Preliminary study on the mechanism of halofuginone inhibiting the activity of HepG2 cells / 药学学报

This study aimed to investigate halofuginone's inhibitory effect and mechanism on the activity of hepatocellular carcinoma cells. HepG2 cells were used to detect the effects of halofuginone. After treatment, cell activity, cell migration, cell cycle, and cell apoptosis were detected by CCK-8, transwell, and flow cytometry, respectively. The expression levels of growth and metabolism-related factors such as citrate synthase (CS), ketoglutarate dehydrogenase (OGDH), and isocitrate deoxygenase (IDH) were detected by real-time quantitative PCR and Western blot. Compared with the control group, the activity of HepG2 cells was significantly inhibited by halofuginone (P < 0.01), the migration rate of HepG2 cells was decreased (P < 0.01), the apoptosis of HepG2 cells was induced (P < 0.01), and the cell cycle was arrested in S phase (P < 0.01). The expression levels of tricarboxylic acid key enzymes CS, IDH3, and OGDH were up-regulated, the expression level of isocitrate dehydrogenase isoenzymes IDH1 and IDH2 were down-regulation. In conclusion, halofuginone can inhibit the proliferation and migration of HepG2 cells and promote apoptosis in a dose-dependent manner, which may be due to the promotion of the aerobic metabolism of cells.

Evaluation of the efficacy and safety of Nocardia rubra cell wall skeleton immunotherapy for cervical high-risk HPV persistent infection / 中华妇产科杂志

Objective: To evaluate the efficacy and safety of Nocardia rubra cell wall skeleton (Nr-CWS) in the treatment of persistent cervical high-risk human papillomavirus (HR-HPV) infection. Methods: A randomized, double blind, multi-center trial was conducted. A total of 688 patients with clinically and pathologically confirmed HR-HPV infection of the cervix diagnosed in 13 hispital nationwide were recruited and divided into: (1) patients with simple HR-HPV infection lasting for 12 months or more; (2) patients with cervical intraepithelial neoplasia (CIN) Ⅰ and HR-HPV infection lasting for 12 months or more; (3) patients with the same HR-HPV subtype with no CINⅡ and more lesions after treatment with CINⅡ or CIN Ⅲ (CINⅡ/CIN Ⅲ). All participants were randomly divided into the test group and the control group at a ratio of 2∶1. The test group was locally treated with Nr-CWS freeze-dried powder and the control group was treated with freeze-dried powder without Nr-CWS. The efficacy and negative conversion rate of various subtypes of HR-HPV were evaluated at 1, 4, 8, and 12 months after treatment. The safety indicators of initial diagnosis and treatment were observed. Results: (1) This study included 555 patients with HR-HPV infection in the cervix (included 368 in the test group and 187 in the control group), with an age of (44.1±10.0) years. The baseline characteristics of the two groups of subjects, including age, proportion of Han people, weight, composition of HR-HPV subtypes, and proportion of each subgroup, were compared with no statistically significant differences (all P>0.05). (2) After 12 months of treatment, the effective rates of the test group and the control group were 91.0% (335/368) and 44.9% (84/187), respectively. The difference between the two groups was statistically significant (χ2=142.520, P<0.001). After 12 months of treatment, the negative conversion rates of HPV 16, 18, 52, and 58 infection in the test group were 79.2% (84/106), 73.3% (22/30), 83.1% (54/65), and 77.4% (48/62), respectively. The control group were 21.6% (11/51), 1/9, 35.1% (13/37), and 20.0% (8/40), respectively. The differences between the two groups were statistically significant (all P<0.001). (3) There were no statistically significant differences in vital signs (body weight, body temperature, respiration, pulse rate, systolic blood pressure, diastolic blood pressure, etc.) and laboratory routine indicators (blood cell analysis, urine routine examination) between the test group and the control group before treatment and at 1, 4, 8, and 12 months after treatment (all P>0.05); there was no statistically significant difference in the incidence of adverse reactions related to the investigational drug between the two groups of subjects [8.7% (32/368) vs 8.0% (15/187), respectively; χ2=0.073, P=0.787]. Conclusion: External use of Nr-CWS has good efficacy and safety in the treatment of high-risk HPV persistent infection in the cervix.

Comparison of Exosomes Derived from Fibroblasts and Mesenchymal Stem Cells for the Treatment of Acute Wound Healing / 中山大学学报(医学科学版)

ObjectiveTo compare the therapeutical effect of exosomes derived from fibroblasts and mesenchymal stem cells on acute wound healing. MethodsPrimary human dermal fibroblasts （hDF） were isolated， cultured and identified. Human bone marrow mesenchymal stem cell exosomes （hMSC-EXO） and hDF exosomes （hDF-EXO） were extracted by ultracentrifuga tion. After 24 h of coincubation with hDF-EXO or hMSC-EXO， hDFs proliferation and migratory capacity were evaluated by cell counting kit-8 （CCK8） assay and scratch test. Full-thickness cutaneous wounds were created on 8-week-old female C57BL/6 mice， and topically applied with PBS （control）， hDF-EXO or hMSC-EXO. Wounds were measured at day 0， 2， 4， 7， and the uptake of exosomes in wound was observed at day 1. Quantitative PCR （qPCR） analysis was performed to detect the mRNA expression levels of TNF-α， IL-6， IL-1β， IL-10 in wound at day 1. HE staining was conducted to analyze the histological structure of wounds at day 7， while immunofluorescence staining was used to examine expression of PDGFR-α、α-SMA、Ki67. ResultshDF exhibited certain fibrolast-like characteristics with respect to expression of cell surface markers and specific proteins. hDF-EXO and hMSC-EXO presented exosomal morphology， size， and markers， and both concentrations were not statistically different （P>0.05）； CCK8 assay showed that both exosomes promoted hDF cell viability， compared with the negative control （P<0.01）， and hDF-EXO group had greater cell viability than hMSC-EXO group （P<0.01）. Scratch test indicated that hDF-EXO induced a significant increase in scratch healing rate versus the negative control （P<0.01）， hMSC-EXO （P<0.05）. In vivo experiments showed wound tissues took up exosomes at day 1. qPCR detected TNF-α， IL-6， IL-1β expression levels in wound at day 1 were lower in exosomes group than in the control group， and were the lowest in hMSC-EXO group （all P<0.01）. Wound areas were measured smaller at day 7 in exosomes group than in the control group （all P<0.01） and hDF-EXO group had better closure than hMSC-EXO group （P<0.05）. HE staining revealed that compared with control group， scar， incomplete epidermis and few collagen deposition remained in the hMSC-EXO group， whereas hDF-EXO group showed re-epithelialization， continuous neo-epidermis and regenerated dermis. Immunofluorescence staining suggested that the number of fibroblasts， myofibroblasts， proliferating cells was higher in both exosomes group than that in the control group， especially the highest in hDF-EXO group. ConclusionOur study shows both exosomes accelerate wound healing， whereas hDF-EXO is more effective in promoting fibroblasts proliferation， migration， transition to myofibroblasts， and hMSC-EXO may play a role in inhibiting inflammatory reaction during early stage of wound healing.

Progress on Prevention and Treatment of Cerebral Small Vascular Disease Using Integrative Medicine / 中国结合医学杂志

Cerebral small vessel disease (CSVD) is a senile brain lesion caused by the abnormal structure and function of arterioles, venules and capillaries in the aging brain. The etiology of CSVD is complex, and disease is often asymptomatic in its early stages. However, as CSVD develops, brain disorders may occur, such as stroke, cognitive dysfunction, dyskinesia and mood disorders, and heart, kidney, eye and systemic disorders. As the population continues to age, the burden of CSVD is increasing. Moreover, there is an urgent need for better screening methods and diagnostic markers for CSVD, in addition to preventive and asymptomatic- and mild-stage treatments. Integrative medicine (IM), which combines the holistic concepts and syndrome differentiations of Chinese medicine with modern medical perspectives, has unique advantages for the prevention and treatment of CSVD. In this review, we summarize the biological markers, ultrasound and imaging features, disease-related genes and risk factors relevant to CSVD diagnosis and screening. Furthermore, we discuss IM-based CSVD prevention and treatment strategies to stimulate further research in this field.

Ershiwuwei Shanhu Pills regulate Akt/mTOR/GSK-3β signaling pathway to alleviate Alzheimer's disease mice / 中国中药杂志

The present study investigated the mechanism of the Tibetan patent medicine Ershiwuwei Shanhu Pills(ESP) in alleviating Alzheimer's disease in mice via Akt/mTOR/GSK-3β signaling pathway. BALB/c mice were randomly assigned into a blank control group, a model group, low(200 mg·kg~(-1)), medium(400 mg·kg~(-1)) and high(800 mg·kg~(-1)) dose groups of ESP, and donepezil hydrochloride group. Except the blank control group, the other groups were given 20 mg·kg~(-1) aluminum chloride by gavage and 120 mg·kg~(-1) D-galactose by intraperitoneal injection for 56 days to establish Alzheimer's disease model. Morris water maze was used to detect the learning and memory ability of mice. The level of p-tau protein in mouse hippocampus and the levels of superoxide dismutase(SOD), malondialdehyde(MDA), catalase(CAT), and total antioxidant capacity(T-AOC) in hippocampus and serum were detected. Hematoxylin-eosin staining and Nissl staining were performed for the pathological observation of whole brain in mice. TdT-mediated dUTP nick-end labeling(TUNEL) staining was employed for the observation of apoptosis in mouse cortex. Western blot was adopted to detect the protein levels of p-mTOR, p-Akt, and GSK-3β in the hippocampus. Compared with the model group, the ESP groups showcased alleviated pathological damage of the whole brain, decreased TUNEL positive cells, reduced level of p-tau protein in hippocampus, and risen SOD, CAT, and T-AOC levels and declined MDA level in hippocampus and serum. Furthermore, the ESP groups had up-regulated protein levels of p-mTOR and p-Akt while down-regulated protein level of GSK-3β in hippocampus. Therefore, ESP can alleviate the learning and memory decline and oxidative damage in mice with Alzheimer's disease induced by D-galactose combined with aluminum chloride, which may be related to Akt/mTOR/GSK-3β signaling pathway.

Intraperitoneal chemotherapy combined with intravenous chemotherapy for neoadjuvant chemotherapy in advanced ovarian cancer:a phaseⅠclinical trial / 中国实用妇科与产科杂志

OBJECTIVE: To evaluate the efficacy,safety,and potential benefits of neoadjuvant intraperitoneal chemotherapy(NIPC)in patients with newly diagnosed advanced ovarian cancer.METHODS: From December 2011 to December 2015,in Sun Yat-sen Memorial Hospital of Sun Yat-sen University,27 patients with stage ⅢC-Ⅳ ovarian cancer were enrolled in the study.NIPC was used as the initial treatment.The regimen was paclitaxel(T)intravenous chemotherapy combined with cisplatin/carboplatin(P/C)intraperitoneal chemotherapy.The primary endpoint were complication and toxicity.Secondary endpoints were progression-free survival(PFS)and overall survival(OS).RESULTS: Nine patients completed 3 times of NIPC,7 had once and 7 had twice.Nine patients completed NIPC,18 patients discontinued,includeding disease progression(n=3),patient refusal(n=3),unknown reason(n=3),myelosuppression(n=2),nephrotoxicity(n=2),arrhythmia(n=2),abdominal pain(n=1),diarrhea(n=1),and headache(n=1);there was no treatment-related death.Fourteen accepted intermittent cytoreduction surgery,and 13 were R0.There were 13 patients without surgery,of whom 4 progressed,3 gave up,and 6 had negative CA125.The median follow-up time was 36 months(10-82 months),the median follow-up time was 53.8±5.59 months,the 3-year OS rate was 57.2%,and the median PFS was 20 months(0-82 months);the 3-year PFS rate was 24.7%.CONCLUSION: It is safe and feasible to use NIPC for neoadjuvant chemotherapy in patients with advanced ovarian cancer.It may improve the satisfactory operation rate and prolong survival.

Clinical evaluation of cervicectomy in the treatment of cervical intraepithelial neoplasia with cervicovaginal shortening / 中国实用妇科与产科杂志

OBJECTIVE: To investigate the clinical efficacy of cervicectomy for cervical intraepithelial neoplasia(CIN)in patients with cervicovaginal shortening.METHODS: Retrospectively analyze the clinical data of the 120 cases of CIN treated in Shengjing Hospital of China Medical University from April 2014 to November 2018.Cervicectomy was performed because of cervicovaginal shortening caused by menopausal or peri-menopausal cervical atrophy or cervical surgery.The clinical treatment,efficacy and prognosis of the patients were reviewed.RESULTS: The mean age of the 120 patients was 55.2 years(range:35-77 years).The indications of operation included:persistent abnormal cervical cytology test(7),CIN2(42),CIN3(70),squamous carcinoma of the cervix(1);peri-menopausal and menopausal patients with obvious cervicovaginal atrophy(100),premenopausal patients with natural short cervix(2),and obvious cervicovaginal shortening caused by cervical surgery(18).The mean operating time was 23.2 min(range 10-30 min),the mean bleeding volume was 7.8 mL(range:5-20 mL),and the mean height of cervix resected was 2.59 cm(range:2-3 cm).No secondary injury,bleeding or other postoperative complications occurred during surgery;cervical postoperative wounds healed well;only one case developed cervical adhesion after surgery.The postoperative histologic diagnosis were compared with the preoperative histologic diagnosis,in which 45 degraded(37.50%),42 consistent(35.00%),and 33 upgraded(27.50%).HPV conversion rate 3 months after cervicectomy was 80.81%(80/99),and total HPV conversion rate was 88.89%(88/99).A total of 29 patients underwent secondary surgery,23 underwent total hysterectomy,and 6 underwent extensive hysterectomy and pelvic lymphadenectomy.All patients were followed up,once every 3 to 6 months,and median follow-up time was 29.5 months(range 4-59 months).All patients recovered well after surgery;only 2 cases showed positive margins,and only 2 cases of residual disease and 1 case of recurrence were found during follow-up.CONCLUSION: For patients with cervical intraepithelial neoplasia of cervicovaginal shortening,cervicectomy is a safe,effective and relatively microinvasive treatment.

Resistance Reversion of Rapamycin on Ovarian Cancer Cell Line SKOV3/DDP and Its Molecular Mechanisms / 中山大学学报(医学科学版)

[Objective]To study the resistance reversion of rapamycin on ovarian cancer cell line SKOV3/DDP,and ex-plore its underlying molecular mechanisms.[Methods]MTT method was used to detect the cell toxicity,drug-resistant multi-ple and reversing multiple of cisplatin-resistant ovarian cancer cell line SKOV3/DDP;Western blot was used to detect the changes of Akt/mTOR Pathway induced by rapamycin.[Results]① MTT detected that when rapamycin concentration was 25,50,100,500 and 1 000 μg/L,its inhibition rates on cisplatin-resistant ovarian cancer cell line SKOV3/DDP were 4.48%,25.30%,35.86%,67.82%,81.43%.The concentration of 25 μg/L was selected to be the reversal concentration,be-cause its maximum rate was less than 5%.②The resistant index(RI)of cisplatin-resistant ovarian cancer cell line SKOV3/DDP was 2.21. ③ The reversal fold of 25 μg/L rapamycin on cisplatin-resistant ovarian cancer cell line SKOV3/DDP was 1.63.④Western blot results:After the addition of rapamycin,expression of p-mTOR and its downstream protein p-p70s6k in SKOV3 and SKOV3/DDP was significantly reduced. Meanwhile,there was a feedback increase in p-Akt.[Conclusions]Rapamycin has a reversal effect on cisplatin-resistant ovarian cancer cell line SKOV3/DDP. Its reversal mechanism may be inhibiting the cell proliferation and promoting cell apoptosis by depressing the expression of p-mTOR and its downstream pro-tein p-p70s6k in Akt/mTOR Pathway.

Effect analysis of topical fluoride varnish on caries prevention of first permanent molars in school-age children / 口腔疾病防治

Objective @#To investigate the effectiveness of fluoride varnish in preventing first permanent molars caries inschool-age children and provide necessary information for oral health instruction. @*Methods@#378 children aged 6-7 years old in the first grade of primary school in dahua country, hechi city, Guangxi province (1 053 first permanent molars) were randomly recruited into 2 groups. The test group (542 first permanent molars in 191 children) was treated with fluoride varnish one time in a half year and given oral hygiene instruction 3 times; The control group (511 first permanent molars in 187 children) was only given oral hygiene instruction 3 times. All first permanent molars were checked after 18 months later for caries. @*Results@#After intervention, the caries prevalence rate in the test group raised from 21.99% to 27.75% compared with the control group from 24.60% to 37.43%. The caries incidence rate in test and control group was 5.76% and 12.83% respectively. There was a significant difference between 2 groups regardless of caries prevalence, caries incidence, the DMFT reduction, the DMFs reduction, the occlusal caries prevalence, the pit and fissure caries prevalence, the proximal caries prevalence. @*Conclusion @#Semi-annual application of fluoride varnish is effective in the prevention of dental caries in first permanent molars , which was worth of being popularized in clinic.

Clinical effect of superselective arterial embolization for the treatment of massive haemorrhage from pelvic fracture / 中国骨伤

<p><b>OBJECTIVE</b>To investigate feasibility and curative effect of superselective arterial embolization for the treatment of massive haemorrhage from pelvic fracture.</p><p><b>METHODS</b>From March 2008 to February 2016, clinical data of 65 patients with massive haemorrhage from pelvic fracture were collected and analyzed, and patients were divided into non-embolic and embolic group according to whether perform vascular thrombosis. Thirty-three patients were in non-embolic group including 26 males and 7 females aged from 21 to 64 years old with an average of(39.2±5.7) years old, the time from injury to operation ranged from 1.1 to 4.8 h with an average of (2.2±0.4) h; 12 cases were type B and 21 cases were type C according to AO/Tile classification; injury severity score (ISS) ranged from 25 to 42 with an average of (37.7±7.5); shock index score ranged from 1.7 to 2.4 with an average of 2.1±0.3; treated with blood transfusion and fluid infusion. Thirty-two patients in embolic group, including 25 males and 7 females aged from 22 to 65 years old with an average of(38.1±4.5) years old; the time from injury to operation ranged from 1.2 to 4.8 h with an average of (2.1± 0.5) h; 14 cases were type B and 18 cases were type C according to AO/Tile classification; ISS ranged from 26 to 43 with an average of 38.9±4.5; shock index score ranged from 1.6 to 2.4 with an average of 2.2±0.2; treated by blood transfusion and fluid infusion with superselective arterial embolization. Blood transfusion volume, fluid infusion volume, shock correction time and survival rate were observed and compared, effective rate of hemostasis and postoperative complications were compared.</p><p><b>RESULTS</b>Thirty-seven artery were injured in embolic group, hemostasis were controlled at 3 h after operation, and hemodynamics turned to stable. There were significant difference in blood transfusion volume, fluid infusion volume, shock correction time between non-embolic and embolic group, and embolic group performed better. Survival rate in embolic group was also better than that of non-embolic group, and had significant difference. While there was obvious differences in complications(χ²=4.03,=0.045).</p><p><b>CONCLUSIONS</b>Superselective arterial embolization for massive haemorrhage from pelvic fracture could effective hemostasis, reduce blood transfusion and fluid infusion volume and occurrence rate of shock, moreover improve survival rate and deserves promotion.</p>

Targeting Myocyte-specific Enhancer Factor 2D Contributes to the Suppression of Cardiac Hypertrophic Growth by MiR-92b-3p in Cardiomyocytes / 中山大学学报(医学科学版)

[Objective]To investigate the role and the potential target of miR-92b-3p in angiotensin Ⅱ(Ang-Ⅱ)-induced mouse cardiac hypertrophy.[Methods]Ang-Ⅱ-induced cardiac hypertrophy models were established in adult C57BL/6 mice. AgomiR-92b-3p,the cholesterol-modified miR-92b-3p mimic,was delivered to increase the level of miR-92b-3p in mouse myocar?dium via tail vein injection. In the present study,three groups of mice were used in the animal experiment as follows,the agomiR-negative control(agomiR-NC)+saline group,the agomiR-NC+Ang-Ⅱgroup and the agomiR-92b-3p+Ang-Ⅱgroup. A cell model of cardiac hypertrophy was also established in Ang-Ⅱ-induced neonatal mouse cardiomyocytes in this study Luciferase activity was assayed after transfection using a luciferase reporter assay system. The expression of Myocyte-specific enhancer factor 2D( MEF2D) and hypertrophy-related genes atrial natriuretic peptide (ANP),cardiac muscle α-actin (ACTA1) and β-myosin heavy chain (MHC)at mRNA and protein levels in Ang-Ⅱ-induced hypertrophic myocardium and cardiomyocytes were detected by qRT-PCR and Western blot,respectively.[Results]The expression of ANP,ACTA1,β-MHC were markedly increased in Ang-Ⅱ-induced hypertrophic myocardium and cardiomyocytes. Dual luciferase reporter assay revealed that MEF2D is a potential target gene of miR-92b-3p. And miR-92b-3p can reduce the expression of MEF2D at the post-transcriptional level. Functionally,miR-92b-3p mimic, consistent with MEF2D siRNA,inhibited cell size increase and protein expression of ANP,ACTA1 andβ-MHC in Ang-II-treated mouse cardiomyocytes.[Conclusions]MEF2D is a novel target of miR-92b-3p,a target gene of miR-92b-3,which mediates the ef?fect of miR-92b-3p on attenuating cardiomyocyte hypertrophy.

Electroacupuncture inhibits the ultrastructural degeneration of osteoarthritic chondrocytes mediated by Ras/Raf/MEK1/2/ERK1/2 signaling pathways / 中国组织工程研究

BACKGROUND: Previous studies have found that electroacupuncture (EA) could effectively inhibit the expression of p38 and Fas mRNA mediated by MAPK signaling pathways, to further inhibit the apoptosis of chondrocytes. Meanwhile,EA delays the degeneration of articular cartilage mediated by JAK-STAT signaling pathway through upregulating the expression levels of transforming growth factor β1 as well as the mRNA expression levels of STAT3, Smad3 and LepR.OBJECTIVE: To explore the effect of EA on the cartilage ultrastructure and mRNA expression levels of Ras, Raf,MEK1/2 and ERK1/2 in the rat with knee osteoarthritis.METHODS: The rat models of knee osteoarthritis were established, and randomized into four groups at 2 weeks after modeling: model group received no interventions; 15- and 30-minute EA groups were given EA at the Hsiyen (medical,extra) of bilateral knee joints for 15 and 30 minutes, respectively; PD98059 group was given the intravenous injection of extracellular signal-regulated kinase inhibitor PD98059. The intervention time was 3 months. Those rats received normal feeding served as blank control group.RESULTS AND CONCLUSION: Transmission electron microscopy showed that compared with the model group, the chondrocytes in the 15- and 30-minute EA and PD98059 groups changed little, the nucleus was larger, partial endoplasmic reticulum cisterna expanded, and the mitochondria structure was clear. ELISA results showed that the 15-and 30-minute EA and PD98059 groups had a significant decrease in the level of tumor necrosis factor α compared with the model group (P < 0.01). RT-PCR revealed that the mRNA expression levels of Ras, Raf, MEK1/2 and ERK1/2 in the 15- and 30-minute EA and PD98059 groups were significantly downregulated (P < 0.05 or P < 0.01). These results indicate that EA can alleviate chondrocyte injury in the rat osteoarthritic model, reduce the level of tumor necrosis factor α in the synovium, and downregulated the expression levels of Ras, Raf, MEK1/2 and ERK1/2 mRNA, further delaying the chondrocyte degeneration in osteoarthritis.

miR-199a-5p enhances expression of myocardial fibrosis-related genes by targeting SIRT1 / 中国病理生理杂志

AIM:To investigate the role of microRNA (miR)-199a-5p in myocardial fibrosis and the potential target of miR-199a-5p.METHODS:C57BL/6 mouse cardiac fibroblasts were isolated and cultured for cellular experimen-tal study.Dual-luciferase reporter assay was performed to confirm the interaction between miR-199a-5p and the 3'-untrans-lated region (3'-UTR) of silent information regulator 1 (SIRT1).The expression of SIRT1 and fibrosis markers collagen (Col) 1a1, Col3a1 and α-smooth muscle actin (α-SMA) at mRNA and protein levels was determined by RT-qPCR and Western blot, respectively.RESULTS:The expression levels of miR-199a-5p, Col1a1, Col3a1 andα-SMA were marked-ly increased in cardiac fibroblasts after treatment with angiotensin Ⅱ(AngⅡ).The over-expression of miR-199a-5p signif-icantly increased the expression of Col1a1, Col3a1 andα-SMA in cardiac fibroblasts.Moreover, the results of dual-lucifer-ase reporter assay revealed that miR-199a-5p interacted with the 3'-UTR of SIRT1.miR-199a-5p inhibited SIRT1 expres-sion at post-transcriptional level.Meanwhile, miR-199a-5p mimic, in parallel to SIRT1 siRNA, inhibited SIRT1 expres-sion, increased the expression of Col1a1, Col3a1 and α-SMA in cardiac fibroblasts.Inactivation of NF-κB signaling con-tributed to the decrease in miR-199a-5p in Ang II-treated cardiac fibroblasts .CONCLUSION:SIRT1 is a target gene of miR-199a-5p, which mediates the pro-fibrotic effect of miR-199a-5p on cardiac fibroblasts .

Therapeutic effect of QQL prescription on type 2 diabetic rats / 中国病理生理杂志

AIM:To investigate the therapeutic effect of Qingqianliu ( QQL) antidiabetic prescription , contai-ning Cyclocarya paliurus, on type 2 diabetic rats.METHODS: Ten rats were randomly chosen as normal control group , and other rats were used to establish diabetic rat models by high-fat diet feeding plus streptocin intraperitoneal injection . Successfully modeling rats were randomly divided into high (300 mg· kg -1· d-1), medium (150 mg· kg-1· d-1) and low (75 mg· kg-1· d-1) doses of QQL treatment groups, and model control group (10 rats in each group).The rats re-ceived daily treatment for 6 weeks.Meanwhile, the therapeutic effect of QQL on these type 2 diabetic rats were evaluated via the body weight , the levels of serum glucose , insulin and glycosylated hemoglobin , the glucose tolerance , the pathologi-cal changes of pancreatic islands , antioxidative indexes and inflammaory factors .RESULTS:Compared with model control group, the body weight, serum insulin, glucose tolerance, serum SOD and serum GSH were increased , the serum glucose, glycosylated hemoglobin , MDA, IL-1βand TNF-αwere decreased , and the pathological changes of pancreatic islands were improved in type 2 diabetic rats with QQL treatment at high and low doses (P<0.05 or P<0.01).CONCLUSION:The QQL reduces the blood glucose , improves the glucose tolerance , and attenuates the damage of pancreatic islands .Its me-chanism may be related to antioxidative and anti-inflammatory effects .

miR-199a-5p enhances expression of myocardial fibrosis-related genes by targeting SIRT1 / 中国病理生理杂志

AIM:To investigate the role of microRNA (miR)-199a-5p in myocardial fibrosis and the potential target of miR-199a-5p.METHODS:C57BL/6 mouse cardiac fibroblasts were isolated and cultured for cellular experimen-tal study.Dual-luciferase reporter assay was performed to confirm the interaction between miR-199a-5p and the 3'-untrans-lated region (3'-UTR) of silent information regulator 1 (SIRT1).The expression of SIRT1 and fibrosis markers collagen (Col) 1a1, Col3a1 and α-smooth muscle actin (α-SMA) at mRNA and protein levels was determined by RT-qPCR and Western blot, respectively.RESULTS:The expression levels of miR-199a-5p, Col1a1, Col3a1 andα-SMA were marked-ly increased in cardiac fibroblasts after treatment with angiotensin Ⅱ(AngⅡ).The over-expression of miR-199a-5p signif-icantly increased the expression of Col1a1, Col3a1 andα-SMA in cardiac fibroblasts.Moreover, the results of dual-lucifer-ase reporter assay revealed that miR-199a-5p interacted with the 3'-UTR of SIRT1.miR-199a-5p inhibited SIRT1 expres-sion at post-transcriptional level.Meanwhile, miR-199a-5p mimic, in parallel to SIRT1 siRNA, inhibited SIRT1 expres-sion, increased the expression of Col1a1, Col3a1 and α-SMA in cardiac fibroblasts.Inactivation of NF-κB signaling con-tributed to the decrease in miR-199a-5p in Ang II-treated cardiac fibroblasts .CONCLUSION:SIRT1 is a target gene of miR-199a-5p, which mediates the pro-fibrotic effect of miR-199a-5p on cardiac fibroblasts .

Therapeutic effect of QQL prescription on type 2 diabetic rats / 中国病理生理杂志

AIM:To investigate the therapeutic effect of Qingqianliu ( QQL) antidiabetic prescription , contai-ning Cyclocarya paliurus, on type 2 diabetic rats.METHODS: Ten rats were randomly chosen as normal control group , and other rats were used to establish diabetic rat models by high-fat diet feeding plus streptocin intraperitoneal injection . Successfully modeling rats were randomly divided into high (300 mg· kg -1· d-1), medium (150 mg· kg-1· d-1) and low (75 mg· kg-1· d-1) doses of QQL treatment groups, and model control group (10 rats in each group).The rats re-ceived daily treatment for 6 weeks.Meanwhile, the therapeutic effect of QQL on these type 2 diabetic rats were evaluated via the body weight , the levels of serum glucose , insulin and glycosylated hemoglobin , the glucose tolerance , the pathologi-cal changes of pancreatic islands , antioxidative indexes and inflammaory factors .RESULTS:Compared with model control group, the body weight, serum insulin, glucose tolerance, serum SOD and serum GSH were increased , the serum glucose, glycosylated hemoglobin , MDA, IL-1βand TNF-αwere decreased , and the pathological changes of pancreatic islands were improved in type 2 diabetic rats with QQL treatment at high and low doses (P<0.05 or P<0.01).CONCLUSION:The QQL reduces the blood glucose , improves the glucose tolerance , and attenuates the damage of pancreatic islands .Its me-chanism may be related to antioxidative and anti-inflammatory effects .

China Patient-centered Evaluative Assessment of Cardiac Events Prospective Study of Acute Myocardial Infarction: Study Design / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Despite the rapid growth in the incidence of acute myocardial infarction (AMI) in China, there is limited information about patients' experiences after AMI hospitalization, especially on long-term adverse events and patient-reported outcomes (PROs).</p><p><b>METHODS</b>The China Patient-centered Evaluative Assessment of Cardiac Events (PEACE)-Prospective AMI Study will enroll 4000 consecutive AMI patients from 53 diverse hospitals across China and follow them longitudinally for 12 months to document their treatment, recovery, and outcomes. Details of patients' medical history, treatment, and in-hospital outcomes are abstracted from medical charts. Comprehensive baseline interviews are being conducted to characterize patient demographics, risk factors, presentation, and healthcare utilization. As part of these interviews, validated instruments are administered to measure PROs, including quality of life, symptoms, mood, cognition, and sexual activity. Follow-up interviews, measuring PROs, medication adherence, risk factor control, and collecting hospitalization events are conducted at 1, 6, and 12 months after discharge. Supporting documents for potential outcomes are collected for adjudication by clinicians at the National Coordinating Center. Blood and urine samples are also obtained at baseline, 1- and 12-month follow-up. In addition, we are conducting a survey of participating hospitals to characterize their organizational characteristics.</p><p><b>CONCLUSION</b>The China PEACE-Prospective AMI study will be uniquely positioned to generate new information regarding patient's experiences and outcomes after AMI in China and serve as a foundation for quality improvement activities.</p>

Effects of Tongxinluo Capsule on Platelet Activating Factor, Vascular Endothelial Function, Blood Flow of Thrombolysis in Myocardial Infarction in Acute Myocardial Infarction Patients after Delayed Percutaneous Coronary Intervention / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore effects of Tongxinluo Capsule (TC) on platelet activating factor (PAF), vascular endothelial function, thrombolysis in myocardial infarction (TIMI) blood flow, and heart function in acute myocardial infarction (AMI) patients after delayed percutaneous coronary intervention (PCI).</p><p><b>METHODS</b>Totally 80 AMI inpatients were recruited at Department of Cardiology, People's Hospital of Jiangxi Province, from Jan. 2008 to Sep.2013. Those in line with inclusion criteria were randomly assigned to TC treatment group and the conventional treatment group by random digit table, 40 in each group. Besides, another 40 healthy subjects from examinees at Outpatient Department were recruited as a healthy control group. PCI was performed after 1-week treatment. Then blood samples were collected, and then blood contents of CD62P, CD63, GP II b/III a, ET-1, NO, and plasma von Willebrand factor (vWF) levels were detected. Coronary TIMI blood flow and corrected TIMI frame count (CTFC) were determined during PCI. Meanwhile, noninvasive blood pressure (BP) and heart rate (HR) were recorded before and after PCI, and cardiac function measured. They were compared with the healty control group.</p><p><b>RESULTS</b>Compared with the healthy control group, blood contents of CD62p, CD63, GP II b/IIIa receptor compound, vWF, and ET-1 significantly increased, but NO significantly decreased in AMI patients (all P < 0.05). After 1-week intervention of TC, blood contents of CD62p, CD63, GP II b/IIIa receptor compound, vWF, NO, and ET-1 significantly decreased (P < 0.05, P < 0.01). Compared with the conventional treatment group at the same time point, blood contents of CD62p, CD63, GP II b/IIIa receptor compound, vWF, and ET-1 decreased more significantly in the TC group (P < 0.05, P < 0.01), increased NO levels were also more obviously seen (P < 0.01). The aforesaid parameters changed more obviously at day 30, as compared with those changes at week 1 (P < 0.05, P < 0.01). The TIMI blood flow grade and CTFC were more obviously improved after PCI in the two treatment groups. Better TIMI blood flow was seen in the TC group. TIMI level 3 blood flow rate was higher in the TC group than in the conventional treatment group with statistical difference (P < 0.05). The left ventricular ejective factor (LVEF) after PCI was obviously elevated in the TC group and the conventional treatment group (P < 0.01), and the improvement was more obviously seen in the TC group (P < 0.05). There were 6 cases of recurrent angina, 3 cases of ventricular tachycardial (VT)/ventricular fibrillation (VF), 6 cases of heart failure (HF), 1 case of cardiac sudden death in the conventional treatment group, with the total incidence of cardiovascular events being 40% (16/40). There were 2 cases of recurrent angina, 2 cases of VT/VF, 2 cases of HF, no cardiac sudden death in the TC treatment group, with the total incidence of cardiovascular events being 15% (6/40). There was statistical difference in the recurrent rate of cardiovascular events between the two groups (χ² = 2.27, P < 0.05).</p><p><b>CONCLUSION</b>TC not only could prevent coronary embolism of AMI patients after delayed PCI, attenuate vascular endothelial injury, but also could improve TIMI blood flow, and strengthen cardiac systolic function.</p>

Can radical parametrectomy be omitted in occult cervical cancer after extrafascial hysterectomy? / 癌症

<p><b>BACKGROUND</b>Occult invasive cervical cancer discovered after simple hysterectomy is not common, radical parametrectomy (RP) is a preferred option for young women. However, the morbidity of RP was high. The aim of our study is to assess the incidence of parametrial involvement in patients who underwent radical parametrectomy for occult cervical cancer or radical hysterectomy for early-stage cervical cancer and to suggest an algorithm for the triage of patients with occult cervical cancer to avoid RP.</p><p><b>METHODS</b>A total of 13 patients with occult cervical cancer who had undergone RP with an upper vaginectomy and pelvic lymphadenectomy were included in this retrospective study. Data on the clinicopathologic characteristics of the cases were collected. The published literature was also reviewed, and low risk factors for parametrial involvement in early-stage cervical cancer were analyzed.</p><p><b>RESULTS</b>Of the 13 patients, 9 had a stage IB1 lesion, and 4 had a stage IA2 lesion. There were four patients with grade 1 disease, seven with grade 2 disease, and two with grade 3 disease. The median age of the entire patients was 41 years. The most common indication for extrafascial hysterectomy was cervical intraepithelial neoplasia 3. Three patients had visible lesions measuring 10-30 mm, in diameter and ten patients had cervical stromal invasions with depths ranging from 4 to 9 mm; only one patient had more than 50% stromal invasion, and four patients had lymph-vascular space invasion (LVSI). Perioperative complications included intraoperative bowel injury, blood transfusion, vesico-vaginal fistula, and ileus (1 case for each). Postoperative pathologic examination results did not show residual disease or parametrial involvement. One patient with positive lymph nodes received concurrent radiation therapy. Only one patient experienced recurrence.</p><p><b>CONCLUSIONS</b>Perioperative complications following RP were common, whereas the incidence of parametrial involvement was very low among selected early-stage cervical cancer patients. Based on these results, we thought that patients with very low-risk parametrial involvement(tumor size ≤ 2 cm, no LVSI, less than 50% stromal invasion, negative lymph nodes) may benefit from omitting RP. Further prospective data are warranted.</p>

Application of percutaneous balloon mitral valvuloplasty in patients of rheumatic heart disease mitral stenosis combined with tricuspid regurgitation / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Tricuspid regurgitation (TR) is frequently associated with severe mitral stenosis (MS), the importance of significant TR was often neglected. However, TR influences the outcome of patients. The aim of this study was to investigate the efficacy and safety of percutaneous balloon mitral valvuloplasty (PBMV) procedure in rheumatic heart disease patients with mitral valve (MV) stenosis and tricuspid valve regurgitation.</p><p><b>METHODS</b>Two hundred and twenty patients were enrolled in this study due to rheumatic heart disease with MS combined with TR. Mitral balloon catheter made in China was used to expand MV. The following parameters were measured before and after PBMV: MV area (MVA), TR area (TRA), atrial pressure and diameter, and pulmonary artery pressure (PAP). The patients were followed for 6 months to 9 years.</p><p><b>RESULTS</b>After PBMV, the MVAs increased significantly (1.7 ± 0.3 cm 2 vs. 0.9 ± 0.3 cm 2 , P < 0.01); TRA significantly decreased (6.3 ± 1.7 cm 2 vs. 14.2 ± 6.5 cm 2 , P < 0.01), right atrial area (RAA) decreased significantly (21.5 ± 4.5 cm 2 vs. 25.4 ± 4.3 cm 2 , P < 0.05), TRA/RAA (%) decreased significantly (29.3 ± 3.2% vs. 44.2 ± 3.6%, P < 0.01). TR velocity (TRV) and TR continue time (TRT) as well as TRV × TRT decreased significantly (183.4 ± 9.4 cm/s vs. 254.5 ± 10.7 cm/s, P < 0.01; 185.7 ± 13.6 ms vs. 238.6 ± 11.3 ms, P < 0.01; 34.2 ± 5.6 cm vs. 60.7 ± 8.5 cm, P < 0.01, respectively). The postoperative left atrial diameter (LAD) significantly reduced (41.3 ± 6.2 mm vs. 49.8 ± 6.8 mm, P < 0.01) and the postoperative right atrial diameter (RAD) significantly reduced (28.7 ± 5.6 mm vs. 46.5 ± 6.3 mm, P < 0.01); the postoperative left atrium pressure significantly reduced (15.6 ± 6.1 mmHg vs. 26.5 ± 6.6 mmHg, P < 0.01), the postoperative right atrial pressure decreased significantly (13.2 ± 2.4 mmHg vs. 18.5 ± 4.3 mmHg, P < 0.01). The pulmonary arterial pressure decreased significantly after PBMV (48.2 ± 10.3 mmHg vs. 60.6 ± 15.5 mmHg, P < 0.01). The symptom of chest tightness and short of breath obviously alleviated. All cases followed-up for 6 months to 9 years (average 75 ± 32 months), 2 patients with severe regurgitation died (1 case of massive cerebral infarction, and 1 case of heart failure after 6 years and 8 years, respectively), 2 cases lost access. At the end of follow-up, MVA has been reduced compared with the postoperative (1.4 ± 0.4 cm 2 vs. 1.7 ± 0.3 cm 2 , P < 0.05); LAD slightly increased compared with the postoperative (45.2 ± 5.7 mm vs. 41.4 ± 6.3 mm, P < 0.05), RAD slightly also increased compared with the postoperative (36.1 ± 6.3 mm vs. 28.6 ± 5.5 mm, P < 0.05), but did not recover to the preoperative level. TRA slightly increased compared with the postoperative, but the difference was not statistically significant (P > 0.05). The PAP and left ventricular ejection fraction appeared no statistical difference compared with the postoperative (P > 0.05), the remaining patients without serious complications.</p><p><b>CONCLUSIONS</b>PBMV is a safe and effective procedure for MS combined with TR in patients of rheumatic heart disease. It can alleviate the symptoms and reduce the size of TR. It can also improve the quality-of-life and prognosis. Its recent and mid-term efficacy is certain. While its long-term efficacy remains to be observed.</p>