Effect of exposure to second-hand smoke from husbands on biochemical hyperandrogenism, metabolic syndrome and conception rates in women with polycystic ovary syndrome undergoing ovulation induction.

STUDY QUESTION: Does second-hand smoke (SHS) exposure from husbands have adverse effects on sex hormones, metabolic profiles, clinical phenotypes and fertility outcomes in women with polycystic ovary syndrome (PCOS) undergoing ovulation induction? SUMMARY ANSWER: SHS exposure is associated with worsened biochemical hyperandrogenism, higher incidence of metabolic syndrome and reduced conception rates in women with PCOS. WHAT IS KNOWN ALREADY: Smoking in women impairs fecundity at some stages of the reproductive process including folliculogenesis, embryo transport, endometrial angiogenesis and uterine blood flow. Yet little is known about the hazard of SHS exposure in women with PCOS. STUDY DESIGN, SIZE, DURATION: This study was a secondary analysis of the Polycystic Ovary Syndrome Acupuncture and Clomiphene Trial (PCOSAct), a large randomized controlled trial conducted at 27 hospitals from 2012 to 2015 in mainland China. PARTICIPANTS/MATERIALS, SETTING, METHODS: Out of 1000 women with PCOS, SHS exposure status were available in 500 women, of whom 271 women were non-exposed and 229 exposed to cigarette smoke (170 women ≤10 cigarettes per day as low-SHS exposed and 59 women >10 cigarettes per day as high-SHS exposed). We compared circulating sex steroids, glucose and lipid metabolism, metabolic syndrome and phenotypes, fertility and obstetric outcomes between non-exposed and exposed women. MAIN RESULTS AND THE ROLE OF CHANCE: Women exposed to SHS, compared to non-exposed women, had a higher serum total testosterone (1.7 vs 1.5 nmol/L, P = 0.01), free androgen index (5.7 vs 4.0, P = 0.001) and lower sex hormone binding globulin (30.1 vs 35.6 nmol/L, P = 0.03). Metabolic syndrome, but not other phenotypes, was more frequent in exposed women as compared to non-exposed women (21.8 vs 13.3%, adjusted odds ratio (OR)=1.66; 95% CI, 1.02-2.71, P = 0.04). Ovulation rates between exposed and non-exposed groups were not significantly different (76.9 vs 82.9%, adjusted OR=0.72; 95% CI, 0.45-1.15, P = 0.17). Conception rates were significant lower in the exposed group (26.6 vs 36.9%; adjusted OR=0.61; 95% CI, 0.41-0.91; P = 0.01), while clinical pregnancy and live birth rates showed a similar trend that was not statistically significant. Gestational age, birth weight and other obstetric outcomes were not affected by SHS exposure. LIMITATIONS, REASONS FOR CAUTION: Data on SHS exposure were missing in 50% of the women. We did not assay serum nicotine or cotinine levels to quantify the SHS exposure status. WIDER IMPLICATIONS OF THE FINDINGS: These data suggest that smoking partners of infertile women with PCOS who seek treatment should be advised to quit smoking. STUDY FUNDING/COMPETING INTEREST(S): Funding was provided by the National Public Welfare Projects for Chinese Medicine (201107005 and 200807002) and the National Clinical Trial Base in Chinese Medicine Special Projects (JDZX2012036 and 2015B009). There are no conflicts of interest. TRIAL REGISTRATION NUMBER: ClinicalTrial.gov number: NCT01573858 and chictr.org.cn number: ChiCTR-TRC-12002081.

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.

[Effect of huangqin tang on the regulatory NF-κB p65 signal pathway in rats with ulcerative colitis].

To investigate the effect of huangqin tang on expression of cytokines and NF-κB p65 in rats with ulcerative colitis (UC), and to probe into its underlying mechanisms of action. The mode of UC rats with cell immunoreactivity was made using compound method (trinitrobenzene sulfonic acid and ethanol). Rats were randomly divided into control group, model group, SASP group and high dose, middle dose and low dose of huangqin tang group. The food intake, body weight and microscopic damage of rats in each group were evaluated after being treated for five days. The blood and colon tissue were also collected. Production of NO was detected by Griess assay, the expression levels of IL-6, TNF-α, PGE2 were detected by ELISA. ICH method was undertaken to determine the expression of NF-κB p65 protein in colon tissue. The food intake and body weight of model group rats were lower than that of control group. The expression levels of NO, IL-6, TNF-α, PGE2 in serum and NF-κB p65 protein of colon tissue in model group were higher than that of control group. The above indexes were ameliorated in high and middle dose of huangqin tang groups. But there was no significant difference with SASP group. NF-κB p65 may be involved in the pathogenesis of UC, and huangqin tang can inhibit the relative activity of NF-κB p65, and decrease the expression levels of NO, IL-6, TNF-α and PGE2.

[Pharmacokinetics and pharmacodynamics of huangqin tang in febrile rats].

The pharmacodynamic (PD) and pharmacokinetic (PK) properties of Huangqin Tang (HQT) were investigated in yeast-induced febrile rats. Blood sample and rectal temperature data of the rats were collected at different times after single oral administration of HQT at 20 g x kg(-1). The plasma concentrations of paeoniflorin, baicalin, wogonoside, baicalein, wogonin, oroxylin A, glycyrrhizic acid and glycyrrhetinic acid were quantified by a sensitive liquid chromatography-tandem mass spectrometric (LC-MS) method. The blood concentrations of PGE2, 1L-1ß and TNF-α were detected by radioimmunoassay (RIA). All pharmacokinetic parameters were processed by non-compartmental analysis using WinNonlin software. The potential relationship between the mean concentration of eight constituents and the antifebrile efficacy was investigated by calculating Pearson correlation coefficients. It was found that HQT had significant antifebrile efficacy in yeast-induced febrile rats, but had no effect to normal rats. The antifebrile effect of HQT can be attributed to the inhibition of PGE2, 1L-1ß and TNF-α. The constituents (baicalin, wogonoside, baicalein, wogonin, oroxylin A, glycyrrhizic acid and glycyrrhetinic acid) in febrile rats had delayed absorption and elimination, a longer residence time in the body, and higher C(max) and AUC than those in normal rats. Febrile condition could affect the pharmacokinetic behaviour of HQT in vivo; the flavonoids with the same backbone showed the similar fate in the body; baicalein and wogonin had a strong positive correlation (R > 0.66, P ≤ 0.02) with the antifebrile efficacy determined. Together, these constituents demonstrated different pharmacokinetic properties in the febrile body.

[LC-MS quantification and pharmacokinetics of the multi-constituents of Huangqin Tang in rat plasma after different single oral doses].

The current study aims to investigate the pharmacokinetic properties of Huangqin Tang on different oral doses. An LC-MS method for simultaneous determination of flavonoids and terpenoids in rat plasma was developed and validated. Plasma samples were treated with hydrochloric acid (containing 1% ascorbic acid), precipitated with acetonitrile, separated on a Zorbax SB-C18 column, detected by single quadruple mass spectrometry with an electrospray ionization interface, and quantified using selected ion monitoring mode. All pharmacokinetic parameters were processed by non-compartmental analysis using WinNonlin software. The results of specificity, linearity, intra-day and inter-day precisions, accuracy, and stability for LC-MS assay were suitable for the quantification of paeoniflorin, baicalin, wogonoside, baicalein, wogonin, oroxylin A, glycyrrhizic acid and glycyrrhetinic acid in rat plasma. The concentration-time profiles of baicalin, wogonoside, baicalein, wogonin, oroxylin A and glycyrrhizic acid showed double-peak phenomenon after Huangqin Tang was orally administered at 40 g x kg(-1) dose; all eight constituents in rat plasma showed good dose-exposure relationship within the dosage of 10-40 g x kg(-1); although plasma concentrations were different, the flavonoids with the same backbone showed the similar fate in the body with the corresponding dosage. In conclusion, the LC-MS assay was successfully applied for the pharmacokinetic study of multi-constituents of Huangqin Tang with different doses. Additionally, these constituents demonstrated good pharmacokinetic properties in the body.

[Effects and safety of varying doses of guizhi fuling capsule in patients with primary dysmenorrhea: a multi-center, randomized, double-blind, placebo-controlled clinical study].

To evaluate the effects and safety of varying doses of Guizhi Fuling capsule on treating primary dysmenorrhea. From August 2010 to March 2011, 240 subjects (aged 18-30) with primary dysmenorrheal, were enrolled in 8 sites. They were randomized into Guizhi Fuling capsule high dose group, low dose group and placebo control group, 80 cases in each group. These patients were treated for three consecutive menstrual cycles, then were followed up in another three consecutive menstrual cycles. Visual analogue scales (VAS) was used to determine the pain intensity. During the treatment, the high-, low-dose and placebo groups efficiency on pain relief are 68.42%, 67.57% and 47.89% respectively. Guzhi Fuling (included high- and low- dose group) significantly relieves the pain compared to placebo. In follow-up, Guzhi Fuling groups are still superior to the placebo group (73.68%, 72.97% and 53.52%). During the treatment, pain duration reduces 57.88% in high dose group, while 46.17% in low dose group, and 30.40% in placebo group. In follow-up, pain lasting time decrease 67.93%, 53.56%, 47.46%, respectively. Guizhi Fuling significantly reduces the pain duration compared to placebo and high-dose is better than low-dose. The efficacy of Guzhi Fuling (high- and low-dose) displays certain dosage-effect relationship. Among these group, no serious adverse event was reported. Guizhi Fuling capsule at high or low dose significantly relieves the pain, improves symptoms, reduces the duration of pain, and has a better overall treatment effect and long-term treatment effect in patients with primary dysmenorrhea.

Impact of Low Frequency Electro-acupuncture on Glucose and Lipid Metabolism in Unmarried PCOS Women: A Randomized Controlled Trial.

OBJECTIVE: To explore the effect of electro-acupuncture (EA) on glucose and lipid metabolism in unmarried patients with polycystic ovary syndrome (PCOS). METHODS: Fifty-four PCOS patients were equally randomized into true acupuncture group and sham acupuncture group (control) for totally 16 weeks of treatment by random method with a computerized randomization program. Patients in true acupuncture group accepted traditional acupuncture methods with EA and two sets of acupoint groups were used alternatively. The first set consisted of Zhongji (CV 3), Qihai (CV 6), Guilai (ST 29), Sanyinjiao (SP 6), Yinlingquan (SP 9), Hegu (LI4) and Baihui (GV 20), and the second set consisted of Tianshu (ST 25), ST 29, CV 3, CV 6, SP 6, Taichong (LR 3), Neiguan (PC) 6 and GV 20. Patients in the sham acupuncture group accepted shallow acupuncture methods through EA without electricity at 4 non-meridian points in each shoulder and upper arm. Outcome measures included body mass index (BMI), waist-hip-ratio (WHR), oral glucose tolerance test (OGTT), insulin release test, glucose and lipid metabolism indicators such as total cholesterol (TC), triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, adiponectin, leptin, visfatin, resistin, and interleukin (IL-6). RESULTS: Twenty-six subjects in the true acupuncture group and 20 subjects in the sham group completed the clinical trial. After 16 weeks of treatment, no significant difference in the outcome measures were observed between the two groups (P>0.05). However, as compared with baseline data, a reduction in weight, BMI, hipline, WHR, fasting glucose, homeostatic model assessment of insulin sensitivity, visfatin and HDL-C, and an increase in resistin and IL-6 were observed in the true acupuncture group (P<0.05). In addition, a reduction in visfatin and an increase in TC were also observed in the sham group (P<0.05). CONCLUSIONS: Acupuncture may have a beneficial effect in the treatment of PCOS by improving glucose and lipid metabolism. Moreover, the sham acupuncture may be not completely ineffective. Sham acupuncture may improve some of the aspects of the glucose and lipid metabolism of PCOS patients through a placebo effect. (Registration Nos. ChiCTR-TRC-12002529 and NCT01812161).

[Studies on effects of aluminum compounds on aluminum contents in serum and brain of mice with high performance capillary electrophoresis].

OBJECTIVE: To study the effects of alum, aluminum chloride and aluminum hydroxide on aluminum contents in serum and brain of mice with high performance capillary. METHOD: 60 days after the mice were given daily alum, aluminum chloride and aluminum hydroxide with the same aluminum content of 14.25, 57 mg x kg(-1) x d(-1), respectively, the aluminum content in serum and brain of mice were determined with high performance capillary chromatography. RESULT: The average recoveries of serum aluminum determination was 96.5%-103%. The average recoveries of brain aluminum assay was 92.2%-105.3%. Except control group, serum aluminum increased obviously. Brain aluminum increased in all the large doses groups. 2 weeks after the mice were stopped being given these drugs, serum and brain aluminum recovered to normal level, except aluminum chloride large doses group. CONCLUSION: The metabolism and excretion mechanism of aluminum in mice depends on the chemical states of the aluminum compound.

[Comparative study on antibacterial effects of huangqin-tang and its metabolites produced by intestinal flora].

OBJECTIVE: To compare the antibacterial effects of Huangqin-Tang with its metabolites produced by intestinal flora. METHOD: The antibacterial tests in vitro and in vivo were performed by agar dilution method and lethal protection of animal respectively. RESULT: Huangqin-Tang and its metabolites had antibacterial action on bacteria in vitro, however the antibacterial activity of metabolites of Huangqin-Tang on Salmomella, Dysentery bacillus and Proteus in vitro was stronger than Huangqin-Tang. The metabolites of Huangqin-Tang had protective effect on the animals infected by Staphylococcus aureus and Escherichia coli respectively from death, but Huangqin-Tang had no lethal protection action. CONCLUSION: The antibacterial effects of metabolites of Huangqin-Tang in vitro and in vivo are stronger than that of Huangqin-Tang, which shows that intestinal flora play a very important role in antibacterial effects of Huangqin-Tang.

[Pharmacodynamical research of Jingu Tongxiao granule].

OBJECTIVE: To study functions of Jingu Tongxiao granule (JGTXG, treatmenting ache of bones and muscles) in antiphlogistic and antalgic aspect, invigorating the circulation of blood and absorbing clots and antitraumatic soft tissue. METHOD: Animal models of inflammation, ache, gore and traumatic soft tissue were adopted, and pharmacodynamic actions of Jingu Tongxiao granule were observed. RESULT: JGTXG could conspicuously restrain inflammatory reactions of mouse ear tumid model treated by croton oil tumid and rat foot metatarsus tumid model treated by carrageenan, and restrain pain responses of mouse caused with whipping back end method by heat stimulating and of mouse caused with wriggling body method by acetic acid being injected in its abdominal cavity. It could significantly improve petechia degree in traumatic rat blood stasis model, and prominently improve raumatized limb's tumefaction degree and alleviate blood stasis, swelling and phlogistic cell soakage in traumatic rat soft tissue model. At the same time, it could prominently restrain platelet aggregation and improve whole blood viscosity. CONCLUSION: Jingu Tongxiao granule has antiphlogistic and antalgic functions, invigorating the circulation of blood and absorbing clots and antitraumatic soft tissue, and it could keep curative effect of original dosage form.

[A comparison of the protective activity of liver injury induced by D-galact-osamine between huangqin-tang and their metabolites by human intestinal bacteria].

OBJECTIVE: To compare the protective activity of liver injury induced by D-galactosamine (GalN) between Huangqin-Tang and their metabolites by human intestinal bacteria(HIB). METHOD: The liver injuries in conventional and pseudo-germfree mice were induced by GalN. After oral administration of Huangqin-Tang and their metabolites mixtures by HIB, the serum transaminase (ALT and AST) activities were detected. RESULT: In conventional mice, large and medium doses (20 and 10 g.kg-1) of Huangqin-Tang decoction significantly reduced the increase of serum ALT activity after 18 h GalN treatment. In pseudo-germfree mice, metabolites significantly reduced the ALT levels. However, Huangqing-Tang didn't affect the ALT levels in this kind of mice. To all of the animals, AST levels remained the same after oral Huangqin-tang or their metabolites. CONCLUSION: The metabolism by intestinal bacteria plays a role in pharmacological effects of constituents of Chinese herbal medicine. The metabolites of the constituents by intestinal bacteria were the real active components in vivo.

Metabolism of constituents in Huangqin-Tang, a prescription in traditional Chinese medicine, by human intestinal flora.

In the course of studies on the metabolism of active components of Huangqin-Tang by human intestinal flora (HIF), Huangqin-Tang and all individual herbs in the decoctions were incubated with a human fecal suspension separately. By using a high-performance liquid chromatographic (HPLC) method which was previously established in our laboratory, the metabolites in both the compound prescription and all the single herb decoctions were identified and determined both qualitatively and quantitatively. We found that the constituents of Huangqin-Tang, incluing baicalin (baicalein 7-glucuronide; BG), wogonoside (wogoninoglucuronide; WG), oroxylin-A-glucuronide (OG) from Scutellariae Radix, paeoniflorin (PF) from Paeoniae Radix, liquiritin (liquiritigenin 4'-O-glucoside; LG), isoliquirtin (isoliquiritigenin 4-glucoside; ILG) and glycyrrhizic acid (GL) from Glycyhhizea Radix, were converted to their metabolites baicalein (B), wogonin (W), oroxylin-A (O), paeonimetabolin-I (PM-I), liquiritigenin (L), isoliquiritigenin (IL) and glycyrrhetinic acid (GA) by HIF. The contents of the metabolites in Huangqin-Tang and in each single herb decoction increased significantly after incubation with intestinal flora. Comparing with single herb decoctions, the transformation of BG, WG, OG, LG and ILG in the compound prescription was promoted, however, that of PF and GL was inhibited. All the results suggested that the glycosides of many medicinal herbs could be converted to aglycones by HIF, and the metabolism of most glycosides was improved in the compound prescription.

Pharmacokinetic study on the multi-constituents of Huangqin-Tang decoction in rats.

Using a validated high-performance liquid chromatographic (HPLC) method, the pharmacokinetics of multi-constituents in Huangqin-Tang decoction were simultaneously studied both in the compound prescription and in each single herb decoction. At different intervals (0, 1, 2, 4, 8, 12, 24, 36, 48 h) after oral administration of the Huangqin-Tang decoction or a single herb decoction at a dose of 10 g x kg(-1), the concentrations of the constituents and their metabolites: baicalin (BG), wogonoside (WG), oroxylin-A-glucuronide (OG), baicalein (B), wogonin (W), oroxylin-A (O), paeoniflorin (PF), paeonimetabolin-I (PM-I), liquiritin (LG), liquiritigenin (L), glycyrrhizic acid (GL) and glycyrrhetinic acid (GA), were detected in the rat plasma. A new metabolite-3,5,7,2',6'-penta hydroxy flavone (visidulin I, VD-I) was found in rat plasma after oral administration of Huangqin-Tang or a single herb Huangqin decoction, and the quality was identified by HPLC and LC/MS. The pharmacokinetic parameters of the constituents and metabolites in the compound prescription and single herb decoctions were compared. All concentration-time curves corresponded to the one-compartment model. The constituents of BG, WG, OG, VD-I and LG had higher C(max) and AUC(0-lim) in the compound prescription than in the single herb decoction, and WG had significant difference. The constituents of PF, W and O only had a higher AUC(0-lim) in the compound prescription, and O had a significant difference. It was concluded, in brief, that there were obvious differences in the pharmacokinetic parameters of most constituents (especially constituent WG) between the compound prescription and single herb decoction. The constituents in the compound prescription had delayed absorption and elimination, a longer residence time in the body, and higher C(max) and AUC(0-lim), than those in the single herb decoction. Therefore, they were more efficient and durable, making them promising to exerting pharmacological effects in vivo.