Objective To explore the predictive value of growth differentiation factor 15(GDF-15)for atrial fibrillation(AF)in patients with coronary heart disease(CHD).Methods A prospective observation cohort of 1261 elderly CHD patients was randomly sampled from the First Medical Center of Chinese PLA General Hospital from January 2012 to December 2015.ELISA was used to detect GDF-15 level in all the subjects,and their baseline data were collected.Until March 2023,93 patients were lost during the follow-up period,and finally 1168 patients completed the follow-up,with a median time of 9.4 years.According to AF occurred or not during the period,the eligible patients were divided into an AF group(197 cases)and a non-AF group(971 cases),and based on their medical history,also assigned into a stable angina pectoris(SAP,n=304)and an acute coronary syndrome group(ACS,n=864).Logistic regression analysis was used to determine whether GDF-15 is a risk factor for AF in elderly CHD patients.ROC curve was plotted to assess the predictive value of GDF-15,guideline recommended CHARGE-AF scoring model,and their combination for AF events in the patients.Results The AF group had significantly advanced age,larger proportions of smoking history,type 2 diabetes,hypertension,old myocardial infarction,stroke,ACS and administration of statins,higher ratio of angiotensin converting enzyme inhibi-tor/angiotensin receptor blocker,and elevated levels of GDF-15 and N-terminal pro-B-type natri-uretic peptide,and lower left ventricular ejection fraction,SAP incidence,and low-density lipopro-tein cholesterol,total cholesterol and triglycerides levels when compared with the non-AF group(P＜0.05,P＜0.01).Multivariate logistic regression analysis showed that GDF-15 was not a risk factor for AF in elderly CHD patients(OR=0.92,95％CI:0.74-1.16,P=0.489),but was a risk factor for AF in SAP patients(OR=1.38,95％CI:1.07-2.79,P=0.015),and in ACS patients,still not a risk factor for AF(OR=0.81,95％CI:0.63-1.05,P=0.814).ROC curve analysis showed that the AUC value of GDF-15 combined with the CHARGE-AF scoring model in predic-ting AF was 0.682 in the elderly CHD patients,0.746 in the SAP patients,and 0.680 in the ACS patients.Conclusion Elevated GDF-15 level is an independent risk factor and predictor of AF in elderly SAP patients.In SAP patients,the combination of GDF-15 and CHARGE-AF scoring model further improves the predictive performance of AF occurrence.

Objective To explore the molecular mechanisms by which cytochrome P4502C regulates ferroptosis in hu-man retinal microvascular endothelial cells(hRMECs)under high-glucose conditions.Methods Human retinal microvas-cular endothelial cells(hRMECs)were cultured in vitro and divided into six groups:the NG group(cells cultured in ser-um-free DMEM medium containing 5.5 mmol·L-1 glucose);the NG+fenofibrate group(10 μmol·L-1 fenofibrate added to the NG group);the NG+rifampicin group(10 μmol·L-1 rifampicin added to the NG group);the HG group(cells cul-tured in serum-free DMEM medium containing 25.5 mmol·L-1 glucose);the HG+fenofibrate group(10 μmol·L-1 feno-fibrate added to the HG group);and the HG+rifampicin group(10 μmol·L-1 rifampicin added to the HG group).After 48 hours of culture,subsequent experiments were conducted.Cell viability was assessed using the CCK-8 assay.The levels of malondialdehyde(MDA)and iron content in hRMECs were measured using commercial assay kits.The relative fluores-cence intensity of Liperfluo was quantified by flow cytometry.The mRNA expression levels of glutathione peroxidase 4(GPX4),cytochrome P4502C,and acyl-CoA synthetase long-chain family member 4(ACSL4)in hRMECs were analyzed using real-time quantitative PCR.The protein expression levels of GPX4,cytochrome P4502C,and ACSL4 in hRMECs were evaluated using Western blot analysis.Results Optimal concentration analysis showed that the 10 μmnol·L-1 fenofibrate group had the highest cell viability compared to the HG group(P＜0.05),while the 10 μmol·L-1 rifampicin group had the lowest cell viability(P＜0.05).Thus,10 μmol·L-1 was selected as the optimal concentration for both fenofibrate and rif-ampicin for subsequent experiments.Cell viability in the NG,NG+fenofibrate,NG+rifampicin,HG,HG+fenofibrate,and HG+rifampicin groups was(100.00±7.85)％,(102.15±9.07)％,(69.97±4.22)％,(61.74±6.13)％,(83.64±7.58)％,and(56.96±5.34)％,respectively.Compared with the NG group,the HG group had significantly lower cell via-bility(P＜0.05).Compared with the HG group,the HG+fenofibrate group had significantly higher cell viability(P＜0.05).Compared with the NG group,the HG group had higher levels of MDA,iron content,and Liperfluo relative fluores-cence intensity(all P＜0.05).Compared with the HG group,the HG+fenofibrate group had lower levels of MDA,iron content,and Liperfluo relative fluorescence intensity(all P＜0.05);the HG+rifampicin group had higher levels of these parameters(all P＜0.05).Compared with the NG group,the HG group had higher mRNA and protein expression levels of cytochrome P4502C and ACSL4,but lower levels of GPX4 mRNA and protein(all P＜0.05).Compared with the HG group,the HG+fenofibrate group had lower mRNA and protein expression levels of cytochrome P4502C and ACSL4,but higher lev-els of GPX4 mRNA and protein(all P＜0.05);the HG+rifampicin group had higher mRNA and protein expression levels of cytochrome P4502C and ACSL4,but lower levels of GPX4 mRNA and protein(all P＜0.05).Conclusion Cytochrome P4502C can promote ferroptosis of hRMECs under high-glucose conditions by regulating the GPX4/ACSL4 signaling axis;in-hibition of cytochrome P4502C expression can exert a protective effect on DR;modulation of the expression levels or bal-ance of the key factors GPX4 and ACSL4 in this pathway may hold promise as a potential strategy to slow the progression of DR.

Objective To explore the molecular mechanisms by which cytochrome P4502C regulates ferroptosis in hu-man retinal microvascular endothelial cells(hRMECs)under high-glucose conditions.Methods Human retinal microvas-cular endothelial cells(hRMECs)were cultured in vitro and divided into six groups:the NG group(cells cultured in ser-um-free DMEM medium containing 5.5 mmol·L-1 glucose);the NG+fenofibrate group(10 μmol·L-1 fenofibrate added to the NG group);the NG+rifampicin group(10 μmol·L-1 rifampicin added to the NG group);the HG group(cells cul-tured in serum-free DMEM medium containing 25.5 mmol·L-1 glucose);the HG+fenofibrate group(10 μmol·L-1 feno-fibrate added to the HG group);and the HG+rifampicin group(10 μmol·L-1 rifampicin added to the HG group).After 48 hours of culture,subsequent experiments were conducted.Cell viability was assessed using the CCK-8 assay.The levels of malondialdehyde(MDA)and iron content in hRMECs were measured using commercial assay kits.The relative fluores-cence intensity of Liperfluo was quantified by flow cytometry.The mRNA expression levels of glutathione peroxidase 4(GPX4),cytochrome P4502C,and acyl-CoA synthetase long-chain family member 4(ACSL4)in hRMECs were analyzed using real-time quantitative PCR.The protein expression levels of GPX4,cytochrome P4502C,and ACSL4 in hRMECs were evaluated using Western blot analysis.Results Optimal concentration analysis showed that the 10 μmnol·L-1 fenofibrate group had the highest cell viability compared to the HG group(P＜0.05),while the 10 μmol·L-1 rifampicin group had the lowest cell viability(P＜0.05).Thus,10 μmol·L-1 was selected as the optimal concentration for both fenofibrate and rif-ampicin for subsequent experiments.Cell viability in the NG,NG+fenofibrate,NG+rifampicin,HG,HG+fenofibrate,and HG+rifampicin groups was(100.00±7.85)％,(102.15±9.07)％,(69.97±4.22)％,(61.74±6.13)％,(83.64±7.58)％,and(56.96±5.34)％,respectively.Compared with the NG group,the HG group had significantly lower cell via-bility(P＜0.05).Compared with the HG group,the HG+fenofibrate group had significantly higher cell viability(P＜0.05).Compared with the NG group,the HG group had higher levels of MDA,iron content,and Liperfluo relative fluores-cence intensity(all P＜0.05).Compared with the HG group,the HG+fenofibrate group had lower levels of MDA,iron content,and Liperfluo relative fluorescence intensity(all P＜0.05);the HG+rifampicin group had higher levels of these parameters(all P＜0.05).Compared with the NG group,the HG group had higher mRNA and protein expression levels of cytochrome P4502C and ACSL4,but lower levels of GPX4 mRNA and protein(all P＜0.05).Compared with the HG group,the HG+fenofibrate group had lower mRNA and protein expression levels of cytochrome P4502C and ACSL4,but higher lev-els of GPX4 mRNA and protein(all P＜0.05);the HG+rifampicin group had higher mRNA and protein expression levels of cytochrome P4502C and ACSL4,but lower levels of GPX4 mRNA and protein(all P＜0.05).Conclusion Cytochrome P4502C can promote ferroptosis of hRMECs under high-glucose conditions by regulating the GPX4/ACSL4 signaling axis;in-hibition of cytochrome P4502C expression can exert a protective effect on DR;modulation of the expression levels or bal-ance of the key factors GPX4 and ACSL4 in this pathway may hold promise as a potential strategy to slow the progression of DR.

Objective To explore the predictive value of growth differentiation factor 15(GDF-15)for atrial fibrillation(AF)in patients with coronary heart disease(CHD).Methods A prospective observation cohort of 1261 elderly CHD patients was randomly sampled from the First Medical Center of Chinese PLA General Hospital from January 2012 to December 2015.ELISA was used to detect GDF-15 level in all the subjects,and their baseline data were collected.Until March 2023,93 patients were lost during the follow-up period,and finally 1168 patients completed the follow-up,with a median time of 9.4 years.According to AF occurred or not during the period,the eligible patients were divided into an AF group(197 cases)and a non-AF group(971 cases),and based on their medical history,also assigned into a stable angina pectoris(SAP,n=304)and an acute coronary syndrome group(ACS,n=864).Logistic regression analysis was used to determine whether GDF-15 is a risk factor for AF in elderly CHD patients.ROC curve was plotted to assess the predictive value of GDF-15,guideline recommended CHARGE-AF scoring model,and their combination for AF events in the patients.Results The AF group had significantly advanced age,larger proportions of smoking history,type 2 diabetes,hypertension,old myocardial infarction,stroke,ACS and administration of statins,higher ratio of angiotensin converting enzyme inhibi-tor/angiotensin receptor blocker,and elevated levels of GDF-15 and N-terminal pro-B-type natri-uretic peptide,and lower left ventricular ejection fraction,SAP incidence,and low-density lipopro-tein cholesterol,total cholesterol and triglycerides levels when compared with the non-AF group(P＜0.05,P＜0.01).Multivariate logistic regression analysis showed that GDF-15 was not a risk factor for AF in elderly CHD patients(OR=0.92,95％CI:0.74-1.16,P=0.489),but was a risk factor for AF in SAP patients(OR=1.38,95％CI:1.07-2.79,P=0.015),and in ACS patients,still not a risk factor for AF(OR=0.81,95％CI:0.63-1.05,P=0.814).ROC curve analysis showed that the AUC value of GDF-15 combined with the CHARGE-AF scoring model in predic-ting AF was 0.682 in the elderly CHD patients,0.746 in the SAP patients,and 0.680 in the ACS patients.Conclusion Elevated GDF-15 level is an independent risk factor and predictor of AF in elderly SAP patients.In SAP patients,the combination of GDF-15 and CHARGE-AF scoring model further improves the predictive performance of AF occurrence.

Objective To investigate the effects and possible mechanisms of the growth differentia-tion factor 15(GDF-15)/glial-derived neurotrophic factor receptor alpha-like(GFRAL)pathway on the progression of atherosclerosis in ApoE-/-mice.Methods Eight 8-week-old male ApoE-/-mice were randomly divided into control group and rGDF-15 group.The mice in the control group received an injection of phosphate-buffered saline via tail vein once a week after 4 weeks of high-fat diet feeding,and those in the rGDF-15 group received an injection of recombinant GDF-15(0.05 mg/kg)via tail vein once a week after 4 weeks of high-fat diet feeding.The mice were fed with high-fat diet for another 8 weeks,the body weight was monitored during this period.After 12 weeks'feeding,the mice were euthanized.Another 4 normal mice(at the same age,20 weeks old)were subjected and served as normal control group.The levels of fasting blood glucose,blood lip-ids,cortisol,and aldosterone were compared among the three groups.Oil red O staining was used to evaluate plaque size in the aorta,and immunohistochemistry was employed to assess the expression of GDF-15 and GFRAL in the brain tissue.Results The serum level of GDF-15 was higher in the rGDF-15 group than in the control group(52.59±2.90 ng/ml vs 20.09±1.27 ng/ml,P＜0.01).The weight of mice was significantly lower in the rGDF-15 group than the con-trol group during Week 11(28.60±0.22 g vs 29.47±0.25 g,P＜0.01)and 12(28.98±0.22 g vs 30.35±0.13 g,P＜0.01).The rGDF-15 group had a statistically lower level of triglycerides(0.22±0.02 mmol/L vs 0.38±0.09 mmol/L,P＜0.05),lighter plaque burden[(22.22±2.58)％vs(31.61±3.51)％,P＜0.01],and enhanced expression levels of GDF-15 and GFRAL in the brain tissue(0.088±0.007 vs 0.030±0.006,0.031±0.003 vs 0.010±0.001,P＜0.01).The levels of cor-tisol and aldosterone in the control group and rGDF-15 group were significantly higher than those in the normal group(P＜0.01).The aldosterone level in the rGDF-15 group was significantly re-duced compared to the control group(22.013.67 mg/ml vs 87.29±8.63 mg/ml,P＜0.01).Conclusion GDF-15 may regulate body weight and triglyceride and aldosterone levels through GFRAL,and then affect the progression of atherosclerosis.

Objective To investigate the effect of arthroscopic debridement and meniscectomy in treatment of moderate or severe meniscus injury combined with knee osteoarthritis in early or middle stage. Methods 156 cases diagnosed with moderate or severe meniscus injury combined with knee osteoarthritis in early or middle stage were collected from October 2011 to October 2014. Lysholm knee score and preoperative examinations such as anteroposterior, lateral, axial radiographs, the standing full leg length X-ray film and MRI scan of the knee were recommended to definitively understand the osteoarthritis staging and meniscus injury grading. All patients were treated with arthroscopic debridement and meniscectomy. After operation, physical rehabilitation exercises and regular clinical follow-up were carried out as planned. The Lysholm knee score data from preoperation and terminal follow-up was statistical analyzed. Results No patient experienced any perioperative and postoperative complications. Statistical analysis showed that the Lysholm knee score of postoperation was significantly higher than that of preoperation [(87.3 ± 7.9) vs (67.5 ± 4.9), P < 0.05). Conclusion Arthroscopic debridement and meniscectomy in treatment of moderate or severe meniscus injury combined with knee osteoarthritis in early or middle stage, gains beneficial effects for its minimal invasion and quick recovery.

Background:Single-balloon enteroscopy(SBE)is a new method for the examination of small intestine,its clinical value in suspected small intestinal diseases need to be further studied. Aims:To evaluate the diagnostic and therapeutic value of SBE in suspected small intestinal diseases. Methods:A total of 73 suspected small intestinal diseases patients who had undergone 81 SBE examinations from July 2011 to October 2013 at Chengdu Military General Hospital were retrospectively examined,indications,diagnostic and therapeutic value of SBE in suspected small intestinal diseases were analyzed. Results:Of all the 81 examinations,33(40. 7% )were obscure gastrointestinal bleeding,29(35. 8% ) incomplete intestinal obstruction,and 19(23. 5% )chronic abdominal pain or diarrhea. The intubation depth was 230 cm for the oral approach,and 100 cm for the anal approach. The diagnostic yield of SBE was 67. 9% ,the main lesions were small intestinal ulcer,small intestinal inflammation,small intestinal tumor,small intestinal polyp. A total of 8 patients underwent endoscopic therapy,of whom 5 underwent endoscopic hemostatic therapy and 3 underwent resection of polyp. No serious complications were found. Conclusions:SBE is a safe and reliable diagnostic and therapeutic method for suspected small intestinal diseases,and its main indications are obscure gastrointestinal bleeding and incomplete intestinal obstruction.

OBJECTIVE: To analyse the effect of low intensity pulsed ultrasound stimulation (LIPUS) on accelerating the fibrocartilage layer repair of patella-patellar tendon junction. METHODS: A total of 60 mature female New Zealand white rabbits undergoing standard partial patellectomy were divided into 2 groups randomly. The control group was given comfort treatment and the treatment group was given LIPUS treatment starting from day 3 to the end of week 6 postoperatively. The scheduled time points of animal euthanization would be at week 6, week 12 and week 18 postoperatively. The patella-patellar tendon (PPT) complex would be harvested and cut into sections after decalcification for H&E staining, Safranine o/fast green staining. The thickness and gray value of fibrocartilage layer were analyzed by SANO Microscope Partner image analyzer. RESULTS: At week 6, week 12 and week 18 postoperatively, the fibrocartilage layer in the treatment group was significantly thicker than that in the control group (P<0.01), and the gray value of fibrocartilage layer was significantly smaller than that in the control group (P<0.01). CONCLUSION LIPUS helps to accelerate the fibrocartilage layer repair of patella-patellar tendon junction in rabbit models.
Animals ; Female ; Fibrocartilage ; pathology ; physiopathology ; Patella ; surgery ; Patellar Ligament ; injuries ; pathology ; physiopathology ; surgery ; Rabbits ; Tendon Injuries ; therapy ; Ultrasonic Therapy ; methods ; Wound Healing ; physiology

BACKGROUND: Experiments has demonstrated that low-intensity pulse ultrasound stimulations(LIPUS) can accelerate bone healing. However, Its affect mechanisms on maturation of regenerated bone remain unclear.OBJECTIVE: The hypothesis that LIPUS has positive effect on maturation of regenerate bone was put forward creatively, and wants to vedfy the hypothesis by compare the difference between LIPUS intervention and no intervention.METHODS: Thlrty-six adult, healthy, New Zealand White rabbits were randomly assigned to LIPUS treatment group and control.group, with 18 animals in each group.All animals were undergone mid-diaphyeaal tibia ostactomy and were immobilized in Orthofix M103 Mini lengtheners. After a eaven-day latency period, gradual distraction of 0.5 mm per twelve hours for 10 days to produce 10 mm distraction. A 4-weeks course of LIPUS treatment was applled over the distraction site for twenty minutes daily starting immediately after the completion of distraction. At weeks 4, 8, 12 after distraction, the bone healing was evaluated by X-ray film, and total mineralized areas were measured by Image J software. The newly formed bone In the lerigthening field was harvested and stained with haematoxylin-eosin, Masson's tdchroma end VG. Thearaas of newly formed bone were measured to calculate a percentage of the total callus area.RESULTS AND CONCLUSION: Thirty-six rabbits ware included in the final analysis, At week 4 after distraction, the maturation of newly formed bone in LIPUS treatment group appeared eadier than that in the control groups. The bona callus image presented in the marginal and center region of experimental defect, increased greatly and had higher density until filled of the lengthening fields. Many bone-like masses appeared in the newly formed tissues and the tissues surrounding the bone granules partially changed Into bone-like tissues, and the rate of callus production was increased (P ＜ 0.05). There was no significant difference between two groups at weeks 8 and 12 after distraction. Histological results showed that that new bone formation of the LIPUS group was earlier than the control group at weeks 4, 8, and 12 after distraction. The percentage of new bona on total callus area of the LIPUS group was greater than that of the control group at weak 4, but there was no obvious difference at weeks 8 and 12 after distraction. LIPUS accelerates new bone formation, increases the size of the distraction callus, exhibits highly effective in achieving maturation of bone in the animal modal with distraction osteogenesis.

Objective To explore the effect of low intensity pulsed ultrasound stimulation (LI-PUS) on the maturation of regenerate bone in a rabbit limb lengthening model. Methods Sixty skeletal mature female New Zealand white rabbits were randomly divided into an LIPUS treatment group and a control group. All rabbits were underwent mid-diaphyseal tibial osteotomy and immobilized in an Orthofix M103 Mini lengther. Gradual distraction at 0. 5 mm every 12 h for 10 d was performed at day 7 postoperatively. A 4-week course of LIPUS treatment group was applied over the distraction site for 20 min daily starting immediately after the completion of the distraction only for the treatment group. Rabbits were euthanized and the mid-diaphyseal tibia was harvested for evaluation at 4, 8, and 12 wk after the completion of the bone lengthening protocol. Radiographic analysis was performed to study the formation of bone callus using the ImageJ software at 12 wk after the completion of the bone lengthening protocol. Bone mineral density (BMD) of regenerate bone was measured by Dual energy X-ray absorptiometry (DEXA) . Torsional testing to failure was performed on the tibia specimens at 8 and 12 wk after the completion of the bone lengthening protocol. Results Radio-graphic measurement showed higher relative gray scale of bone callus in the LIPUS group than that in the control group at 12 wk (P ＜ 0. 05) . BMD in the LIPUS group was significantly higher than that in control group at 8 and 12 wk (P ＜ 0. 05). Biomechanical testing showed that the ultimate torque, ultimate torsional stiffness, and energy absorption at failure of regenerated bone at 8 and 12 wk in the LIPUS treatment group were better than those in the control group (P ＜ 0. 05) Conclusion LIPUS as a biophysical stimulation may accelerate the formation and maturation of regenerate bone in rabbit tibia lengthening model.