ObjectiveTo analyze the epidemiological trends and characteristics of brucellosis in humans (hereinafter referred to as brucellosis) in Tangshan City, Hebei Province from 2016 to 2023, and to provide a scientific basis for formulating brucellosis prevention and control strategies in the region. MethodsThe incidence data of human brucellosis in Tangshan City from 2016 to 2023 were collected from the China Disease Prevention and Control Information System. The diagnosis time, infection route, and clinical characteristics of the cases were obtained from the case investigation reports. Descriptive epidemiological methods were used to analyze the temporal, spatial, demographic distributions, and clinical characteristics of human brucellosis. Brucella species were identified using agglutination tests with bacterial suspension and A/M antigen-positive serum. ResultsA total of 2 193 cases of human brucellosis were confirmed and clinically diagnosed in Tangshan City from 2016 to 2023, with the peak incidence occured from March to August, and which exhibited distinct geographic distribution patterns. The highest incidence rate was found in people aged 60‒<70 years. The occupation of cases were primarily farmers. The incidence rate in males (528/100 000) was higher than that in females (184/100 000). All cases had confirmed exposure to infected animals or contaminated animal products. ConclusionThe epidemic of human brucellosis in Tangshan exhibited an overall steady downward trend from 2016 to 2023, except for a slight increase in 2016 and 2021, with the incidence rate controlled at 289/100 000‒335/100 000. The prevention and control situation of human brucellosis still remains severe, with the highest incidence rate in the eastern region of Tangshan, which are characterized by the breeding, slaughtering, and processing of cattle and sheep. Therefore, it it is necessary to enhance the prevention and control of human brucellosis among the personnel engaged in these industries in the eastern areas.

ObjectiveTo compare the clinical features of patients with hepatitis B virus （HBV）-related early-onset liver cancer and those with late-onset liver cancer， to assess the severity of the disease， and to provide a theoretical basis for the early diagnosis and treatment of liver cancer. MethodsA retrospective analysis was performed for 695 patients who were diagnosed with HBV-related liver cancer for the first time in Guangzhou Eighth People’s Hospital， Guangzhou Medical University， from January 2019 to August 2023， among whom 93 had early-onset liver cancer （defined as an age of50 years for female patients and40 years for male patients） and 602 had late-onset liver cancer （defined as an age of ≥50 years for female patients and ≥40 years for male patients）. Related clinical data were collected， including demographic data， clinical symptoms at initial diagnosis， comorbidities， smoking history， drinking history， family history， routine blood test results， biochemical parameters of liver function， serum alpha-fetoprotein（AFP）， virological indicators， coagulation function， and imaging findings. The pan-inflammatory indices neutrophil-to-lymphocyte ratio （NLR）， platelet-to-lymphocyte ratio （PLR）， and lymphocyte-to-monocyte ratio （LMR） were calculated， as well as FIB-4 index， aspartate aminotransferase-to-platelet ratio index （APRI）， S index， Model for End-Stage Liver Disease （MELD） score， Child-Turcotte-Pugh （CTP） score， albumin-bilirubin （AIBL） grade， and Barcelona Clinic Liver Cancer （BCLC） stage. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test or Fisher’s exact test were used for comparison of categorical data between two groups. ResultsThere were significant differences between the two groups in the proportion of male patients and the incidence rates of diabetes， hypertension， and fatty liver disease （χ²=6.357， 15.230， 11.467， and 14.204， all P0.05）， and compared with the late-onset liver cancer group， the early-onset liver cancer group had a significantly higher proportion of patients progressing to liver cancer without underlying cirrhosis （χ²=24.657， P0.001） and a significantly higher proportion of patients with advanced BCLC stage （χ²=6.172， P=0.046）. For the overall population， the most common clinical symptoms included abdominal distension， abdominal pain， poor appetite， weakness， a reduction in body weight， edema of both lower limbs， jaundice， yellow urine， and nausea， and 55 patients （7.9%） had no obvious symptoms at the time of diagnosis and were found to have liver cancer by routine reexamination， physical examination suggesting an increase in AFP， or radiological examination indicating hepatic space-occupying lesion； compared with the late-onset liver cancer group， the patients in the early-onset liver cancer group were more likely to have the symptoms of abdominal distension， abdominal pain， and jaundice （all P0.05）. Compared with the late-onset liver cancer group， the early-onset liver cancer group had a significantly larger tumor diameter （Z=2.845， P=0.034）， with higher prevalence rates of multiple tumors and intrahepatic， perihepatic， or distant metastasis （χ²=5.889 and 4.079， both P0.05）， and there were significant differences between the two groups in tumor location and size （χ²=3.948 and 11.317， both P0.05）. Compared with the late-onset liver cancer group， the early-onset liver cancer group had significantly lower FIB-4 index， proportion of patients with HBsAg ≤1 500 IU/mL， and levels of LMR and Cr （all P0.05）， as well as significantly higher positive rate of HBeAg and levels of log₁₀ HBV DNA， AFP， WBC， Hb， PLT， NLR， PLR， TBil， ALT， Alb， and TC （all P0.05）. ConclusionCompared with late-onset liver cancer， patients with early-onset liver cancer tend to develop liver cancer without liver cirrhosis and have multiple tumors， obvious clinical symptoms， and advanced BCLC stage， which indicates a poor prognosis.

The relationship between hyperuricemia (HUA) and erectile dysfunction (ED) remains inadequately understood. Given that HUA is often associated with various metabolic disorders, this study aims to explore the multivariate linear impacts of metabolic parameters on erectile function in ED patients with HUA. A cross-sectional analysis was conducted involving 514 ED patients with HUA in the Department of Andrology, Jiangsu Province Hospital of Chinese Medicine (Nanjing, China), aged 18 to 60 years. General demographic information, medical history, and laboratory results were collected to assess metabolic disturbances. Sexual function was evaluated using the 5-item version of the International Index of Erectile Function (IIEF-5) questionnaire. Based on univariate analysis, variables associated with IIEF-5 scores were identified, and the correlations between them were evaluated. The effects of these variables on IIEF-5 scores were further explored by multiple linear regression models. Fasting plasma glucose ( β = -0.628, P < 0.001), uric acid ( β = -0.552, P < 0.001), triglycerides ( β = -0.088, P = 0.047), low-density lipoprotein cholesterol ( β = -0.164, P = 0.027), glycated hemoglobin (HbA1c; β = -0.562, P = 0.012), and smoking history ( β = -0.074, P = 0.037) exhibited significant negative impacts on erectile function. The coefficient of determination ( R ²) for the model was 0.239, and the adjusted R ² was 0.230, indicating overall statistical significance ( F -statistic = 26.52, P < 0.001). Metabolic parameters play a crucial role in the development of ED. Maintaining normal metabolic indices may aid in the prevention and improvement of erectile function in ED patients with HUA.
Humans ; Male ; Erectile Dysfunction/metabolism* ; Hyperuricemia/metabolism* ; Adult ; Middle Aged ; Cross-Sectional Studies ; Glycated Hemoglobin/metabolism* ; Blood Glucose/metabolism* ; Uric Acid/blood* ; Young Adult ; Triglycerides/blood* ; Adolescent ; Cholesterol, LDL/blood* ; Penile Erection/physiology* ; Surveys and Questionnaires

Lingguizhugan Decoction (LGZG) demonstrates significant efficacy in treating various cardiovascular diseases clinically, yet its precise mechanism of action remains elusive. This study aimed to elucidate the potential mechanisms and effects of LGZG on isoproterenol (ISO) continuous stimulation-induced chronic heart failure (CHF) in mice, providing direct experimental evidence for further clinical applications. In vivo, continuous ISO infusion was administered to mice, and ventricular myocytes were utilized to explore LGZG?s potential mechanism of action on the ?1-adrenergic receptor (?1-AR)/Gs/G protein-coupled receptor kinases (GRKs)/?-arrestin signaling deflection system in the heart. The findings reveal that LGZG significantly reduced the messenger ribonucleic acid (mRNA) expression of hypertrophy-related biomarkers [atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP)] and improved cardiac remodeling and left ventricular diastolic function in mice with ISO-induced CHF. Furthermore, LGZG inhibited the overactivation of Gs/cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling and downregulated the downstream transcriptional activity of cAMP-response element binding protein (CREB) and the expression of the coactivator CBP/P300. Notably, LGZG downregulated the expression of ?-arrestin1 and GRK 2/3/5 while upregulating the expression of ?1-AR and ?-arrestin2. These results suggest that LGZG inhibits Gs/cAMP/PKA signaling and ?-arrestin/GRK-mediated desensitization and internalization of ?1-AR, potentially exerting cardioprotective effects through the synergistic regulation of the ?1-AR/Gs/GRKs/?-arrestin signaling deflection system via multiple pathways.
Animals ; Heart Failure/genetics* ; Signal Transduction/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Mice ; Male ; G-Protein-Coupled Receptor Kinases/genetics* ; Mice, Inbred C57BL ; Humans ; Isoproterenol ; Arrestins/genetics* ; Chronic Disease

Objective To investigate the distribution of traditional Chinese medicine(TCM)constitution in chronic hepatitis B(CHB)patients complicated with metabolism associated fatty liver disease(MAFLD),and to explore the correlation of the complication of MAFLD with TCM constitution and body composition,thus to determine their predictive values for the complication of MAFLD in CHB patients.Methods A retrospective study was adopted.The study started from the collection of the clinical data of 235 outpatients who attended the Department of Hepatology of Guangdong Provincial Hospital of Integrated Traditional Chinese and Western Medicine from January 2022 to December 2023,and was diagnosed as CHB following the diagnostic criteria.According to the controlled attenuation parameter(CAP)value,134 cases of CHB patients were allocated to the non-MAFLD group(CAP＜238 dB/m)and 101 cases were allocated to the MAFLD group(CAP≥238 dB/m).And then the distribution of TCM constitution in the two groups was observed.In addition,according to the body mass index(BMI)value,the patients were divided into the non-obese group(141 cases,BMI＜24.0 kg/m2)and the overweight/obese group(94 cases,BMI≥24.0 kg/m2).And then the logistic regression was used to analyze the independent risk factors for the complication of MAFLD in CHB patients,multivariate logistic regression was used to analyze the influencing factors,and receiver operating characteristic(ROC)curve was used to analyze the predictive value of the influencing factors for the complication of MAFLD in CHB patients and to determine their optimal cut-off values.Results(1)The constitutions of CHB patients in the MAFLD group were predominated by balanced constitution(36.6%),damp-heat constitution(20.8%),and phlegm-damp constitution(14.9%),which accounted for 72.3%in total.(2)In CHB patients complicated with MAFLD,the overweight/obese group had higher levels of γ-glutamyl-transpeptidase(γ-GT),BMI,total body fat mass(TBFM),total muscle mass(TMM),total body water(TBW),interacel1ular water(ICW),extracellular water(ECW),body fat ratio(BFR),visceral fat area(VFA),basal metabolism(BM),and trunk fat mass(TFM)than the non-obese group,and the differences were statistically significant(P＜0.05 or P＜0.01).(3)The results of multivariate logistic regression analysis showed that the white blood cell(WBC)count,blood uric acid(UA),triglyceride(TG),high-density lipoprotein cholesterol(HDL-C),and VFA were the influencing factors for the complication of MAFLD in the CHB patients in clinic.(4)The results of ROC curve analysis showed that in CHB patients,the areas under the ROC curve(AUC)for age,TG,UA,and VFA were 0.532,0.680,0.738,and 0.859 respectively;the optimal cut-off values of VFA in CHB patients,non-obese CHB patients,and overweight/obese CHB patients were 74.98,66.5 and 112.2 cm2 respectively,and the optimal cut-off values of VFA in patients with balanced constitution,phlegm-damp constitution,and damp-heat constitution were 85.50,66.50,and 74.98 cm2 respectively.The AUC values of VFA in various populations were significantly higher than those of age,TG,and UA,and the combined prediction by multivariate analysis has higher predictive value than that by univariate analysis.Conclusion The AUC value of VFA for predicting the risk of MAFLD is the highest in patients with CHB,and the possibility of the complication of MAFLD increased with the increase of the cut-off point level of VFA.The optimal cut-off values of VFA varies in non-obese group and overweight/obese group of CHB patients and in CHB patients with different TCM constitution.

Objective:To establish a mesenchymal stem cell(MSC)-based in vitro cell model for the evaluation of mouse bone marrow acute graft-versus-host disease(aGVHD).Methods:Female C57BL/6N mice aged 6-8 weeks were used as bone marrow and lymphocyte donors,and female BALB/c mice aged 6-8 weeks were used as aGVHD recipients.The recipient mouse received a lethal dose(8.0 Gy,72.76 cGy/min)of total body γ irradiation,and injected with donor mouse derived bone marrow cells(1× 107/mouse)in 6-8 hours post irradiation to establish a bone marrow transplantation(BMT)mouse model(n=20).In addition,the recipient mice received a lethal dose(8.0 Gy,72.76 cGy/min)of total body γ irradiation,and injected with donor mouse derived bone marrow cells(1 × 107/mouse)and spleen lymphocytes(2 × 106/mouse)in 6-8 hours post irradiation to establish a mouse aGVHD model(n=20).On the day 7 after modeling,the recipient mice were anesthetized and the blood was harvested post eyeball enucleation.The serum was collected by centrifugation.Mouse MSCs were isolated and cultured with the addition of 2％,5％,and 10％recipient serum from BMT group or aGVHD group respectively.The colony-forming unit-fibroblast(CFU-F)experiment was performed to evaluate the potential effects of serums on the self-renewal ability of MSC.The expression of CD29 and CD105 of MSC was evaluated by immunofluorescence staining.In addition,the expression of self-renewal-related genes including Oct-4,Sox-2,and Nanog in MSC was detected by real-time fluorescence quantitative PCR(RT-qPCR).Results:We successfully established an in vitro cell model that could mimic the bone marrow microenvironment damage of the mouse with aGVHD.CFU-F assay showed that,on day 7 after the culture,compared with the BMT group,MSC colony formation ability of aGVHD serum concentrations groups of 2％and 5％was significantly reduced(P＜0.05);after the culture,at day 14,compared with the BMT group,MSC colony formation ability in different aGVHD serum concentration was significantly reduced(P＜0.05).The immunofluorescence staining showed that,compared with the BMT group,the proportion of MSC surface molecules CD29+and CD 105+cells was significantly dereased in the aGVHD serum concentration group(P＜0.05),the most significant difference was at a serum concentration of 10％(P＜0.001,P＜0.01).The results of RT-qPCR detection showed that the expression of the MSC self-renewal-related genes Oct-4,Sox-2,and Nanog was decreased,the most significant difference was observed at an aGVHD serum concentration of 10％(P＜0.01,P＜0.001,P＜0.001).Conclusion:By co-culturing different concentrations of mouse aGVHD serum and mouse MSC,we found that the addition of mouse aGVHD serum at different concentrations impaired the MSC self-renewal ability,which providing a new tool for the field of aGVHD bone marrow microenvironment damage.

Objective:To discover the relationship between the RNF213 gene and acute myeloid leukemia(AML),and explore the effect of RNF213 on the proliferation and apoptosis of THP-1 cells.Methods:Analyze the expression of RNF213 gene in AML and its relationship with prognosis through the GEPIA database.Collecting 30 AML patients and non-tumor hematological patients who went to the Affiliated Hospital of Zunyi Medical University from January 2017 to January 2022.RT-qPCR and Western blot were used to detect the expression levels of RNF213 mRNA and protein.Perform survival of patients was analysed by Kaplan-Meier.Meanwhile,the expression levels of RNF213 mRNA and protein were detected in AML cell lines(THP-1,OCI-AML2).CRISPR-Cas9 was used to knockdown the RNF213 gene in THP-1 cells;flow cytometry was used to detect apoptosis rate of cell.CCK-8 and colony formation assay were used to detect cell proliferation.Western blot was used to detect the expression level of Cleaved-Caspase 3 protein.Results:Compared with the control group,the expression level of RNF213 in AML patients was significantly increased,and patients with high expression of RNF213 have a worse prgnosis.Higher expression level of RNF213 protein in THP-1 cells.After knocking down the RNF213 gene of THP-1 cells,cell proliferation was significantly reduced,and the apoptosis rate and expression of apoptosis related protein Cleared-Caspase3 were significantly increased.Conclusion:AML patients have high expression of RNF213,and the prognosis of high expression patients is poor.The RNF213 gene affects AML cell proliferation and apoptosis,and may be a prognostic marker and potential therapeutic target for AML.