Sophorae Flavescentis Radix is one of the commonly used traditional Chinese medicine in China, and a large amount of pharmaceutical residue generated during its processing and production is discarded as waste, which not only wastes resources but also pollutes the environment. Therefore, elucidating the chemical composition of the residue of Sophorae Flavescentis Radix and the differences between the residue and Sophorae Flavescentis Radix itself is of great significance for the comprehensive utilization of the residue. This study, based on ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) technology combined with multivariate statistical methods, provides a thorough characterization, identification, and differential analysis of the overall components of Sophorae Flavescentis Radix and its residue. Firstly, 61 compounds in Sophorae Flavescentis Radix were rapidly identified based on their precise molecular weight, fragment ions, and compound abundance, using a self-constructed compound database. Among them, 41 compounds were found in the residue, mainly alkaloids and flavonoids. Secondly, through principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA), 15 key compounds differentiating Sophorae Flavescentis Radix from its residue were identified. These included highly polar alkaloids, such as oxymatrine and oxysophocarpine, which showed significantly reduced content in the residue, and less polar flavonoids, such as kurarinone and kuraridin, which were more abundant in the residue. In summary, this paper clarifies the overall composition, structure, and content differences between Sophorae Flavescentis Radix and its residue, suggesting that the residue of Sophorae Flavescentis Radix can be used as a raw material for the extraction of its high-activity components, with promising potential for development and application in cosmetics and daily care. This research provides a scientific basis for the future comprehensive utilization of Sophorae Flavescentis Radix and its residue.
Drugs, Chinese Herbal/chemistry* ; Chromatography, High Pressure Liquid/methods* ; Mass Spectrometry/methods* ; Sophora/chemistry* ; Flavonoids/chemistry* ; Alkaloids/chemistry*

This study aimed to explore the therapeutic mechanisms of Colquhounia Root Tablets(CRT) in treating diabetic kidney disease(DKD) by integrating biomolecular network mining with animal model verification. By analyzing clinical transcriptomics data, an interaction network was constructed between candidate targets of CRT and DKD-related genes. Based on the topological eigenvalues of network nodes, 101 core network targets of CRT against DKD were identified. These targets were found to be closely related to multiple pathways associated with type 2 diabetes, immune response, and metabolic reprogramming. Given that immune-inflammatory imbalance driven by metabolic reprogramming is one of the key pathogenic mechanisms of DKD, and that many core network targets of CRT are involved in this pathological process, receptor for advanced glycation end products(RAGE)-reactive oxygen species(ROS)-phosphatidylinositol 3-kinase(PI3K)-protein kinase B(AKT)-nuclear factor-κB(NF-κB)-NOD-like receptor family pyrin domain containing 3(NLRP3) signaling axis was selected as a candidate target for in-depth research. Further, a rat model of DKD induced by a high-sugar, high-fat diet and streptozotocin was established to evaluate the pharmacological effects of CRT and verify the expression of related targets. The experimental results showed that CRT could effectively correct metabolic disturbances in DKD, restore immune-inflammatory balance, and improve renal function and its pathological changes by inhibiting the activation of the RAGE-ROS-PI3K-AKT-NF-κB-NLRP3 signaling axis. In conclusion, this study reveals that CRT alleviates the progression of DKD through dual regulation of metabolic reprogramming and immune-inflammatory responses, providing strong experimental evidence for its clinical application in DKD.
Animals ; Diabetic Nephropathies/metabolism* ; Receptor for Advanced Glycation End Products/genetics* ; NF-kappa B/genetics* ; Signal Transduction/drug effects* ; Rats ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Proto-Oncogene Proteins c-akt/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Phosphatidylinositol 3-Kinases/genetics* ; Reactive Oxygen Species/metabolism* ; Humans ; Plant Roots/chemistry* ; Rats, Sprague-Dawley ; Tablets/administration & dosage*

This paper aimed to investigate the therapeutic effect and mechanism of action of the Yiqi Fumai Formula(YQFM), a kind of traditional Chinese medicine(TCM), on mice with experimental heart failure based on the "heart-gut axis" theory. Based on the network pharmacology integrated with the group collaboration algorithm, the active ingredients were screened, a "component-target-disease" network was constructed, and the potential pathways regulated by the formula were predicted and analyzed. Next, the model of experimental heart failure was established by intraperitoneal injection of adriamycin at a single high dose(15 mg·kg~(-1)) in BALB/c mice. After intraperitoneal injection of YQFM(lyophilized) at 7.90, 15.80, and 31.55 mg·d~(-1) for 7 d, the protective effects of the formula on cardiac function were evaluated using indicators such as ultrasonic electrocardiography and myocardial injury markers. Combined with inflammatory factors in the cardiac and colorectal tissue, as well as targeted assays, the relevant indicators of potential pathways were verified. Meanwhile, 16S rDNA sequencing was performed on mouse fecal samples using the Illumina platform to detect changes in gut flora and analyze differential metabolic pathways. The results show that the administration of injectable YQFM(lyophilized) for 7 d significantly increased the left ventricular end-systolic internal diameter, fractional shortening, and ejection fraction of cardiac tissue of mice with experimental heart failure(P<0.05). Moreover, markers of myocardial injury were significantly decreased(P<0.05), indicating improved cardiac function, along with significantly suppressed inflammatory responses in cardiac and intestinal tissue(P<0.05). Additionally, the species of causative organisms was decreased, and the homeostasis of gut flora was improved, involving a modulatory effect on PI3K-Akt signaling pathway-related inflammation in cardiac and colorectal tissue. In conclusion, YQFM can affect the "heart-gut axis" immunity through the homeostasis of the gut flora, thereby exerting a therapeutic effect on heart failure. This finding provides a reference for the combination of TCM and western medicine to prevent and treat heart failure based on the "heart-gut axis" theory.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Heart Failure/microbiology* ; Mice ; Mice, Inbred BALB C ; Male ; Disease Models, Animal ; Gastrointestinal Microbiome/drug effects* ; Heart/physiopathology* ; Humans ; Signal Transduction/drug effects*

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Objective To evaluate the bioequivalence and safety of two cilostazol tablets 50 mg in healthy Chinese subjects.Methods This study was an open-lable,randomized,two-period crossover design.A total of 32 subjects respectively for fasting state were given a single oral dose of test or reference tedizolid phosphate tablets 50 mg.The plasma concentration of cilostazol was determined by liquid chromatography tandem mass spectrometry(LC-MS/MS),and the concentration-time data was processed by SAS 9.4,the model method of the non-compartmental was used to calculate the pharmacokinetic parameters of tedizolid and to evaluate the bioequivalence.Results The Cmax of cilostazol test and reference were(358.10±125.80)and(346.90±115.30)ng·mL-1;tmax were 3.50 and 4.00 h;t1/2 were(9.63±7.12)and(8.57±5.15)h;AUC0_twere(5 235.00±2 268.00)and(5 190.00±1 747.00)h·ng·mL-1;AUC0-∞ were(5 377.00±2 367.00)and(5 308.00±1 848.00)h·ng·mL-1.The 90％confidence intervals of the geometric mean ratios of the main pharmacokinetic parameters of the test drug and reference drug were within the range of 80.00％to 125.00％.Conclusion Single oral test and reference cilostazol tablets were bioequivalent and safe in healthy Chinese subjects.

In recent years,studies have shown that C/EBP β plays an important role in the occurrence and development of liver cancer,but its specific molecular regulatory mechanism is still unclear.In this study,we analyzed the GEO database and the Kaplan-Meier Plotter database and found that the mRNA expression of C/EBP β was low in hepatocellular carcinoma(HCC)cells(P＜0.05),and its low ex-pression was closely related to the prognosis of HCC patients.Furthermore,functional enrichment analy-sis and TIMER database analysis showed that C/EBP β was mainly involved in biological processes such as cell cycle and DNA transcription,and the expression level of C/EBP β had a strong correlation with the immune infiltration of CD4+T cells and macrophages(P＜0.05).To further investigate the effect of C/EBP β on the proliferation and migration of HCC cells.In the experiment,HCC cells were transiently transfected with C/EBP β siRNA and divided into si-NC group and siC/EBP β group.The mRNA and protein levels of C/EBP β in HCC cells were significantly reduced by qRT-PCR and Western blot(P＜0.05),and MTT detection,plate cloning assay,and 5-ethynyl-2'deoxyuracil nucleoside(Edu)assay confirmed that knockdown of C/EBP β promotes the proliferation of HCC cells(P＜0.05);Transwell and scratch assays confirmed that knockdown of C/EBP β promote the migration of HCC cells;Western blot method was used to detect the effect of knockdown of C/EBP β on the expression of migration-related proteins(E-cadherin,N-cadherin)and Wnt/β-catenin signaling pathway proteins.The results showed that knockdown of C/EBP β promotes epithelial-mesenchymal transition(EMT)and activates gene ex-pression of Wnt/β-catenin signaling pathway in HCC cells(P＜0.05).In conclusion,C/EBP β was un-derexpressed in HCC tissues and was positively correlated with the survival prognosis of patients.Knock-down of C/EBP β may promote the proliferation,migration,and epithelial-mesenchymal transformation of HCC cells by activating the Wnt/β-catenin signaling pathway,which provides a basis for the role of C/EBP β in the occurrence and development of HCC and may be a potential target in the diagnosis and treatment of HCC.

Objective To provide a longitudinal evaluation tool based on the frequency of aggressive be-havior for the aggression assessment of schizophrenia patients.Methods The Life History of Aggression was translated and revised to form the Life History of Aggression-Chinese Version(LHA-CV)based on 369 patients diagnosed with schizophrenia in the Chengdu community and compulsory medical insti-tution.The reliability of LHA-CV was analyzed by means of split-half reliability,test-retest reliability and inter-evaluator consistency.The validity was analyzed by item analysis,construct validity and crite-rion validity.Results Item analysis found that LHA-CV had good homogeneity and discriminant validity.Exploratory factor analysis found that the Kaiser-Meyer-Olkin(KMO)test value was 0.80,and the Bartlett's sphericity test χ2=1203.46(P<0.05),and it revealed four factors including non-physical ag-gression,physical aggression,self-directed aggression and antisocial behavior/consequences.The factor loadings for all 11 items were greater than 0.40.Confirmatory factor analysis was performed on the factor model,Chi-square degree of freedom(χ2/df)was 3.61,root mean square error of approxima-tion(RMSEA)was 0.07,goodness-of-fit index(GFI)was 0.92,comparative fit index(CFI)was 0.90,incremental fit index(IFI)was 0.90,and the discriminant validity of each factor was good.The criterion validity test showed the total score of LHA-CV was positively correlated with the aggressive behavior level of MacArthur Community Violence Instrument,the total score of Buss-Perry Aggression Scale,and the score of Antisocial Personality Disorder Subscale of Personality Diagnostic Question-naire-4th Edition Plus(PDQ-4+_ASPD,P<0.05).The Cronbach's α coefficient of non-physical aggres-sion,physical aggression,self-directed aggression,antisocial behavior/consequences and LHA-CV total score were 0.82,0.73,0.74,0.56 and 0.79,respectively.The test-retest reliability,Spearman-Brown split-half reliability and intra-class correlation coefficient of LHA-CV total score were 0.82(P<0.05),0.66 and 0.99,respectively.Conclusion LHA-CV has good reliability and validity,and can be used as an evaluation tool for longitudinally assessing aggressive behavior in schizophrenia patients.

OBJECTIVE: To examine the anti-inflammatory effects and potential mechanisms of polypeptide from Moschus (PPM) in lipopolysaccharide (LPS)-induced THP-1 macrophages and BALB/c mice. METHODS: The polypeptide was extracted from Moschus and analyzed by high-performance liquid chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Subsequently, LPS was used to induce inflammation in THP-1 macrophages and BALB/c mice. In LPS-treated or untreated THP-1 macrophages, cell viability was observed by cell counting kit 8 and lactate dehydrogenase release assays; the proinflammatory cytokines and reactive oxygen species (ROS) were measured by enzyme-linked immunosorbent assay and flow cytometry, respectively; and protein and mRNA levels were measured by Western blot and real-time quantitative polymerase chain reaction (qRT-PCR), respectively. In LPS-induced BALB/c mice, the proinflammatory cytokines were measured, and lung histology and cytokines were observed by hematoxylin and eosin (HE) and immunohistochemical (IHC) staining, respectively. RESULTS: The SDS-PAGE results suggested that the molecular weight of purified PPM was in the range of 10-26 kD. In vitro, PPM reduced the production of interleukin 1β (IL-1β), IL-18, tumor necrosis factor α (TNF-α), IL-6 and ROS in LPS-induced THP-1 macrophages (P<0.01). Western blot analysis demonstrated that PPM inhibited LPS-induced nuclear factor κB (NF-κB) pathway and thioredoxin interacting protein (TXNIP)/nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain containing 3 (NLRP3) inflammasome pathway by reducing protein expression of phospho-NF-κB p65, phospho-inhibitors of NF-κB (Iκ Bs) kinase α/β (IKKα/β), TXNIP, NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and pro-caspase-1 (P<0.05 or P<0.01). In addition, qRT-PCR revealed the inhibitory effects of PPM on the mRNA levels of TXNIP, NLRP3, ASC, and caspase-1 (P<0.05 or P<0.01). Furthermore, in LPS-induced BALB/c mice, PPM reduced TNF-α and IL-6 levels in serum (P<0.05 or P<0.01), decreased IL-1β and IL-18 levels in the lungs (P<0.01) and alleviated pathological injury to the lungs. CONCLUSION PPM could attenuate LPS-induced inflammation by inhibiting the NF-κB-ROS/NLRP3 pathway, and may be a novel potential candidate drug for treating inflammation and inflammation-related diseases.

Objective: To explore the prognostic factors of extracellular NK/T cell lymphoma (ENKTL) treated with pegaspargase/L-asparaginase. Methods: The clinical data of 656 ENKTL patients diagnosed at 11 medical centers in the Huaihai Lymphoma Working Group from March 2014 to April 2021 were retrospectively analyzed. The patients were randomly divided into two groups: a training set (460 cases) and a validation set (196 cases) at 7∶3, and the prognostic factors of the patients were analyzed. A prognostic scoring system was established, and the predictive performance of different models was compared. Results: Patients' median age was 46 (34, 57) years, with 456 males (69.5% ) and 561 nasal involvement (85.5% ). 203 patients (30.9% ) received a chemotherapy regimen based on L-asparaginase combined with anthracyclines, and the 5-year overall survival rate of patients treated with P-GEMOX regimen (pegaspargase+gemcitabine+oxaliplatin) was better than those treated with SMILE regimen (methotrexate+dexamethasone+cyclophosphamide+L-asparaginase+etoposide) (85.9% vs 63.8% ; P=0.004). The results of multivariate analysis showed that gender, CA stage, the Eastern Cooperative Oncology Group performance status (ECOG PS) score, HGB, and EB virus DNA were independent influencing factors for the prognosis of ENKTL patients (P<0.05). In this study, the predictive performance of the prognostic factors is superior to the international prognostic index, Korean prognostic index, and prognostic index of natural killer lymphoma. Conclusion: Gender, CA stage, ECOG PS score, HGB, and EB virus DNA are prognostic factors for ENKTL patients treated with pegaspargase/L-asparaginase.
Male ; Humans ; Middle Aged ; Asparaginase/therapeutic use* ; Prognosis ; Retrospective Studies ; Lymphoma, Extranodal NK-T-Cell/drug therapy* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Etoposide ; Cyclophosphamide ; Methotrexate/therapeutic use* ; DNA/therapeutic use* ; Treatment Outcome

Aim To investigate the effect of methionine restriction on the proliferation, migration and invasion of human oral squamous carcinoma CAL-27 cells. Methods Cell proliferation and colony formation ability were detected by cell counting and colony forming assay. The changes in cell cycle and apoptosis were detected by propidium iodide (PI) staining flow cytometry and Annexin V/7-amino-actinomycin staining flow cytometry. The migration and invasion ability of CAL-27 was detected by scratch and Transwell assay. The expression levels of apoptosis proteins Bax and Bcl-2, cyclins CDK2 and CDK4 and migration and invasion proteins N-cadherin and E-cadherin were examined by Western blot. Results Methionine restriction significantly inhibited the proliferation and clone formation of oral squamous cancer cell CAL-27 (P < 0. 01), induced cell cycle arrest at G