[Expert consensus statement on Kangfu Xiaoyan Suppository in treatment of pelvic inflammatory in clinical practice].

Kangfu Xiaoyan Suppository is widely used in the treatment of gynecological inflammatory diseases. Long-term clinical application and a certain amount of research evidences show that Kangfu Xiaoyan Suppository can alleviate the clinical symptoms of pelvic inflammatory diseases,reduce the recurrence rate,and relieve sequelae,with a better safety and economic characteristics. As a type of nationally protected traditional Chinese medicine and type B medicine included in medical insurance,it has been selected as a Chinese patent medicine for rectal administration. It was included in the Guidelines for diagnosis and treatment of common gynecological diseases of traditional Chinese medicine published by the Chinese Academy of Traditional Chinese Medicine in 2012,the Pelvic inflammatory diseases diagnosis and treatment guidelines issued by the Infectious Diseases Collaborative Group of the Obstetrics and Gynecology Branch of the Chinese Medical Association in 2014,and the group standard of Single use of traditional Chinese medicine/combined antibiot guidelines for clinical practice-pelvic inflammatory diseases of the Chinese Academy of Traditional Chinese Medicine in 2017. To further enhance clinicians' understanding of the drug and better guide its rational clinical use,experts from the field of gynecology of traditional Chinese and Western medicine were invited to develop and compile this expert consensus. This consensus takes full account of clinical evidences and expert clinical experience,and form recommendations for clinical problems based on evidences and consensus recommendations for clinical problems without evidence by nominal grouping method. The expert consensus is mainly formed in the consideration of six factors: quality of evidence,economy,efficacy,adverse reactions,patient acceptability and others. Based on clinical research evidences and expert experience,this consensus provides a preliminary reference for the clinical use of the drug in a concise and clear format. However,evidence-based support is still required in a large number of high-quality studies,and this consensus will be revised in the future according to new clinical problems and the update of evidence-based evidence in practical application.

Effect of Acupuncture and Clomiphene in Chinese Women With Polycystic Ovary Syndrome: A Randomized Clinical Trial.

Importance: Acupuncture is used to induce ovulation in some women with polycystic ovary syndrome, without supporting clinical evidence. Objective: To assess whether active acupuncture, either alone or combined with clomiphene, increases the likelihood of live births among women with polycystic ovary syndrome. Design, Setting, and Participants: A double-blind (clomiphene vs placebo), single-blind (active vs control acupuncture) factorial trial was conducted at 21 sites (27 hospitals) in mainland China between July 6, 2012, and November 18, 2014, with 10 months of pregnancy follow-up until October 7, 2015. Chinese women with polycystic ovary syndrome were randomized in a 1:1:1:1 ratio to 4 groups. Interventions: Active or control acupuncture administered twice a week for 30 minutes per treatment and clomiphene or placebo administered for 5 days per cycle, for up to 4 cycles. The active acupuncture group received deep needle insertion with combined manual and low-frequency electrical stimulation; the control acupuncture group received superficial needle insertion, no manual stimulation, and mock electricity. Main Outcomes and Measures: The primary outcome was live birth. Secondary outcomes included adverse events. Results: Among the 1000 randomized women (mean [SD] age, 27.9 [3.3] years; mean [SD] body mass index, 24.2 [4.3]), 250 were randomized to each group; a total of 926 women (92.6%) completed the trial. Live births occurred in 69 of 235 women (29.4%) in the active acupuncture plus clomiphene group, 66 of 236 (28.0%) in the control acupuncture plus clomiphene group, 31 of 223 (13.9%) in the active acupuncture plus placebo group, and 39 of 232 (16.8%) in the control acupuncture plus placebo group. There was no significant interaction between active acupuncture and clomiphene (P = .39), so main effects were evaluated. The live birth rate was significantly higher in the women treated with clomiphene than with placebo (135 of 471 [28.7%] vs 70 of 455 [15.4%], respectively; difference, 13.3%; 95% CI, 8.0% to 18.5%) and not significantly different between women treated with active vs control acupuncture (100 of 458 [21.8%] vs 105 of 468 [22.4%], respectively; difference, -0.6%; 95% CI, -5.9% to 4.7%). Diarrhea and bruising were more common in patients receiving active acupuncture than control acupuncture (diarrhea: 25 of 500 [5.0%] vs 8 of 500 [1.6%], respectively; difference, 3.4%; 95% CI, 1.2% to 5.6%; bruising: 37 of 500 [7.4%] vs 9 of 500 [1.8%], respectively; difference, 5.6%; 95% CI, 3.0% to 8.2%). Conclusions and Relevance: Among Chinese women with polycystic ovary syndrome, the use of acupuncture with or without clomiphene, compared with control acupuncture and placebo, did not increase live births. This finding does not support acupuncture as an infertility treatment in such women. Trial Registration: clinicaltrials.gov Identifier: NCT01573858.

[Impact of Cryptotanshinone on the reproductivity and metabolism of male mice with Akt2 deletion].

OBJECTIVE: To investigate the impact of protein kinase B (Akt2) allele deletion on testicular reproductive function, and to discuss the regulatory effect of Cryptotanshinone on the reproductivity of male mice with Akt2 allele deletion and its molecular mechanism. METHODS: Fifteen Akt2 +/+ male mice were randomly divided into Groups A (baseline control, n = 7) and B (stimulation, n = 8), and another 29 Akt2 -/- male mice into C (baseline control, n = 7), D (stimulation, n = 8), E (solvent, n = 7) and F (Cryptotanshinone, n = 7). Groups B and D underwent human chorionic gonadotropin (HCG) stimulation tests at 5 IU / 20 g, while A and C received physiological saline, all for 4 hours; Group F were given gastric lavage of Cryptotanshinone, while E solvent only, at 600 mg/kg twice a day for 8 weeks, both subjected to oral glucose tolerance tests (OGTT) at 2 g/kg before and after the treatment. The body and bilateral testis weights were obtained, the serum testosterone (T) level measured, and the expressions of testicular steroid hormone synthesis and glycometabolism-related genes determined by RT-PCR. RESULTS: OGTT showed that the level of blood glucose was significantly higher in Groups C and D than in A and B ([10.38 +/- 1.42] and [10.96 +/- 1.81] mmol/L vs [7.92 +/- 0.63] and [8.32 +/- 0.44] mmol/L, P < 0.05), but had no significant differences at different time points in E and F (P > 0.05). The testis weight was remarkably higher in Groups C and D than in A and B ([0.17 +/- 0.01] and [0.17 +/- 0.01] g vs [0.15 +/- 0.01] and [0.15 +/- 0.02] g, P < 0.05), but exhibited no obvious difference in E and F, nor were there any significant differences in body weight among different groups (P > 0.05). The serum T level was markedly higher in Group C than in A ([9.08 +/- 1.59] nmol/L vs [6.42 +/- 0.95] nmol/L, P < 0.05), but evidently lower in F than in E ([5.94 +/- 0.49] nmol/L vs [8.18 +/- 1.44] nmol/L, P < 0.05). The baseline expression levels of Cyp11, Cyp17, 3B-HSD, Star, Gsk3beta, Erk-1, and MCM2 mRNA were significantly higher in Group C than in A (P < 0.05). After HCG stimulation, the expressions of Cyp11, Cyp17, 3B-HSD, and Star mRNA were remarkably increased in B and D, but with no obvious difference between the two groups (P > 0.05), while the expressions of Cyp11, Cyp17, 3B-HSD, Star, Gsk3beta, Erk-1, and MCM2 mRNA markedly decreased in F as compared with E (P < 0.05). CONCLUSION: Akt2 gene deletion may affect glycometabolism and testicular function, and cause abnormal glycometabolism and androgen secretion in male mice, whose molecular mechanism is associated with the elevated expressions of the key glycometabolic molecules and of the key enzymes for androgen synthesis. Cryptotanshinone can reduce the levels of androgens by down-regulating the expressions of the key enzymes for androgen synthesis.

[Disorder of Tiangui (kidney essence) and reproductive dysfunction in patients with polycystic ovary syndrome].

Traditional Chinese medicine (TCM) usually views polycystic ovary syndrome (PCOS) as a menstrual disease or infertility disease. Reproductive dysfunction in PCOS is characterized by ovarian androgen excess and disturbance of follicular development, and its main clinical manifestations include delayed menstruation, scant menstruation, amenorrhea or infertility. Insulin resistance is a key pathological mechanism of PCOS. "Tiangui" (kidney essence) as a sex-stimulating essence in female in TCM theory, is essential to the menstruation and pregnancy of women. The disturbance of Tiangui (including time, status and rhythm) would result in female reproductive problems. Current studies of Tiangui indicate that ovary is the target organ of PCOS treatment, and its functional characteristics are consistent with the properties of Tiangui in time frame, state form and rhythm cycle. It is then concluded that ovarian dysfunction in PCOS can be expressed as disorder of Tiangui.

[Study on the apoptosis inducing effect of pseudolaric acid B on cervical carcinoma cell line HeLa cells].

OBJECTIVE: To investigate the biological effect and mechanism of action of pseudolaric acid B (PAB) on the cultured human HeLa cells in vitro. METHODS: MTT and flow cytometric assays were used to detect the cells proliferation inhibitory rate and apoptosis of HeLa cell in exposure to PAB; the morphological changes of apoptosis were observed with electron microscope; and the expressions of p53/bcl-2/bax mRNA were detected by RT-PCR. RESULTS: (1) HeLa cell proliferation was inhibited by PAB in a dose-dependent manner, the IC50 being about 10 micromol/L; (2) flow cytometry showed that the distribution of HeLa cell cycle was changed time-dependently by 10 micromol/L PAB-treatment, showing decrease of G0/G1 phase cell percentage and increase of G2/M phase cell percentage; (3) the bax mRNA expression elevated and bcl-2 protein expression decreased markedly after being treated by 10 micromol/L PAB for 12 h, 24 h, and 48 h; while the expression of p53 mRNA could not be detected. CONCLUSION: PAB can inhibit the proliferation and induce the apoptosis of Hela cells in vitro, and its molecular mechanism may be associated with up-regulating bax mRNA expression and down-regulating bcl-2 mRNA expression.

[Insulin resistance enhanced the response of the ovary].

OBJECTIVE: To search for the role of impaired insulin signaling in the ovary reproductive failure and abnormal metabolic profiles in the AKT2- mouse. METHODS: Adult, female 129/C57BL/6 (AKT2-) mice were used in these studies. Littermate wide types C57BL/6J (AKT2+), as well as mutant genotypes (AKT2-). The ovaries were abstained from 6 AKT2+ type mice as wall as 6 mutant genotypes, which was used for insulin stimulated glucose uptake study. By ovary transplantation on the day of 12 weeks, three genotypic mice were constructed with body AKT2+ and ovary AKT2+ in Group A, body AKT2+ and ovary AKT2- in Group B, body AKT2- and ovary AKT2+ in Group C. The vaginal smear was done to evaluate the recovery and cyclicity of transplanted ovaries with mutant or intact AKT2. Before execution, every group was randomly separated into basal and stimulated groups in which the mice were injected recombination FSH (0.75 IU/g), and then AKT2, GSK3beta, ERK-1, CYP17 and CYP19 were determined by RT-PCR in the ovaries, and the serum were reserved for the assay of HDL-C, CHO, TG, 17-OHP progesterone, E(2), T, and LH. The weight of each mouse, their ovary and their fat pads and the estrus cycle, were also recorded. RESULTS: (1) The weight of fat pads beside ovaries and fold inguen in C group were significant higher than the other groups. (2) The level of 17-OHP progesterone in B group was higher than A or C group both in basal and FSH-stimulated groups. (3) In the basal group the expression of ERK-1 and CYP17 were enhanced. Moreover in FSH-d stimulated group, the expression of ERK-1, CYP17, CYP19 and GSK3B in B group were higher as compared with the other groups. CONCLUSION: (1) IR existed in the ovary of AKT2- type, and the mice with AKT2-type ovary had delayed cycle, PCO and high level of 17-OHP, which were similar with PCOS. (2) Metabolic dysfunction in the AKT2- mice has close relationship with whole body condition, but not defective insulin signal within ovaries. (3) Defects of insulin activity in the metabolic pathway could induce the increased expression of ERK-1 and mitogenic potential indicating the cross-talk between two pathways of insulin signaling within ovarian cells. Consequently, ovarian hyperovarianism was induced in the defective ovaries, which contribute to the enhanced response to gonadotropin and synthesis of steroid hormone.

[Effects of ginseng total saponins on nerve growth factor expression in rat with estradiol valerate-induced polycystic ovaries].

OBJECTIVE: To investigate the effect of ginseng total saponins (GTS) on expression of nerve growth factor in rat with polycystic ovaries. METHODS: A total of thirty rats were randomly divided into normal control group, untreated group and GTS group. Polycystic ovaries were induced by a single intramuscular injection of 4 mg estradiol valerate (EV) in rats of the untreated group and GTS group. The rats in the GTS group were administered 50 mg/kg GTS every other day by intraperitoneal injection for 30 days after the EV injection. The expressions of NGF in the ovaries, pituitary and hippocampus were observed by method of immunohistochemistry. RESULTS: Comparison with the normal control group revealed that the expressions of NGF in ovaries, pituitary and hippocampus of rats in the untreated group were increased (P<0.05). The ovarian morphology of the GTS group was almost as normal as that of the normal control group. As compared with the untreated group, the expression of NGF in ovaries of the rats in GTS group was obviously decreased (P<0.05), while the expression of NGF in pituitary and hippocampus showed on difference. CONCLUSION: GTS can decrease the expression of NGF in ovary tissue in rats with polycystic ovaries induced by EV, which may be its mechanism in lessening the polycystic ovary.

[Induction of insulin resistance induced by PI-3K inhibitor in porcine granulosa cells].

OBJECTIVE: To investigate the biological effects of insulin resistance (IR) on the porcine granulosa cells which is induced by wortmannin, the PI-3K inhibitor and mediated by key molecules including GLUT4 and MAPK during insulin signaling. METHODS: The model of IR porcine granulosa cell was established in in vitro culture by treatment of wortmannin, and was assessed the amount of 3H glucose uptake as well as medium glucose levels by glucose oxidase method. The protein and mRNA expression of GLUT4 and MAPK were evaluated by immunofluorescence and RT-PCR respectively. RESULTS: The glucose intake was decreased by 40% with treatment of wortmannin at 1.5 micromol/L (P<0.05). GLUT4 and MAPK were localized mainly to cytoplasm of granulose cells. When granulosa cells were insulin resistant, the expression of GLUT4 was down-regulated whereas MAPK was up-regulated as compared with the controls. CONCLUSIONS: Wortmannin treatment can lead to decreased expression of GLUT4 and increase of IR granulose cells. This metabolic phenotype could induce increased expression of MAPK and mitogenic potential, indicating the cross-talk between two pathways of insulin signaling within ovarian cells.

[Comparison of clinical efficacies for treatment of 93 patients with chronic pelvic inflammation by Chinese composite yanting decoction medicated via two different paths].

OBJECTIVE: To compare the clinical efficacies of Chinese composite Yanting Decoction medicated via two different paths (via oral and via retention enema) in treating chronic pelvic inflammation. METHODS: Adopting the randomized multicentered parallel contrast principle, 93 patients were assigned to the retention enema (RE) group (47 cases) and the oral medicated (OM) group (46 cases) at random, Yanting Decoction was administered via respective paths for 10 days as one course. The changes of syndromes (qi-stagnance and blood stasis) and local signs were observed before and after treatment. RESULTS: In the 47 patients of the RE group, 3 were cured, the treatment was markedly effective in 20, effective in 22 and ineffective in 2, the total effective rate being 95.7%; while in the 46 patients of the OM group, the corresponding number were 1, 8, 30, 7 and 84.8%, respectively, the difference of the total effective rate between groups was statistically significant (P <0.05). The total effective rate for TCM syndromes in the RE and the OM group was 95.7% (45/47) and 82.6% (38/46) respectively, and that for local signs, 97.9% (46/47) and 84.8% (39/46) respectively, the improvements in the RE group were better than those in the OM group (P <0.05). CONCLUSION: Chinese preparation Yanting Decoction shows good clinical efficacy in treating chronic pelvic inflammation of qi-stagnant blood-stasis type, the effect could be enhanced by medicating via retention enema than that via oral.

[Advances of modern studies of acupuncture and moxibustion for treatment of ovulation disorders].

OBJECTIVE: To introduce the modern advances of studies on acupuncture and moxibustion for treatment of ovulation disorders. METHODS: The recent years' literature of acupuncture and moxibustion for treatment of ovulation disorders were reviewed from clinical studies and treatment mechanisms. RESULTS: Acupuncture and moxibustion can regulate the hypothalamus-pituitary-gonadal axis, the nervous system and immune system of the organism. CONCLUSION: Acupuncture and moxibustion has very good clinical effects on ovulation disorders, and it is a safe and effective adjuvant way for modern assisted reproductive technique.

[Therapeutic effects of Jinqi Jiangtang tablet on women with polycystic ovary syndrome].

OBJECTIVE: To observe the therapeutic effects of Jinqi Jiangtang Tablet (JQJTT), a commonly prescribed recipe for type 2 diabetes in traditional Chinese medicine, on obese women with polycystic ovary syndrome (PCOS). METHODS: Twenty-four obese women with PCOS were prescribed JQJTT for 3 months and the changes of carbohydrate metabolism and biochemical indicators, including menstrual cycle, body mass index (BMI), the level of blood sex hormone, area under curve (AUC) of glucose and insulin during oral glucose tolerance test (OGTT), and testosterone responses during human chorionic gonadotrophin stimulation ovary test were observed. RESULTS: After treatment, there were significantly reductions in BMI (P<0.05), serum glucose level at 30 min during OGTT (P<0.05) and testosterone levels at eighteen hours during human chorionic gonadotrophin stimulation ovary test (P<0.05). In addition, nine patients had improved cycles among sixteen completed patients, and one patient with clomifene resistance got pregnant with response to clomifene treatment. CONCLUSION: The beneficial effects of JQJTT may result from improvement of carbohydrate metabolism and reduction in androgen biosynthesis in women with PCOS.

Progress of integrative Chinese and Western medicine in treating polycystic ovarian syndrome caused infertility.

Polycystic ovarian syndrome (PCOS) is one of the most popular diseases that cause menstrual dysfunction and infertility in women. The present paper is a brief retrospection on the progress in treatment of PCOS caused infertility with integrative Chinese and Western medicine (ICWM). It can be seen from these materials that using traditional Chinese medicine (TCM) recipes formulated by Shen-replenishing herbs or acupuncture to reinforce Gan-Shen, regulate Chong-Ren Channels in treating PCOS, stable clinical efficacy could be obtained, with less adverse reaction, though the effect initiated somewhat late. Whereas, when Shen-replenishing recipe and acupuncture are combined with hormone or ovulation promoting drugs of Western medicine, the above-mentioned shortcomings would be overcome. So, this combined therapy is frequently used in clinical practice.

[Microsatellite polymorphism of (tttta) n in the promoter of CYP11a gene in Chinese women with polycystic ovary syndrome].

OBJECTIVE: To investigate the distribution of (tttta) n microsatellite polymorphism in the promoter of CYP11a gene in Chinese women with polycystic ovary syndrome (PCOS) and the relationship between such polymorphism and PCOS. METHODS: Peripheral blood samples were obtained from 201 women with PCOS, aged 26 +/- 4, and 147 women without PCOS, aged 29 +/- 5. Radioimmunoassay was used to examine the levels of testosterone, follicle-stimulating hormone, luteinizing hormone, progesterone, estradiol, and prolactin. Locus-specific prime PCR was used to detect the frequencies of the CYP11a alleles. Body mass index (BMI) was calculated. RESULTS: The average BMI of the women with PCOS was 22 kg/m(2) +/- 4 kg/m(2), and that of the non-PCOS women was 22 kg/m(2) +/- 6 kg/m(2). The six-repeat allele variant genotypic distribution of CYP11a was statistically different between the women with PCOS and those without PCOS [Fisher's exact test (2-tail), P = 0.031]. The frequency of 6//6 genotype in the PCOS patients was 57.7% (116/201), significantly higher than that of the non-PCOS women [44.9% (66/147), chi(2) = 5.588, P = 0.018]. The BMI of the PCOS patients with 4//4 genotype was 19.4 kg/m(2) +/- 1.7 kg/m(2), statistically lower than those of the PCOS patients with 4//6, 6//6, and 6//8 genotypes (23.6 kg/m(2) +/- 3.3 kg/m(2), 22.5 kg/m(2) +/- 3.8 kg/m(2), 22.2 kg/m(2) +/- 4.2 kg/m(2) respectively, P = 0.0037, 0.0027, and 0.059 respectively). The PCOS patients with the allele (tttta) 6 had markedly higher BMI (22.7 kg/m(2) +/- 3.7 kg/m(2)) than those without the allele (tttta) 6 (19.4 kg/m(2) +/- 1.7 kg/m(2), P = 0.0075). No differences were observed in the serum levels of reproductive hormones among the individuals with different genotypic features in the PCOS patients. CONCLUSION: The six-repeat allele is the most common fragment of (tttta) n microsatellite polymorphism in Chinese Han woman. The 6//6 genotype is significantly more frequent and is associated with greater BMI in the women with PCOS. The six-repeat allele variant may play a certain role in the pathogenesis of PCOS.

Expression and activity of the signaling molecules for mitogen-activated protein kinase pathways in human, bovine, and rat lenses.

PURPOSE: The mitogen-activated protein kinase (MAPK) pathways play distinct roles in the lens. However, the expression patterns and activity levels of various components for these pathways have not been well-documented in vertebrate lenses, especially human lens. In the present study, the expressions and activities of extracellular signal-regulated kinase (ERK)-1/2/3, c-Jun NH2-terminal kinase (JNK)-1/2, p38 kinase, mitogen-activated protein kinase kinase (MEK)-1/2, and RAF1 were recorded in human, bovine, and rat lenses. METHODS: Human, bovine, and rat lenses were isolated from intact eyes. The epithelia and different layers of fiber cells were isolated from these lenses. Total proteins extracted from these samples were subject to analysis of the expression patterns and activity levels of the MAPKs and the activating kinases of ERK1/2. RESULTS: ERK1 and ERK2 were the most abundant MAPKs in terms of both protein and activity levels in all lenses. JNK1 and JNK2 were highly expressed in bovine lens, which differed from the pattern shared by human and rat lenses. p38 kinase was similarly expressed in bovine and rat lenses, but different from that in human lens. However, p38 kinase activity was exclusively detected in the epithelia. All lenses had MEK1/2 activity in their epithelia but the expression patterns of MEK1 and MEK2 differed in these lenses. RAF1 was expressed in the epithelia of all lenses, but its activity was detected only in rat lens. CONCLUSIONS: ERK1 and ERK2 are the most abundant MAPKs in the ocular lens, providing the basis for their multiple functions in lens development and pathogenesis. The dominant epithelial distribution of JNK1/2 and p38 kinase suggests that the lens epithelium is a major site for stress response. ERK1, p38 kinase, and PKCalpha can be used as molecular markers for aging.