Objective To study the effect of TGF?β1 gene therapy on the rat model of postpartum stress urinary incontinence and explore a novel non?operative treatment of this disease. Methods Two hundred and forty 6?month old SD female rats were used to prepare the model of postpartum stress urinary incontinence by vaginal dilation with a water sac. 148 rats from the 185 successfully prepared model rats were selected, and randomly divided into 5 groups: the TGF?β1 gene therapy, clentuterol treatment, electric stimulation therapy, injection of empty vector plasmid, and non?treated groups. In addition, 20 normal rats were selected as blank control group. Sneeze test and urodynamic test were conducted, the pelvic floor pubococcygeus muscle contractile force/muscle weight ratio was calculated, serum TGF?1 was detected by ELISA, and TGF?1 protein was detected by immunohistochemistry at 1, 21, 42 and 63 days after the treatment. Results At 21 days after treatment, all the maximum bladder capacity, leak point pressure, and urine or contractile force / muscle weight ratio of the TGF?β1 gene therapy group showed even better effects than those of the electrical stimulation group, but the differences were statistically not significant ( P>0?05 ) . Conclusions TGF?β1 gene therapy shows good therapeutic effect on the rat models of postpartum stress urinary incontinence, suggesting that TGF?β1 gene therapy may become a new type of non?surgical treatment for this disease.

Objective To study the effect of IGF-1 gene therapy and electric stimulation therapy on the rat models of postpartum stress urinary incontinence, and explore the ideal treatment for this disease.Methods 240 SD female rats were used to establish the model of postpartum stress urinary incontinence by water sac vaginal dilation.148 model rats were randomly selected from 185 successful models and divided into 5 groups:IGF-1 gene therapy, clenbuterol treatment, electric stimulation therapy, injection of empty vector plasmid, and untreated groups.Besides, 20 non-modeled rats were used as blank control group.Urodynamic test was performed, pelvic floor pubococcygeus muscle/muscle weight ratio was calculated, and serum biochemical indices (LDH, CK) were detected, and the morphological changes of pubococcygeus muscle fibers were observed by light microscopy at 1, 21, 42 and 63 days after treatment.Results At 21 days after treat-ment, the maximum bladder capacity, leak point pressure, the contractile force/muscle weight ratio in the IGF-1 group and electric stimulation treatment group were significantly better (P>0.05), and the differences between the IGF-1 group and electric stimulation group were not significant ( P>0.05 ) .Conclusions The effect of IGF-1 gene therapy and electric stimulation on the rat models of postpartum stress urinary incontinence is better than that in the drug therapy group and oth-er groups.

Objective To investigate the influence of gonadotropin-releasing hormone (GnRH) analogues on ovarian cancer and ovarian function in vivo.Methods ES-2 cells were cultured and xenotransplanted into 36 nude mice,which were divided into 6 groups:normal saline (NS) group:NS 0.1 nd/day subcutaneous injection,and then NS 0.2 ml/week peritoneal injection; cisplatin (DDP) group:NS 0.1 ml/day subcutaneous injection,and then DDP 5 mg/kg ( diluted to 0.2 ml ) per week peritoneal injection; goserelin group:100 μg goserelin ( diluted to 0.1 ml) per day subcutaneous injection,and then NS 0.2 ml/week peritoneal injection; goserelin + DDP group:100 μg goserelin ( diluted to 0.1 ml) per day subcutaneous injection,and DDP 5 mg/kg (diluted to 0.2 ml) per week peritoneal injection; cetrorelix group:100 μg cetrorelix (diluted to 0.1 ml) per day subcutaneous injection and NS 0.2 ml/week peritoneal injection; cetrorelix + DDP group:100 μg cetrorelix (diluted to 0.1 ml) per day subcutaneous injection and DDP 5 mg/kg ( diluted to 0.2 ml) per week peritoneal injection.All the peritoneal injection started from subcutaneous injection one week later.To compare the weight of nude mice,the volumes of transplanted tumors,the expression of Ki-67 antigen in transplanted tumors,the estrus,the ratio of atretic follicles,the ratio of primary and preantral follicles,the levels of serum anti-Mullerian hormone ( AMH ),folliclestimulating hormone ( FSH),estradio ( E2 ) and progesterone (P) in each group.Results There were no significant difference in the weight of nude mice among 6 groups ( P ＞ 0.05 ),which on day 29 in NS group was ( 19.8 ±2.2) g,DDP group (20.5 ± 1.4) g,gosereline group ( 19.6 ±0.9) g,goserelin + DDP group ( 19.7 ± 1.6) g,cetrorelix group (20.7 ±2.2) g,and cetrorelix + DDP group ( 19.0 ± 1.7) g.The tumor volumes of different groups on the 12th day:NS group (241 ± 179) mm3,DDP group (78 ±20) mm3,gosereline group (78 t±55) mm3,goserelin + DDP group (64 ±48) mm3,cetrorelix group (78 ±64) mm3,or cetrorelix + DDP group (70 ± 19) mm3,in which there were significant difference between NS group and the other groups ( P ＜ 0.05 ) ; and the same result was obtained on day 15,19,22,26 and 29 ( P ＜ 0.05 ).The expression of Ki-67 in NS group was ( 33 ± 10 ) ％,in which it was higher than those in DDP group 3.5％,goserelin group 8.8％,goserelin + DDP group 1.5％,cetrorelix group (23 ± 11 ) ％,or cetrorelix + DDP group ( 8 ± 6 ) ％ ( P ＜ 0.05 ).The ratio of primary and preantral follicles in goserehn group was (71.5 ± 8.1 ) ％,in goserelin + DDP group was (62.4 ± 4.1 ) ％,in cetrorelix group was (71.2 ± 7.4) ％,and in cetrorelix + DDP group was (63.8 ±3.1 )％,in which they were much higher than that in DDP group ( 47.0 ± 4.8 ) ％ ( P ＜ 0.05 ).The level of AMH in goserelin group was ( 98 ± 27 ) ng/ml,which was much higher than that in NS group (66.2 ± 17.4) ng/ml (P ＜0.05),while there were no difference in the levelsof FSH,E2 or P among different groups ( P ＞ 0.05).Conclusion GnRH analogues could inhibit the growth of transplanted tumors in nude mice,meanwhile increase the secretion of AMH,decrease the frequencies and prolong the lasting time of estrus,decrease the ratio of atretic follicles,raise the ratio of primary and preantral follicles,which may be protect the ovarian function of nude mice.

Objective To investigate clinical significance and application of modified pelvic floor reconstruction developed by Peking Union Medical College Hospital ( MPFR ) in treatment of severe pelvic organ prolapse (POP) by comparing the effectiveness, quality of postoperative sexual life, life satisfaction and risk factors for POP recurrence with the following two surgical procedures: traditional total vaginal hysterectomy with anterior-posterior colporrhaphy (TVH-APC) and total vaginal hysterectomy with lateral colporrhaphy and sacrospinous ligament fixation and vaginal bridge repair and episiotomy (TVH-LC-SSLFVBR-EP). Methods Totally 173 patients with severe POP and at least two compartments defects of pelvic floor underwent surgeries in the study, 86 patients (group A) were treated by MPFR with polypropylene mesh application, 58 (group B) were treated by TVH-APC, and 29 patients (group C) were treated by TVH-LC-SSLF-VBR-EP. Peri-operative data and outcomes of postoperative courses at 6, 12, 18 months were collected and analyzed, in the meantime, the risk factors of recurrence were studied. Results (1) No statistical difference was observed among the above 3 groups in terms of length of operation, amount of blood loss, length of hospital stay, and morbidity after surgery ( P ＞ 0.05). ( 2 ) Cost hospitalization was ( 11 448 ±3049) Yuan in group A, which was significantly higher than (7262 ± 1607) Yuan in group B and (7140 ± 1817 ) Yuan in group C (P ＜ 0.05 ). (3) The length of vaginal cuff of (7.5 ± 1.4) cm in group A and ( 5.6 ± 1.1 ) cm in group C were significantly longer than (7.1±0.6) cm in group B ( P＜0.05). The width of vaginal cuff of (4.3±0.3) cm in group A was larger than (3.4±0.3) cm in group B and (3.3±0.4) cm in group C (P＜0.05). (4) The recurrence rate at 12 months after surgery was 12.8% (11/86)in group A, which was similar with 17.2%(5/29) in group C (P＞0.05) and significantly less than 36.2% (21/58) in group B (P＜0.05). The rate of active sexual life of 16.3% (14/86) in group A was significantly higher than 1.7% (1/58) in group B and 0 in group C ( P ＜ 0. 05 ). The index of life quality improvement at 12 months after surgery was 48±12 in group A, which was no less than 53±16 in group C ( P＞0.05) and higher than 27 ± 9 in group B ( P＜0.05). (5 ) Mesh rejection was observed in 6 patients in group A within 3 months after surgery, while the posterior vaginal wall was exclusively involved. No difference was found in urinary retention or urinary incontinence among three groups (P ＞0. 05 ). (6) The severe degree of POP, type of surgical procedure ( TVT-APC), anterior compartment defect of pelvic floor,and early days of performing pelvic floor reconstruction surgeries were high risk factors for POP recurrence (P＜ 0.05). Conclusions MPFR has a better curative effect and lower recurrence rate on patients with POP. It can help patients regain integrity of anatomical structure and functions of pelvic floor. TVH-LCSSLF-VBR-EP is also effective.

Objective:To evaluate the oncologic outcomes of different laparoscopic radical hysterectomy.Methods:From January 2011 to December 2014, the laparoscopic operation cases of cervical cancer at stage Ⅰb1, Ⅰb2, Ⅱa1 and Ⅱa2, including the histologic subtypes of squamous-cell carcinoma, adenocarcinoma and adenosquamous carcinoma, were collected in five clinical centers. The data were divided into two groups according to the surgical procedures, that is, modified laparoscopic-vaginal radical hysterectomy (mLVRH) and total laparoscopic radical hysterectomy (TLRH). The overall survival rate (OS), disease-free survival rate (DFS) at 5 years were retrospectively analyzed in this study.Results:There were 674 cases in total, including 377 cases of mLVRH, 297 cases of TLRH. (1) The OS at 5 years: the mLVRH was 96.1% and the TLRH was 92.0%, and the mLVRH was higher than that of TLRH （ P=0.010）. Stratify analysis， including stage of disease （Ⅰb1 and Ⅱa1）， histologic subtypes （squamous-cell carcinoma, adenocarcinoma）， lymph node metastasis， revealed that, ① Stage of disease: in stage Ⅰb1, the OS at five years of mLVRH was higher than that in TLRH group （98.6% vs 93.6%, P=0.012）. In stage Ⅱa1, there was significant difference between the two groups, the OS at five years of mLVRH and TLRH were 93.6% and 77.6% （ P=0.007）. ② Histologic subtypes: for the OS at five years of squamous-cell carcinoma, mLVRH and TLRH were 96.1% and 92.3%, and there was significant difference （ P=0.046）； for adenocarcinoma, the OS at five years were 91.0% and 88.6%， and there was no difference between two groups （ P=0.230）. ③ Lymph node metastasis： the mLVRH and TLRH with lymph node metastasis, the OS at five years were 98.6% and 96.4%; the mLVRH and TLRH without lymph node metastasis, the OS at five years were 89.3% and 80.8%. There were no significant differences between the two groups,respectively ( P=0.156， P=0.093）. (2) The DFS at 5 years: there was no significant difference between mLVRH and TLRH (94.1% vs 90.9%, P=0.220). Stratify analysis for stage of disease, the mLVRH group was higher than that in the TLRH group in stage Ⅰb1 (97.0% vs 92.8%, P=0.039). However, for stage Ⅱa1, there was no significant difference between mLVRH and TLRH group （88.2% vs 75.8%, P=0.074）. Conclusions:The results of this retrospective study indicated that different laparoscopy surgical procedures had diverse oncologic outcomes. The OS at 5 years of the mLVRH is superior to the TLRH. The DFS at 5 years in Ⅰb1 stage, the mLVRH is higher than the TLRH. Therefore, the modified laparoscopy is still an alternative surgery for early cervical cancer patients when following the principle of no-tumor-exposure.

Objective: To investigate the value of 1H-magnetic resonance spectroscopy (¹H-MRS) in determining the content of liver triglyceride in patients with fatty liver disease (FLD), as well as its influencing factors. Methods: A total of 124 patients with nonalcoholic fatty liver disease (NAFLD), chronic hepatitis B (CHB), or hepatitis B complicated by FLD who underwent liver biopsy in the Affiliated Hospital of Hangzhou Normal University were enrolled, and the clinical data, serological markers, FibroScan results, and ¹H-MRS results were collected. A correlation analysis was performed with the results of liver biopsy as the gold standard, and the influence of factors including hepatitic B virus (HBV) infection and obesity on accuracy was analyzed. A one-way analysis of variance was used for comparison of means between the three groups, and the LSD or SNK test (for homogeneity of variance) or the Tamhane’s or Dunnett’s test (heterogeneity of variance) was used for comparison between any two groups. The t-test was used for comparison of continuous data between groups, and the chi-square test was used for comparison of categorical data. The MRS-PDFF receiver operating characteristic (ROC) curve was plotted, the area under the ROC curve (AUC) was calculated, the optimal cut-off points for the diagnosis of NAFLD were estimated, and sensitivity and specificity were calculated. Results: The NAFLD group (42 patients) and the CHB + NAFLD group (40 patients) had a significantly higher proton density fat fraction (PDFF, the content of triglyceride in the liver) than the CHB group (42 patients) (16.84±9.76/9.39 ± 5.50 vs 3.45 ± 1.63, P < 0.001). The results were significantly correlated with the degree of steatosis confirmed by liver biopsy (P < 0.001), but it was not significantly correlated with inflammation or fibrosis grade. The correlation analysis showed that the MRS-PDFF value measured by 1H-MRS was significantly correlated with body mass index (BMI), blood lipids, alkaline phosphatase, and blood glucose, while it was not significantly correlated with age, sex, or the presence or absence of hepatitis B. The ROC curve analysis showed that the AUCs of PDFF measured by 1H-MRS were 0.93, 0.974, and 0.976, respectively, for the diagnosis of steatosis S1(≥5%), S2(≥34%), and S3(≥66%), and the corresponding optimal thresholds were 5.14%, 11.16%, and 16.7%, respectively. Conclusion 1H-MRS has a high diagnostic value in quantitative evaluation of the degree of liver steatosis in patients with FLD and is not affected by the factors such as HBV infection, age, and sex, while it is correlated with BMI and lipid metabolism.

ObjectiveTo observe the effects of the water extracts of Trichosanthis Radix-Polygonati Rhizoma at different ratios on glucose and lipid metabolism in KKAy mice with spontaneous type 2 diabetes and explore the mechanism of the extract in alleviating insulin resistance based on phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/forkhead box O1 （FoxO1） signaling pathway. MethodThe 8-week-old C57BL/6J male mice were taken as the normal control group， and KKAy male mice of the same age were randomly assigned into a model group， a metformin group， Trichosanthis Radix-Polygonati Rhizoma groups at the ratios of 1∶1 （Trichosanthis Radix 30 g， Polygonati Rhizoma 30 g）， 1∶3 （Trichosanthis Radix 15 g， Polygonati Rhizoma 45 g）， and 1∶5 （Trichosanthis Radix 10 g， Polygonati Rhizoma 50 g） according to blood glucose level and body weight， with 6 mice in each group. The administration lasted for 8 weeks， and the body weight （BW） and fasting blood glucose （FBG） of mice were recorded at the same time points of the 2nd， 4th， 6th， and 8th weeks， respectively. Oral glucose tolerance test （OGTT） was performed at the 7th week. After drug administration， the serum levels of total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， and fasting insulin （FINS） were measured， and homeostasis model assessment-insulin resistance （HOMA-IR） index was calculated. The liver tissue samples were stained with hematylin-eosin （HE） and periodic acid-Schiff （PAS） for observation of the fat distribution and glycogen content. The protein levels of PI3K， Akt， p-Akt， FoxO1， and p-FoxO1 in the liver were determined by Western blot. ResultCompared with the normal group， the model group showed increased food intake， FBG， glucose tolerance， FINS， HOMA-IR， TC， TG， and LDL-C （P<0.01）， and down-regulated protein levels of PI3K， Akt， phosphorylaison （p）-Akt， FoxO1， and p-FoxO1 in the liver （P<0.01）. Compared with the model group， Trichosanthis Radix-Polygonati Rhizoma lowered FBG and HOMA-IR （P<0.05， P<0.01）. In particular， the combination at the ratio of 1∶3 showed the best performance （P<0.01） comparable to metformin. Furthermore， Trichosanthis Radix-Polygonati Rhizoma at different ratios lowered blood glucose at different time points of OGTT （P<0.05） and TC and LDL-C （P<0.01）. Additionally， the combination at the ratio of 1∶3 reduced TG （P<0.01）. The liver of mice in the drug administration groups showed regular morphology， with few lipid droplets and rich glycogen. Western blot showed that Trichosanthis Radix-Polygonati Rhizoma up-regulated the protein levels of PI3K and p-Akt， down-regulated the protein level of FoxO1， and up-regulated the protein level of p-FoxO1 （P<0.05）. ConclusionTrichosanthis Radix-Polygonati Rhizoma， especially at the ratio of 1∶3， lowered the FBG， TC， LDL-C， and HOMA-IR index， promoted liver glycogen synthesis， and reduced steatosis in KKAy mice， which may be related to the regulation of PI3K/Akt/FoxO1 signaling pathway in the liver.

Type 2 diabetes mellitus （T2DM） is a chronic metabolic disease characterized by insulin resistance， hyperinsulinemia， and disturbance of glucose and lipid metabolism， with elevated blood glucose as the main clinical manifestation. Due to its complex etiology and pathogenesis， there is no effective treatment， which critically threatens human health and places a heavy burden on society and families. Saponins are a class of glycosides with complex structures that have the advantage of a wide range of sources， elevated safety， and low adverse effects. As an essential active ingredient in Chinese medicine， Chinese medicine saponins have a variety of biological activities such as hypoglycemia， hypoglycaemia， anti-inflammation， antioxidation， anti-tumor， and immune modulation. In recent years， numerous studies have shown that Chinese medicine saponins are effective in preventing and treating T2DM. Although there have been numerous studies on the hypoglycemic effects and mechanisms of Chinese medicine saponins， there has been no systematic review of the mechanisms of Chinese medicine saponins in the treatment of T2DM. Therefore， to provide a theoretical basis for an in-depth study of the hypoglycemic effects of Chinese medicine saponins and a scientific basis for the development and clinical application of drugs， this paper systematically summarized the hypoglycemic mechanisms of Chinese medicine saponins， such as improving islet β-cell function， improving insulin resistance， inhibiting glycosidase activity， reducing the inflammatory response， anti-oxidative stress， and regulating intestinal flora， and analyzed the current research problems and development trends.

OBJECTIVE：To identif y and analyze the flavonoids and coumarins in Radix Ardisiae from different sources. METHODS：UPLC-QE-HF-MS/MS was adopted. The determination was performed on Zorbax Eclipse-C 18 column with mobile phase consisted of acetonitrile- 0.1％ formic acid solution （gradient elution ）at the flow rate of 0.3 mL/min. The column temperature was 30 ℃，and the temperature of injector was 4 ℃. The sample size was 2 µL；ESI source was applied in negative and positive scanning ion mode ，the heater temperature was 325 ℃，the sheath gas pressure was 45 arb，the auxiliary gas pressure was 15 arb，the purge gas pressure was 1 arb，the electrospray voltage was 3.5 kV，the capillary temperature was 330 ℃， S-lens RF level was 55％，scan mode was first-order full sca m/z 100-1 500，data-dependent secondary mass spectrometry scanning （dd-MS2，Top N ＝10），the resolution was 70 000 （first mass spectrometry ） ， 17 500 （secondary mass spectrometry），the collision mode was high-energy collision dissociation. Through retrieving foreign and domestic databases as ChemSpider ，mzCloud，mzVault，PubChem，the structure of the compound was identified on the basis of related literatures and reference data ，and the conten ts were compared. RESULTS & CONCLUSIONS：A total of 47 components were separated from Radix Ardisiae of 3 kinds of sources as Ardisia crenata Sims，A. crispa（Thunb.）A. DC. ，A. crenata Sims var . bicolor （Walk）C. Y. Wu et C. Chen. A total of 17 flavonoids were identified ，including 9 flavonols （quercetin 3-O-rhamnoside-7-O-glucoside， myricetin， rutin， mauritanin， kaempferol， quercetin， isorhamnetin， quercetin，mearnsitrin），3 flavan-3-ols [（-）-epigallocatechin，catechin，epigallocatechin gallate ）2 dihydroflavonoids [fustin ， eriodictyol] and 3 other types [ 3-（2，3-dihydro-benzo[1，4]dioxin-6-yl）-7-hydroxy-2-trifluoromethyl-chromen-4-one，methadone， oriciacridone F] ，10 coumarins {bergenin ，（[ 7-hydroxy-4-methyl-2-oxo-2H-chromen-6-yl）oxy]acetic acid ，[7-（carboxymethoxy）- 4-methyl-2-oxo-2hydroxychromo-3-yl]acetic acid ，4，9-dihydroxy-7H-furo[3，2-g]chromen-7-one，6，7-dihydroxy-4-methylcoumarin， esculetin，fraxetin，7，8-dihydroxy-4-methylcoumarin，4-methylumbelliferyl glucuronide ，scoparone}. Results of content analysis showed that in flavonoids and coumarins ，there were 5 common components in Radix Ardisiae from 3 kinds of sources ，i.e. bergenin（peak 2），[7-（carboxymethoxy）-4-methyl-2-oxo-2-hydroxychromo-3-yl] acetic acid （peak 5），methadone（peak 16）， quercetin（peak 18），oriciacridone F （peak 26）；the contents of common components were significantly different. In addition to 5 common components ，there were 22 different chemical components ，which were compounds corresponding to peaks 1，3，4， 6-15，17，19-25 and 27，respectively. Among them ，compounds corresponding to peaks 3，6，8 and 23 were only found in A. crenata Sims var. bicolor（Walk）C. Y. Wu et C. Chen ；compounds corresponding to peaks 12-15，19 were only found in A. crispa （Thunb.）A. DC. UPLC-QE-HF-MS/MS method can efficiently ，accurately and quickly identify the flavonoids and coumarins in Radix Ardisiae from different sources.

OBJECTIVE To analyze the chemical constituents and components absorbed into plasma of the extract of Ardisia crenata and to elucidate its possible pharmacodynamic material basis. METHODS Overall， 12 rats were randomly assigned to the blank group （n＝6） and A. crenata group （n＝6） by the paired comparison method. The drug was administered once daily in the morning and afternoon for three days. Serum samples were prepared from serum after redosing on 4th day. The UPLC-QE-HF-MS/ MS was used to analyze and identify the chemical constituents in A. crenata extract and serum samples. Compound Discoverer 3.0 was employed for retention time correction， peak identification， and peak extraction. According to the secondary mass spectrometry information， the Thermo mzCloud online and Thermo mzVault local databases， referring to the relevant literature and control quality spectrum information were used to preliminarily identify the chemical constituents and components absorbed into plasma of A. crenata. RESULTS A total of 34 compounds were identified from the extract of A. crenata， mainly coumarins， flavonoids， organic acids， amino acids， including bergenin， quercetin， gallic acid， L-pyroglutamic acid， etc. Besides， 5 components absorbed into plasma were identified from serum samples: L-pyroglutamic acid， syringic acid， bergenin， cinnabar root saponin A， and mycophenolic acid. CONCLUSIONS L-pyroglutamic acid， syringic acid， bergenin， cinnabar root saponin A， and mycophenolic acid may act as the pharmacodynamic material basis of A. crenata.