Thromboelastography (TEG) parameters as potential predictors of malignancy and tumor progression in colorectal cancer.

PURPOSE: The purpose of this study was to investigate the use of thromboelastography (TEG) in patients with colorectal cancer and to examine whether the TEG parameters can be used as potential markers for disease screening and prediction of disease severity. METHODS: One-hundred fifteen healthy controls (HC), 43 patients with benign adenoma (BA), and 387 patients with colorectal cancers (CRC) were included in the study. TEG parameters (reaction time, R; clot kinetics, K; alpha angle, α-angle; maximum amplitude, MA), conventional laboratory parameters, and clinical information were collected and analyzed among the HC, BA, and CRC groups. Receiver operating characteristics (ROC) were used for differential analysis. The correlation between TEG parameters and pathological information of CRC (differentiation degree, vaso-nerve infiltration, TNM stage) was analyzed. The differences in TEG parameters at different stages of disease and pre-/post operation were compared. RESULTS: Shorter K and higher α-angle/MA were found in patients with CRC compared with HC and BA (P < 0.001). TEG parameters demonstrated moderate diagnostic value (distinguish CRC from HC + BA: K-AUC = 0.693, α-angle-AUC = 0.687, MA-AUC = 0.700) in CRC but did not outperform traditional laboratory parameters. TEG hypercoagulability was closely associated with tumor markers (carcinoma embryonic antigen and carbohydrate antigen 19-9) and pathological information (differentiation degree, vaso-nerve infiltration, and TNM stage) (P < 0.05). Trend analysis showed that K decreased, but α-angle/MA increased gradually as the tumor progressed (P < 0.001). K- and α-angle showed slightly better sensitivity in predicting advanced tumors compared to traditional laboratory parameters. In CRC patients, 3-6 months after tumor resection, K [from 1.8 (1.5, 2.3) to 1.9 (1.6, 2.6)], α-angle [from 65.3 (59.0, 68.6) to 63.7 (56.6, 68.5)], and MA [from 61.0 (58.2, 66.0) to 58.9 (55.8, 61.3)] exhibited modest improvements compared to their preoperative values (P < 0.05). CONCLUSION: TEG parameters possess moderate diagnostic value in CRC diagnosis and predicting advanced tumors, and they are closely linked to surgical interventions. Although TEG parameters do not significantly outperform traditional laboratory parameters, they still hold promise as potential alternative indicators in CRC patients.

Highly Ion-Permselective Porous Organic Cage Membranes with Hierarchical Channels.

Membranes of high ion permselectivity are significant for the separation of ion species at the subnanometer scale. Here, we report porous organic cage (i.e., CC3) membranes with hierarchical channels including discrete internal cavities and cage-aligned external cavities connected by subnanometer-sized windows. The windows of CC3 sieve monovalent ions from divalent ones and the dual nanometer-sized cavities provide pathways for fast ion transport with a flux of 1.0 mol m-2 h-1 and a mono-/divalent ion selectivity (e.g., K+/Mg2+) up to 103, several orders of magnitude higher than the permselectivities of reported membranes. Molecular dynamics simulations illustrate the ion transport trajectory from the external to internal cavity via the CC3 window, where ions migrate in diverse hydration states following the energy barrier sequence of K+ < Na+ < Li+ ≪ Mg2+. This work sheds light on ion transport properties in porous organic cage channels of discrete frameworks and offers guidelines for developing membranes with hierarchical channels for efficient ion separation.

[Mean microvessel density of the prepuce and its relationship with the severity of hypospadias and early postoperative complications].

OBJECTIVE: To investigate the mean preputial microvessel density (mMVD) and features of hypospadias and their relationship with the severity and early postoperative complications of the disease. METHODS: Sixty children with hypospadias and another 14 age-matching ones with phimosis (the control group) underwent penile curvature correction, Snodgrass procedure or staged surgery, the excessive dorsal foreskin trimmed and retained. We determined the mMVD in the prepuce tissue of the patients by immunohistochemistry, and followed up those treated by Snodgrass procedure. RESULTS: The mMVD was significantly lower in the patients with severe hypospadias than in those with mild hypospadias and the controls (15.51 ± 3.53 vs 19.27 ± 4.42 and 22.09 ± 6.15, P < 0.05), with a median of 21.8 in the control group. The incidence of postoperative complications was obviously lower in the high mMVD (≥ 21.8) than in the low mMVD (< 21.8) group. CONCLUSIONS: The preputial mMVD is significantly lower in patients with severe hypospadias than in normal children, decreasing in a severity-dependent manner. The lower the preputial mMVD, the higher the incidence rate of postoperative complications. The preputial mMVD of 21.8 can be used as a reference index for evaluating the prognosis of surgery clinically. ?

Features of branch occlusive disease-type intracranial atherosclerotic stroke in young patients.

BACKGROUND: Young ischemic stroke patients are common while classification and analysis based upon imaging characteristics are rarely reported. We intend to compare the clinical and MRI characteristics of cerebral stroke induced by intracranial atherosclerosis between young patients with branch occlusive disease (BOD) and those with non-branch occlusive disease (non-BOD) or small artery disease (SAD). METHODS: A total of 151 subjects with acute infarction within the middle cerebral artery (MCA) territory were included and patients with ipsilateral internal carotid artery stenosis or cardioembolism were excluded. Based on the distribution characteristics of infarction and the presence of ipsilateral MCA stenosis, the patients were divided into three groups: BOD-striatocapsular area infarction with ipsilateral MCA stenosis; non-BOD -infarction size exceeds the striatocapsular area and accompanied by ipsilateral MCA stenosis; SAD. The clinical and MCA stenosis characteristics of the three groups were compared. RESULTS: The number of BOD patients with hypertension was significantly higher than that of SAD (92.9% vs 53.7%, p = 0.000) and non-BOD (92.9% vs 57.1%, p = 0.001); subjects with smoking history significantly exceeded that of SAD (50% vs 26.9%, p = 0.03) and subjects with family history of cardiovascular disease was significantly less than that of non-BOD (14.3% vs 41.1%). Baseline NIHSS scores and mRS scores at discharge in patients with BOD were significantly lower than those with non-BOD (p = 0.000, p = 0.001). Majority of patients in non-BOD group displayed severe MCA stenosis (39 cases, 69.6%) while that in BOD group displayed mild stenosis (26 cases, 92.9%), and the difference was statistically significant (p = 0.000). Compared with non-BOD group, the stenosis in BOD group located at a relatively distal end in the M1 segment of MCA (S/M1, 58% vs 40%, p = 0.000) and was more localized (stenosis level/ (SL/M1), 1.86 (1.35-2.6) vs 2.9 (2.0-5.0), p = 0.002). CONCLUSION: BOD in young patients with ischemic stroke induced by intracranial atherosclerosis is not rare (33.3%) and its clinical manifestations and prognosis are similar to those of SAD. This may be related to the mild localized stenosis at the distal end in the M1 segment of MCA. Control of hypertension might play a positive role in secondary prevention.

The correlation between LIN28B gene potentially functional variants and Wilms tumor susceptibility in Chinese children.

BACKGROUND: Wilms tumor (WT) is the most common urologic cancer in children. However, genetic bases underlying WT remain largely unknown. Previous studies indicated that Lin28 homolog B (LIN28B) level is significantly elevated in some WTs. Enforced expression of Lin28b during kidney development could induce WT. Genetic variations in the LIN28B gene may be related to WT susceptibility. METHOD: In this study, we aimed to assess the association between LIN28B gene polymorphisms and WT susceptibility in Chinese children. Four potentially functional polymorphisms in the LIN28B gene (rs314276 C>A, rs221634 A>T, rs221635 T>C and rs9404590 T>G) were genotyped in 145 cases and 531 cancer-free controls, using Taqman method. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the associations. RESULTS: Our results showed that the rs314276 CA genotype was associated with a decreased WT risk (CA vs CC: adjusted OR=0.65, 95% CI=0.43-0.98, P=.042). Moreover, we found that carriers of the 1-3 risk genotypes had a significantly increased WT risk when compared to the non-carriers (adjusted OR=1.51, 95% CI=1.03-2.20, P=.035). The association with risk genotypes was more predominant in children 18 month old or younger and in females. CONCLUSION: In summary, these results indicated that the LIN28B gene rs314276 C>A polymorphism alone and three combined polymorphisms may be able to modify WT susceptibility in Southern Chinese children. Our findings call for further validation in large studies with different ethnicities involved.

Meta-analysis of the effect of preoperative chemotherapy on Wilms' tumor.

PURPOSE: To evaluate the effect of preoperative chemotherapy on the event-free survival (EFS) and overall survival (OS) of Wilms' tumor in children, and to provide a basis for further improvement of clinical therapeutic effect and research level. METHODS: Relevant studies before July 2017 were retrieved from PubMed, EMBASE, Web of Science and other databases, and two evaluators were responsible independently for the studies' selection, data extraction and cross-checking according to the inclusion and exclusion criteria. EFS and OS of patients were assessed using hazard ratio (HR) and 95% confidence interval (CI). All analyses, including publication bias assessment, were performed using Stata 12 software. RESULTS: 12 studies meeting the criteria, with a total of 1639 patients, were finally enrolled. Meta-analysis showed that the preoperative chemotherapy combined with surgery, compared with surgery alone, could improve the EFS and OS of patients with Wilms' tumor (HR=1.26, 95% CI 1.07, 1.48 and 1.12 (1.03, 1.22, respectively). Both sensitivity analysis and publication bias assessment revealed that the results were reliable with no significant publication bias. CONCLUSIONS: Compared with surgery alone, preoperative chemotherapy combined with surgery can increase the EFS and OS and improve the prognosis of patients.

MicroRNA-197 Mediates the Overgrowth and Anti-Apoptotic Effects by Downregulating Insulin-Like Growth Factor-Binding Protein-3 During Nephroblastoma Tumorigenesis.

MiR-197 is frequently upregulated to induce a series of oncogenic effects, which is closely associated with poor survival and prognosis of multiple malignancies. However, the roles of miR-197 in tumorigenesis and the detailed molecular mechanism in Wilms tumor (WT) have rarely been reported. This study aimed to evaluate the expression of miR-197 in WT in vivo and the potential effects of miR-197 on the proliferation and apoptosis in SK-NEP-1 cells. A total of 15 patients with a pathologically confirmed diagnosis of WT and 15 paraneoplastic controls were enrolled. Real-time quantitative PCR (RT-qPCR) identified the upregulation of miR-197 and downregulation of insulin-like growth factors binding protein 3 (IGFBP3) in WT tissues in comparison with adjacent normal tissue (p < 0.001). CCK-8 and flow cytometry assay found that inhibition of miR-197 caused a significantly reduced proliferation along with a dramatically enhanced apoptosis of SK-NEP-1 cells (p < 0.01). IGFBP3 was overexpressed in SK-NEP-1 cells by pEGFP-C1-IGFBP3 plasmid transfection. Overexpression of IGFBP3 suppressed the proliferation and induced the apoptosis of SK-NEP-1 cells (p < 0.01). Further study detected the decreased IGFBP3 expression with miR-197 mimics SK-NEP-1 cells and increased IGFBP3 expression with miR-197 inhibitor SK-NEP-1 cells compared with mock (p < 0.01). Dual luciferase reporter assay revealed a direct interaction between miR-197 and 3'-UTR site of IGFBP3. Overall, the above results indicated that miR-197 targeted IGFBP3 to induce the overgrowth and anti-apoptotic effects of WT cells, which could promote nephroblastoma tumorigenesis. Therefore, miR-197 may be further assessed as a potential target for the treatment of WT.

Study on the microbial diversity of ear canal secretions from patients with otomycosis.

Otomycosis is caused by fungi, which usually cause discharge and additional discomfort. The highest incidence of otomycosis occurs in summer. To better treat this disease, it is necessary to study the microbial diversity of otomycosis secretions. In this regard, this study used high-throughput sequencing technology to determine the microbial diversity of the ear canal secretions of six typical patients with otomycosis in Wuhan via internal transcribed spacer (ITS) and 16S rRNA analyses and proposed a reasonable clinical treatment plan. Six patients with otomycosis in the Department of Otorhinolaryngology, Hubei Third People's Hospital Affiliated with Jianghan University, were selected from June 2022 to August 2022. The results showed that Staphylococcus spp. (average abundance 29.05%) was the dominant bacteria and Aspergillus spp. (average abundance 90.68%) was the dominant fungus involved in otomycosis secretion. Aspergillus spp. can cause inflammation of the external auditory canal combined with bacterial infections such as Staphylococcus spp., which can cause discharge in the ear canal. High-throughput sequencing provides comprehensive information on the microbial community involved in otomycosis discharge and will aid in evaluating the efficacy of clinical treatment and medication.

CircACTR2 promotes bladder cancer progression through IKBKB-mediated NF-κB signaling pathway activation.

Background: Circular RNAs (circRNAs) have significant roles in tumor progression. The role of circRNA derived from ARP2 actin-related protein 2 homolog (circACTR2) has been reported in various human diseases. However, the functions and regulatory mechanisms of circACTR2 in Bladder Cancer (BCa) remain unknown. Objectives: This study aims to explore the biological role and regulatory mechanism of circACTR2 in BCa. Methods: We analyzed the effects of circACTR2 on BCa through bioinformatics analyses, RT-qPCR, and cell function assays. Results: We observed the upregulation of circACTR2 in BCa tissues and validated its circular structure. Loss-of-function assays demonstrated that silencing circACTR2 suppressed the proliferation, invasion, and migration of BCa cells. Mechanistic investigation revealed that circACTR2 sponges miR-219a-2-3p to elevate the expression of the inhibitor of nuclear factor kappa B kinase subunit beta (IKBKB). This induced upregulation of IKKß protein promoted the nuclear translocation of p65, thereby activating the NF-κB signaling pathway. Conclusions: Our findings indicate that circACTR2 promotes BCa cell proliferation, migration, and invasion by activating the NF-κB signaling pathway via the miR-219a-2-3p/IKBKB axis, potentially unveiling a new therapeutic target for BCa.

Radiomic analysis based on magnetic resonance imaging for the prediction of VEGF expression in hepatocellular carcinoma patients.

OBJECTIVE: The purpose of this study was to investigate the ability of radiomic characteristics of magnetic resonance images to predict vascular endothelial growth factor (VEGF) expression in hepatocellular carcinoma (HCC) patients. METHODS: One hundred and twenty-four patients with HCC who underwent fat-suppressed T2-weighted imaging (FS-T2WI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) one week before surgical resection were enrolled in this retrospective study. Immunohistochemical analysis was used to evaluate the expression level of VEGF. Radiomic features were extracted from the axial FS-T2WI, DCE-MRI (arterial phase and portal venous phase) images of axial MRI. Least absolute shrinkage and selection operator (LASSO) and stepwise regression analyses were performed to select the best radiomic features. Multivariate logistic regression models were constructed and validated using tenfold cross-validation. Receiver operating characteristic (ROC) curve analysis, calibration curve analysis and decision curve analysis (DCA) were employed to evaluate these models. RESULTS: Our results show that there were 94 patients with high VEGF expression and 30 patients with low VEGF expression among the 124 HCC patients. The FS-T2WI, DCE-MRI and combined MRI radiomics models had AUCs of 0.8713, 0.7819, and 0.9191, respectively. There was no significant difference in the AUC between the FS-T2WI radiomics model and the DCE-MRI radiomics model (p > 0.05), but the AUC for the combined model was significantly greater than the AUCs for the other two models (p < 0.05) according to the DeLong test. The combined model had the greatest net benefit according to the DCA results. CONCLUSION: The radiomic model based on multisequence MR images has the potential to predict VEGF expression in HCC patients. The combined model showed the best performance.

Osiris17 is essential for stable integrin localization and function during insect wing epithelia remodeling.

The dynamic adhesion between cells and their extracellular matrix is essential for the development and function of organs. During insect wing development, two epithelial sheets contact each other at their basal sites through the interaction of ßPS integrins with the extracellular matrix. We report that Osiris17 contributes to the maintenance of ßPS integrins localization and function in developing wing of Drosophila and locust. In flies with reduced Osiris17 expression the epithelia sheets fail to maintain the integrity of basal cytoplasmic junctional bridges and basal adhesion. In contrast to the continuous basal integrin localization in control wings, this localization is disrupted during late stages of wing development in Osiris17 depleted flies. In addition, the subcellular localization revealed that Osiris17 co-localizes with the endosomal markers Rab5 and Rab11. This observation suggests an involvement of Osiris17 in endosomal recycling of integrins. Indeed, Osiris17 depletion reduced the numbers of Rab5 and Rab11 positive endosomes. Moreover, overexpression of Osiris17 increased co-localization of Rab5 and ßPS integrins and partially rescued the detachment phenotype in flies with reduced ßPS integrins. Taken together, our data suggest that Osiris17 is an endosome related protein that contributes to epithelial remodeling and morphogenesis by assisting basal integrins localization in insects.

Neoadjuvant sintilimab plus chemotherapy in EGFR-mutant NSCLC: Phase 2 trial interim results (NEOTIDE/CTONG2104).

The clinical efficacy of neoadjuvant immunotherapy plus chemotherapy remains elusive in localized epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). Here, we report interim results of a Simon's two-stage design, phase 2 trial using neoadjuvant sintilimab with carboplatin and nab-paclitaxel in resectable EGFR-mutant NSCLC. All 18 patients undergo radical surgery, with one patient experiencing surgery delay. Fourteen patients exhibit confirmed radiological response, with 44% achieving major pathological response (MPR) and no pathological complete response (pCR). Similar genomic alterations are observed before and after treatment without influencing the efficacy of subsequent EGFR-tyrosine kinase inhibitors (TKIs) in vitro. Infiltration and T cell receptor (TCR) clonal expansion of CCR8+ regulatory T (Treg)hi/CXCL13+ exhausted T (Tex)lo cells define a subtype of EGFR-mutant NSCLC highly resistant to immunotherapy, with the phenotype potentially serving as a promising signature to predict immunotherapy efficacy. Informed circulating tumor DNA (ctDNA) detection in EGFR-mutant NSCLC could help identify patients nonresponsive to neoadjuvant immunochemotherapy. These findings provide supportive data for the utilization of neoadjuvant immunochemotherapy and insight into immune resistance in EGFR-mutant NSCLC.

Identification and characterization of novel Helicobacter pylori apo-fur-regulated target genes.

In Helicobacter pylori, the ferric uptake regulator (Fur) has evolved additional regulatory functions not seen in other bacteria; it can repress and activate different groups of genes in both its iron-bound and apo forms. Because little is understood about the process of apo-Fur repression and because only two apo-Fur-repressed genes (pfr and sodB) have previously been identified, we sought to expand our understanding of this type of regulation. Utilizing published genomic studies, we selected three potential new apo-Fur-regulated gene targets: serB, hydA, and the cytochrome c553 gene. Transcriptional analyses confirmed Fur-dependent repression of these genes in the absence of iron, as well as derepression in the absence of Fur. Binding studies showed that apo-Fur directly interacted with the suspected hydA and cytochrome c553 promoters but not that of serB, which was subsequently shown to be cotranscribed with pfr; apo-Fur-dependent regulation occurred at the pfr promoter. Alignments of apo-regulated promoter regions revealed a conserved, 6-bp consensus sequence (AAATGA). DNase I footprinting showed that this sequence lies within the protected regions of the pfr and hydA promoters. Moreover, mutation of the sequence in the pfr promoter abrogated Fur binding and DNase protection. Likewise, fluorescence anisotropy studies and binding studies with mutated consensus sequences showed that the sequence was important for apo-Fur binding to the pfr promoter. Together these studies expand the known apo-Fur regulon in H. pylori and characterize the first reported apo-Fur box sequence.

The effectiveness and influencing factors of the "Y" line technique in reducing the leg length discrepancy after total hip arthroplasty.

Objective: To introduce a surgical technique (the "Y" line technique) that will control leg length discrepancy (LLD) after total hip arthroplasty and to observe its effectiveness and influencing factors. Methods: According to the inclusion and exclusion criteria, a total of 350 patients were selected in this study; 134 patients in whom used the "Y" line technique was used to control lower limb length were included in Group A and 166 patients treated with freehand methods to control lower limb length were included in Group B. A total of 50 patients in whom the standard anteroposterior x-ray of bilateral hips was taken preoperatively and in whom the "Y" line technique was used during the operation were included in Group C. Results: The postoperative LLD of Group A was 4.74 mm (3.93), that of Group B was 5.85 mm (4.60), and that of Group C was 2 mm (1.00)-the difference was statistically significant (p < 0.001). There were significant statistical differences when comparisons were made between any two groups (p < 0.01). The distribution of postoperative LLD in Group A was better than that in Group B, and this factor was better in Group C than in Group A-the difference was statistically significant (p < 0.001). Severe unequal length rates of the lower extremities (LLD > 10 mm) were 5.97% (8/134) in Group A, 14.3% (24/166) in Group B, and 0% (0/50) in Group C-the difference was statistically significant (p < 0.001). There were significant differences between Group A and Group B and between Group B and Group C (p < 0.05), but there was no significant difference between Group A and Group C (p = 0.078). Conclusion: The "Y" line technique, which does not increase the operating time and patient cost, can effectively reduce postoperative LLD. Insufficient internal rotation of the healthy lower extremity and the low projection position in the preoperative anteroposterior x-ray of the bilateral hips were important factors affecting the accuracy of the "Y" line technique.

Early surgical outcomes and influencing factors of high tibial osteotomy.

Objective: To investigate the influencing factors of functional recovery after high tibial osteotomy (HTO). Methods: A retrospective research was carried on 98 patients who underwent HTO between January 2018 and December 2020. In each case, the medial proximal tibial angle (MPTA), joint line convergence angle (JLCA), femoral tibial angle (FTA), hip-knee-ankle (HKA), weight bearing line (WBL) ratio of the knee joint, opening gap, opening angle, American knee society knee score (KSS), US Hospital for Special Surgery (HSS) score, Lysholm score, and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were measured to determine postoperative function and influential factors of pain through logistic regression analysis. Results: The follow-up time was between 18 and 42 months after operation with an average of 27.66 ± 12.9 per month. Overall functional scores were significantly improved. The influencing factors that may affect the postoperative effect of HTO include age and preoperative WBL ratio of the knee joint (WBL%). After incorporating these two factors into the multivariate logistic regression analysis, for every 1 unit increase in the preoperative WBL%, the probability of postoperative HSS being superior is 1.06 times higher than before [Exp(ß): 1.062, 95% CI: 1.01-1.1, p = 0.018]. For every year increase in age, the probability of an excellent HSS score after surgery was 0.84 times higher than that before surgery [Exp(ß): 0.843, 95% CI: 0.718-0.989, p = 0.036]. Preoperative WBL% ≥ 14.37 was 17.4 times more likely to be rated as excellent postoperative HSS than that <14.37 [Exp(ß): 17.406, 95% CI: 1.621-186.927, p = 0.018]. Conclusion: The postoperative functional scores of the patients significantly improved. Patients with preoperative WBL% ≥ 14.37% had better function after surgery.

A meta-analysis: retrograde intrarenal surgery vs. percutaneous nephrolithotomy in children.

Backgrounds: The increasing prevalence of pediatric kidney stones worldwide makes minimally invasive lithotripsy like retrograde intrarenal surgery (RIRS) and percutaneous Nephrolithotomy (PCNL) more prevalent. However, their safety and efficacy are controversial. Consequently, a meta-analysis of the comparison between RIRS and PCNL is conducted. Methods: Clinical trials were selected from PubMed, EMBASE, Scopus, and Cochrane Library databases. The data extraction and study quality assessment were performed by two individuals independently. The data relating to therapeutic effects were extracted and analyzed by Review manager 5.4. Results: Thirteen studies involving 1,019 patients were included. The micro-PCNL excelled in stone-free rate (P = 0.003), postoperative fever rate (P = 0.02), and Clavien-Dindo II complications (P = 0.05). Notably, the mean age of the micro-PCNL group was younger than other groups (P = 0.0005). The operation time in mini-PCNL was longer than RIRS (P < 0.00001) but with high heterogeneity (I2 = 99%). There was no difference in Clavien-Dindo I, II, and III complications between the PCNL and the RIRS, but mini-PCNL showed a higher probability than RIRS in Clavien-Dindo I (P = 0.0008) and II complications (P = 0.007). Conclusions: Compared with RIRS, micro-PCNL could be a better therapeutic option for kidney stones in children. Of note, more parameters should be analyzed to illustrate the efficacy of different minimally invasive surgeries for pediatric kidney stones due to poor cases in our study. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/#recordDetails, PROSPERO CRD42022323611.

Exposure to elevated temperature affects the expression of PIWI-interacting RNAs and associated transcripts in mouse testes.

BACKGROUND: Exposure to heat waves could result in adverse effects on human health, especially in male testicles. PIWI-interacting RNA (piRNA) is a novel type of small non-coding RNA, which can notably impact mRNA turnover and preserve germline maintenance in germline cells. However, piRNA's expression status when adapting to testicular heat stress remains largely unclear. OBJECTIVES: To investigate the function and mechanisms of relevant piRNAs during testicular heat stress. MATERIALS AND METHODS: In this study, a mouse testicular heat stress model was constructed, and the testes were removed for piRNA-sequencing. Bioinformatics analysis was used to discover the differential expressed piRNAs, piRNA clusters, and enriched pathways. A cell heat stress model was constructed to validate the top five upregulated piRNAs. Proliferation and apoptosis assays were utilized to validate the function of selected piRNA. Bioinformatics prediction, western blotting, and immunohistochemistry were used to illustrate the downstream mechanisms. RESULTS: Through the bioinformatics analysis, we identified the differential expression profile and enriched pathways of piRNAs and piRNA clusters during testicular hyperthermia. Besides, piR-020492 was proved to be upregulated in heat stress mouse testes and a germ cell model. A series of in vitro assays illustrated that an overexpression of piR-020492 could restrain the proliferation and promote the apoptosis of mouse germ cells. Kyoto Encyclopedia of Genes and Genomes analysis of piRNA-generating genes in the testicular heat stress model and piR-020492 targeting genes showed that the overlap pathways are adenosine monophosphate-activated protein kinase (AMPK) and insulin pathways. Validation experiments demonstrated that the key genes of AMPK and insulin pathway exhibit differential expression after an overexpression of piR-020492 or testicular heat stress. DISCUSSION AND CONCLUSION: In conclusion, our findings revealed the expression profile of piRNAs in testicular heat stress and illustrated the function and mechanisms of piR-020492 in germ cells, which could provide novel insights into the mechanism of hyperthermia-induced testicular injury.

A meta-analysis: single or double dartos flap layer in tubularized incised plate urethroplasty to prevent urethrocutaneous fistula?

Backgrounds: Urethrocutaneous fistula is one of the most common complications after urethroplasty. This meta-analysis aims to evaluate the superiority of double dartos flap to single dartos flap in preventing fistula during tubularized incised plate urethroplasty (TIPU), which is one of the most frequently used operations for hypospadias. Methods: We extracted clinical trials under the following included criteria: (1) children with TIPU; (2) a comparison of single and double flap layer; and (3) record of complications with the following excluded criteria: (1) non-comparison and (2) lack of data. Finally, 13 studies from PubMed, Cochrane Library, Scopus, and Embase have been investigated, with a total of 1,185 patients from 2005 to 2022. The quality assessment was conducted according to the Cochrane handbook and the Newcastle-Ottawa scale. A mixed-effect model was utilized to weigh the risk of fistula, phallic rotation, meatal stenosis, and wound dehiscence by the Review Manager V.5.4 software. Results: The double dartos flap layer group excels in descending the risk of postoperative fistula [odds ratio (OR) = 9.56; 95% confidence interval (CI) (4.76, 19.22); P < 0.00001] and phallic rotation [OR = 31.26; 95% CI (9.60, 101.84); P < 0.00001], while there are no differences in the rate of meatal stenosis [OR = 1.49; 95% CI (0.73, 2.70); P = 0.31] and wound dehiscence [OR = 2.30; 95% CI (0.80, 6.63); P = 0.12]. Conclusions: The routine utility of a double dartos flap layer is recommended as a potential treatment during the tubularized incised plate urethroplasty. Systematic Review Registration: identifier PROSPERO CRD42022366294.

Melatonin alleviates oxidative stress-induced injury to nucleus pulposus-derived mesenchymal stem cells through activating PI3K/Akt pathway.

Background: The changes in the microenvironment of degenerative intervertebral discs cause oxidative stress injury and excessive apoptosis of intervertebral disc endogenous stem cells. The purpose of this study was to explore the possible mechanism of the protective effect of melatonin on oxidative stress injury in NPMSCs induced by H2O2. Methods: The Cell Counting Kit-8 assay was used to evaluate the cytotoxicity of hydrogen peroxide and the protective effects of melatonin. ROS content was detected by 2'7'-dichlorofluorescin diacetate (DCFH-DA). Mitochondrial membrane potential (MMP) was detected by the JC-1assay. Transferase mediated d-UTP Nick end labeling (TUNEL) and Annexin V/PI double staining were used to determine the apoptosis rate. Additionally, apoptosis-associated proteins and PI3K/Akt signaling pathway-related proteins were evaluated by immunofluorescence, immunoblotting and PCR. ECMs were evaluated by RT‒PCR and immunofluorescence. In vivo, X-ray, Magnetic resonance imaging (MRI) and Histological analyses were used to evaluate the protective effect of melatonin. Results: Melatonin had an obvious protective effect on NPMSCs treated with 0-10 µM melatonin for 24 h. In addition, melatonin also had obvious protective effects on mitochondrial dysfunction, decreased membrane potential and cell senescence induced by H2O2. More importantly, melatonin could significantly reduce the apoptosis of nucleus pulposus mesenchymal stem cells induced by H2O2 by regulating the expression of apoptosis-related proteins and decreasing the rate of apoptosis. After treatment with melatonin, the PI3K/Akt pathway was significantly activated in nucleus pulposus mesenchymal stem cells, while the protective effect was significantly weakened after PI3K-IN-1 treatment. In vivo, the results of X-ray, MRI and histological analyses showed that therapy with melatonin could partially reduce the degree of intervertebral disc degeneration. Conclusion: Our research demonstrated that melatonin can effectively alleviate the excessive apoptosis and mitochondrial dysfunction of nucleus pulposus mesenchymal stem cells induced by oxidative stress via the PI3K/Akt pathway, which provides a novel idea for the therapy of intervertebral disc degeneration. The translational potential of this article: This study indicates that melatonin can effectively alleviate the excessive apoptosis and mitochondrial dysfunction of NPMSCs through activating the PI3K/Akt pathway. Melatonin might serve as a promising candidate for the prevention and treatment of Intervertebral disc degeneration disease (IVDD) in the future.

Efficacy and Safety of Endoscopic Tympanic Membrane Catheterization Plus Ofloxacin Ear Drops in the Treatment of Secretory Otitis Media in Infants and Toddlers.

Objective: To investigate the efficacy and safety of endoscopic tympanic membrane catheterization and ofloxacin ear drops in the treatment of secretory otitis media in infants and toddlers. Methods: A total of 80 children suffering from secretory otitis media who underwent treatment in our hospital from July 2018 to April 2020 were divided into the control group (n = 40) and experimental group (n = 40) by randomization. The control group was treated with endoscopic tympanic membrane catheterization alone, while the experimental group was treated with ofloxacin ear drops based on the same treatment as the control group. The treatment effect, air conduction hearing level, clearance rate of pathogenic bacteria secreted by the ear canal, recurrence rate, and adverse reactions were compared between the two groups. Results: The treatment in the experimental group led to a significantly better outcome than that in the control group (P < 0.05). After treatment, a substantially improved air conduction hearing level in the experimental group was observed (P < 0.001). A chi-square test showed a significantly higher clearance rate of pathogenic bacteria secreted from the ear canal of the children in the experimental group compared to that of the control group (P < 0.05). The treatment in the experimental group resulted in a lower recurrence rate and adverse reaction rate as compared to the control group (P < 0.05). Conclusion: Concurrent endoscopic tympanic membrane catheterization and ofloxacin ear drops showed excellent efficacy in the treatment of secretory otitis media in infants and toddlers. The therapy offers promising solutions for the improvement of hearing level, increase of clearance rate of pathogenic bacteria secreted from the ear canal, and decrease of disease recurrence and adverse reactions during treatment.