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.

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.

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.

Promotion of trophoblast invasion by lncRNA MVIH through inducing Jun-B.

Preeclampsia (PE), a pregnancy-specific disorder, is associated with impaired uterine spiral artery remodelling, which is related to the dysfunction of trophoblast cells. Lately, mounting evidence has indicated that aberrant expression of long non-coding RNAs (lncRNAs) is associated with various human diseases. The lncRNA MVIH transcript has been shown to decrease the severity of several diseases. However, the biological function of MVIH, which is down-regulated in placental tissues in PE, has not yet been clarified. Here, we report that MVIH may act as a vital factor in the pathogenesis of PE. In this study, functional analysis revealed that the silencing of MVIH expression via transfection with small interfering RNA (siRNAs) inhibited cell growth, migration, invasion, and angiogenesis in various trophoblast cell lines, and stimulation with MVIH could promote these functions. Mass spectrometry analysis revealed that MVIH could modulate Jun-B protein expression, which has been reported to potentially regulate cell growth and angiogenesis. Further cotransfection assays were performed, revealing that MVIH and Jun-B have a synergistic effect on the regulation of angiogenesis and cell proliferation. Taking these findings together, MVIH could be associated with PE and may be a candidate biomarker for its diagnosis and treatment.

Upregulation of FoxO 1 Signaling Mediates the Proinflammatory Cytokine Upregulation in the Macrophage from Polycystic Ovary Syndrome Patients.

BACKGROUND: Chronic activation of macrophage-mediated inflammatory signals in insulin-sensitive metabolic tissues is thought to be one of the causes of insulin resistance-one of the hallmarks of the metabolic syndrome. Insulin resistance is a feature of polycystic ovary syndrome (PCOS) and is related to mitochondrial and endothelial function. METHODS: In the present study, we investigated the phosphorylation level of FoxO 1, which is suppressed by the action of AKT, triggers the TLR4 inflammatory signaling pathway in the macrophages, from polycystic ovary syndrome patients or normal subjects. Then we investigated the influence of phosphorylation level of FoxO 1FoxO 1 on the induction of proinflammatory cytokines in the macrophages and the influence by FoxO FoxO 1 knockdown on the insulin-induced glucose uptake in PCOS macrophages. RESULTS: Our results demonstrated that the significantly high level of FoxO 1FoxO 1 phosphorylation correlated with the production of proinflammatory cytokines, such as IL-6, IL-1ß, and TNF-α in the macrophages from PCOS patients. The high level of FoxO 1FoxO 1 phosphorylation enhanced the TLR-4 signaling in response to LPS, and the FoxO FoxO 1 knockdown inhibited the insulin-induced glucose uptake in PCOS macrophages. CONCLUSIONS: The findings of this paper suggest an intriguing regulatory transcriptional/signaling loop in macrophages that may contribute to maintain and exacerbate inflammation and insulin resistance in PCOS macrophages.

Association of downregulated HDAC 2 with the impaired mitochondrial function and cytokine secretion in the monocytes/macrophages from gestational diabetes mellitus patients.

Gestational diabetes mellitus (GDM) is associated with an increased risk of type 2 diabetes (T2DM) and cardiovascular diseases in later life, yet with underlying mechanisms unclear. The present study was to explore the association of upregulated histone deacetylase 2 (HDAC 2) with the impaired mitochondrial function and the cytokine secretion in the monocytes/macrophages from GDM patients. In this study, we examined the mitochondrial function, proinflamatory cytokine secretion and the HDAC 2 level in the serum or in the monocytes/macrophages from GDM patients, investigated the influence by HDAC 2 inhibitor, AR-42 (N-hydroxy-4-[[(2S)-3-methyl-2-phenylbutanoyl]amino]benzamide), on the mitochondrial function and cytokine secretion in the isolated GDM monocytes/macrophages. Results demonstrated an increased mitochondria size, mitochondrial superoxide and reactive oxygen species (ROS) production, and an undermined mitochondria membrane potential (MMP) in the GDM monocytes/macrophages. And the serum levels of interleukin (IL)-1ß, tumor necrosis factor (TNF)-α and IL-6 were also markedly higher in the GDM pregnancies, while the expression and activity of HDAC 2 was downregulated. Moreover, AR-42-mediated HDAC 2 inhibition in vitro contributed to the impaired mitochondrial function and the proinflamatory cytokine secretion. In conclusion, this study suggests an association of the impaired mitochondrial function and the promoted proinflamatory cytokine secretion with the reduced HDAC 2 activity in GDM. These findings may present HDAC 2 as a target for GDM treatment.

Chromatin composition alterations and the critical role of MeCP2 for epigenetic silencing of progesterone receptor-B gene in endometrial cancers.

OBJECTIVE: To understand the epigenetic mechanism underlying the PR-B gene silencing in endometrial cancer (EC) cells, we compared the chromatin composition between transcriptionally active and silenced PR-B genes in EC cell lines and cancer tissues. METHODS: Chromatin Immunoprecipitation (ChIP) assay was performed to measure MBD occupancy and histone acetylation/methylation in transcriptionally active and silenced PR-B genes. PR-B-positive/-negative, as well as epigenetic inhibitor-treated/-untreated EC cells were used as study models. Real-time polymerase chain reaction (PCR) and Western blot analysis were applied to measure the mRNA and protein levels of PR-B, MBD, and histones. RESULTS: A close association among PR-B methylation, MBD binding and PR-B gene silencing was observed. Treatment with epigenetic inhibitors led to dynamic changes in the PR-B chromatin composition and gene expression. Increased H3/H4 acetylation and H3-K4 methylation, and decreased H3-K9 methylation were found to be associated with re-activation of silenced PR-B genes. MeCP2 knockdown resulted in a decreased MeCP2 binding to PR-B genes and an increased PR-B expression. ChIP analysis of MeCP2 binding to PR-B genes in the PR-B-positive/-negative EC samples confirmed the significant role of MeCP2 in PR-B silencing. CONCLUSION: PR-B gene expression is regulated by a concerted action of epigenetic factors including DNA methylation, MBD binding, and histone modifications. MeCP2 occupancy of PR-B genes plays a critical role in PR-B gene silencing. These findings enriched our knowledge of the epigenetic regulation of PR-B expression in EC, and suggested that the epigenetic re-activation of PR-B could be explored as a potential strategy to sensitize the PR-B-negative endometrial cancers to progestational therapy.

Relationship between tyrosine phosphorylation and protein expression of insulin receptor and insulin resistance in gestational diabetes mellitus.

The relationship between tyrosine phosphorylation (TP) and protein expression of insulin receptor (InsR) and insulin resistance (IR) in patients with gestational diabetes mellitus (GDM) was investigated. The InsR expression and TP in skeleton muscle tissue were determined by Western blotting and immunoprecipitation in women with GDM (GDM group, n=22), normal pregnant women (normal pregnancy group, n=22) and normal non-pregnant women (normal non-pregnant group, n=13). Fasting plasma glucose (FPG) and fasting insulin (FINS) were measured by oxidase assay and immunoradioassay. The results showed that the levels of FPG (5.61±0.78 mmol/L), FINS (15.42±5.13 mU/L) and Homeostasis model assessment-IR (HOMA-IR) (1.21±0.52) in GDM group were significantly higher than those in normal pregnancy group (4.43±0.46 mmol/L, 10.56±3.07 mU/L and 0.80±0.31 respectively) (P<0.01). The levels of FINS and HOMA-IR in normal pregnancy group were significantly higher than those in normal non-pregnant group (7.56±2.31 mU/L and 0.47±0.26 respectively) (P<0.01). There was no significant difference in the InsR expression level among the three groups (P>0.05). TP of InsR with insulin stimulation was significantly decreased in GDM group (0.20±0.05) as compared with normal pregnancy group (0.26±0.06) (P<0.01). TP of InsR with insulin stimulation in normal pregnancy group was lower than that in normal non-pregnant group (0.31±0.06) (P<0.01). TP of InsR with insulin stimulation was negatively related with HOMA-IR in GDM group (r=-0.525, P<0.01). There was no correlation between the protein expression of InsR and HOMA-IR in GDM group (r=-0.236, P>0.05). It was suggested that there is no significant correlation between the protein expression of InsR in skeletal muscle and IR in GDM, but changes in TP of InsR are associated with IR in GDM.

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.

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.

NOD2 deficiency protects against cardiac remodeling after myocardial infarction in mice.

BACKGROUND/AIMS: Although the pathogenesis of myocardial infarction (MI) is multifactorial, activation of innate immune system to induce inflammation has emerged as a key pathophysiological process in MI. NOD2, one member of the NOD-like receptor (NLR) family, plays an important role in the innate immune response. This study was to examine the role of NOD2 during MI. METHODS: MI was induced by permanent ligation of the left coronary artery in wild type and NOD2(-/-) mice and cardiac fibroblasts were isolated. RESULTS: NOD2 expression was significantly increased in myocardium in post-MI mice. NOD2 deficiency improved cardiac dysfunction and remodeling after MI as evidenced by echocardiographic analysis, reduced the levels of cytokines, inflammatory cell infiltration and matrix metalloproteinase-9 (MMP-9) activity. In vitro, we further found that NOD2 activation induced the activation of MAPK signaling pathways, production of proinflammatory mediators and MMP-9 activity in cardiac fibroblasts. CONCLUSIONS: Our studies demonstrate that NOD2 is a critical component of a signal transduction pathway that links cardiac injury by exacerbation of inflammation and MMP-9 activity. Pharmacological targeting of NOD2-mediated signaling pathways may provide a novel approach to treatment of cardiovascular diseases.

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.

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.

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.