ObjectiveTo investigate the effects of modified Xiaoyaosan （JJXYS） on behavioral abnormalities and hippocampal mitochondrial quality control （MQC） in the rat model of post-myocardial infarction depression （PMD） and preliminarily explore its potential mechanism. MethodsA rat model of PMD was established by left anterior descending coronary artery ligation combined with chronic unpredictable mild stress （CUMS）. Rats were randomized into a control group， a model group， a fluoxetine （FLX， 10 mg·kg^-1） group， and low-， medium-， and high-dose JJXYS （JJXYS-L/M/H， 1.12， 2.24， 4.48 g·kg^-1， respectively） groups. Depressive-like behaviors were evaluated by body weight monitoring， sucrose preference test， open field test， and forced swimming test. Hematoxylin-eosin staining and Nissl staining were used to observe hippocampal histomorphology and neuronal changes. Enzyme-linked immunosorbent assay was conducted to determine the serum levels of 5-hydroxytryptamine （5-HT）， dopamine （DA）， interleukin-1 beta （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-alpha （TNF-α）. The mRNA levels of MQC-related genes including peroxisome proliferator-activated receptor-gamma coactivator-1 alpha （PGC-1α）， nuclear respiratory factor 1 （Nrf1）， and transcription factor A， mitochondrial （TFAM） in the hippocampal tissue were measured by real-time PCR. The expression of proteins related to the dynamin-related protein 1 （Drp1）/PTEN-induced putative kinase 1 （PINK1）/Parkin signaling pathway was determined by Western blot. ResultsCompared with the control group， the model group showed restricted body weight gain， aggravated depressive-like behaviors， declined serum 5-HT and DA levels， evident hippocampal neuronal damage and reduced Nissl bodies， as well as downregulated expression of MQC-related genes and proteins （P<0.05）. Compared with the model group， both FLX and JJXYS alleviated the above changes to varying degrees. Moreover， the JJXYS-M and JJXYS-H groups showed more pronounced effects， improving behavioral performance， restoring 5-HT and DA levels， alleviating hippocampal pathological injury， and upregulating the expression of PGC-1α/Nrf1/TFAM mRNA and Drp1/PINK1/Parkin signaling pathway-related proteins （P<0.05）. ConclusionJJXYS can significantly alleviate depressive-like behaviors and neurotransmitter imbalance in the rat model of PMD by regulating hippocampal MQC and upregulating the Drp1/PINK1/Parkin-related pathway. This study provides experimental evidence for the intervention of PMD with JJXYS.

To investigate the impact of high salt stress on the metabolic pathways and regulatory mecha-nisms involved in synthesizing hydroxyectoine(5-HE)in Virgibacillus salexigens,cultures were supple-mented with 1.5 and 2.5 mol/L NaCl as control and experimental groups,respectively.High-perform-ance liquid chromatography(HPLC)was used to detect the difference in the amount of 5-HE synthesis.Transcriptomic and metabolomic analyses identified differential genes and metabolites under varying salt concentrations.Key differential gene expressions related to 5-HE synthesis were validated using qRT-PCR.Results showed that 5-HE synthesis reached 121.9 mg/L at 2.5 mol/L NaCl.Transcriptomic anal-ysis identified 652 differentially expressed genes across 348 KEGG pathways,with 210 upregulated and 442 downregulated,primarily enriched in pathways such as purine metabolism,amino acid biosynthesis,sulfur metabolism,and biotin metabolism.Validation of 13 genes,including lysC,asd,ectA,ectB,ectC,ectD,thrB,thrC,ilvA,ilvE,AGXT,YckA and GlnQ,showed expression trends consistent with transcriptome data.Metabolomic analysis identified 1153 metabolites predominantly enriched in histidine metabolism,lysine degradation,and arginine and proline metabolism.This study preliminarily elucidated the effect of high salt on the 5-HE synthesis pathway,and provided a basis for the subsequent construc-tion of 5-HE high-yielding strains.

Diabetic foot (DF) is one of the most serious chronic complications of diabetes. The incidence rate among global diabetes patients is as high as 15% to 25%, and about 50% of patients will develop contralateral foot ulcers within 5 years after the first unilateral ulcer. As a non-invasive prevention and control solution, the application progress of functional insoles is mainly reflected in the following aspects:(1) Material innovation. The application of new composite materials and smart materials has significantly enhanced the pressure reduction effect and comfort. (2) Structural optimization. The development of multi-layer design and local pressure reduction structure has achieved more precise pressure distribution regulation. (3) Manufacturing process. 3D printing and parametric design have enabled the personalized customization of functional insoles. (4) Intelligent monitoring. It integrates functions such as pressure sensing and temperature monitoring, achieving real-time monitoring and early warning of foot conditions. Clinical research has confirmed that personalized functional insoles could reduce the incidence of foot ulcers and shorten the healing time of ulcers. At present, the research hotspots mainly focus on the development of smart materials, the construction of multi-functional integration and remote monitoring systems. However, in-depth research is still needed in the aspects of biomechanical mechanisms, standardized evaluation systems and long-term efficacy assessment. The development of future functional insoles should focus on the coordinated advancement of "personalization-intelligence-standardization", with the aim of providing more effective solutions for the prevention and treatment of DF.
Humans ; Diabetic Foot/therapy* ; Foot Orthoses

To investigate the impact of high salt stress on the metabolic pathways and regulatory mecha-nisms involved in synthesizing hydroxyectoine(5-HE)in Virgibacillus salexigens,cultures were supple-mented with 1.5 and 2.5 mol/L NaCl as control and experimental groups,respectively.High-perform-ance liquid chromatography(HPLC)was used to detect the difference in the amount of 5-HE synthesis.Transcriptomic and metabolomic analyses identified differential genes and metabolites under varying salt concentrations.Key differential gene expressions related to 5-HE synthesis were validated using qRT-PCR.Results showed that 5-HE synthesis reached 121.9 mg/L at 2.5 mol/L NaCl.Transcriptomic anal-ysis identified 652 differentially expressed genes across 348 KEGG pathways,with 210 upregulated and 442 downregulated,primarily enriched in pathways such as purine metabolism,amino acid biosynthesis,sulfur metabolism,and biotin metabolism.Validation of 13 genes,including lysC,asd,ectA,ectB,ectC,ectD,thrB,thrC,ilvA,ilvE,AGXT,YckA and GlnQ,showed expression trends consistent with transcriptome data.Metabolomic analysis identified 1153 metabolites predominantly enriched in histidine metabolism,lysine degradation,and arginine and proline metabolism.This study preliminarily elucidated the effect of high salt on the 5-HE synthesis pathway,and provided a basis for the subsequent construc-tion of 5-HE high-yielding strains.

Objective:To investigate the completion rate of tumor evaluation at initial assessment and after neoadjuvant therapy for mid and low rectal cancer patients in the national multicenter real-world database.Methods:The prospective real-world study was conducted. The clinicopathological data of 1 074 patients who underwent surgical treatment for mid and low rectal cancer in 47 national medical institutions, including Peking Union Medical College Hospital et al, from May 12,2023 to May 11,2024 were collected. Observation indicators: (1) clinical characteristics of patients with mid and low rectal cancer; (2) initial colonoscopy and pathologic evaluation of tumors in patients with mid and low rectal cancer; (3) initial imaging evaluation of patients with mid and low rectal cancer; (4) imaging evaluation after neoadjuvant therapy for patients with mid and low rectal cancer. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M( Q1, Q3). Count data were described as absoluter numbers and/or percentages. Results:(1) Clinical characteristics of patients with mid and low rectal cancer. Of the 1 074 patients, there were 713 males and 361 females, aged 63(56,70)years. The body mass index of 1 074 patients was 24(21,26)kg/m 2.For American Society of Anesthesiologists classification, there were 147 cases of stage Ⅰ, 641 cases of stage Ⅱ, 157 cases of stage Ⅲ, 2 cases of stage Ⅳ, and there were 127 cases missing data. (2) Initial colonoscopy and pathologic evaluation of tumors in patients with mid and low rectal cancer. Of the 1 074 patients, there were 787 cases (73.28%) undergoing complete colonoscopy, and there were only 197 cases (18.34%) undergoing immunohistochemical evaluation of all four mismatch repair proteins. (3) Initial imaging evaluation of patients with mid and low rectal cancer. Of the 1 074 patients, there were 842(78.40%) patients completing magnetic resonance imaging (MRI) or ultrasound evaluation, and there were 914(85.10%) patients completing chest, abdomen, and pelvis enhanced computed tomography (CT) evaluation. In the 149 patients completing rectal ultrasound evaluation, there were 122 cases (81.88%) comple-ting T staging evaluation, and there were 81 cases (54.36%) completing N staging evaluation. In the 808 patients completing rectal MRI evaluation, there were 708 cases (87.62%) completing T staging evaluation, and there were 590 cases (73.02%) completing N staging evaluation. (4) Imaging evalua-tion after neoadjuvant therapy for patients with mid and low rectal cancer. Of the 388 patients with neoadjuvant therapy, there were 332 patients (85.57%) completing MRI or ultrasound evaluation, and there were 327 patients (84.28%) completing chest, abdomen, and pelvis enhanced CT evalua-tion. In the 70 patients completing rectal ultrasound evaluation, there were 65 cases (92.86%) com-pleting T staging evaluation, and there were 49 cases (70.00%) completing N staging evaluation. In the 327 patients completing rectal MRI evaluation, there were 246 cases (75.23%) completing T staging, and there were 228 cases (69.72%) completing N staging evaluation. Conclusion:The com-pletion rate of tumor imaging evaluation at initial assessment and after neoadjuvant therapy for mid and low rectal cancer patients on a national scale is relatively good.

OBJECTIVE: To investigate the therapeutic potential of pseudolaric acid B (PAB) on non-alcoholic fatty liver disease (NAFLD) and its underlying molecular mechanism in vitro and in vivo. METHODS: Eight-week-old male C57BL/6J mice (n=32) were fed either a normal chow diet (NCD) or a high-fat diet (HFD) for 8 weeks. The HFD mice were divided into 3 groups according to a simple random method, including HFD, PAB low-dose [10 mg/(kg·d), PAB-L], and PAB high-dose [20 mg/(kg·d), PAB-H] groups. After 8 weeks of treatment, glucose metabolism and insulin resistance were assessed by oral glucose tolerance test (OGTT) and insulin tolerance test (ITT). Biochemical assays were used to measure the serum and cellular levels of total cholesterol (TC), triglycerides (TG), aspartate aminotransferase (AST), alanine aminotransferase (ALT), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). White adipose tissue (WAT), brown adipose tissue (BAT) and liver tissue were subjected to hematoxylin and eosin (H&E) staining or Oil Red O staining to observe the alterations in adipose tissue and liver injury. PharmMapper and DisGeNet were used to predict the NAFLD-related PAB targets. Peroxisome proliferator-activated receptor alpha (PPARα) pathway involvement was suggested by Kyoto Encyclopedia of Genes and Genomes (KEGG) and search tool Retrieval of Interacting Genes (STRING) analyses. Luciferase reporter assay, cellular thermal shift assay (CETSA), and drug affinity responsive target stability assay (DARTS) were conducted to confirm direct binding of PAB with PPARα. Molecular dynamics simulations were applied to further validate target engagement. RT-qPCR and Western blot were performed to assess the downstream genes and proteins expression, and validated by PPARα inhibitor MK886. RESULTS: PAB significantly reduced serum TC, TG, LDL-C, AST, and ALT levels, and increased HDL-C level in HFD mice (P<0.01). Target prediction analysis indicated a significant correlation between PAB and PPARα pathway. PAB direct target binding with PPARα was confirmed through luciferase reporter assay, CETSA, and DARTS (P<0.05 or P<0.01). The target engagement between PAB and PPARα protein was further confirmed by molecular dynamics simulations and the top 3 amino acid residues, LEU321, MET355, and PHE273 showed the most significant changes in mutational energy. Subsequently, PAB upregulated the genes expressions involved in lipid metabolism and mitochondrial biogenesis downstream of PPARα (P<0.05 or P<0.01). Significantly, the PPARα inhibitor MK886 effectively reversed the lipid-lowering and PPARα activation properties of PAB (P<0.05 or P<0.01). CONCLUSION PAB mitigates lipid accumulation, ameliorates liver damage, and improves mitochondrial biogenesis by binding with PPARα, thus presenting a potential candidate for pharmaceutical development in the treatment of NAFLD.
Animals ; PPAR alpha/metabolism* ; Non-alcoholic Fatty Liver Disease/pathology* ; Male ; Mice, Inbred C57BL ; Lipid Metabolism/drug effects* ; Diterpenes/therapeutic use* ; Organelle Biogenesis ; Diet, High-Fat ; Humans ; Mice ; Liver/metabolism* ; Insulin Resistance ; Mitochondria/metabolism* ; Molecular Docking Simulation

Objective:To establish a stable rat model of sequelae of pelvic inflammatory disease(SPID)with clinical characteristics,and to provide a reliable experimental model for the study of the pharmcological effect and mechanism of SPID.Methods:Twenty-four 7-week-old SD rats were divided into sham operation group,model-A(108 cfu/mL mixed bacterial solution,0.2 mL),model-B(109 cfu/mL mixed bacterial solution 0.2 mL),and model-C(108 cfu/mL E.coli 0.2 mL).The weight of the rat's uterine was weighed and the uterine index was calculated.The automatic hematology analyzer was used to detect the blood routine;hematoxylin-eosin staining(HE)and masson staining were used to detect uterine pathlogical changes in rats.Enzyme-linked immunosorbent assay(ELISA)was used to detect interleukin-1β(IL-1β),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in rat uterine tissue homogenates.Western blot was used to detect the expression of proteins related to NF-κB signaling pathway.Results:Compared with the sham operation group,the uterine index of model-A,model-B,and model-C were significantly increased(P＜0.05,P＜0.01).The levels of WBC and NE in the model-A increased significantly(P＜0.01).The level of LY in model-B decreased significantly(P＜0.01).The levels of IL-1β,TNF-α in model-A,model-B,and model-C were significantly increased(P＜0.01).The levels of IL-6 in model-A and model-B were significantly increased(P＜0.05,P＜0.01).The collagen volume fraction of model-A and model-B were significantly increased(P＜0.01).Mechanism study indicates that the expression levels of p-IKKβ/IKKβ,p-IκBα/IκBα and p-p65/p65 in model-A were significantly increased(P＜0.01),and the expression levels of IκBα/β-actin were significantly decreased(P＜0.01).The expression level of p-IKKβ/IKKβ in model-B was significantly increased(P＜0.01).Conclusions:A stable rat model of SPID that conforms to clinical characteristics can be successfully constructed by combining 0.2 mL of mixed bacterial solution with a concentration of 108 cfu/mL and mechanical injury.This modeling method intervened in the expression of the NF-κB inflammatory signaling pathway.

Objective:To establish a stable rat model of sequelae of pelvic inflammatory disease(SPID)with clinical characteristics,and to provide a reliable experimental model for the study of the pharmcological effect and mechanism of SPID.Methods:Twenty-four 7-week-old SD rats were divided into sham operation group,model-A(108 cfu/mL mixed bacterial solution,0.2 mL),model-B(109 cfu/mL mixed bacterial solution 0.2 mL),and model-C(108 cfu/mL E.coli 0.2 mL).The weight of the rat's uterine was weighed and the uterine index was calculated.The automatic hematology analyzer was used to detect the blood routine;hematoxylin-eosin staining(HE)and masson staining were used to detect uterine pathlogical changes in rats.Enzyme-linked immunosorbent assay(ELISA)was used to detect interleukin-1β(IL-1β),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in rat uterine tissue homogenates.Western blot was used to detect the expression of proteins related to NF-κB signaling pathway.Results:Compared with the sham operation group,the uterine index of model-A,model-B,and model-C were significantly increased(P＜0.05,P＜0.01).The levels of WBC and NE in the model-A increased significantly(P＜0.01).The level of LY in model-B decreased significantly(P＜0.01).The levels of IL-1β,TNF-α in model-A,model-B,and model-C were significantly increased(P＜0.01).The levels of IL-6 in model-A and model-B were significantly increased(P＜0.05,P＜0.01).The collagen volume fraction of model-A and model-B were significantly increased(P＜0.01).Mechanism study indicates that the expression levels of p-IKKβ/IKKβ,p-IκBα/IκBα and p-p65/p65 in model-A were significantly increased(P＜0.01),and the expression levels of IκBα/β-actin were significantly decreased(P＜0.01).The expression level of p-IKKβ/IKKβ in model-B was significantly increased(P＜0.01).Conclusions:A stable rat model of SPID that conforms to clinical characteristics can be successfully constructed by combining 0.2 mL of mixed bacterial solution with a concentration of 108 cfu/mL and mechanical injury.This modeling method intervened in the expression of the NF-κB inflammatory signaling pathway.

Objective:To investigate the completion rate of tumor evaluation at initial assessment and after neoadjuvant therapy for mid and low rectal cancer patients in the national multicenter real-world database.Methods:The prospective real-world study was conducted. The clinicopathological data of 1 074 patients who underwent surgical treatment for mid and low rectal cancer in 47 national medical institutions, including Peking Union Medical College Hospital et al, from May 12,2023 to May 11,2024 were collected. Observation indicators: (1) clinical characteristics of patients with mid and low rectal cancer; (2) initial colonoscopy and pathologic evaluation of tumors in patients with mid and low rectal cancer; (3) initial imaging evaluation of patients with mid and low rectal cancer; (4) imaging evaluation after neoadjuvant therapy for patients with mid and low rectal cancer. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M( Q1, Q3). Count data were described as absoluter numbers and/or percentages. Results:(1) Clinical characteristics of patients with mid and low rectal cancer. Of the 1 074 patients, there were 713 males and 361 females, aged 63(56,70)years. The body mass index of 1 074 patients was 24(21,26)kg/m 2.For American Society of Anesthesiologists classification, there were 147 cases of stage Ⅰ, 641 cases of stage Ⅱ, 157 cases of stage Ⅲ, 2 cases of stage Ⅳ, and there were 127 cases missing data. (2) Initial colonoscopy and pathologic evaluation of tumors in patients with mid and low rectal cancer. Of the 1 074 patients, there were 787 cases (73.28%) undergoing complete colonoscopy, and there were only 197 cases (18.34%) undergoing immunohistochemical evaluation of all four mismatch repair proteins. (3) Initial imaging evaluation of patients with mid and low rectal cancer. Of the 1 074 patients, there were 842(78.40%) patients completing magnetic resonance imaging (MRI) or ultrasound evaluation, and there were 914(85.10%) patients completing chest, abdomen, and pelvis enhanced computed tomography (CT) evaluation. In the 149 patients completing rectal ultrasound evaluation, there were 122 cases (81.88%) comple-ting T staging evaluation, and there were 81 cases (54.36%) completing N staging evaluation. In the 808 patients completing rectal MRI evaluation, there were 708 cases (87.62%) completing T staging evaluation, and there were 590 cases (73.02%) completing N staging evaluation. (4) Imaging evalua-tion after neoadjuvant therapy for patients with mid and low rectal cancer. Of the 388 patients with neoadjuvant therapy, there were 332 patients (85.57%) completing MRI or ultrasound evaluation, and there were 327 patients (84.28%) completing chest, abdomen, and pelvis enhanced CT evalua-tion. In the 70 patients completing rectal ultrasound evaluation, there were 65 cases (92.86%) com-pleting T staging evaluation, and there were 49 cases (70.00%) completing N staging evaluation. In the 327 patients completing rectal MRI evaluation, there were 246 cases (75.23%) completing T staging, and there were 228 cases (69.72%) completing N staging evaluation. Conclusion:The com-pletion rate of tumor imaging evaluation at initial assessment and after neoadjuvant therapy for mid and low rectal cancer patients on a national scale is relatively good.

Objective:To investigate the effect of interleukin-12(IL-12)on liver lesions and oxidative stress pathway in Sjo-gren's syndrome mice,and to clarify the possible mechanism of liver lesions in Sjogren's syndrome.Methods:Saliva flow rate,liver function,liver pathology and IL-12 level were measured in NOD,IL-12 knockout(IL-12KO)NOD and C57BL/6(B6)mice.Different concentrations of IL-12 and JAK2,TYK2 inhibitors were applied to mouse hepatoma cells.The oxidative stress index of mouse serum and cell culture supernatants of each group were determined.Results:Compared with the other two groups of mice,the NOD mice had significantly higher GOT and GPT(P<0.05),and decreased serum GSH-PX,SOD and CAT(P<0.05).CAT,GSH,GSH-PX and SOD were decreased,while MDA was increased in mice treated with different concentrations of IL-12.JAK2/TYK2 inhibitors reversed regulatory effects of IL-12 on SOD,GSH and MDA in hepatoma cells(P<0.05).Conclusion:IL-12 may aggravated liver damage of Sj?gren's syndrome through promoting oxidative stress of hepatocytes.