This study employed the "disease-medicine-dose" pattern to mine the medication rules of traditional Chinese medicine(TCM) prescriptions containing Astragali Radix in ancient Chinese medical books, aiming to provide a scientific basis for the clinical application of Astragali Radix and the development of new medicines. The TCM prescriptions containing Astragali Radix were retrieved from databases such as Chinese Medical Dictionary and imported into Excel 2020 to construct the prescription library. Statical analysis were performed for the prescriptions regarding the indications, syndromes, medicine use frequency, herb effects, nature and taste, meridian tropism, dosage forms, and dose. SPSS statistics 26.0 and IBM SPSS Modeler 18.0 were used for association rules analysis and cluster analysis. A total of 2 297 prescriptions containing Astragali Radix were collected, involving 233 indications, among which sore and ulcer, consumptive disease, sweating disorder, and apoplexy had high frequency(>25), and their syndromes were mainly Qi and blood deficiency, Qi and blood deficiency, Yin and Yang deficiency, and Qi deficiency and collateral obstruction, respectively. In the prescriptions, 98 medicines were used with the frequency >25 and they mainly included Qi-tonifying medicines and blood-tonifying medicines. Glycyrrhizae Radix et Rhizoma, Angelicae Sinensis Radix, Ginseng Radix et Rhizoma, Atractylodis Macrocephalae Rhizoma, and Citri Reticulatae Pericarpium were frequently used. The medicines with high frequency mainly have warm or cold nature, and sweet, pungent, or bitter taste, with tropism to spleen, lung, heart, liver, and kidney meridians. In the treatment of sore and ulcer, Astragali Radix was mainly used with the dose of 3.73 g and combined with Glycyrrhizae Radix et Rhizoma to promote granulation and heal up sores. In the treatment of consumptive disease, Astragali Radix was mainly used with the dose of 37.30 g and combined with Ginseng Radix et Rhizoma to tonify deficiency and replenish Qi. In the treatment of sweating disorder, Astragali Radix was mainly used with the dose of 3.73 g and combined with Glycyrrhizae Radix et Rhizoma to consolidate exterior and stop sweating. In the treatment of apoplexy, Astragali Radix was mainly used with the dose of 7.46 g and combined with Glycyrrhizae Radix et Rhizoma to dispell wind and stop convulsions. Astragali Radix can be used in the treatment of multiple system diseases, with the effects of tonifying Qi and ascending Yang, consolidating exterior and stopping sweating, and expressing toxin and promoting granulation. According to the manifestations of different diseases, when combined with other medicines, Astragali Radix was endowed with the effects of promoting granulation and healing up sores, tonifying deficiency and Qi, consolidating exterior and stopping sweating, and dispelling wind and replenishing Qi. The findings provide a theoretical reference and a scientific basis for the clinical application of Astragali Radix and the development of new medicines.
Drugs, Chinese Herbal/history* ; Humans ; Medicine, Chinese Traditional/history* ; History, Ancient ; Astragalus Plant/chemistry* ; China ; Astragalus propinquus

OBJECTIVE: To explore the relationship between serum chloride levels and prognosis in patients with hepatic coma in the intensive care unit (ICU). METHODS: We analyzed 545 patients with hepatic coma in the ICU from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Associations between serum chloride levels and 28-day and 1-year mortality rates were assessed using restricted cubic splines (RCSs), Kaplan-Meier (KM) curves, and Cox regression. Subgroup analyses, external validation, and mechanistic studies were also performed. RESULTS: A total of 545 patients were included in the study. RCS analysis revealed a U-shaped association between serum chloride levels and mortality in patients with hepatic coma. The KM curves indicated lower survival rates among patients with low chloride levels (< 103 mmol/L). Low chloride levels were independently linked to increased 28-day and 1-year all-cause mortality rates. In the multivariate models, the hazard ratio ( HR) for 28-day mortality in the low-chloride group was 1.424 (95% confidence interval [ CI]: 1.041-1.949), while the adjusted hazard ratio for 1-year mortality was 1.313 (95% CI: 1.026-1.679). Subgroup analyses and external validation supported these findings. Cytological experiments suggested that low chloride levels may activate the phosphorylation of the NF-κB signaling pathway, promote the expression of pro-inflammatory cytokines, and reduce neuronal cell viability. CONCLUSION Low serum chloride levels are independently associated with increased mortality in patients with hepatic coma.
Humans ; Male ; Female ; Middle Aged ; Intensive Care Units ; Prognosis ; Chlorides/blood* ; Aged ; Coma/blood* ; Adult

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a complex disease that is often accompanied by mental health disorders. However, the potential mechanisms underlying the heterogeneous clinical presentation of CP/CPPS remain uncertain. This study analyzed widely targeted metabolomic data of expressed prostatic secretions (EPS) and plasma to reveal the underlying pathological mechanisms of CP/CPPS. A total of 24 CP/CPPS patients from The Second Nanning People's Hospital (Nanning, China), and 35 asymptomatic control individuals from First Affiliated Hospital of Guangxi Medical University (Nanning, China) were enrolled. The indicators related to CP/CPPS and psychiatric symptoms were recorded. Differential analysis, coexpression network analysis, and correlation analysis were performed to identify metabolites that were specifically altered in patients and associated with various phenotypes of CP/CPPS. The crucial links between EPS and plasma were further investigated. The metabolomic data of EPS from CP/CPPS patients were significantly different from those from control individuals. Pathway analysis revealed dysregulation of amino acid metabolism, lipid metabolism, and the citrate cycle in EPS. The tryptophan metabolic pathway was found to be the most significantly altered pathway associated with distinct CP/CPPS phenotypes. Moreover, the dysregulation of tryptophan and tyrosine metabolism and elevation of oxidative stress-related metabolites in plasma were found to effectively elucidate the development of depression in CP/CPPS. Overall, metabolomic alterations in the EPS and plasma of patients were primarily associated with oxidative damage, energy metabolism abnormalities, neurological impairment, and immune dysregulation. These alterations may be associated with chronic pain, voiding symptoms, reduced fertility, and depression in CP/CPPS. This study provides a local-global perspective for understanding the pathological mechanisms of CP/CPPS and offers potential diagnostic and therapeutic targets.
Humans ; Male ; Prostatitis/blood* ; Adult ; Pelvic Pain/blood* ; Metabolomics ; Prostate/metabolism* ; Middle Aged ; Chronic Pain/blood* ; Metabolome ; Case-Control Studies ; Tryptophan/blood* ; Depression/blood* ; Oxidative Stress/physiology* ; Chronic Disease ; Lipid Metabolism/physiology*

Patients suffering from nerve injury often experience exacerbated pain responses and complain of memory deficits. The dorsal hippocampus (dHPC), a well-defined region responsible for learning and memory, displays maladaptive plasticity upon injury, which is assumed to underlie pain hypersensitivity and cognitive deficits. However, much attention has thus far been paid to intracellular mechanisms of plasticity rather than extracellular alterations that might trigger and facilitate intracellular changes. Emerging evidence has shown that nerve injury alters the microarchitecture of the extracellular matrix (ECM) and decreases ECM rigidity in the dHPC. Despite this, it remains elusive which element of the ECM in the dHPC is affected and how it contributes to neuropathic pain and comorbid cognitive deficits. Laminin, a key element of the ECM, consists of α-, β-, and γ-chains and has been implicated in several pathophysiological processes. Here, we showed that peripheral nerve injury downregulates laminin β1 (LAMB1) in the dHPC. Silencing of hippocampal LAMB1 exacerbates pain sensitivity and induces cognitive dysfunction. Further mechanistic analysis revealed that loss of hippocampal LAMB1 causes dysregulated Src/NR2A signaling cascades via interaction with integrin β1, leading to decreased Ca²⁺ levels in pyramidal neurons, which in turn orchestrates structural and functional plasticity and eventually results in exaggerated pain responses and cognitive deficits. In this study, we shed new light on the functional capability of hippocampal ECM LAMB1 in the modulation of neuropathic pain and comorbid cognitive deficits, and reveal a mechanism that conveys extracellular alterations to intracellular plasticity. Moreover, we identified hippocampal LAMB1/integrin β1 signaling as a potential therapeutic target for the treatment of neuropathic pain and related memory loss.
Animals ; Laminin/genetics* ; Hippocampus/metabolism* ; Neuralgia/metabolism* ; Cognitive Dysfunction/etiology* ; Male ; Peripheral Nerve Injuries/metabolism* ; Extracellular Matrix/metabolism* ; Integrin beta1/metabolism* ; Pyramidal Cells/metabolism* ; Signal Transduction

[Objective]To investigate the effect of nicotinamide adenine dinucleotide on vascular endothelial injury in hypertension and its molecular mechanism.[Methods]C57BL/6J mice were randomly divided into saline group(Saline)and hypertension group(Ang Ⅱ,which were infused with Ang Ⅱ via subcutaneously implanted osmotic pumps),and supplemented daily with nicotinamide mononucleotide(300 mg/kg),a precursor of NAD+.Blood pressure,endothelial relaxation function and pulse wave velocity were measured after 4 weeks.Wound healing assay and adhesion assay were used to evaluate the function of endothelial cells in vitro.mtROS levels were detected by immunofluorescence staining.RT-PCR was used to detect the mRNA expression of mtDNA,SIRT3 and isocitrate dehydrogenase 2(IDH2).8-hydroxy-2'-deoxyguanosine levels were detected by enzyme-linked immunosorbent assay.The protein expression levels of p-eNOS,eNOS,SIRT3 and IDH2 were detected by Western blot.[Results]NMN supplementation reduced blood pressure(P<0.001)and improved endothelial function and arterial stiffness(P<0.001)in hypertensive mice.In vitro,NMN improved endothelial function in Ang Ⅱ-stimulated endothelial cells(P<0.05)and attenuated mitochondrial oxidative stress levels(P<0.001).Mechanistically,NMN elevated SIRT3 activity(P<0.001),which subsequently enhanced IDH activity(P<0.001)and reduced oxidative stress levels in endothelial cells.Conversely,knockdown of IDH2 would reverse the effect of SIRT3 in improving endothelial function(P<0.001).[Conclusion]NAD+lowers blood pressure and enhances vascular function in hypertension by reducing the level of oxidative stress in endothelial cells through activation of the SIRT3/IDH2 signal pathway.

Objective To investigate the effect of exogenous luteinizing hormone (LH) on vitrification granulosa cells and its mecha-nisms. Methods The granulosa cells of 4-week-old preadolescent mice were selected and divided into the fresh group (without vitrification procedure),the vitrification group (treated according to vitrification procedure) and the LH group (treated with 0.3 IU/L of LH intervention on the basis of the vitrification group). Granulocyte count was performed,and Realtime PCR and Western blot were used to detect the expression changes of Foxl2,PI3K,AKT and mTOR mRNAs and proteins in each group. Results Compared with the vitrification group,the total number of granulosa cells in the LH group was significantly increased (P<0.05),and the expression of Foxl2,PI3K,AKT and mTOR mRNAs and proteins were elevated (P<0.05). Conclusion The intevention of exogenous LH is beneficial for the survival of vitrifi-cation granulosa cells,and the mechanism may be related to the activation of PI3K/AKT/mTOR pathway.

OBJECTIVE To explore the effectiveness and possible mechanism of Shangke Lengtong Patch in treating knee osteo-arthritis with cold-dampness arthralgia obstruction.METHODS A total of 70 patients who met the inclusion criteria of knee osteoar-thritis with cold-dampness arthralgia obstruction in the Orthopedics Department of Affiliated Hospital of Nanjing University of Chinese Medicine from November to December 2024 were randomly divided into an experimental group and a control group,with 35 cases in each group.During the treatment,1 case dropped out of the experimental group,3 cases dropped out of the control group,and 1 case was discontinued.The experimental group was treated with Shangke Lengtong Patch,and the control group was treated with Compound Nanxing Zhitong Ointment.The WOMAC scores and TCM syndrome scores of the two groups before and after treatment were compared to comprehensively evaluate the clinical efficacy.The changes in the expression levels of CGRP,substance P,HMGB1,IL-1β,CX-CL12,and CXCR4 in the serum of the two groups were detected by ELISA.RESULTS After 3,7,and 14 d of treatment,the WOMAC scores and TCM syndrome scores of the two groups were significantly reduced(P<0.05,P<0.01),and the score of aggrava-ted cold in the experimental group was better than that in the control group at 7 d of treatment(P<0.05);after 14 d of treatment,the expression levels of CGRP,substance P,HMGB1,IL-1β,CXCL12,and CXCR4 in the serum of the two groups were significantly re-duced(P<0.05),and there was no statistical difference between the two groups.CONCLUSION Shangke Lengtong Patch can sig-nificantly relieve the pain symptoms of knee osteoarthritis patients with cold-dampness arthralgia obstruction and improve the joint func-tion of patients.It may improve synovial inflammation by inhibiting the HMGB1/CXCL12/CXCR4 pathway,thereby exerting a thera-peutic effect.

Albendazole-glucan particles(ABZ-GPS)and abendazole(ABZ)were used to treat secondary alveolar echinococ-cosis in mice.The therapeutic effects of ABZ-GPS on alveolar echinococcosis in vivo were evaluated,and the feasibility of using glucan particles as anti-hydatid drug carriers was further verified.Mice with echinococcosis were randomly divided into an ABZ group,glucan nanoparticle(GP)group,ABZ-GPS group,and control group.After four courses of administration with a final concentration of 50 mg/mL,the therapeutic effects of ABZ-GPS were evaluated on the basis of imaging,histopathological changes,ultrastructure,and immunology.After ABZ-GPS and ABZ administration,clear liver lesion tissue necrosis and large numbers of infiltrating lymphocytes were observed.Significant differences in the average cyst wet weight(t=7.83,P＜0.05),were observed between the ABZ-GPS group and ABZ group.Imaging revealed that ABZ-GPs were targeted to liver tissue.Pa-thology and ultrastructure analyses demonstrated that the alveolar hydatid cells in the liver in the control group and GP group grew well,and the vesicles were large,filled with cystic fluid,and translucent or transparent;the cyst wall tension was high;no calcification was observed;the stratum corneum and germinal layer were clear;and more fertile capsules and different num-bers of protocephalospora were present in the liver.In the ABZ group,the capsular cavity collapsed,and showed partial necro-sis and lymphocyte infiltration.In the ABZ-GP group,the corneum and germinal layer of echinococcus vesicles were difficult to identify,and we observed bulbous necrosis,central calcification,fibrous tissue hyperplasia,inflammatory cell infiltration,coarser,shorter or absent microvilli of the germinal layer,nuclear shrinkage,dissolution or disappearance,clear expansion of cytoplasmic microtubules,and myelin-like or vacuole-like changes.Therefore,ABZ-GPs showed good targeting and killing ac-tivity in vivo in mice with secondary alveolar coccosis.

Objective:To explore the protocol for handgrip exercise stress echocardiography by comparing different maximal voluntary contraction（MVC）handgrip groups with bicycle exercise stress.Methods:Forty-one healthy volunteers were enrolled prospectively from June to October 2024 in Tangdu Hospital and utilized a color Doppler echocardiography system，supine cycle ergometer，and handgrip dynamometer to collect echocardiographic data at baseline，during handgrip exercises at 20%（3 min），30%（3 min），and 40%（2 min）of MVC，and spine bicycle exercise stress at peak. Parameters measured included left ventricular ejection fraction（EF），stroke volume（SV），cardiac output（CO），mitral inflow E-wave and A-wave velocities，lateral and septal mitral annular e' velocities，E/A and E/e' ratios，global longitudinal strain（GLS），left atrial reservoir strain（LAS R），conduit strain（LAS CD），and contractile strain（LAS CT）. The non-invasive myocardial work indices were also assessed，including global work index（GWI），global constructive work（GCW），global wasted work（GWW），and global work efficiency（GWE）. Statistical analyses were performed using repeated measures analysis of variance，with corrected paired t-test for comparisons between two exercise stress states. Results:Compared with the baseline state，heart rate，blood pressure，CO、GWI、GCW、GWW and LAS CT gradually increased，while EF、E/A、GLS、GWE、LAS R and LAS CD gradually decreased under 20%，30% and 40% of MVC states. The changes were most obvious at 40% of MVC state，which was selected for the handgrip exercise stress echocardiography protocol.Compared with the peak of bicycle exercise，at 40% of MVC，heart rate was significantly lower［（81.2 ± 9.7）bpm vs.（164.6 ± 11.3）bpm， P<0.05）］，systolic blood pressure was slightly lower［（152.9 ± 13.2）mmHg vs.（165.1 ± 20.4）mmHg， P<0.05］，diastolic blood pressure was higher［（96.0 ± 9.5）mmHg vs.（89.5 ± 10.9）mmHg， P<0.05］，GLS was lower［（19.1 ± 1.5）% vs.（23.5 ± 1.7）%， P<0.05］，GWI was similar［（2 254.2 ± 417.3）mmHg% vs.（2 227.5 ± 389.0）mmHg%， P>0.05］，but GWE was higher［（95.3 ± 2.0）% vs.（93.7 ± 2.0）%， P<0.05］，and LAS R was lower［（39.4 ± 4.2）% vs.（43.9 ± 4.1）%， P<0.05］. Conclusions:The 40% of MVC lasting 2 min can cause the most significant handgrip-related changes in cardiac function and can be used as the standard protocol for handgrip exercise stress echocardiography. Handgrip stress exercise can cause significant changes in cardiac systole，diastole，and work performance，showing different characteristics compared with bicycle exercise stress.