ObjectiveTo explore the effects of Bushen Tiaojing Formula （补肾调经方） on the quality of early embryos in repeated controlled ovarian stimulation （COS） and its possible mechanism. MethodsA total of 150 ICR female mice were divided into a normal group， a model group， an inhibitor group， a low-dose and a high-dose Bushen Tiaojing Formula group. Mice in the normal group， inhibitor group and model group were gavaged with distilled water 0.25 ml a day， and mice in the low- and high-dose groups were given 25.6 and 51.2 g/（kg·d） of Bushen Tiaojing Formula， respectively. All groups were gavaged once a day for 13 days as a cycle. Mice in the normal group were injected intraperitoneally with 0.1 ml normal saline on the 11th day of gavage， while mice in the other four groups were used to establish COS models. The inhibitor group was injected with the endoplasmic reticulum stress inhibitor 4-phenylbutyric acid 0.2 ml one hour before modelling. All groups were injected by gavage and intraperitoneal injection for 3 consecutive cycles， with an interval of 4 days between cycles. Immediately after the third intraperitoneal injection， mice were grouped with male mice of the same strain in a ratio of 2∶1， and at 8AM of the second day， the mice were examined， and those with spermatozoa or spermatozoa in the vaginal smears were recorded as pregnant. The mice were executed in the afternoon of the 4th day of pregnancy， and the blastocysts were obtained under an inverted microscope. The morphology of the blastocysts was observed， and the total number of blastocysts and the number of high-quality blastocysts were recorded to calculate the rate of high-quality blastocysts； the apoptosis of blastocyst cells was detected by the Tunel method， and the apoptosis rate was calculated； the endoplasmic reticulum molecular chaperone protein glucose-regulated protein 78 （GRP78）， C/EBP homologous protein （CHOP）， B-lymphoblastoma 2 （Bcl-2）， Bcl-2-associated X protein （Bax）， cystathionin 3 （Caspase-3） and cystathionin 12 （Caspase-12） protein levels and their mRNA expression were detected by immunofluorescent assay and RT-qPCR assay， respectively. ResultsIn the normal group， blastocysts had regular morphology， good morphological development and low fragmentation rate； in the model group， blastocysts were poorly developed， cell morphology was irregular， fragmentation rate was high， and there was some stagnation； in the inhibitor group and high-dose， low-dose Bushen Tiaojing Formula groups， cell morphology could be seen to be better developed， with regular morphology and less fragmentation rate. Compared with the normal group， the rate of high-quality blastocysts in the model group reduced， the rate of apoptosis of blastocyst cells increased， the levels of GRP78， CHOP， Caspase-12， Caspase-3， Bax protein and its mRNA expression in blastocysts increased， while the level of Bcl-2 protein and its mRNA reduced （P＜0.01）. Compared with the model group， the rate of high-quality blastocysts increased， the rate of apoptosis of blastocysts decreased， the levels of GRP78， CHOP， Caspase-12， Caspase-3， Bax protein and their mRNA expression decreased， and the levels of Bcl-2 protein and its mRNA expression increased in the blastocysts in the inhibitor group and the high-dose and low-dose Bushen Tiaojing Formula groups （P＜0.01）. Compared with the inhibitor group， GRP78， CHOP， Caspase-12， Bax protein levels and their mRNA expressions increased in the high-dose Bushen Tiaojing Formula group， and Caspase-12， Caspase-3， Bax protein levels and their mRNA expressions increased in the low-dose formula group （P＜0.05 or P＜0.01）. ConclusionBushen Tiaojing Formula can inhibit the apoptosis of blastocyst cells caused by repeated controlled ovarian stimulation by improving endoplasmic reticulum stress， which plays a role in improving the quality of early embryos.

Threatened abortion is a common disease of obstetrics and gynecology and one of the diseases responding specifically to traditional Chinese medicine （TCM）. The China Association of Chinese Medicine organized experts in TCM obstetrics and gynecology， Western medicine obstetrics and gynecology， and pharmacology to deeply discuss the advantages of TCM and integrated Chinese and Western medicine treatment as well as the medication plans for threatened abortion. After discussion， the experts concluded that chromosome， endocrine， and immune abnormalities were the key factors for the occurrence of threatened abortion， and the Qi and blood disorders in thoroughfare and conception vessels were the core pathogenesis. In the treatment of threatened abortion， TCM has advantages in preventing miscarriages， alleviating clinical symptoms and TCM syndromes， relieving anxiety， regulating reproductive endocrine and immune abnormalities， personalized and diversified treatment， enhancing efficiency and reducing toxicity， and preventing the disease before occurrence. The difficulty in diagnosis and treatment of threatened abortion with traditional Chinese and Western medicine lies in identifying the predictors of abortion caused by maternal factors and the treatment of thrombophilia. Recurrent abortion is the breakthrough point of treatment with integrated traditional Chinese and Western medicine. It is urgent to carry out high-quality evidence-based medicine research in the future to improve the modern diagnosis and treatment of threatened abortion with TCM.

It is believed that the pathogenesis of white lesions on the vulva lies in liver and kidney dysharmony， and the principle of regulating liver and kidney is recommended， with a combination of internal and external treatment， and using multiple methods. Clinically， it is differentiated into deficiency and excess. For deficient patients， liver-kidney yin deficiency is most common， for which self-prepared Zidi Yanghu Decoction （紫地养户汤）is used for internal treatment to nourish the kidney and liver， invigorate blood and dispel wind； self-made Shougui Xiyang Formula （首归息痒方） for fumigation， washing and sitz bath is used as external treatment to supplement and invigorate blood， dispel wind and relieve itching. Damp-heat in the liver channel is the most common excess syndrome， for which the internal treatment is self-made Xiaoyao Xiegan Decoction （逍遥泻肝汤） to clear the liver and drain dampness， unblock collaterals and relive itching， and the external treatment is self-made Kubai Zhiyang Formula （苦柏止痒方） for fumigation， washing and sitz bath in order to clear heat， drain dampness and relieve itching. If there is accompanied local hypopigmentation， obvious itching， painful ulcers， or scratching due to itching， self-made Zima Yukui Oil （紫麻愈溃油） is often applied topically to eliminate macules and engender flesh.

Objective: To provide high-quality clinical evidence of the efficacy of Tibetan medicine Honghua Ruyi (HHRY) pills for endometriosis-associated dysmenorrhea. Methods: This study constitutes a multicenter, randomized, double-blind, placebo-controlled trial encompassing a three-menstrual cycle intervention followed by a three-menstrual cycle follow-up period. A total of 164 eligible females with endometriosis-associated dysmenorrhea were randomly divided into HHRY pills and placebo groups in a 1:1 ratio. The primary outcome included dysmenorrhea symptoms assessed using Visual Analog Scale (VAS) scores and quality of life, whereas the secondary outcome measures included the maximum VAS for non-menstrual pelvic pain, duration of pain episodes (in days), frequency and quantity of the consumption of ibuprofen sustained-release capsules (or other non-steroidal anti-inflammatory drugs), and days off work/study for staff/student due to dysmenorrhea, ovarian cyst, and/or pelvic nodule size. The safety was monitored throughout the treatment period. All the analyses were based on the intention-to-treat principle. For continuous outcomes, simple or multiple linear regressions were used to estimate the differences between the HHRY pills and placebo groups, with categorical data expressed as the number and percentage of occurrences. Differences were compared using the chi-square test or Fisher's exact test. The predefined analysis was adjusted for concomitant treatment, a variable considered to be associated with outcomes but unaffected by treatment allocation. Estimates of treatment effects were reported with 95% confidence intervals. Two-tailed P values ≤ .05 were considered statistically significant. Conclusion Positive results from this trial, upon completion would provide robust evidence for the efficacy and safety of HHRY pills in treating dysmenorrhea in patients with endometriosis.

ObjectiveTo explore the possible mechanisms of Shoutai Wan （寿胎丸） in treating recurrent miscarriage （RSA） from the perspective of immune tolerance under the acidic microenvironment at the maternal-fetal interface. MethodsFemale CBA/J mice were randomly divided into normal group， model group， progesterone group， and Shoutai Wan group， with 15 mice in each group. The mice in the normal group and model group were given 0.2 ml distilled water by gavage each day， the Shoutai Wan group given Shoutai Wan decoction 0.15 g/（10 g·d） by gavage， the progesterone group given progesterone tablets 0.44 mg/（10 g·d） by gavage. After gavage for 14 days， the mice were cohabited. Female CBA/J mice in the normal group were mated with male BALB/c mice at a ratio of 2∶1， and female CBA/J mice in the other groups were mated with male DBA/2 mice at a ratio of 2∶1 to establish the RSA mouse model. Vaginal smears were taken from the female mice the next morning， and the appearance of a large number of spermatozoa and the presence of a vaginal plug were considered as the first day of pregnancy. After the appearance of the plug， the mice were continued to be administered according to the previous method until the 10th day of pregnancy. On the 10th day of pregnancy， maternal-fetal interface tissues were collected from each group of mice， and lactate dehydrogenase colorimetric method was used to detect lactate （LA） content； qPCR method and Western blot method were used to detect the expression of immune-related factors interleukin-4 （IL-4）， interferon-gamma （IFN-γ）， transforming growth factor beta 1 （TGF-β1）， and forkhead box protein 3 （Foxp3） mRNA and protein； flow cytometry was used to detect the numbers of helper T lymphocyte 1 （Th1）， helper T lymphocyte 2 （Th2）， regulatory T cell （Treg）， classical macrophage （M1）， and alternative macrophage （M2）. The bivariate Pearson test was used to analyze the correlation between LA content and the numbers of Th1， Th2， Treg， M1， and M2 cells， as well as the correlation between LA content and the expression of IL-4， IFN-γ， TGF-β1， Foxp3 protein， and mRNA. ResultsOn the 10th day of pregnancy， compared with the normal group， the LA content decreased in the model group， and the expression of IL-4， TGF-β1， Foxp3 protein and mRNA in the maternal-fetal interface tissues decreased， while the expression of IFN-γ protein and mRNA increased. The numbers of Th1 and M1 cells increased， while the numbers of Th2， Treg， and M2 cells decreased （P＜0.05 or P＜0.01）. Compared with the model group， the LA content increased in the Shoutai Wan group and progesterone group. The expression of IL-4， TGF-β1， Foxp3 protein and mRNA in the maternal-fetal interface tissues increased， while the expression of IFN-γ protein and mRNA decreased. The numbers of Th1 and M1 cells decreased， while the numbers of Th2， Treg， and M2 cells increased （P＜0.05 or P＜0.01）. The LA content was positively correlated with the numbers of Th2， Treg， and M2 cells， and the expression of IL-4， TGF-β1， Foxp3 protein， and mRNA （P＜0.05 or P＜0.01）； the LA content was negatively correlated with the numbers of Th1， M1 cells， and the expression of IFN-γ protein and mRNA （P＜0.05 or P＜0.01）. ConclusionShoutai Wan may improve immune tolerance by regulating the expression of immune-related factors in the acidic microenvironment at the maternal-fetal interface of RSA model mice， thereby exerting its role in preventing miscarriage.

At present, the success rate of embryo implantation is 30%-40%, of which 50%-75% of pregnancy failure originates from abnormal embryo implantation. Embryo implantation is a key link in the establishment of normal pregnancy. The main causes of embryo implantation failure are the damage of endometrial receptivity and the failure of endometrial stromal decidualization. Embryo implantation involves a range of signaling molecules and cytokines, and many studies have shown that connexin proteins are involved in the regulation of embryo implantation and endometrial decidualization. This article reviews the role of connexin in endometrial receptivity, decidualization, vascular remodeling, implantation and its regulatory mechanism, in order to provide theoretical basis for the treatment of infertility and repeated implantation failure patients, and provide new research targets for drug development.

In recent years, the rapid development of assisted reproductive technology has brought good news to infertility patients, but the current success rate of embryo implantation is low. The studies have confirmed that about 50% to 75% of pregnancy failures are due to abnormal embryo implantation. Embryo implantation is a key link in the establishment of a normal pregnancy. Impaired uterine-embryo crosstalk is the main reason for embryo implantation failure. Many studies have confirmed that extracellular vesicles (EVs), as a new method of intercellular communication, play an important role in the process of embryo implantation and can carry drugs as a potential treatment for female infertility. This article reviewed the role of EVs in preimplantation uterine-embryo crosstalk and its regulatory mechanism, in order to provide a theoretical basis for the treatment of infertility and repeated implantation failure patients.

At present, the success rate of embryo implantation is 30%-40%, of which 50%-75% of pregnancy failure originates from abnormal embryo implantation. Embryo implantation is a key link in the establishment of normal pregnancy. The main causes of embryo implantation failure are the damage of endometrial receptivity and the failure of endometrial stromal decidualization. Embryo implantation involves a range of signaling molecules and cytokines, and many studies have shown that connexin proteins are involved in the regulation of embryo implantation and endometrial decidualization. This article reviews the role of connexin in endometrial receptivity, decidualization, vascular remodeling, implantation and its regulatory mechanism, in order to provide theoretical basis for the treatment of infertility and repeated implantation failure patients, and provide new research targets for drug development.

In recent years, the rapid development of assisted reproductive technology has brought good news to infertility patients, but the current success rate of embryo implantation is low. The studies have confirmed that about 50% to 75% of pregnancy failures are due to abnormal embryo implantation. Embryo implantation is a key link in the establishment of a normal pregnancy. Impaired uterine-embryo crosstalk is the main reason for embryo implantation failure. Many studies have confirmed that extracellular vesicles (EVs), as a new method of intercellular communication, play an important role in the process of embryo implantation and can carry drugs as a potential treatment for female infertility. This article reviewed the role of EVs in preimplantation uterine-embryo crosstalk and its regulatory mechanism, in order to provide a theoretical basis for the treatment of infertility and repeated implantation failure patients.

Oxidative stress is the imbalance between oxidation and anti-oxidation, and reactive oxygen species participate in the physiological and pathological process of reproductive system. Nuclear factor erythroid 2 related factor 2/antioxidant response element (Nrf2/ARE) is an important antioxidant stress pathway. Nrf2 can be activated into the nucleus by various factors such as reactive oxygen species and antioxidants, and combine with small Maf protein and ARE to regulate the expression of various antioxidant enzymes, thus playing an antioxidant role. Studies have shown that the Nrf2/ARE antioxidant pathway plays an important regulatory role in reproductive system diseases. In this paper, the research progress of Nrf2/ARE signaling pathway in reproductive system at home and abroad in recent years is reviewed, and the existing problems and future research directions are discussed and prospected.