Diabetic nephropathy （DKD）， as a common microvascular complication of diabetes mellitus （DM）， is a major cause of end-stage renal disease （ESRD）. Its clinical manifestations include increased urinary protein excretion， thickening of the glomerular basement membrane， and renal tubulointerstitial fibrosis. The pathogenesis of DKD is complex and involves multiple factors， including disordered glucose metabolism， hemodynamic alterations， and oxidative stress. Although modern medical approaches can alleviate certain symptoms， they still have limitations such as insufficient therapeutic targeting and prominent adverse effects. The transforming growth factor-β/Smad （TGF-β/Smad） signaling pathway is not only a tissue fibrosis pathway that has attracted considerable attention in recent years， but also regulates multiple protein molecules， including the glomerular podocyte slit diaphragm protein Podocin， interleukin-1β （IL-1β）， and superoxide dismutase （SOD）， thereby participating in various pathological processes and ultimately mediating renal injury. Flavonoid compounds， owing to their sustained pharmacological effects， broad spectrum of action， and high safety profile， have become ideal candidates for targeted therapy research in DKD. Existing studies have shown that these compounds can exert inhibitory effects on renal fibrosis， alleviate inflammatory responses， protect podocytes， and reduce oxidative stress by regulating the interactions between the TGF-β/Smad signaling pathway and the aforementioned protein molecules， thereby maintaining renal structure and function， reducing proteinuria， and significantly improving DKD lesions. This review briefly outlines the composition and functions of the TGF-β/Smad signaling pathway， elucidates the mechanisms by which this pathway regulates DKD， and focuses on summarizing major studies from the past decade on flavonoid-based interventions in DKD through targeted inhibition of the TGF-β/Smad signaling pathway. Furthermore， it discusses the considerable therapeutic potential of flavonoids in the treatment of this disease， aiming to provide a scientific basis for future clinical prevention and treatment of DKD and to promote the development of targeted drugs.

OBJECTIVE To analyze the chemical constituents and absorbed prototype components in blood of Zhenyang jiuxin decoction， and explore its potential active substances in the treatment of chronic heart failure （CHF）. METHODS SD rats were divided into a blank group （distilled water） and administration groups with blood collection at 0， 15， 30 and 60 min after dosing （14.96 g/kg calculated by crude drug）， with 2 rats in each group. Intragastric administration was conducted once every 12 hours for 3 consecutive days. After the last administration， rat blood was collected to prepare drug-containing serum. UPLC-Q-Exactive Orbitrap HRMS combined with the Global Natural Products Social Molecular Networking technology was adopted to identify the chemical constituents of Zhenyang jiuxin decoction and the absorbed prototype components in blood in drug-containing serum. Moreover， network pharmacology， molecular docking and molecular dynamics simulation were used to predict the potential active components and action targets for CHF treatment. RESULTS A total of 116 chemical constituents were identified from Zhenyang jiuxin decoction， including flavonoids （29 species）， terpenoids （26 species）， saponins （22 species） and other compounds. Twenty absorbed prototype components in blood were detected in drug-containing serum， including icariin， ginsenoside Rg 1 and atractylenolide Ⅰ. Six key active components （icariin， ginsenoside Rg 1 ， atractylenolide Ⅰ， hexadecanamide， etc.） and six core k ey targets such as glycogen synthase kinase-3β （GSK-3β）， amyloid precursor protein （APP） and epidermal growth factor receptor （EGFR） were screened out via network pharmacology. Molecular docking results showed that all key active components had favorable binding activity with core targets； among them， icariin had the strongest binding capacity to APP. Molecular dynamics simulation verified that the complex formed by icariin and APP possessed excellent stability. CONCLUSIONS The potential active substances of Zhenyang jiuxin decoction against CHF are icariin， ginsenoside Rg₁， atractylenolide Ⅰ and other ingredients， which act on APP， EGFR， GSK-3β and other targets. APP may serve as one of the important action targets of icariin.

OBJECTIVE To analyze the chemical constituents and absorbed prototype components in blood of Zhenyang jiuxin decoction， and explore its potential active substances in the treatment of chronic heart failure （CHF）. METHODS SD rats were divided into a blank group （distilled water） and administration groups with blood collection at 0， 15， 30 and 60 min after dosing （14.96 g/kg calculated by crude drug）， with 2 rats in each group. Intragastric administration was conducted once every 12 hours for 3 consecutive days. After the last administration， rat blood was collected to prepare drug-containing serum. UPLC-Q-Exactive Orbitrap HRMS combined with the Global Natural Products Social Molecular Networking technology was adopted to identify the chemical constituents of Zhenyang jiuxin decoction and the absorbed prototype components in blood in drug-containing serum. Moreover， network pharmacology， molecular docking and molecular dynamics simulation were used to predict the potential active components and action targets for CHF treatment. RESULTS A total of 116 chemical constituents were identified from Zhenyang jiuxin decoction， including flavonoids （29 species）， terpenoids （26 species）， saponins （22 species） and other compounds. Twenty absorbed prototype components in blood were detected in drug-containing serum， including icariin， ginsenoside Rg 1 and atractylenolide Ⅰ. Six key active components （icariin， ginsenoside Rg 1 ， atractylenolide Ⅰ， hexadecanamide， etc.） and six core k ey targets such as glycogen synthase kinase-3β （GSK-3β）， amyloid precursor protein （APP） and epidermal growth factor receptor （EGFR） were screened out via network pharmacology. Molecular docking results showed that all key active components had favorable binding activity with core targets； among them， icariin had the strongest binding capacity to APP. Molecular dynamics simulation verified that the complex formed by icariin and APP possessed excellent stability. CONCLUSIONS The potential active substances of Zhenyang jiuxin decoction against CHF are icariin， ginsenoside Rg₁， atractylenolide Ⅰ and other ingredients， which act on APP， EGFR， GSK-3β and other targets. APP may serve as one of the important action targets of icariin.

OBJECTIVE To study the toxic mechanism of Mahuang xixin fuzi decoction （MXF） on normal mice. METHODS Totally 48 SPF grade BABL/C mice were randomly divided into blank group， MXF low-dose， medium-dose and high-dose groups， with 12 mice in each group. MXF low-dose， medium-dose and high-dose groups were given drug intragastrically at the dose of 11.262， 33.786， 45.050 g/kg， respectively. Blank group was administered with equal volume of normal saline， once a day， for consecutive 7 d. The body weight， anal temperature and survival rate were recorded， organ index and serum biochemical factors were detected. After the last administration， fecal samples of mice were collected and detected by UHPLC-QE/MS. RESULTS Compared with blank group， the body weight was decreased significantly from the 3rd to the 5th day after administration in MXF medium-dose group， and from the 2nd to the 7th day after administration in MXF high-dose group significantly （P＜0.05）. There was no significant difference in anal temperature among the treatment groups； the average survival rates of MXF medium-dose and high-dose groups were 58.33% and 50.00%， respectively. Compared with blank group， there were significant difference in the indexes of spleen， lung， thymus， adrenal gland and creatine kinase in MXF low-dose， medium-dose and high-dose groups， the testis index in MXF low-dose and high-dose groups， the creatine kinase isoenzyme/creatine kinase ratio in MXF low-dose group， the α-hydroxybutyrate dehydrogenase， lactate dehydrogenase and alkaline phosphatase in MXF medium-dose group， the urine and cystatin C in MXF medium-dose and high-dose groups （P＜0.05）. The fecal metabonomic analysis showed that 19 biomarkers such as phenylpyruvate， L-tyrosine， phosphatidylcholine， glycerol 3-phosphate in MXF low-dose， medium-dose and high-dose groups were significantly different from those in the blank group. CONCLUSIONS When MXF reaches a certain dose， it will have adverse effects on the body weight， multiple organs and serum biochemical indicators of mice， thus showing a certain toxic effect. Its mechanism may be related to disrupting the intestinal flora metabolism， causing inflammatory reaction and immune disorders.

ObjectiveTo characterize the efficacy components of Guizhi Jia Gegentang（GGT） in intervening influenza virus pneumonia by ultra-performance liquid chromatography-quadrupole-electrostatic field orbitrap high resolution mass spectrometry（UPLC-Q-Exactive Orbitrap MS）. MethodBALB/c mice were randomly divided into normal group and GGT group（36 g·kg^-1·d^-1） with six mice in each group. GGT group was continuously administered GGT extract for 5 d， while the normal group was administered an equal amount of ultrapure water. Serum and lung tissue were collected after administration， and UPLC-Q-Exactive Orbitrap MS was used to characterize the prototypical and metabolic components of GGT in serum and lung tissue of mice. The components existed simultaneously in the serum and lung tissue of mice from the GGT group were defined as its functional components， and the targets of efficacy components were searched by SwissTargetPrediction database， and GeneCards database was used to query the target of influenza virus pneumonia， and then the intersection was taken to obtain potential targets of GGT for intervening in the disease. Protein-protein interaction（PPI） network analysis of potential targets was performed by STRING database， and Kyoto Encyclopedia of Genes and Genomes（KEGG） pathway enrichment analysis on potential targets was performed by Metascape. ResultA total of 29 prototypical components and 28 metabolic components of GGT were detected in the drug-containing serum of mice， of which 11 prototypical components and 4 metabolic components were detected in the lung tissue of mice. The main metabolic pathways included reduction， hydroxylation， methylation， glucuronidation and sulfation. The results of PPI network and KEGG analysis showed that these functional components may act through their effects on targets such as albumin（ALB）， epidermal growth factor receptor（EGFR）， steroid receptor coactivator（SRC）， Toll-like receptor 4（TLR4）， nuclear transcription factor（NF）-κB and adhesion junction. ConclusionThe 11 prototypical components and 4 metabolites present simultaneously in the drug-containing serum and lung tissue of mice may be the potential therapeutic components of GGT in interfering with influenza viral pneumonia， and act through interfering with inflammatory metabolic pathways. This study can provide a reference for the mechanism study of GGT in the treatment of influenza viral pneumonia.

Objective To study the mechanism of Chaihu Guizhi Decoction(CGD)in the treatment of influenza and staphylococcus aureus co-infection.Methods The co-infection model of influenza and staphylococcus aureus was established and CGD was used to intervene.The chemical components of CGD were qualitatively analyzed by UPLC-Q-Exactive/MS technology.The potential action targets of chemical components in CGD and the related targets of influenza Staphylococcus aureus co-infection were mined by network pharmacology method.The"component target disease"network was constructed.Core targets were selected according to degree ranking.Core action pathways were enriched by KEGG analysis and GO annotation analysis.The core target was verified by RT-qPCR,and the interaction between the core component and the key target was verified by molecular docking.Results CGD could significantly improve the decrease of body weight and thymus index(P<0.05)caused by co-infection.The lung index(P<0.05),relative amount of MmRNA expression(P<0.05)and bacterial load(P<0.05)were decreased,and the survival rate was improved.51 chemical constituents were identified from CGD.Through network pharmacological analysis,107 related targets corresponding to CGD treatment of bacterial pneumonia secondary to influenza were excavated.TNF,AKT1,ALB,VEGFA,MAPK3,PTGS2,STAT3,EGFR and other targets with strong correlation,mainly involved Fc epsilon RI signal pathway,GnRH signal pathway,NF-κB signal path,etc.Molecular docking study showed that the main active component of CGD,including oroxyloside,baicalein and wogonin have strong affinity with TNF,PTGS2 and EGFR targets.Compared with co-infection model group,in CGD group TNF-α、EGFR and PTGS2 increased significantly(P<0.05).Conclusion The main active ingredient of CGD is oroxyloside,baicalein and wogonin.TNF-α,PTGS2,EGFR and other targets to played a role in the treatment of influenza staphylococcus aureus co-infection.

The aim of this study was to evaluate the roles of interleukin (IL)-17A in risk stratification and prognosis of patients with sepsis-associated acute kidney injury (SAKI). Methods: We enrolled 146 sepsis patients (84 non-SAKI and 62 SAKI patients) admitted to the emergency department from November 2020 to November 2021. Patients with SAKI were differentiated based on the severity of acute kidney injury. All clinical parameters were evaluated upon admission before administering antibiotic treatment. Inflammatory cytokines were assessed using flow cytometry and the Pylon 3D automated immunoassay system (ET Healthcare). In addition, a receiver operating characteristic (ROC) curve was utilized to determine the prognostic values of IL-17A in SAKI. Results: The levels of creatinine, IL-2, IL-4, IL-6, IL-17A, tumor necrosis factor alpha, C-reactive protein, and procalcitonin (PCT) were significantly higher in the SAKI group than in the non-SAKI group (p < 0.05). The level of IL-17A revealed significant differences among stages 1, 2, and 3 in SAKI patients (p < 0.05). The mean levels of PCT, IL-4, and IL-17A were significantly higher in the non-survival group than in the survival group in SAKI patients (p < 0.05). In addition, the area under the ROC curve of IL-17A was 0.811. Moreover, the IL-17A cutoff for differentiating survivors from non-survivors was 4.7 pg/mL, of which the sensitivity and specificity were 77.4% and 71.0%, respectively. Conclusion: Elevated levels of IL-17A could predict that SAKI patients are significantly prone to worsening kidney injury with higher mortality. The usefulness of IL-17A in treating SAKI requires further research.

Background: Naohuan Dan is a prescription used to treat dementia. This study aims to assess the effectiveness and safety of Naohuan Dan combined with idebenone in treating mild cognitive impairment (MCI) with kidney deficiency and phlegm stasis. Materials and methods: This retrospective, observational clinical trial enrolled 64 MCI patients treated in the Sun Yat-sen Memorial Hospital, Zhongshan University, from May 1, 2019, to April 30, 2022. The 32 patients in the treatment group received Naohuan Dan combined with idebenone, whereas the 32 patients in the control group were treated with idebenone alone. The observation lasted for 12 weeks. The primary outcomes were the Mini-Mental State Examination (MMSE) score and clinical efficacy, whereas secondary outcomes included the Montreal Cognitive Assessment (MCS) score, the activities of daily living (ADL) score, the Geriatric Depression Scale (GDS) score, the traditional Chinese medicine (TCM) syndrome score, and changes in serum markers. Neuron-specific enolase (NSE), interleukin 8 (IL-8), and tumor necrosis factor α (TNF-α) were taken as the serological indicators for evaluating cognitive function. Adverse events in both groups were recorded during the treatment period. Results: The treatment group demonstrated higher MMSE scores and clinical efficacy than the control group, specifically in the scores of spatial orientation, attention and calculation, and language proficiency in the MMSE scale. The treatment group outperformed the control group in MCS, ADLs, GDS, and TCM syndrome scores. Furthermore, the treatment group was superior to the control group in recovering the levels of NSE, IL-8, and TNF-α. In addition, the treatment group had lower incidence of adverse reactions such as nausea and poor appetite than the control group. Conclusions: The 12-week treatment with Naohuan Dan combined with idebenone significantly improved the cognitive function and daily life abilities, lowered the depression levels, and reduced the occurrence of adverse events among patients with MCI. These findings offer valuable insights into the efficacy of integrating TCM with Western medicine in the clinical management of MCI. (ClinicalTrials.gov ID: NCT05931029; https://clinicaltrials.gov/study/NCT05931029?cond=Naohuan%20Dan&rank=1)

Heilongjiang Province has unique geographical environment, which makes the difference in population morbidity. This paper summarizes the physiological and pathological characteristics of stroke in Longjiang area from the regional factors and dietary factors. The paper also summarizes the treatment thoughts of acupuncture and moxibustion doctors in Longjiang area, mainly including five aspects: Knowing all diseases but treating the essence one, combining theory and practice, combining Chinese and western medicine, combining acupuncture and Chinese medicine, preventing diseases through learning and observing tiny clues. This article aims to summarize the experience of Longjiang acupuncture scholars and enriches the medical connotation of Longjiang area.

OBJECTIVE：To study the effects of Mahuang xixin fuzi decoction on Toll-like receptors （TLRs）response and cytochrome C oxidase （Cyt-CO）-mediated apoptosis regulation in mice with influenza disease of kidney-yang deficiency. METHODS：Totally 48 male Balb/c mice were randomly divided into normal group （n＝12）and modeling group （n＝36）. The modeling group was intraperitoneally injected with estradiol benzoate solution （8 mg/kg）and intranasally injected with influenza virus H 1N1（20 μL/mice）to establish the influenza disease compound model of kidney-yang deficiency. After modeling ，the mice were randomly divided into model group ，positive drug group （Oseltamivir phosphate capsules ，0.195 g/kg），Mahuang xixin fuzi decoction group （1.802 g/kg，by crude dru g），with 12 mice in each group. Each group was given relevant medicine intragastrically，normal group and model group were given， corresponding volume of normal saline intragastrically 20 mL/kg，once a day ，for consecutive 6 days. During admi-nistration，body weight and anal temperature of mice were mail：xsy407861520@163.com measured daily ；the percentage of initial body weight was calculated. After last medication ，the organ （spleen，thymus and lung ）indexes were calculated ；the pathological changes of lung tissue were observed. The viral load of influenza A virus H 1N1 in lung tissue was detected （reflected by M gene mRNA expression）；mRNA expressions of TLR3，TLR7，myeloid differentiation factor （MyD88）and Caspase- 3 in cardiac tissue as well as the activity of Cyt-CO and the content of cytochrome C （Cyt-C）were also determined. RESULTS ：Compared with normal group，initial body weight percentage and anal temperature of the model group continued to decrease （P＜0.05）；the spleen and thymus indexes were decreased significantly （P＜0.05），while lung index was increased significantly （P＜0.05）；the lung tissue lesions were serious. Viral load in lung tissue ，mRNA expressions of TLR 3，TLR7，MyD88 and Caspase- 3 in cardiac tissue as well as the content of Cyt-C were increased significantly （P＜0.05 or P＜0.01），while the activity of Cyt-CO in cardiac tissue was significantly decreased （P＜0.01）. Compared with model group ，initial body weight percentage and anal temperature of mice in Mahuang xixin fuzi decoction group showed an increasing trend from the fourth day of administration （P＜0.05 or P＜0.01）. The spleen and thymus indexes were increased significantly （P＜0.05），while the lung index was significantly decreased （P＜0.05）；the pathological injury of lung tissue was significantly improved ；viral load in lung tissue ，mRNA expressions of TLR 3 and Caspase- 3 as well as the content of Cyt-C in cardiac tissue were decreased significantly （P＜0.05 or P＜0.01），while the activity of Cyt-CO was increased significantly in cardiac tissue （P＜0.01）. CONCLUSIONS ：Mahuang xixin fuzi decoction can improve influenza disease of kidney-yang deficiency in mice ，the effect may related to inhibit TLRs response and apoptosis regulation pathway mediated by Cyt-CO.