressive symptoms were identified with a multivariable logistic regression model. Results: Totally 5 146 rural elderly patients with chronic diseases were enrolled, including 2 373 men (46.11%) and 2 773 women (53.89%). The prevalence of depressive symptoms was 27.13%. Multivariable logistic regression analysis identified having two and more children (OR=0.614, 95%CI: 0.387-0.975), living alone (OR=1.450, 95%CI: 1.192-1.764), life satisfaction (general, OR=1.933, 95%CI: 1.651-2.264; low, OR=5.366, 95%CI: 3.488-8.254), self-assessed health status (general, OR=2.697, 95%CI: 2.284-3.185; poor, OR=5.338, 95%CI: 4.262-6.685), disability in instrumental activities of daily living (OR=1.592, 95%CI: 1.328-1.908), sleep duration (normal, OR=0.502, 95%CI: 0.429-0.586; too long, OR=0.494, 95%CI: 0.405-0.603), exercise (OR=0.721, 95%CI: 0.607-0.856), watching TV (OR=0.787, 95%CI: 0.664-0.933), and gardening activities (OR=0.781, 95%CI: 0.626-0.975) as factors affecting depressive symptoms among rural elderly patients with chronic diseases. Conclusions The prevalence of depressive symptoms was 27.13% among rural elderly patients with chronic diseases. Number of children, living style, life satisfaction, health status, sleep duration, exercise, watching TV, and gardening activities are associated with the development of depressive symptoms among rural elderly patients with chronic diseases.