ObjectiveTo elucidate the mechanism by which total flavonoids of Abelmoschi Corolla （TFA） treat immunoglobulin A （IgA） nephropathy （IgAN） through serum metabolomics analysis. MethodsSPF-grade male SD rats were randomly assigned into six groups （n=10）： blank， model， low-dose TFA （TFA-L， 27 mg·kg^-1）， medium-dose TFA （TFA-M， 54 mg·kg^-1）， high-dose TFA （TFA-H， 108 mg·kg^-1）， and losartan potassium （LST， 4.5 mg·kg^-1） groups. The remaining five groups， excluding the blank group， were modeled with bovine serum albumin （BSA）， lipopolysaccharide （LPS）， and carbon tetrachloride （CCl₄）. Specifically， from weeks 1 to 10， BSA was administered via gavage every other day， and a mixture of castor oil and CCl₄ was injected subcutaneously once a week， with LPS injected into the tail vein at weeks 6 and 8. After successful modeling， each intervention group was administrated with the medication prepared with distilled water once daily by gavage for a continuous period of 4 weeks. The levels of 24-hour urinary total protein （24 h UP） and serum creatinine （SCr） were quantified by kits， and the serum IgA level was determined by enzyme-linked immunosorbent assay （ELISA）. Renal pathological changes were observed by hematoxylin-eosin （HE） staining and periodic acid-Schiff （PAS） staining. Renal IgA deposition was assessed by immunofluorescence （IF）. Endoplasmic reticulum （ER） stress was observed by transmission electron microscopy. Western blot and immunohistochemistry （IHC） were employed to detect the expression of ER stress-related factors. Non-targeted metabolomics was used to screen differential metabolites for analysis， and key metabolites arachidonic acid （AA）， prostaglandin E₂ （PGE₂）， and cyclooxygenase-2 （COX-2） were validated. ResultsCompared with the blank group， the model group showed increased 24-hour urine protein （24 h UP） and serum creatinine （SCr） levels （P<0.01）， obvious renal pathological damage， elevated serum IgA level （P<0.01）， increased renal AA and PGE₂ levels （P<0.01）， and up-regulated protein levels of COX-2， glucose-regulated protein 78 （GRP78）， phosphorylated eukaryotic initiation factor 2α （P-EIF2α）， activating transcription factor 4 （ATF4）， inositol-requiring enzyme 1α （IRE1α）， and spliced X-box binding protein 1 （XBP1s） in the renal tissue （P<0.05， P<0.01）. Compared with the model group， the intervention groups showed reductions in 24 h UP and SCr levels （P<0.05， P<0.01）， alleviated renal pathological injury， decreased serum IgA level （P<0.05， P<0.01）， and reduced renal AA and PGE₂ levels （P<0.01）. Western blot and IHC results showed that TFA reduced the levels of COX-2， GRP78， P-EIF2α， ATF4， IRE1α， and XBP1s in the renal tissue （P<0.05， P<0.01）. Metabolomics results indicated that 51 commonly differential metabolites were found among the normal， model， and TFA-M groups. TFA ameliorated IgAN by affecting metabolic pathways related to the biosynthesis of arachidonic acid and arginine through L-aspartic acid， prostaglandin 2α， leukotriene B₄， leukotriene D₄， among others. ConclusionTFA can regulate the arachidonic acid metabolism pathway， thereby modulating ER stress， reducing renal damage， and ameliorating IgA nephropathy.

BackgroundThe global prevalence of depressive disorders is high， with a significant treatment gap remaining. Escitalopram oxalate， as a commonly used antidepressant in clinical practice， has a single target and is prone to cause adverse reactions such as gastrointestinal discomfort. The traditional Mongolian medicine Zadi-5 pills has a multi-target anti-depression mechanism and unique advantages such as improving the intestinal flora. However， there is currently a lack of randomized controlled trial evidence for the combined treatment of first-episode depression， along with insufficient research on its metabolic safety and potential drug interactions. ObjectiveTo explore the efficacy and safety of Zadi-5 pills combined with escitalopram oxalate in the treatment of the first-episode depression， so as to provide references for Mongolian medicine in depression management. MethodsA randomized controlled trial was conducted. A total of 103 patients with first-episode depression who were treated in the outpatient or inpatient departments of the Inner Mongolia Autonomous Region Mental Health Center from January 2023 to December 2024 and met the diagnostic criteria for depressive episode as defined in International Classification of Diseases， tenth edition （ICD-10） were included. Random numbers were generated using the RAND function in Excel software， and the patients were divided into the study group （n=52） and the control group （n=51）. Both groups received escitalopram oxalate treatment， starting from 5 mg/d and gradually increasing to 20 mg/d. The study group additionally received Zadi-5 pills， 13 pills per day. The treatment duration for both groups was 6 weeks. Before treatment and at the 2^nd， 4^th， and 6^th weeks of treatment， the severity of depressive symptoms was evaluated using the Hamilton Depression Scale-24 item （HAMD-24）. At these time points， blood was collected on an empty stomach at 7∶00 for the detection of liver function （aspartate aminotransferase， alanine aminotransferase）， triglycerides， and the blood concentration of escitalopram oxalate. ResultsA total of 100 patients completed the study， with 50 cases in the study group and the control group. The results of the repeated measures ANOVA showed that the interaction effect between group and time in the HAMD-24 score was statistically significant （F _interaction= 18.070， P<0.01）. At the end of the 4^th and 6^th weeks of treatment， the HAMD-24 score of the study group was lower than those of the control group （P<0.05）. At each time point after treatment， the reduction rate of the HAMD-24 score in the study group was higher than those of the control group， and the differences were all statistically significant （P<0.05）. The interaction effect between the triglyceride level groups and time was statistically significant （F_interaction=3.381， P<0.05）.After treatment， the triglyceride levels in the study group showed a downward trend， while those in the control group showed an upward trend. There was no statistically significant interaction effect between the groups and time for liver function （aspartate aminotransferase and alanine aminotransferase） and the blood concentration of escitalopram oxalate （P>0.05）. ConclusionCompared with escitalopram oxalate treatment alone， the combination of Zadi-5 pills and escitalopram oxalate is more effective in treating the first-episode depression， without increasing the risk of liver damage. The combined medication may have a potential beneficial effect on lipid metabolism. ［Funded by Inner Mongolia Autonomous Region Health Science and Technology Planning Project （number， 202202107）］

ObjectiveTo investigate the mechanisms of Tongmai Yangxin pills （TMYX） and Tongxinluo capsules （TXL） in treating no-reflow （NR） after myocardial ischemia and reperfusion following the concept of treating the same disease with different methods， based on integrative pharmacology and experimental validation. MethodsEighty 8-week-old SPF-grade SD rats were randomly assigned into four groups （n=20）： sham operation， NR， TMYX （4 g·kg^-1）， and TXL （2 mg·kg^-1）. A rat model of myocardial ischemia-reperfusion no-reflow was established by in-situ ligation of the left anterior descending coronary artery. Gastric gavage was first performed 4 h after the operation， and samples were collected on day 7. Thioflavin S staining was used to observe the NR area in rat myocardium. Echocardiography was performed to examine the cardiac function. Hematoxylin-eosin （HE） staining was conducted to observe the pathological changes of the myocardial tissue. An automatic biochemical analyzer was adopted to measure myocardial enzyme activity. Then， integrated pharmacology was applied for Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis. Finally， Western blot was employed to quantify the protein levels of key targets in the myocardial tissue， including soluble guanylyl cyclase （sGC）， cyclic guanosine monophosphate （cGMP）/dependent protein kinase （PKG）， phosphorylated phosphatidylinositol 3-kinase （p-PI3K）， phosphorylated protein kinase B （p-Akt）， and hypoxia-inducible factor-1α （HIF-1α）. ResultsCompared with the sham operation group， the NR group showed increased NR area of myocardium， decreased left ventricular ejection fraction （EF）， left ventricular fractional shortening （FS）， left ventricular outflow tract peak velocity （LVOT Peak）， and left ventricular stroke volume （LVSV） （P<0.01）， fractured and disordered myocardial fibers as well as inflammatory cell infiltration in the myocardial tissue， enhanced activities of creatine kinase （CK）， creatine kinase isoenzyme （CK-MB）， and lactate dehydrogenase （LDH） in the myocardial tissue （P<0.01）， and downregulated protein levels of sGC， PKG， phosphorylated （p）-PI3K （Tyr458）， and p-Akt （Tyr315） in the myocardial tissue （P<0.05， P<0.01）. The expression level of HIF-1α protein showed a downward trend. Compared with the NR group， the TMYX group and TXL group exhibited a decreasing trend in myocardial NR area， EF， FS， and LVOT Peak significantly increased （P<0.05， P<0.01）， LVSV showed an upward trend， ameliorated myocardial pathological morphology and inflammatory infiltration， reductions in CK， CK-MB， and LDH activities （P<0.05， P<0.01）， and upregulated protein levels of sGC， PKG， p-PI3K （Tyr458） in myocardial tissue （P<0.05， P<0.01）， the protein expressions of p-Akt （Tyr315） and HIF-1α showed an upward trend. A comparison of the therapeutic effects between the two compound prescriptions showed that TMYX tended to exert a better effect in restoring cardiac function and protecting cardiac structure in NR rats， whereas TXL was more effective in reducing myocardial NR area and lowering myocardial enzyme activities in NR rats. Integrative pharmacology analysis combined with experimental verification demonstrated that both TMYX and TXL could alleviate NR through the following mechanisms： activating the cyclic cGMP/PKG signaling pathway to regulate vascular tone， activating the PI3K/Akt signaling pathway to dilate blood vessels， and activating the HIF-1 signaling pathway to inhibit oxidative stress. However， TMYX had an advantage in activating the cGMP/PKG pathway， while TXL was superior in activating the PI3K/Akt pathway. The two compound prescriptions exerted comparable effects on the HIF-1 signaling pathway， which might serve as their common therapeutic pathway. ConclusionBoth TMYX and TXL could alleviate NR damage. TMYX exerts its protective effect against NR mainly by activating the cGMP/PKG signaling pathway， while TXL exerts its effect mainly through the PI3K/Akt pathway. The HIF-1α signaling pathway may be a common pathway for the two compound prescriptions to exert their protective effects against NR. This study reveals the similarities and differences between TMYX and TXL in the treatment effect and mechanism for NR， providing an experimental basis and a theoretical basis for better clinical application of the two compound prescriptions.

ObjectiveTo develop and validate a nomogram for predicting the risk of concurrent cognitive impairment in older adults with heart disease. MethodsSelf-reported data from 2 673 respondents in the 2020 China Health and Retirement Longitudinal Study were analyzed. The participants were randomly divided into a training set (n = 1 871) and a validation set (n = 802). Heart disease status was determined using a self-report questionnaire. Logistic regression analysis was performed to identify predictors, and a nomogram for predicting the risk of concurrent cognitive impairment in older adults with heart disease was developed using R software. Bootstrap resampling was used for internal validation, and model performance was further evaluated in the randomly split validation set. The predictive performance of the model was assessed using the area under the receiver operating characteristic curve (AUC) and calibration curves.. ResultsA total of 2 673 older adults with heart disease were included, out of whom 315 participants in the training set had cognitive impairment. Lasso regression analysis identified age, education level, place of residence, instrumental activities of daily living and depression as predictors of concurrent cognitive impairment. A prediction model incorporating these five variables was constructed. The AUC were 0.827 (95%CI 0.804 to 0.850) in the training set and 0.847 (95%CI 0.812 to 0.882) in the validation set. The Hosmer-Lemeshow test yielded P = 0.154 and P = 0.716 in the training and validation sets, respectively. Calibration curves showed good agreement between predicted and observed probabilities. Decision curve analysis indicated that the model provided favorable net benefit and predictive performance. ConclusionThe nomogram may provide a useful reference for risk screening and early intervention for cognitive impairment in older adults with heart disease.

Objective:To investigate the relationship between alterations in dynamic functional connectivity (dFC) and spatial navigation abilities in individuals with subjective cognitive decline (SCD) across different Traditional Chinese Medicine (TCM) constitutions.Methods:Seventy-five participants with SCD, comprising 34 individuals with balanced constitutions and 41 individuals with biased constitutions, were recruited from the Affiliated Drum Tower Hospital of Nanjing University Medical School between August 2022 and January 2025. The participants underwent TCM constitution assessment, spatial navigation ability testing, and neuropsychological scale evaluation. Additionally, each participant was assessed using 3.0 T resting-state functional magnetic resonance imaging (rs-fMRI) and high-resolution T1-weighted imaging scans. Based on prior research, 20 spatial navigation-related regions of interest (ROIs) were defined. Afterwards, rs-fMRI time series were segmented using a sliding time window approach before calculating the dFC within the spatial navigation brain network.Results:Compared to the balanced constitution group, the biased constitution SCD group showed significantly lower scores on the Mini-Mental State Examination (MMSE) ( z=-3.05, P=0.002) and the Auditory Verbal Learning Test (AVLT) measures: immediate recall ( z=-2.12, P=0.035), short-delay recall ( z=-2.22, P=0.026), long-delay recall ( z=-2.88, P=0.004), cued recall ( z=-2.91, P=0.004), and recognition ( z=-2.20, P=0.028). They also exhibited significantly higher average error distances in ego-allocentric navigation ( z=-2.28, P=0.023), egocentric navigation ( z=-2.31, P=0.021), and delayed navigation ( z=-2.02, P=0.043). Participants with SCD who had a biased constitution also demonstrated significantly reduced dFC between the left parahippocampal gyrus (PHG) and left prefrontal cortex (PFC) ( t=2.43), right precuneus and right retrosplenial cortex (RSC) ( t=2.96), and left inferior parietal lobule (IPL) and left hippocampus ( t=2.42) (all P<0.05, Bonferroni-corrected). Conversely, the dFC was significantly increased between the right PHG and left PFC ( t=-2.29, P<0.05, Bonferroni-corrected). Significant correlations were also found in participants with SCD who had biased constitutions: the dFC between the left PHG and left PFC positively correlated with the egocentric navigation average total error ( r=0.34, P=0.030) and negatively correlated with the visuospatial memory cognitive domain ( r=-0.35, P=0.026); the dFC between the left IPL and left hippocampus negatively correlated with the egocentric navigation average total error ( r=-0.32, P=0.043); and the dFC between the right PHG and left PFC positively correlated with the delayed navigation average total error ( r=0.33, P=0.037). The area under the ROC curve for the combined differences in cognitive assessments, spatial navigation behavior, and navigation-related brain network dFC was 0.966 in predicting biased constitution versus balanced constitution in participants with SCD. Conclusions:Individuals with SCD and biased constitutions demonstrated poorer spatial navigation ability, possibly due to altered dFC within the spatial navigation brain network. Furthermore, the integrated model based on spatial navigation behaviors and dFC exhibited a high predictive value in distinguishing between individuals with SCD who had balanced and biased constitutions.

Chronic atrophic gastritis(CAG)is a chronic gastric disorder characterized by recurrent damage to the gastric mucosal epithelium,resulting in the reduction of intrinsic glands,with or without concurrent intestinal metaplasia.The"hyperactive stomach qi"theory,derived from Huang Di Nei Jing Su Wen Ji Zhu,proposes that the core pathogenesis of CAG lies in excessive stomach qi activity,grounded in the physiological principle of"strong yang qi in earth and weak yin qi in earth".This theory synthesizes the clinical manifestations and pathological progression of CAG,asserting that its development often involves intertwined pathological factors such as stagnation,dryness-heat,phlegm-dampness and stasis-toxicity.A triphasic therapeutic framework is proposed:the spleen qi deficiency phase,marked by impaired spleen transport function and dysregulated qi-fluid distribution,requiring spleen fortification and qi-fluid regulation;the hyperactive stomach qi phase,characterized by intensified stomach qi activity coupled with dryness-damp stagnation,necessitating stagnation resolution,dampness elimination and yin nourishment;the decline and disorder of middle qi phase,characterized by the deficiency of the middle qi,with phlegm,blood stasis and toxins forming the terminal stage.Treatment should focus on reinforcing the middle and restoring balance,detoxifying and dissipating accumulation.By exploring CAG pathogenesis and treatment through the lens of"hyperactive stomach qi",this study aimed to provide novel theoretical insights and therapeutic strategies for TCM in the prevention and treatment of CAG.

Coptis chinensis Franch. and Panax ginseng C. A. Mey. are traditional herbal medicines with millennia of documented use and broad therapeutic applications, including anti-diabetic properties. However, the synergistic effect of total alkaloids from Coptis chinensis and total ginsenosides from Panax ginseng on type 2 diabetes mellitus (T2DM) and its underlying mechanism remain unclear. The research demonstrated that the optimal ratio of total alkaloids from Coptis chinensis and total ginsenosides from Panax ginseng was 4∶1, exhibiting maximal efficacy in improving insulin resistance and gluconeogenesis in primary mouse hepatocytes. This combination demonstrated significant synergistic effects in improving glucose tolerance, reducing fasting blood glucose (FBG), the weight ratio of epididymal white adipose tissue (eWAT), and the homeostasis model assessment of insulin resistance (HOMA-IR) in leptin receptor-deficient (db/db) mice. Subsequently, a T2DM liver-specific network was constructed based on RNA sequencing (RNA-seq) experiments and public databases by integrating transcriptional properties of disease-associated proteins and protein-protein interactions (PPIs). The network recovery index (NRI) score of the combined treatment group with a 4∶1 ratio exceeded that of groups treated with individual components. The research identified that activated adenosine 5'-monophosphate-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC) signaling in the liver played a crucial role in the synergistic treatment of T2DM, as verified by western blot experiment in db/db mice. These findings demonstrate that the 4∶1 combination of total alkaloids from Coptis chinensis and total ginsenosides from Panax ginseng significantly improves insulin resistance and glucose and lipid metabolism disorders in db/db mice, surpassing the efficacy of individual treatments. The synergistic mechanism correlates with enhanced AMPK/ACC signaling pathway activity.
Animals ; Panax/chemistry* ; Ginsenosides/administration & dosage* ; Diabetes Mellitus, Type 2/metabolism* ; Mice ; Male ; Alkaloids/pharmacology* ; Coptis/chemistry* ; Drug Synergism ; Insulin Resistance ; Mice, Inbred C57BL ; Humans ; Transcriptome/drug effects* ; Blood Glucose/metabolism* ; Hypoglycemic Agents/administration & dosage* ; Drugs, Chinese Herbal/administration & dosage* ; Hepatocytes/metabolism*

Objective:Using ecological niche width and situation model,the operation and management of public Traditional Chinese Medicine(TCM)hospitals in 16 cities in Shandong Province were evaluated to put forward countermeasures.Methods:The relevant index data of public TCM hospitals in 16 cities in Shandong Province from 2019 to 2022 were collected to analyze the development status.The ecological niche width model and niche situation model were applied to evaluate the operation and management of public TCM hospitals in 16 cities in Shandong.Results:The top three public TCM hospitals in terms of average ecological niche width were City G,City P and City F.The ecological niche situation value of public TCM hospitals in City K,City A and City J ranked the top three.Conclusion:The dimensions of operation management structure of public TCM hospitals in Shandong need to be enhanced and the development of operation management space needs to be balanced.It is feasible to evaluate operation management by using ecological niche width and situation model.It is suggested to improve the allocation efficiency of health personnel,facilities,funds and other resources;promote the spatial balanced development of operation management;promote the application of ecological niche width and situation model in the field of medicine and health management.

Chronic atrophic gastritis(CAG)is a chronic gastric disorder characterized by recurrent damage to the gastric mucosal epithelium,resulting in the reduction of intrinsic glands,with or without concurrent intestinal metaplasia.The"hyperactive stomach qi"theory,derived from Huang Di Nei Jing Su Wen Ji Zhu,proposes that the core pathogenesis of CAG lies in excessive stomach qi activity,grounded in the physiological principle of"strong yang qi in earth and weak yin qi in earth".This theory synthesizes the clinical manifestations and pathological progression of CAG,asserting that its development often involves intertwined pathological factors such as stagnation,dryness-heat,phlegm-dampness and stasis-toxicity.A triphasic therapeutic framework is proposed:the spleen qi deficiency phase,marked by impaired spleen transport function and dysregulated qi-fluid distribution,requiring spleen fortification and qi-fluid regulation;the hyperactive stomach qi phase,characterized by intensified stomach qi activity coupled with dryness-damp stagnation,necessitating stagnation resolution,dampness elimination and yin nourishment;the decline and disorder of middle qi phase,characterized by the deficiency of the middle qi,with phlegm,blood stasis and toxins forming the terminal stage.Treatment should focus on reinforcing the middle and restoring balance,detoxifying and dissipating accumulation.By exploring CAG pathogenesis and treatment through the lens of"hyperactive stomach qi",this study aimed to provide novel theoretical insights and therapeutic strategies for TCM in the prevention and treatment of CAG.

Objective:To explore the mechanism of Ginkgo biloba extract(EGb)on cerebral ischemia reperfusion injury(CIRI)in rats via the advanced glycation end products(AGEs)/receptor for AGEs(RAGE)pathway.Methods:SD rats were randomly divided into sham operation group(Sham group),CIRI group,CIRI+EGb pretreat-ment group(CIRI+EGb group),CIRI+AGEs inhibitor alagebrium chloride(ALT711)group(CIRI+ALT711 group)and CIRI+EGb+ALT711 group.HE,Nissl and Prussion blue staining were used to observe pathological chan-ges in the cerebral cortical area.The expression of AGEs,RAGE and nicotinamide adenine dinucleotide phosphate oxi-dase 4(NOX4)in the cerebral cortical area was detected by immunohistochemistry,the expression of AGEs,RAGE,NOX4,ferritin heavy chain 1(FTH),glutathione peroxidase 4(GPX4)and solute carrier family 7 member 11(SLC7A11)in the cerebral cortical area was detected by Western blot,and the expression of RAGE and NOX4 mRNA in the cerebral cortical area was detected by RT-qPCR.Results:Compared with the Sham group,the pathological dam-age in the brain tissue of rats in the CIRI group was observed;the expression of AGEs,RAGE and NOX4 was increased(P<0.01),the expression of FTH,GPX4 and SLC7A11 was reduced(P<0.01),the expression of RAGE and NOX4 mRNA was increased(P<0.01);compared with the CIRI group,the pathological damage in the brain tissue of rats in the CIRI+EGb group and CIRI+ALT711 group was reduced,the expression of AGEs,RAGE and NOX4 was reduced(P<0.01),the expression of FTH,GPX4 and SLC7A11 was increased(P<0.01),the expression of RAGE and NOX4 mRNA was reduced(P<0.05);compared with the CIRI+ALT711 group,the pathological damage in the brain tissue of rats,as well as the expression of AGEs,RAGE and NOX4 in the CIRI+EGb+ALT711 group were re-duced(P<0.01),the expression of FTH,GPX4 and SLC7A11 was increased(P<0.01),the expression of RAGE and NOX4 mRNA was reduced(P<0.01).Conclusion:EGb could protect CIRI by inhibiting NOX4 and ameliorating ferroptosis through the AGEs/RAGE pathway.