Objective:To explore the effects of treadmill training during pregnancy on the development of dendritic spines and the expression of brain-derived neurotrophic factor (BDNF) in hippocampal neurons of offspring rats.Methods:According to the random number table, the natural pregnant healthy SPF female rats were divided into control group (CON group) and treadmill training group (TE group), with 6 rats in each group. The pregnant rats in CON group were fed quietly, while those in TE group were given treadmill exercise intervention 60 minutes a day with 5 days a week for 3 weeks. The setting parameters of treadmill training: the slope of electric flat plate was 0°, the track transmission speed was 8 m/min in the first 5 min, 10 m/min in the middle 25 min, and 12 m/min in the last 30 min.The body weight changes of pregnant rats in the two groups were recorded every two days from gestation of 0 day (G0). On day 21 of gestation (G21), the pregnant mice were placed in a quiet environment for labor. The expression of BDNF in hippocampus was detected by Western blot at 0, 7, 14 and 28 days after birth (P0, P7, P14, P28) respectively. The density of dendritic spines in hippocampus was detected by Golgi staining on P28. SPSS 19.0 software was used to analyze the data. Repeated measurement ANOVA was used to analyze the body weight of pregnant rats. t-test was used to analyze the data of neuronal dendritic spines. Results:Golgi staining showed that at P28, the density of dendritic spines in hippocampal CA1 area of TE group(11.330±0.558) was significantly higher than that of CON group (9.667±0.422), and the difference was statistically significant ( t=2.384, P<0.05). Compared with CON group, the relative expression level of BDNF protein in the hippocampus of offspring rats of TE group was significantly higher at P0: ((1.001±0.206), (2.027±0.240), t=3.244, P<0.05), P7: ((1.003±0.152), (2.077±0.172), t=4.669, P<0.05), P14: ((1.005±0.160), (1.562±0.178), t=3.329, P<0.05) and P28: ((1.004±0.196), (1.790±0.191), t=2.875, P<0.05), and the differences were statistically significant. Conclusion:Treadmill training during pregnancy can promote the development of dendritic spines in hippocampal neurons of offspring rats, which may be related to the promotion of BDNF expression in hippocampus.

Objective To investigate the frequency and distribution characteristics of gene mutations in children with phenylalanine hydroxylase(PAH)deficiency in Xinjiang.Methods A total of 230 children diag-nosed with PAH deficiency in Urumqi Maternal and Child Health Care Hospital from January 1st,2015 to February 28th,2023 were enrolled in the study.The variation of PAH gene was analyzed and the variation sites of PAH gene in children with different phenotypes were compared.Results A total of 441 PAH gene va-riants were detected in 230 children with PAH deficiency in Xinjiang,with a total detection rate of 95.87％.A-mong them,2 variants were detected in 227 cases,only 1 variant was detected in 2 cases,and 3 variants were detected in 1 case.217 cases were complex heterozygous variants,and 10 cases were homozygous variants.The high-frequency variant loci were c.158G＞A[23.39％(102/441)],c.728G＞A[11.70％(51/441)],c.688G＞A[5.05％(22/441)],c.721C＞T[3.90％(17/441)],c.611A＞G[3.67％(16/441)],c.1238G＞C[3.21％(14/441)].The high-frequency variant loci for classic PKU were c.728G＞A,c.331C＞T,and c.782G＞A;the high-frequency variant loci for mild PKU were c.721C＞T,c.1068C＞A,and c.1301C＞A;the high-frequency variant loci for children with mild HPA were c.158G＞A and c.688G＞A.There were significant differences in the frequency of high frequency mutations among the above three phenotypes(P＜0.05).Conclusion Mild HPA predominates in children with PAH deficiency in Xinjiang.The hotspot loci of the PAH gene in Xinjiang have been clarified,and specific PAH gene loci have been observed in the three different phenotypes,which can provide theoretical basis for prenatal diagnosis and clinical genetic counselling.

Objective To evaluate the role of hippocampal CD200 receptor 1(CD200R1)in peri-operative neurocognitive disorders(PND)in mice.Methods Sixty clean-grade male C57BL/6 mice,aged 9-10 months,weighing 32-38 g,were used in the study.The experiment was performed in two parts.Ex-periment Ⅰ Thirty-six mice were divided into 2 groups(n＝18 each)using a random number table meth-od: control group(group C)and PND group.Group C only received isoflurane anesthesia.Partial left lo-bectomy of the liver was performed under isoflurane anesthesia in group PND.Contextual fear conditioning test was performed at 1,3 and 7 days after surgery,and the freezing time was recorded.The mice were then sacrificed,and the hippocampus was isolated for determination of interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF-α)contents(by enzyme-linked immunosorbent assay)and CD200 and CD200R1 expression(by Western blot).ExperimentⅡ Twenty-four mice were divided into 2 groups(n＝12 each)using a random number table method: CD200-Fc group and IgG1-Fc group.Recombinant proteins CD200-Fc and human IgG1-Fc were injected into the lateral cerebral ventricle in CD200-Fc group and IgG1-Fc group,respectively.Partial left lobectomy of the liver was performed after the end of injection.Contextual fear conditioning test was performed at 1 and 3 days after surgery,and the freezing time was recorded.Re-sults Experiment Ⅰ Compared with group C,the freezing time in the contextual fear conditioning test was significantly shortened,and the contents of IL-1β were increased at 1 and 3 days after surgery,the contents of TNF-α were increased at 3 and 7 days after surgery,and the expression of CD200 and CD200R1 was up-regulated at 1 day after surgery in group PND(P＜0.05).ExperimentⅡ Compared with IgG1-Fc group,the freezing time in the contextual fear conditioning test was significantly prolonged at 1 day after surgery in CD200-Fc group(P＜0.05).Conclusion Up-regulated expression of hippocampal CD200R1 is the endogenous protective mechanism of PND in mice.

Objective:To study the genetic profiles of phenylalanine hydroxylase (PAH) gene mutations in neonates with phenylketonuria (PKU) in Xinjiang.Methods:From January 2015 to December 2021,neonates born and genetically diagnosed with PKU in our region were retrospectively included. The genetic profiles of different ethnic groups were analyzed and compared with PKU patients from central, northwest and northern regions of China.Results:A total of 131 neonates with PKU were enrolled, including 82 Han, 25 Hui and 20 Uyghur patients, 4 cases of other ethnic groups. 46, 20 and 14 types of pathogenic variants were detected in each ethnic group with detection rates of 95.1% (156/164), 66.0% (33/50), and 60.0% (24/40), respectively. The variants were mainly missense mutations and located in exons 2, 3, 6,7 and 11. The most common loci in Hui patients were c.158G>A (18.2%), c.728G>A (18.2%) and c.898G>T (9.1%). The most common loci in Uyghur patients were c.158G>A (33.3%), c.355C>T (12.5%) and c.1068C>A (8.3%). c. 898G>T might be most unique in Hui patients and c.355C>T most unique in Uyghur patients in Xinjiang. A novel variant of PAH gene, c.828G>C (p.M276I) in exon 7 was identified. Compared with northern, central and northwestern regions of China, PKU patients in Xinjiang had significantly higher incidence of c.158G>A mutation and lower incidence of c.728G>A mutation ( P<0.05). Conclusions:Missense mutations of PAH gene are common in some regions of Xinjiang. The compositions of PAH gene variations are similar to northwest and northern China with significant differences in hotspots of mutations.

Objective This study aims to investigate the primary target and potential mechanism of mangiferin(MF)in treating oral submucous fibrosis(OSF)through Gene Expression Omnibus(GEO)database chip mining,network pharmacology,and molecular docking techniques.Methods Potential therapeutic targets for OSF were identified using GEO chip data.The potential targets of MF were predicted,and disease-related targets for OSF were col-lected from databases.A Venn diagram was created using the EVenn platform to identify overlapping targets.The protein-protein interaction(PPI)network was constructed using the STRING database.Gene ontology(GO)and Kyoto Encyclope-dia of Genes and Genomes(KEGG)enrichment analyses were performed using the DAVID platform.Cytoscape 3.10.1 software was used to visualize a drug-target-pathway-disease network,while AutoDocktools 1.5.6 software was employed for molecular docking analysis.Results A total of 356 potential targets for MF and 360 disease-related targets for OSF were obtained from multiple databases.The top 15 key target proteins in the PPI network were selected as significant candi-dates.GO function and KEGG pathway enrichment analyses revealed that MF treatment primarily involved advanced gly-cation end products-receptor(AGE-RAGE),epidermal growth factor receptor(EGFR),and other signaling pathways associ-ated with OSF pathogenesis.Molecular docking analysis demonstrated that MF exhibited a strong binding activity toward AKT serine kinase 1(AKT1),tumor necrosis factor(TNF),and other core targets.Conclusion These findings suggest that MF may exert its therapeutic effects on OSF through a multitarget approach involving various signaling pathways.

Objective To observe the value of cardiac CT angiography(CCTA)for left atrial appendage closure(LAAC).Methods Twelve Labradors were enrolled and underwent LAAC.CCTA examinations were performed before and 7,45 and 90 days after LAAC,and the left atrial appendage(LAA)parameters before and post LAAC occluder compression ratio were recorded.Ninety days after LAAC,the dogs were euthanized for gross anatomical observation,micro CT imaging and pathological examination,and the value of CCTA for LAAC was analyzed.Results Based on CCTA before LAAC,LAA opening depth was(18.8±2.6)mm,the minimum diameter was(16.3±2.0)mm and the maximum diameter was(22.6±3.2)mm,so 28 mm diameter occluders were selected for LAAC.Seven,45 and 90 days after LAAC,no displacement of occluder,thrombi nor device leakage was found on CCTA,while no significant difference of compression ratio was found among different time points(P＞0.05),nor between those measured with CCTA and micro CT 90 days after LAAC(P＞0.05).Ninety days after LAAC,gross dissection revealed complete endothelialization of occlude in 11 dogs and incomplete endothelialization in 1 dog.Pathological examination showed that collagen fibers arranged neatly,with endothelial cells covering the surface,and no inflammatory cell infiltration was observed.Conclusion CCTA could be used to observe LAA and surrounding structures before LAAC,hence guiding to select appropriate occluder,evaluate occlusion effect and monitor complications of LAAC in dogs.

Background and objective A reasonable and standardized dietary plan and procedure can help patients recovering quickly from lung cancer surgery.The aim of this study is to optimize the diet plan and procedure mainly based on medium chain triglyceride(MCT)diet and explore its clinical advantages for postoperative lung cancer patients.Methods From October 2023 to December 2023,a total of 156 patients were collected,who underwent lung cancer surgery in Lung Cancer Cen-ter,West China Hospital of Sichuan University.The patients were randomized into MCT group(76 cases)and routine diet(RD)group(80 cases).Clinical symptoms,biochemical index,postoperative hospitalization time and cost,dietary satisfaction and hospitalization comfort between the two groups were analyzed.Results The mean anus exhausting time in MCT group[24.00(9.75,36.97)h]was significantly shorter than that in RD group[28.50(24.00,48.00)h](P＜0.001).And the incidence of dizzi-ness(18.42％),nausea and vomiting(6.58％)in MCT group were remarkably lower than those in RD group(51.25％,31.25％)(P＜0.001).Hospitalization comfort score in MCT group[(16.74±1.70)]was significantly higher than that in RD group[(14.83±2.34)](P=0.016).Meanwhile,the average hospitalization cost in MCT group[(39,701.82±8105.47)￥]showed an obvious decrease compared with RD group[(44,511.79±9593.19)￥](P=0.007).Conclusion Optimizing the dietary plan and procedure mainly based on MCT diet for postoperative lung cancer patients can help the recovery of gastrointestinal function and improve hospitalization comfort,which promoted overall postoperative rehabilitation of patients with lung cancer surgery.

Objective: To evaluate the role of hippocampal CD200 receptor 1 (CD200R1) in perioperative neurocognitive disorders (PND) in mice. Methods: Sixty clean-grade male C57BL/6 mice, aged 9-10 months, weighing 32-38 g, were used in the study.The experiment was performed in two parts.Experiment Ⅰ Thirty-six mice were divided into 2 groups (n=18 each) using a random number table method: control group (group C) and PND group.Group C only received isoflurane anesthesia.Partial left lobectomy of the liver was performed under isoflurane anesthesia in group PND.Contextual fear conditioning test was performed at 1, 3 and 7 days after surgery, and the freezing time was recorded.The mice were then sacrificed, and the hippocampus was isolated for determination of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) contents (by enzyme-linked immunosorbent assay) and CD200 and CD200R1 expression (by Western blot). Experiment Ⅱ Twenty-four mice were divided into 2 groups (n=12 each) using a random number table method: CD200-Fc group and IgG1-Fc group.Recombinant proteins CD200-Fc and human IgG1-Fc were injected into the lateral cerebral ventricle in CD200-Fc group and IgG1-Fc group, respectively.Partial left lobectomy of the liver was performed after the end of injection.Contextual fear conditioning test was performed at 1 and 3 days after surgery, and the freezing time was recorded. Results: Experiment Ⅰ Compared with group C, the freezing time in the contextual fear conditioning test was significantly shortened, and the contents of IL-1β were increased at 1 and 3 days after surgery, the contents of TNF-α were increased at 3 and 7 days after surgery, and the expression of CD200 and CD200R1 was up-regulated at 1 day after surgery in group PND (P<0.05). Experiment Ⅱ Compared with IgG1-Fc group, the freezing time in the contextual fear conditioning test was significantly prolonged at 1 day after surgery in CD200-Fc group (P<0.05). Conclusion Up-regulated expression of hippocampal CD200R1 is the endogenous protective mechanism of PND in mice.

Renal interstitial fibrosis（RIF） is the main pathological manifestation of chronic kidney disease. Due to the complexity of the mechanism， there is no specific treatment for RIF in clinical practice. The abnormal activation of the phosphatidylinositol 3-kinase （PI3K）/protein kinase B（Akt） signaling pathway and the activation of downstream target genes are key drivers of RIF induction and progression. Traditional Chinese medicine has the characteristics of precise efficacy and minimal toxic side effects， and the occurrence and development of RIF can be regulated by multiple targets and mutual coordination. This review focuses on the PI3K/Akt signaling pathway and summarizes the potential targets and regulatory mechanisms of traditional Chinese medicine in the treatment of RIF. It is found that various effective ingredients （such as sinomenine， mangiferin， coumarin derivates from Hydrangea paniculata， etc.） and formulas （such as Fushengong decoction， Qi-Bang-Yi-Shen formula， etc.） of traditional Chinese medicine can inhibit fibroblast proliferation， improve inflammation and oxidative stress， maintain mitochondrial stability， and slow down ferroptosis through this pathway， thereby delaying the occurrence and progression of RIF.

BACKGROUND: Systemic lupus erythematosus (SLE) is a complex autoimmune disease, and the mechanism of SLE is yet to be fully elucidated. The aim of this study was to explore the role of two-pore segment channel 2 (TPCN2) in SLE pathogenesis. METHODS: Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the expression of TPCN2 in SLE. We performed a loss-of-function assay by lentiviral construct in Jurkat and THP-1 cell. Knockdown of TPCN2 were confirmed at the RNA level by qRT-PCR and protein level by Western blotting. Cell Count Kit-8 and flow cytometry were used to analyze the cell proliferation, apoptosis, and cell cycle of TPCN2-deficient cells. In addition, gene expression profile of TPCN2-deficient cells was analyzed by RNA sequencing (RNA-seq). RESULTS: TPCN2 knockdown with short hairpin RNA (shRNA)-mediated lentiviruses inhibited cell proliferation, and induced apoptosis and cell-cycle arrest of G2/M phase in both Jurkat and THP-1 cells. We analyzed the transcriptome of knockdown-TPCN2-Jurkat cells, and screened the differential genes, which were enriched for the G2/M checkpoint, complement, and interleukin-6-Janus kinase-signal transducer and activator of transcription pathways, as well as changes in levels of forkhead box O, phosphatidylinositol 3-kinase/protein kinase B/mechanistic target of rapamycin, and T cell receptor pathways; moreover, TPCN2 significantly influenced cellular processes and biological regulation. CONCLUSION TPCN2 might be a potential protective factor against SLE.
Apoptosis/genetics* ; Cell Division ; Humans ; Jurkat Cells ; Lupus Erythematosus, Systemic/genetics* ; RNA, Small Interfering/genetics*