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.

ObjectiveTo explore the role of neuroimaging features monitored by functional near-infrared spectroscopy （fNIRS） in postoperative delirium （POD） in elderly patients undergoing joint replacement during perioperative period， and to provide a basis for early clinical prediction. MethodsA total of 105 elderly patients who underwent joint replacement under general anesthesia were included. The Mini-Mental State Examination （MMSE） scale was used to evaluate the patient's cognition one day before the operation. Before the start of the surgery， fNIRS was used to monitor the changes of cerebral blood oxygen saturation when the patient performed the task state. The 3-minute delirium diagnostic scale （3D-CAM scale） was used to evaluate the occurrence of POD at 24， 48 and 72 h after operation. Brain network analysis was performed and Logistic regression analysis was used to explore the relationship between fNIRS monitoring data and POD in elderly patients undergoing joint replacement surgery during preoperative task state. The receiver operating characteristic curve （ROC curve） was constructed to evaluate the diagnostic efficacy， and the Hosmer-Lemeshow goodness-of-fit test was used to test the goodness of fit of the model. ResultsAmong 105 patients， 100 cases were effectively analyzed， of which 20 cases （20%） had POD. Brain network analysis showed that the r value of functional connectivity correlation coefficient in POD group （0.069±0.118） was lower than that in non-POD group （0.073±0.084）. The low channel connectivity of right primary somatosensory cortex-right primary motor cortex （RS1-RM1） and left anterior pole-right Broca's triangle （LFP-RBA44） was an important factor affecting the occurrence of POD （P < 0.05）. Based on this result， the area under the ROC curve was 0.797 and 0.784， respectively. The results of Hosmer-Lemeshow goodness-of-fit test showed that the model fitted well （all P>0.5）. ConclusionThe neuroimaging features extracted from the cerebral oxygen saturation data monitored by fNIRS are significantly correlated with the risk of POD in elderly patients undergoing joint replacement during perioperative period. Among them， the low connectivity of preoperative RS1-RM1 and LFP-RBA44 brain network channels is an important influencing factor of POD occurrence. Predicting the occurrence of POD based on fNIRS is conducive to the early intervention and risk reduction of perioperative complications， improving medical quality and promoting precision medical practice.

Objective:To investigate the efficacy and safety of endovascular therapy (EVT) for early neurological deterioration (END) in patients with minor stroke due to acute anterior circulation large vessel occlusion.Methods:Consecutive patients with mild stroke due to acute anterior circulation large vessel occlusion admitted to Mianyang Central Hospital from October 2015 to October 2023 were included retrospectively. Minor stroke was defined as a baseline National Institutes of Health Stroke Scale (NIHSS) score <6. END was defined as an increase of ≥4 in NIHSS score compared to baseline within 12 hours of onset. According to whether EVT was performed or not, they were divided into EVT group and standard medical treatment (SMT) group. At 90 days after onset, the modified Rankin Scale was used to evaluate the outcome. 0-1 was defined as excellent outcome (primary outcome measure) and 0-2 was defined as good outcome (secondary outcome measure). The safety endpoints included symptomatic intracranial hemorrhage (sICH) within 72 hours after EVT and all-cause mortality within 90 days. Multivariate logistic regression analysis was used to determine the correlation between EVT and clinical outcome. Results:A total of 164 patients with minor stroke due to acute anterior circulation large vessel occlusion were included. Eighty-four patients (51.2%) developed END, of which 52 (61.9%) underwent EVT and 32 (38.1%) received SMT; 60 patients (71.4%) had excellent outcome, and 64 (76.2%) had good outcome. There was no significant difference in demographic and baseline clinical data between the EVT group and the SMT group. The excellent outcome rate of the EVT group at 90 days after onset showed a trend higher than that of SMT group (78.8% vs. 59.4%; χ2=3.680, P=0.055), but there was no significant difference in the good outcome rate and safety endpoints between the two groups. Multivariate logistic regression analysis showed that after adjusting for confounding factors, EVT was significantly and independently associated with excellent outcome at 90 days (odds ratio 4.955, 95% confidence interval 1.331-22.284; P=0.024). Conclusion:For patients with minor stroke due to anterior circulation large vessel occlusion who experience END, EVT may improve their functional outcome without increasing the risk of sICH and mortality.

Objective: To investigate the effect of sirtuin 2(SIRT2) on the proliferation and migration of cardiac fibroblasts(CFs)in C57BL/6 mice under angiotensin II(Ang Ⅱ) stimulation. Methods : The hearts were taken from 1 to 2 days C57BL/6 milk mice. After cutting and digesting, CFs were extracted by different adhesion centrifugation. After CFs attachment, the cells were cultured under control medium and Ang Ⅱ(100 nmol/L) medium and treated using OE-SIRT2 plasmid to overexpression the SIRT2 gene. RT-qPCR was used to detect mRNA expression of SIRT2 proliferating cell nuclear antigen(PCNA), periostin(POSTN)and type Ⅰ collagen procollagen A1(Col1A1), Western blot assay was used to measure the protein expression levels of SIRT2, PCNA, POSTN and Col1A1, CCK-8 assay and EdU assay were used to evaluate CFs proliferation rate, Transwell experiment was used to assess CFs migration activity. Results: Compared with control group, Ang Ⅱ stimulation led to down-regulation of SIRT2 expression in CFs, increased collagen expression, and promoted CFs proliferation and migration. The expression of SIRT2 was up regulated in CFs treated with OE-SIRT2 plasmid under Ang Ⅱ stimulation, Col1A1, POSTN and PCNA expression was down regulated, and CFs proliferation and migration ability decreased. Conclusion Overexpression of SIRT2 can inhibit the proliferation and migration of CFs under Ang Ⅱ stimulation, indicating that SIRT2 may be a key regulatory point in the onset and progression of cardiac fibrosis.

Objective To screen prognostic biomarkers for lung adenocarcinoma by integrating proteomics and transcriptomics.Methods Proteomics,transcriptomics and clinical characteristics da-ta of lung adenocarcinoma patients were downloaded from the TCGA public database.The dataset was split into training set and validation set at a ratio of 7∶3.Univariate prognostic analysis of protein ex-pression was conducted in the training set based on patients'clinical survival time,survival status,and protein expression data.A prognostic model for lung adenocarcinoma patients was constructed using the lasso-step cox method,and risk scores were calculated.Patients were divided into high-risk and low-risk groups based on the median risk score,and the prognosis of the two groups was analyzed.A prog-nostic nomogram model and calibration curves were constructed to clinically validate and correlate the model.The protein expression of the model was analyzed based on the HPA database,and enrichment analysis was performed on the risk proteins.Immunohistochemical and clinical characteristic analyses were conducted in 20 newly diagnosed lung adenocarcinoma patients from our hospital.Results Five proteins associated with prognosis were screened out,and a risk protein model was constructed.The risk score had a predictive effect on the prognosis of lung adenocarcinoma patients.The risk model demonstrated strong and independent prognostic predictive ability.The nomogram model showed high accuracy in predicting individual prognosis.Furthermore,there were intrinsic relationship of the risk model and its calculated risk scores with clinical staging characteristics.HPA database anal-ysis revealed significant overexpression of CD38,CD49B,ADAR1,and cdc25C4 in lung adenocar-cinoma tissues.The 20 clinical specimens from our hospital validated the high expression of CD49B in newly diagnosed lung adenocarcinoma patients with distant metastasis and its sensitivity to treat-ment.Conclusion The combined analysis of proteomics and transcriptomics for prognostic biomar-kers of lung adenocarcinoma yields reliable results.CD49B plays a crucial role in lung adenocarci-noma,and the prognostic prediction model based on this gene is expected to provide important refer-ences for clinical treatment of lung adenocarcinoma.

Objective:To compare the infection status of severe fever with thrombocytopenia syndrome (SFTS) between the non-endemic area (Yixian county, Huangshan city) and the endemic area (Qianshan city, Anqing city) in Anhui province, and to explore the possibility of Yixian county being a natural focus of SFTS, thereby providing a scientific basis for the formulation of prevention and control strategies.Methods:In Xidi town, Yixian county, and Shuihou town, Qianshan city, one administrative village with the highest number of reported cases in the past three years was selected as the study village in each area, along with one control village with no reported cases. The study investigated the total antibody positivity rates of SFTS virus (SFTSV) in natural populations and host animals, as well as the density and virus-carrying rate of the vector ticks. Differences in total antibody positivity rates between the two regions were compared.Results:The total SFTSV antibody positivity rates in the natural population and host animals in the surveyed villages (control villages) of Qianshan city and Yi county were 8.7% and 8.0% (3.3%, 4.1%) and 0.0%, 9.1% (50.0%, 66.7%), respectively. There was no statistically significant difference in the infection rates of the natural population and host animals between the surveyed villages (control villages) in different endemic regions (all P>0.05). In the surveyed villages of Qianshan city and Yi county, the free-living tick densities were 1.4 ticks/hour per flag and 1.7 ticks/hour per flag, respectively; the parasitic tick densities were 0.4 ticks/host and 2.5 ticks/host, respectively; the tick infestation rates were 33.3% and 35.3%, respectively; and the tick density indices were 1.3 ticks/host and 7.2 ticks/host, respectively. Conclusions:The natural populations and host animals in some areas of Yixian county exhibit high SFTSV infection rates, and the tick density is also high, suggesting that the region may have become a natural focus of SFTS. Therefore, it is necessary to further strengthen capabilities in surveillance, diagnosis, and clinical treatment to address the potential risk of SFTS outbreaks.

Autism spectrum disorder(ASD) is a neurodevelopmental disorder, and social impairment was one of the core symptoms of ASD, which can seriously affects the social life of patients.The pathogenesis of social impairment in ASD is unclear and it may involves many brain abnormalities.The related theories and hypotheses are numerous and there is no unified conclusion. Studies have shown that the cerebellum has extensive connections with brain networks and is involved in the regulation of social cognition, but its role in ASD has not been fully emphasized.The structural and functional abnormalities of the cerebellar-cortex (CC) loop in ASD patients can lead to language communication disorders, empathy disorders, difficulties in interpreting social cues, abnormal social reward processing and emotional regulation disorders, which are closely related to ASD social impairment. Noninvasive brain stimulation of the superficial cerebellum can improve the abnormal CC circuit in ASD patients, and the cerebellum can be considered as a target for the treatment of social disorders in ASD in the future.Based on the clinical and basic researches on social impairment in ASD in recent years, this article reviews the relevant manifestations of disorders which cerebellar and CC circuit involved, aiming to promote the development of related research in the future.

As the incidence of autism rises annually,its unknown pathogenesis makes it challenging to treat the varied repetitive and stereotyped behaviors that characterize its core symptoms.The striatum is an important brain region for the control of locomotor behaviors,featuring a unique mosaic structure,complex neural origin,and finely regulated developmental process that is highly susceptible to genetic and environmental influences.Both clinical and basic studies have indicated that abnormal development of the striatal nuclei may contribute to the pathogenesis of these repetitive stereotyped behaviors in autism.Clinical imaging data have primarily identified gross anatomical variations in the stratum(e.g.,its general outline),but lack the resolution necessary to detect the cellular and subcellular alterations within the region.By introducing the abnormalities in the spatiotemporal development of the striatum and their links to the characteristic behaviors of autism,this review aims to advance our understanding of the role of the striatum in autism pathogenesis and to inform future animal studies and clinical research.

Autism spectrum disorder(ASD) is a neurodevelopmental disorder, and social impairment was one of the core symptoms of ASD, which can seriously affects the social life of patients.The pathogenesis of social impairment in ASD is unclear and it may involves many brain abnormalities.The related theories and hypotheses are numerous and there is no unified conclusion. Studies have shown that the cerebellum has extensive connections with brain networks and is involved in the regulation of social cognition, but its role in ASD has not been fully emphasized.The structural and functional abnormalities of the cerebellar-cortex (CC) loop in ASD patients can lead to language communication disorders, empathy disorders, difficulties in interpreting social cues, abnormal social reward processing and emotional regulation disorders, which are closely related to ASD social impairment. Noninvasive brain stimulation of the superficial cerebellum can improve the abnormal CC circuit in ASD patients, and the cerebellum can be considered as a target for the treatment of social disorders in ASD in the future.Based on the clinical and basic researches on social impairment in ASD in recent years, this article reviews the relevant manifestations of disorders which cerebellar and CC circuit involved, aiming to promote the development of related research in the future.