Antioxidants and Fertility in Women with Ovarian Ageing: a Systematic Review and Meta-Analysis.

Ovarian ageing is a major factor for female subfertility. Multiple antioxidants have been applied in different clinical scenarios, but their effects on fertility in women with ovarian ageing are still unclear. To address this, a meta-analysis was performed to evaluate the effectiveness and safety of antioxidants on fertility in women suffering from ovarian ageing. A total of 20 randomized clinical trials (RCTs) with 2617 participants were included. The results showed that use of antioxidants not only significantly increased the number of retrieved oocytes and high-quality embryos rates but also reduced the dose of gonadotropin, contributing to higher clinical pregnancy rates. According to the subgroup analysis, with regard to different dose settings, better effects were more pronounced with lower doses; in terms of antioxidant types, Coenzyme Q10 (CoQ10) tended to be more effective than melatonin, myo-inositol and vitamins, since when compared with placebo or no treatment, CoQ10 showed more advantages, while small improvements were observed in other drugs. In addition, based on subgroup analysis of CoQ10, the optimal treatment regimen of CoQ10 for improving pregnancy rate was 30 mg/d for three months before the controlled ovarian stimulation cycle, and women with diminished ovarian reserve clearly benefited from CoQ10 treatment, especially those younger than 35 years old. Our study suggests that antioxidant is an effective and safe complementary therapy for women with ovarian ageing. Appropriate antioxidant treatment should be offered from a low dose according to patients' age and ovarian reserve. This study was registered at PROSPERO (CRD42022359529).

Yueomyces silvicola sp. nov., a novel ascomycetous yeast species unable to utilize ammonium, glutamate, and glutamine as sole nitrogen sources.

Five yeast strains isolated from tree bark and rotten wood collected in central and southwestern China, together with four Brazilian strains (three from soil and rotting wood collected in an Amazonian rainforest biome and one from Bromeliad collected in Alagoas state) and one Costa Rican strain isolated from a flower beetle, represent a new species closely related with Yueomyces sinensis in Saccharomycetaceae, as revealed by the 26S ribosomal RNA gene D1/D2 domain and the internal transcribed spacer region sequence analysis. The name Yueomyces silvicola sp. nov. is proposed for this new species with the holotype China General Microbiological Culture Collection Center 2.6469 (= Japan Collection of Microorganisms 34885). The new species exhibits a whole-genome average nucleotide identity value of 77.8% with Y. sinensis. The two Yueomyces species shared unique physiological characteristics of being unable to utilize ammonium and the majority of the amino acids, including glutamate and glutamine, as sole nitrogen sources. Among the 20 amino acids tested, only leucine and tyrosine can be utilized by the Yueomyces species. Genome sequence comparison showed that GAT1, which encodes a GATA family protein participating in transcriptional activation of nitrogen-catabolic genes in Saccharomyces cerevisiae, is absent in the Yueomyces species. However, the failure of the Yueomyces species to utilize ammonium, glutamate, and glutamine, which are generally preferred nitrogen sources for microorganisms, implies that more complicated alterations in the central nitrogen metabolism pathway might occur in the genus Yueomyces.

Membrane-bound transcription factor LRRC4 inhibits glioblastoma cell motility.

Membrane-bound transcription factors (MTFs) have been observed in many types of organisms, such as plants, animals and microorganisms. However, the routes of MTF nuclear translocation are not well understood. Here, we reported that LRRC4 is a novel MTF that translocates to the nucleus as a full-length protein via endoplasmic reticulum-Golgi transport, which is different from the previously described nuclear entry mechanism. A ChIP-seq assay showed that LRRC4 target genes were mainly involved in cell motility. We confirmed that LRRC4 bound to the enhancer element of the RAP1GAP gene to activate its transcription and inhibited glioblastoma cell movement by affecting cell contraction and polarization. Furthermore, atomic force microscopy (AFM) confirmed that LRRC4 or RAP1GAP altered cellular biophysical properties, such as the surface morphology, adhesion force and cell stiffness. Thus, we propose that LRRC4 is an MTF with a novel route of nuclear translocation. Our observations demonstrate that LRRC4-null glioblastoma led to disordered RAP1GAP gene expression, which increased cellular movement. Re-expression of LRRC4 enabled it to suppress tumors, and this is a potential for targeted treatment in glioblastoma.

Effect of Repetitive Transcranial Magnetic Stimulation in Inducing Weight Loss in Patients with Chronic Schizophrenia: A Randomized, Double-Blind Controlled 4-Week Study.

OBJECTIVES: There is emerging evidence that high-frequency (HF) repetitive transcranial magnetic stimulation (rTMS) may promote weight loss in individuals with obesity in the general population. However, no study has been conducted on patients with schizophrenia (SZ). This study evaluated the efficacy of 10Hz rTMS in reducing body weight in patients with chronic SZ. METHODS: Forty-seven SZ patients were randomly assigned to two groups: 10Hz rTMS or sham stimulation over DLPFC (applied once daily) for 20 consecutive treatments. Body weight was assessed at baseline, at the end of week 1, week 2, week 3 and week 4. Clinical symptoms were evaluated with the Positive and Negative Syndrome Scale (PANSS) at baseline and at the end of week 4. RESULTS: We found that compared with patients in the sham group, 10Hz rTMS treatment significantly reduced body weight in patients with chronic SZ after a period of 4 weeks of stimulation. Interestingly, further analysis found that from the first week (5 sessions) of treatment, there was a significant difference in body weight between active and sham groups after controlling for baseline weight. However, active rTMS treatment did not improve the psychotic symptoms compared to sham stimulation. CONCLUSION: Our results suggest that add-on HF rTMS could be an effective therapeutic strategy for body weight control in patients with chronic SZ.

Neuronavigated Repetitive Transcranial Stimulation Improves Neurocognitive Functioning in Veterans with Schizophrenia: A Possible Role of BDNF Polymorphism.

It has been reported in the previous literatures that high-frequency (HF) neuronavigated repetitive transcranial magnetic stimulation (rTMS) may improve neurocognitive functioning in patients with schizophrenia. Nonetheless, the heterogeneity of the research findings with regards to the effectiveness of HF-rTMS on the neurocognitive functioning in patients with schizophrenia greatly hinders its clinical application. The current study was designed to determine the predictive role of BDNF variants for neurocognitive improvements after rTMS administration in veterans with schizophrenia. 109 hospitalized veterans with schizophrenia were randomly allocated to active HF-rTMS (n=63) or sham stimulation (n=46) over left DLPFC for 4 consecutive weeks. Neurocognitive functions were assessed by using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) at baseline and at the end of week 4. BDNF polymorphism was genotyped by the technicians. Compared with sham stimulation sessions, the immediate memory performance was significantly increased in active sessions after neuronavigated HF-rTMS administration. In addition, patients with the CC homozygotes demonstrated greater improvement of immediate memory after rTMS treatment, while T allele carriers showed no significant improvement in immediate memory domain relative to baseline performance of immediate memory. Our findings suggest that add-on neuronavigated HF-rTMS is beneficial on immediate memory only in patients with CC homozygotes, but not in T allele carriers. This pilot study provides further evidence for BDNF as a promise biomarker in predicting the clinical response to rTMS stimulation.

Repetitive transcranial magnetic stimulation for psychiatric symptoms in long-term hospitalized veterans with schizophrenia: A randomized double-blind controlled trial.

Multiple lines of evidence demonstrate that high-frequency (HF) repetitive transcranial magnetic stimulation (rTMS) may improve clinical outcomes in patients with schizophrenia (SCZ). However, the efficacy of HF-rTMS on psychiatric symptoms remains unknown in veterans with SCZ. This study aimed to investigate whether HF-rTMS was beneficial in alleviating the clinical symptoms in veterans with SCZ. Forty-seven long-term hospitalized veterans with SCZ were randomly allocated to receive neuronavigated 10 Hz rTMS or sham stimulation over the left dorsolateral prefrontal cortex once daily for four consecutive weeks. Symptoms were assessed by using the Positive and Negative Syndrome Scale at baseline and at the end of week 4. We also collected easily available routine biochemical markers including blood sugar, lipid profiles, hormone, and blood cell counts, considering that these markers may potentially be used to predict the outcomes of rTMS treatment. We found that there was a significant interaction effect of time and group on the positive symptoms. Compared with the sham group, the positive factor score of veterans with SCZ was significantly decreased after treatment in the real rTMS group. Interestingly, the improvement of positive symptoms from baseline to 4-week follow-up was significantly associated with the whole white blood cells (WBC) counts at baseline in the real rTMS group, and baseline WBC counts were predictive of the symptom improvement after rTMS treatment. Our findings indicate that add-on 10 Hz rTMS is beneficial for clinical symptoms in veterans with SCZ. In addition, the baseline WBC counts were predictive of the outcomes after treatment. Clinical trial registration: clinicaltrials.gov, identifier NCT03774927.

Deep Sparse Autoencoder and Recursive Neural Network for EEG Emotion Recognition.

Recently, emotional electroencephalography (EEG) has been of great importance in brain-computer interfaces, and it is more urgent to realize automatic emotion recognition. The EEG signal has the disadvantages of being non-smooth, non-linear, stochastic, and susceptible to background noise. Additionally, EEG signal processing network models have the disadvantages of a large number of parameters and long training time. To address the above issues, a novel model is presented in this paper. Initially, a deep sparse autoencoder network (DSAE) was used to remove redundant information from the EEG signal and reconstruct its underlying features. Further, combining a convolutional neural network (CNN) with long short-term memory (LSTM) can extract relevant features from task-related features, mine the correlation between the 32 channels of the EEG signal, and integrate contextual information from these frames. The proposed DSAE + CNN + LSTM (DCRNN) model was experimented with on the public dataset DEAP. The classification accuracies of valence and arousal reached 76.70% and 81.43%, respectively. Meanwhile, we conducted experiments with other comparative methods to further demonstrate the effectiveness of the DCRNN method.

The effectiveness and safety of Chinese herbal medicine in infertile women with luteal phase deficiency: a systematic review and meta-analysis.

BACKGROUND: Chinese herbal medicine (CHM) has been reported to treat infertile women with luteal phase deficiency (LPD) in some clinical studies, however, the efficacy and safety of CHM for LPD are still under controversy. Here, we aim to evaluate the efficacy and safety of CHM using meta-analysis, and further compare it with conventional Western therapies (CWT) to elucidate the improvement in progestin and clinical pregnancy rates. METHODS: Eight randomized controlled trials (RCTs) involving 465 women were included in our systematic review; these RCTs compared CHM with CWT in treating LPD in infertile women. The methodological quality of the included RCTs was assessed according to the Cochrane risk-of-bias assessment criteria. The data were analyzed by Review Manager 5.3 software. We estimated the risk ratio (RR) for dichotomous data and calculated the mean difference for continuous data. RESULTS: In contrast to CWT, CHM was superior in improving clinical pregnancy rates (RR 0.19; 95% CI: 0.11-0.27; P<0.001), increasing progesterone levels in the luteal phase [mean difference (MD) 2.28; 95% CI: 1.91-2.64; P<0.001] and luteal phase estrogen (MD 9.88; 95% CI: 4.53-15.24; P=0.0003), reducing traditional Chinese medicine (TCM) syndrome scores (MD -3.06; 95% CI: -3.95 to -2.17; P<0.001), and the incidence of adverse reactions (RR 0.12; 95% CI: 0.02-0.70; P=0.02). CONCLUSIONS: Evidence from eight small studies suggested that CHM has a therapeutic effect on infertile women with luteal insufficiency. We indicated that CHM may improve the level of progesterone and estradiol in the luteal phase, and the clinical pregnancy rate, with few side effects based on the current studies. However, given the relatively small number of included studies, further studies about the higher quality of study designs, larger population and the underlying mechanism are required to elucidate the role of CHM in LPD treatment.

Ponder: Enabling Balloon-Borne Based Solar Unmanned Aerial Vehicle's Take Off Diagnosis under Little Data.

Balloon-borne based solar unmanned aerial vehicle (short for BS-UAV) has been researched prevalently due to the promising application area of near-space (i.e., 20-100 km above the ground) and the advantages of taking off. However, BS-UAV encounters serious fault in its taking off phase. The fault in taking off hinders the development of BS-UAV and causes great loss to human property. Thus, timely diagnosing the running state of BS-UAV in taking off phase is of great importance. Unfortunately, due to lack of fault data in the taking off phase, timely diagnosing the running state becomes a key challenge. In this paper, we propose Ponder to diagnose the running state of BS-UAV in the taking off phase. The key idea of Ponder is to take full advantage of existing data and complement fault data first and then diagnose current states. First, we compress existing data into a low-dimensional space. Then, we cluster the low-dimensional data into normal and outlier clusters. Third, we generate fault data with different aggression at different clusters. Finally, we diagnose fault state for each sampling at the taking off phase. With three datasets collected on real-world flying at different times, we show that Ponder outperforms existing diagnosing methods. In addition, we demonstrate Ponder's effectiveness over time. We also show the comparable overhead.

Administration of growth hormone improves endometrial function in women undergoing in vitro fertilization: a systematic review and meta-analysis.

BACKGROUND: The positive effects of growth hormone (GH) on IVF are often attributed to improvements in oocyte and embryo quality. While emerging evidence emphasizes GH-induced improvements in the endometrium, these results are controversial. OBJECTIVE AND RATIONALE: This meta-analysis aimed to evaluate whether GH administration improved endometrial function and reproductive outcomes during IVF cycles and to thus guide clinical practice. SEARCH METHODS: A literature search in the Cochrane Central Register of Controlled Trials, PubMed and Embase was performed through to 30 November 2021, without language restrictions. Randomized controlled trials (RCTs) evaluating the effects of GH on IVF outcomes were included. Risk of bias and quality of evidence (QoE) were assessed according to the Cochrane Collaboration's tool and the Grading of Recommendations Assessment, Development and Evaluation system. Odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals (CIs) were assessed by random-effects models. OUTCOMES: A total of 25 trials with 2424 women were included. Seventeen RCTs with poor responders (n = 1723) showed that GH administration significantly increased endometrial thickness (EMT) (MD = 0.38, 95% CI: 0.18-0.59; moderate QoE), which contributed to an improved live birth rate (OR = 1.67, 95% CI: 1.13-2.49; very low QoE) and clinical pregnancy rate (CPR) (OR = 1.97, 95% CI: 1.43-2.72; low QoE). Subgroup analyses showed a dose- and time-dependent relationship between GH cotreatment and IVF outcomes; the optimal recommendation for improving CPR was consistent with that for EMT, rather than for oocytes and embryos. Hence, GH might improve fertility via effects on the endometrium. Administration of GH daily from the follicular phase of previous cycle until the hCG trigger with < 5 IU/day led to a thicker endometrium and a greater chance of becoming pregnant, while 5-10 IU/day or administration from the luteal phase of the previous cycle until the hCG trigger resulted in higher oocyte and embryo quality. Poor responders might benefit from cotreatment with the GnRH agonist long protocol more than other stimulation protocols. Pooled data from four trials (n = 354) on women with a thin endometrium indicated that improved endometrial function might be critical for improving reproductive outcomes during GH treatment, as no improvements in embryo quality were found. GH administration not only increased EMT (MD = 1.48, 95% CI: 1.21-1.75; moderate QoE) but also promoted endometrial morphology (OR = 2.67, 95% CI: 1.36-5.23; low QoE) and perfusion (OR = 5.84, 95% CI: 1.30-26.17; low QoE), thereby improving the CPR (OR = 2.71, 95% CI: 1.69-4.34; P < 0.0001; low QoE). There was insufficient evidence to reach a conclusion regarding the effects of GH in normal responders (n = 80). Due to obvious improvements in the CPR, women with a thin endometrium might be the most appropriate population to benefit from GH administration. WIDER IMPLICATIONS: Improving endometrial function might be another vital mechanism by which GH improves IVF outcomes. Optimal treatment should be offered to the target population according to their personal conditions and needs. The QoE was moderate to very low, due to limited sample sizes and methodological problems; thus, the results should be interpreted with caution. More rigorous RCTs with large sample sizes are needed to confirm the effects and determine optimal GH protocols.

Dietary Modification for Reproductive Health in Women With Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis.

Objective: Diet has been reported as the first-line management of polycystic ovary syndrome (PCOS). However, the relationship between diet and fertility in PCOS is still controversial. This meta-analysis aimed to evaluate whether diet could promote reproductive health in women with PCOS while providing evidence-based nutrition advice for clinical practice. Methods: Seven databases, including Cochrane Central Register of Controlled Trials, PubMed, Embase, Web of Science, and some Chinese database, were searched up to January 31, 2021. Randomized controlled trials evaluating the effects of diet in women with PCOS were included. Based on a preregistered protocol (PROSPERO CRD42019140454), the systematic review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Two reviewers made study selection, data extraction and bias assessment independently. Risk ratios and mean difference with 95% confidence intervals were assessed by a random-effects model. Statistical heterogeneity within comparisons was evaluated by Cochran's Q test and quantified by the I-squared (I2 ) statistic. Results: Twenty RCTs with 1113 participants were included. Results showed diet significantly related to improved fertility outcomes (increasing clinical pregnancy, ovulation and menstrual regularity rate; reducing miscarriage rate), reproductive endocrine [increasing sex hormone-binding globulin (SHBG); decreasing Anti-Müllerian Hormone (AMH), free androgen index (FAI), total testosterone (T)] and clinical hyperandrogenism (hirsutism assessed by Ferriman-Gallwey score) in PCOS. Specifically, subgroup analyses indicated low-carbohydrate diets were superior in optimizing reproductive outcomes and calorie restriction was critical in ameliorating hyperandrogenism. Additionally, the positive effects were associated with the treatment duration. The longer the duration, the greater the improvement was. Conclusion: Overall, diet is an effective intervention for improving fertility health, thus professional and dynamic dietary advice should be offered to all PCOS patients, based on the changeable circumstances, personal needs and expectations of the individuals.

Genetic polymorphisms of BDNF on cognitive functions in drug-naive first episode patients with schizophrenia.

Brain-derived neurotrophic factor (BDNF) is reported to be involved in cognitive decline in patients with schizophrenia (SZ). Previous studies have found that cognitive deficits remain stable during the chronic disease phase in SZ, but the findings were inconsistent. The role of BDNF in cognitive deficits at different stage of illness remains unclear. This study aimed to examine the effect of BDNF polymorphisms on cognitive deficits in drug-naïve first-episode (DNFE) patients and chronic patients with SZ. 262 DNFE patients, 844 chronic patients, and 1043 healthy controls were recruited to compare 4 polymorphisms in BDNF gene and cognitive function. We found that there was no significant difference in genotype and allele frequencies between SZ patients and controls. However, they were closely related to cognitive functioning. BDNF rs2030324 polymorphism played a strong role in language performance only in DNFE patients with SZ. The language index of DNFE patients with rs2030324 TT and TC genotypes was worse than that of chronic patients, but there was no significant difference in CC genotypes between DNFE and chronic patients. Rs6265 had no significant effect on cognitive functioning in patients and controls. Our result suggests BDNF gene polymorphisms were related to different domains of cognitive function at the different stage of SZ, especially language in DNFE patients.

Bu-Shen-Zhu-Yun decoction induces PRLR deubiquitination and JAK2/STAT5 activation via CSN5 in vitro.

PURPOSE: To determine the effect of Bu-Shen-Zhu-Yun Decoction (BSZY-D) on the kisspeptin through JAK2/STAT5 signaling pathway in hyperprolactinemia (HPRL) infertility. METHOD: SD rats were treated with BSZY-D for cerebrospinal fluid (CSF) extraction. GT1-7 cells were subjected to different treatments. The phosphorylation levels of JAK2 and STAT5, and the expressions of PRLR and kisspeptin of GT1-7 cells in different groups were detected by western blot, RT-qPCR and immunofluorescence. The expressions of CSN5 and GATA1 and other molecular features were checked by western blot, RT-PCR, co-immunoprecipitation and renilla luciferase activity. RESULTS: The phosphorylation levels of JAK2 and STAT5, and the expressions of PRLR and kisspeptin in the HPRL group were significantly decreased, and these changes could be reversed after BSZY-D treatment. In addition, the presence of PRLR deubiquitination was detected in the HPRL group, which could be reversed by shRNA-CSN5, suggesting that BSZY-D played a role through targeting CSN5. The binding level of GATA1 and CSN5 promoter in the HPRL group was significantly decreased, but elevated in the HPRL (BSZY-D/CSF) group (P < 0.05). CONCLUSION: BSZY-D improved the transcription activity of GATA1 and increased the binding of GATA1 and CSN5. BSZY-D was involved in the deubiquitination of PRLR, which contributes to alleviating the symptoms of HPRL infertility.

Network Pharmacology-Based Prediction of Bioactive Compounds and Potential Targets of Wenjing Decoction for Treatment of Endometriosis.

Endometriosis is a chronic estrogen-dependent inflammatory disorder that negatively affects the quality of life in women. The Wenjing decoction (WJD) is a traditional Chinese medicine that has been shown to have a therapeutic effect on endometriosis. Our study systematically explored the mechanism of WJD against endometriosis using a network pharmacology approach. Potentially bioactive compounds of WJD and their possible targets were retrieved from the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform. The protein-protein interaction network and herbs-compounds-genes multinetwork were constructed using Cytoscape for visualization. Subsequently, the signaling pathways of common targets were retrieved from the Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, and molecular docking was performed using PyRx software. In total, 48 common targets were screened, such as IL6 and ESR1, which were related to inflammation and the endocrine system. The top five bioactive compounds were quercetin, kaempferol, wogonin, beta-sitosterol, and stigmasterol. KEGG enrichment analysis revealed 65 pathways containing inflammatory- and endocrine-related signaling pathways, such as the "TNF signaling pathway" and the "estrogen signaling pathway." Taken together, the results of our network pharmacology analysis predicted that certain active ingredients of WJD might treat endometriosis by regulating inflammation and/or endocrine, which provided references for further understanding and exploration of WJD on endometriosis.

Effect of Diet on Insulin Resistance in Polycystic Ovary Syndrome.

OBJECTIVE: The effect of diet on insulin resistance (IR) in polycystic ovary syndrome (PCOS) is controversial. Thus, we conducted this systematic review and meta-analysis to evaluate whether diet could reduce IR in women with PCOS while providing optimal and precise nutrition advice for clinical practice. DESIGN: The search was conducted in 8 databases through June 30, 2019. The systematic review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. A random-effects model was adopted to calculate the overall effects. RESULTS: A total of 19 trials (1193 participants) were included. The analysis showed that diet was significantly related to improvements in IR and body composition (eg, homeostasis model assessment of insulin resistance, fasting insulin, fasting plasma glucose, body mass index [BMI], weight, and waist circumference) in PCOS patients. The Dietary Approaches to Stop Hypertension diet and calorie-restricted diets might be the optimal choices for reducing IR and improving body composition, respectively, in the PCOS population. Additionally, the effects were associated with the course of treatment. The longer the duration, the greater the improvement was. Compared with metformin, diet was also advantageous for weight loss (including BMI and weight) and had the same effects on insulin regulation. CONCLUSION: Overall, our findings suggest that diet is an effective, acceptable and safe intervention for relieving IR, and professional dietary advice should be offered to all PCOS patients.

Chinese herbal medicines for the treatment of non-structural abnormal uterine bleeding in perimenopause: A systematic review and a meta-analysis.

OBJECTIVE: Chinese herbal medicines (CHM) have been the mainstream therapy in Asia for thousands of years and become more popular as the alternative treatment recently. The objective of this study is to evaluate the efficacy and safety of CHM for non-structural abnormal uterine bleeding (AUB) in perimenopause. METHODS: Seven databases were searched from inception to December 31 st, 2017. Randomized controlled trials (RCTs) which compared CHM versus western therapy in treating non-structural AUB in perimenopause were extracted. The primary outcome measures were hemostasis rate, normalization rate of menstruation, hemoglobin count, and improvement of menopausal symptoms. The secondary outcome measures were adverse effects and recurrence rate. The methodological quality of included trials was assessed in line with the criteria of the Cochrane Risk of Bias assessment tool. Data analyses were performed by Review Manager 5.3 software. The results were expressed as risk ratio (RR) or mean difference (MD) with a 95% confidence interval (CI). RESULTS: Fifteen RCTs with 1344 participants were analyzed. Compared with Western therapies, CHM showed advantages in normalization rate of menstruation (RR 1.20; 95% CI 1.06-1.34;P = 0.003), improving menopausal symptoms (RR 1.20, 95% CI 1.10-1.31, P <0.0001; MD -2.80, 95% CI -3.35 to -2.25, P <0.00001) and the hemoglobin count (MD 7.85, 95% CI 4.05-11.65, P <0.0001) with lower incidence of adverse reactions (RR 0.23, 95% CI 0.12 to 0.43, P <0.00001) and lower recurrence rate (RR 0.38, 95% CI 0.26 to 0.54, P <0.00001). However, we found insufficient evidence that CHM was any more or less effective than CWT for hemostasis rate (RR 1.02, 95% CI 0.95-1.10, P = 0.62). CONCLUSIONS: The findings of our study suggest that CHM may be the effective, acceptable and safe treatment for non-structural abnormal uterine bleeding during perimenopause when compared with Western medicine. However, due to high clinical heterogeneity, low methodological quality and without a proper placebo control, the conclusion is inconclusive and limited, and it should be further examined and updated in future work.

Increasing thermal stability of glutamate decarboxylase from Escherichia. coli by site-directed saturation mutagenesis and its application in GABA production.

Gamma-amino butyric acid (GABA) is an important bio-product used in pharmaceuticals, functional foods, and a precursor of the biodegradable plastic polyamide 4 (Nylon 4). Glutamate decarboxylase B (GadB) from Escherichia. coli is a highly active biocatalyst that can convert l-glutamate to GABA. However, its practical application is limited by the poor thermostability and only active under acidic conditions of GadB. In this study, we performed site-directed saturation mutagenesis of the N-terminal residues of GadB from Escherichia coli to improve its thermostability. A triple mutant (M6, Gln5Ile/Val6Asp/Thr7Gln) showed higher thermostability, with a 5.6 times (560%) increase in half-life value at 45 °C, 8.7 °C rise in melting temperature (Tm) and a 14.3 °C rise in the temperature at which 50% of the initial activity remained after 15 min incubation (T1550), compared to wild-type enzyme. Protein 3D structure analysis showed that the induced new hydrogen bonds in the same polypeptide chain or between polypeptide chains in E. coli GadB homo-hexamer may be responsible for the improved thermostability. Increased thermostability contributed to increased GABA conversion ability. After 12 h conversion of 3 mol/L l-glutamate, GABA produced and mole conversion rate catalyzed by M6 whole cells was 297 g/L and 95%, respectively, while those by wild-type GAD was 273.5 g/L and 86.2%, respectively.