This paper aimed to explore the effects of Duzhong Decoction(DZD)-containing serum on the proliferation and osteoblast differentiation of MC3T3-E1 cells through L-type voltage-gated calcium channels(L-VGCCs). L-VGCCs inhibitors, nifedipine and verapamil, were used to block L-VGCCs in osteoblasts. MC3T3-E1 cells were divided into a control group, a low-dose DZD-containing serum(L-DZD) group, a medium-dose DZD-containing serum(M-DZD) group, a high-dose DZD-containing serum(H-DZD) group, a nifedipine group, a H-DZD + nifedipine group, verapamil group, and a H-DZD + verapamil group. The CCK-8 method was used for cell proliferation analysis, alkaline phosphatase(ALP) assay kits for intracellular ALP activity measurement, Western blot for protein expression level in cells, real-time fluorescence quantitative PCR technology for intracellular mRNA expression level determination, fluorescence spectrophotometer for free Ca~(2+) concentration determination in osteoblasts, and alizarin red staining(ARS) for mineralized nodule formation in osteoblasts. The experimental results show that compared to the control group, DZD groups can promote MC3T3-E1 cell proliferation, ALP activity, and mineralized nodule formation, increase intracellular Ca~(2+) concentrations, and upregulate the protein expression of bone morphogenetic protein 2(BMP2), collagen Ⅰ(COL1), α2 subunit protein of L-VGCCs(L-VGCCα2), and the mRNA expression of Runt-related transcription factor 2(RUNX2), and BMP2. After blocking L-VGCCs with nifedipine and verapamil, the intervention effects of DZD-containing serum were inhibited to varying degrees. Both nifedipine and verapamil could inhibit ALP activity, reduce mineralized nodule areas, and downregulate the expression of bone formation-related proteins. Moreover, the effects of DZD-containing serum on increasing MC3T3-E1 cell proliferation, osteoblast differentiation, and Ca~(2+) concentrations, upregulating the mRNA expression of osteoprotegerin(OPG) and protein expression of phosphorylated protein kinase B(p-Akt) and phosphorylated forkhead box protein O1(p-FOXO1), and upregulating phosphatase and tensin homolog(PTEN) expression were reversed by nifedipine. The results indicate that DZD-containing serum can increase the Ca~(2+) concentration in MC3T3-E1 cells to promote bone formation, which may be mediated by L-VGCCs and the PTEN/Akt/FoxO1 signaling pathway, providing a new perspective on the mechanism of DZD in treating osteoporosis.
Animals ; Osteoblasts/metabolism* ; Cell Proliferation/drug effects* ; Cell Differentiation/drug effects* ; Mice ; Drugs, Chinese Herbal/pharmacology* ; Calcium Channels, L-Type/genetics* ; Alkaline Phosphatase/genetics* ; Serum/chemistry* ; Cell Line ; Osteogenesis/drug effects* ; Bone Morphogenetic Protein 2/genetics*

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male ; Female ; Humans ; Aged ; Natriuretic Peptide, Brain ; Simendan/therapeutic use* ; Non-ST Elevated Myocardial Infarction ; Heart Failure/drug therapy* ; Peptide Fragments ; Arrhythmias, Cardiac ; Biomarkers ; Prognosis

OBJECTIVE: To explore the expression of microRNA-132 (miR-132) and its potential role in the development of atherosclerosis (AS). METHODS: Thirty AS samples and 30 samples of normal peripheral vessels were collected from atherosclerotic patients undergoing peripheral angiostomy in our hospital for detecting the expression level of miR-132 using RT-qPCR. The expression of miR-132 in human umbilical vein endothelial cells (HUVEC) was up-regulated by liposome transfection, and intracellular reactive oxygen species (ROS), localization relationship between ROS and mitochondria, functional changes of mitochondrial reactive oxygen superoxide species (mtROS), mitochondrial membrane potential (MMP) and opening of mitochondrial permeability transition pore (mPTP) were analyzed by flow cytometry and laser confocal microscopy. The activity of mitochondrial redox respiratory chain complex (type I, II, III, IV and V) in HUVECs was detected using ELISA, and the expression levels of key iron death proteins were detected with Western blotting. RESULTS: RT-qPCR results showed that miR-132 was significantly up-regulated in atherosclerotic plaques compared with normal vascular samples (P < 0.001). Compared with control HUVECs, HUVECs overexpressing miR-132 showed a significantly increased level of intracellular ROS (P < 0.001), and most of ROS was colocalized with mitochondria. HUVECs overexpressing miR-132 also showed significantly decreased MMP (P < 0.001) and obviously increased mtROS (P < 0.001) and opening of mPTP (P < 0.001), which led to mitochondrial REDOX respiratory chain stress disorder. The key iron death protein GPX4 was significantly down-regulated and the oxidized protein NOX4 was significantly increased in miR-132-overexpressing HUVECs (P < 0.001). CONCLUSION MiR-132 promotes atherosclerosis by inducing mitochondrial oxidative stress-mediated ferroptosis, which may serve as a promising therapeutic target for AS.
Apoptosis ; Atherosclerosis/genetics* ; Ferroptosis ; Human Umbilical Vein Endothelial Cells/metabolism* ; Humans ; Membrane Potential, Mitochondrial ; MicroRNAs/metabolism* ; Mitochondria/metabolism* ; Oxidation-Reduction ; Oxidative Stress ; Reactive Oxygen Species/metabolism*

Objective: To compare the postoperative function, the short-term and long-term outcomes between fascia-oriented and vascular-oriented lateral lymph node dissection (LLND) in patients with rectal cancer. Methods: A retrospective cohort study was performed. Clinical data of patients who received total mesorectal excision (TME) with LLND at National Cancer Center, Cancer Hospital of Chinese Academy of Medical Science from January 2014 to December 2019 were retrospectively collected. Inclusion criteria were as follows: (1) rectal cancer was pathologically diagnosed, and the lower margin was below the peritoneal reflection. (2) resectable advanced rectal cancer with suspected lateral lymph node metastasis was evaluated based on rectal MRI assessment. (3) preoperative MRI showed lateral lymph node short diameter ≥5 mm and/or lymph node morphology (spike, blur, irregular) as well as heterogenous signal intensity. Lymph node shrinkage was less than 60% after receiving neoadjuvant therapy based on the reassessment of rectal MRI. (4) TME+LLND surgery was performed synchronously. Exclusion criteria were as follows: (1) previous history of pelvic surgery; (2) preoperative cystitis, urethritis, moderate and severe prostatic hyperplasia and other diseases resulting in abnormal urination function; (3) preoperative sexual dysfunction or loss of function; (4) patients receiving LLND due to lateral recurrence after TME; (5) distant metastasis of the tumor at initial diagnosis; (6) Incomplete collection of clinical data. A total of 73 consecutive patients were enrolled in this study. Based on the surgical approaches in performing LLND, patients were divided into fascia-oriented group (n=30) and vascular-oriented group (n=43). There were no significant differences in baseline data between the two groups (all P>0.05). The main outcome indicators of this study were the incidence of postoperative urinary and male sexual dysfunction, the efficacy, the number of lateral lymph nodes harvested and the detection rate of positive lymph nodes. Overall survival (OS) rates and progression free survival (PFS) rates were calculated by the Kaplan-Meier method and compared by log-rank test. Results: All patients in both groups completed surgery successfully. There were no significant differences in operation time, intraoperative blood loss, postoperative complications, and the length of hospital stay between the two groups (all P>0.05). In the whole group, the incidence of postoperative urinary dysfunction and male sexual dysfunction was 43.8% (32/73) and 62.5% (25/40), respectively. The median number of lateral lymph nodes harvested was 8.0(4.0,11.0) with a positive rate of 20.5%(15/73). Compared to the vascular-oriented group, the fascia-oriented group demonstrated a decreased rate of urinary dysfunction [26.7% (8/30) vs. 55.8% (24/43), χ(2)=6.098, P=0.014], lower rate of sexual dysfunction in males [6/15 vs. 76% (19/25), χ(2)=5.184, P=0.023], more harvested lateral lymph nodes [M (P25, P75): 9.5 (6.8, 15.3) vs. 6.0 (3.0, 9.0), Z=-2.849, P=0.004]. There was no significant difference in the positvie rate of lateral lymph nodes between the two groups [20% (6/30) versus 20.9% (9/43), χ(2)=0.009, P=0.923]. Three(4.1%) patients were lost during a median follow-up of 34 (1-66) months. The 3-year PFS and OS of the whole cohort were 69.5% and 88.3%, respectively. No significant difference in 3-year PFS rates (79.6% vs. 62.0%, P=0.172) and 3-year OS rates (91.2% vs. 85.9%, P=0.333) were observed between the fascia-oriented group and the vascular-oriented group (both P>0.05). Conclusion: Fascia-oriented LLND is associated with lower risk of postoperative urinary and male sexual dysfunction in patients with rectal carcinoma, and harvest of more lymph nodes, but no significant advantage in long-term survival.
Fascia ; Humans ; Lymph Node Excision ; Lymph Nodes ; Male ; Neoplasm Recurrence, Local ; Rectal Neoplasms/surgery* ; Retrospective Studies ; Treatment Outcome

Objective To investigate the hyperglycemia rate and its correlative factors for the undiagnosed diabetes population in Xuhui District of Shanghai, and to provide the basis for early intervention of diabetes mellitus. Methods Multi-stage cluster sampling was adopted by probability proportionate to size method, and physical examination information and questionnaires were made and collected from 10 130 and 9085 people in 2010 and 2015 respectively from 5 000 households, blood-glucose being examined at the same time.Univariate analysis was made by t test and χ² test and logistic regression was used for analysis of related factors. Results In 2010 and 2015, the diabetes incidence rate was 2.21% and 1.93% respectively, and the hyperglycemia incidence rate in 2015 was higher than that in 2010 (15.28% vs. 12.63%), both increased with age and BMI value.The rate was higher in those with lower education, abnormal blood pressure, self-reported hypertension, self-reported coronary heart disease and smokers.The logistic regression analysis results showed the incidence of diabetes was positively correlated with age, BMI, abnormal blood pressure and smoking, while the incidence of hyperglycemia was positively correlated with the survey year, sex, age, BMI and abnormal blood pressure; both were negatively correlated with educational level. Conclusion The hyperglycemia incidence rate is high among the community undiagnosed diabetic population.We should focus on high-risk screening for diabetes mellitus, and key intervention of the population with low educational level, overweight and obesity, hypertension and unhealthy lifestyle.

Bronchoscopy ; Female ; Fiber Optic Technology ; Humans ; Infant, Newborn ; Male ; Respiratory Sounds ; diagnosis ; etiology

OBJECTIVETo retrospective analysis the complications after treatment of metacarpal and phalangeal fractures with internal fixation, and propose measures to prevent or reduce surgical complications.

METHODSFrom July 2007 to October 2009, 342 patients with metacarpal and phalangeal fractures were treated with internal fixation,including 203 males and 139 females with an average age of 30.4 years old ranging from 18 to 56 years. There were 217 right hands and 125 left hands, 38 cases of the first metacarpal fracture, 47 cases of the second metacarpal fracture, 52 cases of the third metacarpal fracture, 40 cases of the forth metacarpal fracture, 39 cases of the fifth metacarpal fracture, 43 cases of the proximal phalangeal fractures, 52 cases of the middle phalangeal fractures, and 48 case of the distal phalangeal fractures. The fractures were fixed with K-wires in 129 patients, mini plates in 153 cases, screws in 48 cases, wires in 12 cases.

RESULTSAll 324 patients were followed up for 3 to 15 months (averaged 8.5 months) and complications occurred in 74 patients (22.84%). The main complication was unhealthy wound healing in 24 patients (7.4%), others was adhesion of tendon in 54 patients (16.67%), malunion in 34 patients (10.49%), nonunion in 13 patients (4.01%) and shortening of metacarpal and phalangeal in 21 patients (7.41%).

CONCLUSIONThe important reasons responsible for complications are iatrogenic factors such as unsuitable implant selection, unskillful surgical technique and improper post-operative functional rehabilitation.

Adolescent ; Adult ; Female ; Finger Phalanges ; diagnostic imaging ; injuries ; physiopathology ; surgery ; Follow-Up Studies ; Fracture Fixation, Internal ; adverse effects ; Fractures, Bone ; diagnostic imaging ; physiopathology ; surgery ; Humans ; Male ; Metacarpal Bones ; diagnostic imaging ; injuries ; physiopathology ; surgery ; Middle Aged ; Postoperative Complications ; prevention & control ; Recovery of Function ; Tomography, X-Ray Computed ; Young Adult

BACKGROUNDRandomized studies have shown beneficial effects of drug-eluting stent (DES) in reducing the risk of repeated revascularization. Other studies have shown higher proportion of death, myocardial infarction (MI) and increased cost concerning DES. However the long term safety and effectiveness of DES have been questioned recently.

METHODSTo compare long term clinical outcomes, health-related quality of life (HRQOL) and cost-utility after sirolimus-eluting stent (SES) and bare metal stent (BMS) implantation in angina patients in China, 1241 patients undergoing percutaneous coronary revascularization (PCI) with either SES (n = 632) or BMS (n = 609) were enrolled continuously in this prospective, nonrandomized, multi-center registry study.

RESULTSTotally 1570 stents were implanted for 1334 lesions. Follow-up was completed in 1205 (97.1%) patients at 12 months. Rates of MI, all causes of death were similar between the two groups. Significant differences were found at rate of cardiovascular re-hospitalization (136 (22.4%) in BMS group vs. 68 (10.8%) in SES group, P = 0.001) and recurrent angina (149 (24.5%) vs. 71 (11.3%), P = 0.001). Dramatic difference was observed when compared the baseline and 9-month HRQOL scores intra-group (P < 0.001). However no significant difference was found inter-group either in baseline or follow-up HRQOL. Compared with SES, the total cost in BMS was significantly lower on discharge (62 546.0 vs. 78 245.0 Yuan, P = 0.001). And follow-up expenditure was remarkably higher in the BMS group than that in the SES group (13 412.0 vs. 8 812.0 Yuan, P = 0.0001).

CONCLUSIONSThere were no significant differences on death, in-stent thrombosis, MI irrespective of stent type. SES was superior to BMS on improvement of life quality. SES was with higher cost-utility compared to BMS.

Adult ; Aged ; Angioplasty, Balloon, Coronary ; economics ; mortality ; Coronary Angiography ; Drug-Eluting Stents ; economics ; Female ; Health Care Costs ; Humans ; Immunosuppressive Agents ; administration & dosage ; Male ; Metals ; Middle Aged ; Prospective Studies ; Quality of Life ; Sirolimus ; administration & dosage ; Stents ; economics ; Treatment Outcome

OBJECTIVETo investigate the health care status of female workers exposed to occupational hazards in Haidian district of Beijing and improve the labor protection of female workers.

METHODSA questionnaire provided by National Center for Women and Children's Health of Chinese CDC was used in the survey conducted to collect information about health care status of female workers in 141 factories with occupational hazards including chemical poisons and physical factors (noise, libration, microwave, high frequency and low temperature).

RESULTS141 factories were investigated, including 53 state-owned enterprises, 21 collective enterprises, 46 joint-stock enterprises, and 21 non-public enterprises. 12 251 female workers were surveyed, 10.19% (1249/12 251) of whom were exposed to occupational hazards. Of 141 factories studied, 16.31% (23/141) had no labor protection management organization.27.66% (39/141) did not provide pre-employment physical examination service to female workers.48.94% (69/141) didn't establish labor protection system for female workers in menstrual period. While, 21.28% (30/141) of the studied institutes deducted some salaries in the pregnancy, and 32.62% (46/141) deducted their wages during the puerperal period. 2.13% (3/141) arranged female workers in the posts which are forbidden by law (continuous heavy work load operation).9.93% (14/141) arranged pregnant female workers on the post forbidden by law.31.91% (45/141) and 33.33% (47/141) would deduct the time of prenatal medical examination and lactation from their working hours, respectively.39.01% (55/141) didn't afford the cost of fertility. 68.09% (96/141) had annual gynecological examination.45 factories were collected occupational examination reports, accounted for 31.91% (45/141). No female workers were found suffering from occupational disease. Of the 1865 occupational hazard factor monitoring points in 34 factories, there were 155 monitoring points, which were all noise monitoring points, did not meet the standard.

CONCLUSIONThe current health-care status of female workers is not optimistic. It is necessary to consistently improve health care legislations, establish coordinated management mechanism and strengthen the publicity of policy to protect female workers.

China ; epidemiology ; Female ; Humans ; Occupational Diseases ; epidemiology ; Occupational Exposure ; statistics & numerical data ; Occupational Health ; Surveys and Questionnaires ; Women's Health Services ; Work Capacity Evaluation ; Workplace