Meta-analysis of perioperative outcomes and safety of percutaneous nephrostomy versus retrograde ureteral stenting in the treatment of acute obstructive upper urinary tract infection.

Background: The debate regarding the optimal drainage method for acute obstructive upper urinary tract infection persists, focusing on the choice between percutaneous nephrostomy (PCN) and retrograde ureteral stenting (RUS). Aims: This study aims to systematically examine the perioperative outcomes and safety associated with PCN and RUS in treating acute obstructive upper urinary tract infections. Methods: A comprehensive investigation was conducted using the Medline, Embase, Web of Science, and Cochrane databases up to December 2022, following the guidelines of the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. The utilized keywords included 'PCN', 'RUS', 'acute upper obstructive uropathy', and 'RCT'. Inclusion criteria encompassed studies providing accurate and analyzable data, which incorporated the total subject count, perioperative outcomes, and complication rates. The assessed perioperative outcomes included fluoroscopy time, normalization of temperature, normalization of serum creatinine, normalization of white blood cell (WBC) count, and operative time. Safety outcomes encompassed failure rate, intraoperative and postoperative hematuria, postoperative fever, postoperative pain, and postoperative nephrostomy tube or stent slippage rate. The study protocol was prospectively registered at PROSPERO (CRD42022352474). Results: The meta-analysis encompassed 7 trials involving 727 patients, with 412 assigned to the PCN group and 315 to the RUS group. The outcome of the meta-analysis unveiled a reduced occurrence of postoperative hematuria in the PCN group [odds ratio (OR) = 0.54, 95% confidence interval (CI) 0.30-0.99, p = 0.04], along with a decreased frequency of insertion failure (OR = 0.42, 95% CI 0.21-0.81, p = 0.01). In addition, the RUS group exhibited a shorter fluoroscopy time than the PCN group (mean difference = 0.31, 95% CI 0.14-0.48, p = 0.0004). Conclusion: Given the significant impact of hematuria and catheterization failure on postoperative quality of life, the preference for PCN appears more advantageous than RUS.

Meta-analysis of perioperative outcomes and safety of percutaneous nephrostomy vs retrograde ureteral stenting in the treatment of acute obstructive upper urinary tract infection The optimal drainage method for acute obstructive upper urinary tract infection between PCN and RUS is currently debatable. Our meta-analysis found PCN performed better than RUS in hematuria and catheterization failure rate, although PCN was associated with longer exposure time.

sh- Ambra1 inhibits IRS-1/PI3K/Akt signalling pathway to reduce autophagy in gestational diabetes.

INTRODUCTION: Gestational diabetes mellitus (GDM) is the most common metabolic disease in pregnancy. However, studies of activating molecule of Beclin1-regulated autophagy (Ambra1) affecting the insulin substrate receptor 1/phosphatidylinositol 3 kinase/protein kinase B (IRS-1/PI3K/Akt) signalling pathway in GDM have not been reported. The aim of the study was to detect the difference of Ambra1 expression in the placenta of normal pregnant women and GDM patients. MATERIAL AND METHODS: An in vitro model of gestational diabetes mellitus was established by inducing HTR8/Svneo cells from human chorionic trophoblast layer with high glucose. The changes of cell morphology were observed by inverted microscope, and the expression levels of Ambra1 gene and protein in model cells were detected. After this, Ambra1 gene was silenced by shRNA transfection, and PI3K inhibitor was added to detect changes in Ambra1, autophagy, and insulin (INS) signalling pathways. RESULTS: The protein expression levels of Ambra1, Bcl-2 interacting protein (Beclin-1), and microtubule-associated proteins 1A/1B light chain 3B (LC3-II) in the placentas of GDM pregnant women were higher than those of normal pregnant women. High glucose induces morphological changes in HTR8/Svneo cells and increases Ambra1 transcription and translation levels. sh-Ambra1 increased survival of HTR8/SvNEO-HG cells and inhibited Ambra1, Beclin1, and LC3-II transcription and translation levels. Also, sh-Ambra1 increased IRS-1/PI3K/Akt protein phosphorylation levels and inhibited the IRS-1/PI3K/Akt signalling pathway and its resulting autophagy. CONCLUSIONS: sh-Ambra1 increased IRS-1/PI3K/Akt protein phosphorylation levels to reduce autophagy in gestational diabetes.

Engineered Extracellular Vesicles Expressing Siglec-10 Camouflaged AIE Photosensitizer to Reprogram Macrophages to Active M1 Phenotype and Present Tumor-Associated Antigens for Photodynamic Immunotherapy.

Cancer immunotherapy has attracted considerable attention due to its advantages of persistence, targeting, and ability to kill tumor cells. However, the efficacy of tumor immunotherapy in practical applications is limited by tumor heterogeneity and complex tumor immunosuppressive microenvironments in which abundant of M2 macrophages and immune checkpoints (ICs) are present. Herein, two type-I aggregation-induced emission (AIE)-active photosensitizers with various reactive oxygen species (ROS)-generating efficiencies are designed and synthesized. Engineered extracellular vesicles (EVs) that express ICs Siglec-10 are first obtained from 4T1 tumor cells. The engineered EVs are then fused with the AIE photosensitizer-loaded lipidic nanosystem to form SEx@Fc-NPs. The ROS generated by the inner type-I AIE photosensitizer of the SEx@Fc-NPs through photodynamic therapy (PDT) can convert M2 macrophages into M1 macrophages to improve tumor immunosuppressive microenvironment. The outer EV-antigens that carry 4T1 tumor-associated antigens directly stimulate dendritic cells maturation to activate different types of tumor-specific T cells in overcoming tumor heterogeneity. In addition, blocking Siglec-10 reversed macrophage exhaustion for enhanced antitumor ability. This study presents that a combination of PDT, immune checkpoints, and EV-antigens can greatly improve the efficiency of tumor immunotherapy and is expected to serve as an emerging strategy to improve tumor immunosuppressive microenvironment and overcome immune escape.

The pooled analysis evaluates the therapeutic efficacy of desmopressin combined with anticholinergic drugs in the treatment of pediatric nocturnal enuresis.

OBJECTIVE: This pooled analysis aims to demonstrate the clinical efficacy and safety of combined desmopressin and anticholinergic therapy in the treatment of pediatric nocturnal enuresis (NE). METHODS: A systematic search was conducted through PubMed, MEDLINE, EMBASE, ResearchGate, and Cochrane Library to identify all randomized controlled trials (RCTs) comparing monotherapy with desmopressin versus combined therapy with desmopressin and anticholinergic agents for the treatment of NE. Data analysis was performed using RevMan version 5.4.1. RESULTS: This study included 8 RCTs involving a total of 659 patients. The frequencies of complete response (CR), partial response (PR), and nonresponse (NR) were computed for both short-term treatment (1 month) and long-term treatment (3 months). Additionally, alterations in the mean number of NE episodes, adverse events, and relapse were assessed. Our analysis indicates that, in comparison to the monotherapy group, the combination therapy group plays a pivotal role in augmenting the CR odds and diminishing the NR ratios in both short-term and long-term treatments (1 month CR ratio [risk ratio (RR): 1.84; 95% confidence interval (CI): 1.22-2.76; p = 0.003, I2 = 72%]; 3 months CR ratio [RR: 1.48; 95% CI: 1.25-1.76; p < 0.00001, I2 = 0%]; 1 month NR ratio [RR: 0.67; 95% CI: 0.55-0.82; p = 0.0001, I2 = 0%]; 3 months CR ratio [RR: 0.37; 95% CI: 0.19-0.73; p = 0.004, I2 = 0%]). Furthermore, in both short-term and long-term treatment, the combined therapy group exhibits a greater magnitude of change in the average number of NE episodes compared to patients receiving monotherapy (1 month, mean difference [MD] = -2.97; 95% CI: -4.23 to -1.71, p < 0.0001; 3 months, MD = -4.30; 95% CI: -7.18 to -1.43, p = 0.003). Moreover, the combination therapy group exhibits a significant reduction in the recurrence rate (RR: 0.36; 95% CI: 0.15-0.86; p = 0.02). There is no significant difference in the incidence of adverse events between the two groups (RR: 1.16; 95% CI: 0.58-2.31; p = 0.67). CONCLUSION: Combining desmopressin with anticholinergic medications is more effective for NE than desmopressin alone, with lower recurrence and minimal adverse effects.

Targeting hnRNPC suppresses thyroid follicular epithelial cell apoptosis and necroptosis through m6A-modified ATF4 in autoimmune thyroid disease.

Both environmental and genetic factors contribute to the etiology of autoimmune thyroid disease (AITD) including Graves' disease (GD) and Hashimoto's thyroiditis (HT). However, the exact pathogenesis and interactions that occur between environmental factors and genes remain unclear, and therapeutic targets require further investigation due to limited therapeutic options. To solve such problems, this study utilized single-cell transcriptome, whole transcriptome, full-length transcriptome (Oxford nanopore technology), and metabolome sequencing to examine thyroid lesion tissues from 2 HT patients and 2 GD patients as well as healthy thyroid tissue from 1 control subject. HT patients had increased ATF4-positive thyroid follicular epithelial (ThyFoEp) cells, which significantly increased endoplasmic reticulum stress. The enhanced sustained stress resulted in cell death mainly including apoptosis and necroptosis. The ATF4-based global gene regulatory network and experimental validation revealed that N6-methyladenosine (m6A) reader hnRNPC promoted the transcriptional activity, synthesis, and translation of ATF4 through mediating m6A modification of ATF4. Increased ATF4 expression initiated endoplasmic reticulum stress signaling, which when sustained, caused apoptosis and necroptosis in ThyFoEp cells, and mediated HT development. Targeting hnRNPC and ATF4 notably decreased ThyFoEp cell death, thus ameliorating disease progression. Collectively, this study reveals the mechanisms by which microenvironmental cells in HT and GD patients trigger and amplify the thyroid autoimmune cascade response. Furthermore, we identify new therapeutic targets for the treatment of autoimmune thyroid disease, hoping to provide a potential way for targeted therapy.

Updated recommendations on the therapeutic role of extracorporeal shock wave therapy for peyronie's disease: systematic review and meta-analysis.

BACKGROUND: The therapeutic role of extracorporeal shockwave therapy (ESWT) for Peyronie's disease (PD) has been controversial in a long term. We aimed to further evaluate the therapeutic effect of ESWT for PD on the basis of available high-quality studies. METHODS: The PubMed, CENTRAL and Embase databases were searched for articles published from January 1st, 2000 to December 31, 2022. Only randomized controlled trials (RCTs) using ESWT to treat PD were included. Meta-analysis and forest plots were carried out using Review Manager 5.4.1 software, and outcomes were reviewed by 2 authors independently. Using the Risk of Bias assessment form (ROB-2) by Cochrane Collaboration for quality assessment. PRISMA 2020 guidelines were used in this article to achieve the quantitative and qualitative synthesis of data. RESULTS: A total of four RCTs were included. 151 patients in the ESWT group and 150 patients in the control group. The meta-analysis results showed that ESWT could significantly reduce plaque size (OR 2.59, 95%CI 1.15 to 5.85, P = 0.02) and relieve pain (MD -1.55, 95%CI -2.46 to -0.64, P = 0.0008); but it has no significant effect on reducing the penile curvature (OR 1.93, 95%CI 0.87-4.26, P = 0.11) and improving sexual function (MD 2.6, 95%CI -1.63 to 6.83, P = 0.23), there is also no significant difference in complication rates between groups (OR 2.94, 95%CI 0.66 to 13.03, P = 0.16). The risk of bias of results is low. The limitations of this study are that the number of included studies is too small, some experimental outcomes are missing, and the expression of outcomes is not unified. CONCLUSIONS: For PD, ESWT can be considered as a safe short-term treatment, which can reduce plaque size and relieve pain, but cannot improve penile curvature and sexual function. Its long-term efficacy remains to be discussed. REGISTRATION NUMBER: PROSPERO (ID: CRD42023436744).

Robot-assisted radical cystectomy vs open radical cystectomy in patients with bladder cancer: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: Even though there isn't enough clinical evidence to demonstrate that robot-assisted radical cystectomy (RARC) is preferable to open radical cystectomy (ORC), RARC has become a widely used alternative. We performed the present study of RARC vs ORC with a focus on oncologic, pathological, perioperative, and complication-related outcomes and health-related quality of life (QOL). METHODS: We conducted a literature review up to August 2022. The search included PubMed, EMBASE and Cochrane controlled trials register databases. We classified the studies according to version 2 of the Cochrane risk-of-bias tool for randomized trials (RoB 2). The data was assessed by Review Manager 5.4.0. RESULTS: 8 RCTs comparing 1024 patients were analyzed in our study. RARC was related to lower estimated blood loss (weighted mean difference (WMD): -328.2; 95% CI -463.49--192.92; p < 0.00001), lower blood transfusion rates (OR: 0.45; 95% CI 0.32 - 0.65; p < 0.0001) but longer operation time (WMD: 84.21; 95% CI 46.20 -121.72; p < 0.0001). And we found no significant difference in terms of positive surgical margins (P = 0.97), lymph node yield (P = 0.30) and length of stay (P = 0.99). Moreover, no significant difference was found between the two groups in terms of survival outcomes, pathological outcomes, postoperative complication outcomes and health-related QOL. CONCLUSION: Based on the present evidence, we demonstrated that RARC and ORC have similar cancer control results. RARC is related to less blood loss and lower transfusion rate. We found no difference in postoperative complications and health-related QOL between robotic and open approaches. RARC procedures could be used as an alternate treatment for bladder cancer patients. Additional RCTs with long-term follow-up are needed to validate this observation.

The efficacy of CO2 laser in the treatment of genitourinary syndrome of menopause: a systematic review and meta-analysis of randomized controlled trials.

CO2 laser has been proposed as a treatment strategy for genitourinary syndrome of menopause (GSM). In order to assess its efficacy for treating GSM, we conducted a systematic review and meta-analysis. To identify the current state of randomized controlled trials on CO2 laser therapy for GSM, a literature review was conducted. We systematically searched the following databases: PUBMED, EMBASE and the Cochrane Controlled Trials Register. In addition, a review of the references in the retrieved studies was carried out. Of 562 identified studies, 9 were eligible and were included in our analysis, involving 523 patients in total. Based on our analysis, CO2 laser has no statistical difference compared with estrogen in VHI (p = 0.87), FSFI total score (p = 0.19), FSFI-Arousal (p = 0.11), FSFI-Desire (p = 0.72), FSFI-Orgasm (p = 0.45) and FSFI-Satisfaction (p = 0.08). The meta-analysis also showed that CO2 laser significantly improved FSFI-Lubrication scores compared with estrogen therapy (p = 0.0004). Furthermore, compared with the sham group, CO2 laser group had statistically improved VHI scores (p = 0.003) and FSFI scores (p < 0.00001). CO2 laser therapy may be an effective alternative to estrogen therapy for GSM both in cases where estrogen is not applicable because of comorbidities and in cases in which women do not desire to take estrogen.

The Efficacy of Cyclooxygenase-2 Inhibitors for the Male Treatment of Lower Urinary Tract Symptoms: A Systematic Review and Meta-Analysis.

To investigate the potential use of cyclooxygenase-2 (COX-2) inhibitors in the treatment of lower urinary tract symptoms (LUTS) in male patients, we conducted a comprehensive meta-analysis. Our study involved the identification and collection of randomized controlled trials (RCTs) from leading databases including PubMed, MEDLINE, EMBASE, and Cochrane Library. The primary objective of this analysis was to evaluate the effectiveness of COX-2 inhibitors for the treatment of LUTS. Our analysis involved six short-term (within 3 months) RCTs involving 707 patients. We found that COX-2 inhibitor treatment significantly improved the International Prostate Symptom Score (IPSS) of patients (mean difference [MD] = -2.99, 95% confidence interval (CI): -3.65 to -2.33, p < .00001), nocturia frequency (MD = -1.90; 95% CI: -3.18 to -0.61, p = .004), and maximum flow rate (Qmax) (MD = 1.02; 95% CI: 0.06 to 1.98, p = .04). However, no significant differences were found between patients in terms of changes in prostate-specific antigen (PSA) (MD = 0.02; 95% CI: -0.39 to 0.43, p = .92) and total prostate volume (TPV) (MD = -2.93; 95% CI: -6.45 to 0.59, p = .10). Therefore COX-2 inhibitors are an effective treatment for LUTS.

The ambulatory transoral endoscopic thyroidectomy vestibular approach is safe and economical for patients with thyroid nodules.

Background: Ambulatory thyroid surgery has been increasingly performed in recent years. However, the feasibility of the ambulatory transoral endoscopic thyroidectomy vestibular approach (TOETVA) has not been evaluated. We aimed to evaluate the safety, economy, and mental health outcomes of ambulatory TOETVA. Methods: We retrospectively reviewed the data of patients who underwent TOETVA between March 2019 and August 2022. The procedure was performed by a skilled surgical team from the Department of Thyroid Surgery of the affiliated Yantai Yuhuangding Hospital of Qingdao University. Patients were enrolled in the ambulatory (n=166) and conventional (n=290) groups, based on their chosen procedure. We analyzed patients' clinical characteristics, surgical outcomes, Hamilton Anxiety Rating Scale (HAM-A) scores, and hospitalization costs. Results: Of 456 patients, 166 underwent ambulatory TOETVA and 290 underwent conventional TOETVA. No significant differences were found in clinical and surgical characteristics between the groups, including sex (P=0.363), age (P=0.077), body mass index (P=0.351), presence of internal diseases (P=0.613), presence of Hashimoto's thyroiditis (P=0.429), pathology (P=0.362), maximum tumor diameter (P=0.520), scope of surgery (P=0.850), or operative time (P=0.351). There were no significant differences in maximum tumor diameter (P=0.349), extrathyroidal tissue invasion (P=0.516), number of retrieved central lymph nodes (P=0.069), or metastatic central lymph nodes (P=0.897) between the groups. No significant differences were found in complications, including transient hypoparathyroidism (P=0.438), transient vocal cord palsy (P=0.876), transient mental nerve injury (P=0.749), permanent mental nerve injury (P=0.926), and other complications (P=1.000). Ambulatory patients had shorter hospital stays (P<0.001) and reduced hospitalization costs (P<0.001). There was no significant difference in HAM-A scores between the groups (P=0.056). Conclusions: Ambulatory TOETVA is a safe, feasible, and cost-effective procedure for selected patients. This procedure resulted in shorter hospital stays, decreased medical costs, and did not increase patient anxiety. To ensure patient safety, surgical teams must inform patients of the indications, when to seek help, and how to receive the fastest medical attention.

Is the long-acting gonadotropin-releasing hormone agonist long protocol better for patients with endometriosis undergoing IVF?

OBJECTIVE: To investigate the effect of the long-acting gonadotropin-releasing hormone agonist (GnRHa) long protocol on in vitro fertilization (IVF) outcomes of patients with endometriosis (EMs). METHODS: This retrospective cohort study was carried out from July 1, 2016 to June 30, 2021. In all, 798 patients with EMs who underwent first IVF were enrolled. The patients were classified by the ovarian stimulation protocols. The clinical outcomes of IVF were compared in each group. RESULTS: Those EMs patients who received the long-acting GnRHa long protocol had significantly higher clinical pregnancy rate (72.00%, 60.70% and 50.90%, respectively; P = 0.047 and 0.010) and implantation rate (51.0%, 44.6%, and 38.7%, respectively; P = 0.006 and <0.001) compared with the short-acting GnRHa long protocol and the GnRH antagonist protocol. Live birth rate was also significantly higher than the GnRH antagonist protocol (60.10% vs. 40.0%, P = 0.032), but not statistically different from the short-acting GnRHa (60.10% vs. 53.80%, P = 0.443). In addition, they also had significantly higher duration of stimulation, total dose of gonadotropin, and number of high-quality embryos transferred compared with other groups (P < 0.001). CONCLUSIONS: The long-acting GnRHa long protocol could improve IVF outcomes of patients with EMs compared with the short-acting GnRHa long protocol and the GnRH antagonist protocol.

Aggregation-Induced-Emission Photosensitizer-Loaded Nano-Superartificial Dendritic Cells with Directly Presenting Tumor Antigens and Reversed Immunosuppression for Photodynamically Boosted Immunotherapy.

The success of tumor immunotherapy highlights the potential of harnessing immune system to fight cancer. Activating both native T cells and exhausted T cells is a critical step for generating effective antitumor immunity, which is determined based on the efficient presentation of tumor antigens and co-stimulatory signals by antigen-presenting cells, as well as immunosuppressive reversal. However, strategies for achieving an efficient antigen presentation process and improving the immunosuppressive microenvironment remain unresolved. Here, aggregation-induced-emission (AIE) photosensitizer-loaded nano-superartificial dendritic cells (saDC@Fs-NPs) are developed by coating superartificial dendritic cells membranes from genetically engineered 4T1 tumor cells onto nanoaggregates of AIE photosensitizers. The outer cell membranes of saDC@Fs-NPs are derived from recombinant lentivirus-infected 4T1 tumor cells in which peptide-major histocompatibility complex class I, CD86, and anti-LAG3 antibody are simultaneously anchored. These saDC@Fs-NPs could directly stimulate T-cell activation and reverse T-cell exhaustion for cancer immunotherapy. The inner AIE-active photosensitizers induce immunogenic cell death to activate dendritic cells and enhance T lymphocyte infiltration by photodynamic therapy, promoting the transformation of "cold tumors" into "hot tumors," which further boosts immunotherapy efficiency. This work presents a powerful photoactive and artificial antigen-presenting platform for activating both native T cells and exhausted T cells, as well as facilitating tumor photodynamic immunotherapy.

Nanomaterial-mediated low-temperature photothermal therapy via heat shock protein inhibition.

With the continuous development of nanobiotechnology in recent years, combining photothermal materials with nanotechnology for tumor photothermal therapy (PTT) has drawn many attentions nanomedicine research. Although nanomaterial-mediated PTT is more specific and targeted than traditional treatment modalities, hyperthermia can also damage normal cells. Therefore, researchers have proposed the concept of low-temperature PTT, in which the expression of heat shock proteins (HSPs) is inhibited. In this article, the research strategies proposed in recent years based on the inhibition of HSPs expression to achieve low-temperature PTT was reviewed. Folowing this, the synthesis, properties, and applications of these nanomaterials were introduced. In addition, we also summarized the problems of nanomaterial-mediated low-temperature PTT at this stage and provided an outlook on future research directions.

A Global Regulatory Network for Dysregulated Gene Expression and Abnormal Metabolic Signaling in Immune Cells in the Microenvironment of Graves' Disease and Hashimoto's Thyroiditis.

Background: Although the pathogenetic mechanisms of Hashimoto's thyroiditis (HT) and Graves' disease (GD) have been elucidated, the molecular mechanisms by which the abnormal immune function of cellular subpopulations trigger an autoimmune attack on thyroid tissue largely remains unexplained. Methods: The study included 2 HT patients, 2 GD patients, and 1 control donor. The thyroid samples were extracted for single-cell RNA sequencing, whole transcriptome, full-length transcriptome (Oxford Nanopore Technologies), and metabolome sequencing. Identification of immune cells with dysregulated gene expression and abnormal metabolic signaling was performed in the microenvironment, both at the bulk and single-cell levels. Based on functional enrichment analysis, the biological processes and pathways involved in abnormal immune cells were further explored. Finally, according to cell communication analysis, the global regulatory network of immune cells was constructed. Results: CD4+ T cells, CD8+ T cells, and macrophages were abnormally increased in patients with HT and GD. The differentially expressed genes of these cells were significantly involved in signaling pathways, including Th1 and Th2 cell differentiation, Th17 cell differentiation, cytokine-cytokine receptor interaction, and NF-kappa B signaling pathway. Moreover, in HT, CD4+ T cells interact with macrophages via the IL16-CCR5/FGF10-FGFR1/CXCL13-CXCR3 axis, and macrophages interact with CD8+ T cells via the CD70-CD27 axis, thereby activating the T-cell receptor signaling pathway and NF-kappa B signaling pathway. In GD, CD4+ T cells interact with macrophages via the CXCR3-CXCL10/PKM-CD44/MHCII-NFKBIE axis, and macrophages interact with CD8+ T cells via the IFNG-IFNGR1/CCR7-CCL21 axis, thereby activating T-cell receptor signaling pathway, Th1 and Th2 cell differentiation, and chemokine signaling pathway. Conclusion: In HT and GD, immune dysregulated cells interact and activate relevant immune pathways and further aggravate the immune response. This may trigger the immune cells to target the thyroid tissue and influence the development of the disease.

Long noncoding RNA ALOX12-AS1 inhibits cervical cancer cells proliferation via targeting miR-3171.

Cervical cancer is a common female malignancy worldwide, and the molecular mechanism of cervical tumorigenesis remains poorly understood. A large piece of evidence have demonstrated the important roles of long noncoding RNAs (lncRNAs) in tumorigenesis, cancer progression and drug resistance. In this study, we comprehensively analyzed the lncRNAs expression pattern in cervical cancer using RNA sequencing and microarray data from the cancer genome atlas, gene expression omnibus and Genotype Tissue Expression. Moreover, we assessed the correlation between lncRNA expression levels and cervical cancer patient's survival. We uncovered hundreds of lncRNAs that are upregulated or downregulated in cervical cancer tissues. Among these aberrantly lncRNAs, some are significantly associated with cervical patients' poorer prognosis, such as ALOX12-AS1 and LINC00173. ALOX12-AS1 expression is downregulated in cervical cancer, and over-expression of ALOX12-AS1 could inhibit cervical cancer cells proliferation in vitro. Further, mechanistically investigation revealed that ALOX12-AS1 could interact with AGO2 and sponge miR-3171, thereby antagonizing its' repression of tumor suppressor phosphatase and tensin homolog expression in cervical cancer cell. Taken together, this study provides lncRNA candidates in cervical cancer and highlights the critical role of ALOX12-AS1 in cervical cancer.

Efficacy of the depot gonadotropin-releasing hormone agonist protocol on in vitro fertilization outcomes in young poor ovarian responders from POSEIDON group 3.

OBJECTIVE: To investigate whether the depot gonadotropin-releasing hormone (GnRH) agonist protocol could improve in vitro fertilization (IVF) outcomes for young poor responders from POSEIDON group 3. METHODS: This retrospective cohort study was carried out from June 2017 to June 2020. A total of 451 patients were assigned to three groups depending on the ovarian stimulation protocols. The outcome parameters of IVF were compared in each group. RESULTS: Patients who received the depot GnRH agonist had significantly higher cumulative clinical pregnancy rates (50.88%, 32.02%, and 31.88%, respectively; P = 0.009 and P = 0.007) and cumulative live birth rate (48.25%, 26.97%, and 28.99%, respectively; P = 0.004 and P = 0.009) compared with mild ovarian stimulation protocol and GnRH antagonist protocol. They also had higher live birth rate per fresh embryo transfer cycle (47.78%, 32.35%, and 36.62%, respectively), but these differences were not statistically significant. Moreover, duration of stimulation, total dose of gonadotropins and endometrial thickness were significantly higher among women who received the depot GnRH agonist (P < 0.001). However, they had lower embryo transfer cancellation rate, and abnormal endometrium rate (P < 0.001). CONCLUSION: The depot GnRH agonist protocol may improve cumulative clinical pregnancy rate and cumulative live birth rate for young women with poor ovarian response from POSEIDON group 3.

Hsa_circ_0038383-mediated competitive endogenous RNA network in recurrent implantation failure.

BACKGROUND: Inadequate endometrial receptivity contributes to recurrent implantation failure (RIF) during IVF-embryo transfer. Though multiple circRNAs have been confirmed differentially expression in RIF, the potential function of novel circRNAs needed to be detected. RESULTS: The top ten DEcircRNAs were selected as initial candidates. A ceRNA network was conducted on the basis of circRNA-miRNA-mRNA potential interaction, consisting of 10 DEcircRNAs, 28 DEmiRNAs and 59 DEmRNAs. Three down-regulation circRNAs with high degree of connectivity were verified by RT-qPCR, and results suggested that only hsa_circ_0038383 was significantly downregulation in RIF compared with control group. Subsequently, three hub genes (HOXA3, HOXA9 and PBX1) were identified as hub genes. Ultimately, a subnetwork was determined based on one DEcircRNA (hsa_circ_0038383), two DEmiRNAs (has-miR-196b-5p and has-miR-424-5p), and three DEmRNAs (HOXA3, HOXA9 and PBX1). Following verification, hsa_circ_0038383/miR-196b-5p/HOXA9 axis may be a key pathway in affecting RIF. CONCLUSION: In summary, a hsa_circ_0038383-mediated ceRNA network related to RIF was proposed. This network provided new insight into exploring potential biomarkers for diagnosis and clinical treatment of RIF. METHODS: We retrieved the expression profiles of RIF from GEO databases (circRNA, microRNA and mRNA) and constructed a competing endogenous RNAs (ceRNA) network based on predicted circRNA-miRNA and miRNA-mRNA pairs. The expression levels of three hub DEcircRNAs identified by cytoscape were validated by RT-qPCR.

hUMSC transplantation restores ovarian function in POI rats by inhibiting autophagy of theca-interstitial cells via the AMPK/mTOR signaling pathway.

BACKGROUND: Previous studies of primary ovarian insufficiency (POI) have focused on granulosa cells (GCs) and ignored the role of theca-interstitial cells (TICs). This study aims to explore the mechanism of the protective effects of human umbilical cord-derived mesenchymal stem cells (hUMSCs) on ovarian function in POI rats by regulating autophagy of TICs. METHODS: The POI model was established in rats treated with cisplatin (CDDP). The hUMSCs were transplanted into POI rats by tail vein. Enzyme-linked immunosorbent assay (ELISA) analysis, hematoxylin and eosin (HE) staining, and immunohistochemistry were used to measure the protective effects of hUMSCs. The molecular mechanisms of injury and repairment of TICs were assessed by immunofluorescence, transmission electron microscope (TEM), flow cytometry (FCM), western blot, and quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: In vivo, hUMSC transplantation restored the ovarian function and alleviated the apoptosis of TICs in POI rats. In vitro, hUMSCs reduced the autophagy levels of TICs by reducing oxidative stress and regulating AMPK/mTOR signaling pathway, thereby alleviating the apoptosis of TICs. CONCLUSION: This study indicates that hUMSCs protected ovarian function in POI by regulating autophagy signaling pathway AMPK/mTOR.

Effect of vitamin D status on normal fertilization rate following in vitro fertilization.

BACKGROUND: Vitamin D plays critical role in the female reproductive system. It seems that vitamin D is associated with clinical pregnancy outcomes of assisted reproductive technologies (ART), but its role remains elusive. This study is aimed to establish whether vitamin D is associated with clinical outcomes of in vitro fertilization (IVF). METHODS: The cross-sectional study was carried out from January 1st 2017 to December 31st 2017. A total of 848 patients who had indications for IVF were enrolled. The patients were classified by serum 25 (OH) D quartiles. The outcome parameters of IVF were compared in each group, including normal fertilization rate, high quality embryo rate, clinical pregnancy rate, implantation rate and live birth rate. RESULTS: The median 25 (OH) D concentration was 15.25 ng/ml. Serum 25 (OH) D levels in women varied with the seasons. We found that serum 25 (OH) D levels were higher in autumn than other seasons, and the lowest level occurred in spring. Follicular fluid (FF) vitamin D levels were positively correlated with serum vitamin D levels (r = 0.85, P < 0.001). The levels of FF vitamin D were significantly higher than the levels of serum vitamin D (P < 0.001). Normal fertilization rates were significantly different among four groups (P = 0.007). The group of women with the highest serum 25 (OH) D levels had the highest normal fertilization rate. However, the clinical pregnancy rate, implantation rate and live birth rates were not significantly different among the four groups when the age, BMI, AMH, seasons of blood drawing, COH protocol, high quality embryo rate and number of embryos transferred were adjusted. In addition, we found that serum 25 (OH) D levels were significantly higher in patients received IVF than patients received R-ICSI (P = 0.013). CONCLUSIONS: Among Chinese women, lower serum vitamin D levels are associated with a lower fertilization rate in IVF. However, vitamin D level was not associated with the clinical pregnancy and live birth rate following IVF.