The present study aimed to establish an LC-MS/MS method for the quantification of tiamulin in minipig plasma and to further conduct a pharmacokinetic comparison of different formulations. The plasma samples were extracted with acetonitrile (meloxicam as internal standard), separated on a C18 column, and quantified by multiple reaction monitoring mode (ESI+). Sanyuan minipigs were used as experimental animals. Plasma samples were collected after intravenous injection (10 mg/kg) and intragastric administration (20 mg/kg). The method showed good linearity, with intra- and inter-batch RSD of 1.00%–8.13% and RE within ±15%. The extraction recovery, matrix effect and stability of the analytical methods met the relevant requirements. Tiamulin fumarate active pharmaceutical ingredient was intravenously administered, with c0 of about (4383.73±2676.78) ng/mL, AUC0-t of about (4803.50±965.68) h·ng/mL, t1/2 of about (4.66±1.68) h, and CL of about (2.14±0.46) L/(kg·h). Three tiamulin formulations were intragastrically administered, with cmax of (552.00±328.55), (545.00±136.97) and (590.60±237.02) ng/mL, tmax of (1.47±0.68), (0.69±0.75) and (0.72±0.72) h, and F of 24.85%, 15.28% and 16.97%, respectively. The validated method meets the requirements for biological sample analysis and is applicable for the pharmacokinetic evaluation of tiamulin formulations in minipigs.

Kidney-Yang deficiency syndrome is a common geriatric disease that underlies chronic conditions such as diabetic nephropathy, chronic kidney disease, and osteoporosis. As age progresses, the kidney-Yang deficiency syndrome showcases increasingly pronounced manifestations, emerging as a key factor in the comorbidities experienced by elderly patients and affecting their quality of life and overall health status. Traditional Chinese medicine(TCM) has been extensively utilized in the treatment of kidney-Yang deficiency syndrome, with Epimedii Folium, Cinnamomi Cortex, and Lycii Fructus widely used in clinical settings. Despite the complexity of the molecular mechanisms involved in treating kidney-Yang deficiency syndrome, the potential therapeutic value of TCM remains compelling. Delving into the mechanisms of TCM treatment of kidney-Yang deficiency syndrome by regulating the neuro-endocrine-immune system can provide a scientific basis for targeted treatments of this syndrome and lay a foundation for the modernization of TCM. The pathophysiology of kidney-Yang deficiency syndrome involves multiple systems, including the interaction of the neuro-endocrine-immune system, the decline in renal function, the intensification of oxidative stress responses, and energy metabolism disorders. Understanding these mechanisms and their interrelationships can help untangle the etiology of kidney-Yang deficiency syndrome, aiding clinicians in making more precise diagnoses and treatments. Furthermore, the research on the specific applications of TCM in research on these pathological mechanisms can enhance the international recognition and status of TCM, enabling it to exert a greater global influence.
Humans ; Yang Deficiency/physiopathology* ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Kidney Diseases/physiopathology* ; Neurosecretory Systems/physiopathology* ; Animals ; Kidney/physiopathology* ; Endocrine System/physiopathology* ; Immune System/physiopathology*

Objective To investigate the effect of miR-129-1-3p on the osteogenic differentiation of human bone marrow mesenchymal stem cells(hBMSCs)and its potential mechanism.Methods Negative control group,the miR-129-1-3p mimic group,the miR-129-1-3p inhibitor group and the corresponding negative control were constructed and transfected into hBMSCs.The formation of calcium-mineralized nodules was observed by alkaline phosphatase staining and alizarin red S staining.The expression levels of miR-129-1-3p and osteogenic differentiation markers were detected by qRT-PCR.Western blot detected the protein expressions of bone mor-phogenetic protein 2(BMP2),SMAD1 and p-SMAD1.Results After transfection,the expression level of miR-129-1-3p in mimic group was significantly increased(P＜0.05),the number of mineralized nodules was significantly decreased,and the expression levels ofBMP2,Runt-related transcription factor 2(RUNX2),osteocalcin(OCN)mRNA were significantly down-regulated(P＜0.05).BMP2 and p-SMAD1 protein were also significantly down-regulated(P＜0.05)compared with Mimic-NC group.The expression levels of BMP2,RUNX2,OCN mRNA were significantly up-regulated in inhibitor group(P＜0.05)compared with Inhibitor-NC group.BMP2 and p-SMAD1 protein were significantly up-regulated in inhibitor group(P＜0.05).Conclusion miR-129-1-3p can inhibit the osteo-genic differentiation of human bone marrow mesenchymal stem cells by suppressing BMP2/SMAD1 signaling pathway.

OBJECTIVES: To evaluate the impact of HBV infection on pre- and postpartum health-related quality of life (HRQoL) in pregnant women. METHODS: A prospective matched cohort consisting of 70 HBV-infected and 70 healthy pregnant women was recruited from the Fifth Affiliated Hospital of Guangzhou Medical University between April 17 and September 25, 2023. HRQoL of the participants was assessed at 16-24 weeks of gestation, between 32 weeks and delivery, and 5-13 weeks postpartum. Mixed linear models were used for evaluating temporal trends of HRQoL changes, and univariate ANOVA with multiple linear regression was used to identify the predictors of HRQoL. RESULTS: Compared with healthy pregnant women, HBV-infected pregnant women had consistently lower total HRQoL scores across all the 3 intervals, with the lowest scores observed between 32 weeks of gestation and delivery, during which these women had significantly reduced mental component scores (74.27±13.43 vs 80.21±12.9, P=0.009) and postpartum mental (76.52±16.19 vs 85.02±6.51, P<0.001) and physical component scale scores (77.17±14.71 vs 83.09±10.1, P=0.009). HBV infection was identified as an independent risk factor affecting HRQoL during late pregnancy and postpartum periods. Additional independent risk factors for postpartum HRQoL reduction included self-pay medical expenses, spouse's neutral attitude toward the current pregnancy, and preexisting comorbidities (all P<0.05). CONCLUSIONS HRQoL of pregnant women deteriorates progressively in late pregnancy, and HBV infection exacerbates reductions of physical function and role emotion in late pregnancy and after delivery, suggesting the importance of targeted interventions for financial burdens, partner support and comorbid conditions to improve HRQoL of pregnant women with HBV infection.
Humans ; Female ; Pregnancy ; Quality of Life ; Prospective Studies ; Postpartum Period ; Hepatitis B, Chronic/psychology* ; Adult ; Pregnancy Trimester, Third ; Pregnancy Trimester, Second ; Pregnancy Complications, Infectious

Objective To investigate the effect of miR-129-1-3p on the osteogenic differentiation of human bone marrow mesenchymal stem cells(hBMSCs)and its potential mechanism.Methods Negative control group,the miR-129-1-3p mimic group,the miR-129-1-3p inhibitor group and the corresponding negative control were constructed and transfected into hBMSCs.The formation of calcium-mineralized nodules was observed by alkaline phosphatase staining and alizarin red S staining.The expression levels of miR-129-1-3p and osteogenic differentiation markers were detected by qRT-PCR.Western blot detected the protein expressions of bone mor-phogenetic protein 2(BMP2),SMAD1 and p-SMAD1.Results After transfection,the expression level of miR-129-1-3p in mimic group was significantly increased(P＜0.05),the number of mineralized nodules was significantly decreased,and the expression levels ofBMP2,Runt-related transcription factor 2(RUNX2),osteocalcin(OCN)mRNA were significantly down-regulated(P＜0.05).BMP2 and p-SMAD1 protein were also significantly down-regulated(P＜0.05)compared with Mimic-NC group.The expression levels of BMP2,RUNX2,OCN mRNA were significantly up-regulated in inhibitor group(P＜0.05)compared with Inhibitor-NC group.BMP2 and p-SMAD1 protein were significantly up-regulated in inhibitor group(P＜0.05).Conclusion miR-129-1-3p can inhibit the osteo-genic differentiation of human bone marrow mesenchymal stem cells by suppressing BMP2/SMAD1 signaling pathway.

Objective To assess the efficacy of an innovative operational management model in enhancing the refined operational management of a public hospital.Methods An innovative operational management model,"One Body,Two Wings and Three Drives",was developed,which involved establishing a systematic operational management system,strengthening per-formance and cost control,and reinforcing the supporting roles of discipline construction,scientific and technological innovation,and smart hospital initiatives.This comprehensive approach aimed to systematically promote hospital operational management re-forms and improve overall efficiency and quality.Results After using this model,the hospital presented continuous improve-ments in operational efficiency and medical quality,with key performance indicators trending positively.Over the past three years,the average annual growth rate of outpatient and emergency service visits reached 6.6％,inpatient service visits increased by 5.7％,and the Case Mix Index(CMI)rose by 0.22 over two consecutive years.Conclusion This model is highly systemat-ic,practical,and policy-compatible,providing a replicable path for the high-quality development of public hospitals.

Objective:To explore the clinical and pathological features and survival outcomes of patients with early-onset intrahepatic cholangiocarcinoma (EOICC).Methods:This is a multicenter, retrospective cohort study. Data of 1 160 intrahepatic cholangiocarcinoma patients undergoing radical resection in 14 tertiary Grade A hospitals in China from January 2010 to November 2021 were retrospectively collected. The cohort included 632 males and 528 females, aged( M (IQR)) 61 (14) years (range: 22 to 93 years). ICC aged ≤50 years at the time of diagnosis was defined as EOICC and >50 years as late-onset intrahepatic cholangiocarcinoma (LOICC). Of these, there were 247 cases in the EOICC group and 913 cases in the LOICC. The clinical and pathological characteristics of both groups were analyzed and compared using the independent sample t-test, Mann-Whitney U test or Kaplan-Meier method. Univariate and multivariate Cox regression models for patient outcomes were constructed and forest graphed. Results:Compared with the patients in the LOICC group, patients in the EOICC group had lower carcinoembryonic antigen levels (2.5(4.0) μg/L vs. 3.1(5.2)μg/L, U=124 899, P=0.009) and CA19-9 level (63.4(524.7)U/ml vs. 77.9(611.3)U/ml, U=120 320, P=0.013), higher levels of ALT (29(35)U/L vs. 24(26)U/L, U=101 214, P=0.013), a lower score of the Eastern US Cooperative Oncology Group (0 score patients: 54.7% vs. 44.1%, χ2=12.472, P=0.014), higher TNM stage ( χ2=11.807, P=0.038), and proportion of lymph node dissection (62.3% vs. 54.1%, χ2=5.355, P=0.021). Patients in the two groups in sex, first diagnosis symptoms, intrahepatic bile duct stone history, nail protein, albumin, total bilirubin, transaminase, liver function Child-Pugh grade, T stage, stage, N stage, preoperative laparoscopic exploration proportion, tumor diameter, vascular invasion proportion, differentiation, margin, intraoperative bleeding, postoperative complications, postoperative hospital days were no statistical significance (all P>0.05). Patients in the EOICC group had better outcomes than the LOICC group (median survival time: 29.7 months vs. 25.0 months, 3-year overall survival: 45.1% vs. 37.8%, P=0.027). Conclusion:EOICC patients are better than LOICC patients in carcinoembryonic antigen, CA19-9, ALT, physical strength status and TNM stage, and the long-term prognosis is also better than LOICC patients.

Objective To investigate the clinical diagnostic value of serum sTREM2 level in patients with cerebral small vessel disease(CSVD)and its correlation with depression and its severity.Methods A total of 208 CSVD inpatients admitted in Department of Neurology of the First Affiliated Hospital of Shihezi University from December 2023 to November 2024 were en-rolled,and according to their score of HAMD,they were divided into a depression group(CSVD+D group,112 cases)and a non-depression group(CSVD—D group,96 cases).According to the 17-item HAMD,the depression group(CSVD+D group)was further divided into mild(8-17,n=80),moderate(18-24,n=27)and severe depression(≥25,n=5)subgroups.Another 208 healthy individuals who taking health checkups in the same period were selected and served as the control group.The general clinical data were compared among the groups and subgroups,and mul-tivariate logistic regression analysis was applied to identify the risk factors for the occurrence of depression and the relationship between sTREM2 and depression severity in the CSVD patients.ROC curve was plotted to evaluate the predicative performance of serum sTREM2 level for the occurrence of depression in the CSVD patients.Results The serum sTREM2 level was remark-ably higher in the CSVD patients than the control group(5.95±3.82 μg/L vs 1.40±1.21 μg/L,P＜0.01).ROC curve analysis indicated that the AUC value of serum sTREM2 level in predicting CSVD was 0.917,with a sensitivity of 87.52％and a specificity of 85.64％,and an optimal cut-ff value of 2.272 μg/L.The CSVD+D group also had significantly higher serum sTREM2 level than the CSVD—D group(6.40±3.93 μg/L vs 5.01±2.87 μg/L,P＜0.01).Multivariate logistic regression analysis showed that serum sTREM2 level was an independent influencing factor for occurrence of depression in the CSVD patients(OR=1.115,95％CI:1.019-1.220,P=0.018).Statistical difference was also observed in the patients without and with mild,moderate and severe depression(P＜0.05).Multivariate ordinal logistic regression analysis revealed that serum sTREM2 level was an independent influencing factor for mild,moderate and severe depression(OR=1.113,95％CI:1.013-1.223,P=0.026;OR=1.135,95％CI:1.004-1.284,P=0.043).The AUC value of serum sTREM2 level in predicting depressive symptoms in CSVD patients was 0.603.Conclusion Serum sTREM2 is closely associated with CSVD patients.Its level may provide certain reference value for clinical diagnosis of CSVD,and has potentially predictive value for the occurrence of depression in the CSVD patients.

Objective:To analyze the epidemiological and clinical characteristics of respiratory pathogens in China.Methods:This study was a cross-sectional study, which encompassed 19 core units of the clinical pathogen network and established a three-tiered clinical pathogen surveillance system. Thirty respiratory samples were collected every two weeks from various units from January to December 2024, and the clinical and pathogen diagnostic information were gathered. A total of 11 864 samples were tested using this system. The tier-1 clinical pathogen surveillance system covered influenza A virus (Flu-A), influenza B virus (Flu-B), respiratory syncytial virus (RSV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The tier-2 clinical pathogen surveillance system focused on 18 key respiratory pathogens. The tier-3 clinical pathogen surveillance system further clarified whether any emerging infectious diseases had occurred.Results:The tier-1 clinical pathogen surveillance system showed Flu-A predominated in December, Flu-B predominated in January, SARS-CoV-2 peaked in March and August, whereas RSV circulated sporadically throughout the year. Geographic trends were broadly consistent across the seven major regions, although Flu-A detection in December was notably higher in Northeast China (48.1%(111/231)) and East China (36.2%(148/409)), and RSV detection was concentrated in the Northwest and South China from January to March. Data from the tier-2 clinical pathogen surveillance system indicated that Streptococcus pneumoniae, Mycoplasma pneumoniae, rhinovirus, and adenovirus were detected year-round, of these, Streptococcus pneumoniae and rhinovirus showed elevated positive detection rates from August to September, while adenovirus peaked in January. Legionella pneumophila was not detected throughout the year, and other pathogens fluctuated throughout the year without a consistent pattern. The predominant etiologic agents of pediatric pneumonia were Mycoplasma pneumoniae (35.0%(105/300)), rhinovirus (25.7%(77/300)), and adenovirus (17.3%(52/300)), whereas adult pneumonia was mainly caused by Streptococcus pneumoniae (10.5%(29/277)), Staphylococcus aureus (6.9%(19/277)), Mycoplasma pneumoniae (6.9%(19/277)), and Flu-A (6.1%(17/277)). The tier-3 clinical pathogen surveillance system did not identify any emerging respiratory pathogens. Conclusion:Respiratory pathogens in China in 2024 exhibit distinct temporal and spatial distribution patterns and vary among different populations.

Objective::There is limited evidence regarding the choice of P2Y 12 receptor inhibitors as a component of dual antiplatelet therapy in patients with left main (LM) disease undergoing percutaneous coronary intervention (PCI). This study aimed to evaluate long-term clinical outcomes of ticagrelor- vs. clopidogrel-based dual antiplatelet therapy strategy in acute coronary syndrome (ACS) patients undergoing LM PCI. Methods::This is a post-hoc analysis from a prospective, single-center, real-world PCI registry. A total of 1,163 patients discharged post-ACS who underwent LM PCI and received ticagrelor or clopidogrel between March 2016 and March 2019 were included in the study. The primary endpoint was ischemic events at 12 months, including cardiac death, myocardial infarction, or stroke. Secondary outcomes included all-cause death and Bleeding Academic Research Consortium types 2, 3, and 5, and types 3 and 5 bleeding. Propensity score matching was used to adjust for bias due to confounders between the 2 groups.Results::The ticagrelor and clopidogrel groups comprised 529 (45.49%) and 634 (54.51%) patients, respectively. During the follow-up period, the rate of ischemic events was significantly lower with ticagrelor than with clopidogrel before (1.32% (7/529) vs. 3.63% (23/634), P = 0.013,6) and after propensity score matching (1.41% (6/425) vs. 4.00% (17/425), P = 0.020,1). The rates of all-cause death, Bleeding Academic Research Consortium-defined type 2, 3, and 5 bleeding, and type 3 and 5 bleeding were similar between the ticagrelor group and clopidogrel group before or after propensity score matching adjustment (all P > 0.05). Conclusion::Among patients with ACS undergoing LM PCI, ticagrelor use was associated with ischemic events benefit without excessive risk of bleeding at 12 months compared with clopidogrel.