Patients suffering from nerve injury often experience exacerbated pain responses and complain of memory deficits. The dorsal hippocampus (dHPC), a well-defined region responsible for learning and memory, displays maladaptive plasticity upon injury, which is assumed to underlie pain hypersensitivity and cognitive deficits. However, much attention has thus far been paid to intracellular mechanisms of plasticity rather than extracellular alterations that might trigger and facilitate intracellular changes. Emerging evidence has shown that nerve injury alters the microarchitecture of the extracellular matrix (ECM) and decreases ECM rigidity in the dHPC. Despite this, it remains elusive which element of the ECM in the dHPC is affected and how it contributes to neuropathic pain and comorbid cognitive deficits. Laminin, a key element of the ECM, consists of α-, β-, and γ-chains and has been implicated in several pathophysiological processes. Here, we showed that peripheral nerve injury downregulates laminin β1 (LAMB1) in the dHPC. Silencing of hippocampal LAMB1 exacerbates pain sensitivity and induces cognitive dysfunction. Further mechanistic analysis revealed that loss of hippocampal LAMB1 causes dysregulated Src/NR2A signaling cascades via interaction with integrin β1, leading to decreased Ca²⁺ levels in pyramidal neurons, which in turn orchestrates structural and functional plasticity and eventually results in exaggerated pain responses and cognitive deficits. In this study, we shed new light on the functional capability of hippocampal ECM LAMB1 in the modulation of neuropathic pain and comorbid cognitive deficits, and reveal a mechanism that conveys extracellular alterations to intracellular plasticity. Moreover, we identified hippocampal LAMB1/integrin β1 signaling as a potential therapeutic target for the treatment of neuropathic pain and related memory loss.
Animals ; Laminin/genetics* ; Hippocampus/metabolism* ; Neuralgia/metabolism* ; Cognitive Dysfunction/etiology* ; Male ; Peripheral Nerve Injuries/metabolism* ; Extracellular Matrix/metabolism* ; Integrin beta1/metabolism* ; Pyramidal Cells/metabolism* ; Signal Transduction

Objective To predict potential quality markers(Q-Markers)of Gastrodia elata using fingerprinting,chemical pattern recognition and network pharmacology methods.Methods A total of 46 batches of Gastrodia elata were analyzed using high-performance liquid chromatography(HPLC)to establish fingerprint profiles,and common peaks were identified.Systematic cluster analysis(HCA),principal component analysis(PCA),and orthogonal partial least squares discriminant analysis(OPLS-DA)were employed to evaluate the 46 batches of samples.Additionally,The network diagram of"components-targets-pathways"was constructed using network pharmacology.Q-Marker of Gastrodia elata was predicted and quantitative analysis was conducted simultaneously.Results Seven substances were identified among the 13 common peaks in the fingerprint profiles.Results from HCA,PCA,and OPLS-DA were consistent,while network pharmacology identified 17 core active ingredients,86 core targets,and 181 key pathways.Integrating fingerprinting and network pharmacology,Gastrodin,p-hydroxybenzyl alcohol,parishin A,parishin B,parishin C,and parishin E were selected as potential Q-Markers of Gastrodia elata.The total contents of GAS and HBA alcohol in 46 batches of Gastrodia gastrodia decoction pieces ranged from 0.17%to 2.08%.Conclusion Integration of fingerprinting and network pharmacology analyses predicted potential Q-Markers of Gastrodia elata,and providing a scientific basis for comprehensive quality control and evaluation.

Aim To investigate the antidepressant mechanism of hyperforin via the utilization of single-cell sequencing technology.Methods C57BL/6 mice were randomly divided into the control group,depres-sion model group,and hyperforin intervention group.The chronic unpredictable mild stress(CUMS)model was induced and drug interventions were administered for 28 d.Behavioral experiments were conducted to as-sess depressive symptoms,and hippocampal tissue was collected for single-cell RNA sequencing.Key cell populations and differentially expressed genes across groups were identified,followed by PPI network,GO,and KEGG enrichment analysis.Results Behavioral experiments indicated that CUMS successfully induced depressive symptoms in mice,while hyperforin im-proved depressive behavior.In the depression model group,the proportion of brain perivascular macrophages(PVM)increased,and this proportion decreased after hyperforin intervention,approaching the level seen in the control group.The top 20 common differentially ex-pressed genes in the PVM subpopulation were Saa3,Hbb-bs and Ccl24.PPI network analysis identified core targets,including Ccl2,Dhx9,C3,Msr1,Cxcl2 and Cx3cr1.KEGG enrichment analysis revealed pathways related to chemokines,phagosome formation,and inosi-tol phosphate metabolism.Conclusion The antide-pressant mechanism of hyperforin may be related to the regulation of Ccl24 and its related chemokine signaling pathway by PVM.

Objective:To explore the effect of Lactobacillus reuteri on testicular injury in mice exposed to neonicotinoid insec-ticides(NNI).Methods:Fifteen C57BL/6 male mice were randomly divided into control group(CTRI.group),exposure group(NNI group)and Lactobacillus intervention group(NNI-L group).The mice in CTRL group were given 0.02ml/g of 0.5％carboxym-ethyl cellulose sodium solution by gavage for 14 days.The mice in NNI group were given 0.02 ml/g of NNI mixture by gavage for 14 days.The mice in NNI-L group were given 0.02 ml/g of NNI mixture by gavage and 5 × 108cfu/ml of Lactobacillus reuteri powder so-lution for 14 days.Then,the histomorphology and function of testicle were evaluated by hematoxylin-eosin staining,immunofluores-cence staining and RNA sequencing.Results:Compared with CTRL group,the thickness of testicular seminiferous epithelium in the NNI group was significantly thinner.And the decline in the number of spermatogenic cells and sperm was observed.And the expression of spermatogonial stem cell marker UCHL1 was down-regulated which was significantly improved in NNI-L group compared with the NNI group.The abnormal expressions of hormone and sperm methylation related genes in testis of NNI group were detected by RNA sequen-cing,with significant down-regulation being found in NPFF and IGF2.While the expression of HSD3B8 was significantly up-regulated.The abnormal expression of these genes could be significantly improved after oral administration of Lactobacillus reuteri.Conclusion:Testicular spermatogenesis and endocrine function can be damaged by NNI exposure.And oral administration of Lactoba-cillus reuteri protects testis from the adverse effects of NNI toxicity.

Aim To investigate the antidepressant mechanism of hyperforin via the utilization of single-cell sequencing technology.Methods C57BL/6 mice were randomly divided into the control group,depres-sion model group,and hyperforin intervention group.The chronic unpredictable mild stress(CUMS)model was induced and drug interventions were administered for 28 d.Behavioral experiments were conducted to as-sess depressive symptoms,and hippocampal tissue was collected for single-cell RNA sequencing.Key cell populations and differentially expressed genes across groups were identified,followed by PPI network,GO,and KEGG enrichment analysis.Results Behavioral experiments indicated that CUMS successfully induced depressive symptoms in mice,while hyperforin im-proved depressive behavior.In the depression model group,the proportion of brain perivascular macrophages(PVM)increased,and this proportion decreased after hyperforin intervention,approaching the level seen in the control group.The top 20 common differentially ex-pressed genes in the PVM subpopulation were Saa3,Hbb-bs and Ccl24.PPI network analysis identified core targets,including Ccl2,Dhx9,C3,Msr1,Cxcl2 and Cx3cr1.KEGG enrichment analysis revealed pathways related to chemokines,phagosome formation,and inosi-tol phosphate metabolism.Conclusion The antide-pressant mechanism of hyperforin may be related to the regulation of Ccl24 and its related chemokine signaling pathway by PVM.

Objective:The aim of this study is to re-evaluate the systematic reviews and meta-analyses on statins for the treat-ment of erectile dysfunction(ED)and construct an umbrella review,thereby providing robust evidence-based for the clinical applica-tion of statins in ED treatment.Methods:A comprehensive computerized search was conducted across CNKI,Wanfang Database,VIP,WOS,Embase,PubMed,and Cochrane Library databases from their inception to September 12,2024,for all systematic reviews and meta-analyses addressing statin interventions in ED.The methodological quality,reporting quality,and evidence quality of the in-cluded studies were assessed and summarized using PRISMA 2020,AMSTAR 2,and GRADE systems.Results:Four systematic re-views and meta-analyses were included.According to the AMSTAR 2 evaluation,one paper was rated as low quality,while the remai-ning three were classified as very low quality.PRISMA 2020 evaluation results indicated that the average score of the four included studies was 29,with all being of medium quality but exhibiting partial deficiencies.The proportion of fully consistent items across the four studies ranged from 52.38％to 80.95％.GRADE system tool evaluation revealed 11 outcome indicators,of which only one was rated as intermediate evidence.The remainders were categorized as low or very low evidence,with no high-quality evidence identified.Conclusion:Statins demonstrate efficacy in treating ED.However,the current quality of relevant systematic reviews is suboptimal,with notable deficiencies in methodological,reporting,and evidential quality.Further high-quality studies are warranted to provide more reliable evidence-based medical guidance for clinical practice.

Objective To predict potential quality markers(Q-Markers)of Gastrodia elata using fingerprinting,chemical pattern recognition and network pharmacology methods.Methods A total of 46 batches of Gastrodia elata were analyzed using high-performance liquid chromatography(HPLC)to establish fingerprint profiles,and common peaks were identified.Systematic cluster analysis(HCA),principal component analysis(PCA),and orthogonal partial least squares discriminant analysis(OPLS-DA)were employed to evaluate the 46 batches of samples.Additionally,The network diagram of"components-targets-pathways"was constructed using network pharmacology.Q-Marker of Gastrodia elata was predicted and quantitative analysis was conducted simultaneously.Results Seven substances were identified among the 13 common peaks in the fingerprint profiles.Results from HCA,PCA,and OPLS-DA were consistent,while network pharmacology identified 17 core active ingredients,86 core targets,and 181 key pathways.Integrating fingerprinting and network pharmacology,Gastrodin,p-hydroxybenzyl alcohol,parishin A,parishin B,parishin C,and parishin E were selected as potential Q-Markers of Gastrodia elata.The total contents of GAS and HBA alcohol in 46 batches of Gastrodia gastrodia decoction pieces ranged from 0.17%to 2.08%.Conclusion Integration of fingerprinting and network pharmacology analyses predicted potential Q-Markers of Gastrodia elata,and providing a scientific basis for comprehensive quality control and evaluation.

The incidence of male infertility has been increasing year by year,and one of the major causes is testicular spermato-genic epithelial injury,which affects the spermatogenic function of the testis.Ferroptosis is a novel mode of cell death and plays an im-portant role in testicular cell injury.Some traditional Chinese medicines can intervene in the progression of testicular injury by regula-ting the ferroptosis pathway in testicular spermatogenic epithelia.This paper focuses on the effect of traditional Chinese drugs in regula-ting the ferroptosis pathway in testicular cells,and summarizes the advances in the studies of traditional Chinese medicines in the treat-ment of testicular spermatogenic epithelial injury,aiming to provide a theoretical basis for the selection of relevant medicines and their clinical application.

The Piezo protein is a non-selective mechanosensitive cation channel that exhibits sensitivity to mechanical stimuli such as pressure and shear stress. It converts mechanical signals into bioelectric activity within cells, thus triggering specific biological responses. In the digestive system, Piezo protein plays a crucial role in maintaining normal physiological activities, including digestion, absorption, metabolic regulation, and immune modulation. However, dysregulation in Piezo protein expression may lead to the occurrence of several pathological conditions, including visceral hypersensitivity, impairment of intestinal mucosal barrier function, and immune inflammation.Therefore, conducting a comprehensive review of the physiological functions and pathological roles of Piezo protein in the digestive system is of paramount importance. In this review, we systematically summarize the structural and dynamic characteristics of Piezo protein, its expression patterns, and physiological functions in the digestive system. We particularly focus on elucidating the mechanisms of action of Piezo protein in digestive system tumor diseases, inflammatory diseases, fibrotic diseases, and functional disorders. Through the integration of the latest research findings, we have observed that Piezo protein plays a crucial role in the pathogenesis of various digestive system diseases. There exist intricate interactions between Piezo protein and multiple phenotypes of digestive system tumors such as proliferation, apoptosis, and metastasis. In inflammatory diseases, Piezo protein promotes intestinal immune responses and pancreatic trypsinogen activation, contributing to the development of ulcerative colitis, Crohn’s disease, and pancreatitis. Additionally, Piezo1, through pathways involving co-action with the TRPV4 ion channel, facilitates neutrophil recruitment and suppresses HIF-1α ubiquitination, thereby mediating organ fibrosis in organs like the liver and pancreas. Moreover, Piezo protein regulation by gut microbiota or factors like age and gender can result in increased or decreased visceral sensitivity, and alterations in intestinal mucosal barrier structure and permeability, which are closely associated with functional disorders like irritable bowel sydrome (IBS) and functional consitipaction (FC). A thorough exploration of Piezo protein as a potential therapeutic target in digestive system diseases can provide a scientific basis and theoretical support for future clinical diagnosis and treatment strategies.

Objective To analyze the epidemiological characteristics,causes and disposal of blood-borne occupa-tional exposure of health care workers(HCWs)in a tertiary traditional Chinese medicine hospital,and provide ref-erence for reducing exposure risks.Methods Data on blood-borne occupational exposure reported by a traditional Chinese medicine hospital from January 2014 to December 2023 were collected retrospectively,and analyzed descrip-tively.Results The reported incidence of blood-borne occupational exposure among HCWs from 2014 to 2023 was 3.08％(527/17 098).Among them,55 cases had damaged skin or mucous membrane exposure,with an incidence of 0.32％;472 cases had sharp device injuries,with an incidence of 2.76％.Difference between the two was statis-tically significant(x2=335.125,P＜0.001).The main characteristcs of blood-borne occupational exposures were sharp device injuries(89.56％),female(83.49％),HCWs with less than 5 years of service(42.69％)and inter-mediate professional titles(67.93％).Damaged skin or mucous membrane exposure mainly occurred in doctors(58.18％),while sharp device injury occurred mainly in nurses(73.73％).Department of internal medicine had the highest exposure to sharp device injuries(42.80％),and operating room had the highest damaged skin or mucous membranes exposure(47.27％).The main occurrence timing of sharp device injuries were needle pulling(21.82％),disposal of used sharp devices and randomly placed sharp devices(20.34％),as well as injection,puncture,acu-puncture,tube sealing or blood collection(19.49％).71.73％exposure sources were clear,and the top three detec-ted blood-borne pathogens were hepatitis B virus(70.86％),hepatitis C virus(11.92％),and Treponema pallidum(9.27％).The correct disposal rate after exposure was 88.05％.Conclusion From 2014 to 2023,blood-borne oc-cupational exposure in this traditional Chinese medicine hospital was mainly caused by sharp device injuries.Nurses experienced more incidents during needle pulling and sharp device handling.Damaged skin or mucous membrane ex-posure was mainly due to splashing patient's blood into the eyes of doctors during surgery.