Liver fibrosis is a chronic liver injury resulting from factors like viral hepatitis, autoimmune hepatitis, non-alcoholic steatohepatitis, fatty liver disease, and cholestatic liver disease. Liver transplantation is currently the gold standard for treating severe liver diseases. However, it is limited by a shortage of donor organs and the necessity for lifelong immunosuppressive therapy. Mesenchymal stem cells (MSCs) can differentiate into various liver cells and enhance liver function when transplanted into patients due to their differentiation and proliferation capabilities. Therefore, it can be used as an alternative therapy for treating liver diseases, especially for liver cirrhosis, liver failure, and liver transplant complications. However, due to the potential tumorigenic effects of MSCs, researchers are exploring a new approach to treating liver fibrosis using extracellular vesicles (exosomes) secreted by stem cells. Many studies show that exosomes released by stem cells can promote liver injury repair through various pathways, contributing to the treatment of liver fibrosis. In this review, we focus on the molecular mechanisms by which stem cell exosomes affect liver fibrosis through different pathways and their potential therapeutic targets. Additionally, we discuss the advantages of exosome therapy over stem cell therapy and the possible future directions of exosome research, including the prospects for clinical applications and the challenges to be overcome.

Liver fibrosis is a chronic liver injury resulting from factors like viral hepatitis, autoimmune hepatitis, non-alcoholic steatohepatitis, fatty liver disease, and cholestatic liver disease. Liver transplantation is currently the gold standard for treating severe liver diseases. However, it is limited by a shortage of donor organs and the necessity for lifelong immunosuppressive therapy. Mesenchymal stem cells (MSCs) can differentiate into various liver cells and enhance liver function when transplanted into patients due to their differentiation and proliferation capabilities. Therefore, it can be used as an alternative therapy for treating liver diseases, especially for liver cirrhosis, liver failure, and liver transplant complications. However, due to the potential tumorigenic effects of MSCs, researchers are exploring a new approach to treating liver fibrosis using extracellular vesicles (exosomes) secreted by stem cells. Many studies show that exosomes released by stem cells can promote liver injury repair through various pathways, contributing to the treatment of liver fibrosis. In this review, we focus on the molecular mechanisms by which stem cell exosomes affect liver fibrosis through different pathways and their potential therapeutic targets. Additionally, we discuss the advantages of exosome therapy over stem cell therapy and the possible future directions of exosome research, including the prospects for clinical applications and the challenges to be overcome.

Liver fibrosis is a chronic liver injury resulting from factors like viral hepatitis, autoimmune hepatitis, non-alcoholic steatohepatitis, fatty liver disease, and cholestatic liver disease. Liver transplantation is currently the gold standard for treating severe liver diseases. However, it is limited by a shortage of donor organs and the necessity for lifelong immunosuppressive therapy. Mesenchymal stem cells (MSCs) can differentiate into various liver cells and enhance liver function when transplanted into patients due to their differentiation and proliferation capabilities. Therefore, it can be used as an alternative therapy for treating liver diseases, especially for liver cirrhosis, liver failure, and liver transplant complications. However, due to the potential tumorigenic effects of MSCs, researchers are exploring a new approach to treating liver fibrosis using extracellular vesicles (exosomes) secreted by stem cells. Many studies show that exosomes released by stem cells can promote liver injury repair through various pathways, contributing to the treatment of liver fibrosis. In this review, we focus on the molecular mechanisms by which stem cell exosomes affect liver fibrosis through different pathways and their potential therapeutic targets. Additionally, we discuss the advantages of exosome therapy over stem cell therapy and the possible future directions of exosome research, including the prospects for clinical applications and the challenges to be overcome.

OBJECTIVES: The purinergic receptor P2X2 (P2RX2) encodes an ATP-gated ion channel permeable to Na⁺, K⁺, and especially Ca²⁺. Loss-of-function mutations in P2RX2 are known to cause autosomal dominant nonsyndromic deafness 41 (DFNA41), which manifests as high-frequency hearing loss, accelerated presbycusis, and increased susceptibility to noise-induced damage. Zebrafish, owing to their small size, rapid development, high fecundity, transparent embryos, and high gene conservation with humans, provide an ideal model for studying human diseases and developmental mechanisms. This study aims to generate a p2rx2 knockout zebrafish model using CRISPR/Cas9 gene editing system to investigate the effect of p2rx2 deficiency on the auditory system, providing a basis for understanding P2RX2-related hearing loss and developing gene therapy strategies. METHODS: Two CRISPR targets (sgRNA1 and sgRNA2) spaced 47 bp apart were designed within the zebrafish p2rx2 gene. Synthesized sgRNAs and Cas9 protein were microinjected into single-cell stage Tübingen (TU)-strain zebrafish embryos. PCR and gel electrophoresis verified editing efficiency at 36 hours post-fertilization (hpf). Surviving embryos were raised to adulthood (F0), tail-clipped, genotyped, and screened for positive mosaics. F1 heterozygotes were generated by outcrossing, and F2 homozygous mutants were obtained by intercrossing. Polymerase chain reaction (PCR) combined with sequencing verified mutation type and heritability. At 5 days post-fertilization (dpf), YO-PRO-1 staining was used to examine hair cell morphology and count in lateral line neuromasts and the otolith region. Auditory evoked potential (AEP) thresholds at 600, 800, 1 000, and 2 000 Hz were measured in nine 4-month-old wild type and mutant zebrafish per group. RESULTS: A stable p2rx2 knockout zebrafish line was successfully established. Sequencing revealed a 66 bp insertion at the first target site introducing a premature stop codon (TAA), leading to early termination of protein translation and loss of function. Embryos developed normally with no gross malformations. At 5 dpf, mutants exhibited significantly reduced hair cell density in the otolith region compared with wild type, although lateral line neuromasts were unaffected. AEP testing showed significantly elevated auditory thresholds at all 4 frequencies in homozygous mutants compared with wild type (all P<0.001), indicating reduced hearing sensitivity. CONCLUSIONS We successfully generated a p2rx2 loss-of-function zebrafish model using CRISPR/Cas9 technology. p2rx2 deficiency caused hair cell defects in the otolith region and increased auditory thresholds across frequencies, indicating its key role in maintaining zebrafish auditory hair cell function and hearing perception. The phenotype's restriction to the otolith region suggests tissue-specific roles of p2rx2 in sensory organs. This model provides a valuable tool for elucidating the molecular mechanisms of P2RX2-related hearing loss and for screening otoprotective drugs and developing gene therapies.
Animals ; Zebrafish/genetics* ; Receptors, Purinergic P2X2/deficiency* ; CRISPR-Cas Systems/genetics* ; Gene Knockout Techniques ; Phenotype ; Zebrafish Proteins/genetics* ; Disease Models, Animal

ObjectiveTo observe the clinical efficacy of Tongdu Huoxue decoction in the treatment of acute lumbar disc herniation （LDH）. MethodA total of 316 patients with acute LDH admitted to the orthopedic outpatient department of Hubei Provincial Hospital of Traditional Chinese Medicine and Honghu City Hospital of Traditional Chinese Medicine from January 2020 to June 2023 were randomly divided into two groups. 156 cases in the control group （two cases with stopped follow-up） were treated with meloxicam tablets， while 153 cases in the observation group （five cases with stopped follow-up） were treated with Tongdu Huoxue decoction. Both groups were treated for three months. The clinical efficacy， McGill Pain Score Scale （SF-MPQ）， Oswestry Dysfunction Index （ODI） score， and the Japanese Orthopaedic Association （JOA） scores of the two groups before and after treatment were compared. The serum levels of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） of the patients before and after treatment were determined by using enzyme-linked immunosorbent assay （ELISA）. The NDI-092 type electromyography-evoked potential instrument was adopted to measure the motor conduction velocity and clinical efficacy of the tibial and common peroneal nerves in patients of the two groups before and after treatment， and the clinical safety of the two groups of patients was compared. ResultAfter treatment， the total effective rate in the observation group was 95.4% （146/153）， significantly higher than that in the control group of 76.3% （119/156） （χ² =23.18， P<0.05）. After treatment， both groups showed significant reductions in SF-MPQ and ODI scores， as well as the levels of IL-1β， IL-6， and TNF-α （P<0.05）， with the observation group showing a more significant reduction （P<0.05）. Both groups showed a significant increase in JOA scores and motor conduction velocities of the tibial and common peroneal nerves after treatment （P<0.05）， with the observation group showing a more significant increase （P<0.05）. ConclusionTongdu Huoxue decoction can alleviate lumbar and leg pain in acute LDH， improve lumbar spine function， and suppress inflammatory reactions. It is highly safe and is worthy of clinical promotion.

Objective:To describe the characteristics, etiology and patterns of outpatients and inpatients patients with moderate or severe valvular heart disease (VHD).Methods:This is a cross-sectional study. Outpatients and inpatients with moderate or severe VHD who underwent transthoracic echocardiography for first examination from 1 st January 2001 to 1 st January 2020 in Southwest Hospital, Army Medical University were enrolled. Data were collected from medical records and big data platform of Southwest Hospital. Characteristics of age and gender, etiology and types of VHD were descriptively analysed. Results:A total of 68 354 patients with moderate or severe VHD were enrolled. The age was 63 (50, 72) years. And 35 706 (52.24%) patients were female. (1) Age characteristics: There was similar age trend between male and female patients with moderate or severe VHD. The number of patients increased firstly and then decreased and reached its peak in the age group of 65-69 years old. The peak age of mitral stenosis patients was 45-49 years, which was earlier than that of whole patients with moderate or severe VHD. The median age of patients with bicuspid aortic valve was 42 years. (2) Gender characteristics: The proportion of tricuspid regurgitation, pulmonary regurgitation, mitral regurgitation, mitral stenosis and valve surgery in female patients with moderate or severe VHD were higher than those in male patients. The proportion of aortic regurgitation, aortic stenosis and bicuspid aortic valve in male patients with moderate or severe VHD were significantly higher than those in female patients (all P<0.05). (3) Etiology: The proportion of rheumatic VHD was 13.07% (8 934/68 354), which was higher than that of degenerative VHD (0.67% (458/68 354)). (4) Types of VHD: Tricuspid regurgitation made contribution to the largest proportion with 60.72% (41 503/68 354), followed by mitral regurgitation, aortic regurgitation, mitral stenosis, pulmonary regurgitation and aortic stenosis. Conclusions:There are certain regional characteristics in the prevalence of moderate or severe VHD in southwest China, suggesting different attention should be paid on the whole process of refined management of moderate or severe VHD.

Objective:To explore the latent categories of outpatient nurses' conflict management styles and analyze their influencing factors.Methods:A total of 408 outpatient nurses from six hospitals of Jiangsu Province were selected as study participants by convenience sampling. Data were collected using a general information questionnaire, the Rahim Organizational Conflict Inventory Scale, the Nurse Burnout Scale, the Caring Ability Inventory Scale and the Wong and Law Emotional Intelligence Scale. Latent profile analysis was used to classify the conflict management styles of outpatient nurses, and logistic regression analysis was applied to identify the influencing factors of different categories.Results:A total of 408 questionnaires were distributed, and 372 valid responses were received, with an effective response rate of 91.18%. Outpatient nurses' conflict management styles were divided into two categories: the "Integration-Concession Group" and the "Dominance-Avoidance Group." Logistic regression analysis showed that being an only child, receiving interpersonal communication training, nurse burnout, humanistic care ability, and emotional intelligence were significant influencing factors of the latent categories of conflict management styles ( P<0.05) . Conclusions:There is heterogeneity in outpatient nurses' conflict management styles. It is recommended that nursing administrators adopt a comprehensive approach, conduct thorough assessments of nurses' general conditions and personality traits, guide nurses toward adopting positive conflict management methods, and enhance their abilities in problem-solving and conflict resolution. This can improve interpersonal relationships and work efficiency in medical settings, stabilize the outpatient nursing workforce, and improve the overall quality of nursing services.

Objective To investigate the effect of Inonotus obliquus extract on Crohn's disease and its mechanism by proteomics technology.Methods Crohn's disease(CD)model was induced by 2,4,6-trinitrobenzene sulfonic acid(TNBS).A total of 48 SD male rats were randomized into control,model,Inonotus obliquus low-dose(200 mg/kg),medium-dose(400 mg/kg),high-dose(800 mg/kg)groups,and positive control group(mesalazine,225 mg/kg).The disease activity index(DAI)score and the colonic mucosal injury index(CMDI)score were assessed after one week of drug intervention.HE staining was used to observe the histopathological changes in the colon,and ELISA was used to detect the levels of IL-1β,IL-6,and TNF-α in the serum.Proteins were extracted from the colonic tissues of the control group,model group,and Inonotus obliquus high-dose group,and bioinformatics analysis was performed for the proteins identified by quantitative proteomics.Finally,Western blot and RT-qPCR were employed to verify the key proteins.Results Compared with the model group,the DAI,CMDI and HE staining scores were significantly decreased in the medium and high dose groups(P＜0.05 or P＜0.01),as well as the levels of inflammatory factors IL-1β,IL-6 and TNF-αin serum(P＜0.05 or P＜0.01).Proteomic tests showed that there were 199 differentially expressed proteins(DEPs)between the Inonotus obliquus high-dose group and the model group,of which 63 DEPs were related to CD.Bioinformatics analysis showed that these 63 DEPs were mainly involved in NOD-like receptor signaling pathway,calcium signaling pathway,necroptosis,and other pathways.Consistent with proteomic result,expressions of Vdac1 and Trpv2 were confirmed by Western blot and RT-qPCR in colon tissue.Conclusions Inonotus obliquus extract may regulate NOD-like receptor signaling pathway,calcium signaling pathway,and necroptosis by interfering with the expression of Vdac1 and Trpv2,so as to achieve the effect of treating CD.