OBJECTIVE To study the mechanism of action of Rehmannia glutinosa-medicated serum （RG） in regulating lipopolysaccharide （LPS）-induced polarization of BV2 microglia to interfere with neuroinflammation. METHODS An in vitro neuroinflammation model of BV2 cells induced by LPS was established. Cells were divided into control group， LPS group， 10%RG group， 20%RG group， BAY 11-7082 [nuclear factor kappa B （NF-κB） inhibitor] group， and 20%RG+BAY 11-7082 group. Except for the control group， cells in all other groups were pretreated with corresponding drugs for 12 h and then stimulated with LPS for 24 h. The morphology of cells in each group was observed， and the fluorescence intensity of ionized calcium binding adaptor molecule 1 （Iba-1）， inducible nitric oxide synthase （iNOS）， CD206， the mRNA expression of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， IL-1β， iNOS， IL-4， IL-10， transforming growth factor-β （TGF-β）， arginase-1 （Arg-1）， and the Toll-like receptor 4 （TLR4）/NF-κB/NOD-like receptor thermal protein domain associated protein 3 （NLRP3） signaling pathway-related protein expression were detected. RESULTS Compared with the control group， the LPS group showed significant changes in cell morphology， exhibiting a typical M1 activated morphology. The fluorescence intensity of Iba-1 and iNOS， the relative expression levels of TNF-α， IL-6， IL-1β， iNOS mRNA， the relative expression levels of TLR4， NLRP3， caspase-1 p20， IL-1β p17 protein， and the phosphorylation levels of NF-κB p65 and inhibitor of nuclear factor kappa B α were significantly increased （P＜0.05）. The fluorescence intensity of CD206 and the relative expression levels of IL-4， IL-10， TGF-β， and Arg-1 mRNA were significantly reduced （P＜0.05）. Compared with the LPS group， the changes in the above indicators in the cells of the 10%RG group， 20%RG group， BAY 11-7082 group， and 20%RG+BAY 11-7082 group were significantly reversed （P＜0.05）， and there was no statistically significant difference in the comparison of the last three groups （P＞0.05）. CONCLUSIONS RG can effectively inhibit the overall activation of microglia and correct their M1/M2 polarization imbalance， and its mechanism may be closely related to the inhibition of excessive activation of the TLR4/NF-κB/NLRP3 signaling pathway.

ObjectiveTo preliminarily explore the active components and target pathways of Angelicae Sinensis Radix-Polygonati Rhizoma （ASR-PR） herb pair in the treatment of simple obesity through network pharmacology and molecular docking， and to verify and investigate its mechanism of action via animal experiments. MethodsThe chemical constituents and targets of ASR and PR were predicted using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）. Targets related to simple obesity were identified by retrieving the GeneCards， Online Mendelian Inheritance in Man （OMIM）， Pharmacogenomics Knowledgebase （PharmGKB）， and DisGeNET databases. The intersection of drug and disease targets was used to construct an active component-target network using Cytoscape software. This network was imported into the STRING database to construct a protein-protein interaction （PPI） network， and topological analysis was conducted to identify core genes. Gene Ontology （GO） analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis and mapping were performed using the DAVID database and the Microbioinformatics platform. AutoDock 1.5.7 software was used to perform molecular docking between the top five active components and core targets. An animal model of simple obesity was established by feeding C57BL/6J mice a high-fat diet. The mice were administered ASR （2.06 g·kg^-1）， PR （2.06 g·kg^-1）， or ASR-PR （4.11 g·kg^-1） for 10 weeks， while the model group received an equal volume of purified water by gavage. After the administration period， the mice were sacrificed to measure body fat weight and serum levels of total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein （HDL）， and low-density lipoprotein （LDL）. Hematoxylin-eosin （HE） staining was used to observe histopathological sections of liver and adipose tissue. Serum levels of leptin， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） were determined by enzyme-linked immunosorbent assay （ELISA）， and the mRNA expression levels of epidermal growth factor receptor （EGFR） and signal transducer and activator of transcription 3 （STAT3） in liver tissue were detected by real-time quantitative polymerase chain reaction （Real-time PCR）. ResultsNetwork pharmacology and molecular docking results indicated that the treatment of simple obesity by ASR-PR may involve the regulation of protein expression of core targets EGFR and STAT3 by its main components MOL009760 （Siberian glycoside A_qt）， MOL003889 （methyl protodioscin_qt）， MOL009766 （resveratrol）， MOL006331 （4′，5-dihydroxyflavone）， and MOL004941 （baicalin）， thereby modulating the PI3K/Akt and JAK/STAT signaling pathways. The animal experiment results showed that compared with the normal group， the model group had significantly increased body weight， body fat weight， and serum levels of TG， TC， TNF-α， IL-6， and leptin （P<0.01）. EGFR mRNA expression was significantly elevated （P<0.05）， while STAT3 mRNA expression was significantly decreased （P<0.01）. Histological analysis revealed disordered hepatic architecture in the model group， with pronounced lipid vacuoles， cytoplasmic loosening， lipid accumulation， and steatosis. Adipocytes in white adipose tissue （WAT） and brown adipose tissue （BAT） of the model group exhibited markedly increased diameters， reduced cell counts per unit area， and irregular morphology. Compared with the model group， the ASR-PR group significantly reduced body weight， body fat weight， serum TC， IL-6， TNF-α， leptin levels， and EGFR mRNA expression （P<0.01）. TG levels were also significantly decreased （P<0.05）， while STAT3 mRNA expression was significantly increased （P<0.01）. Histopathological improvements included reduced size and number of hepatic lipid vacuoles and restoration of liver cell morphology toward that of the normal group. The diameter of adipocytes significantly decreased， and the number of adipocytes per unit area increased. ConclusionASR-PR may regulate the expression of key target proteins such as EGFR and STAT3 via its core active components， modulate the PI3K/Akt and JAK/STAT signaling pathways， repair damaged liver and adipose tissues， and thereby alleviate the progression of obesity in mice.

ObjectiveTo preliminarily explore the active components and target pathways of Angelicae Sinensis Radix-Polygonati Rhizoma （ASR-PR） herb pair in the treatment of simple obesity through network pharmacology and molecular docking， and to verify and investigate its mechanism of action via animal experiments. MethodsThe chemical constituents and targets of ASR and PR were predicted using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）. Targets related to simple obesity were identified by retrieving the GeneCards， Online Mendelian Inheritance in Man （OMIM）， Pharmacogenomics Knowledgebase （PharmGKB）， and DisGeNET databases. The intersection of drug and disease targets was used to construct an active component-target network using Cytoscape software. This network was imported into the STRING database to construct a protein-protein interaction （PPI） network， and topological analysis was conducted to identify core genes. Gene Ontology （GO） analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis and mapping were performed using the DAVID database and the Microbioinformatics platform. AutoDock 1.5.7 software was used to perform molecular docking between the top five active components and core targets. An animal model of simple obesity was established by feeding C57BL/6J mice a high-fat diet. The mice were administered ASR （2.06 g·kg^-1）， PR （2.06 g·kg^-1）， or ASR-PR （4.11 g·kg^-1） for 10 weeks， while the model group received an equal volume of purified water by gavage. After the administration period， the mice were sacrificed to measure body fat weight and serum levels of total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein （HDL）， and low-density lipoprotein （LDL）. Hematoxylin-eosin （HE） staining was used to observe histopathological sections of liver and adipose tissue. Serum levels of leptin， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） were determined by enzyme-linked immunosorbent assay （ELISA）， and the mRNA expression levels of epidermal growth factor receptor （EGFR） and signal transducer and activator of transcription 3 （STAT3） in liver tissue were detected by real-time quantitative polymerase chain reaction （Real-time PCR）. ResultsNetwork pharmacology and molecular docking results indicated that the treatment of simple obesity by ASR-PR may involve the regulation of protein expression of core targets EGFR and STAT3 by its main components MOL009760 （Siberian glycoside A_qt）， MOL003889 （methyl protodioscin_qt）， MOL009766 （resveratrol）， MOL006331 （4′，5-dihydroxyflavone）， and MOL004941 （baicalin）， thereby modulating the PI3K/Akt and JAK/STAT signaling pathways. The animal experiment results showed that compared with the normal group， the model group had significantly increased body weight， body fat weight， and serum levels of TG， TC， TNF-α， IL-6， and leptin （P<0.01）. EGFR mRNA expression was significantly elevated （P<0.05）， while STAT3 mRNA expression was significantly decreased （P<0.01）. Histological analysis revealed disordered hepatic architecture in the model group， with pronounced lipid vacuoles， cytoplasmic loosening， lipid accumulation， and steatosis. Adipocytes in white adipose tissue （WAT） and brown adipose tissue （BAT） of the model group exhibited markedly increased diameters， reduced cell counts per unit area， and irregular morphology. Compared with the model group， the ASR-PR group significantly reduced body weight， body fat weight， serum TC， IL-6， TNF-α， leptin levels， and EGFR mRNA expression （P<0.01）. TG levels were also significantly decreased （P<0.05）， while STAT3 mRNA expression was significantly increased （P<0.01）. Histopathological improvements included reduced size and number of hepatic lipid vacuoles and restoration of liver cell morphology toward that of the normal group. The diameter of adipocytes significantly decreased， and the number of adipocytes per unit area increased. ConclusionASR-PR may regulate the expression of key target proteins such as EGFR and STAT3 via its core active components， modulate the PI3K/Akt and JAK/STAT signaling pathways， repair damaged liver and adipose tissues， and thereby alleviate the progression of obesity in mice.

Approximately 30%-40% of epilepsy patients do not respond well to adequate anti-seizure medications (ASMs), a condition known as pharmacoresistant epilepsy. The management of pharmacoresistant epilepsy remains an intractable issue in the clinic. Its early prediction is important for prevention and diagnosis. However, it still lacks effective predictors and approaches. Here, a classical model of pharmacoresistant temporal lobe epilepsy (TLE) was established to screen pharmacoresistant and pharmaco-responsive individuals by applying phenytoin to amygdaloid-kindled rats. Ictal electroencephalograms (EEGs) recorded before phenytoin treatment were analyzed. Based on ictal EEGs from pharmacoresistant and pharmaco-responsive rats, a convolutional neural network predictive model was constructed to predict pharmacoresistance, and achieved 78% prediction accuracy. We further found the ictal EEGs from pharmacoresistant rats have a lower gamma-band power, which was verified in seizure EEGs from pharmacoresistant TLE patients. Prospectively, therapies targeting the subiculum in those predicted as "pharmacoresistant" individual rats significantly reduced the subsequent occurrence of pharmacoresistance. These results demonstrate a new methodology to predict whether TLE individuals become resistant to ASMs in a classic pharmacoresistant TLE model. This may be of translational importance for the precise management of pharmacoresistant TLE.
Epilepsy, Temporal Lobe/diagnosis* ; Animals ; Drug Resistant Epilepsy/drug therapy* ; Electroencephalography/methods* ; Rats ; Anticonvulsants/pharmacology* ; Neural Networks, Computer ; Male ; Humans ; Phenytoin/pharmacology* ; Adult ; Disease Models, Animal ; Female ; Rats, Sprague-Dawley ; Young Adult ; Convolutional Neural Networks

Gentiopicroside(GPS)is the main active ingredient extracted from Gentiaceae.It has anti-inflammatory,antioxidant,analgesic,anti-fibrosis,inhibition of tumor cell proliferation and improvement of glucose and lipid metabolism.Gentiaceae shows a wide range of application prospects in the treatment of diabetes,liver diseases,bone and joint diseases and other diseases.This paper reviewed the pharmacokinetics of gentiopicrin,including its pharmacokinetic properties in different animal models,and its mechanism and targets in the treatment of diabetes mellitus and its complications,liver injury,bone and joint diseases.Studies have shown that gentiopictin exerts its therapeutic effects by regulating various signaling pathways,such as PI3K/AKT,FOXO1,PPAR-γ,NF-κB,etc.Although the current research has made some progress,there are still limitations,such as most studies focused on animal models and in vitro experiments,lack of high-quality clinical evidence-based trials support.Future studies should further explore the new targets and signal transduction pathways of gentiopicroside,improve its bioavailability,and strengthen the research of traditional Chinese medicine compounds,so as to give full play to the advantages of holistic treatment of traditional Chinese medicine.

Objective:To evaluate the efficacy and safety of Rituximab (RTX) combined with short-term use of glucocorticoids in the treatment of the initial episode of steroid-sensitive nephrotic syndrome (SSNS).Methods:A retrospective case summary.A total of 30 children with SSNS treated in the Department of Intrarenal Rheumatism and Immunology, Xuzhou Children′s Hospital from December 2021 to March 2023, were enrolled in this study.They were given a standard dose of RTX (375 mg/m 2) and glucocorticoids for a short term.The patients were followed up for 1 year, and the general condition, changes in CD19 + B lymphocytes expression after RTX treatment, the relapse rate, the median relapse-free survival and adverse reactions of RTX were recorded.Kaplan-Meier method was used to analyze the relapse-free survival time. Results:CD19 + B lymphocytes were depleted 2 weeks after RTX treatment, and the median time required for CD19 + B lymphocytes reconstitution was 5 months after RTX treatment.The 1-year relapse-free rate was 90.00%, and the median relapse-free survival was 11 months.The glucocorticoid discontinuation rate was 93.33% in 3 months after RTX treatment, and 100% in 6 and 12 months after RTX treatment.Adverse reactions included infusion reactions in 7 cases (23.33%), neutropenia/leukopenia in 5 cases (16.67%), hypoimmunoglobulinemia in 10 cases (33.33%), infections in 4 cases.One case was complicated with severe influenza A virus infection after CD19 + B lymphocytes reconstruction. Conclusions:A standard dose of RTX can significantly reduce the relapse frequency, maintain long-term remission of proteinuria, and reduce the dose of glucocorticoids in patients at the initial episode of SSNS.Thus, it is worthy of clinical promotion.

Development of curative drugs for hepatitis B virus (HBV) infection is facing challenges currently. Current treatment of chronic hepatitis B (CHB) still bases on optimizing the existing therapeutic regimens. Meanwhile, with the rapid development of immunology and molecular technologies, high-sensitivity and quantification have become the mainstream of diagnostic kits development in terms of HBV laboratory diagnosis, and new biomarkers are being developed and widely used clinically. Advancement of laboratory technology favors the personalized management of HBV infection and CHB in one hand and on the other hand, it makes the interpretation of the results of these biomarkers more complicated. The sensitivity of HBV DNA assay is closely related to the natural history of HBV infection and the indication of antiviral therapy. Application of ultra-sensitive HBV DNA assay may cause unnecessary excessive concern for the management of low level viremia on nucleos(t)ide analogue treatment. Availability of ultra-sensitive HBsAg assay challenges the antiviral therapy indication in special populations and the concept of clinical cure of CHB. Necessity of quantification of all HBV serological (immunological) markers remains an issue of debate. Meanwhile, the clinical scenarios of novel markers such as HBV pregenomic RNA and hepatitis B core-related antigen should be defined to avoid misuse, overuse and over-interpretation of their clinical significance.

Gentiopicroside(GPS)is the main active ingredient extracted from Gentiaceae.It has anti-inflammatory,antioxidant,analgesic,anti-fibrosis,inhibition of tumor cell proliferation and improvement of glucose and lipid metabolism.Gentiaceae shows a wide range of application prospects in the treatment of diabetes,liver diseases,bone and joint diseases and other diseases.This paper reviewed the pharmacokinetics of gentiopicrin,including its pharmacokinetic properties in different animal models,and its mechanism and targets in the treatment of diabetes mellitus and its complications,liver injury,bone and joint diseases.Studies have shown that gentiopictin exerts its therapeutic effects by regulating various signaling pathways,such as PI3K/AKT,FOXO1,PPAR-γ,NF-κB,etc.Although the current research has made some progress,there are still limitations,such as most studies focused on animal models and in vitro experiments,lack of high-quality clinical evidence-based trials support.Future studies should further explore the new targets and signal transduction pathways of gentiopicroside,improve its bioavailability,and strengthen the research of traditional Chinese medicine compounds,so as to give full play to the advantages of holistic treatment of traditional Chinese medicine.

ObjectiveTo evaluate the effects of Wuhua herbal tea on chronic unpredictable mild stress (CUMS)-induced depression and explore its mechanism of action in combating depression.MethodsWe tested the antidepressant effects of Wuhua herbal tea in a rat model of CUMS-induced depression using fluoxetine as a positive control. The rats were divided into four groups: control group, model group, fluoxetine group, and Wuhua herbal tea group. The rats underwent body weight measurements, sucrose preference test, and open-field test. Enzyme-linked immunosorbent assay kits were used to detect the serum levels of serotonin, dopamine, adrenocorticotropic hormone (ACTH), corticosterone, norepinephrine, and interleukin-6. Intergroup comparisons and detection of brain-derived neurotrophic factor (BDNF), cAMP-response element binding protein (CREB), Janus kinase 2 (JAK2), and signal transducer and activator of transcription 3 (STAT3) mRNA expression in the hippocampus were performed using RT-PCR. Immunohistochemistry was used to identify the expression of phosphorylated JAK2 (p-JAK2) and phosphorylated STAT3 (p-STAT3) proteins in hippocampal paraffin sections of CUMS rats.ResultsCompared with the control group, the model group rats had depressive tendencies, exhibiting low vitality and interest in various behavioral indicators which were signs of despair. The Wuhua herbal tea group statistically increased the levels of serotonin and dopamine in the serum of CUMS rats to varying degrees (P = .015 and P = .002); reduced serum levels of ACTH, corticosterone, norepinephrine, and interleukin-6 (all P .05); and decreased mRNA expression of BDNF, CREB, JAK2, and STAT3 in the hippocampus (all P .05); and decreased p-STAT3 protein levels (P = .006).ConclusionWuhua herbal tea shows antidepressant potential in CUMS rats by modulating the HPA axis and inhibiting JAK2-STAT3 overactivation, alleviating neuroinflammation. It also restores BDNF-CREB pathway function, reducing depressive symptoms.