BACKGROUND:Bone relies on the close connection between blood vessels and bone cells to maintain its integrity.Bones are in a physiologically hypoxic environment.Therefore,the study of angiogenesis and osteogenesis in hypoxic environment is closer to the microenvironment in vivo. OBJECTIVE:To explore the influence of Wenshen Tongluo Zhitong(WSTLZT)formula on H-type bone microvascular endothelial cell/bone marrow mesenchymal stem cell co-culture system in hypoxia environment and its related mechanism. METHODS:Enzyme digestion method and flow sorting technique were used to isolate and identify H-type bone microvascular endothelial cells.Mouse bone marrow mesenchymal stem cells were isolated and obtained by bone marrow adhesion method.H-type bone microvascular endothelial cell/bone marrow mesenchymal stem cell hypoxic co-culture system was established using Transwell chamber and anoxic culture workstation.WSTLZT formula powder was used to intervene in each group at a mass concentration of 50 and 100 μg/mL.The angiogenic function of H-type bone microvascular endothelial cells in the co-culture system was evaluated by scratch migration test and tube formation test.The osteogenic differentiation ability of bone marrow mesenchymal stem cells in the co-cultured system was evaluated by alkaline phosphatase staining and alizarin red staining.The protein and mRNA expression changes of PDGF/PI3K/AKT signal axis related molecules in H-type bone microvascular endothelial cells in the co-cultured system were detected by Western Blotting and q-PCR,respectively. RESULTS AND CONCLUSION:(1)Compared with the normal oxygen group,the scratch mobility and new blood vessel length of H-type bone microvascular endothelial cells were significantly higher(P<0.05);the osteogenic differentiation capacity of bone marrow mesenchymal stem cells was higher(P<0.05);the expression of PDGF/PI3K/AKT axis-related molecular protein and mRNA increased(P<0.05)in the hypoxia group.(2)Compared with the hypoxia group,scratch mobility and new blood vessel length were significantly increased in the H-type bone microvascular endothelial cells(P<0.05);bone marrow mesenchymal stem cells had stronger osteogenic function(P<0.05);the expression of PDGF/PI3K/AKT axis-related molecular proteins and mRNA further increased(P<0.05)after treatment with different dose concentrations of WSTLZT formula.These findings conclude that H-type angiogenesis and osteogenesis under hypoxia may be related to the PDGF/PI3K/AKT signaling axis,and WSTLZT formula may promote H-type vasculo-dependent bone formation by activating the PDGF/PI3K/AKT signaling axis,thereby preventing and treating osteoporosis.

Objective: To evaluate the performance of platelet efficacy score (PEscore) in predicting platelet transfusion efficacy in hematological patients. Methods: A total of 485 patients with hematological diseases, including 298 males (62.09±15.45 years) and 187 females (59.17±16.52 years) who received platelet transfusion from January 1, 2021 to December 31, 2024 were enrolled in this study. Clinical data of the patients such as diagnosis, gender, age, number of platelet transfusion, and platelet antibody data were analyzed to investigate the incidence and influencing factors of platelet transfusion refractoriness in hematological patients at our hospital. ROC curve was used to evaluate the performance of PEscore model in predicting platelet transfusion efficacy. The predictive performance of PEscore model was validated by calculating its sensitivity, specificity, and accuracy in 115 clinical cases. Results: The incidence of platelet transfusion refractoriness in 485 cases was 29.90% (145/485). Significant differences (P<0.05) were observed between the effective and ineffective platelet transfusion groups regarding the following factors: diagnosis: lymphoma [55.32% (26/47) vs 44.68% (21/47)], the number of previous platelet transfusions [≥25: 60.78% (31/51) vs 39.22% (20/51)], platelet antibody screening result [positive: 33.76% (53/157) vs 66.24% (104/157)], and platelet transfusion volume (×10 /L) [>6: 62.71% (74/118) vs 37.29% (44/118)]. The area under the ROC curve of PEscore was 0.876. The cut-off points and corresponding sensitivity and specificity were 19.90.59% and 69.44%, respectively. The results of clinical application showed that the sensitivity, specificity and accuracy of the PEscore model for predicting platelet transfusion were 87.50%, 93.41% and 92.17%, respectively. Conclusion: The incidence of platelet transfusion refractoriness in hematological patients is relatively high. PEscore prediction model has a good performance in predicting the effect of platelet transfusion, which can provide a reliable basis for predicting the effect of platelet transfusion in hematological patients before blood transfusion.

ObjectiveTo evaluate the effect of women's body mass index （BMI） on pregnancy outcomes of ovulation induction intrauterine insemination （OI-IUI） in patients with unexplained primary infertility. MethodsThe study included 764 OI-IUI cycles from January 2016 to December 2022 in reproductive center of Sun Yat-sen Memorial Hospital. According to BMI，patients were divided into three groups：low BMI （BMI<18.5 kg/m²）， normal BMI （18.5 kg/m² ≤BMI＜23.0 kg/m²）， and high BMI （BMI≥23.0 kg/m²）. Comparison of clinical data and pregnancy outcomes was performed between the groups. Logistic regression was used to analyze the association between BMI and live birth rate. ResultsFrom the low BMI group to the high BMI group， the HCG positive rate （7.08%，9.74%， 13.19%）， clinical pregnancy rate（5.51%， 7.91%， 13.19%）， and live birth rate （4.72%， 6.90%， 12.50%） increased. Among them， the live birth rate of the high BMI group was significantly higher than that of the low BMI group and the normal BMI group， with a statistically significant difference （P=0.034）. While the early miscarriage rate （14.28%， 10.26%， 5.26%） decreased from the low BMI group to the high BMI group. The binary logistic regression analysis revealed that BMI was an independent factor in live birth， and high BMI resulted in a better live birth rate than low BMI （OR=3.15，95%CI=1.191-8.329，P=0.021）. ConclusionLow BMI is associated with poor OI-IUI outcomes in patients with unexplained primary infertility. These patients are encouraged to gain weight in a healthy manner.

Objective To analyze the correlation between inflammation,nutritional indicators and hy-poproteinemia in patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD).Meth-ods The clinical data of patients with AECOPD admitted to the Department of Respiratory and Critical Care Medicine of the First Affiliated Hospital of Xiamen University from January 2020 to September 2022 were ret-rospectively analyzed,and the patients were divided into the hypoproteinemia group(n=73)and the non-hy-poproteinemia group(n=141)according to whether the serum albumin(ALB)was lower than 35 g/L.The clinical data,inflammatory indicators and nutritional indicators of the two groups were compared,Spearman correlation analysis was performed,and binary logistic regression analysis was performed to analyze the influ-encing factors of patients with AECOPD complicated with hypoproteinemia.Results There were statistically significant differences in age,length of hospital stay,and body weight between the two groups(P＜0.05).There were no significant differences in gender,number of hospitalizations in the past 1 year,height,diabetes,hypertension and proportion of coronary heart disease(P＞0.05).Compared with the non-hypoproteinemia group,the hypoproteinemia group had longer hospital stays and higher levels of C-reactive protein,neutrophil/albumin ratio(NAR),neutrophil to lymphocyte ratio(NLR),platelet-lymphocyte ratio(PLR),and systemic immunoinflammatory index(SII).The prognostic nutritional index(PNI),body mass index(BMI),hemoglo-bin and total protein levels were lower,and the difference was statistically significant(P＜0.05).Body weight,BMI,hemoglobin,total protein,PNI and AECOPD patients with hypoproteinemia were negatively cor-related(P＜0.05),while age,length of hospital stay,C-reactive protein,NAR,NLR,PLR,SII and AECOPD patients with hypoproteinemia were positively correlated(P＜0.05).Binary logistic regression analysis showed that PNI,SII and NLR were the influencing factors of hypoproteinemia in AECOPD patients.Conclusion In clinical practice,attention should be paid to and timely correction of hypoproteinemia in pa-tients with AECOPD,improvement of inflammatory indicators and nutritional status of patients,and preven-tion of acute exacerbation.

Objective To explore the feasibility and safety of MCCE in gastrointestinal examination of elderly patients with malignant tumors.Methods Clinical data of 127 patients who underwent MCCE examination from April 2019 to September 2022 were retrospectively analyzed.According to age,the patients were divided into the elderly group(age≥65 year-old,n = 88)and the middle-aged group(40≤age<65 year-old,n = 39),and the clinical data of patients with malignant tumors were screened from the two groups for analysis and comparison.Results 131 patients received MCCE examination,and 4 elderly patients were excluded from this study due to swallowing failure,so 88 elderly patients were actually included in the study.In the elderly group,45.4%had serious cardiovascular diseases(40/88),27.3%had malignant tumors(24/88),8.0%had serious respiratory diseases(7/88),6.8%had anesthesia problems(6/88),and 9.1%had neurological diseases(8/88).Among the 24 elderly patients with malignant tumors,25.0%had severe cardiovascular disease,25.0%had poor general status,20.8%had brain metastases,and 12.5%had severe respiratory dysfunction.The positive diagnosis rate of gastric P2 lesions in the elderly group(52/88,59.1%)was significantly higher than that in the middle-aged group(13/39,33.3%)(P = 0.013).There was significant difference in positive rate of ulcer diagnosis between the two groups(29.5%and 10.2%)(P = 0.032).In patients with malignant tumors,the positive rate of ulcer diagnosis between the two groups(45.8%and 11.1%)was statistically significant(P = 0.038).The cleanliness and visualization scores of proximal stomach in the middle-aged group were higher than those in the elderly group,and the differences were statistically significant(P<0.05).Conclusion MCCE is generally effective and safe in elderly patients,especially those with malignant tumors,without missing any significant gastric lesions.

Objective To analyze the frailty of patients with long-term maintenance dialysis(MD)and its influencing factors,and to explore the correlation of different dialysis modalities with the re-infection of novel coronavirus infection(COVID-19)and frailty syndrome.Methods Patients with regular dialysis in Nephrology Department of the Second Affiliated Hospital of Kunming Medical University from February to June 2023 were selected.A cross-sectional survey was conducted to collect clinical data of the patients,including dialysis modality(i.e.maintenance hemodialysis,abbreviated as hemodialysis,and continuous ambulatory peritoneal dialysis,abbreviated as peritoneal dialysis),and whether with re-infection of COVID-19.Patients were divided into 3 groups using Fried's frailty phenotype(FP):non-frailty group,pre-or-intermediate frailty group,and frailty syndrome group.The clinical characteristics of the FP were compared among the three groups.The correlation of frailty with clinical data,dialysis modality,re-infection of COVID-19 in each group was compared.Multifactorial logistic regression was used to analyze the factors influencing the development of frailty syndrome in patients.Results A total of 246 dialysis patients were included in this study,with 77(31.3%)in the non-frailty group,83(33.7%)in the pre-frailty group and 86(35.0%)in the frailty syndrome group.The frailty syndrome group showed characteristics of advanced age,high pre-dialysis creatinine level,low serum albumin level and combined pleural effusion(all P＜0.05).There was no statistically significant difference in the comparison of frailty between the hemodialysis and peritoneal dialysis group(P = 0.960).COVID-19 re-positive patients had higher frailty score than non-re-positive patients.Multifactor logistic regression showed that age,COVID-19 re-infection of COVID-19,serum albumin,pre-dialysis creatinine,and pleural effusion were factors influencing the development of frailty syndrome in dialysis patients(P＜0.05).Conclusion There is high incidence of frailty syndrome in dialysis patients,and there is no correlation of frailty with dialysis modality.High serum albumin level is a protective factor for the development of frailty syndrome in patients,whereas re-infection of COVID-19,advanced age,high pre-dialysis blood creatinine level and pleural effusion are risk factors for the development of frailty syndrome.

BACKGROUND:Clinical studies have shown that aerobic exercise is an important supplement to the clinical treatment of patients with pulmonary hypertension,which can alleviate the disease condition,increase exercise tolerance and improve the quality of life.However,it is not clear whether patients at different stages of pulmonary hypertension can benefit equally from exercise training. OBJECTIVE:To compare the intervention effects of early or late aerobic training on right heart failure in rats with pulmonary hypertension and explore its possible mechanism. METHODS:Sixty male Wistar rats were randomly divided into control group,model sedentary group,model early exercise group and model late exercise group,with 15 rats in each group.The model of pulmonary hypertension was established by intraperitoneal injection of monocrotaline(60 mg/kg)in the latter three groups.The model early exercise group was given 8 weeks of treadmill aerobic exercise(60%maximum running speed,60 minutes per day,5 days a week)after modeling,while the model late exercise group was trained for 6 weeks after 2 weeks of modeling.The control and model sedentary groups were fed quietly in the rat cage for 8 weeks.After training,the exercise performance,right ventricular hemodynamics,cardiopulmonary function,cardiopulmonary histopathology,reactive oxygen species level in mitochondria,activity of mitochondrial respiratory chain complex and expressions of myocardial tissue proteins were detected. RESULTS AND CONCLUSION:Compared with the model sedentary group,exercise performance and right ventricular function improved(P<0.05),myocardial collagen content,endothelin-1,tumor necrosis factor-α/interleukin-10 ratio and β-myosin heavy chain/α-myosin heavy chain ratio decreased(P<0.05),vascular endothelial growth factor and sarcoplasmic reticulum calcium-adenosine triphosphate enzyme expression increased(P<0.05),immunofluorescence intensity of mitochondrial reactive oxygen species and the protein expression of 3-nitrotyrosine decreased(P<0.05),the activities of complex I,II,IV and V increased in the model early exercise and model late exercise groups(P<0.05),but there were no significant changes in right ventricular maximum pressure,pulmonary acceleration time and pulmonary artery wall area/total vascular area ratio(P>0.05).Compared with the model late exercise group,the model early exercise group further improved exercise performance and right ventricular function,and downregulated collagen content,brain natriuretic peptide protein expression,tumor necrosis factor-α/interleukin-10 ratio and β-myosin heavy chain/α-myosin heavy chain ratio(P<0.05).To conclude,although pulmonary vascular remodeling and right ventricular overload persist in rats with pulmonary hypertension,exercise training at different stages of the disease has a cardioprotective effect.The mechanism is related to the improvement of cardiac remodeling,neurohormone system imbalance,inflammatory response and mitochondrial oxidative stress.Greater benefit is gained from initiating exercise in the early stage of the disease.

BACKGROUND:Aging is associated with increased susceptibility to cardiovascular disease,and mitochondrial dysfunction plays a key role in the pathogenesis of cardiovascular disease.Regular physical activity is beneficial to cardiovascular health and can prevent and treat chronic heart disease.However,the specific mechanism of mitochondria in the protective effect of exercise on the aging heart has not yet been clarified. OBJECTIVE:To explore the effect of aerobic exercise on cardiac pathological remodeling in aging rats and to investigate the possible mechanism of mitochondrial quality control system. METHODS:Sixty Wistar rats were randomly divided into young sedentary group(6 months old),old sedentary group(20 months old)and old exercise group(20 months old)with 20 rats in each group.Rats in the young sedentary and old sedentary groups were fed in cages for 12 weeks,while those in the old exercise group underwent moderate-intensity aerobic treadmill exercise(60%of the maximal running speed,slope 0°,60 minute per day,5 days per week)for 12 weeks.After the experiment,the heart was extracted for relevant indicator tests. RESULTS AND CONCLUSION:Cardiac morphology and myocardial histopathology:compared with the young sedentary group,the rats in the old sedentary group presented with concentric cardiac hypertrophy,myocardial fibrosis,myocardial cell apoptosis and loss,and cardiac diastolic dysfunction(P＜0.05);compared with the old sedentary group,animals in the old exercise group showed reduced myocardial fibrosis and apoptosis rates,increased cell numbers,improved cardiac function(P＜0.05),and a transition in cardiac phenotype from pathological to physiological hypertrophy.Mitochondrial function:compared with the young sedentary group,the generation rate of mitochondrial hydrogen peroxide increased(P＜0.05),respiration rate and respiratory control ratio of state 3 and state 4 decreased(P＜0.05),activities of respiratory chain complexes Ⅰ,Ⅱ and Ⅳ decreased(P＜0.05),mitochondrial calcium retention capacity decreased(P＜0.05),and mitochondrial permeability transition pore opening increased(P＜0.05)in the old sedentary group.Compared with the old sedentary group,all of the above indicators were significantly improved in the old exercise group(P＜0.05).Mitochondrial quality control:compared with the young sedentary group,mitochondrial biogenesis decreased(P＜0.05),mitophagy activity increased(P＜0.05),mitochondrial fusion reduced(P＜0.05),and fission raised(P＜0.05)in the old sedentary group;compared with the old sedentary group,mitochondrial biogenesis and mitophagy activity increased(P＜0.05),mitochondrial fusion raised(P＜0.05)and fission decreased(P＜0.05)in the old exercise group.To conclude,regular aerobic exercises exert cardioprotective effects in aging rats by regulating the mitochondrial quality control system,thus reversing pathological cardiac remodeling and improving cardiac function.

AIM: To investigate the application of biological amniotic membrane soaked in pirfenidone(PFD)and to evaluate its anti-scarring effect and toxic side effects on glaucoma model of rabbit eyes.METHODS: The right eyes of 72 healthy New Zealand white rabbits were randomly divided into 0.5%PFD+ biological amniotic membrane group, biological amniotic membrane group, mitomycin C(MMC)group and blank control group after the glaucoma model was established by anterior chamber injection of compound carbomer solution, and 18 rabbits in each group underwent trabeculectomy, in which the 0.5% PFD+ biological amniotic membrane group was placed with 0.5% PFD solution-soaked biological amniotic membrane under the scleral flap, and the biological amniotic membrane group was placed with normal saline-soaked rehydrated biological amniotic membrane under the scleral flap. In the MMC group, a cotton pad soaked in MMC was placed under the scleral flap for 3 min and immediately rinsed with normal saline, while the blank control group received no implant after the scleral flap was made. The intraocular pressure(IOP), filtration blebs, toxic side effects and complications were evaluated, and the histopathological changes in the filtration area were observed by hematoxylin-eosin(HE), Masson staining and immunohistochemical staining.RESULTS: The mean IOP at 14, 21 and 28 d after trabeculectomy were 0.5%PFD+ biological amniotic membrane group<MMC group<biological amniotic membrane group<blank control group(all P<0.05). At 28 d after trabeculectomy, 0.5%PFD+ biological amniotic membrane group had the best effect of anti-inflammatory hyperplasia and inhibition of collagen formation, the highest survival rate of filtration blebs, and the inflammatory reaction was mild.CONCLUSION: Biological amniotic membrane soaked in pirfenidone has more obvious anti-scarring effect on glaucoma model, with less toxic side effects and good safety.

Background Exposure to diisononyl phthalate (DINP), an endocrine disruptor associated with metabolic diseases and widely used in plastic products, has been linked to the development of several adverse health outcomes in the liver, including non-alcoholic fatty liver disease (NAFLD). Objective To investigate the effects and the possible molecular mechanisms of DINP exposure on lipid metabolism in human hepatocellular carcinoma cells (HepG2 cells). Methods First, HepG2 cells were treated with DINP at three time spots (24, 48, and 72 h) and eleven doses (0, 0.003, 0.01, 0.03, 0.1, 0.3, 1, 3, 10, 30, and 100 mmol·L⁻¹). Cell viability were detected using cell counting kit 8 (CCK8). Intracellular lipid deposition was determined by oil red O staining and lipid content detection, and triglyceride (TG) and cholesterol (TC) were further detected. Finally, the mRNA expression levels were detected by fluorescence quantitative PCR, including fatty acid synthesis related genes [acetyl-CoA carboxylase alpha (Accα), fatty acid synthase (Fasn), malonyl-CoA decarboxylase (Mlycd), and sterol regulatory element binding protein 1 (Srebp1)] and β-oxidation related genes [peroxisome proliferator activated receptor alpha (Pparα), AMP-activated protein kinase (Ampk), carnitine palmitoyltransferase 1A (Cpt-1a), transcription factor A, mitochondrial (Tfam), nuclear respiratory factor 1 (Nrf1), and peroxisome proliferator-activated receptor gamma and coactivator 1 alpha (Pgc1-α)]. Results Compared with the control group (0 mmol·L⁻¹), the no observed adverse effect levels (NOAEL) of HepG2 cell viability were 0.3, 0.1, and 0.1 mmol·L⁻¹ after 24, 48, and 72 h exposure to DINP, respectively, and the corresponding lowest observed adverse effect levels (LOAEL) were 1, 0.3, and 0.3 mmol·L⁻¹, respectively (P<0.05). After exposure to 30 mmol·L⁻¹ and 100 mmol·L⁻¹ DINP for 24 h, the intracellular lipid content, lipid deposition, TG, and TC levels were increased significantly compared with the control group (P<0.01). Compared with the control group, the mRNA expression levels of genes related to fatty acid synthesis, such as Mlycd, Srebp1, Fasn, and Accα, were down-regulated after the 100 mmol·L⁻¹ DINP exposure for 24 h, while the mRNA expression level of Mlycd was up-regulated in the 30 mmol·L⁻¹ group. The β-oxidation related genes such as Ampk, Pparα, and Tfam were up-regulated significantly after the 100 mmol·L⁻¹ DINP exposure, while Cpt-1a mRNA expression level was down-regulated (P<0.05). Conclusion Exposure to DINP at 30 mmol·L⁻¹ and 100 mmol·L⁻¹ can interfere with fatty acid synthesis and β-oxidation in lipid metabolism of HepG2 cells, resulting in lipid deposition.