Efficacy and Safety of Sacubitril-valsartan in the Treatment of Heart Failure without Reduced Ejection Fraction ： A Meta-analysis / 中国药房

OBJECTIVE：To systematically evaluate the efficacy and saf ety of sacubitril-valsartan in the treatment of heart failure without reduced ejection fraction （non-HFrEF）patients，and to provide evidence-based reference for its clinical treatment. METHODS：Retrieved from Cochrane Library ，PubMed，Embase，CNKI，VIP and Wanfang data ，during the inception to Feb. 29th，2020，randomized controlled trials （RCTs）about sacubitril-valsartan （trial group ）versus routine medicine as renin- angio- tensin converting enzyme inhibitors/angiotensin Ⅱ receptor antagonists （control group ） in the treatment of non-HFrEF were collected. After literature screening and data extraction ，the quality of included literatures were evaluated with Cochrane bias risk evaluation tool 5.3.0. Meta-analysis was conducted with Stata 14.0 software，and the publication bias analysis and sensitivity analysis were performed. RESULTS ：Totally 6 RCTs were included ，involving 5 502 patients. Results of Meta-analysis showed that the HF re-hospitalization rate [RR ＝0.84，95％CI（0.77，0.91），P＜0.001] and the serum creatinine elevation rate [RR ＝0.78，95％ CI（0.67，0.91），P＝0.001] in trial group were significantly lower than control group. NYHA classification improvement rate [RR ＝ 1.25，95％CI（1.10，1.43），P＝0.001] and the hypotension rate [RR ＝1.43，95％CI（1.24，1.65），P＜0.001] were significantly higher than control group. There was no statistical significance in the cardiovascular mortality [RR ＝0.94，95％CI（0.79，1.12）， P＝0.481]，all-cause mortality [RR ＝0.95，95％CI（0.83，1.08），P＝0.417]，the levels of NT-proBNP [WMD ＝－301.16，95％CI （－602.77，0.44），P＝0.050] and LVEF [WMD ＝1.49，95％CI（－1.33，4.32），P＝0.300] after treatment ，and the hyperkalaemia rate [RR ＝0.88，95％CI（0.77，1.01），P＝0.070] between 2 groups. The results of publication bias analysis and sensitivity analysis showed there was a high possibility of publication bias ，and the results of several indexes were not stable. CONCLUSIONS ： Sacubitril-valsartan may effectively reduce HF re-hospitalization rate and the risk of elevated serum creatinine in non-HFrEFpatients，improve the heart function but the risk of hypotension is high. The results should be interpreted carefully.

Effect of exogenous gonadotropin dosage on embryo aneuploidy rate and pregnancy outcome in patients of preimplantation genetic test / 中华妇产科杂志

Objective:To investigate the effect of gonadotropin (Gn) on embryo aneuploidy rate and pregnancy outcome during preimplanptation genetic testing for aneuploidy (PGT-A) cycles.Methods:The clinical data of patients undergoing PGT-A cycle at the First Medical Center of the PLA General Hospital from January 1, 2013 to May 31, 2019 were retrospectively analyzed. Patients were divided into younger patient group (<35 years old) and elder patient group (≥35 years old) by maternal age, then divided into two groups in line with Gn dosage (≤2 250 U, >2 250 U), and into four groups by number of oocytes retrieved (1-5, 6-10, 11-15 and ≥16 oocytes). The embryo aneuploidy rate and pregnancy outcome between the groups were compared. Logistic regression was used to analyze the relationship between the cumulative amount of Gn, embryo aneuploidy rate and live-birth rate.Results:A total of 402 cycles (338 patients) and 1 883 embryos were included in the study. (1) In the younger patients, the aneuploidy rate was 52.5% (304/579) in the group of Gn≤2 250 U and 48.6% (188/387) in the group of Gn >2 250 U, with no significant difference between them ( P=0.232). In the elderly patients, the difference in embryo aneuploidy rate between the two Gn group [57.9% (208/359) versus 60.6% (319/526)] was not statistically significant ( P=0.420). (2) The embryonic aneuploidy rate in different protocol of ovary stimulation was analyzed,in the younger group, the embryonic aneuploidy rate in patients using antagonist long protocol was 50.3% (158/314), it was 50.0% (121/242) in agonist long protocol, 52.1% (207/397) in agonist short protocol and 6/13 in luteal phase protocol, no statistical difference was found in above groups ( P=0.923); in the elder group, embryonic aneuploidy rate was 60.8% (191/314) in antagonist protocol, 58.4% (132/226) in agonist long protocol, 59.2%(199/336) in agonist short protocol, 5/9 in luteal phase protocol, respectively,no significant difference was found ( P=0.938). (3) In the younger patients, the aneuploidy rate in 1-5 oocytes group, 6-10 oocytes group, 11-15 oocytes group and ≥16 oocytes group was 37.9% (11/29), 54.0% (94/174), 52.5% (104/198) and 50.1% (283/565) respectively, no significant difference was found between the groups ( P=0.652); while in the elder patients, the difference between aneuploidy rate in each retrieved oocytes group [73.6% (89/121), 57.5% (119/207), 56.3% (108/192), 57.8% (211/365)] was statistically significant ( P=0.046). (4) Logistic regression analysis of age, cumulative dosage of Gn, number of oocytes obtained, and embryo aneuploidy rate showed that there was no association between the amount of Gn and embryo aneuploidy rate ( P>0.05); the increase in maternal age would increase the risk of aneuploidy rate of embryos, which was statistically significant ( OR=1.031, 95 %CI: 1.010-1.054, P=0.004); the increase in oocytes retrived would significantly decrease the risk of aneuploidy ( OR=0.981, 95 %CI: 0.971-0.991, P<0.01). (5) There was no significant difference in biochemical pregnancy rate [55.6% (80/144) versus 52.1% (63/121)], clinical pregnancy rate [50.0% (72/144) versus 47.9% (58/121)] and live-birth rate [46.5% (67/144) versus 40.5% (49/121)] between different Gn dosage groups ( P=0.613, P=0.738, P=0.324). The logistic regression analysis showed that the maternal age, the cumulative dosage of Gn, the number of oocytes obtained, and the ovarian stimulation protocol had no effect on the live-birth rate (all P>0.05). Conclusions:In PGT-A cycle, the dosage of Gn has no association with the embryo aneuploidy rate and pregnancy outcome. In the patients ≥35 years old, the increase in number of oocytes obtained may decrease the risk of aneuploidy. Age is an important factor affecting the embryo aneuploidy in PGT-A cycle.

Correlation between HLA-G and tumor immunity and its advances / 军事医学

HLA-G belongs to non-classical HLA-class Ⅰ genes.It is expressed in the fetal-maternal interface on the extravillous cytotrophoblast and in such immune privilege tissues as the cornea and pancreas.However, under pathological conditions, such as tumor, inflammatory diseases and post transplantation, HLA-G is expressed abnormally.HLA-G can interact with its acceptors or immune cells and suppress the function of immune cells, which facilitates the escape of the surveillance of the human immune system and the consequent damage.In clinical studies,HLA-G is related to some clinical parameters.This review will focus on the expression, function and regulatory mechanisms of HLA-G in cancer immunology.

Robotic surgery in the management of early ovarian malignancy tumors / 中华妇产科杂志

Objective To apply robotic surgery of early ovarian malignancy tumors clinically and evaluate its feasibility in management for early ovarian cancer. Methods Using the da Vinci robotic surgical system, seven patients with early ovarian malignancy tumors (stage Ⅰ) underwent robotic surgery from April 2012 to September 2013. The average age was 45.7 years. Robotic surgeries approaches contained salpingo-oophorectomy,para-aortic lymphadenectomy, pelvic lymphadenectomy, omentectomy and appendectomy. Perioperative and follow-up clinical data were recorded. Results All robotic surgeries were successfully completed without the conversion to laparotomy. The mean operative time was 225 minutes (100-330 minutes). The average estimated blood loss was 171 ml (20-600 ml). No patients received blood transfusions. No intraoperative and postoperative complications were observed. The average number of pelvic lymph node dissected were 18.3 (11-34). The average number of para-aortic lymph node dissected were 3.7 (3-4). The mean follow-up time was 26.0 months after surgery (20-36 months). Currently, all patients had no tumor recurrence and survived. Conclusion Robotic surgery is feasible as a novel alternative approach in the treatment of early ovarian malignancy tumors.

Ultrasound-guided focused ultrasound ablation of intramural, submucosal and subserosal uterine fibroids: 12-month follow-up results / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the effect of ultrasound-guided focused ultrasound ablation (US-FUA) in the treatment of intramural, submucosal and subserosal uterine fibroids.</p><p><b>METHODS</b>We prospectively assessed the efficacy of US-FUA for treatment of symptomatic uterine fibroids by determining the volume ablation ratio immediately after the treatment and evaluating the volume changes of the uterine fibroids on contrast-enhanced MRI at 6 and 12 months after the treatment. The symptom severity score (SSS) was examined before and at 6 and 12 months after the treatment.</p><p><b>RESULTS</b>A total of 110 women with 145 symptomatic fibroids undergoing US-FUA between August 2011 and December 2012 were enrolled. The fibroids were located intramurally in 72 (49.7%), submucosally in 49 (33.8%) and subserosally in 24 (16.6%) patients, who had comparable mean volume ablation ratios [(93.± 13.1)% vs (94.9 ± 9.3)% vs (89.6 ± 19.3)%, P>0.05]. The volume of the treated fibroids was reduced by (47.3 ± 20.8)%, (70.3 ± 22.2)% and (47.8 ± 13.6)% at 6 months after US-FUA and by (58.9 ± 19.9)%, (82.0 ± 21.2)%, and (50.5 ± 17.8)% at 12 months, respectively, demonstrating a more obvious volume reduction for submucosal fibroids (P<0.05). The SSS scores of the 3 groups before treatment were 29.1 ± 15.2, 34.8 ± 14.5 and 26.6 ± 23.4, respectively, which decreased significantly to 18.4 ± 15.8, 15.5 ± 10.7, and 11.6 ± 11.7 at 6 months (P<0.05) and to 18.9 ± 13.2, 16.8 ± 14.0, 11.5 ± 9.1 at 12 months (P<0.05). No major complications occurred in these patients during the 12-month follow-up.</p><p><b>CONCLUSION</b>US-FUA can yield high ablation ratios for intramural, submucosal and subserosal fibroids and result in significant volume reduction and symptomatic improvement at 6 and 12 months after the treatment, suggesting its value as a new noninvasive option for fibroid treatment in patients who wish to preserve the uterus.</p>

Preliminary study on clinical application of robotic sacral hysteropexy in treatment of uterine prolapse / 中华妇产科杂志

Objective To study the clinical efficacy of robotic sacral hysteropexy in treatment of uterine prolapse.Methods From January 2012 to December 2013,3 patients undergoing robotic sacral hysteropexy in treatment of uterine prolapse in General Hospital of People's Liberation Army were studied retrospectively.Operation time,blood loss and postoperative recovery exhaust time and pelvic organ prolapse quantification (POP-Q) staging were evaluated.Results Three patients were treated by robotic sacral hysteropexy successfully.The mean operation time was 221 minutes (210-240 minutes),mean blood loss was 45 ml.One case with Ⅱ degree perineal laceration patients simultaneously perineal repair,neither intranor post-operative complications occurred.The mean postoperative recovery exhaust time was 16 hours.At three months of follow-up,all 3 patients got satisfaction.Although one patient at the first six months of postoperation had leakage of urine when coughing,instruct exercise pelvic floor muscle function and acupuncture one month their symptoms disappear.Conclusion Robotic sacral hysteropexy pave the way for an effective option in the management of uterine prolapse.

A meta-analysis of preventing bone mineral loss in patients with endometriosis treated by gonadotrophin-releasing hormone analogues with add-back therapy / 中华妇产科杂志

Objective To evaluate the role and efficacy of preventing bone mineral loss in patients with endometriosis treated by gonadotrophin-releasing hormone analogues (GnRH-a) combined with addback therapy.Methods Prospective,randomized controlled studies of the use of GnRHa with add-back therapy in treatment of endometriosis were enrolled in this study from Medline,Embase,Cochrane library,China National Knowledge Internet (CNKI),Chinese Biological Medicine Disk (CBM) and Data Base of Wanfang.After quality assessment and data extraction,meta-analysis were conducted in the change of BMD,reproductive hormone (E2) and visual pain score (VAS) by Stata 11.0 software.Results A total of 785patients from 13 randomized controlled trail (RCT) studies enrolled in this study after exclude no following up,poor quality and repeat published studies.377 patients were in group of GnRH-a with add-back treatment and 408 patients were in group of GnRna alone.The findinds were showed in meta-analysis:(1) there was a significant difference in percentage change of bone mineral density (BMD) between two groups,the addback therapy was more effective in prevention of bone loss which was (SMD =0.223,95％ CI:0.003 to 0.443,P =0.047).(2) There was no significant difference in the level of reproductive hormone between two groups (SMD =-0.053,95％ CI:-0.479 to 0.373,P =0.807).(3) There was also no significant difference in the visual pain score between the two groups (SMD =-0.157,95％ CI:-0.474 to 0.160,P=0.332).Conclusions GnRH-a with add-back therapy have been shown to be more effective in preventing loss of BMD than GnRH-a treatment alone.However,the long term effect of preventing BMD should be studied.

Fertilization method for primary infertility patients without definite cause undergoing in vitro fertilization and embryo transfer / 南方医科大学学报

<p><b>OBJECTIVE</b>To determine the optimal fertilization method for primary infertility patients without definite causes undergoing in vitro fertilization and embryos transfer (IVF-ET).</p><p><b>METHODS</b>A total of 321 IVF-ET cycles for primary infertility without definite causes were divided into two groups, namely group A with infertility period ≥ 5 years (165 cycles) and group B with infertility period <5 years (156 cycles). Each group was further divided into IVF, ICSI, and partial ICSI subgroups. The fertilization rate, incidence of low fertilization rate and clinical pregnancy rate were analyzed.</p><p><b>RESULTS</b>The fertilization rate of IVF in group A was 67.5%, significantly lower than that of ICSI and partial ICSI in the same group (82.0% and 77.7% respectively) and that in IVF control group (76.3%, P<0.05). The incidence of low fertilization rate of IVF in group A was 33.3%, significantly lower than that of ICSI and partial ICSI (8.3% and 15.8%, P<0.05); in group B, the incidence of low fertilization rate of IVF was 12.3%, significantly lower than that of IVF in group A but showed no significant differences from that of ICSI and partial ICSI in group B (P>0.05). In group A, IVF resulted in a significantly lower clinical pregnancy rate (21.1%) than ICSI (43.3%, P<0.05), half ICSI (40.0%, P<0.05), IVF in the control group (48%, P<0.05), and IVF in group B (50.0%, P<0.05).</p><p><b>CONCLUSION</b>ICSI treatment can increase the fertilization rate in IVF-ET cycles in patients with primary infertility for unknown causes, and may improve the clinical outcome of patients with long infertility period.</p>

Transvaginal Contrast-enhanced Sonography in the Differentiation of Benign from Malignant Adnexal Masses / 中国医学影像学杂志

Purpose:The study was designed to investigate the feasibility of contrast-enhanced ultrasound in the differentiation of benign and malignant adnexal masses.Materials and Methods:Sixty-nine consecutive patients with adnexal masses received trans vaginal contrast-enhanced ultrasound.The image and perfusion features were assessed.Results:All of 26 malignant tumors showed detectable contrast enhancement,including 24 cases with a quick,heterogeneous or branching pattern.Among 39 benign lesions,24 were cystic with circle or half-circle enhancement,including 5 cases with intra-cystic septum or papillae slightly enhanced.The other 15 cases were solid,8 of them had slightly dotted enhancement.There are significant difference in enhancement patterns between benign and malignant masses ( P < 0.0001).The 4 cases of borderline tumors showed progressive,heterogeneous enhancement.Conclusion:Contrast-enhanced ultrasound is of value in the differentiation of benign and malignant adnexal masses.

Preliminary study on laparoscopically robotic assisted radical hysterectomy and pelvic lymphadenectomy on cervical cancer / 中华妇产科杂志

Objective To evaluate the feasibility of laparoscopically robotic assisted radical hysterectomy and pelvic lymphadenectomy in treatment of cervical cancer.Methods From Dec.2008 to Aug.2009,5 cervical cancer patients at stage Ⅰ bl to Ⅱ a underwent laparoscopically robotic assisted radical hysterectomy and pelvic lymphadenectomy.The following clinical parameters were recorded and compared,including operative time,blood loss,intraoperative and postoperative complications,the changes of hemoglobin before and after surgery,postoperative temperature,the time of postoperative anus exhaust and urination,hospitalization,pathologic exam,and the number of lymph nodes.Results Laparoscopically robotic assisted radical hysterectomy and pelvic lymphadenectomy were performed successfully on those 5 patients without the conversion to laparotomy.No intraoperative and postoperative complications were observed.The operative time were 305,365,275,240 and 245 minutes,respectively,with a mean value of 286 minutes.Estimated blood loss was 200,400,650,300 and 400 ml,respectively.The mean blood loss was 390 ml.Temperatures of all patients were not higher than 37.5℃ and anus exhaust was recovered at 36 hours after surgery.Those five patients were hospitalized for 11,13,9,12 and 12 days respectively.Squamous carcinoma of cervix were diagnosed by the pathologic examination.The resected margin of vagina and parametrium was clear.The numbers of pelvic lymph nodes were 14,22,16,21 and 18,respectively.No evidence of lymph nodes metastasis was found.Conclusion Laparoscopically robotic assisted radical hysterectomy and pelvic lymphadenectomy is feasible as a novel approach in the treatment of cervical cancer.

Changes of rat testicular germ cell apoptosis after high power microwave radiation / 中华男科学杂志

<p><b>OBJECTIVE</b>To study the effect of high power microwave (HPM) radiation on the testicular germ cell apoptosis.</p><p><b>METHODS</b>One hundred and twenty-five Spraque-Dawley rats were randomly divided into two groups, unexposed control group and experimental group(further divided into four subgroups: 10 mW/cm2 5 min, 10 mW/cm2 10 min, 20 mw/cm2 5 min, and 20 mW/cm2 10 min), and then the experimental group was radiated with S wave band of 10 mW/cm2, 20 mW/cm2 high power microwave for 5 or 10 min. Testicular samples were taken at 6 h, 24 h, 48 h, 72 h and 5 d after radiation and separately studied. At the end of the process, testicular germ cell apoptosis was detected by in situ terminal deoxynucleotityl transferase mediated dUTP nick end labeling (TUNEL).</p><p><b>RESULTS</b>The number of apoptotic cells of the 6 h, 24 h and 48 h experimental groups at 5 min after 10 and 20 mW/cm2 radiation was remarkably larger than that of the controls (P < 0.01), especially after 10 mW/cm2 radiation, the number of the 6 h group reached the peak (161.27 +/- 5.90) /5 convoluted seminiferous tubules. The changes in the other experimental groups had no significant difference compared with the controls (P > 0.05).</p><p><b>CONCLUSION</b>HPM can increase germ cell apoptosis of the rat testis, which is related to the time of radiation and sample acquisition. In the condition of the present test, 5 minutes of HPM radiation may significantly enhance testicular germ cell apoptosis and damage, which in turn may influence the reproductive function of the rats.</p>

Cloning of the genes associated with the pathogenesis of pregnancy induced hypertension using subtractive hybridization / 中华妇产科杂志

Objective To clone the genes related to pregnancy induced hypertension (PIH) for the study of PIH pathogenesis. Methods The differential expressed cDNA of PIH and normal pregnant placenta were cloned using modified polymerase chain reaction based subtractive hybridization. The differential cDNA were sequenced. Results Ammong 86 clones from subtractive hybridization, 14 clones containing differential expressed gene fragments in PIH and normal placenta were identified, and these might be the genes associated with PIH. Compared with the expressed sequence tags (EST) in dbEST of National Center for Biotechnology Information, it showed that 11 of them were known gene fragments, and three were unknown. The three unknown gene fragments were registered in GenBank, the accession number is AF 232216, AF 232217, AF 233648 respectively. Conclusions Fourteen PIH related genes were cloned with subtractive hybridization. A new approach to study on the pathogenesis of PIH is presented.

Screening and confirmation of differentially expressed genes in placentas from PIH patients / 中华围产医学杂志

Objective To unmask clues for the investigation of PIH pathogenesis by detecting the altered gene expression profile of placentas from PIH patients. Methods Clinical data and placentas were collected from 42 PIH patients and 22 normotensive pregnancies in seclective cesarean section to construct PIH database from Mar. 2001 to Sep. 2002 in Xi’an district. Suppression subtractive hybridization (SSH) was performed to set the subtractive cDNA library and differential screening was used to identify the positive clones;insertion of positive clones were sequenced by T7 primer method. RT-PCR and immunohistochemistry were employed to confirm the putative gene inhibin A expression. Results A database was set up that consists of pre- and postpartum clinical data and placenta samples of 42 preeclamptic pregnancies and 22 normotensive ones From which,150 features of placental tissue microarray were made. One hundred and three positive clones were isolated by SSH and differential screening. Sequencing and BLAST analysis showed that 90 insertion shared more than 95% homology with sequences in the GenBank/EMBL database. We identified 36 putative genes including pregnancy-specific glycoproteins gene (BC005924),serine protease inhibitor gene (BC012868),VEGFR-1 gene (AF063657),cytokeratine 7 gene(CK7) (AF509887),etc. Inhibin beta A gene was highly expressed in placentas in PIH patients. Conclusion The gene expression profile in PIH placenta was greatly changed;it might be necessary to investigate the role of VEGFR1,serine protease inhibitor,inhibin and CK7 in the pathogenesis of PIH.

Effect of hypoxia-inducible factor-2? on VEGF expression in villous explants under hypoxia / 中华围产医学杂志

Objective To investigate the effect of hypoxia on the expression of vascular endothelial growth factor (VEGF) in villous explants, and the effect of hypoxia-inducible factor 2? (HIF-2?) on the VEGF expression. Methods The villous were obtained from women who underwent suction and curettage for termination at 6-8 gestational weeks. Four groups were divided: normoxia group; hypoxia group; sense HIF-2? oligonucleotide group and anti-sense HIF-2? oligonucleotide group. All villous were cultured in vitro. In anti-sense and sense group, villous were incubated under hypoxia with HIF-2? oligonucleotide. The villous explants were collected after 48 h of cultivation. The protein level of HIF-2? was detected by Western blot and the mRNA of HIF-2? and VEGF were examined by real-time PCR. Results The expression of HIF-2? mRNA and VEGF mRNA as well as the protein level of HIF-2? were increased in hypoxic group comparing with the normoxia group. Compared with the sense group, the expression of HIF-2? protein and HIF-2?, VEGF mRNA showed significant decrease in anti-sense group. Conclusions Hypoxia may result in the increased expression of VEGF in villous explants during the early trimester, which might be mediated by HIF-2?.