Objective To explore the mechanism of honey-processed Hedysari Radix in the regulation of intestinal immunity in rats with spleen qi deficiency,which was based on G protein-coupled receptor 41(GPR41)/GPR43-mediated mitogen-activated protein kinase(MAPK)signaling pathway.Methods The three-factor composite modeling method of eating disorder,diarrhea and fatigue was used to establish a model of spleen qi deficiency,and the rats were randomly divided into model,honey-processed Hedysari Radix,probiotics and blank groups with 15 rats per group.The honey-processed Hedysari Radix group was given by gavage 12.6 g·kg-1 aqueous extract of honey-processed Hedysari Radix.The probiotics group was given 0.625 g·kg-1 bifidobacterium triple viable solution by gavage.The blank and model groups were given the same dose of distilled water by gavage.Four groups were treated for 15 d with once a day.The expression levels of GPR41,GPR43,P38 MAPK,c-Jun N-terminal kinase(JNK)and extracellular regulatory protein kinase 1/2(ERK1/2)in colon tissues were detected by Western blotting.Results The relative expression levels of GPR41 in the blank,model,honey-processed Hedysari Radix and probiotics groups were 0.95±0.07,0.45±0.03,0.84±0.19 and 0.86±0.20;the relative expression levels of GPR43 were 1.17±0.11,0.41±0.06,0.66±0.03 and 0.57±0.01;the phosphorylated ERK1/2/ERK1/2 ratios were 0.16±0.01,0.43±0.01,0.39±0.01 and 0.36±0.02;the phosphorylated JNK/JNK ratios were 0.58±0.05,1.47±0.10,0.90±0.11 and 0.90±0.11;the phosphorylated P38 MAPK/P38 MAPK ratios were 1.77±0.33,3.19±0.03,2.01±0.17 and 2.23±0.59,respectively.Compared with the model group,the differences of above indexes were statistically significant in the honey-processed Hedysari Radix and probiotics groups(P＜0.05,P＜0.01).Conclusion The mechanism of honey-processed Hedysari Radix regulating intestinal immunity in rats with spleen qi deficiency is related to the regulation of GPR41/GPR43 mediated MAPK signaling pathway.

Aim To investigate the effect of chrysoeriol on pulmonary vascular remodeling in pulmonary hyper-tension by animal experiments combined with cell ex-periments,and to explore its potential therapeutic tar-gets by network pharmacology.Methods The target of chrysoeriol was collected in Targetnet,SEA and SwissTargetPrediction database.Pulmonary arterial hy-pertension(PAH)targets were collected in the Dis-GeNET and GeneCards databases,and PPI network map was drawn in the STRING database,and key tar-gets were screened.The GO and KEGG pathway en-richment analysis was carried out through DAVID data-base and Weishengxing platform.AutoDock software was used for molecular docking of key core targets.The PAH model of rats was constructed,and the pulmo-nary hemodynamics and vascular remodeling were de-tected by echocardiography,HE and Masson staining.Primary pulmonary smooth muscle cells were extracted,and the effects of drugs on pathway proteins were de-tected in vitro.Results The results of network phar-macology showed that chrysoeriol exerted therapeutic effects on pulmonary hypertension by affecting key tar-gets such as AKT1,SRC,EGFR,MMP9 and gsk3 β,and signaling pathways such as EGFR and PI3K-AKT.Molecular docking showed that chrysoeriol had good binding ability with 5 key target genes.Animal experi-ments showed that the pulmonary hemodynamic func-tion of PAH rats was significantly improved after ad-ministration of chrysoeriol.The remodeling of small pulmonary arteries was significantly reduced.Cell ex-periments showed that chrysoeriol could inhibit the ex-pression of proliferation,migration and phenotypic transformation genes.Conclusion Chrysoeriol may play a role in the treatment of pulmonary hypertension through multiple targets.

Aim To investigate the effect of chrysoeriol on pulmonary vascular remodeling in pulmonary hyper-tension by animal experiments combined with cell ex-periments,and to explore its potential therapeutic tar-gets by network pharmacology.Methods The target of chrysoeriol was collected in Targetnet,SEA and SwissTargetPrediction database.Pulmonary arterial hy-pertension(PAH)targets were collected in the Dis-GeNET and GeneCards databases,and PPI network map was drawn in the STRING database,and key tar-gets were screened.The GO and KEGG pathway en-richment analysis was carried out through DAVID data-base and Weishengxing platform.AutoDock software was used for molecular docking of key core targets.The PAH model of rats was constructed,and the pulmo-nary hemodynamics and vascular remodeling were de-tected by echocardiography,HE and Masson staining.Primary pulmonary smooth muscle cells were extracted,and the effects of drugs on pathway proteins were de-tected in vitro.Results The results of network phar-macology showed that chrysoeriol exerted therapeutic effects on pulmonary hypertension by affecting key tar-gets such as AKT1,SRC,EGFR,MMP9 and gsk3 β,and signaling pathways such as EGFR and PI3K-AKT.Molecular docking showed that chrysoeriol had good binding ability with 5 key target genes.Animal experi-ments showed that the pulmonary hemodynamic func-tion of PAH rats was significantly improved after ad-ministration of chrysoeriol.The remodeling of small pulmonary arteries was significantly reduced.Cell ex-periments showed that chrysoeriol could inhibit the ex-pression of proliferation,migration and phenotypic transformation genes.Conclusion Chrysoeriol may play a role in the treatment of pulmonary hypertension through multiple targets.

ObjectiveTo obtain the epidemiological characteristics of re-positive cases infected with SARS-CoV-2 in Pudong New Area from March to July 2022, including clinical manifestations, duration of a negative nucleic acid conversion after tested for re-positive, and length of time from the discharge of the initial infection to the most recent re-positivity, so as to provide a scientific basis for the prevention and control of COVID-19. MethodsA questionnaire survey was conducted among the re-positive cases infected with SARS-CoV-2 after discharged from hospital/quarantine facility in Pudong New Area, and descriptive epidemiological methods were used for characteristics analysis. ResultsA total of 2 422 re-positive cases met the inclusive and exclusive criteria, with males accounting for 61.02%. The age distribution mainly fell between 18 and <60 years old, accounting for 62.39%. Clinical manifestations were predominantly asymptomatic (72.15%), followed by cough (12.03%) and sore throat (6.58%). Among the stratified randomized sample of 416 individuals, there were statistically significant differences in symptoms (χ²=262.667, P<0.001), clinical typing (χ²=12.996, P=0.001), and duration of a negative nucleic acid conversion (χ²=142.578, P<0.001) between the initial positive and re-positive instances. Besides, statistically significant differences in symptoms (χ²=13.696, P=0.016) and self-perception of the severity of re-infection (χ²=7.923, P=0.048) between the initial and re-positive cases were observed by different genders. ConclusionAmong re-positive cases, males experienced milder symptoms compared to females, and the self-perception of symptoms during re-positivity is milder than that in the initial positive infection. The length of time for negative nucleic acid conversion during the initial positive period is shorter than that during the re-positive period.

AIM To establish a GC-MS/MS method for the analysis of volatile components in Yinhu Ganmao Powder,and to determine the contents of α-pinene,camphene,sabinene,β-pinene,α-terpinene,(+)-limonene,p-cymene,1,8-cineole,linalool,L-menthol,terpinen-4-ol,DL-menthol,α-terpineol,tridecane,pulegone,caryophyllene,humulene,n-hexadecane and patchouli alcohol.METHODS The analysis was performed on a DB-624 UI capillary column(30 m×0.25 mm×1.40 μm ),and electron ionization source was adopted with multiple reaction monitoring mode.RESULTS Fifty volatile components and twenty-five liposoluble components were identified in volatile oils and medicinal material powder,respectively.Nineteen constituents showed good linear relationships within their own ranges(r ≥ 0.999 0),whose average recoveries were 84.43％-113.31％with the RSDs of less than 9.15％.CONCLUSION This stable,accurate and reproducible method can provide a reference for the quality evaluation of Yinhu Ganmao Powder.

Objective To explore the mechanism of honey-processed Hedysari Radix in the regulation of intestinal immunity in rats with spleen qi deficiency,which was based on G protein-coupled receptor 41(GPR41)/GPR43-mediated mitogen-activated protein kinase(MAPK)signaling pathway.Methods The three-factor composite modeling method of eating disorder,diarrhea and fatigue was used to establish a model of spleen qi deficiency,and the rats were randomly divided into model,honey-processed Hedysari Radix,probiotics and blank groups with 15 rats per group.The honey-processed Hedysari Radix group was given by gavage 12.6 g·kg-1 aqueous extract of honey-processed Hedysari Radix.The probiotics group was given 0.625 g·kg-1 bifidobacterium triple viable solution by gavage.The blank and model groups were given the same dose of distilled water by gavage.Four groups were treated for 15 d with once a day.The expression levels of GPR41,GPR43,P38 MAPK,c-Jun N-terminal kinase(JNK)and extracellular regulatory protein kinase 1/2(ERK1/2)in colon tissues were detected by Western blotting.Results The relative expression levels of GPR41 in the blank,model,honey-processed Hedysari Radix and probiotics groups were 0.95±0.07,0.45±0.03,0.84±0.19 and 0.86±0.20;the relative expression levels of GPR43 were 1.17±0.11,0.41±0.06,0.66±0.03 and 0.57±0.01;the phosphorylated ERK1/2/ERK1/2 ratios were 0.16±0.01,0.43±0.01,0.39±0.01 and 0.36±0.02;the phosphorylated JNK/JNK ratios were 0.58±0.05,1.47±0.10,0.90±0.11 and 0.90±0.11;the phosphorylated P38 MAPK/P38 MAPK ratios were 1.77±0.33,3.19±0.03,2.01±0.17 and 2.23±0.59,respectively.Compared with the model group,the differences of above indexes were statistically significant in the honey-processed Hedysari Radix and probiotics groups(P＜0.05,P＜0.01).Conclusion The mechanism of honey-processed Hedysari Radix regulating intestinal immunity in rats with spleen qi deficiency is related to the regulation of GPR41/GPR43 mediated MAPK signaling pathway.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective To investigate the mechanism by which suppressor of cytokine signaling 3(SOCS3)regulates microglial inflammation through nuclear factor-kappaB(NF-κB),providing novel mechanistic insights into microglial involvement in Parkinson's disease(PD)pathogenesis.Methods ① Ten male C57BL/6 mice(12 weeks old,weighing 20～25 g)were subjected to intraperitoneal injection of 15 mg/kg MPTP to establish a PD model.Rotarod test was used to assess motor function.Western blotting was employed to detect the protein expression of tyrosine hydroxylase(TH)and ionized calcium-binding adapter molecule 1(IBA-1)in the substantia nigra.RT-qPCR was utilized to measure the mRNA level of SOCS3 in the substantia nigra.Immunohistochemistry was performed to assess NF-κB p65 subunit expression.The expression of SOCS3,NF-κB and p-NF-κB was measured with Western blotting.② Microglial cell line BV2 was stimulated with 1 000 ng/mL lipopolysaccharide(LPS)for 6 h to establish an inflammatory model.Subsequently,SOCS3 was knocked down.NF-κB inhibitor BAY 11-7082 was used to treat the cells.RT-qPCR and Western blotting were used to measure the expression of SOCS3 at mRNA and protein levels.Western blotting was also applied to detect the expression of NF-κB and p-NF-κB,and ELISA was conducted to measure TNF-α and IL-1β levels in the culture supernatant.Immunofluorescence assay was carried out to localize NF-κB(nuclear vs cytoplasmic).③ A co-culture system of BV2 microglia and N2a neuroblastoma cells was established to investigate the regulatory effects of microglia on neuronal cells.MTT assay and TUNEL staining were used respectively to determine cell viability and apoptosis of N2a cells.Results ① Compared to the control mice,the PD mouse model exhibited reduced rotarod fall latency,down-regulation in TH and SOCS3(P<0.01),up-regulation in IBA-1 and increased p-NF-κB/NF-κB ratio(P<0.01).② In BV2 cells,LPS stimulation increased TNF-α,IL-1β,and p-NF-κB/NF-κB ratio(P<0.01),while down-regulated SOCS3 expression(P<0.01).SOCS3 knockdown in LPS-stimulated BV2 cells further increased the p-NF-κB/NF-κB ratio(P<0.01),increased nuclear localization of NF-κB,and elevated TNF-α and IL-1β levels(P<0.01).BAY 11-7082 treatment in these SOCS3-knockdown,LPS-stimulated cells resulted in reduced p-NF-κB/NF-κB ratio,TNF-α,and IL-1β(P<0.01),and decreased NF-κB nuclear distribution.③ LPS-stimulated BV2 cells reduced cell viability and increased cell apoptosis in N2a cells(P<0.01).SOCS3 knockdown in BV2 cells exacerbated the reduction in N2a cell viability(P<0.01)and the increase in cell apoptosis in N2a cells(P<0.01).BAY 11-7082 treatment of these SOCS3-knockdown BV2 microglia attenuated the reduction in N2a cell viability and decreased apoptosis in N2a cells(P<0.01).Conclusion SOCS3 inhibits microglia inflammatory response through down-regulation of NF-kB activity,and in turn attenuates neuronal cell death and ameliorates PD nerve injury.

Objective To demonstrate that neferine(Nef)alleviates Parkinson's disease(PD)by inhibiting microglial pyroptosis mediated through the reactive oxygen species(ROS)/NOD-like receptor protein 3(NLRP3)/Caspase-1 pathway.Methods BV2 microglial cells were divided into:control group,lipopolysaccharides(LPS)-adenosine triphosphate(ATP)group,and LPS-ATP+Nef group.Pyroptosis was induced by 1 μg/mL LPS+5 mmol/L ATP,with 2 mmol/L Nef pretreatment.Eighteen 10-12-week-old male C57BL/6 mice(22～25 g)were randomly assigned to:control(n=6),1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)(n=6),and MPTP+Nef(n=6)groups.Detection methods included:flow cytometry for pyroptosis,Cell Counting Kit-8(CCK-8)for viability,2',7'-dichlorodihydrofluorescein diacetate(DCFH-DA)for ROS,commercial kits for malondialdehyde(MDA),superoxide dismutase(SOD),glutathione(GSH),ELISA/Western blot for interleukin-1β(IL-1β)/IL-18,immunofluorescence/immunohistochemistry for NLRP3/Caspase-1,tyrosine hydroxylase(TH)immunohistochemistry,hematoxylin-eosin staining for neuropathology,and modified neurological severity score(mNSS).Results Versus control,LPS-ATP group showed decreased viability(P=0.002),increased pyroptosis(P<0.001),elevated ROS(P<0.001)/MDA(P<0.001)/IL-1β(P<0.001)/IL-18(P<0.001),upregulated NLRP3(P<0.001)/Caspase-1(P<0.001),and reduced GSH(P<0.001)/SOD(P<0.001).Nef treatment reversed these effects(all P<0.05).According to the results of murine studies,compared with the control group,the MPTP group had increased mNSS(P<0.001)/tissue ROS(P<0.001),downregulated TH(P<0.001),upregulated NLRP3(P<0.001)/Caspase-1(P<0.001).Nef treatment significantly attenuated the MPTP-induced deleterious effects(P<0.05).Histopathological analysis revealed that control group exhibited uniformly distributed hippocampal neurons with distinct nuclear morphology;MPTP group showed neuronal swelling,interstitial edema,and nuclear atrophy;MPTP+Nef group demonstrated ameliorated neuronal damage.Conclusion Nef inhibits microglial pyroptosis via ROS/NLRP3/Caspase-1 axis,ameliorating PD neuroinflammation and pathology.