BACKGROUND:Previous studies of the research group have found that icariin-containing serum can delay the progression of knee osteoarthritis,promote chondrocyte proliferation and stem cell cartilage differentiation in rats,but there is still a lack of sufficient basis for clinical application.OBJECTIVE:To investigate the repair effect of icariin-containing serum on lipopolysaccharide-induced inflammatory damage of human chondrocytes.METHODS:The effect of icariin-containing serum on chondrocyte viability was detected by cell counting kit-8 method,and the optimal volume fraction and time of icariin-containing serum were screened.The cells were then divided into blank group,lipopolysaccharide group,icariin-containing serum group and lipopolysaccharide+icariin-containing serum group.After grouping,immunofluorescence was used to detect the secretion of type Ⅱ collagen in chondrocytes in each group.Real-time PCR was used to detect the expression of related genes.RESULTS AND CONCLUSION:(1)Icariin-containing serum showed good biosafety characteristics for human chondrocytes,and the cell viability reached the highest level after 48 hours of intervention when the icariin-containing serum volume fraction was 15％,and the follow-up experiments were carried out according to the conditions.(2)Compared with the blank group,lipopolysaccharide significantly inhibited the expression of type Ⅱ collagen in chondrocytes,while icariin-containing serum showed a positive mobilization effect,which could effectively promote the secretion of type Ⅱ collagen in chondrocytes under normal and inflammatory conditions.(3)The mRNA expression of type Ⅱ collagen and Aggrecan in chondrocytes decreased significantly under lipopolysaccharide stimulation,and the mRNA expression levels of matrix metalloproteinase 13 and a disintegrin-like and metalloproteinase with thrombospondin motifs-5 increased significantly.Icariin-containing serum promoted the mRNA expression of type Ⅱ collagen in human chondrocytes under inflammatory conditions and reduced the mRNA expression of matrix metalloproteinase 13 and a disintegrin-like and metalloproteinase with thrombospondin motifs-5 in chondrocytes after lipopolysaccharide intervention.Therefore,these findings indicate that the icariin-containing serum has good safety for human chondrocytes and plays an important role in maintaining the normal physiological functions of chondrocytes,promoting the synthesis of extracellular matrix,and inhibiting the secretion of inflammatory factors.

BACKGROUND:Previous studies of the research group have found that icariin-containing serum can delay the progression of knee osteoarthritis,promote chondrocyte proliferation and stem cell cartilage differentiation in rats,but there is still a lack of sufficient basis for clinical application.OBJECTIVE:To investigate the repair effect of icariin-containing serum on lipopolysaccharide-induced inflammatory damage of human chondrocytes.METHODS:The effect of icariin-containing serum on chondrocyte viability was detected by cell counting kit-8 method,and the optimal volume fraction and time of icariin-containing serum were screened.The cells were then divided into blank group,lipopolysaccharide group,icariin-containing serum group and lipopolysaccharide+icariin-containing serum group.After grouping,immunofluorescence was used to detect the secretion of type Ⅱ collagen in chondrocytes in each group.Real-time PCR was used to detect the expression of related genes.RESULTS AND CONCLUSION:(1)Icariin-containing serum showed good biosafety characteristics for human chondrocytes,and the cell viability reached the highest level after 48 hours of intervention when the icariin-containing serum volume fraction was 15％,and the follow-up experiments were carried out according to the conditions.(2)Compared with the blank group,lipopolysaccharide significantly inhibited the expression of type Ⅱ collagen in chondrocytes,while icariin-containing serum showed a positive mobilization effect,which could effectively promote the secretion of type Ⅱ collagen in chondrocytes under normal and inflammatory conditions.(3)The mRNA expression of type Ⅱ collagen and Aggrecan in chondrocytes decreased significantly under lipopolysaccharide stimulation,and the mRNA expression levels of matrix metalloproteinase 13 and a disintegrin-like and metalloproteinase with thrombospondin motifs-5 increased significantly.Icariin-containing serum promoted the mRNA expression of type Ⅱ collagen in human chondrocytes under inflammatory conditions and reduced the mRNA expression of matrix metalloproteinase 13 and a disintegrin-like and metalloproteinase with thrombospondin motifs-5 in chondrocytes after lipopolysaccharide intervention.Therefore,these findings indicate that the icariin-containing serum has good safety for human chondrocytes and plays an important role in maintaining the normal physiological functions of chondrocytes,promoting the synthesis of extracellular matrix,and inhibiting the secretion of inflammatory factors.

Objective To systematically analyze the trend of incidence, mortality and disease burden of chronic obstructive pulmonary disease (COPD) in China from 1994 to 2023, reveal the influence of age-period-cohort factors on COPD in China and the attribution characteristics of risk factors, and provide empirical basis for formulating precise prevention and control strategies. Methods The Global Burden of Disease (GBD) 2023 database was used to extract the data of the whole population, gender and age groups of COPD in China from 1994 to 2023. The Joinpoint regression model was used to calculate the annual percentage change (APC) and average annual percentage change (AAPC) of the standardized rate. The age-period-cohort model was adopted to quantify its impacts on the incidence and mortality of COPD. It also analyzed the attributable effects as well as temporal trend characteristics of seven GBD level-3 risk factors (including smoking, ambient particulate matter pollution, occupational exposure, etc.) in Chinese population in 1994 and 2023 on the standardized mortality rate and standardized disability-adjusted life years (DALYs) rate of COPD. Results From 1994 to 2023, the incidence and mortality of COPD in China showed an upward trend, but the standardized incidence [AAPC=−1.16%, 95%CI (−1.18, −1.14), P<0.001] and standardized mortality [AAPC=−2.87%, 95%CI (−3.02, −2.73), P<0.001] decreased significantly, and the decline rate of standardized incidence in females (AAPC=−1.29%) was slightly higher than that in males (AAPC=−1.04%). The decline rate of standardized mortality in males (AAPC=−3.65%) was higher than that in females (AAPC=−1.94%). The age-period-cohort model revealed a nonlinear increase in the age effect, a graded decline in the cohort effect, and a significant period effect on mortality and male morbidity (P<0.001). In terms of attribution of risk factors, the top three attribution risks of the whole population in 2023 were still smoking, particulate matter pollution and second-hand smoke. Compared with 1994, the attribution of environmental ozone pollution, second-hand smoke, high temperature, smoking and occupational particulate matter/gas/smoke exposure increased, and the attribution of particulate matter pollution decreased. Conclusion From 1994 to 2023, the overall disease burden of COPD in China shows a downward trend. Age and cohort are the core driving factors of the disease, and period factors have a more significant impact on death. The changes in the attribution structure suggest that while consolidating the effectiveness of particulate matter pollution control, it is necessary to strengthen the comprehensive prevention and control strategies of tobacco control, coordinated emission reduction of ozone and multiple pollutants, extreme temperature protection and protection of key occupational groups, so as to continuously reduce the disease burden of COPD.

Immunoinflammation mediates the development of hypertensive nephropathy,and aberrant activation of the complement system,an important component of the innate immune system,plays an important role in the development of hypertensive nephropathy.Complement inhibition is expected to be a potential strategy for the treatment of hypertensive nephropathy.In this article,we summarized and reviewed relevant studies on the complement system in the development of hypertensive nephropathy,and complement-targeted drug therapy,aiming to provide new ideas for clinicians on the clinical diagnosis and treatment of hypertensive nephropathy.

Objective:To evaluate the mediating effect of electrocardiographic (ECG) indicators in the association between short-term exposure to fine particulate matter (PM 2.5) and blood pressure and to explore the key PM 2.5 element constituents that produce the mediating effect. Methods:Based on a cross-sectional survey across 10 cities in the Beijing-Tianjin-Hebei region and surrounding areas, PM 2.5 and its element constituents were collected from the nearest air monitoring superstation. Blood pressure and ECG indicators of participants were obtained through physical examinations. A multivariate linear regression was used to evaluate the effect of short-term exposures to PM 2.5 on blood pressure. A mediation analysis was used to identify the mediating effect of ECG indicators in the association between exposure to PM 2.5 and its element constituents and blood pressure. Results:The age of the 1 793 participants was (65.1±13.3) years, and 885 (49.4%) were males. During the study period, the daily mean concentration of PM 2.5 was (70±45) μg/m 3, and the systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and pulse pressure (PP) were (139±20), (82±11), (101±13), and (57±17) mmHg (1 mmHg=0.133 kPa), respectively. The results of the multivariate linear regression showed that for every 10 μg/m 3 increase in PM 2.5 on the same day (lag 0), DBP increased by 0.15 (95% CI: 0.02-0.28) mmHg, and PP decreased 0.18 (95% CI: 0.36-0.01) mmHg. The exposure to 14 elemental constituents, such as Ga, Co and Se, was associated with an increase in DBP, while the exposure to 17 elemental constituents, such as Cs, Se and Ag, was associated with a decrease in PP. At lag 0, the PM 2.5-induced increase in DBP was mediated by the QRS interval (mediation percentage of 18.98%), and the PM 2.5-induced decrease in PP was mediated by the QT interval (mediation percentage of -6.31%). The exposure to K, Br, Pb, Zn, Ca, Co, Pd, Cu, and As constituents was associated with increases in DBP mediated by prolonged QRS interval. The exposure to Pb, Zn, K, and As constituents was associated with decreases in PP mediated by prolonged QRS interval. Conclusion:ECG indicators such as QRS interval may mediate the association between short-term exposure to PM 2.5 and its element constituents and blood pressure.

Immunoinflammation mediates the development of hypertensive nephropathy,and aberrant activation of the complement system,an important component of the innate immune system,plays an important role in the development of hypertensive nephropathy.Complement inhibition is expected to be a potential strategy for the treatment of hypertensive nephropathy.In this article,we summarized and reviewed relevant studies on the complement system in the development of hypertensive nephropathy,and complement-targeted drug therapy,aiming to provide new ideas for clinicians on the clinical diagnosis and treatment of hypertensive nephropathy.

Objective:To investigate the clinical application value of a novel filter's retraction hook capture technique of pull-assisted method for the endovascular retrieval of conical inferior vena cava (IVC) filters whose hook attached to the wall.Methods:From January 2020 to December 2024, patients with conical filters whose hook attached to the wall admitted at Beijing Jishuitan Hospital were enrolled consecutively.Results:A total of 46 patients underwent filter retrieval using filter's retraction hook capture technique of pull-assisted method. Among these patients, 39 cases (84.8%) were successful in filter retrieval, with the penetration distance of cranial anchor vertex of 3.3(2.5, 4.4) mm, and 13 (33.3%) filters were deformed. The other 7 cases were unsuccessful, with a penetration distance of cranial anchor vertex of 5.0 (4.3, 5.0) mm, and 6 (85.7%) filters were deformed. There was a statistically significant difference between the two groups ( P<0.05). One case (2.2%) had IVC injury, one case (2.2%) experienced filter fracture, and no symptomatic pulmonary embolism occurred. Logistic regression analysis showed that filter deformation was an independent dangerous factor for filter's retraction. Conclusions:Filter's retraction hook capture technique of pull-assisted method is effective in removing conical filters whose hook attached to the wall, with no symptomatic PE occurring. This method can be considered as a new adjuvant technique for filter retrieval.

Objective:To explore the prognostic value of assessing plasma thrombin-antithrombin complex (TAT) and D-dimer (D-D) in patients with acute ischemic stroke (AIS).Methods:This prospective cohort study enrolled 538 AIS patients admitted to the General Hospital of Tianjin Medical University from July 2021 to May 2024, including 306 males and 232 females, with an average age of (69.5±11.5) years. Among them, there were 147 cases of lacunar infarction, 166 cases of large artery atherosclerosis type, 122 cases of cardioembolic type, and 103 cases of cancer-related type. Follow-up observations were conducted on enrolled patients, data within 30 days after the initiation of acute phase treatment for one week were collected, thrombus-related cerebral ischemic events recurrence served as the endpoint event, starting from August 5, 2021, to June 19, 2024. During the follow-up period, 68 patients experienced endpoint events, including 14 cases of large artery atherosclerosis type, 23 cases of cardioembolic type, and 31 cases of cancer-related type. The plasma levels of TAT and D-D were determined by chemiluminescence method and enzyme-linked immunofluorescence assay respectively. The receiver operating characteristic (ROC) curve was used to analyze the prediction performance of TAT and D-dimer for recurrent ischemic events in AIS patients during the 30-day follow-up period, and the Kaplan-Meier curve was used for survival analysis.Results:Statistically differences were observed in the plasma TAT and D-D levels among patients with different types of AIS ( P<0.05), with cancer-related type had higher levels than cardioembolic type ( P<0.05), and cardioembolic type had higher levels than large artery atherosclerosis type ( P<0.05). In the non-recurrent ischemic event group, the plasma TAT and D-D levels of patients with large artery atherosclerosis type, cardioembolic type and cancer-related type were lower in post-treatment than pre-treatment ( P<0.05). In the recurrent ischemic event group, the plasma D-D levels were higher in post-treatment than pre-treatment in the patients with large artery atherosclerosis type ( P<0.05); there was no statistically difference between the post-treatment and pre-treatment in plasma TAT and D-D levels in patients with cardioembolic type ( P>0.05); in patients with cancer-related type, the TAT and D-D levels were lower in post-treatment than pre-treatment ( P<0.05), but higher than those in the non-recurrence group ( P<0.05). The ROC curve showed that the area under the curve for predicting the risk of ischemic event recurrence within 30 days in AIS patients by plasma TAT combined with D-D on day 7 after treatment was all >0.9 (0.950 for large artery atherosclerosis type, 0.965 for cardioembolic type, and 0.907 for cancer-related types). Survival analysis indicated that various patients with both indicators above the critical value had an increased cumulative risk probability of adverse events (log-rank χ 2=93.667, 109.266, and 58.433, respectively, with all P<0.001). Conclusion:The changes of plasma TAT and D-D levels in AIS patients are associated with stroke type and coagulation activation, and dynamic monitoring of these two indicators could help evaluate the treatment effect and predict the risk of recurrent ischemic events.

In the progression process of liver diseases, pathological changes occur in the vascular endothelium, platelets, coagulation, anticoagulation, fibrinolysis systems of patients, and "rebalancd haemostasis" is formed. The coexistence of hypocoagulation and hypercoagulation tendency in the peripheral blood of patients made the laboratory testing data complex and difficult to interpret, especially prothrombin time and activated partial thromboplastin time could not truly reflect the net effect of haemostasis disorder in patients with liver diseases, which often led to misjudgment and overtreatment by doctors and led to adverse clinical consequences. In recent years, thromboelastography, rotational thromboelastometry and thrombin generation assay had been used to assess bleeding risk in patients with liver diseases and had made progress in transfusion management. On the other hand, von Willebrand factor and thrombospondin type 1 motif member 13 has been shown to be closely related to the progression of liver diseases and could warn the adverse clinical outcomes effectively.

Objective This study aims to evaluate the therapeutic efficacy of Compound Fufangteng Mixture(CFM)on myocardial fibrosis(MF)and explore its action targets and mechanisms through a combination of animal pharmacodynamics,cell biology,and network pharmacology approaches.Methods Thirty-five male C57BL/6J mice were divided into the normal group,model group,CFM low-dose(0.72 g/kg)group,CFM high-dose(1.44 g/kg)group,and sacubitril valsartan sodium group(20 mg/kg)based on random number table,with 7 mice in each group.Except for the normal group,the mice in the other groups were subcutaneously injected with isoproterenol(20 mg/kg)at multiple points once daily for 21 consecutive days to establish the MF model.The CFM groups were pre-administered by gavage 3 days before modeling,the sacubitril valsartan sodium group was administered starting from the day of modeling,and the normal group and model group were given an equal volume of distilled water.The active ingredients in CFM were analyzed using ultra-performance liquid chromatography(UPLC).On days 7,14,and 21 of modeling,the left ventricular ejection fraction(LVEF),left ventricular fractional shortening(LVFS),left ventricular end-diastolic diameter(LVIDd),and left ventricular end-systolic diameter(LVIDs)of mice were detected by ultrasound.The degree of myocardial fibrosis in mice was assessed by Masson staining.The levels of transforming growth factor-β1(TGF-β1),α-smooth muscle actin(α-SMA),type I collagen(COL I),and type Ⅲcollagen(COL Ⅲ)in the myocardial tissue of mice were detected by enzyme-linked immunosorbent assay(ELISA).The average fluorescence intensity of α-SMA in myocardial tissue was detected by immunofluorescence.In addition,by integrating Cellular Thermal Shift Assay(CETSA),QE proteomic analysis,and network pharmacology techniques,we systematically explored the potential core targets and mechanisms of action by which CFM improves MF,and validated these findings using western blotting analysis.Results Main eight chemical components were identified from CFM.Compared with the normal group,the model group exhibited a decrease in LVEF and LVFS,an increase in LVIDd and LVIDs,a higher heart weight to tibia length ratio,and an increased collagen volume fraction(P<0.05),along with aggravated MF.Concurrently,the myocardial tissue showed elevated levels of TGF-β1,α-SMA,COL I,and COL Ⅲ(P<0.05),with enhanced α-SMA fluorescence signal intensity.In comparison to the model group,all groups of CFM and the sacubitril valsartan sodium group demonstrated an increase in LVEF and LVFS,and a decrease in LVIDd,LVIDs,and the heart weight to tibia length ratio(P<0.05).Simultaneously,the collagen volume fraction decreased,and the levels of TGF-β1,α-SMA,COL I,and COL Ⅲ in myocardial tissue were down-regulated(P<0.05).The degree of MF was reduced,and the fluorescence signal intensity of α-SMA expression was weakened.Furthermore,the combined analysis of CETSA,QE proteomics,and network pharmacology revealed that heat shock protein A family member 8(HSPA8)may be a potential core target for CFM in ameliorating MF.CETSA-western blotting analysis further confirmed that CFM could enhance the thermal stability of HSPA8 protein and down-regulate the relative expression level of HSPA8 protein in mouse myocardial tissue(P<0.05).Conclusion CFM can ameliorate isoproterenol-induced cardiac dysfunction in mice,reduce collagen deposition,and reverse the pathological progression of MF.The underlying mechanism may be associated with the regulation of HSPA8.