ObjectiveTo comprehensively assess the clinical value of Duliang soft capsules in the treatment of migraine with wind-cold blood stasis syndrome， and to provide guidance for national medical decision-making， clinical drug promotion， and pharmaceutical services. MethodThe evaluation of Duliang soft capsules' clinical value was conducted in accordance with the Guidelines for the Management of Comprehensive Clinical Evaluation of Drugs （Trial Version， 2021） using a combination of qualitative and quantitative methods. Utilizing the CSC v2.0 software， this study conducted a comprehensive clinical evaluation of Duliang soft capsules across the "6+1" dimensions， including safety pre- and post-market launch， effectiveness in treating migraine， economy （cost-effectiveness）， and innovation， suitability， accessibility， and traditional Chinese medicine （TCM） characteristics in both its technology and clinical applications. ResultSafety： Duliang soft capsules were found to have good safety based on evidence from known adverse reactions （spontaneous reporting system （SRS） data， literature data， etc.）， pre-marketing toxicological research， and post-marketing drug monitoring. Effectiveness： A meta-analysis indicated that the combination of Duliang soft capsules and western medicine was more effective than Western medicine alone in the treatment of migraine. The product's effectiveness was rated as "Best" based on the quality and value of the evidence. Economy： Duliang soft capsules are moderately priced and categorized as a Type B medical insurance product. Economic research indicated that the combination of Western medicine and Duliang soft capsules was more cost-effective than Western medicine alone. The product's economy was rated as "Better". Innovation： Duliang soft capsules， with Angelicae Dahuricae Radix and Chuanxiong Rhizoma as the main components， hold one invention patent and have been awarded the China Patent Excellence Award. The pharmaceutical company has introduced innovative extraction （CO₂ supercritical extraction technology） and formulation （soft capsule） processes. The product's innovation was rated as "Better". Suitability： A questionnaire survey on Duliang soft capsules showed that it was well-suited for both patients and healthcare professionals. The product received a comprehensive assessment of suitability through the "Evaluation of Chinese Patent Medicine Information Services". The product's suitability was rated as "Best". Accessibility： Duliang soft capsules are moderately priced， making them accessible and affordable. The product's accessibility was rated as "Good" based on evidence from these three aspects. TCM characteristics： The formulation of Duliang soft capsules can be traced back to WANG Qiu's Selected Formulas from the Praiseworthy Studio （Shi Zhai Bai Yi Xuan Fang） from the Song Dynasty， and it was documented in ZHANG Jiebin's The Complete Works of Zhang Jing-yue （Jing Yue Quan Shu） as "Duliangwan". The product has been extensively studied with over 2000 clinical cases since its market launch， and its TCM characteristics were rated as outstanding with sufficient evidence. ConclusionThe comprehensive clinical value evaluation of Duliang soft capsules demonstrated its high effectiveness， suitability， and accessibility， and outstanding TCM characteristics. The product's safety， economy， and innovation received good ratings. In summary， Duliang soft capsules exhibited significant clinical value and outstanding TCM characteristics， the evidence was sufficient， and the result was confirmed， providing crucial references for clinical decision-making and pharmaceutical management.

OBJECTIVE: To investigate the effect of microRNA-509-3p (miR-509-3p) on the apoptosis of atherosclerotic vascular endothelial cells. METHODS: Mouse aortic endothelial cells (MAECs) were divided into normal control group, oxidized low-density lipoprotein (ox-LDL) group, miR-509-3p overexpression group, miR-509-3p overexpression control group, miR-509-3p inhibitor + ox-LDL group, and miR-509-3p inhibitor control + ox-LDL group. MAEC were induced with 100 mg/L ox-LDL for 24 hours, and then transfected with miR-509-3p overexpression/inhibitor and corresponding control for 48 hours. The miR-509-3p expression in MAECs exposed to ox-LDL was detected using real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). Flow cytometry was used to detect the level of apoptosis, and cell counting kit (CCK-8) was used to detect the proliferation activity of MAECs. The direct gene targets of miR-509-3p were predicted using bioinformatics analyses and confirmed using a dual luciferase reporter assay. The expression of Bcl-2 mRNA and protein was detected by RT-qPCR and Western blotting, respectively. RESULTS: Compared with the normal control group, miR-509-3p was significantly upregulated in ox-LDL-stimulated MAECs (1.68±0.85 vs. 1.00±0.30, t = 2.398, P < 0.05). After transfection of MAECs with miR-509-3p overexpression, the luciferase activity of the BCL2 3'UTR WT reporter gene was significantly lower than that of miR-509-3p overexpression control group (0.83±0.06 vs. 1.00±0.07, t = 4.531, P = 0.001). The luciferase activity of the BCL2 3'-UTR mutant (MUT) reporter gene was not significantly different from that of miR-509-3p overexpression control group (0.94±0.05 vs. 1.00±0.08, t = 1.414, P = 0.188). Compared with the normal control group and miR-509-3p mimics control group, the cell proliferation activity was decreased [(0.60±0.06)% vs. (1.00±0.09)%, (0.89±0.04)%, both P < 0.01], the percentage of apoptotic cells were increased [(23.46±2.02)% vs. (7.66±1.52)%, (10.40±0.78)%, both P < 0.05], and the mRNA and protein expression of Bcl-2 were significantly downregulated (Bcl-2 mRNA: 0.52±0.13 vs. 1.00±0.36, 1.10±0.19, Bcl-2 protein: 0.42±0.07 vs. 1.00±0.11, 0.93±0.10, both P < 0.01) in miR-509-3p overexpression group. Compared with the ox-LDL group, inhibition of miR-509-3p expression could increase the proliferation activity of MAECs induced by ox-LDL [(0.64±0.35)% vs. (0.34±0.20%)%, P < 0.05], and reduce the apoptosis rate [(13.59±2.22)% vs. (29.84±5.19)%, P < 0.01], and up-regulated the expression of Bcl-2 mRNA and protein in MAECs induced by ox-LDL (Bcl-2 mRNA relative expression: 0.82±0.09 vs. 0.52±0.10, Bcl-2 protein relative expression: 0.83±0.17 vs. 0.40±0.07, both P < 0.05). CONCLUSIONS Bcl-2 was one of the target genes of miR-509-3p. miR-509-3p can reduce the proliferation activity of endothelial cells, reduce the expression of Bcl-2, and promote cell apoptosis, thereby promoting the occurrence and development of atherosclerosis. Inhibition of miR-509-3p expression may be a potential therapeutic target for atherosclerosis.
Animals ; Mice ; Humans ; Endothelial Cells ; MicroRNAs/metabolism* ; Signal Transduction ; Lipoproteins, LDL/metabolism* ; Apoptosis ; RNA, Messenger/metabolism* ; Proto-Oncogene Proteins c-bcl-2/pharmacology* ; Atherosclerosis/metabolism* ; Luciferases/pharmacology* ; Cell Proliferation ; Human Umbilical Vein Endothelial Cells

BACKGROUND: The literature recommends that reduced dosage of CPT-11 should be applied in patients with UGT1A1 homozygous mutations, but the impact of UGT1A1 heterozygous mutations on the adverse reactions of CPT-11 is still not fully clear. METHODS: A total of 107 patients with UGT1A1 heterozygous mutation or wild-type, who were treated with CPT-11 from January 2018 to September 2021 in Peking University Third Hospital, were retrospectively enrolled. The adverse reaction spectra of patients with UGT1A1*6 and UGT1A1*28 mutations were analyzed. Adverse reactions were evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) 5.0. The efficacy was evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The genotypes of UGT1A1*6 and UGT1A1*28 were detected by digital fluorescence molecular hybridization. RESULTS: There were 43 patients with UGT1A1*6 heterozygous mutation, 26 patients with UGT1A1*28 heterozygous mutation, 8 patients with UGT1A1*6 and UGT1A1*28 double heterozygous mutations, 61 patients with heterozygous mutation at any gene locus of UGT1A1*6 and UGT1A1*28. Logistic regression analysis showed that the presence or absence of vomiting (P=0.013) and mucositis (P=0.005) was significantly correlated with heterozygous mutation of UGT1A1*28, and the severity of vomiting (P<0.001) and neutropenia (P=0.021) were significantly correlated with heterozygous mutation of UGT1A1*6. In colorectal cancer, UGT1A1*6 was significantly correlated to diarrhea (P=0.005), and the other adverse reactions spectrum was similar to that of the whole patient cohort, and efficacy and prognosis were similar between patients with different genotypes and patients treated with reduced CPT-11 dosage or not. CONCLUSIONS In clinical use, heterozygous mutations of UGT1A1*6 and UGT1A1*28 are related to the risk and severity of vomiting, diarrhea, neutropenia and mucositis in patients with Pan-tumor and colorectal cancer post CPT-11 therpy. In colorectal cancer, UGT1A1*6 is significantly related to diarrhea post CPT-11 use, efficacy and prognosis is not affected by various genotypes or CPT-11 dosage reduction.
Camptothecin/therapeutic use* ; Glucuronosyltransferase/genetics* ; Humans ; Lung Neoplasms/drug therapy* ; Mutation ; Polymorphism, Genetic ; Retrospective Studies

BACKGROUND: Malignant pleural effusion is one of the common clinical manifestations of patients with lung adenocarcinoma. Patients with pleural effusion at the initial diagnosis of lung adenocarcinoma usually indicate poor prognosis. Epidermal growth factor receptor (EGFR) mutations mainly occur in patients with lung adenocarcinoma. Patients with different mutant subtypes have different prognosis. The clinical characteristics and prognostic factors of patients with EGFR mutated lung adenocarcinoma of different molecular subtypes combined with pleural effusion at initial diagnosis are still unclear. This study was designed to explore the clinical characteristics and prognostic factors of these patients in order to provide management recommendations for them. METHODS: A retrospective analysis of the clinical characteristics, treatment, outcomes and progression-free survival (PFS) of first-line treatment in patients with EGFR mutated lung adenocarcinoma combined with pleural effusion at initial diagnosis admitted to Department of Medical Oncology and Radiation Sickness, Peking University Third Hospital from January 2012 to June 2021 was performed. Pearson's chi-square test or Fisher's exact test were performed for comparison between groups. Kaplan-Meier method was performed for survival analysis and Cox proportional risk regression model was performed for multivariate analysis. RESULTS: 76 patients met the inclusion criteria in this study. The incidences of EGFR classical mutations 19del, 21L858R and non-classical mutations were 46.0%, 38.2% and 15.8%, respectively among these patients. There was no significant difference between the three mutations in terms of gender, age, presence of dyspnea at presentation, whether other distant metastases were combined, site of pleural effusion, volume of pleural effusion, presence of other combined effusions, tumor-node-metastasis (TNM) stage, presence of other gene mutations, and treatment of pleural effusion (P>0.05). In patients with EGFR classical mutations 19del or 21L858R or non-classical mutations subtype, the proportion of chemotherapy in first-line regimens were 17.1%, 20.7% and 58.3%, respectively (P=0.001); and first-line disease control rates were 94.3%, 75.9% and 50%, respectively (P=0.003); pleural effusion control rates were 94.3%, 79.3% and 66.7%, respectively (P=0.04); PFS were 287 d, 327 d and 55 d, respectively (P=0.001). Univariate analysis showed that EGFR mutation subtype, control of pleural effusion, first-line treatment agents, and first-line treatment efficacy were significantly associated with PFS (P<0.05). Cox multifactorial analysis showed that only EGFR mutation subtype and first-line treatment efficacy were independent prognostic factors for PFS (P<0.05). CONCLUSIONS PFS was significantly better for classical mutations than for non-classical mutations in patients with EGFR mutated lung adenocarcinoma combined with pleural effusion at initial diagnosis. Improving the efficacy of first-line therapy is the key to improve the prognosis of these patients.
Adenocarcinoma of Lung/genetics* ; ErbB Receptors/genetics* ; Humans ; Lung Neoplasms/pathology* ; Mutation ; Pleural Effusion/complications* ; Prognosis ; Retrospective Studies

Objective:To explore the possibility of repairing partial nasal alar defects with individualized design of localized skin flaps.Methods:The clinical data of 38 patients with nasal alar region tumor from October 2015 to June 2019 in Dalian Municipal Central Hospital were retrospectively analyzed, including 5 cases with intradermal nevus, 8 cases with junction nevus, 21 cases with basal cell carcinoma, 3 cases with trichoepithelioma, and 1 case with nasal alar sulcus fistula combined with infection. Surgical treatment with local anaesthesia was applied, and intraoperative freezing pathology was used to confirm the diagnosis and determine the safe margin. There was no nasal alar cartilage infiltration in all patients. The defect areas after resection of nasal alar lesions ranged from 1.0 cm × 1.0 cm to 3.0 cm × 2.5 cm. Local skin flap was aesthetically designed in accordance with the location and size of the nasal alar defect to primarily repair the defect. Among them, 15 cases were repaired with pedicled nasolabial groove flap, 10 cases with modified rhomboid flap, 6 cases with rotatory nasolabial groove flap, 5 cases with V-Y push flap, and 2 cases with double lobe flap.Results:One case had blood transportation obstacle after operation caused by compression and bandaging, 1 case had postoperative infection. Healing of the two cases delayed after treatment, and other patients healed properly. All the flaps survived without facial deformity, and the cosmetic effect was good.Conclusions:The primary repair of the nasal alar defect needs to follow the aesthetic requirements of the nose and face, which varies with diseases and experience of doctors. Flap selection should be individualized to achieve both the purpose of repairing defects and beauty.

Objective To explore the relationship between serum levels of osteoprotein (OPG), soluble nuclear factor-κB receptor activator ligand (sRANKL), inflammatory factors and coronary heart disease (CHD) and its severity. Methods The patients who underwent coronary angiography (CAG) due to chest pain admitted to department of cardiology of Tianjin Chest Hospital from April 2017 to December 2018 were enrolled, and they were divided into CHD group and non-CHD group according to the CAG results. The gender, age, history of hypertension, smoking history, diabetes, the levels of cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), apolipoprotein AI (apoAI), apolipoprotein B (apoB), lipoprotein (a) [Lp (a)], MB isoenzyme of creatine kinase (CK-MB) and other clinical data of patients were collected. The serum levels of OPG, sRANKL, matrix metalloproteinase-9 (MMP-9), monocyte chemotactic protein-1 (MCP-1), insulin-like growth factor-1 (IGF-1) and interleukin-6 (IL-6) were determined by enzyme-linked immunosorbent assay (ELISA). According to the results of CAG, the patients with CHD were divided into single-, double-, triple-branch coronary artery lesion groups, and the relationship between the levels of serum OPG, sRANKL, inflammatory factors and the degree of coronary artery lesions was observed. Multivariate Logistic regression was used to analyze the risk factors of CHD, and receiver operating characteristic (ROC) curve was plotted to analyze the predictive value of main risk factors for CHD. Results A total of 472 patients were enrolled in the final analysis during the study period, including 264 patients in the CHD group, 208 patients in the non-CHD group, 79 patients in the CHD group with single-branch disease, 75 patients with double-branch disease, and 110 patients with three-branch disease. ① Compared with the non-CHD group, the CHD group had more older male patients, as well as higher proportion of hypertension and diabetes, the levels of serum Lp (a) and CK-MB were significantly increased, and the levels of serum HDL-C and apoAI were significantly lowered. There was no statistically significant difference in serum TC, LDL-C, or apoB between the two groups. The levels of serum OPG, MMP-9, MCP-1, IGF-1 and IL-6 in the CHD group were significantly higher than those in the non-CHD group [OPG (μg/L): 1.79±0.50 vs. 1.50±0.30, MMP-9 (μg/L): 57.91 (33.50, 130.46) vs. 38.33 (29.43, 109.78), MCP-1 (μg/L):298.30 (207.96, 537.16) vs. 252.73 (165.22, 476.01), IGF-1 (μg/L): 734.03±486.11 vs. 217.75±126.45, IL-6 (ng/L):64.76±40.25 vs. 48.60±15.80, all P < 0.05], and the levels of serum sRANKL was significantly lower than that in the non-CHD group (ng/L: 344.31±122.14 vs. 378.74±109.27, P < 0.05). ② The serum OPG level showed a slight upward tendency with the increase in the number of coronary artery lesions, and the sRANKL level showed a slight downward tendency [OPG (μg/L) in the single-, double-, triple-branch coronary artery lesion groups was 1.74±0.49, 1.76±0.50, 1.85±0.52, and sRANKL (ng/L) was 354.96±116.64, 340.05±124.24, 339.57±125.03, respectively) without statistically significant differences (all P > 0.05). The levels of IGF-1 and IL-6 were increased with the number of coronary artery lesions [IGF-1 (μg/L) in the single-, double- and triple-branch coronary artery lesions groups was 372.13±258.42, 676.06±350.29, 1 033.47±468.06, and IL-6 (ng/L) was 48.87±16.72, 65.36±18.84, 75.76±22.72, respectively], and the differences among different lesion groups were statistically significant (all P < 0.01). Correlation analysis showed that IGF-1 level was significantly positively correlated with the number of coronary artery lesions (r = 0.612, P < 0.01), while IL-6 was not correlated with the number of coronary artery lesions (r = 0.185, P > 0.05).③ Multivariate Logistic regression analysis showed that elevated serum OPG and IGF-1 levels were risk factors for CHD [OPG: odds ratio (OR) = 1.995, 95% confidence interval (95%CI) = 1.936-2.067, P = 0.012; IGF-1: OR = 1.009, 95%CI = 1.004-1.015, P = 0.001]. ④ ROC curve analysis showed that the area under ROC curve (AUC) of OPG and IGF-1 was 0.716 and 0.867, respectively. When the cut-off value of OPG was 1.13 μg/L, the sensitivity was 81.7%, the specificity was 58.1%; when the cut-off value of sRANKL was 401.20 μg/L, the sensitivity was 69.7%, the specificity was 95.7%. Conclusions CHD was associated with increased in OPG, related inflammatory cytokines including MMP-9, MCP-1, IGF-1 and IL-6, and decreased in sRANKL. The level of IGF-1 was positively correlated with the severity of CHD. The serum levels of OPG and IGF-1 were risk factors for CHD, which had good predictive value for CHD.

Objective To investigate the relationship between mean platelet volume(MPV)and saphenous vein graft restenosis in patients receiving coronary artery bypass grafting(CABG),and to analyze the clinical significance of MPV in the prediction of restenosis after CABG.Methods A total of 354 patients admitted into Tianjin chest hospital from September 2009 to September 2014 with suspected myocardial ischemic events 3 to 5 years after CABG treatment was enrolled for a retrospective analysis.According to the coronary angiography(CAG)results,patients were divided into the vein bridge vascular lesion group(saphenous vein graft diseases,SVGD)(n=233)and the venous bridge vascular patency group(saphenous vein graft,SVG)(n=121).Paired t test was used to analyze the relationship between different factors and the bridge vascular patency.The binary logistic regression was used to analyze the effects of MPV and other factors on bridge vascular patency.Venous bridge stenosis ＞ 50％ was considered to be clinically significant and to damage myocardial blood supply.Results The MPV was higher in the SVGD group than the SVG group [(10.2±1.5)fl vs.(9.6±1.5)fl,P＜0.01].The logistic regression analysis showed that MPV(OR =1.268,95％CI:1.053-1.570,P=0.014),age(OR =1.007,95％CI:1.038-1.117,P=0.000),gender (OR=0.452,95％CI:0.250-0.816,P=0.008),diabetes mellitus(OR=2.319,95％CI:1.221-4.405,P =0.010)were the independent risk factors for venous bridge stenosis in the two groups,gender(OR=0.495,95％CI:0.251-0.976,P=0.042),diabetes mellitus(OR =2.237,95％CI:1.105-4.527,P =0.025),MPV(OR=1.334,95％CI;1.050 1.694,P=0.018),fibrinogen(OR=1.654,95％CI:1.020-2.682,P =0.041)were the independent risk factors for venous bridge stenosis in non-elderly patients,and age(OR =1.178,95％CI:1.116-1.244,P =1.178)was an independent risk factor for vein graft stenosis in elderly patients.The restenosis rate was higher in patients with MPV ≥ 12 fl(92.6％ or 25/27) than in the patients with MPV ＜ 12 fl(63.6％ or 208/327).The receiver operating characteristics(ROC) curve showed that the areas under the curve of MPV,age,gender,diabetes,fibrinogen were 0.610,0.657,0.394,0.626,0.654,respectively,and the area under the curve of joint diagnosis was 0.796,showing that joint prediction value was higher than any single prediction value(P＜0.01).Conclusions MPV level is an independent risk factor for vein graft stenosis,and has higher predictive value in combination with age,gender,diabetes and fibrinogen.

BACKGROUND: Patients with lung cancer have high risk of developing venous thromboembolism (VTE), which has been shown to have a significant impact on mortality. This study was to identify the incidence of VTE in lung cancer patients during systemic therapy and to analyze the risk factors associated with it. METHODS: We retrospectively analyzed the cases of 283 patients with lung cancer who received systemic therapy in the Department of Medical Oncology and Radiation Sickness, Peking University Third Hospital, from January 2016 to December 2018. Chi-square test and multivariate analyses were used to assess the correlation between clinical features and VTE. RESULTS: Of the patients we observed, 34 developed VTE, with an incidence of 12.01% (34/283). In patients with lower extremity varicose vein (LVV), there was an increase in the incidence of VTE (50.00% vs 9.89%, P=0.001). The incidence VTE in patients with distant metastasis was higher than that in patients without distant metastasis, and higher than that in patients with tumor-free (14.05% vs 14.00% vs 2.08%, P=0.024). The incidence of VTE in patients with active tumor was also significantly higher than that in patients without it (16.93% vs 8.18%, P=0.025). Patients with hypoalbuminemia (albumin <35 g/L) had more VTE events more than those without did (22.00% vs 9.87%, P=0.017), and patients with an elevated D-dimer level (>0.3 µg/mL) developed more VTE than those without did (17.93% vs 5.80%, P=0.006). There were no significant correlations between pathological types, blood cell count before systemic therapy including leukocyte, hemoglobin and platelet, or antiangiogenic drugs and VTE. Multivariate analysis showed that LVV, hypoalbuminemia and elevated level of D-dimer were independent risk factors of VTE. CONCLUSIONS LVV, serum albumin and D-dimer level may be potential and more effective predictors of VTE in lung cancer patients during systemic therapy. Basing on these factors, new predictive model can be built, and further study to validate its efficacy is required.

OBJECTIVE: To explore the polymorphisms of T149C and T950C gene in osteoprotectin (OPG) promoter sites and the levels of serum OPG and soluble nuclear factor-ΚB receptor activator ligand (sRANKL) and the incidence of coronary heart disease (CHD). METHODS: 528 patients in Tianjin suspected of CHD and underwent coronary angiography (CAG) who admitted to the department of cardiology of Tianjin Chest Hospital from April 2017 to December 2018 were enrolled. According to the CAG results, they were divided into two groups: CHD group (n = 302) and non-CHD group (n = 226). The gender, age, history of hypertension, family history of CHD, diabetes, levels of blood lipid parameters in serum and other clinical data of patients were recorded. The levels of serum OPG and sRANKL were measured by enzyme-linked immunosorbent assay (ELISA). T149C and T950C gene polymorphisms were analyzed by polymerase chain reaction-restriction endonuclease fragment length polymorphism (PCR-RFLP) methods. Hardy-Weinberg genetic balance test was performed for alleles. Binomial classification multivariate non-conditional Logistic regression method was used to analyze the relationship between T149C and T950C gene polymorphisms, serum levels of OPG and sRANKL and CHD. RESULTS: All patients were enrolled in the final analysis. The serum level of OPG in CHD group was significantly higher than that in non-CHD group (μg/L: 1.76±0.49 vs. 1.47±0.29, P < 0.01), the serum level of sRANKL was significantly lower than that in non-CHD group (ng/L: 342.14±121.38 vs. 376.63±108.66, P < 0.05). Logistic regression analysis showed that after adjusting for age, gender, blood lipid parameters, diabetes and other factors, the increase in serum OPG level was an independent risk factor for CHD [odds ratio (OR) = 1.995, 95% confidence interval (95%CI) = 1.935-2.066, P = 0.012]. PCR-RFLP results showed that TT, TC and CC genotypes were found in T149C and T950C of OPG promoter. According to Hardy-Weinberg equilibrium test, the polymorphisms of OPG T149C and T950C accorded with Hardy-Weinberg law, achieving genetic balance with representative of the population. The frequencies of TT, TC, CC and alleles T and C in T149C genotypes of non-CHD group were 53.5%, 42.9%, 3.6%, 75.0% and 25.0%, respectively, and they were 43.1%, 50.3%, 6.6%, 68.2% and 31.8%, respectively in CHD group. There were statistically significant differences in genotype and allele frequencies between the two groups (all P < 0.05). It was shown by Logistic regression analysis that the risk of CHD in TC+CC genotype of T149C was 1.86 of TT genotype (OR = 1.86, 95%CI = 1.24-2.78, P = 0.003). It was suggested that C allele might be a susceptible gene for CHD. In non-CHD group, the frequencies of TT, TC, CC, and alleles T and C in T950C genotypes were 39.8%, 46.5%, 13.7%, 63.1% and 36.9%, respectively. They were 39.4%, 43.4%, 17.2%, 61.1% and 38.9%, respectively in CHD group. There were no significant differences in genotype and allele frequencies between the two groups (all P > 0.05). Logistic regression analysis showed that TC+CC genotype of T950C was not related with CHD. CONCLUSIONS The increased level of serum OPG was closely related with CHD and could be used as a risk factor for CHD. The cases carried OPG T149C TC+CC genotype might have the risk suffering CHD. C allele is might be a susceptible gene.
China/epidemiology* ; Coronary Disease/epidemiology* ; Female ; Humans ; Male ; Osteoprotegerin/genetics* ; Polymorphism, Genetic ; Promoter Regions, Genetic/genetics* ; Risk Factors

Objective Mouse models of sepsis-induced myocardial injury by intraperitoneal injection of lipopolysaccharide (LPS) was established in order to provide a reliable method for the research of pathogenesis of sepsis-induced myocardial injury. Methods According to the method of random number table, a total of 150 male C57BL/6 mice were divided into five groups: NC group, sham group, and LPS 10, 12, 15 mg/kg groups, with 30 in each group. Septic myocardial injury was induced by intraperitoneal injection LPS in mice; sham group was injected with equal 0.9% saline; while there was no treatment in mice of NC group. Fifteen of the 30 mice in each group were used to observe the general status of mice before and after LPS or saline injection. Twenty-four hours after LPS or saline injection, the left ventricular function was assessed by echocardiography, serum level of cardiac troponin (cTnI) was determined by enzyme linked immunosorbent assays (ELISA), and the cardiac histomorphology and ultrastructure were observed; the other 15 mice were used to monitor the 7-day mortality after LPS or saline injection. Results The mice challenged to LPS displayed symptoms of sepsis, such as depression, ruffled fur, and diarrhea. Compared with NC group, left ventricular ejection fraction (LVEF), left ventricular fraction shortening (LVFS) were significantly decreased at 24 hours after LPS administration in LPS 10, 12, 15 mg/kg groups [LVEF: 0.459±0.044, 0.432±0.034, 0.348±0.064 vs. 0.588±0.019, LVFS: (22.36±2.60)%, (20.78±1.91)%, (16.27±3.31)% vs. (30.55±1.30)%, all P < 0.01], and cTnI levels were significantly increased (ng/L: 270.40±43.50, 281.14±41.79, 298.39±42.05 vs. 192.59±16.90, all P <0.01). Myocardium injury was observed in three LPS groups, myocardial fibrosis, interstitial edema, erythrocyte leakage and infiltrating inflammatory cells were observed under light-microscope; ultrastructural changes disorderly arranged in cardiac muscle fibers, mitochondrial swelling and even partly missing mitochondria cristae were found under transmission electron microscope (TEM), and the higher of the dose, the more sever of the damage. There was no significant difference between sham group and NC group. The 7-day mortality in LPS 10, 12, 15 mg/kg groups were 33.3%, 53.3% and 86.7%, respectively, while no death in the NC group and sham group. Conclusion For establishing the mouse model of sepsis-induced myocardial injury, intraperitoneal injection with 12 mg/kg LPS is a preferable choice in our research.