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Structural variants (SVs) significantly contribute to human genome diversity and play a crucial role in precision medicine. Although advancements in single-molecule long-read sequencing offer a groundbreaking resource for SV detection, identifying SV breakpoints and sequences accurately and robustly remains challenging. We introduce VolcanoSV, an innovative hybrid SV detection pipeline that utilizes both a reference genome and local de novo assembly to generate a phased diploid assembly. VolcanoSV uses phased SNPs and unique k-mer similarity analysis, enabling precise haplotype-resolved SV discovery. VolcanoSV is adept at constructing comprehensive genetic maps encompassing SNPs, small indels, and all types of SVs, making it well-suited for human genomics studies. Our extensive experiments demonstrate that VolcanoSV surpasses state-of-the-art assembly-based tools in the detection of insertion and deletion SVs, exhibiting superior recall, precision, F1 scores, and genotype accuracy across a diverse range of datasets, including low-coverage (10x) datasets. VolcanoSV outperforms assembly-based tools in the identification of complex SVs, including translocations, duplications, and inversions, in both simulated and real cancer data. Moreover, VolcanoSV is robust to various evaluation parameters and accurately identifies breakpoints and SV sequences. Detecting genomic structural variants (SVs) using long-read sequencing remains challenging. Here the authors introduce a hybrid pipeline for precise haplotype-resolved SV discovery that outperforms current tools across diverse long-read sequencing datasets. [ABSTRACT FROM AUTHOR]

To accurately measure the vaginal mucosa thickness across different age groups using histopathologic techniques and investigate the factors that may influence the thickness changes. This study aims to provide clinicians with objective evidence of variations in vaginal mucosal thickness, facilitating personalized medical decisions for patients. A retrospective analysis was conducted on clinical data from 348 patients who underwent local vaginal wall resection at the West China Second University Hospital, Sichuan University, from January 2021 and May 2022. The thickness of vaginal mucosa, epithelium and lamina propria was measured precisely under the microscope. And the 10th, 25th, 50th, 75th, and 90th percentile values of vaginal mucosa thickness across different age groups were counted and charted a dot-line plot. The percentile values for vaginal mucosa thickness exhibited a decreasing trend with increasing age; vaginal mucosa thickness showed significant correlations with times of delivery (P = 0.031) and age (P < 0.001), both of which were negatively associated. And vaginal mucosa thickness demonstrated no significant correlation with body mass index (BMI) (P = 0.325), times of abortions (P = 0.511), times of gestation (P = 0.101), menstrual cycle (P = 0.533), or types of delivery (P = 0.056); epithelial thickness showed significant associations with age (P < 0.001) and types of delivery (P = 0.017), both of which were negative correlations. Moreover, BMI (P = 0.429), times of abortions (P = 0.764), delivery (P = 0.079), gestation (P = 0.475), and menstrual cycle (P = 0.950) were nonassociated with epithelial thickness; lamina propria thickness displayed a significant correlation only with age (P = 0.002), and there were no obvious correlations observed between lamina propria thickness and BMI (P = 0.374), times of abortion (P = 0.417), delivery (P = 0.053), gestation (P = 0.101), types of delivery (P = 0.132) and menstrual cycle (P = 0.495). Moreover, when the age segmentation was thresholded at 35 and 50 years, both epithelial thickness and vaginal mucosa thickness were significantly correlated with age (P < 0.05). Lamina propria thickness was associated with age when the age threshold was set at 35 years (P = 0.007), whereas it showed no strong link with age when the age threshold was 50 years (P = 0.072). This study has innovatively established percentile reference values for vaginal mucosa thickness based on histopathology, furnishing clinicians with objective evidence of variations in vaginal mucosal thickness to facilitate personalized medical decisions for patients. The findings demonstrated a strong link between vaginal mucosa thickness and age, with epithelium likely playing a predominant role, while the association with lamina propria appeared to be less significant. Further research involving a larger sample size is warranted to elucidate the potential relationship with the lamina propria. [ABSTRACT FROM AUTHOR]

To identify different patterns of neurogenic lower urinary tract dysfunction management among Chinese community-dwelling individuals with spinal cord injury and explore the factors associated with latent classes. This was a cross-sectional study conducted in communities throughout China Mainland. Participants were recruited through the China Association of Persons with Physical Disability and a total of 2582 participants was included in the analysis. The data were collected by a questionnaire consisting of socio-demographic factors, disease-related factors, and a list of 8 bladder management methods. Latent class analysis was used to identify different latent classes of neurogenic lower urinary tract dysfunction management. Then the multinomial logistic regression was applied to analyze the relationship between neurogenic lower urinary tract dysfunction management patterns and socio-demographic and disease-related factors. Neurogenic lower urinary tract dysfunction management pattern among community-dwelling individuals with spinal cord injury was divided into four latent classes: "urinal collecting apparatus dominated pattern" (40.3%), "bladder compression dominated pattern" (30.7%), "intermittent catheterization dominated pattern" (19.3%) and "urethral indwelling catheterization dominated pattern" (9.6%). Multinomial logistic regression analysis found that the employment status, residential region, nursing need, payment method for catheterization products, hand function, time since spinal cord injury, urinary incontinence and concerns about social interaction affected by urination problems were significantly associated with latent classes. Only 19.3% of people used the intermittent catheterization as their main neurogenic lower urinary tract dysfunction management method. More attention needs to be paid to the promotion of the standardization process of intermittent catheterization in community-dwelling individuals with spinal cord injury. The associated factors of the four classes can be used for tailored and targeted interventions to increase the use of intermittent catheterization. [ABSTRACT FROM AUTHOR]

Chirality constitutes an inherent attribute of nature. The catalytic asymmetric synthesis of molecules with central, axial, and helical chirality is a topic of intense interest and is becoming a mature field of research. However, due to the difficulty in synthesis and the lack of a prototype, less attention has been given to planar chirality arising from the destruction of symmetry on a single planar ring. Herein, we report the catalytic asymmetric synthesis of planar-chiral dianthranilides, a unique class of tub-shaped eight-membered cyclic dilactams. This protocol is enabled by cinchona alkaloid-catalyzed (dynamic) kinetic resolution. Under mild conditions, various C2- or C1-symmetric planar-chiral dianthranilides have been readily prepared in high yields with excellent enantioselectivity. These dianthranilides can serve as an addition to the family of planar-chiral molecules. Its synthetic value has been demonstrated by kinetic resolution of racemic amines via acyl transfer, enantiodivergent synthesis of the natural product eupolyphagin, and preliminary antitumor activity studies. Chirality has long fascinated chemists, but asymmetric synthesis has largely focused on central, axial, and helical chirality to date. Here, the authors synthesize dianthranilides with planar chirality, via cinchona alkaloid-catalyzed (dynamic) kinetic resolution. [ABSTRACT FROM AUTHOR]

Long-read sequencing offers long contiguous DNA fragments, facilitating diploid genome assembly and structural variant (SV) detection. Efficient and robust algorithms for SV identification are crucial with increasing data availability. Alignment-based methods, favored for their computational efficiency and lower coverage requirements, are prominent. Alternative approaches, relying solely on available reads for de novo genome assembly and employing assembly-based tools for SV detection via comparison to a reference genome, demand significantly more computational resources. However, the lack of comprehensive benchmarking constrains our comprehension and hampers further algorithm development. Here we systematically compare 14 read alignment-based SV calling methods (including 4 deep learning-based methods and 1 hybrid method), and 4 assembly-based SV calling methods, alongside 4 upstream aligners and 7 assemblers. Assembly-based tools excel in detecting large SVs, especially insertions, and exhibit robustness to evaluation parameter changes and coverage fluctuations. Conversely, alignment-based tools demonstrate superior genotyping accuracy at low sequencing coverage (5-10×) and excel in detecting complex SVs, like translocations, inversions, and duplications. Our evaluation provides performance insights, highlighting the absence of a universally superior tool. We furnish guidelines across 31 criteria combinations, aiding users in selecting the most suitable tools for diverse scenarios and offering directions for further method development. Long-read sequencing can greatly improve detection of genomic structural variants (SVs), and numerous methods have been developed to identify SVs using long-read data. Here the authors compare the performance of these methods and provide guidelines to aid users in selecting the most suitable tools for various scenarios. [ABSTRACT FROM AUTHOR]

Background: Sacral nerve neuromodulation (SNM) has been considered the optimal second-line treatment for fecal incontinence (FI). However, SNM involves high cost and requires highly skilled operators. Percutaneous tibial nerve stimulation (PTNS) has emerged as an alternative treatment modality for FI, yielding varying clinical outcomes. We conducted this meta-analysis to evaluate the effectiveness and safety of PTNS compared to sham electrical stimulation for FI. Methods: PubMed, Embase, Web of Science, and the Cochrane Library were searched for studies from May 12, 2012 to May 12, 2022. Results: Four randomized controlled studies were included in this review, involving a total of 439 adult patients with FI (300 in the PTNS group and 194 in the sham electrical stimulation group). Our meta-analysis revealed that PTNS demonstrated superior efficacy in reducing weekly episodes of FI compared to the control groups (MD − 1.6, 95% CI − 2.94 to − 0.26, p = 0.02, I2 = 30%). Furthermore, a greater proportion of patients in the PTNS group reported more than a 50% reduction in FI episodes per week (RR 0.73, 95% CI 0.57–0.94, p = 0.02, I2 = 6%). However, no significant differences were observed in any domains of the FI Quality of Life (QoL) and St Mark's incontinence scores (MD – 2.41, 95% CI – 5.1 to 0.27, p = 0.08, I2 = 67%). Importantly, no severe adverse events related to PTNS were reported in any of the participants. Conclusions: Our meta-analysis revealed that PTNS was more effective than sham stimulation in reducing FI episodes and led to a higher proportion of patients reporting more than a 50% reduction in weekly FI episodes. [ABSTRACT FROM AUTHOR]

We conducted a cross-sectional study using an online questionnaire to investigate the current status of urinary tract infections (UTIs) and the use of clean intermittent catheterization (CIC) in Chinese community-based SCI patients and to explore the risk factors for UTIs in patients using CIC. Our findings suggest that the prevalence of UTIS is higher in Chinese community-based SCI patients compared with patients in medically developed countries. In addition, we found that CIC had the lower incidence of UTIs than urinary indwelling catheter (UIC) and suprapubic catheter (SPC), and that SCI patients with CIC had low rates of use and poor compliance. Further analysis indicated that most of the risk factors for UTIs in CIC patients were associated with irregular use of CIC. Therefore, we call for not only the need to provide stronger caregiver support and financial assistance to improve CIC adherence in Chinese community SCI patients, but also the establishment of a database of Chinese SCI patients in order to enhance the management of bladder emptying methods and further standardize the CIC operation in such patients, thus reducing the risk of UTIs in Chinese community SCI patients. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "Is percutaneous tibial nerve stimulation (PTNS) effective for fecal incontinence (FI) in adults compared with sham electrical stimulation? A meta-analysis." The correction addresses incorrect values in figures related to fecal incontinence, and provides updated versions of the figures. Additionally, two references were incorrectly placed under the wrong heading and have been moved to the correct section. The original article has been corrected. The publisher, Springer Nature, remains neutral and unbiased in relation to jurisdictional claims and institutional affiliations. [Extracted from the article]

T cell mediated adoptive immune response has been characterized as the key to anti-tumor immunity. Scientists around the world including in China, have been trying to harness the power of T cells against tumors for decades. Recently, the biosynthetic chimeric antigen receptor engineered T cell (CAR-T) strategy was developed and exhibited encouraging clinical efficacy, especially in hematological malignancies. Chimeric antigen receptor research reports began in 2009 in China according to our PubMed search results. Clinical trials have been ongoing in China since 2013 according to the trial registrations on clinicaltrials. gov.. After years of assiduous efforts, research and clinical scientists in China have made their own achievements in the CAR-T therapy field. In this review, we aim to highlight CAR-T research and clinical trials in China, to provide an informative reference for colleagues in the field. [ABSTRACT FROM AUTHOR]

Introduction: Chronic prostatitis (CP) is a frequent prostate-related complaint, impacts negatively on quality of life and is mostly of unclear etiology. Increasing attention has been paid to the prevalence of sexual dysfunctions in CP patients; however, the impact of specific types of CP and the correlation of sexual dysfunctions with psychological disorders associated with CP are not well understood. Type IIIa CP is characterized by chronic pelvic pain, urination symptoms and white blood cells in expressed prostatic secretion, but free of bacterial infection. Methods: A population of 600 type IIIa CP patients were randomly selected and 40 normal man were included as the control group. Queries were conducted by urologists. The National Institute of Health Chronic Prostatitis Symptom Index (NIH-CPSI), the International Index of Erectile Function (IIEF-5) and the Symptom Checklist 90-R were used to evaluate the symptoms and severity of prostatitis, erectile dysfunctions and psychological problems, respectively. Scores of ejaculatory pain and premature ejaculation were also collected. Results: Our study revealed that sexual dysfunctions are frequently associated with this specific type of CP. The prevalence of erectile dysfunction, premature ejaculation and ejaculatory pain was 19, 30 and 30 %, respectively. A variety of psychological problems exist among type IIIa CP patients, including depression, anxiety, somatization, obsessive-compulsive and interpersonal sensitivity. In particular, the severity of erectile dysfunctions, but not premature ejaculation and ejaculatory pain, correlated significantly with depression and anxiety. Conclusion: Our data indicate that a moderate level of sexual dysfunctions exists among the type IIIa CP patients, and highlight the association of depression and anxiety with erectile dysfunction in CP patients, suggestting that special attention should be paid to these psychological issues in clinical treatments of the prostatitis symptoms and the associated erectile dysfunctions. [ABSTRACT FROM AUTHOR]

Aberrant fibroblast growth factor (FGF) and FGF receptor (FGFR) system have been associated with breast cancer. The objectives of our study were to investigate the effects and mechanisms of FGFR inhibition on tumor growth and metastasis on breast cancer. Our studies showed that the FGFR inhibitor PD173074 decreased the viability of several human breast cancer cells, as well as 4T1 murine mammary tumor cells. Therefore, we chose 4T1 cells to study PD173074's antitumor mechanism. Flow cytometry showed that PD173074 induced 4T1 cell apoptosis in a concentration-dependent manner. Western blot demonstrated that PD173074-induced apoptosis was correlated with the inhibition of Mcl-1 and survivin. Moreover, PD173074 also significantly increased the ratio of Bax/Bcl-2. PD173074 could also block 4T1 cell migration and invasion in vitro. In 4T1 tumor-bearing mice, PD173074 significantly inhibited tumor growth without obvious side effects. Meanwhile, PD173074 functionally reduced microvessel density and proliferation index and induced tumor apoptosis. Importantly, we found that FGFR inhibition by PD173074 reduced myeloid-derived suppressor cells (MDSCs) in the blood, spleens and tumors, accompanied by the increased infiltration of CD4 and CD8 T cells in the spleens and tumors. Furthermore, PD173074 significantly inhibited breast tumor metastasis to the lung of inoculated 4T1 breast cancer cells, which was accompanied by a reduction in MDSCs. Our findings suggested that FGFR inhibition could delay breast tumor progression, impair lung metastasis and break immunosuppression by effecting on tumor microenvironment, which may provide a promising therapeutic approach for breast cancer patient. [ABSTRACT FROM AUTHOR]

A novel series of diaryl urea derivatives bearing sulfonamide moiety have been designed and synthesized. Their in vitro antitumor effect against human cancer cell lines MX-1, A375, HepG2, Ketr3 and HT-29 was screened and evaluated by the standard MTT assay with sorafenib as the positive control. Some of the compounds showed significant inhibitory activity against multiple cell lines compared to sorafenib. In particular, 2,6-dimethyl-4-{6-[3-(4-chloro-3-(trifluoromethyl)phenyl)urea]naphthalen-2-yl}sulfonyl morpholine (10d) was found to be the most potent against A375, HepG2 and Ketr3 with IC values of 0.65-0.97 μmol/L, which were 5-20-fold more potent than sorafenib. Compound 10d emerged as a valuable lead for further optimization. [ABSTRACT FROM AUTHOR]

Previous studies have demonstrated that the expression of prostate-specific membrane antigen (PSMA) is restricted to endothelium from tumor-associated neovasculature. But the expression of PSMA in osteosarcoma and its clinical significance are unknown. Using immunohistochemical analysis and quantum dot probes, we found that 46.7% (21/45) of the osteosarcoma showed positive staining for PSMA while no PSMA staining in osteofibrous dysplasia. The expression and localization of PSMA was confirmed by CD34 staining. More importantly, the expression of PSMA is correlated with tumor size, pulmonary metastasis and worse survival (survival rate 63.2% in the PSMA-negative group versus 36.6% in the PSMA-positive group). Thus, PSMA could be used as an independent prognostic marker for the osteosarcoma patients, and PSMA staining in tumor-associated neovasculature may be a potential target for antineovasculature-based therapy in osteosarcoma. [ABSTRACT FROM AUTHOR]

Purpose: Epidermal growth factor receptor (EGFR) plays an important role in the growth and metastasis of many solid tumors. Strategies that target EGFR hold promising therapeutic potential for the treatment for non-small cell lung cancer (NSCLC), as EGFR is normally overexpressed in these tumors. This study was designed to determine whether an anti-EGFR immunotoxin has anti-tumor activity against NSCLC, and if so, to further investigate the possible mechanisms of cytotoxicity. Methods: A fusion protein of anti-EGFR single-chain variable fragment (anti-EGFR scFv) and the plant toxin gelonin (rGel) was constructed, expressed in bacteria, and purified to homogeneity. Cytotoxicity of anti-EGFR scFv/rGel (E/rG) immunotoxin was assessed on A549, HCC827, and H1975 cells (EGFR-overexpressing NSCLC-derived cell lines) and A549 xenografts in nude mice. Results: Cytotoxicity experiments using E/rG on A549, HCC827, and H1975 cells demonstrated that E/rG can specifically inhibit proliferation of these cells, whereas it did not affect the proliferation of Raji cells that do not express EGFR. Treatment for A549 xenografts in nude mice with E/rG resulted in significant suppression of tumor growth compared to controls. Immunofluorescence in frozen tissue sections confirmed that E/rG could specifically bind to tumor tissues in nude mice bearing A549 tumor xenografts, while rGel alone showed no binding activity. Furthermore, E/rG inhibited the growth of A549 cells by cytotoxic effects that blocked tumor proliferation, and the immunotoxin-induced cell death may be mediated by autophagy. Conclusions: These results showed that E/rG might have significant potential as a novel clinical therapeutic agent against human NSCLC. [ABSTRACT FROM AUTHOR]

Objective: Mice injected with Bacillus Calmette-Guérin (BCG) were challenged with lipopolysaccharide (LPS) to induce inflammatory liver injury. This study was performed to explore the protective effects of interleukin (IL)-4 against liver injury induced by BCG and LPS in mice. Materials and methods: Mice injected with BCG (125 mg/kg) were challenged with LPS (10 μg/kg) to induce the model of inflammatory liver injury. Half an hour after injection of LPS, mice were subcutaneously administered rmIL-4 at 5 and 0.5 μg/kg, respectively. Liver injury was evaluated by serum transaminase assay and H & E staining. Liver cytokine concentrations were determined by enzyme-linked immunosorbent assay, and intrahepatic cytokine and iNOS mRNA levels by reverse transcriptase polymerase chain reaction. Intrahepatic apoptosis was evaluated by terminal deoxynucleotidyl transferase mediated nick end labeling. NF-κB p65 and ERK signal pathway was detected by Western-blotting. NF-κB signal pathway was also detected by electrophoretic mobility shift assay. Results: IL-4 reduced the serum ALT, AST and LDH, alleviated the inflammatory cells infiltration, down regulated the expression of TNF-α, IL-1β, IFN-γ, IL-6 and iNOS mRNA in liver, and alleviated hepatic glutathione depletion (GSH). In addition, IL-4 displayed inhibition of extracellular signal-regulated kinase phosphorylation and NF-κB activation. Conclusion: IL-4 may protect mice against BCG/LPS-induced immune liver injury, besides ERK and NF-κB signal pathways were involved in the effects. [ABSTRACT FROM AUTHOR]