Clinical efficacy of acupuncture combined with Chinese herbal medication for recurrent implantation failure infertility of kidney deficiency and blood stasis and its effects on serum p38MAPK and JAK/STAT protein expression. / é’ˆè¯ç»“åˆæ²»ç–—è‚¾è™šè¡€ç˜€åž‹åå¤ç§æ¤å¤±è´¥ä¸å­•çš„ä¸´åºŠç–—æ•ˆåŠå¯¹è¡€æ¸ p38MAPK、JAK/STAT蛋白表达的影响.

OBJECTIVES: To observe the effects of acupuncture combined with Chinese herbal medication on pregnancy outcomes in patients with recurrent implantation failure (RIF) infertility of kidney deficiency and blood stasis, and to explore its effects on the protein expression of serum p38MAPK and JAK/STAT. METHODS: Sixty-two patients with RIF infertility of kidney deficiency and blood stasis who were scheduled for artificial cycle frozen-thawed embryo transfer were randomly divided into an observation group (31 cases, 4 cases dropped out) and a control group (31 cases, 3 cases were eliminated). The patients in the control group were treated with conventional artificial cycle frozen-thawed embryo transfer. On the basis of the control group, the patients in the observation group were treated with acupuncture combined with Chinese herbal medication. Acupuncture was applied at Baihui (GV 20), Guanyuan (CV 4) and bilateral Neiguan (PC 6), Zigong (EX-CA 1), Guilai (ST 29), Zusanli (ST 36), Taichong (LR 3), Shenshu (BL 23), Ciliao (BL 32), with each session lasting for 30 minutes, once every other day. Chinese herbal medication was administered to Bushen Huoxue (tonifing the kidney and activating blood circulation) decoction, with one dose per day, starting from the 3rd to 5th day of the menstrual cycle and continuing until 1 day before embryo transfer. Clinical pregnancy rate, embryo implantation rate, live birth rate, and biochemical pregnancy rate were compared between the two groups. TCM symptom score, platelet count (PLT), and plasma D-dimer level were assessed before treatment and 1 day before embryo transfer. Western blot method was used to detect the expression of serum P38MAPK, JAK, and STAT proteins before treatment and 1 day before embryo transfer. RESULTS: In the observation group, the clinical pregnancy rate, embryo implantation rate, and live birth rate were higher (P<0.05), while the biochemical pregnancy rate was lower (P<0.05) than those in the control group. One day before embryo transfer, both groups showed a decrease in TCM symptom scores, PLT, and plasma D-dimer levels compared to those before treatment (P<0.05), and the observation group had lower TCM symptom scores and plasma D-dimer levels than the control group (P<0.05). One day before embryo transfer, the expression levels of serum p38MAPK, JAK, and STAT proteins in both groups were lower than those before treatment (P<0.05), and the observation group had lower serum p38MAPK protein expression than the control group (P<0.05). CONCLUSIONS: Acupuncture combined with Chinese herbal medication can improve the clinical pregnancy rate, embryo implantation rate, live birth rate, and reduce the biochemical pregnancy rate in RIF infertility patients of kidney deficiency and blood stasis. Its mechanism of action may be related to down-regulating plasma D-dimer level and protein expression of serum p38MAPK.

[Clinical study on the effect of acupuncture on pregnancy outcome in patients with prethrombotic infertility after repeated implantation failure].

OBJECTIVE: To observe the effect of acupuncture combined with medication on the pregnancy outcome of kidney deficiency and blood stasis type recurrent implantation failure (RIF) in prethrombotic infertility patients. METHODS: A total of 70 RIF patients of kidney deficiency and blood stasis type who were to undergo freeze-thaw embryo transplantation were randomly divided into control and treatment groups, with 35 cases in each group. Patients in the control group were given the basic treatment of artificial periodic freeze-thaw embryo transfer and oral aspirin enteric-coated tablet, 25 mg each time, twice a day, for 3 consecutive menstrual cycles. Patients in the treatment group were treated with acupuncture on the basis of the control group, 30 min each time, 3 times a week, for 3 consecutive menstrual cycles. The clinical pregnancy rate, embryo implantation rate and live birth rate of the two groups were compared. Before treatment and 1 day before transplantation, the scores of kidney deficiency and blood stasis symptom were compared. The blood flow pulse index (PI) and resistance index (RI) of the uterus spiral artery were detected by Doppler ultrasound before treatment and 1 day before transplantation. The endometrial thickness was detected 1 day before transplantation. The contents of plasma D-dimer, serum homocysteine (Hcy) and serum thromboxane B2 (TXB2) were detected. RESULTS: The clinical pregnancy rate, embryo implantation rate and live birth rate in the treatment group were higher than those in the control group (P<0.05). After treatment, the scores of kidney deficiency and blood stasis symptom, the levels of plasma D-dimer, serum Hcy and TXB2, the PI and RI value in both groups were decreased (P<0.05) compared with those before treatment, and the indexes in the treatment group were decreased (P<0.05) more than those in the control group. There was no significant difference in endometrial thickness between the two groups. In the course of treatments, 7 patients in the control group underwent gastric distension pain, poor appetite, constipation, nausea and other gastrointestinal reactions, while only 2 patients in the treatment group had the above discomfort reactions. CONCLUSION: On the basis of medication, acupuncture can reduce the serum TXB2 content in RIF patients in prethrombotic state, improve vascular endothelial function, enhance endometrial tolerance, alleviate the symptoms of kidney deficiency and blood stasis, reduce drug adverse reactions, and ultimately improve the pregnancy outcome and increase the rate of embryo implantation.

[Effects of auricular thumbtack needle on lactation function and TDP-43/Btn1A1/XDH pathway in primiparous women with cesarean section].

OBJECTIVE: To observe the effects of auricular thumbtack needle on breast feeding and lactation function in primiparous women with cesarean section, and to explore its mechanism of action from the perspective of lactation-related gene expression. METHODS: One hundred cases of primiparous women with cesarean section were randomly divided into an observation group (50 cases, 3 cases dropped off) and a control group (50 cases, 2 cases were eliminated). The patients in the control group were treated with routine obstetric care. Based on the treatment of the control group, the patients in the observation group were treated with auricular thumbtack needle at Neifenmi (CO18), Xiong (AH10), Xiongzhui (AH11), Shenmen (TF4), and Jiaogan (AH6a), etc., with one side of auricular point selected, only once for a total of 3 d. The lactation initiation time, lactation adequacy rate at postpartum 72 h, exclusive breastfeeding rate at postpartum 42 d, and breastfeeding score after treatment were compared between the two groups. Real-time quantitative PCR and Western blot method were used to detect the mRNA and protein expression levels of TDP-43, Btn1A1 and XDH. RESULTS: After treatment, the lactation initiation time in the observation group was earlier than that in the control group (P<0.01), and breastfeeding score in the observation group was higher than that in the control group (P<0.01). The lactation adequacy rate at postpartum 72 h was 63.8% (30/47) in the observation group, which was higher than 41.7% (20/48) in the control group (P<0.05). The exclusive breastfeeding rate at postpartum 42 d was 72.3% (34/47) in the observation group, which was higher than 47.9% (23/48) in the control group (P<0.05). The mRNA and protein expression levels of TDP-43 and Btn1A1 in breast milk in the observation group were higher than those in the control group (P<0.01), while there was no statistically significant difference in mRNA and protein expression of XDH in breast milk between the two groups (P>0.05). CONCLUSION: The auricular thumbtack needle in addition to routine care could promote lactation initiation, improve lactation adequacy rate and exclusive breastfeeding rate in primiparous women with cesarean section, and the action mechanism may be related to up-regulation of TDP-43 and Btn1A1 expression.

Association between heavy metals exposure and infertility among American women aged 20-44 years: A cross-sectional analysis from 2013 to 2018 NHANES data.

Background: Infertility has been confirmed as a significant medical and social problem. Heavy metal exposure refers to a risk factor for infertility, which is capable of damaging the reproductive system of males and females. However, heavy metal exposure and female infertility have rarely been investigated. The aim of this study was to analyze the association between heavy metal exposure and female infertility. Methods: A cross-sectional study using data from three cycles of the National Health and Nutrition Examination Survey (NHANES, 2013-2018) was performed. Female infertility was evaluated by positive responses to question rhq074 in the questionnaire. Cadmium (Cd), lead (Pb), mercury (Hg), and arsenic (As) levels in blood or urine were examined by inductively coupled plasma mass spectrometry. The correlation between heavy metal and female infertility was analyzed through weighted logistic regression. Results: A total of 838 American women aged 20-44 years were covered in the study. Among all participants, 112 (13.37%) women were subjected to infertility. Urinary Cd and urinary As levels were significantly higher in infertile women than in control women (P < 0.05, P < 0.05). Urinary As showed a positive correlation with the prevalence of female infertility, and the risk of infertility rose with the increase of urinary As levels (P for trend = 0.045). Urinary Cd was associated with female infertility in some weighted logistic regression (Crude, Q2: OR = 3.99, 95% CI 1.82, 8.74, Q3: OR = 2.90, 95% CI 1.42, 5.92. Model 1, Q2: OR = 3.68, 95% CI 1.64, 8.27, Q3: OR = 2.33, 95% CI 1.13, 4.48. Model 2, Q2: OR = 4.11, 95% CI 1.63, 10.07, Q3: OR = 2.44, 95% CI 1.07, 5.53. Model 3, Q2: OR = 3.77, 95% CI 1.52, 9.35). Moreover, blood Pb (OR = 1.52, 95% CI 1.07, 2.16), urinary Pb (OR = 1.68, 95% CI 1.11, 2.55), and urinary As (OR = 1.02, 95% CI 1.00, 1.03) were positively correlated with the risk of infertility in women aged 35-44 years. The blood Pb (OR = 1.67, 95% CI 1.16, 2.40, 2.49) and urinary Pb (OR = 1.54, 95% CI 1.00, 2.38) in women with BMI ≥25 were positively correlated with the risk of infertility. Conclusions: Urinary As was significantly associated with female infertility, and the risk of infertility increased with higher urinary As levels. To some extent, urinary Cd was correlated with infertility. Blood/urine Pb was related to infertility in advanced age and overweight/obese women. The results of this study need to be further validated in future prospective studies.

[Effect of acupuncture on vascular endothelial function in patients of polycystic ovary syndrome with different glucose tolerance status].

OBJECTIVE: To observe the effect of acupuncture on vascular endothelial function in patients of polycystic ovary syndrome (PCOS) with impaired glucose tolerance (IGT) and normal glucose tolerance (NGT). METHODS: A total of 140 patients with PCOS were divided into an IGT group (70 cases, 11 dropped off) and a NGT group (70 cases, 9 cases dropped off). The patients in the two groups were treated with full-cycle acupuncture at Zhongwan (CV 12), Guanyuan (CV 4), Qihai (CV 6), Tianshu (ST 25), etc. once every other day, 3 times a week, for 3 months. Before and after treatment, TCM symptom score, insulin resistance index [including fasting plasma glucose (FPG), 2-hour blood glucose (2hPG), fasting serum insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR)] and vascular endothelial related factors [including asymmetric dimethylarginine (ADMD), endothelin-1 (ET-1), malondialdehyde (MDA), nitric oxide (NO)] were compared between the two groups; in addition, the obese subgroup and non-obese subgroup of the two groups were further compared. RESULTS: Compared before treatment, the TCM symptom scores, ADMD, ET-1 and MDA after treatment were decreased (P<0.05), and NO was increased (P<0.05) in the two groups; FPG, 2hPG, FINS and HOMA-IR after treatment were decreased in the IGT group (P<0.05), the improvement of the above indexes in the IGT group was more significant than that in the NGT group (P<0.05). After treatment, the serum levels of ADMD, ET-1 and MDA were decreased (P<0.05), and NO was increased (P<0.05) in the obese subgroup. In the IGT group, the improvement of serum ADMD, ET-1, MDA and NO in the obese subgroup was more significant than that in the non-obese subgroup (P<0.05). In the NGT group, the improvement of ET-1, MDA and NO in the obese subgroup was more significant than that in the non-obese subgroup (P<0.05). CONCLUSION: Acupuncture could improve vascular endothelial function in PCOS patients, IGT patients have better efficacy than NGT patients, and obese patients have better efficacy than non-obese patients.

Letrozole Rat Model Mimics Human Polycystic Ovarian Syndrome and Changes in Insulin Signal Pathways.

BACKGROUND The aim of this study was to explore whether letrozole and high-fat diets (HFD) can induce obese insulin-resistant polycystic ovary syndrome (PCOS) with all reproductive and metabolic phenotypes in a rat model. MATERIAL AND METHODS Twenty-four 3-week-old female Sprague-Dawley rats were randomized into 4 groups: control, Letrozole, HFD, and Letrozol+HFD. The PCOS model was induced by 12 weeks of Letrozole treatment (1 mg/kg p.o. dissolved in 0.5% CMC solutions once daily) and HFD. Ovarian morphology, estrous cyclicity, hormonal status, body weight, glucose and insulin tolerance, lipid profile, and insulin signaling pathway were investigated. RESULTS The rat model manifests anovulatory cycles and PCO morphology, increased body weight, elevated testosterone levels, abnormal glucose and lipid metabolism, and insulin resistance. The rat model also expresses significantly decreased phosphorylation of 6 essential signaling proteins - INSR, IRS, PI3K, AKT, ERK1, ERK2 - in the PI3K/AKT and MAPK/ERK pathways in the classic insulin-sensitive tissues (e.g., quadriceps femoris muscle, omentum majus, and liver), as well as non-classic target ovary tissues. Disrupted insulin signaling contributes to the decrease in insulin sensitivity and compensatory hyperinsulinemia in PCOS rats. CONCLUSIONS Continuous administration of letrozole and high-fat diets can induce PCOS, metabolic phenotypes, and disrupted activation of the insulin signaling pathway.

[Effect of combined treatment with acupuncture, moxibustion and medication on endometrial receptivity and expression of serum HOXA10 in polycystic ovary syndrome of kidney deficiency and blood stagnation].

OBJECTIVE: To compare the clinical effect of the combined treatment of acupuncture, moxibustion, Chinese herbal medicine and western medication and simple western medication on polycystic ovary syndrome (PCOS) of kidney deficiency and blood stagnation pattern and explore the effect on endometrial receptivity and the expression of serum homeobox gene A10 (HOXA10). METHODS: A total of 60 patients with PCOS of kidney deficiency and blood stagnation pattern were randomized into a combined treatment group and a western medication group, 30 cases in each one. In the western medication group, on the fifth day of menstruation, clomiphene citrate tablets were taken orally, 50 mg each time, once daily, consecutively for 5 days. On the day when the follicle diameter was ≥ 18 mm, chorionic gonadotrophin for muscular injection, a dose of 10 000 U was given. Before sleep, the aspirin enteric-coated tablets were taken orally, 50 mg (except during menstruation). In the combined treatment group, on the base of the treatment as the western medication group, acupuncture and moxibustion were adopted and the Chinese herbal for tonifying the kidney and activating blood circulation was taken orally. The acupoints were Guanyuan (CV 4), Qihai (CV 6), Zusanli (ST 36), Sanyinjiao (SP 6), Zigong (EX-CA 1), etc. Acupuncture was remained for 30 min each time, once every two days and discontinued during menstruation. Chinese herbal was given from the 3rd day of menstruation till the onset of the next menstruation, one dose each day. After consecutive treatment for 3 menstrual cycles in the two groups, the real-time polymerase chain reaction (RT-PCR) method was adopted to determine the expression of serum HOXA10 before and after treatment in the patients of the two groups. The endometrial thickness at ovulatory phase, uterine arterial flow 7 days after ovulation [including uterine arterial pulsatility index (PI), resistance index (RI), peak systolic velocity (PSV)/end diastolic velocity (EDV), meaning S/D], pregnancy rate and the score of Chinese medicine symptoms before and after treatment were compared in the patients between the two groups. RESULTS: ① After treatment, the expression of serum HOXA10 was higher than that before treatment in the patients of the two groups (P<0.01). The increase range in the combined treatment group was larger than the western medication group (P<0.01). ② After treatment, the endometrial thickness at the ovulatory phase was increased in the patients of the two groups (P<0.01). The increase range of the endometrial thickness in the combined treatment group was larger than the western medication group (P<0.01). ③ The pregnancy rate was 46.7% (14/30) in the combined treatment group, higher than 26.7% (8/30) in the western medication group (P<0.05). ④ After treatment, the bilateral uterine arterial PI, RI and S/D values, as well as TCM symptom score were all lower than those before treatment in the patients of the two groups (P<0.01). The decrease range of each index in the combined treatment group was greater than the western medication group (P<0.01, P<0.05). CONCLUSION: The combined treatment with acupuncture, moxibustion and medication effectively improves endometrial receptivity and uterine arterial flow in the patients with PCOS of kidney deficiency and blood stagnation pattern and increases pregnancy rate. The therapeutic effect is better than the simple western medication and its mechanism is probably related to the regulation of serum HOXA10 expression.

[Acupuncture and Chinese medicine of artificial cycle therapy for insulin resistance of polycystic ovary syndrome with phlegm damp type and its mechanism].

OBJECTIVE: To explore the effect difference between acupuncture combined with Chinese medicine of artificial cycle therapy on the basis of western medication and simple western medication for polycystic ovarian syndrome (PCOS) of phlegm damp type with insulin resistance, and to explore its mechanism. METHODS: Sixty patients were randomly assigned into an observation group and a control group, 30 cases in each group. Patients of the control group began to take letrozole and metformin orally on the third menstrual day. Patients of the observation group were treated with acupuncture combined with Chinese medicine of artificial cycle therapy on the basis of the treatment of the control group. The main acupoints were Guanyuan (CV 4), Qihai (CV 6) and bilateral Zigong (EX-CA 1), Luanchao (Extra), Fenglong (ST 40), Yinlingquan (SP 9), Zusanli (ST 36), Sanyinjiao (SP 6). Dahe (KI 12) was matched in the follicular phase, and warm acupuncture was applied at Guanyuan (CV 4) and Qihai (CV 6); Zhongji (CV 3) and Xuehai (SP 10) were matched in the ovulatory phase, and electroacupuncture were used at Qihai (CV 6) and Zhongji (CV 3), Xuehai (SP 10) and Yinlingquan (SP 9), 2 Hz and continuous wave; The acupoints in the luteal phase were the above main acupoints, at the same time, moxibustion was used at Guanyuan (CV 4) and Qihai (CV 6), the treatment was given once every other day, 30 min a time. There was no treatment in the menstrual phase. Chinese medicine was applied for tonifying kidney and nourishing blood, strengthening spleen and eliminating phlegm. The patients of the two groups were treated for continuous three menstrual cycles. The indexes before and after treatment were detected, including serum microRNA-29 (miR-29) expression, TCM symptom score, insulin (INS), blood-sugar content and homeostasis model assessment-insulin resistance (HOMA-IR) index, the endocrine hormone values of follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), LH/FSH ratio, prolactin (PRL). The pregnancy rates of the two groups were compared. RESULTS: After treatment the expressions of miR-29 and TCM symptom scores of the two groups were lower than those before treatment (P<0.01, P<0.05), with better results in the observation group (P<0.01, P<0.05). The levels of LH LH/FSH and T of the observation group were lower than those before treatment (P<0.01, P<0.05), and the T value in the control group decreased after treatment (P<0.05). The changes of LH and LH/FSH in the observation group were better than those in the control group (both P<0.05). After treatment, The INS, blood-sugar content and HOMA-IR were lower than those before treatment in the two groups (P<0.05, P<0.01), with better results for INS and HOMA-IR improvements in the observation group (both P<0.05). The pregnancy rate in the observation group was 56.7% (17/30), which was significantly higher than 30.0% (9/30) in the control group (P<0.05). CONCLUSION: Acupuncture combined with Chinese medicine of artificial cycle therapy can improve the endocrine levels and insulin resistance of PCOS with phlegm damp type. At the same time, the pregnancy rate is improved. By the view of molecular biology, there may be a pathway trough changing serum miR-29 expression.