ObjectiveTo explore the efficacy and mechanisms of Sini San in the treatment of depression and liver injury based on gut microbiota. MethodsThirty-two male Sprague-Dawley （SD） rats were randomly divided into a normal group， model group （M）， Sini San group （MS， 2.5 g·kg^-1）， and fluoxetine group （MF， 2 mg·kg^-1）. Except for the normal group， rats in the other three groups were subjected to chronic unpredictable mild stress （CUMS）. After 8 weeks， the open-field test and sucrose preference test were conducted. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum corticosterone （CORT）， adrenocorticotropic hormone （ACTH）， corticotropin-releasing factor （CRF）， lipopolysaccharide （LPS）， Zonulin， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， γ-aminobutyric acid （GABA） levels in the hippocampus and prefrontal cortex， and brain-derived neurotrophic factor （BDNF） levels in the hippocampus. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect hippocampal BDNF mRNA expression. Serum alanine aminotransferase （ALT） and aspartate aminotransferase （AST） levels were measured using the ultraviolet lactate dehydrogenase method. The ultrastructure of the intestinal epithelium was observed by electron microscopy， and gut microbiota in rat feces were analyzed using 16S rDNA high-throughput sequencing. ResultsCompared with the normal group， the sucrose preference of rats in the model group was significantly reduced （P0.01）， whereas it was significantly increased in the Sini San group compared with the model group （P0.05）. Compared with the normal group， hippocampal GABA protein levels and BDNF mRNA expression in the model group were significantly decreased （P0.05）， and compared with the model group， both were significantly increased in the Sini San group （P0.05， P0.01）. Compared with the normal group， serum LPS and Zonulin levels in the model group were significantly increased （P0.05， P0.01）， and compared with the model group， Zonulin levels in the Sini San group were significantly decreased （P0.05）. No obvious changes were observed in the ultrastructure of the jejunal mucosa among groups. Compared with the normal group， widened and blurred tight junctions， sparse and shortened microvilli， and mitochondrial swelling with cristae disruption in epithelial cells were observed in the ileal and colonic mucosa of the model group， which were markedly improved in the Sini San and fluoxetine groups. The results of 16S rDNA high-throughput sequencing showed that Sini San improved CUMS-induced dysbiosis of Bacteroidetes and Proteobacteria. Correlation analysis indicated that Bacteroidetes and Proteobacteria were significantly correlated with depression-related indicators， liver function， and intestinal mucosal permeability. ConclusionSini San exerts antidepressant and hepatoprotective effects by improving Bacteroidetes and Proteobacteria and inhibiting the increase in intestinal mucosal permeability in CUMS rats.

ObjectiveTo explore the efficacy and mechanisms of Sini San in the treatment of depression and liver injury based on gut microbiota. MethodsThirty-two male Sprague-Dawley （SD） rats were randomly divided into a normal group， model group （M）， Sini San group （MS， 2.5 g·kg^-1）， and fluoxetine group （MF， 2 mg·kg^-1）. Except for the normal group， rats in the other three groups were subjected to chronic unpredictable mild stress （CUMS）. After 8 weeks， the open-field test and sucrose preference test were conducted. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum corticosterone （CORT）， adrenocorticotropic hormone （ACTH）， corticotropin-releasing factor （CRF）， lipopolysaccharide （LPS）， Zonulin， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， γ-aminobutyric acid （GABA） levels in the hippocampus and prefrontal cortex， and brain-derived neurotrophic factor （BDNF） levels in the hippocampus. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect hippocampal BDNF mRNA expression. Serum alanine aminotransferase （ALT） and aspartate aminotransferase （AST） levels were measured using the ultraviolet lactate dehydrogenase method. The ultrastructure of the intestinal epithelium was observed by electron microscopy， and gut microbiota in rat feces were analyzed using 16S rDNA high-throughput sequencing. ResultsCompared with the normal group， the sucrose preference of rats in the model group was significantly reduced （P<0.01）， whereas it was significantly increased in the Sini San group compared with the model group （P<0.05）. Compared with the normal group， hippocampal GABA protein levels and BDNF mRNA expression in the model group were significantly decreased （P<0.05）， and compared with the model group， both were significantly increased in the Sini San group （P<0.05， P<0.01）. Compared with the normal group， serum LPS and Zonulin levels in the model group were significantly increased （P<0.05， P<0.01）， and compared with the model group， Zonulin levels in the Sini San group were significantly decreased （P<0.05）. No obvious changes were observed in the ultrastructure of the jejunal mucosa among groups. Compared with the normal group， widened and blurred tight junctions， sparse and shortened microvilli， and mitochondrial swelling with cristae disruption in epithelial cells were observed in the ileal and colonic mucosa of the model group， which were markedly improved in the Sini San and fluoxetine groups. The results of 16S rDNA high-throughput sequencing showed that Sini San improved CUMS-induced dysbiosis of Bacteroidetes and Proteobacteria. Correlation analysis indicated that Bacteroidetes and Proteobacteria were significantly correlated with depression-related indicators， liver function， and intestinal mucosal permeability. ConclusionSini San exerts antidepressant and hepatoprotective effects by improving Bacteroidetes and Proteobacteria and inhibiting the increase in intestinal mucosal permeability in CUMS rats.

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is an adult-onset, X-linked clonal autoinflammatory disease caused by somatic mutations in the UBA1 gene, characterized by systemic inflammation accompanied by hematologic clonal abnormalities. Somatic UBA1 mutations result in impaired ubiquitination, disruption of protein homeostasis, and sustained activation of inflammatory signaling pathways, including nuclear factor-κB and Janus kinase-signal transducer and activator of transcription (JAK-STAT), which together constitute the core pathogenic mechanism. The disease involves multiple systems and tissues including the hematologic system, skin, cartilage and respiratory system, showing remarkable clinical heterogeneity. Diagnosis depends primarily on the combination of characteristic clinical manifestations and molecular confirmation of UBA1 mutations. Current therapeutic strategies lack a unified standard: glucocorticoids can rapidly control inflammation but are associated with high relapse rates, whereas targeted therapies such as JAK inhibitors, interleukin inhibitors, and hypomethylating agents show variable efficacy, and allogeneic hematopoietic stem cell transplantation offers curative potential in patients with concomitant myelodysplastic syndrome. This review systematically summarizes the genetic background, molecular mechanisms, clinical spectrum, diagnostic criteria, and therapeutic advances of VEXAS syndrome.

Objective To monitor the concentrations of six disinfection byproducts including trichloromethane,dibromochloromethane,bromodichloromethane, tribromomethane, dichloroacetic acid and trichloroacetic acid in drinking water in the main urban area of Wuhan, and to assess the potential health risks. Methods A total of 373 samples were collected from the central urban area during 2023 to 2024. The concentrations of the substances were tested according to the national Standard Examination Methods for Drinking Water. The detection rates of the six disinfection byproducts were statistically analyzed, and the concentration differences of the six disinfection byproducts in different time periods and different types of water samples were compared. The health risk assessment model recommended by the United States Environmental Protection Agency was used for risk assessment. Results Trichloromethane was the most common substance found in drinking water, followed by dichlorobromomethane, chlorodibromomethane, trichloroacetic acid, tribromomethane, and finally dichloroacetic acid. The concentration of dichlorobromomethane in treated water was higher than that in tap water, while the concentration of dichloroacetic acid was lower than the tap water, both with significant differences. The concentrations of the six chlorination disinfection by-products in the dry season were all significantly higher than those in the wet season. The carcinogenic risks of the disinfection byproducts were trichloroacetic acid > dichloroacetic acid > dichlorobromomethane > chlorodibromomethane > tribromomethane, and the non-carcinogenic risks were trichloromethane > trichloroacetic acid > dichlorobromomethane > chlorodibromomethane > dichloroacetic acid > tribromomethane. Conclusion Trichloroacetic acid is the substance with the highest carcinogenic risk, while trichloromethane is the non-carcinogenic substance with the highest risk, which requires special attention.

ObjectiveThis study aims to compare the modeling effects of submaxillary gland antigen and salivary gland antigen in the establishment of Sjögren syndrome (SS) mouse models, and to characterize the phenotypic and immunological features of these models in comparison with spontaneous SS-prone non-obese diabetic (NOD)/LtJ mice. MethodsAdult C57BL/6J mice (equal numbers of males and females) were immunized with submaxillary gland antigen or salivary gland antigen, respectively, combined with Freund's adjuvant to induce SS models. Mice immunized with phosphate-buffered saline (PBS) combined with Freund's adjuvant served as the control group. Immunization was induced via multiple subcutaneous injections in the back with antigen combined with Freund's complete adjuvant (FCA) on Days 1 and 7. A booster immunization was administered via multiple subcutaneous injections in the back with antigen combined with Freund's incomplete adjuvant (FIA) on Day 14. Female NOD/LtJ mice were used as the spontaneous SS model group, with ICR mice as the corresponding control strain for comparative analysis. Body weight, water intake, and salivary flow rate of mice were dynamically monitored for 4 weeks. At the end of the experiment, tissue and serum samples were collected, the weights of submaxillary glands, thymus, and spleen were measured, and organ indices (organ-to-body weight ratios) were calculated. Pathological morphological analysis of the submaxillary gland and spleen was performed with hematoxylin and eosin (HE) staining. Serum interleukin-17 (IL-17) level was detected using enzyme-linked immunosorbent assay (ELISA). Real-time quantitative polymerase chain reaction was used to detect the mRNA expression levels of SS type A (SSA) and SS type B (SSB) in submaxillary gland tissues. ResultsFemale mice in the submaxillary gland antigen group exhibited significantly increased water intake (P<0.05) and reduced salivary flow rate (P<0.05) compared with the female control group. No statistically significant differences were observed in the submaxillary gland index, thymus index and spleen index (P>0.05). Focal lymphocytic infiltration was observed in the submaxillary glands, and the splenic marginal zone was enlarged. Serum IL-17 levels were significantly increased (P<0.05). There was no significant difference in submaxillary gland SSA/SSB expression levels (P>0.05). Compared with the female control group, female mice in the salivary gland antigen group showed no statistically significant differences in water intake, salivary flow rate, submaxillary gland index, and spleen index (P>0.05), whereas the thymus index was significantly reduced (P<0.01). Mild inflammatory cell infiltration and glandular atrophy were observed in the submaxillary glands, and the splenic white pulp and marginal zone were slightly enlarged. Serum IL-17 levels and submaxillary gland SSB mRNA expression levels were significantly increased (P<0.01), whereas no significant change was observed in submaxillary gland SSA expression levels (P>0.05). Compared with the male control group, mild submaxillary gland atrophy was observed in male mice in the submaxillary gland antigen group, whereas no obvious changes were found in other modeling-related indicators (P>0.05). Compared with the ICR control group, NOD/LtJ model mice exhibited elevated water intake (P<0.05), significantly reduced salivary flow rate (P<0.01), no significant differences in the submaxillary gland index or spleen index (P>0.05), but a significantly increased thymus index (P<0.05). Marked focal infiltration was observed in the submaxillary glands, the splenic marginal zone was obviously enlarged, and serum IL-17 concentrations as well as submaxillary gland SSA/SSB expression levels were significantly increased (P<0.05). ConclusionSubmaxillary gland antigen and salivary gland antigen can induce SS-related features in female C57BL/6J mice. The SS-related phenotype is more pronounced in the submaxillary gland antigen group than in the salivary gland antigen group, but weaker than that in spontaneously SS-prone female NOD/LtJ mice. Immunization of male C57BL/6J mice with submaxillary or salivary gland antigens fails to induce an obvious SS phenotype.

Oculopharyngodistal myopathy （OPDM） is a hereditary neuromuscular disorder occurring in adolescence or early adulthood and is characterized by slowly progressive external ophthalmoplegia， facial muscle weakness， dysphagia， and distal limb weakness. This article reports a patient with OPDM type 4 who had the initial presentation of bilateral pyroptosis and external ophthalmoplegia and was misdiagnosed with thyrotoxic myopathy， and later the patient developed the clinical manifestations of bilateral masticatory and facial muscle weakness， bulbar paralysis， and limb weakness. Genetic testing revealed abnormal CGG repeat expansion in the RILPL1 gene. The clinical data of the patient was analyzed， and a literature review was performed， so as to improve the awareness of this condition among clinicians.

Amyotrophic lateral sclerosis (ALS) is an irreversible, fatal neurodegenerative disorder whose incidence is positively correlated with the aging population. ALS is characterized by the progressive loss of motor neurons, leading to muscle weakness, atrophy, and ultimately respiratory failure. The pathogenesis of ALS involves multiple factors, including genetic and environmental influences, with genetic factors playing a particularly significant role. To date, several causative genes have been identified in ALS, such as the Cu/Zn superoxide dismutase 1 (Cu/Zn SOD1, also known as SOD1) gene, transactive response DNA-binding protein 43 (TDP-43) gene, fused in sarcoma (FUS) gene, and chromosome open reading frame 72 (C9orf72). Mutations in these genes have been found not only in familial ALS but also in sporadic ALS. Based on the identified ALS risk genes, various ALS animal models have been established through multiple approaches, including transgenic models, gene knockout/knock-in models, and adeno-associated virus-mediated overexpression models. These models simulate some typical pathological features of human ALS, such as motor neuron loss, ubiquitinated inclusions, and neuromuscular junction degeneration. However, these models still have limitations: (1) single-gene mutation models are insufficient to fully replicate the complex multi-factorial pathogenesis of sporadic ALS; (2) significant differences in microenvironmental regulation mechanisms and the rate of neurodegeneration between model organisms and humans may affect the accurate reproduction of disease phenotypes and the reliable evaluation of drug efficacy. To better understand the pathogenesis of ALS and promote the development of effective therapies, constructing and optimizing ALS animal models is crucial. This review aims to summarize commonly used ALS gene mutation mouse models, analyze their phenotypes and pathological characteristics, including transgenic mouse models, gene knockout/knock-in mouse models, and adeno-associated virus-mediated overexpression mouse models, and further discuss their specific applications in ALS pathogenesis research and drug development by comparing the advantages and limitations of each model.

Amyotrophic lateral sclerosis (ALS) is an irreversible, fatal neurodegenerative disorder whose incidence is positively correlated with the aging population. ALS is characterized by the progressive loss of motor neurons, leading to muscle weakness, atrophy, and ultimately respiratory failure. The pathogenesis of ALS involves multiple factors, including genetic and environmental influences, with genetic factors playing a particularly significant role. To date, several causative genes have been identified in ALS, such as the Cu/Zn superoxide dismutase 1 (Cu/Zn SOD1, also known as SOD1) gene, transactive response DNA-binding protein 43 (TDP-43) gene, fused in sarcoma (FUS) gene, and chromosome open reading frame 72 (C9orf72). Mutations in these genes have been found not only in familial ALS but also in sporadic ALS. Based on the identified ALS risk genes, various ALS animal models have been established through multiple approaches, including transgenic models, gene knockout/knock-in models, and adeno-associated virus-mediated overexpression models. These models simulate some typical pathological features of human ALS, such as motor neuron loss, ubiquitinated inclusions, and neuromuscular junction degeneration. However, these models still have limitations: (1) single-gene mutation models are insufficient to fully replicate the complex multi-factorial pathogenesis of sporadic ALS; (2) significant differences in microenvironmental regulation mechanisms and the rate of neurodegeneration between model organisms and humans may affect the accurate reproduction of disease phenotypes and the reliable evaluation of drug efficacy. To better understand the pathogenesis of ALS and promote the development of effective therapies, constructing and optimizing ALS animal models is crucial. This review aims to summarize commonly used ALS gene mutation mouse models, analyze their phenotypes and pathological characteristics, including transgenic mouse models, gene knockout/knock-in mouse models, and adeno-associated virus-mediated overexpression mouse models, and further discuss their specific applications in ALS pathogenesis research and drug development by comparing the advantages and limitations of each model.

ObjectiveTo assess the level of health literacy and its influencing factors among middle school students aged 12‒18 years in Jing’an District, Shanghai, so as to provide a solid scientific foundation for further developing more targeted intervention measures. MethodsA stratified cluster random sampling method was used to randomly select 4 middle schools in Jing’an District, Shanghai from November to December 2023, and conducted a health literacy questionnaire survey on non-graduating middle and high school students, respectively. The2023 Survey on the Status of Health Literacy among Middle School Students in Jing’an District, Shanghai was adopted, which consisted of two parts: health literacy and basic information. Health literacy was divided into three dimensions: health knowledge and concept literacy, healthy lifestyle and behavior literacy, and health skill literacy. Three dimensions could be categorized into six types of health literacy issue: scientific health literacy, infectious disease prevention and control literacy, chronic disease prevention and control literacy, safety and first aid literacy, basic health literacy, and health information literacy. ResultsA total of 1 161 middle school students were enrolled into this study, including 571 males and 570 females. The overall health literacy level of middle school students was 33.51%, with 34.81% among middle school students and 31.69% among high school students, respectively. Results of logistic regression analysis showed that health knowledge acquisition and awareness, as well as application frequency of health knowledge, were the influencing factors for the overall health literacy level among middle school students (P<0.05). The degree of family attention to health maintenance, health knowledge acquisition and awareness, and application frequency of health knowledge were the main influencing factors for the three dimensions and literacy of six types of health issues among middle school students (P<0.05). ConclusionThe levels of different types of health literacy among middle school students in Jing’an District are uneven, with the highest being safety and first aid literacy and the lowest being basic health literacy. It is recommended to take targeted measures to comprehensively improve the health literacy level of middle school students.

OBJECTIVE: Based on the PTEN-induced hypothetical kinase 1 (PINK1)/Parkin pathway, the effect of acupuncture pretreatment on the expression of mitochondrial autophagy-related proteins in gastrocnemius muscle tissue of rats with exercise-induced muscle damage (EIMD) was observed, and the underlying mechanism of acupuncture pretreatment for the prevention and treatment of EIMD was explored. METHODS: Of 88 SD male rats, aged 6 weeks, 8 rats were randomly selected as a blank group, and the remaining 80 rats were randomized into a model group and an acupuncture pretreatment group, with 40 rats in each group. Either the model group or the acupuncture pretreatment group was subdivided randomly into 5 subgroups with 8 rats in each one according to the time points of sample collection, 0 h, 12 h, 24 h, 48 h and 72 h after modeling. An intermittent downhill running centrifugal exercise was carried out on an animal experimental treadmill to establish the EIMD model in the model group and the acupuncture pretreatment group. The rats in the acupuncture pretreatment group received acupuncture at "Guanyuan" (CV6) and bilateral "Zusanli" (ST36), once a day for 20 min each time, for 7 consecutive days before EIMD model preparation. Transmission electron microscopy was used to observe the ultrastructure of gastrocnemius muscle tissue in each group. The contents of malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT) in serum were detected by ELISA. Western blot was used to detect the protein expression of PINK1, Parkin, sequestosome 1 (p62) and microtubule-associated protein light chain 3B (LC3B) in rat gastrocnemius muscle tissue. Real-time PCR was adopted to detect the mRNA expression of PINK1, Parkin, p62 and LC3B in rat gastrocnemius muscle tissue. RESULTS: Compared with the blank group, the mitochondria of gastrocnemius muscles showed obvious swelling in the 0 h, 12 h, 24 h, and 48 h model subgroups , autophagosomes were formed in the 12 h and 24 h model subgroups, and the mitochondrial morphology returned to normal gradually in the 72 h model subgroup. The serum MDA contents of rats in 5 model subgroups increased (P<0.01, P<0.05). The contents of SOD and CAT in the subgroups of 0 h, 12 h, 24 h and 48 h decreased (P<0.05, P<0.01). The protein and mRNA expression levels of PINK1, Parkin and LC3B in gastrocnemius muscle tissue of rats in 0 h, 12 h and 24 h subgroups were elevated (P<0.01); and the protein and mRNA expression levels of p62 in the 0 h, 12 h, 24 h and 48 h subgroups were reduced (P<0.01, P<0.05). Compared with the model subgroup at the same time point, the myofibril damage and the degree of mitochondrial swelling were mild in each acupuncture pretreatment subgroup, and the numbers of autophagosomes were fewer. The contents of MDA in the acupuncture pretreatment subgroups decreased at 0 h, 12 h, 24 h, and 48 h (P<0.05, P<0.01). The contents of SOD and CAT in the 12 h acupuncture pretreatment subgroup increased (P<0.05, P<0.01). The protein and mRNA expression levels of PINK1 and Parkin in the 0 h, 12 h, and 24 h acupuncture pretreatment subgroups decreased (P<0.01, P<0.05). The protein and mRNA expression levels of LC3B in the 12 h acupuncture pretreatment subgroup decreased (P<0.01), and that of p62 in the 0 h and 24 h acupuncture pretreatment subgroups increased (P<0.01, P<0.05). CONCLUSION The intermittent downhill running centrifugal exercise induces the excessive mitochondrial autophagy. Acupuncture pretreatment may attenuate EIMD, and the underlying mechanism is related to the regulation of PINK1/Parkin signaling pathway expression, reducing oxidative stress damage in skeletal muscle cells, and inhibiting mitochondrial autophagy overactivation.
Animals ; Ubiquitin-Protein Ligases/genetics* ; Male ; Rats ; Acupuncture Therapy ; Protein Kinases/genetics* ; Rats, Sprague-Dawley ; Mitophagy ; Humans ; Muscle, Skeletal/metabolism* ; Physical Conditioning, Animal ; Muscular Diseases/physiopathology* ; Signal Transduction