This study aims to systematically characterize the targeted effects of Quanduzhong Capsules on cartilage lesions in knee osteoarthritis by integrating spatial transcriptomics data mining and animal experiments validation, thereby elucidating the related molecular mechanisms. A knee osteoarthritis model was established using Sprague-Dawley(SD) rats, via a modified Hulth method. Hematoxylin and eosin(HE) staining was employed to detect knee osteoarthritis-associated pathological changes in knee cartilage. Candidate targets of Quanduzhong Capsules were collected from the HIT 2.0 database, followed by bioinformatics analysis of spatial transcriptomics datasets(GSE254844) from cartilage tissues in clinical knee osteoarthritis patients to identify spatially specific disease genes. Furthermore, a "formula candidate targets-spatially specific genes in cartilage lesions" interaction network was constructed to explore the effects and major mechanisms of Quanduzhong Capsules in distinct cartilage regions. Experimental validation was conducted through immunohistochemistry using animal-derived biospecimens. The results indicated that Quanduzhong Capsules effectively inhibited the degenerative changes in the cartilage of affected joints in rats, which was associated with the regulation of Quanduzhong Capsules on the thioredoxin-interacting protein(TXNIP)-NOD-like receptor family pyrin domain containing 3(NLRP3)-bone morphogenetic protein receptor type 2(BMPR2)-fibronectin 1(FN1)-matrix metallopeptidase 2(MMP2) signal axis in the articular cartilage surface and superficial zones, subsequently inhibiting cartilage matrix degradation leading to oxidative stress and inflammatory diffusion. In summary, this study clarifies the spatially specific targeted effects and protective mechanisms of Quanduzhong Capsules within pathological cartilage regions in knee osteoarthritis, providing theoretical and experimental support for the clinical application of this drug in the targeted therapy on the inflamed cartilage.
Animals ; Osteoarthritis, Knee/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Rats ; Male ; Humans ; Capsules ; Female ; Disease Models, Animal

OBJECTIVE: To investigate the effect of Tongmai Hypoglycemic Capsule (THC) on myocardium injury in diabetic cardiomyopathy (DCM) rats. METHODS: A total of 24 Sprague Dawley rats were fed for 4 weeks with high-fat and high-sugar food and then injected with streptozotocin intraperitoneally for the establishment of the DCM model. In addition, 6 rats with normal diets were used as the control group. After modeling, 24 DCM rats were randomly divided into the model, L-THC, M-THC, and H-THC groups by computer generated random numbers, and 0, 0.16, 0.32, 0.64 g/kg of THC were adopted respectively by gavage, with 6 rats in each group. After 12 weeks of THC administration, echocardiography, histopathological staining, biochemical analysis, and Western blot were used to detect the changes in myocardial structure, oxidative stress (OS), biochemical indexes, protein expressions of myocardial fibrosis, and nuclear factor erythroid 2-related faactor 2 (Nrf2) element, respectively. RESULTS: Treatment with THC significantly decreased cardiac markers such as creatine kinase, lactate dehydrogenase, and creatine kinase-MB, etc., (P<0.01); enhanced cardiac function indicators including heart rate, ejection fraction, cardiac output, interventricular septal thickness at diastole, and others (P<0.05 or P<0.01); decreased levels of biochemical indicators such as fasting blood glucose, total cholesterol, triglycerides, low-density lipoprotein cholesterol, aspartate transaminase, (P<0.05 or P<0.01); and decreased the levels of myocardial fibrosis markers α-smooth muscle actin (α-SMA), and collagen I (Col-1) protein (P<0.01), improved myocardial morphology and the status of myocardial interstitial fibrosis. THC significantly reduced malondialdehyde levels in model rats (P<0.01), increased levels of catalase, superoxide dismutase, and glutathione (P<0.01), and significantly increased the expression of Nrf2, NAD(P)H:quinone oxidoreductase 1, heme oxygenase-1, and superoxide dismutase 2 proteins in the left ventricle of rats (P<0.01). CONCLUSION THC activates the Nrf2 signaling pathway and plays a protective role in reducing OS injury and cardiac fibrosis in DCM rats.
Animals ; Diabetic Cardiomyopathies/physiopathology* ; Oxidative Stress/drug effects* ; Drugs, Chinese Herbal/therapeutic use* ; Rats, Sprague-Dawley ; Myocardium/metabolism* ; Fibrosis ; Male ; Capsules ; Hypoglycemic Agents/therapeutic use* ; NF-E2-Related Factor 2/metabolism* ; Rats ; Diabetes Mellitus, Experimental/drug therapy*

Objective:To evaluate the efficacy and immunological mechanisms of pegylated interferon α-2b (Peg-IFNα-2b) antiviral therapy in treatment-naive patients with chronic hepatitis B(CHB).Methods:A total of 166 treatment-naive CHB patients, who were treated at Department of Infectious Diseases, the Second Affiliated Hospital of Nanchang University from March 2021 to March 2023, were enrolled in this study. All the patients received Peg-IFNα-2b therapy for 48 weeks. Serum hepatitis B virus (HBV) DNA, HBV serological markers, biochemical parameters, peripheral blood lymphocyte subsets and serum cytokine levels were detected and compared before and after treatment. Chi-square test, Mann-Whitney U test and paired sample t test were used for statistical comparison. Multivariate logistic regression analysis was used to analyze the influencing factors of hepatitis B surface antigen (HBsAg) seroconversion by stepwise regression method, and the receiver operator characteristic curve (ROC curve) was used to evaluate the predictive efficacy of immune indicators on HBsAg seroconversion. Results:Among the 166 treatment-naive CHB patients, the rate of HBV DNA negativity following 48 weeks of Peg-IFNα-2b therapy was 71.08%(118/166), the rate of hepatitis B e antigen (HBeAg) negativity was 32.05%(25/78), and the rate of HBsAg negativity was 20.48%(34/166). HBsAg negativity rate was 52.17%(24/46) in patients with baseline HBsAg<200 IU/mL, 10.26%(4/39) in patients with baseline HBsAg 200 to <1 200 IU/mL, and 7.41%(6/81) in patients with baseline HBsAg≥1 200 IU/mL, and the difference was statistically significant( χ2=39.37, P<0.001). After 48 weeks of treatment, serum levels of alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin (TBil), and alpha-fetoprotein (AFP) were significantly lower than those before treatment ( Z=9.33, 8.58, 5.99, 2.36, respectively, all P<0.05). lmmune indicators were detected in 58 patients, and the proportion of peripheral blood lymphocytes increased significantly post-treatment, with notable increases in CD3 + CD8 + T/CD3 + T, CD3 + CD4 + DR + /CD3 + CD4 + , CD3 + CD8 + DR + /CD3 + CD8 + , CD3 + CD8 + CD38 + /CD3 + CD8 + , CD3 + CD8 + CD28 + /CD3 + CD8 + , and CD19 + B cells, and the differences were all statistically significant ( t=-2.56, t=-8.65, Z=-3.58, t=-3.66, Z=-3.04, t=-3.62, t=-3.87, respectively, all P<0.05). Conversely, the proportion of CD3 + , CD3 + CD4 + T/CD3 + T, CD3 + CD4 + CD45RO + /CD3 + CD4 + , CD3 + CD8 + CD45RO + /CD3 + CD8 + and the CD4 + /CD8 + ratio decreased significantly post-treatment ( t=3.13, t=5.61, t=3.69, Z=3.95, Z=7.33, respectively, all P<0.05). No significant differences were observed in the proportion of CD16 + CD56 + natural killer (NK) cells, CD3 + CD4 + CD28 + /CD3 + CD4 + , CD3 + CD4 + CD38 + /CD3 + CD4 + cells before and after treatment (all P>0.05). Serum levels of interleukin(IL)-8, IL-12P70, and IL-17 significantly decreased post-treatment ( Z=2.85, 3.26, 4.12, respectively, all P<0.05), while IL-2, IL-1β, and interferon(IFN)-α levels were significantly elevated compared to baseline ( Z=-4.92, -4.85, -9.01, respectively, all P<0.001). There were no significant differences in IL-4, IL-6, and IL-10 levels before and after treatment (all P>0.05). Logistic regression analysis identified CD3 + CD8 + T/CD3 + T(odd ratios ( OR)=1.198, 95%confidence interval( CI) 1.003 to 1.432, P=0.046), CD3 + CD4 + DR + /CD3 + CD4 + ( OR=1.185, 95% CI 1.035 to 1.357, P=0.014), CD3 + CD8 + DR + /CD3 + CD8 + ( OR=0.813, 95% CI 0.690 to 0.958, P=0.013), CD3 + CD4 + CD38 + /CD3 + CD4 + ( OR=0.678, 95% CI 0.488 to 0.940, P=0.020), CD3 + CD8 + CD38 + /CD3 + CD8 + ( OR=1.272, 95% CI 1.069 to 1.512, P=0.007), CD19 + B cells( OR=0.752, 95% CI 0.582 to 0.971, P=0.029), IL-2( OR=8.568, 95% CI 1.927 to 38.087, P=0.005), and IL-17( OR=0.728, 95% CI 0.535 to 0.989, P=0.042) as independent factors influencing HBsAg seroconversion. The area under the curve (AUC) of the proportion of dCD19 + B cells (the reciprocal of CD19 + B cells) for predicting HBsAg seroconversion was 0.716, the sensitivity was 0.636, and the specificity was 0.809. The AUC of IL-2 was 0.657, the sensitivity was 0.818, and the specificity was 0.404. The AUC of dIL-17 (the reciprocal of IL-17 levels) was 0.624, the sensitivity was 0.727, and the specificity was 0.489. The AUC of IL-2 and dIL-17 as a combined predictor was 0.830, the sensitivity was 0.909, and the specificity was 0.787. Conclusions:Peg-IFNα-2b demonstrates significant antiviral, biochemical, and serological responses in treatment-naive CHB patients, with enhanced efficacy in patients exhibiting HBsAg levels <200 IU/mL. In patients with HBsAg<200 IU/mL, the rate of HBsAg negativity reached 52.17%.Peg-IFNα-2b can regulate the immune function of patients with CHB by increasing the proportion of activated T lymphocyte subsets and functional subsets. The proportion of CD19 + B cells, IL-2 levels, and IL-17 levels hold predictive value for achieving HBsAg seroconversion.

Objective To evaluate the efficacy of the enzyme-linked immunosorbent assay(ELISA),polymerase chain reaction(PCR),and gold chromatographic strip assay(GICA)in diagnosing clonorchiasis through a meta-analysis of diagnostic tests.Methods Relevant databases,including CNKI,the Wan Fang Database,VIP,and PubMed,were searched according to inclusion and exclusion criteria.Literature quality was assessed using RevMan 5.4 and Stata 18,and funnel plots,forest plots,and SROC curves were generated.Results A total of 50 articles met the inclusion criteria.Deeks'funnel plot analysis indicated no significant publication bias among the three methods.The combined effect size analysis revealed that the sensitivity and specificity of ELISA for detecting clonorchiasis were 0.93(0.89-0.95)and 0.94(0.92-0.96),respectively,with an area under the SROC curve of 0.98.For PCR,the sensitivity and specificity were 0.93(0.84-0.97)and 0.92(0.80-0.97),respectively,yielding an area under the SROC curve of 0.97.The sensitivity and specificity of the GICA method for detecting clonorchiasis were 0.91(0.83-0.96)and 0.95(0.87-0.98),respectively,with an area under the SROC curve of 0.97.Conclusions In the diagnosis of clonorchiasis,ELISA,PCR and GICA have high diagnostic value,but their ranges differ from each other.

Blood from a case of group B epidemic cerebrospinal meningitis identified in February 2024 in Ganzhou City,Jiangxi Province,and throat swabs from close contacts were collected for isolation and culture.The isolates were subjected to serogrouping,drug sensitivity testing,and whole genome sequencing and analysis,to provide a basis for epidemiological inves-tigation and clinical drug use.One strain of Neisseria meningitidis was isolated from the blood of the case and denoted group B.The MLST type was ST-7962,with no clonal group attribution.The phylogenetic tree showed that it was genetically close to the 1977 Shanghai carrier isolate(id-52231).Drug sensitivity results indicated that the strain was sensitive to 8 drugs:azithro-mycin,cefotaxime,minocycline,ceftriaxone,chloramphenicol,meropenem,rifampicin,and benzylpenicillin;resistant to cot-rimoxazole,levofloxacin,and ciprofloxacin;and showed an intermediate response to penicillin.This report describes the first case of ST-7962 group B meningoencephalitis found in Jiangxi Province.Monitoring of Neisseria meningitidis carriage,drug re-sistance,and molecular characteristics of strains in the healthy population in this region should be strengthened,to provide la-boratory support for the clinical use of medications,traceability,and control of the pathogen underlying meningoencephalitis infection.

Objective To explore the characteristics of fluid flow within loaded osteons under different boundary conditions.Methods The COMSOL Multiphysics software was used to establish a three-dimensional(3D)finite element model of osteons with different boundary conditions,and the variation rules of pore pressure and flow velocity of osteons under different inner wall pulsating blood pressures and outer wall elastic constraint conditions were analyzed.Results As the pulsatile blood pressure inside the osteon increased from 0 mmHg(1 mmHg=0.133 kPa)to 300 mmHg,the peak pore pressure within the osteon correspondingly increased from 26 kPa to 68 kPa.As the elastic constraint on the outer wall of osteons changed from being completely elastic to completely constrained,the peak pore pressure within osteons increased from 15 kPa to 26 kPa,and the peak flow velocity increased from 0.04 um/s to 0.07 um/s.Conclusions This study reveals the influence laws of changes in boundary conditions such as the pulsatile blood pressure on the inner wall and the elastic constraint on the outer wall of osteons on fluid flow characteristics within loaded osteons.These findings are conducive to a deeper understanding of the mechanical response mechanisms of bone tissues in both physiological and pathological states,and provide an important theoretical basrs for further researches on bone mechanotransduction.

Meniere's disease represents an idiopathic inner ear disorder characterized by endolymphatic hy-drops.Currently,the research methods for identifying genes associated with this disease mainly involve first-genera-tion sequencing and second-generation sequencing.This article reviews research on the genetic study of Meniere's disease,mainly summarizing the candidate genes with repeated pedigree validation in familial Meniere's disease,as well as those frequently reported in sporadic Meniere's disease.

Objective The optimal ventilation mode for patients with obesity undergoing laparoscopic surgery remains unclear.We aimed to compare the effects of pressure-controlled ventilation(PCV)and pressure-controlled ventilation-volume guaranteed(PCV-VG)on perioperative oxygenation and respiratory mechanics in patients undergoing laparoscopic bariatric surgery.Methods In this prospective randomized controlled study,114 subjects who underwent laparoscopic bariatric surgery from Jan 2017 to Mar 2020 were randomly divided into PCV-VG group(n=56)or PCV group(n=54),with 4 lost to follow-up.The perioperative pulmonary mechanics and arterial blood gas results were compared between the two groups.Postoperative extubation time,the incidences of postoperative pulmonary complications(PPCs)and abnormal radiographic changes(ARCs)were also recorded.Results During intraoperative pneumoperitoneum,the pulmonary dynamic compliance(Cdyn)was significantly lower in PCV-VG group than that in PCV group(T2:P=0.022;T3:P=0.039).There were no significant differences in perioperative oxygenation index and respiratory peak pressure(Ppeak)between the two groups.Eighty-six patients(78.2%)had ARCs on the 1st day after surgery,and 10 cases(9.1%)developed PPCs.There was no significant difference in extubation time,ARCs or PPCs between the two groups.After adjustment,anesthesia duration and oxygenation index before anesthesia induction were significantly associated with extubation time.Anesthesia duration of more than 2 hours was a risk factor for postoperative ARCs.Conclusion Compared with PCV-VG mode,PCV mode provides better pulmonary Cdyn during intraoperative pneumoperitoneum for patients undergoing laparoscopic bariatric surgery.

Objective To establish the HPLC analysis method for ketoconazole related substances,and to provide technical support for the improvement of the quality standard and the purity of ketoconazole.Methods Gradient elution conditions were optimized based on the chromatographic parameters outlined in the 2024"British Pharmacopoeia"for ketoconazole cream.A C18 column(4.6 mm×150 mm,3 μm)was used to facilitate the elution process using a gradient of acetonitrile and acetate buffer,and detection performed at a wavelength of 230 nm.Results The known impurities and potentially genotoxic impurities in the material drugs of ketoconazole can be more effectively separated using the established methods,which are both robust and highly sensitive.The content of the two potentially geno toxic impurities,six known impurities and unknown impurities in the 21 batches of ketoconazole sourced from five raw material pharmaceutical companies is below the specified limit requirements.Conclusion This method contributes to improving the quality of ketoconazole ingredients,ensuring the safety of ketoconazole preparations,and better supporting the regulatory supervision.

Objective Network pharmacology and molecular docking techniques were used to predict the potential mechanisms by which the active components of Piper nigrum(PN)regulate depressive-like behaviors in chronic restraint stress(CRS)mice.Methods The major chemical components and targets of PN were screened using the Traditional Chinese Medicine Systems Pharmacology database.Targets related to ferroptosis and depression were obtained from the Online Mendelian Inheritance in Man,GeneCards,and FerrDB databases.The intersecting targets were then subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Gnomes(KEGG)pathway enrichment analyses,and molecular docking was performed to validate the binding capacities between the core targets and their corresponding active components.Finally,we established a CRS mouse model.Mice were treated with PN 75,150,and 300 mg/kg for 4 weeks,followed by behavioral assessments and reverse transcription-quantitative polymerase chain reaction(RT-qPCR)to verify the expression of core genes.Results Nine active components were screened from PN,corresponding to 27 targets,and 8377 targets related to depression and 547 targets associated with ferroptosis were screened from the databases.The intersection of these three sets resulted in 25 target genes.KEGG enrichment analysis revealed that these core targets were predominantly enriched in signaling pathways,including cholinergic synapses,serotonergic synapses,and neuroactive ligand-receptor interactions.Molecular docking result showed that the main active components of PN had strong binding affinities for the targets CHRM2,SLC6A4,PTGS2,and SLC6A2.Behavioral assessments demonstrated that PN significantly increased the sucrose preference index(P＜0.01,P＜0.001),reduced immobility time in the tail suspension and forced swimming tests(P＜0.01,P＜0.001),and enhanced exploratory behavior in the open field test(P＜0.05.P＜0.01,P＜0.001).PN significantly reduced the serum levels of inflammation markers(P＜0.05.P＜0.01,P＜0.001),as shown by enzyme-linked immunosorbent assay,and neurotransmitter analysis revealed that PN significantly increased the levels of serotonin and acetylcholine in the mouse hippocampus(P＜0.05).RT-qPCR showed that PN demonstrated the mRNA expression of SLC6A4(P＜0.05.P＜0.01,P＜0.001).Conclusions PN may improve depressive-like behavior in mice by modulating serotonin and acetylcholine levels,inhibiting inflammatory responses,participating in immune regulation,and exerting neuroprotective effects.