Subcutaneous injection granulocyte colony-stimulating factor (G-CSF) is superior to intrauterine infusion on patients with recurrent implantation failure: A systematic review and network meta-analysis.

Although both subcutaneous injection and intrauterine infusion of granulocyte colony-stimulating factor (G-CSF) have been reported to improve pregnancy outcomes in patients with recurrent implantation failure (RIF), how to administer it is still no consensus. The study aimed to investigate which administration route is optimal. We searched PubMed, Embase, the Cochrane Library (CENTRAL), Web of Science, and China National Knowledge Internet (CNKI) from inception to April 10, 2023, with language in both English and Chinese. The randomized controlled trials (RCTs) compared the effectiveness of G-CSF to treat patients with RIF were included in this network meta-analysis (NMA). The odds ratio (OR) and 95% confidence interval (CI) in pregnancy outcomes (implantation rate, IR; clinical pregnancy rate, CPR; live birth rate, LBR; miscarriage rate, MR; ectopic pregnancy rate, EPR) were summarized by NMA with a random-effects model. A total of 1360 RIF patients from 14 RCTs were included in this NMA, with no publication bias and small sample effects. No direct evidence compared the effectiveness of different administration routes of G-CSF on IR, LBR and MR. Both subcutaneous injection and intrauterine infusion of G-CSF increased the IR (OR = 2.81, 95% CI: 1.10-7.24; OR = 2.15, 95% CI: 1.50-3.07, respectively) and CPR (OR = 2.79, 95% CI: 1.86-4.17; OR = 1.74, 95% CI: 1.30-2.33, respectively) in patients with RIF. According to SUCRA, subcutaneous injection is more likely to be the optimal medication administration route. However, more high-quality studies were also needed to support these, especially IR and LBR.

MiR-135a-5p regulates window of implantation by suppressing pinopodes development and decidualization of endometrial stromal cells.

PURPOSE: The window of implantation (WOI) is a brief period during which the endometrium is receptive to embryo implantation. This study investigated the relationship between miR-135a-5p and endometrial receptivity. METHODS: Peripheral blood was collected on the day of ovulation and the 5th day after ovulation for high-throughput sequencing from women who achieved clinical pregnancy through natural cycle frozen embryo transfer. RT-qPCR assessed miR-135a-5p expression in the endometrium tissue or cells during the mouse implantation window or decidualization. Scanning electron microscopy was utilized to observe pinopode morphology and quantity in mice overexpressing miR-135a-5p during the WOI. Human endometrial stromal cells (HESC) and artificial induction of mouse uterine decidualization were used to explore whether miR-135a-5p overexpression inhibits decidualization by regulating HOXA10 and BMPR2. Furthermore, the impact of miR-135a-5p on HESC proliferation and HTR8/SVneo invasion was explored. RESULTS: A total of 54 women were enrolled in the study. bioinformatics analysis and animal models demonstrated that miR-135a-5p was significantly downregulated during the WOI, and its high expression can lead to abnormal pregnancy outcomes. Overexpression of miR-135a-5p resulted in the absence of pinopode in mouse endometrial tissue during the WOI. High miR-135a-5p levels were found to potentially inhibit endometrial tissue decidualization by downregulating HOXA10 and BMPR2 expression. Finally, CEBPD was identified as a potential regulator of miR-135a-5p, which would explain the decreased miR-135a-5p expression during the WOI. CONCLUSION: MiR-135a-5p expression is significantly downregulated during the WOI. High miR-135a-5p levels suppress pinopode development and endometrial tissue decidualization through HOXA10 and BMPR2, contributing to inadequate endometrial receptivity.

Common mental disorders and risk of spontaneous abortion or recurrent spontaneous abortion: A two-sample Mendelian randomization study.

BACKGROUND: The direct causal relationships between common mental disorders (anxiety disorders, broad depression, major depressive disorder (MDD), bipolar disorder, and insomnia) and miscarriage or recurrent spontaneous abortion (RSA) are unclear. Therefore, this study aimed to explore these, using Mendelian randomization. METHODS: Genome-wide association studies (GWAS) meta-analyses with the largest sample size possible and selected independent single individuals of European ancestry were selected. Inverse variance weighted (IVW) was the main analysis method. The heterogeneity of the instrumental variables (IVs) was assessed using IVW and MR-Egger, and the horizontal pleiotropy of the IVs was assessed using MR-Egger and MR-PRESSO. RESULTS: Based on IVW results, the four mental disorders were found to be causally associated with spontaneous abortion (anxiety disorder: OR (95%CI), 1.230 (1.063-1.420), P = 0.0050; major depressive disorder: 1.690 (1.239-2.307), P = 0.0009; bipolar disorder: 1.110 (1.052-1.170), P = 0.0001; insomnia: 1.292 (1.076-1.552), P = 0.0060). Furthermore, no causal relationship was observed between broad depression and spontaneous abortion. Five common mental disorders were not causally associated with the RSA. LIMITATIONS: (1) Our analysis was limited to the European population; (2) the duration of mental disorders was not analyzed, as no information was available; and (3) it was difficult to completely detect genetic pleiotropy. CONCLUSIONS: Anxiety disorders, MDD, bipolar disorder, and insomnia may contribute to spontaneous abortion. Therefore, we should focus on the mental and sleep health of pregnant women. Future studies may be required on whether mental disorders directly lead to RSA, especially unexplained RSA.

Dynamic peripheral blood microRNA expression landscape during the peri-implantation stage in women with successful pregnancy achieved by single frozen-thawed blastocyst transfer.

STUDY QUESTION: What are the dynamic expression features of plasma microRNAs (miRNAs) during the peri-implantation period in women with successful pregnancy via single frozen-thawed blastocyst transfer? SUMMARY ANSWER: There is a significant change in the plasma miRNA expression profile before and after blastocyst transfer, during the window of implantation. WHAT IS KNOWN ALREADY: The expression of miRNAs in peripheral blood has indicative functions during the peri-implantation period. Nevertheless, the dynamic expression profile of circulating miRNAs during the peri-implantation stage in women with a successful pregnancy has not been studied. STUDY DESIGN SIZE DURATION: Seventy-six women treated for infertility with a single frozen-thawed blastocyst transfer in a natural cycle were included in this study. Among them, 57 women had implantation success and a live birth, while 19 patients experienced implantation failure. Peripheral blood samples were collected at five different time points throughout the peri-implantation period, including D0 (ovulation day), D3, D5, D7, and D9 in this cycle of embryo transfer. The plasma miRNAs in women with blastocyst transfer were isolated, sequenced, and analyzed. PARTICIPANTS/MATERIALS SETTING METHODS: Peripheral blood samples were collected in EDTA tubes and stored at -80°C until further use. miRNAs were isolated from blood, cDNA libraries were constructed, and the resulting sequences were mapped to the human genome. The plasma miRNAs were initially analyzed in a screening cohort (n = 34) with successful pregnancy. Trajectory analysis, including a global test and pairwise comparisons, was performed to detect dynamic differentially expressed (DE) miRNAs. Fuzzy c-means clustering was conducted for all dynamic DE miRNAs. The correlation between DE miRNAs and clinical characteristics of patients was investigated using a linear mixed model. Target genes of the miRNAs were predicted, and functional annotation analysis was performed. The expression of DE miRNAs was also identified in a validation set consisting of women with successful (n = 23) and unsuccessful (n = 19) pregnancies. MAIN RESULTS AND THE ROLE OF CHANCE: Following small RNA sequencing, a total of 2656 miRNAs were determined as valid read values. After trajectory analysis, 26 DE miRNAs (false discovery rate < 0.05) were identified by the global test, while pairwise comparisons in addition identified 20 DE miRNAs. A total of seven distinct clusters representing different temporal patterns of miRNA expression were discovered. Nineteen DE miRNAs were further identified to be associated with at least one clinical trait. Endometrium thickness and progesterone level showed a correlation with multiple DE miRNAs (including two of the same miRNAs, hsa-miR-1-3p and hsa-miR-6741-3p). Moreover, the 19 DE miRNAs were predicted to have 403 gene targets, and there were 51 (12.7%) predicted genes likely involved in both decidualization and embryo implantation. Functional annotation for predicted targets of those clinically related DE miRNAs suggested the involvement of vascular endothelial growth factor and Wnt signaling pathways, as well as responses to hormones, immune responses, and cell adhesion-related signaling pathways during the peri-implantation stage. LARGE SCALE DATA: The raw miRNA sequence data reported in this article have been deposited in the Genome Sequence Archive (GSA-Human: HRA005227) and are publicly accessible at https://ngdc.cncb.ac.cn/gsa-human/browse/HRA005227. LIMITATIONS REASONS FOR CAUTION: Although the RNA sequencing results revealed the global dynamic changes of miRNA expression, further experiments examining the clinical significance of the identified DE miRNAs in embryo implantation outcome and the relevant regulatory mechanisms involved are warranted. WIDER IMPLICATIONS OF THE FINDINGS: Understanding the dynamic landscape of the miRNA transcriptome could shed light on the physiological mechanisms involved from ovulation to the post-implantation stage, as well as identifying biomarkers that characterize stage-related biological process. STUDY FUNDING/COMPETING INTERESTS: The study was funded by the Major clinical research project of Tangdu Hospital (2021LCYJ004) and the Discipline Platform Improvement Plan of Tangdu Hospital (2020XKPT003). The funders had no influence on the study design, data collection, and analysis, decision to publish, or preparation of the article. There are no conflicts of interest to declare.

Comparative effectiveness and safety of 36 therapies or interventions for pregnancy outcomes with recurrent implantation failure: a systematic review and network meta-analysis.

PURPOSE: To investigate the effectiveness and safety of 36 different therapies for recurrent implantation failure (RIF) patients. METHODS: We searched PubMed, Embase, the Cochrane Library (CENTRAL), Web of Science, and China National Knowledge Internet (CNKI) from inception to August 24, 2022, with language in both English and Chinese. Randomized controlled trials (RCTs) and observational studies that provided data with one of pregnancy outcomes on RIF patients were included in the network meta-analysis (NMA). The odds ratios (OR) and 95% credible interval (CrI) on pregnancy outcomes were summarized by NMA with a random-effects model. We also analyzed data from only RCTs and compared whether the optimal treatment is the same for different failed embryo transfer attempts. RESULTS: The total of 29,906 RIF patients from 154 clinical studies (74 RCTs and 80 non-RCTs) were included in the NMA. In terms of implantation rate (IR), growth hormone (GH) (OR: 3.32, 95% CrI: 1.95-5.67) is the best treatment in all included studies; IVIG+PBMC (5.84, 2.44-14.1) is the best for clinical pregnancy rate (CPR); hyaluronic acid (HA) (12.9, 2.37-112.0) for live birth rate (LBR); and aspirin combined with glucocorticoids (0.208, 0.0494-0.777) for miscarriage rate (MR). The two-dimensional graphs showed that GH could maximize IR and CPR simultaneously; HA and GH could simultaneously increase IR and LBR to a large extent; HA could maximize IR and minimize MR. CONCLUSION: IVIG+PBMC, GH, and embryo medium enriched with HA could significantly improve pregnancy outcomes in patients with RIF. It appears that combination therapy is a potential administration strategy. TRIAL REGISTRATION: This study has been registered on PROSPERO (CRD42022353423).

Clinical evaluation of autologous platelet-rich plasma therapy for intrauterine adhesions: a systematic review and meta-analysis.

Objective: This meta-analysis aims to evaluate the efficacy and safety of autologous platelet-rich plasma (PRP) administration in reducing adhesion recurrence and improving pregnancy outcomes in patients with intrauterine adhesion (IUA). Methods: We conducted a comprehensive search of Pubmed, Embase, the Cochrane Library, Web of Science, Scopus, and China National Knowledge Internet (CNKI) from inception to February 10, 2023, without any language or regional restrictions. We used random-effects models to assess odds ratios (OR) and weight mean differences (WMD) with 95% confidence intervals (CI). Results: Our meta-analysis included a total of 730 patients from 10 clinical studies (6 RCTs and 4 non-RCTs). The results showed that PRP administration significantly increased endometrial thickness (WMD = 0.79, 95% CI: 0.40-1.19; P < 0.001; I2 = 0.0%), menstrual volume (WMD = 2.96, 95% CI = 2.30-3.61; P < 0.001; I2 = 0.0%), and days of menstruation (WMD = 1.13, 95% CI = 0.86-1.41; P < 0.001; I2 = 0.0%). Additionally, the clinical pregnancy rate was also improved (OR = 1.82, 95% CI: 1.19-2.78; P = 0.006; I2 = 0.0%). However, there was insufficient evidence to reach a conclusion regarding the effects of PRP on the recurrence rate of moderate to severe IUA, changes in AFS scores, miscarriage rate, and live birth rate. Conclusions: Our analysis confirms that autologous PRP is an effective treatment for IUA. However, the limited sample size suggests that the results should be interpreted with caution. Therefore, larger and well-designed studies are necessary in the future to confirm these findings and explore the optimal PRP dosing regimens further. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42023391115.

High-throughput detection of mycophenolic acid in human plasma based on sensitive and rapid fluorescence nitrogen-doped carbon dots sensing platform.

In this experiment, a water-soluble, nitrogen-doped yellow-green fluorescent N-doped carbon dots (N-CDs) were synthesized by one-step hydrothermal method using ß-cyclodextrin as carbon source and L-phenylalanine as nitrogen source. The fluorescence quantum yield of the obtained N-CDs was as high as 9.96%, and the N-CDs exhibited photostability at different pH, ionic strength and temperature. The morphology of the N-CDs was approximately spherical with an average particle size of about 9.4 nm. Based on the fluorescence enhancement effect of mycophenolic acid (MPA) on N-CDs, a quantitative detection method of MPA was established. This method had good selectivity and high sensitivity for MPA. The fluorescence sensing system was applied to the detection of MPA in human plasma. The linear range of MPA were 0.06-3 µg·mL-1 and 3-27 µg·mL-1 with a detection limit of 0.016 µg·mL-1, and the recoveries were 97.03∼100.64 % with the RSDs of 0.13∼2.90 %. The interference experiment results showed that the interference of other coexisting substances, including Fe3+, can be ignored in the actual detection. Comparing the results measured by the established method with the EMIT method, it was found that the results obtained by the two methods were similar, and the relative error was within ± 5 %. This study provided a simple, rapid, sensitive, selective and effective method for the quantitative analysis of MPA, and was expected to be applied to clinical MPA blood concentration monitoring.

Primary tumor resection improves survival benefit of stage IVB cervical carcinoma: a new perspective.

PURPOSE: Recent studies have revealed that primary tumor resection (PTR) surgery could improve prognosis in some solid tumors. Thus, we aimed to investigate whether patients with stage IVB cervical carcinoma can benefit from PTR surgery and who can benefit. METHODS: We extracted and obtained data on patients with stage IVB cervical carcinoma from the SEER database from 2010 to 2017 and classified them into two groups: the surgery and the non-surgery group. The overall survival (OS) and cancer-specific survival (CSS) of the two groups were compared before and after propensity score matching (PSM). The independent prognostic variables were identified using univariate and multivariate Cox regression analyses. Then, the model was established to select the optimal patients to receive PTR surgery using multivariate logistic regression. RESULTS: After PSM, the study included 476 cervical carcinoma (stage IVB) patients, of whom 238 underwent PTR surgery. Compared to the non-surgery group, the surgery group's median OS and median CSS were both longer (median OS: 27 months vs. 13 months, P < 0.001; median CSS: 52 months vs. 21 months, P < 0.001). The model showed no organ metastasis, adenocarcinoma, G1/2, and chemotherapy were more supportive of performing PTR surgery. The calibration curves and DCA showed that the model had high predictive accuracy and excellent clinical applicability. Finally, the "surgery benefit" group had the OS that was approximately four times better than "surgery non-benefit" group. CONCLUSION: PTR surgery can potentially improve the prognosis of patients with cervical carcinoma at stage IVB. The model could probably select optimal candidates and provide a new perspective on individualized treatment.

Rapid and sensitive fluorescence determination of oxytocin using nitrogen-doped carbon dots as fluorophores.

In this work, a novel nitrogen (N)-doped carbon dots (N-CDs) was prepared with quercetin as the carbon source and o-phenylenediamine as the nitrogen source by hydrothermal synthesis, and their application as fluorophores for selective and sensitive determination of oxytocin were reported. The fluorescence quantum yield of the as-prepared N-CDs, which exhibited good water solubility and photostability, was about 6.45 % using rhodamine 6 G as reference substance, and the maximum excitation (Ex) and emission (Em) wavelength were 460 nm and 542 nm, respectively. The results illustrated that the direct fluorescence quenching of N-CDs fluorophore for the detection of oxytocin achieved good linearity in the range of 0.2-5.0 IU/mL and 5.0-10.0 IU/mL, the correlation coefficients were 0.9954 and 0.9909, respectively, and the detection limit was 0.0196 IU/mL (S/N = 3). The recovery rates were 98.8∼103.8 % with RSD= 0.93 %. The interference experiments showed that common metal ions, possible impurities introduced in production and coexisting excipients in the preparation had little adverse influence on selective detection of oxytocin by the developed N-CDs based fluorescent detection method. The mechanism study on the fluorescence quenching of N-CDs by oxytocin concentrations under the given experimental conditions demonstrated that there were internal filtration effect and static quenching in the system. The developed fluorescence analysis platform for the detection of oxytocin had been proved to be rapid, sensitive, specific and accurate, and to be used for the quality inspection of oxytocin.

Effect of pausing on the cotranscriptional folding kinetics of RNAs.

The pausing event in RNA molecule folding that occurs during the cotranscription process plays a critical role in cellular RNA function. Based on Conformational Resampling through Kinetic Relaxation (CRKR), this paper investigates a method to reveal the specifics of pausing for RNA cotranscriptional folding of 117-nucleotide E. coli SRP RNA and 73-nucleotide HIV-1 TAR RNA. It can be inferred from the results that pausing events generate valid cotranscriptional conformational rearrangement to protect the function structures and influence the folding pathway, which is remarkably consistent with the experimental results. Additionally, different transcription speeds result in different levels of protection capability. The folding pathway or conformational rearrangement can also be affected by a change in transcription speed after pausing site. These findings illuminate that RNAs with functional structures undergo complex rearrangement folding in pausing events, and different RNAs prefer different speeds for specific folding pathways. Moreover, pausing in particular circumstances can be employed to regulate the population of final functional structures. In conclusion, this paper offers fresh perspectives on the pausing event in the cotranscriptional folding of RNAs.

Clinical Characteristics Predict Recurrence in Borderline Ovarian Tumor Patients with Fertility-Preserving Surgery.

PURPOSE: To identify prognostic factors in patients with borderline ovarian tumor (BOT) and establish and validate a nomogram predicting recurrence in BOT patients treated with fertility-preserving surgery. PATIENTS AND METHODS: Patients with BOT who underwent surgery at two institutions between January 2000 and June 2017 were included and categorized into training and validation cohorts. Univariate log rank test and Cox regression analysis were performed in the training cohort to identify prognostic factors, and a nomogram was developed to predict the recurrence rate. The model was validated by calculating the C-index and drawing the calibration curve and receiver operating curve (ROC). CONCLUSION: In the multivariate Cox regression analysis, practice period, past history of benign ovarian disease, past history of benign breast disease, elevated CA125 levels, elevated CA199 levels, surgical methods, greater omentum resection, FIGO stage, postoperative pregnancy, and re-operation were independently associated with recurrence-free survival (p<0.05). The aforementioned prognostic factors were used to develop a nomogram. The nomogram demonstrated a good ability to predict the risk of recurrence (training cohort C-index: 0.866, validation cohort C-index: 0.920). The calibration curve suggested that the predicted recurrence-free survival was closely related to the actual recurrence. ROC analysis showed that the nomogram had a good discriminatory power with the area under curve between 0.776 and 0.956. The nomogram can predict the 1-, 3-, and 5-year recurrence-free survival of BOT patients undergoing fertility-preserving surgery. The predictive model can help guide surgical plans, postoperative monitoring, and prognostic evaluation of BOT patients.

Development and validation of a nomogram risk prediction model for malignancy in dermatomyositis patients: a retrospective study.

BACKGROUND: Dermatomyositis accompanied with malignancy is a common poor prognostic factor of dermatomyositis. Thus, the early prediction of the risk of malignancy in patients with dermatomyositis can significantly improve the prognosis of patients. However, the identification of antibodies related to malignancy in dermatomyositis patients has not been widely implemented in clinical practice. Herein, we established a predictive nomogram model for the diagnosis of dermatomyositis associated with malignancy. METHODS: We retrospectively analyzed 240 cases of dermatomyositis patients admitted to Sun Yat-sen Memorial Hospital, Sun Yat-sen University from January 2002 to December 2019. According to the year of admission, the first 70% of the patients were used to establish a training cohort, and the remaining 30% were assigned to the validation cohort. Univariate analysis was performed on all variables, and statistically relevant variables were further included in a multivariate logistic regression analysis to screen for independent predictors. Finally, a nomogram was constructed based on these independent predictors. Bootstrap repeated sampling calculation C-index was used to evaluate the model's calibration, and area under the curve (AUC) was used to evaluate the model discrimination ability. RESULTS: Multivariate logistic analysis showed that patients older than 50-year-old, dysphagia, refractory itching, and elevated creatine kinase were independent risk factors for dermatomyositis associated with malignancy, while interstitial lung disease was a protective factor. Based on this, we constructed a nomogram using the above-mentioned five factors. The C-index was 0.780 (95% CI [0.690-0.870]) in the training cohort and 0.756 (95% CI [0.618-0.893]) in the validation cohort, while the AUC value was 0.756 (95% CI [0.600-0.833]). Taken together, our nomogram showed good calibration and was effective in predicting which dermatomyositis patients were at a higher risk of developing malignant tumors.

Identification of significant genes signatures and prognostic biomarkers in cervical squamous carcinoma via bioinformatic data.

BACKGROUND: Cervical squamous cancer (CESC) is an intractable gynecological malignancy because of its high mortality rate and difficulty in early diagnosis. Several biomarkers have been found to predict the prognose of CESC using bioinformatics methods, but they still lack clinical effectiveness. Most of the existing bioinformatic studies only focus on the changes of oncogenes but neglect the differences on the protein level and molecular biology validation are rarely conducted. METHODS: Gene set data from the NCBI-GEO database were used in this study to compare the differences of gene and protein levels between normal and cancer tissues through significant pathway selection and core gene signature analysis to screen potential clinical biomarkers of CESC. Subsequently, the molecular and protein levels of clinical samples were verified by quantitative transcription PCR, western blot and immunohistochemistry. RESULTS: Three differentially expressed genes (RFC4, MCM2, TOP2A) were found to have a significant survival (P < 0.05) and highly expressed in CESC tissues. Molecular biological verification using quantitative reverse transcribed PCR, western blotting and immunohistochemistry assays exhibited significant differences in the expression of RFC4 between CESC and para-cancerous tissues (P < 0.05). CONCLUSION: This study identified three potential biomarkers (RFC4, MCM2, TOP2A) of CESC which may be useful to clarify the underlying mechanisms of CESC and predict the prognosis of CESC patients.

Development and Validation of an RNA-Binding Protein-Based Prognostic Model for Ovarian Serous Cystadenocarcinoma.

Ribonucleic acid-binding proteins (RBPs) are reportedly involved in tumor progression and recurrence; however, the functions and mechanisms of action of RBPs in ovarian serous cystadenocarcinoma (OSC) are not known. To address these issues, gene expression profiles of OSC tissues from The Cancer Genome Atlas (TCGA) and normal tissues from the Genotype-Tissue Expression database were compared in order to identify RBPs that are differentially expressed in OSC. We also analyzed the biological functions of these RBPs and their relationship to clinical outcome. There were 190 RBPs that were differentially expressed between OSC and normal tissues, including 93 that were upregulated and 97 that were downregulated. Five of the RBPs were used to construct a prediction model that was evaluated by univariate and multivariate Cox regression analyses. TCGA data were randomly divided into training and test cohorts, and further categorized into high- and low-risk groups according to risk score in the model. The overall survival (OS) of the high-risk group was shorter than that of the low-risk group (training cohort P = 0.0007596; test cohort P = 0.002219). The area under the receiver operating characteristic curve of the training and test cohorts was 0.701 and 0.638, respectively, demonstrating that the model had good predictive power. A nomogram was established to quantitatively describe the relationship between the five prognostic RBPs and OS in OSC, which can be useful for developing individualized management strategies for patients.

Strategies to achieve immune tolerance in allogeneic solid organ transplantation.

Organ transplantation is an effective way to treat many end-stage diseases. In order to overcome post-transplant rejection, immunosuppressive agents have been widely used, but the long-term survival of transplanted organs still has not been achieved in the clinic. For decades, tolerance is the "holy grail" that transplant immunologists have longed for. The well-known approaches to induce immune tolerance are through adoptively transferred regulatory T cells and achieving chimeric states. In addition, there are a variety of promising potential strategies, including costimulatory blockade, regulating differentiation of immune cell subgroups, adoptive infusion of immunoregulatory cells, using apoptotic cells to induce tolerance, stem cell regenerative medicine to reconstitute tissue and organs, helminthic therapy, using exosomes carrying phagocytic antigen and phagocytic vesicles to induce tolerance, and blocking CD3 and targeted clearance of memory T cells. In this paper, we review the current developments and the potential of these strategies to achieve transplantation tolerance.

Four Surgical Strategies for the Treatment of Cesarean Scar Defect: A Systematic Review and Network Meta-analysis.

OBJECTIVE: This network meta-analysis compared treatment via laparoscopy, hysteroscopy (HP), combined laparoscopy with HP (LH), and vaginal repair (VR) for reducing intermittent abnormal uterine bleeding and cesarean scar defect (CSD) diverticulum depth in patients with CSD. DATA SOURCES: Electronic databases (PubMed, EMBASE, The Cochrane Central Register of Controlled Trials, MEDLINE, ClinicalTrials.gov, Chinese Biomedical Literature Database, and China National Knowledge Integrated) were searched for articles published through June 13, 2018. METHODS OF STUDY SELECTION: The search included randomized controlled trials (RCTs) and observational studies of surgical treatment for CSD. Standardized mean difference (SMD) and 95% confidence intervals (CIs) were reported. RCTs were evaluated by the Cochrane risk-of-bias tool, observational studies by Risk of Bias in Nonrandomized Studies of Intervention, and overall evidence quality by grade. Data were analyzed by STATA (version 15.0; StataCorp, College Station, TX) and R software for windows (version 3.5.0; R Core Team, 2018). TABULATION, INTEGRATION, AND RESULTS: Ten studies (n = 858; 4 RCTs and 6 observational studies) were included. Patients who underwent uterine diverticulum resection by LH had a shorter duration of abnormal uterine bleeding than those by HP (SMD = 1.36, 95% CI, 0.37-2.36; p = .007) and VR (SMD = 1.58, 95% CI, 0.97-2.19; p <.0001). LH reduced the CSD diverticulum depth more than VR (SMD = 1.57, 95% CI, 0.54-2.61; p = .003). There was no significant difference in efficacy among the surgical procedures. CONCLUSION: LH reduced intermittent abnormal uterine bleeding and scar depth more than the other surgical interventions. Larger clinical trials are warranted to verify this analysis.

Botulinum Toxin A Injection for Treatment of Chronic Skin Ulcer: A Case Series and Literature Review.

Chronic skin ulcer (CSU) often combines with a variety of refractory factors that respond poorly to routine treatments. Botulinum toxin A (BTX-A) can be injected subcutaneously to improve the local blood supply, to reduce pain, and to promote wound healing. At present, few reports have mentioned BTX-A injection for chronic skin ulcer treatment. We observed the effect of four cases that used BTX-A to treat CSU and provided a brief review of the literature. Four cases of CSUs with 4 different causes were treated with BTX-A injection (4 U/cm2). The specific operation is as follows: local, multipoint, cyclic, equidistant, and subcutaneous injections with a depth of 6 to 8 mm. The ulcer area was significantly reduced. Subsequently, the ulcer healed within 20 to 48 days. Botulinum toxin A is recommended as an important treatment for chronic skin ulcer that can improve healing of skin ulcers with various etiologies.

Surface EMG Pattern Recognition Using Long Short-Term Memory Combined with Multilayer Perceptron.

Motion classification based on pattern recognition of surface EMG (sEMG) signals is a promising approach for prosthetic control. We present a pattern recognition model that combines long short-term memory (LSTM) network with multiplayer perceptron (MLP) for sEMG signals feature learning and classification. The LSTM network captures temporal dependencies of the sEMG signals while the MLP has no inherent temporal dynamics but focuses on the static characteristics. The combination of the two networks would learn a feature space that contains both the dynamic and static information of the sEMG signals, which helps to improve the motion classification accuracy. The architecture of the proposed network was optimized by investigating the appropriate width and depth of the neural network as well as the dropout to achieve the best classification results. The performance of the proposed pattern recognition model was evaluated using Ninapro database. The results show that the proposed model can produce better classification accuracy than most of the well-known recognition techniques.

Efficacy of probiotics on anxiety-A meta-analysis of randomized controlled trials.

BACKGROUND: The concept "psychobiotics" claims potential beneficial effect of probiotics on anxiety, whereas findings from clinical trials are inconsistent. Thus, a meta-analysis is needed to clarify the effect of probiotics on anxiety. METHODS: Randomized controlled trials (RCTs) assessing the effect of probiotics on anxiety were systematically retrieved from online databases and manually screened for references of relevant published literature through September 1, 2017. Standardized mean difference in change from baseline of anxiety rating scales between probiotics groups and placebo groups was selected as the main effect index. Subgroup analyses were conducted with respect to overall health status of the sample, existence of gastrointestinal symptoms, strains of flora, trial duration, and risk of bias assessment. Publication bias was evaluated by funnel plot and Egger's test. The reliability of the result was assessed by leave-one-out sensitivity analysis. RESULTS: Twelve studies with 1,551 subjects (871 in probiotics group and 680 in control group) were included. All the studies were rated as low or moderate risk of bias. The meta-analysis and subgroup analyses all showed no significant difference between probiotics and placebo in alleviating anxiety symptoms. The Egger's test revealed no evidence of significant publication bias. Sensitivity analysis showed that leaving out one study would result in marginal significance. CONCLUSIONS: The evidence for the efficacy of probiotics in alleviating anxiety, as presented in currently published RCTs, is insufficient. More reliable evidence from clinical trials is needed before a case can be made for promoting the use of probiotics for alleviating anxiety.