Reactive astrocytes, which exhibit a correlation with the degeneration of dopaminergic neurons, are present in a considerable number during the progression of Parkinson's disease (PD). However, the underlying factors shaping astrocyte reactivity and neuroinflammation in PD remain inadequately elucidated. Here, we demonstrate that fibroblast growth factor 7 (FGF7)/FGF receptor 2 (FGFR2) autocrine signaling intensifies astrocyte reactivity and inflammation. Genetic deletion of Arrb2, β-Arrestin2 encoding gene, led to escalated astrocyte reactivity in MPTP-treated mice, which was further substantiated in astrocyte-specific Arrb2 knockdown mice. RNA sequencing profiling of Arrb2 knockout astrocytes identified Fgf7 as a critical effector of astrocyte reactivity. Subsequently, conditional knockdown of Fgf7 and its receptor Fgfr2 in astrocytes elicited advantageous effects for MPTP-treated mice by restraining the inflammatory phenotypic transition of reactive astrocytes. Furthermore, deletion of astrocytic Fgf7 mitigated MPTP-induced pathology in Arrb2 knockout mice. Mechanistically, STAT1 was distinguished as the transcription factor suppressing Fgf7 expression, while β-Arrestin2 counteracted the proteasomal degradation of STAT1 by binding to RNF220, an E3 ubiquitin ligase for STAT1. More importantly, selectively engaging dopamine D2 receptor (Drd2)/β-Arrestin2-biased signaling using the agonist UNC9995 exhibited therapeutic potential in MPTP-treated mice via moderation of astrocytic FGF7 production, thereby restoring balance in astrocyte reactivity. Collectively, our study bridges a crucial knowledge gap by elucidating the novel functions of FGF family members within the central nervous system, particularly within the context of PD. The autocrine signaling of FGF7/FGFR2 represents a novel mechanism and a potential druggable target for modulating astrocyte-derived inflammation.

Objective To investigate the prevalence of hyperuricemia among ethnic groups in Gongshan county,Yunnan province through a cross-sectional study.Methods A total of 229 residents aged ≥ 18 years from Dulong,Nu,Tibetan,Bai and Lisu ethnic groups were randomly selected in Gongshan County of Yunnan Province for questionnaire survey,physical examinations and laboratory tests.SPSS 22.0 was used for t test,Chi-square test,correlation analysis,and multivariate logistic regression analysis.Results A total of 107 cases of hyperuricemia were identified,with a detection rate of 46.7％,among which the prevalence was 43.9％in males,52.63％in female,48％in the Dulong,51％in the Lisu,47％in the Nu,37.5％in the Bai,52％in the Tibetan and 50％in the Han.There were no statistically significant differences in prevalence among all nationalities(P＞0.05).The proportion of individuals with a history of diabetes,as well as levels of urea nitrogen and serum creatinine,were significantly higher in the hyperuricemia group compared to the non-hyperuricemia group(P＜0.05).Correlation analysis showed a positive correlation between hyperuricemia and diabetes,urea nitrogen and serum creatinine.(P＜0.05).Multivariate regression analysis showed that diabetes and elevated serum creatinine were independent risk factors for the onset of hyperuricemia(P＜0.05).Conclusion The detection rate of hyperuricemia is relatively high in Gongshan County,Yunnan Province,and there is no significant differences in prevalence among ethnic groups.Diabetes and elevated serum creatinine are associated with hyperuricemia,which increase the risk of developing hyperuricemia.

ObjectiveTo investigate the mechanism of Huangqi Gegentang （HGT） in the treatment of type 2 diabetes mellitus （T2DM） through the application of proteomic techniques. MethodsThe rat model of T2DM was established by streptozotocin combined with a high-fat， high-sugar diet. Thirty-two male SD rats were randomized into four groups： blank， model， HGT （8.10 g·kg^-1·d^-1）， and positive control （metformin hydrochloride， 76.5 mg·kg^-1·d^-1）. After 6 weeks of drug intervention， the fasting blood glucose level was measured， and an oral glucose tolerance test （OGTT） was performed. The area under the curve （AUC） was calculated. Enzyme-linked immunosorbent assay was performed to assess the level of glycated hemoglobin （GHbA1c） in the serum. The limulus amebocyte lysate assay was employed to measure the serum level of lipopolysaccharide （LPS）. Pathological changes in the colon were observed by hematoxylin-eosin staining. The mRNA levels of pro-inflammatory cytokines including tumor necrosis factor （TNF）-α， interleukin （IL）-6， and IL-1β in the colon tissue were quantified via Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. Additionally， the protein and mRNA levels of zonula occludens-1 （ZO-1）， Occludin， and Claudin-1 in the colon tissue were assessed by Western blot and Real-time PCR， respectively. Label-free quantitative proteomics was employed to identify the differentially expressed proteins between the colon tissue samples from the blank， model， and HGT groups. Key proteins identified were subsequently validated by Western blot and Real-time PCR. Finally， bioinformatics analysis was conducted on the differentially expressed proteins. ResultsCompared with the blank group， the model group exhibited increased fasting blood glucose， AUC， and GHbA1c levels （P<0.01）， damaged colonic mucosal epithelial structure and inflammatory cell infiltration， up-regulated mRNA levels of TNF-α， IL-6， and IL-1β in the colon and an increase in serum LPS content （P<0.05， P<0.01）， and down-regulated protein and mRNA levels of ZO-1， Occludin， and Claudin-1 in the colon （P<0.01）. Compared with the model group， the HGT group showed reductions in fasting blood glucose， AUC， and GHbA1c （P<0.01）， alleviated damage to the colonic mucosal epithelium， down-regulated mRNA levels of TNF-α， IL-6， and IL-1β in the colon， a reduction in serum LPS content （P<0.05， P<0.01）， and up-regulated protein and mRNA levels of ZO-1， Occludin， and Claudin-1 in the colon （P<0.05， P<0.01）. Proteomics analysis identified 70 differentially expressed proteins that exhibited a downward trend in the model group relative to the blank group and an upward trend in the HGT group relative to the model group. These findings were corroborated by Western blot and Real-time PCR， which confirmed that the protein and mRNA levels of mucin 2 （Muc2） and transforming growth factor （TGF）-beta receptor 1 （Tgfbr1） in the colon tissue were consistent with the proteomic data. Bioinformatics analysis showed that these 70 differentially expressed proteins identified were significantly enriched in multiple signaling pathways， among which the TGF-β and advanced glycation endproduct （AGE）/receptor for advanced glycation endproduct （RAGE） signaling pathways were closely associated with damage to the intestinal mucosal barrier. This suggests that HGT may ameliorate intestinal mucosal barrier damage by regulating these pathways. ConclusionHGT potentially exerts anti-T2DM effects by influencing AGE/RAGE and TGF-β signaling pathways， thereby contributing to the restoration of the intestinal mucosal barrier.

BackgroundModified electroconvulsive therapy （MECT） is a common front-line strategy widely used in psychiatric practice， and the optimal first stimulus dosage in MECT is usually estimated clinically based on the factors influencing the patient's initial seizure threshold （IST）. However， previous studies on the influencing factors of IST have mostly suffered from limitations such as small sample sizes and single-dimensional research perspectives. ObjectiveTo explore the factors influencing IST in MECT for patients with mental disorders， so as to provide references for stimulus dosing strategies in MECT for the patients. MethodsA retrospective study was used to include 1 446 inpatients fulfilling the diagnostic criteria for any specific mental disorder listed in the ICD-10 and receiving MECT at Shandong Daizhuang Hospital from January 1， 2021 to August 1， 2023. Their general and clinical data were collected， including IST， psychiatric diagnostic categories， gender， ethnicity， age， body weight， body mass index （BMI）， course of disease， family history of psychiatric disorders， first episode status， use of antiepileptic drugs the day before treatment， use of benzodiazepines the day before treatment， and previous MECT treatment history. Pearson correlation analysis was utilized to test the correlation of IST with age， height， body weight， BMI， and course of disease， and stepwise multivariate linear regression analysis was performed to identify the factors affecting IST. ResultsIST yielded statistical difference among patients in terms of gender， first episode status， use of antiepileptic drugs the day before treatment， and use of benzodiazepines the day before treatment （t=2.256， -3.059， -2.136， -3.006， P<0.05 or 0.01）. IST in patients of different ages and psychiatric diagnostic categories also demonstrated statistical difference （F=913.120， 6.212， P<0.01）. Within young population， IST varied significantly based on the psychiatric diagnostic categories （F=2.986， P<0.05）. Correlation analysis indicated that IST was positively correlated with age， body weight， BMI and course of disease （r=0.886， 0.055， 0.184， 0.456， P<0.05 or 0.01）， and negatively correlated with height （r=-0.183， P<0.01）. Stepwise multivariate linear regression analysis revealed that age， gender， and body weight were influencing factors of IST （β=0.888， -0.049， -0.035， P<0.01）. ConclusionsAge， gender and body weight may be factors influencing IST in MECT for patients with mental disorders. ［Funded by Key R&D Plan Projects of Jining City in 2024 (number, 2024YXNS202）］

Objective:To analyze the risk factors for asparaginase-associated pancreatitis (AAP) in children with acute lymphoblastic leukemia (ALL) after treatment with pegaspargase and evaluate the predictive value of pediatric sequential organ failure assessment (SOFA) score, pediatric acute pancreatitis severity (PAPS) score, Ranson′s score and pediatric Ministry of Health, Labour and Welfare of Japan (JPN) score for severe AAP.Methods:Cross-sectional study.The clinical data of 328 children with ALL who received pegaspargase treatment in the Department of Pediatric Hematology, Zhujiang Hospital, Southern Medical University from January 2014 to August 2021, as well as their clinical manifestations, laboratory examinations, and imaging examinations were collected.The SOFA score at the time of AAP diagnosis, PAPS score and Ranson′s score at 48 hours after AAP diagnosis, and JPN score at 72 hours after AAP diagnosis were calculated, and their predictive value for severe AAP was evaluated by the receiver operating characteristic (ROC) curve.Results:A total of 6.7%(22/328) of children had AAP, with the median age of 6.62 years.AAP most commonly occurred in the induced remission phase (16/22, 72.7%). Three AAP children were re-exposed to asparaginase, and 2 of them developed a second AAP.Among the 22 AAP children, 16 presented with mild symptoms, and 6 with severe symptoms.The 6 children with severe AAP were all transferred to the Pediatric Intensive Care Unit (PICU). There were no significant differences in gender, white blood cell count at first diagnosis, immunophenotype, risk stratification, and single dose of pegaspargase between the AAP and non-AAP groups.The age at diagnosis of ALL in the AAP group was significantly higher than that in the non-AAP group ( t=2.385, P=0.018). The number of overweight or obese children in the AAP group was also higher than that in the non-AAP group ( χ2=4.507, P=0.034). The areas under the ROC curve of children′s JPN score, SOFA score, Ranson′s score, and PAPS score in predicting severe AAP were 0.919, 0.844, 0.731, and 0.606, respectively.The JPN score ( t=4.174, P=0.001) and the SOFA score ( t=3.181, P=0.005) showed statistically significant differences between mild and severe AAP. Conclusions:AAP is a serious complication in the treatment of ALL with combined pegaspargase and chemotherapy.Older age and overweight or obesity may be the risk factors for AAP.Pediatric JPN and SOFA scores have predictive value for severe AAP.

BACKGROUND:In recent years,some scholars in the field of tendon bone injury have attached stromal cell-derived factor 1 to tissue engineering scaffolds to promote tendon bone healing,and achieved good results.However,whether stromal cell-derived factor 1 promotes tendon bone healing mechanisms and participates in the repair of natural healing has not yet been defined. OBJECTIVE:To study the expression of stroma-cell derived factor 1 during tendon bone healing after rupture of the whole supraspinatus muscle of the rabbit rotator cuff and its migration effect and optimal in vitro migration promoting concentration on stem cells during tendon bone injury. METHODS:Totally 18 adult New Zealand rabbits were randomly selected to establish rotator cuff injury models,and an additional 3 rabbits were selected as blank controls.At 3,5,7,14,21,and 28 days after modeling,three rabbits were executed separately and the rabbits in the blank group were sacrificed.The tissues of tendon bone junction were taken and stored in a-80℃refrigerator.The expression of stromal cell-derived factor 1 was detected by ELISA at each time point after injury.Mesenchymal stem cells were isolated from the bone marrow of young rabbit femur,cultured,and identified.Transwell assay was performed to verify the migration-promoting effect of stromal cell-derived factor 1 on stem cells and the optimal migration-promoting concentration in vitro.The stem cells cultured to P3 were co-cultured with BrdU and injected into the rabbit ear marginal vein,and immunohistochemical staining was used to verify whether the stem cells migrated to the injury site. RESULTS AND CONCLUSION:(1)Stromal cell-derived factor 1 gene expression was bimodal during rotator cuff tendon bone healing.Stromal cell-derived factor 1 gene expression increased significantly at 3 days post-injury(P<0.01)and then decreased,reaching a minimum at 5 days post-injury.It increased again and reached a peak 14 days after injury(P<0.01)and then decreased.(2)Cell immunohistochemical staining displayed that stem cells labeled with BrdU did migrate to the injury site.(3)The results of the transwell experiment exhibited that 60-80 ng/mL stromal cell-derived factor 1 had the best effect on promoting migration of stem cells,while a concentration of 200 ng/mL inhibited migration.(4)Stromal cell-derived factor 1 is involved in the healing of rotator cuff tendon bone during the inflammatory response phase and the proliferation phase.The mechanism of action may be to promote the migration of stem cells to the injury and their differentiation into various types of cells to promote repair.In addition,the pro-migration effect of stromal cell-derived factor 1 exists at a range of concentrations,beyond which it may act as an inhibitor.

BACKGROUND:The temporal and spatial expression of fibroblast growth factor receptors 1 and 2 remains a controversial issue during kidney development,so the relationship between them and kidney development remains unclear. OBJECTIVE:To observe the dynamic expression of fibroblast growth factor receptors 1 and 2 during kidney development of mice,and to investigate the relationship between them and kidney development. METHODS:The kidneys of fetal mice[embryotic days(E)12,14,16,and 18]and neonatal mice[neonatal days(N)1,3,7,14,24,and 40]were selected to examine the temporal and spatial expression of fibroblast growth factor receptors 1 and 2 by immunohistochemistry method in kidney tissues,and quantitative analysis was performed using western blot assay. RESULTS AND CONCLUSION:(1)Immunohistochemistry showed that fibroblast growth factor receptor 1 was mainly localized in metanephric tissue surrounding the tip of the ureteral bud at E12.Subsequently,fibroblast growth factor receptor 1 was expressed in immature renal corpuscles at various stages,some distal convoluted tubules and capillary loops.The positive site was mainly concentrated in the generative region.Fibroblast growth factor receptor 2 was initially expressed in both ureteral buds and metanephric tissue.Fibroblast growth factor receptor 2 was localized in immature renal corpuscles,distal tubules,collecting ducts and thin segments of medullary loops with kidney development.However,the expression of renal corpuscles was weak.(2)Stereology and western blot assay showed that the expression of fibroblast growth factor receptor 1 was high before birth and gradually decreased after birth,while the expression was very low after N7 day.The expression level of fibroblast growth factor receptor 2 increased gradually with the kidney development and tended to be stable after N7 day.(3)The results exhibit that fibroblast growth factor receptors 1 and 2 are expressed spatially and temporally during kidney development.It is speculated that fibroblast growth factor receptors 1 and 2 may influence nephron development and maturation,and fibroblast growth factor receptor 2 is critical during the formation of ureteral buds and morphology.

Objective:To re-evaluate the effectiveness of exercise interventions in patients with amyotrophic lateral sclerosis (ALS) by conducting a systematic review and provide insights for the implementation and continuous improvement of exercise intervention strategies.Methods:A comprehensive search was conducted across databases, including CNKI, Wanfang, VIP, SinoMed, PubMed, Embase, Cochrane Library, Web of Science, CINAHL, Campbell Collaboration, and the Joanna Briggs Institute Evidence-Based Health Care Center Database. The search covered literature from the inception of the databases until December 19, 2023. Two researchers trained in evidence-based nursing independently screened the literature. The methodological quality of the included studies was assessed using the AMSTAR 2 tool, and the quality of evidence was graded using the GRADE system.Results:Eight systematic reviews were included. The AMSTAR 2 evaluation revealed one review of moderate quality, six of low quality, and one of very low quality. GRADE assessment of 33 outcome indicators showed that one piece of evidence was of moderate quality, 24 were of low quality, and eight were of very low quality.Conclusions:Exercise interventions may improve overall functional outcomes in ALS patients without exacerbating fatigue. However, due to the limitations in the quantity and quality of the included studies, further large-scale, high-quality randomized controlled trials are needed to verify the effects of exercise interventions in ALS patients.

ObjectiveThis study explores the efficacy and pharmacological mechanism of Wujiwan in rats with inflammatory bowel disease （IBD） from the perspectives of the peroxisome proliferator-activated receptor γ （PPARγ） signaling pathway and T-cell immunity， providing reference for the treatment of IBD with traditional Chinese medicine. MethodThe study involved administering 2，4，6-trinitrobenzenesulfonic acid （TNBS） enemas to 35 rats to induce acute IBD. After 24 hours， the animals were divided into the following groups： normal group， model group， Wujiwan treatment group， and positive drug control group. Each group received gastric gavage for 8 consecutive days before the rats were dissected to compare the disease activity index （DAI） of the rat colon tissue， the colon mucosal damage index （CMDI）， and the spleen index. Enzyme-linked immunosorbent assay （ELISA） was used to measure the levels of interleukin-1β （IL-1β）， interleukin-10 （IL-10）， and tumor necrosis factor-α （TNF-α） in the serum. Quantitative real-time polymerase chain reaction （Real-time PCR） was used to determine the mRNA expression levels of T-bet （T-box expressed in T cells） and Gata3 （Gata-binding protein-3） in the colon tissue. Western blot analysis was conducted to detect the protein expression levels of PPARγ， T-bet， and nuclear factor-κB p65 （NF-κB p65） in the rat colon. ResultThe rat model of IBD was successfully established. Compared with the model group， the Wujiwan treatment group showed reduced DAI， CMDI， and spleen index， decreased content of TNF-α in the serum（P<0.01）， significantly increased content of IL-10（P<0.01）， and elevated mRNA content of T-bet and Gata3（P<0.05） in the colon tissue. The expression of PPARγ protein was augmented（P<0.05）， and the expression of T-bet and NF-κB p65 protein was decreased（P<0.05，P<0.01）. ConclusionWujiwan activates or upregulates PPARγ expression in IBD rats to inhibit the generation of pro-inflammatory factors， participates in the inflammatory immune process， and alleviates inflammatory reactions. Its mechanism may involve regulating the NF-κB pathway through PPARγ， enhancing Th2 cell transcription expression， and reducing Th1 cell transcription.

Traditional Chinese medicine （TCM） has a long history of application in China and has consistently played a vital role in treating diseases and saving lives. TCM prescriptions （compounds） constitute the primary form of clinical TCM treatment and significantly differ from western medicine （chemicals） due to the diverse composition and chemical constituents of TCM （compounds）. Nevertheless， the potential multi-component， multi-target， and multi-pathway action characteristics of TCM prescriptions also demonstrate their possible （complementary） therapeutic advantages when compared with single-component chemical drugs. Therefore， driven by the development of modern science and technology and the demands of the modernization and internationalization of TCM， modern theories regarding the complexity of TCM prescription effects have been continuously proposed： Different from the abstract language of traditional prescription theory， the modern TCM prescription theory is more inclined to illustrate the connotation of prescription compatibility concretely and vividly from an experimental and scientific perspective. In this paper， new theories on the complexity of TCM prescriptions proposed in recent years are summarized to provide research references and ideas for the greater role of TCM prescriptions and a better scientific understanding.