1.Molecular mechanisms of autophagy-apoptosis interactions in osteoarthritis
Kui ZHAO ; Runsang PAN ; Fengjun LAN ; Jin DENG ; Houping CHEN
Chinese Journal of Tissue Engineering Research 2024;28(18):2912-2917
BACKGROUND:With the deepening of the aging of the world population,the prevalence rate of osteoarthritis is increasing.In recent years,more and more attention has been paid to the study of osteoarthritis.Studies have shown that autophagy and apoptosis are strongly associated with the occurrence and development of osteoarthritis,and play an important role in it. OBJECTIVE:To review the molecular mechanisms of the interaction between autophagy and apoptosis in osteoarthritis,aiming to explore the relationship between autophagy and apoptosis in osteoarthritis and the coupling mechanism of the two to mediate the occurrence and development of osteoarthritis,so as to provide new ideas for the treatment of osteoarthritis. METHODS:The Chinese and English key words"osteoarthritis,autophagy,apoptosis"were searched in the CNKI and PubMed.After screening by reading the title,abstract and key words,the relevant literature was carefully read.After excluding studies unrelated to the content of the paper and repetitive studies,68 articles were finally included for the summary. RESULTS AND CONCLUSION:(1)The occurrence and development of osteoarthritis are related to autophagy and apoptosis of chondrocytes.Autophagy protects chondrocytes from stress damage,but excessive autophagy also induces or promotes chondrocyte apoptosis and reduces the survival rate of chondrocytes.The two perturb each other to regulate the degeneration of articular cartilage.(2)miRNA,Beclin-1 and oxidative stress are all involved in the regulation of autophagy and apoptosis on osteoarthritis,and affect the development of osteoarthritis.
2.Comparison of Direct and Extraction Immunoassay Methods With Liquid Chromatography-Tandem Mass Spectrometry Measurement of Urinary Free Cortisol for the Diagnosis of Cushing’s Syndrome
Danni MU ; Jiadan FANG ; Songlin YU ; Yichen MA ; Jin CHENG ; Yingying HU ; Ailing SONG ; Fang ZHAO ; Qi ZHANG ; Zhihong QI ; Kui ZHANG ; Liangyu XIA ; Ling QIU ; Huijuan ZHU ; Xinqi CHENG
Annals of Laboratory Medicine 2024;44(1):29-37
Background:
Twenty-four-hour urinary free cortisol (UFC) measurement is the initial diagnostic test for Cushing’s syndrome (CS). We compared UFC determination by both direct and extraction immunoassays using Abbott Architect, Siemens Atellica Solution, and Beckman DxI800 with liquid chromatography-tandem mass spectrometry (LC-MS/MS). In addition, we evaluated the value of 24-hr UFC measured by six methods for diagnosing CS.
Methods:
Residual 24-hr urine samples of 94 CS and 246 non-CS patients were collected.A laboratory-developed LC-MS/MS method was used as reference. UFC was measured by direct assays (D) using Abbott, Siemens, and Beckman platforms and by extraction assays (E) using Siemens and Beckman platforms. Method was compared using Passing–Bablok regression and Bland–Altman plot analyses. Cut-off values for the six assays and corresponding sensitivities and specificities were calculated by ROC analysis.
Results:
Abbott-D, Beckman-E, Siemens-E, and Siemens-D showed strong correlations with LC-MS/MS (Spearman coefficient r = 0.965, 0.922, 0.922, and 0.897, respectively), while Beckman-D showed weaker correlation (r = 0.755). All immunoassays showed proportionally positive bias. The areas under the curve were 0.975 for Abbott-D, 0.972 for LCMS/MS, 0.966 for Siemens-E, 0.948 for Siemens-D, 0.955 for Beckman-E, and 0.877 for Beckman-D. The cut-off values varied significantly (154.8–1,321.5 nmol/24 hrs). Assay sensitivity and specificity ranged from 76.1% to 93.2% and from 93.0% to 97.1%, respectively.
Conclusions
Commercially available immunoassays for measuring UFC show different levels of analytical consistency compared to LC-MS/MS. Abbott-D, Siemens-E, and Beckman-E have high diagnostic accuracy for CS.
3.Clinical trial of rivaroxaban in the treatment of anticoagulation in patients with pulmonary embolism during maintenance period
Hui QIAN ; Kui LIU ; Ya-Lin JIANG ; Xia ZHAO
The Chinese Journal of Clinical Pharmacology 2024;40(7):959-962
Objective To compare the application effect of different doses of rivaroxaban on anticoagulation therapy in patients with pulmonary thromboembolism(PTE)during maintenance period,and to evaluate its benefit-risk.Methods The patients with PTE were divided into conventional-dose group and low-dose group according to the cohort method.Conventional-dose group were given of rivaroxaban 15 mg,twice a day and changed to 20 mg once a day after 3 weeks;low-dose group were given rivaroxaban 10 mg twice a day and changed to 15 mg once a day after 3 weeks,and the anticoagulation treatment time in both groups was ≥ 3 months.The clinical efficacy in the two groups was recorded.Serum indicators[D-dimer(D-D),N-terminal pro-brain natriuretic peptide(NT-proBNP),cardiac troponin Ⅰ(cTn Ⅰ)]and liver-kidney function[glutamic-pyruvic transaminase(GPT),glutamic-oxaloacetic transaminase(GOT),blood urea nitrogen(BUN),creatinine(Cr)]were compared before treatment and after 3 months of treatment.The patients were followed up for 3 months after treatment,and the endpoint events such as PTE recurrence and death and the bleeding events were recorded in the two groups.Results There were 42 cases in conventional-dose group,44 cases in low-dose group.After 3 months of treatment,the total effective rates in low-dose group and conventional-dose group were both 100.00%,with no significant difference(P>0.05).After 3 months of treatment,serum D-D levels in low-dose group and conventional-dose group were(0.31±0.08)and(0.29±0.07)mg·L-1,NT-proBNP levels were(125.49±24.16)and(121.39±22.08)ng·L-1,cTn Ⅰ levels were(0.02±0.00)and(0.02±0.00)μg·L-1,all with significant differences(all P>0.05).There were no significant changes in GPT,GOT,BUN and Cr in the two groups before and after treatment(all P>0.05),and there were no statistically significant differences between the two groups(all P>0.05).The total incidences of bleeding events during follow-up was 6.82%in low-dose group and was 23.81%in conventional-dose group(P<0.05).Conclusion Compared with conventional-dose rivaroxaban,low-dose rivaroxaban has similar anticoagulant effect,but the latter one can better reduce the risk of bleeding events in patients with PTE.
4.Effects and mechanism of rhubarb Tangluo pill on liver injury in type 2 diabetic rats
Dong AN ; Yong-Lin LIANG ; Yan-Kui GAO ; Feng-Zhe YAN ; Min BAI ; Si-Chen ZHAO ; Zhong-Tang LIU ; Xiao NIE
The Chinese Journal of Clinical Pharmacology 2024;40(9):1282-1286
Objective To investigate the effect and mechanism of rhubarb Tangluo pill on liver injury in type 2 diabetic rats.Methods ZDF(fa/fa)rats were given high-fat diet to induce type 2 diabetes model,and were randomly divided into model group,positive control group(0.18 g·kg-1 metformin)and experimental-L,-M,-H groups(0.54,1.08 and 2.16 g·kg-1 rhubarb Tangluo pill),with 8 rats in each group.Eight ZDF(fa/+)rats were selected as control group.The control group and model group were given equal volume of pure water once a day for 12 weeks.An oral glucose tolerance test(OGTT)was performed after administration.Fasting blood glucose level,body mass and liver mass of rats were measured and liver index was calculated.The contents of glutamic-pyruvic transaminase(GPT),glutamic oxalacetic transaminase(GOT),triglyceride(TG)and total cholesterol(TC)in serum were detected.The histomorphologic changes of liver were observed by hematoxylin-eosin(HE)staining and Masson staining.The protein expression of phosphorylated insulin receptor substrate 1(p-IRS1),phosphorylated protein kinase B(p-Akt)and glucose transporter 4(GLUT4)were detected by Western blotting.Results After administration,the fasting blood glucose levels of control group,model group,positive control group and experimental-H group were(4.71±0.45),(29.9±2.97),(15.28±4.52)and(13.84±1.55)mmol·L-1,respectively;the liver index were 2.31±0.46,4.03±0.18,3.37±0.23 and 3.38±0.24;the relative expression level of p-IRS1 protein were 1.00±0.36,4.00±0.11,1.62±0.27 and 1.90±0.17,respectively;the relative expression levels of p-Akt protein were 1.00±0.25,0.21±0.04,0.73±0.15 and 0.54±0.04,respectively;GLUT4 protein relative expression levels were 1.00±0.11,0.40±0.08,0.86±0.04 and 0.70±0.06,respectively.Compared with the model group,the above indexes in the experimental-H group were statistically significant(P<0.01,P<0.05).Conclusion Rhubarb Tanglu pill can effectively improve glycolipid metabolism and liver injury in type 2 diabetes mellitus,and its mechanism may be related to the activation of IRS1/Akt signaling pathway.
5.Myocardial scar area predicts major adverse cardiovascular events after coronary artery bypass grafting in patients with ischemic cardiomyopathy
Wei FU ; Yang ZHAO ; Kui ZHANG ; Qinyi DAI ; Hongkai ZHANG ; Jumatay BIEKAN ; Jubing ZHENG ; Ran DONG
Chinese Journal of Cardiology 2024;52(8):906-913
Objective:To investigate the value of myocardium scar area in predicting adverse cardiovascular events (MACEs) after coronary artery bypass grafting (CABG) in patients with ischemic cardiomyopathy (ICM).Methods:The first part of this study was a retrospective study. Patients diagnosed with ICM and undergoing CABG surgery at Beijing Anzhen Hospital, Capital Medical University from January 2017 to December 2022 were enrolled as the discovery cohort. All patients underwent cardiac magnetic resonance-late gadolinium enhancement (CMR-LGE) before surgery. According to the occurrence of postoperative MACEs, the patients were divided into MACEs group and MACEs-free group. Preoperative clinical and imaging data, intraoperative and postoperative data were collected and compared between the two groups. The primary endpoint was postoperative MACEs. Univariate and multifactor regression analyses were used to analyze the risk factors for MACEs. Receiver operating characteristic (ROC) curves were constructed to evaluate the predictive efficacy and optimal cut-off value of myocardial scar area for endpoint events. The second part of this study was a prospective study. Patients with ICM who received CABG at Beijing Anzhen Hospital, Capital Medical University from January 2023 to June 2023 were enrolled as a validation cohort, and were divided into MACEs group and MACEs-free group according to whether MACEs occurred after surgery. Preoperative clinical and imaging data, intraoperative and postoperative data were collected and compared between the two groups. Verify the reliability of the cut-off value obtained by ROC curve in the validation cohort.Results:A total of 120 patients with ICM (30 patients in MACEs group and 90 patients in MACEs-free group), aged (61.6±8.7) years, including 93 males, were included in the discovery cohort. A total of 22 ICM patients (5 patients in MACEs group and 17 patients in MACEs-free group), aged (59.5±8.2) years, including 18 males, were included in the validation cohort. Multivariate Cox regression showed that myocardial scar area ( HR=1.258, 95% CI 1.096-1.444, P=0.001) was an independent risk factor for the primary endpoint event. The area under ROC curve of myocardial scar area for predicting postoperative MACEs was 0.90 (95% CI 0.83-0.95), and myocardial scar area≥36.0% was the optimal cut-off value for predicting postoperative MACEs, and its sensitivity, specificity and accuracy were 96.7%, 72.2% and 78.3%, respectively. In the validation cohort, the sensitivity, specificity and accuracy of myocardial scar area in predicting postoperative MACEs in patients with ICM after CABG were 80.0%, 82.4% and 81.8%, respectively. Conclusion:Myocardial scar area is an independent risk factor for MACEs after CABG in patients with ICM, and myocardial scar area≥36.0% is the optimal cut-off value for predicting MACEs after CABG. Myocardial scar area can help to identify patients at high risk of surgery and provide a basis for risk stratification of patients.
6.Risk factors and predictive model of cerebral edema after road traffic accidents-related traumatic brain injury
Di-You CHEN ; Peng-Fei WU ; Xi-Yan ZHU ; Wen-Bing ZHAO ; Shi-Feng SHAO ; Jing-Ru XIE ; Dan-Feng YUAN ; Liang ZHANG ; Kui LI ; Shu-Nan WANG ; Hui ZHAO
Chinese Journal of Traumatology 2024;27(3):153-162
Purpose::Cerebral edema (CE) is the main secondary injury following traumatic brain injury (TBI) caused by road traffic accidents (RTAs). It is challenging to be predicted timely. In this study, we aimed to develop a prediction model for CE by identifying its risk factors and comparing the timing of edema occurrence in TBI patients with varying levels of injuries.Methods::This case-control study included 218 patients with TBI caused by RTAs. The cohort was divided into CE and non-CE groups, according to CT results within 7 days. Demographic data, imaging data, and clinical data were collected and analyzed. Quantitative variables that follow normal distribution were presented as mean ± standard deviation, those that do not follow normal distribution were presented as median (Q 1, Q 3). Categorical variables were expressed as percentages. The Chi-square test and logistic regression analysis were used to identify risk factors for CE. Logistic curve fitting was performed to predict the time to secondary CE in TBI patients with different levels of injuries. The efficacy of the model was evaluated using the receiver operator characteristic curve. Results::According to the study, almost half (47.3%) of the patients were found to have CE. The risk factors associated with CE were bilateral frontal lobe contusion, unilateral frontal lobe contusion, cerebral contusion, subarachnoid hemorrhage, and abbreviated injury scale (AIS). The odds ratio values for these factors were 7.27 (95% confidence interval ( CI): 2.08 -25.42, p = 0.002), 2.85 (95% CI: 1.11 -7.31, p = 0.030), 2.62 (95% CI: 1.12 -6.13, p = 0.027), 2.44 (95% CI: 1.25 -4.76, p = 0.009), and 1.5 (95% CI: 1.10 -2.04, p = 0.009), respectively. We also observed that patients with mild/moderate TBI (AIS ≤ 3) had a 50% probability of developing CE 19.7 h after injury (χ 2= 13.82, adjusted R2 = 0.51), while patients with severe TBI (AIS > 3) developed CE after 12.5 h (χ 2= 18.48, adjusted R2 = 0.54). Finally, we conducted a receiver operator characteristic curve analysis of CE time, which showed an area under the curve of 0.744 and 0.672 for severe and mild/moderate TBI, respectively. Conclusion::Our study found that the onset of CE in individuals with TBI resulting from RTAs was correlated with the severity of the injury. Specifically, those with more severe injuries experienced an earlier onset of CE. These findings suggest that there is a critical time window for clinical intervention in cases of CE secondary to TBI.
7.Investigation on vehicle occupant dummy applicability for under-foot impact loading conditions
Teng-Fei TIAN ; Fu-Hao MO ; Hao-Yang SU ; Can HUANG ; Hui ZHAO ; Jun LIU ; Bo SHANG ; Kui LI ; Jin-Long QIU
Chinese Journal of Traumatology 2024;27(4):235-241
Purpose::Under-foot impact loadings can cause serious lower limb injuries in many activities, such as automobile collisions and underbody explosions to military vehicles. The present study aims to compare the biomechanical responses of the mainstream vehicle occupant dummies with the human body lower limb model and analyze their robustness and applicability for assessing lower limb injury risk in underfoot impact loading environments.Methods::The Hybrid III model, the test device for human occupant restraint (THOR) model, and a hybrid human body model with the human active lower limb model were adopted for under-foot impact analysis regarding different impact velocities and initial lower limb postures.Results::The results show that the 2 dummy models have larger peak tibial axial force and higher sensitivity to the impact velocities and initial postures than the human lower limb model. In particular, the Hybrid III dummy model presented extremely larger peak tibial axial forces than the human lower limb model. In the case of minimal difference in tibial axial force, Hybrid III's tibial axial force (7.5 KN) is still 312.5% that of human active lower limb's (2.4 KN). Even with closer peak tibial axial force values, the biomechanical response curve shapes of the THOR model show significant differences from the human lower limb model.Conclusion::Based on the present results, the Hybrid III dummy cannot be used to evaluate the lower limb injury risk in under-foot loading environments. In contrast, potential improvement in ankle biofidelity and related soft tissues of the THOR dummy can be implemented in the future for better applicability.
8.Lung Cancer Risk Attributable to Active Smoking in China: A Systematic Review and Meta-Analysis.
Jian ZHAO ; Yu Lin SHI ; Yu Tong WANG ; Fei Ling AI ; Xue Wei WANG ; Wen Yi YANG ; Jing Xin WANG ; Li Mei AI ; Kui Ru HU ; Xia WAN
Biomedical and Environmental Sciences 2023;36(9):850-861
OBJECTIVE:
No consensus exists on the relative risk ( RR) of lung cancer (LC) attributable to active smoking in China. This study aimed to evaluate the unified RR of LC attributable to active smoking among the Chinese population.
METHODS:
A systematic literature search of seven databases was conducted to identify studies reporting active smoking among smokers versus nonsmokers in China. Primary articles on LC providing risk estimates with their 95% confidence intervals ( CIs) for "ever" "former" or "current" smokers from China were selected. Meta-analysis was used to estimate the pooled RR of active smoking.
RESULTS:
Forty-four unique studies were included. Compared with that of nonsmokers, the pooled RR (95% CI) for "ever" "former" and "current" smokers were 3.26 (2.79-3.82), 2.95 (1.71-5.08), and 5.16 (2.58-10.34) among men, 3.18 (2.78-3.63), 2.70 (2.08-3.51), and 4.27 (3.61-5.06) among women, and 2.71 (2.12-3.46), 2.66 (2.45-2.88), and 4.21 (3.25-5.45) in both sexes combined, respectively.
CONCLUSION
The RR of LC has remained relatively stable (range, 2-6) over the past four decades in China. Early quitting of smoking could reduce the RR to some extent; however, completely refraining from smoking is the best way to avoid its adverse effects.
Male
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Humans
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Female
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Smoking/epidemiology*
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Smoking Cessation
;
Smokers
;
Risk
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Lung Neoplasms/etiology*
;
Risk Factors
9.Current status of surgery for portal hypertension in China: a national multi-center survey analysis
Lei ZHENG ; Haiyang LI ; Jizhou WANG ; Xiao LIANG ; Jian DOU ; Jitao WANG ; Qiang FAN ; Xiong DING ; Wenlong ZHAI ; Yun JIN ; Bo LI ; Songqing HE ; Tao LI ; Jun LIU ; Kui WANG ; Zhiwei LI ; Yongyi ZENG ; Yingmei SHAO ; Yang BU ; Dong SHANG ; Yong MA ; Cheng LOU ; Xinmin YIN ; Jiefeng HE ; Haihong ZHU ; Jincai WU ; Zhidan XU ; Dunzhu BASANG ; Jianguo LU ; Liting ZHANG ; Jianguo ZHAO ; Ling LYU ; Guoyue LYU ; Nim CHOI ; To Tan CHEUNG ; Meng LUO ; Wanguang ZHANG ; Xiaolong QI ; Xiaoping CHEN
Chinese Journal of Organ Transplantation 2023;44(3):152-159
Objective:To explore the current status of surgery for portal hypertension to grasp current status and future development of surgery in China.Methods:This study is jointly sponsored by China Hepatobiliary & Pancreatic Specialist Alliance & Portal Hypertension Alliance in China (CHESS).Comprehensive surveying is conducted for basic domestic situations of surgery for portal hypertension, including case load, surgical approaches, management of postoperative complications, primary effects, existing confusion and obstacles, liver transplantation(LT), laparoscopic procedures and transjugular intrahepatic portosystemic shunt(TIPS), etc.Results:A total of 8 512 cases of portal hypertension surgery are performed at 378 hospitals nationwide in 2021.Splenectomy plus devascularization predominated(53.0%)and laparoscopy accounted for 76.1%.Primary goal is preventing rebleeding(67.0%) and 72.8% of hospitals used preventive anticoagulants after conventional surgery.And 80.7% of teams believe that the formation of postoperative portal vein thrombosis is a surgical dilemma and 65.3% of hospitals practiced both laparoscopy and TIPS.The major reasons for patients with portal hypertension not receiving LT are due to a lack of qualifications for LT(69.3%)and economic factors(69.0%).Conclusions:Surgery is an integral part of management of portal hypertension in China.However, it is imperative to further standardize the grasp of surgical indications, the handling of surgical operation and the management of postoperative complications.Moreover, prospective, multi-center randomized controlled clinical studies should be performed.
10.Mid- and long-term efficacy of off-pump coronary artery bypass grafting in elderly patients with coronary artery disease complicated with moderate ischemic mitral regurgitation
Wei FU ; Kui ZHANG ; Yang ZHAO ; Junsheng MU ; Ran DONG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2023;30(07):982-988
Objective To analyze the efficacy of off-pump coronary artery bypass grafting (OPCABG) in elderly patients with coronary artery disease complicated with moderate ischemic mitral regurgitation. Methods The clinical data of patients aged≥70 years with coronary artery disease complicated with moderate mitral regurgitation, and undergoing OPCABG from January 2009 to January 2020 in Beijing Anzhen Hospital were retrospectively analyzed. The echocardiographic indicators of the patients were compared preoperatively, postoperatively before discharge and during the follow-up. Results Finally 239 patients were enrolled. There were 136 males and 103 females, aged 74.1±3.2 years. Before postoperative discharge, 49 (20.5%) patients had no mitral regurgitation, 144 (60.3%) mild regurgitation, 46 (19.2%) moderate regurgitation, and 0 severe regurgitation. The area of mitral regurgitation was significantly improved (2.5±1.8 cm2 vs. 5.6±1.0 cm2, P<0.001). There were 10 (4.2%) patients of hospital death, 23 (9.6%) of low cardiac output, 3 (1.3%) of myocardial infarction, and 8 (3.3%) of nervous system injury after operation. As a result, 208 (90.8%) patients were followed up and the mean follow-up time was 3.4 years (range 1-9 years). The cumulative survival rates at postoperative 2, 4, 6, and 8 years were 95.8%, 88.0%, 78.4%, and 73.1%, respectively. Postoperative follow-up showed significant improvements compared with those before surgery in the area of mitral regurgitation, left ventricular ejection fraction, left ventricular end-diastolic and left ventricular end-systolic diameters (all P<0.05). Duirng the follow-up, the major adverse cardiac and cerebrovascular events were all cause death in 22 (10.6%) patients, including cardiac death in 17 (8.2%) patients, myocardial infarction in 7 (3.4%) patients, heart failure in 24 (11.5%) patients, cerebrovascular events in 11 (5.3%) patients, re-hospitalization due to heart disease in 23 (11.1%) patients, and none of the patients with myocardial infarction were revascularized. Conclusion The mid- and long-term outcomes of OPCABG in the treatment for elderly patients with coronary artery disease complicated with moderate ischemic mitral regurgitation is good.

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