ObjectiveTo explore the protective effect and underlying mechanism of Gegen Qinliantang on cognitive function in db/db mice with diabetic cognitive impairment （DCI）. MethodsThirty-two 8-week-old male db/db mice were randomly assigned to the model group， dapagliflozin group （1.0 mg·kg^-1·d^-1）， low-dose Gegen Qinliantang group （6.24 g·kg^-1·d^-1）， and high-dose Gegen Qinliantang group （24.96 g·kg^-1·d^-1）. Eight db/m mice served as the normal group. All mice were administered the corresponding treatment once daily by gavage for 10 consecutive weeks. Body weight and fasting blood glucose （FBG） were dynamically monitored. The Morris water maze test was used to evaluate cognitive function. Hematoxylin-eosin （HE） staining and Nissl staining were used to observe pathological changes in the hippocampus. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the levels of tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β） in hippocampal tissue. Immunofluorescence double staining was used to detect the co-expression of M1 microglial marker CD16/32 and ionized calcium-binding adapter molecule 1 （IBA1） in the hippocampus. Western blot analysis was performed to detect the protein expression of postsynaptic density protein 95 （PSD-95）， synapsin （SYN）， nuclear factor-κB p65 （NF-κB p65）， and phosphorylated NF-κB p65 （p-NF-κB p65） in the hippocampus. ResultsCompared with the normal group， the model group showed significantly increased body weight and FBG levels （P<0.01）， significantly prolonged escape latency and reduced platform crossings in the Morris water maze test （P<0.01）， disordered arrangement of hippocampal neurons， nuclear pyknosis， increased neuronal necrosis， reduced Nissl bodies， decreased expression of synaptic proteins PSD-95 and SYN （P<0.01）， increased CD16/32⁺ /IBA1⁺ positive rate， elevated levels of TNF-α and IL-1β， and an increased p-NF-κB p65/NF-κB p65 ratio （P<0.01）. Compared with the model group， the dapagliflozin group exhibited significantly reduced FBG levels at weeks 5 and 10 （P<0.05， P<0.01） and increased body weight. The high-dose Gegen Qinliantang group showed significantly reduced FBG at week 10 （P<0.05）. Escape latency was significantly reduced on days 3 and 5 of the water maze test in the dapagliflozin group and on day 5 in the high-dose Gegen Qinliantang group （P<0.05）. Platform crossings were significantly increased in both the dapagliflozin group and the high-dose Gegen Qinliantang group （P<0.05）. Hippocampal pathological damage was alleviated to varying degrees in the dapagliflozin group and the low- and high-dose Gegen Qinliantang groups， with significantly increased expression of PSD-95 and SYN （P<0.01）. Further studies revealed that both low- and high-dose Gegen Qinliantang reduced hippocampal IL-1β levels and the CD16/32⁺/IBA1⁺ positive rate of microglia， while the high-dose group also significantly reduced hippocampal TNF-α levels and the p-NF-κB p65/NF-κB p65 （P<0.05， P<0.01）. ConclusionGegen Qinliantang can improve hyperglycemia， cognitive dysfunction， and synaptic damage in DCI， inhibit M1 polarization of microglia and neuroinflammation， and its mechanism may be related to the inhibition of NF-κB activation.

ObjectiveTo explore the protective effect and underlying mechanism of Gegen Qinliantang on cognitive function in db/db mice with diabetic cognitive impairment （DCI）. MethodsThirty-two 8-week-old male db/db mice were randomly assigned to the model group， dapagliflozin group （1.0 mg·kg^-1·d^-1）， low-dose Gegen Qinliantang group （6.24 g·kg^-1·d^-1）， and high-dose Gegen Qinliantang group （24.96 g·kg^-1·d^-1）. Eight db/m mice served as the normal group. All mice were administered the corresponding treatment once daily by gavage for 10 consecutive weeks. Body weight and fasting blood glucose （FBG） were dynamically monitored. The Morris water maze test was used to evaluate cognitive function. Hematoxylin-eosin （HE） staining and Nissl staining were used to observe pathological changes in the hippocampus. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the levels of tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β） in hippocampal tissue. Immunofluorescence double staining was used to detect the co-expression of M1 microglial marker CD16/32 and ionized calcium-binding adapter molecule 1 （IBA1） in the hippocampus. Western blot analysis was performed to detect the protein expression of postsynaptic density protein 95 （PSD-95）， synapsin （SYN）， nuclear factor-κB p65 （NF-κB p65）， and phosphorylated NF-κB p65 （p-NF-κB p65） in the hippocampus. ResultsCompared with the normal group， the model group showed significantly increased body weight and FBG levels （P<0.01）， significantly prolonged escape latency and reduced platform crossings in the Morris water maze test （P<0.01）， disordered arrangement of hippocampal neurons， nuclear pyknosis， increased neuronal necrosis， reduced Nissl bodies， decreased expression of synaptic proteins PSD-95 and SYN （P<0.01）， increased CD16/32⁺ /IBA1⁺ positive rate， elevated levels of TNF-α and IL-1β， and an increased p-NF-κB p65/NF-κB p65 ratio （P<0.01）. Compared with the model group， the dapagliflozin group exhibited significantly reduced FBG levels at weeks 5 and 10 （P<0.05， P<0.01） and increased body weight. The high-dose Gegen Qinliantang group showed significantly reduced FBG at week 10 （P<0.05）. Escape latency was significantly reduced on days 3 and 5 of the water maze test in the dapagliflozin group and on day 5 in the high-dose Gegen Qinliantang group （P<0.05）. Platform crossings were significantly increased in both the dapagliflozin group and the high-dose Gegen Qinliantang group （P<0.05）. Hippocampal pathological damage was alleviated to varying degrees in the dapagliflozin group and the low- and high-dose Gegen Qinliantang groups， with significantly increased expression of PSD-95 and SYN （P<0.01）. Further studies revealed that both low- and high-dose Gegen Qinliantang reduced hippocampal IL-1β levels and the CD16/32⁺/IBA1⁺ positive rate of microglia， while the high-dose group also significantly reduced hippocampal TNF-α levels and the p-NF-κB p65/NF-κB p65 （P<0.05， P<0.01）. ConclusionGegen Qinliantang can improve hyperglycemia， cognitive dysfunction， and synaptic damage in DCI， inhibit M1 polarization of microglia and neuroinflammation， and its mechanism may be related to the inhibition of NF-κB activation.

AIM:To investigate the therapeutic effects of botulinum toxin A(BTXA)injection versus strabismus surgery in the treatment of acute acquired comitant esotropia(AACE).METHODS:Patient records of AACE cases treated at First People's Hospital of Nantong from January 2019 to September 2023 were retrospectively analyzed in this study. Patients were categorized into either strabismus surgery or BTXA injection groups based on treatment modality. Further stratification was performed according to preoperative deviation angles [>35 prism diopters(PD)vs ≤35 PD] and age(≥18 years adult group vs <18 years adolescent group). The baseline patient characteristics were collected, deviation angles at multiple timepoints before and after treatment were measured, and stereopsis test results were documented. Through comparative analysis of therapeutic outcomes across subgroups, we systematically evaluated the efficacy of different treatment approaches.RESULTS:A total of 43 AACE patients were included. At the final follow-up, both the surgery and BTXA injection groups showed a statistically significant decrease in deviation angle compared to pretreatment measurements(P<0.001). Significant differences were noted between the two groups in terms of the cure rate of strabismus and the recovery rate of stereopsis(P<0.05). For patients with deviations >35 PD, surgery yielded significantly better outcomes than injection therapy in postoperative angle, success rate, and stereopsis recovery(P<0.05). Similarly, in patients aged ≥18 years, surgical treatment was superior to injections in reducing strabismus angle, improving success rates, and restoring stereopsis(P<0.05).CONCLUSION:Both BTXA injection and strabismus surgery demonstrate therapeutic efficacy in AACE. Surgical treatment demonstrated superior efficacy compared to BTXA injection therapy, particularly in patients with deviations >35 PD and those aged ≥18 years. For patients with angles ≤35 PD or under 18 years, BTXA injection remains a viable treatment option.

OBJECTIVES: To explore the correlation of serum tryptophan level with 90-day mortality risk in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). METHODS: This retrospective study was conducted among 108 patients with HBV-ACLF, whose survival outcomes within 90 days after diagnosis were recorded. The correlation of baseline serum tryptophan levels measured by high-performance liquid chromatography with 90-day mortality of the patients was analyzed, and the predictive value of serum tryptophan for 90-day mortality was explored. RESULTS: Within 90 days after diagnosis, 53 (29.4%) of the patients died and 127 (70.6%) survived. The deceased patients had significantly lower baseline serum tryptophan levels than the survivors (7.31±3.73 pg/mL vs 13.32±7.15 pg/mL, P<0.001). Multivariate analysis suggested that serum tryptophan level was an independent factor correlated with mortality of HBV-ACLF after adjustment for confounding variables. The patients with serum tryptophan levels below the median level (10.14 pg/mL) at admission had significantly higher 90-day mortality risks than those with higher tryptophan levels (43.3% vs 15.6%, HR: 3.157, 95% CI: 1.713-5.817), and the complication by kidney dysfunction further increased the risk to 73.3% as compared with patients with higher serum tryptophan levels with normal kidney function (15.0%; HR: 7.558, 95% CI: 3.369-16.960). Serum tryptophan levels had an area under the receiver operating characteristic curve of 0.771 (95% CI: 0.699-0.844) for predicting 90-day mortality. CONCLUSIONS Serum tryptophan level is closely correlated with the survival outcomes of patients with HBV-ACLF, and a decreased tryptophan level indicates a high 90-day mortality risk, which can be further increased by the complication by kidney dysfunction.
Humans ; Tryptophan/blood* ; Retrospective Studies ; Acute-On-Chronic Liver Failure/virology* ; Male ; Female ; Middle Aged ; Adult ; Prognosis ; Hepatitis B/complications* ; Hepatitis B virus

Adipose-derived mesenchymal stem cell (ADSC) has become a research hotspot in the field of regenerative medicine and stem cells in recent years because of its rich stock, easy access and low immunogenicity. ADSC can regulate immune system not only directly by interacting with immune cells, such as T cells, macrophages and B cells, but also indirectly via secreting soluble cytokines, such as interleukin (IL), growth factors and extracellular vesicles. Meanwhile, the immunomodulatory effects of ADSC have been demonstrated in vitro and in vivo experiments and applied to treat various of immune-related diseases with good results, such as systemic scleroderma, systemic lupus erythematosus and atopic dermatitis, etc. In this article, the direct and indirect immunomodulatory mechanisms and clinical applications of ADSC are described, its research direction and application prospect are also prospected.

Adipose-derived mesenchymal stem cell (ADSC) has become a research hotspot in the field of regenerative medicine and stem cells in recent years because of its rich stock, easy access and low immunogenicity. ADSC can regulate immune system not only directly by interacting with immune cells, such as T cells, macrophages and B cells, but also indirectly via secreting soluble cytokines, such as interleukin (IL), growth factors and extracellular vesicles. Meanwhile, the immunomodulatory effects of ADSC have been demonstrated in vitro and in vivo experiments and applied to treat various of immune-related diseases with good results, such as systemic scleroderma, systemic lupus erythematosus and atopic dermatitis, etc. In this article, the direct and indirect immunomodulatory mechanisms and clinical applications of ADSC are described, its research direction and application prospect are also prospected.

Objective To analyze the effects of extended subxiphoid thymus resection on inflammatory factors,T lymphocyte subsets and stress response in thymoma patients.Methods The clinical data of 118 patients with thymoma admitted to our hospital from May 2021 to May 2023 were retrospectively analyzed,of which 61 patients underwent subxiphoid enlargement thymectomy(recorded as the study group)and 57 patients underwent lateral thoracotomy enlargement thymectomy(recorded as the control group).The postoperative and perioperative pain,stress response,inflammatory response,T lymphocyte subsets and complications were compared between the two groups.Results There was no significant difference in operation time,intraoperative blood loss and postoperative drainage volume between the two groups(P＞0.05).The visual analogue scale(VAS)of the study group(3.21±0.47,2.47±0.34 points)was lower than that of the control group(3.62±0.53,2.61±0.39 points)at 24 h and 48 h after surgery(P＜0.05).The levels of adrenaline(Adr)and cortisol(Cor)48 h after operation were higher than those before operation(P＜0.05).The levels of Adr and Cor[(101.94±12.83)ng/L,(276.84±31.05)nmol/L]in the study group were lower than those in the control group[(108.15±14.72)ng/L,(308.91±35.24)nmol/L]48 hours after operation(P＜0.05).The levels of TNF-α and IL-6 48 h after surgery were higher than those before surgery(P＜0.05).The levels of tumor necrosis factor a(TNF-α)and interleukin-6(IL-6)in the study group[(40.91±6.93)pg/ml,(55.62±8.67)pg/ml]48 h after surgery were lower than those in the control group[(45.85±8.12)pg/ml,(61.98±10.51)pg/ml](P＜0.05).The levels of Thl/Th2 and Th17/Treg in both groups 48 h after surgery were lower than those before surgery(P＜0.05).The levels of Th1/Th2 and Th17/Treg in the study group(4.75±0.74,0.95±0.17)were lower than those in the control group(5.16±0.89,1.06±0.19)48 h after surgery(P＜0.05).The changes of Th1/Th2 and Th17/Treg in two groups were different(P＜0.05).Conclusion Compared with lateral thoracotomy,transxiphoid enlargement of thymus can reduce perioperative pain,inhibit perioperative inflammatory response and stress response,improve T lymphocyte subpopulation,and is safe and reliable.

Objective:To compare the association between body mass index(BMI)trajectories deter-mined by different methods and the risk of overweight in early childhood in a prospective cohort study,and to identify children with higher risk of obesity during critical growth windows of early childhood.Methods:A total of 1 330 children from Peking University Birth Cohort in Tongzhou(PKUBC-T)were included in this study.The children were followed up at birth,1,3,6,9,12,18,and 24 months and 3 years of age to obtain their height/length and weight data,and calculate BMI Z-score.Latent class growth mixture modeling(GMM)and longitudinal data-based k-means clustering algorithm(KML)were used to determine the grouping of early childhood BMI trajectories from birth to 24 mouths.Linear regres-sion was used to compare the association between early childhood BMI trajectories determined by different methods and BMI Z-score at 3 years of age.The predictive performance of early childhood BMI trajecto-ries determined by different methods in predicting the risk of overweight(BMI Z-score＞1)at 3 years was compared using the average area under the curve(AUC)of 5-fold cross-validation in Logistic regres-sion models.Results:In the study population included in this research,the three-category trajectories determined using GMM were classified as low,medium,and high,accounting for 39.7％,54.1％,and 6.2％of the participants,respectively.The two-category trajectories determined using the KML method were classified as low and high,representing 50.3％and 49.7％of the participants,respectively.The three-category trajectories determined using the KML method were classified as low,medium,and high,accounting for 31.1％,47.4％,and 21.5％of the participants,respectively.There were certain differ-ences in the growth patterns reflected by the early childhood BMI trajectories determined using different methods.Linear regression analysis found that after adjusting for maternal ethnicity,educational level,delivery mode,parity,maternal age at delivery,gestational week at delivery,children's gender,and breastfeeding at 1 month of age,the association between the high trajectory group in the three-category trajectories determined by the KML method(manifested by a slightly higher BMI at birth,followed by rapid growth during infancy and a stable-high BMI until 24 months)and BMI Z-scores at 3 years was the strongest.Logistic regression analysis revealed that the three-category trajectory grouping determined by the KML method had the best predictive performance for the risk of overweight at 3 years.The results were basically consistent after additional adjustment for the high bound score of the child's diet balanced index,average daily physical activity time,and screen time.Conclusion:This study used different methods to identify early childhood BMI trajectories with varying characteristics,and found that the high trajectory group determined by the KML method was better able to identify children with a higher risk of overweight in early childhood.This provides scientific evidence for selecting appropriate methods to de-fine early childhood BMI trajectories.

Objective To study the relationship between serum neuron-specific enolase(NSE)and clinical features of pheochromocytoma/paraganglioma(PPGL).Methods Totally 501 PPGL patients diagnosed from January 2019 to December 2022 were divided into normal NSE group(NSE≤16.3 ng/mL)and elevated NSE group(NSE＞16.3 ng/mL).The clinical characteristics were compared between the two groups.Results Compared with normal NSE group,patients in the elevated NSE group had larger diameter in primary tumor(5.00 cm vs.4.60 cm),higher 24-hour urinary norepinephrine(NE)and 24-hour urinary dopamine(DA)levels,and a higher rate of metasta-sis(31.6%vs.13.7%)(P＜0.05).NSE level was positively correlated with the primary tumor size(r=0.131,P＜0.05),24-hour urinary NE level(r=0.195,P＜0.05)and 24-hour urinary DA level(r=0.119,P＜0.05).Conclusions The level of NSE is related to tumor size,secretion function and metastasis in PPGL patients.

BACKGROUND:It is known that N6-methyladenosine(m6A)plays a role in the pathogenesis of various diseases and studies have suggested its involvement in the pathologic changes of steroid-induced femoral head necrosis(SNFH).However,research on m6A methylation modifications in steroid-induced femoral head necrosis is limited. OBJECTIVE:Using bioinformatics methods to identify the differential expression of m6A-related genes in steroid-induced femoral head necrosis and to predict miRNAs associated with these genes to further elucidate the role and mechanism of m6A methylation in steroid-induced femoral head necrosis. METHODS:Differential gene expression between steroid-induced femoral head necrosis and control groups was analyzed using GSE123568 gene expression data and identified using the"limma"package in R.Functional enrichment analysis was performed on the differentially expressed genes.Differential analysis of the related genes was carried out using the"ggstatsplot"package in R.The differential genes were cross-validated using the GSE74089 dataset.An mRNA-miRNA regulatory network was constructed,and co-expression analysis was performed on the module genes followed by enrichment analysis.Differences in immune cell infiltration between steroid-induced femoral head necrosis and control groups were quantified using the ssGSEA method. RESULTS AND CONCLUSION:Correlation analysis revealed 13 m6A-related genes,and further analysis through the protein-protein interaction network identification and receiver operating characteristic curve analysis showed that YTHDF2 was expected to be a core differential gene as a potential early biomarker.Enrichment analysis indicated that differentially expressed genes were mainly involved in inflammation and immune response and were closely related to osteoclasts.Cross-validation analysis showed that differential gene expression results between the two datasets were consistent.mRNA-miRNA regulatory network analysis revealed that YTHDF2 was negatively correlated with miRNA-27a.Immune infiltration analysis revealed an increase in immune cell infiltration in steroid-induced femoral head necrosis,and YTHDF2 was positively correlated with the infiltration of CD4+T cells.To conclude,m6A-related gene YTHDF2 can serve as a potential biomarker of steroid-induced femoral head necrosis and is valuable for the early clinical diagnosis and treatment of steroid-induced femoral head necrosis.The negative correlation between YTHDF2 and mir-27a and the positive correlation between YTHDF2 and CD4+T cell infiltration provide new insights into the early diagnosis and treatment of steroid-induced femoral head necrosis and shed light on the mechanism of m6A in steroid-induced femoral head necrosis.