The prognostic impact of tumor location in non-muscle-invasive bladder cancer patients undergoing transurethral resection: insights from a cohort study utilizing chinese multicenter and SEER registries.

OBJECTIVE: Most bladder cancers are non-muscle invasive bladder cancer (NMIBC), and transurethral resection of bladder tumors (TURBT) is the standard treatment. However, postoperative recurrence remains a significant challenge, and the influence of bladder tumor location on prognosis is still unclear. This study aims to investigate how tumor location affects the prognosis of NMIBC patients undergoing TURBT and to identify the optimal surgical approach. METHODS: A multicenter study was conducted, which included Chinese NMIBC data from 15 hospitals (1996-2019) and data from 17 registries of the Surveillance, Epidemiology, and End Results database (SEER) (2000-2020). Patients initially diagnosed with NMIBC and undergoing TURBT or partial cystectomy were analyzed, with cases lost to follow-up or with missing data excluded. The study investigated the overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) among patients with different tumor locations. Kaplan-Meier, Cox regression, and propensity score matching methods were employed to explore the association between tumor location and prognosis. Stratified populations were analyzed to minimize bias. RESULTS: This study included 118,477 NMIBC patients and highlighted tumor location as a crucial factor impacting post-TURBT prognosis. Both anterior wall and dome tumors independently predicted adverse outcomes in two cohorts. For anterior wall tumors, the Chinese cohort showed hazard ratios (HR) for OS of 4.35 (P < 0.0001); RFS of 2.21 (P < 0.0001); SEER cohort OS HR of 1.10 (P = 0.0001); DSS HR of 1.13 (P = 0.0183). Dome tumors displayed similar trends (Chinese NMIBC cohort OS HR of 7.91 (P < 0.0001); RFS HR of 2.12 (P < 0.0001); SEER OS HR of 1.05 (P = 0.0087); DSS HR of 1.14 (P = 0.0006)). Partial cystectomy significantly improved the survival of dome tumor patients compared to standard TURBT treatment (P < 0.01). CONCLUSION: This study reveals the significant impact of tumor location in NMIBC patients on the outcomes of TURBT treatment, with tumors in the anterior wall and bladder dome showing poor post-TURBT prognosis. Compared to TURBT treatment, partial cystectomy improves the prognosis for bladder dome tumors. This study provides guidance for personalized treatment and prognosis management for NMIBC patients.

Identification of hub genes and potential molecular mechanisms related to drug sensitivity in acute myeloid leukemia based on machine learning.

Background: Acute myeloid leukemia (AML) is the most common form of leukemia among adults and is characterized by uncontrolled proliferation and clonal expansion of hematopoietic cells. There has been a significant improvement in the treatment of younger patients, however, prognosis in the elderly AML patients remains poor. Methods: We used computational methods and machine learning (ML) techniques to identify and explore the differential high-risk genes (DHRGs) in AML. The DHRGs were explored through multiple in silico approaches including genomic and functional analysis, survival analysis, immune infiltration, miRNA co-expression and stemness features analyses to reveal their prognostic importance in AML. Furthermore, using different ML algorithms, prognostic models were constructed and validated using the DHRGs. At the end molecular docking studies were performed to identify potential drug candidates targeting the selected DHRGs. Results: We identified a total of 80 DHRGs by comparing the differentially expressed genes derived between AML patients and normal controls and high-risk AML genes identified by Cox regression. Genetic and epigenetic alteration analyses of the DHRGs revealed a significant association of their copy number variations and methylation status with overall survival (OS) of AML patients. Out of the 137 models constructed using different ML algorithms, the combination of Ridge and plsRcox maintained the highest mean C-index and was used to build the final model. When AML patients were classified into low- and high-risk groups based on DHRGs, the low-risk group had significantly longer OS in the AML training and validation cohorts. Furthermore, immune infiltration, miRNA coexpression, stemness feature and hallmark pathway analyses revealed significant differences in the prognosis of the low- and high-risk AML groups. Drug sensitivity and molecular docking studies revealed top 5 drugs, including carboplatin and austocystin-D that may significantly affect the DHRGs in AML. Conclusion: The findings from the current study identified a set of high-risk genes that may be used as prognostic and therapeutic markers for AML patients. In addition, significant use of the ML algorithms in constructing and validating the prognostic models in AML was demonstrated. Although our study used extensive bioinformatics and machine learning methods to identify the hub genes in AML, their experimental validations using knock-out/-in methods would strengthen our findings.

Multi-omic profiling of clear cell renal cell carcinoma identifies metabolic reprogramming associated with disease progression.

Clear cell renal cell carcinoma (ccRCC) is a complex disease with remarkable immune and metabolic heterogeneity. Here we perform genomic, transcriptomic, proteomic, metabolomic and spatial transcriptomic and metabolomic analyses on 100 patients with ccRCC from the Tongji Hospital RCC (TJ-RCC) cohort. Our analysis identifies four ccRCC subtypes including De-clear cell differentiated (DCCD)-ccRCC, a subtype with distinctive metabolic features. DCCD cancer cells are characterized by fewer lipid droplets, reduced metabolic activity, enhanced nutrient uptake capability and a high proliferation rate, leading to poor prognosis. Using single-cell and spatial trajectory analysis, we demonstrate that DCCD is a common mode of ccRCC progression. Even among stage I patients, DCCD is associated with worse outcomes and higher recurrence rate, suggesting that it cannot be cured by nephrectomy alone. Our study also suggests a treatment strategy based on subtype-specific immune cell infiltration that could guide the clinical management of ccRCC.

The first case report: diagnosis and management of necrotizing fusobacterium lung abscess via BALF next-generation sequencing.

BACKGROUND: Fusobacterium necrophorum (F. necrophorum)-induced necrotizing pneumonia is a rare but severe pulmonary infection. Insufficient microbiological detection methods can lead to diagnostic difficulties. METHODS: We report a case of F. necrophorum lung abscess diagnosed by next-generation sequencing (NGS) of bronchoalveolar lavage fluid (BALF). RESULTS: BALF-NGS detected F. necrophorum, guiding subsequent targeted antibiotic therapy. With active drainage and metronidazole treatment, the patient's condition was effectively treated. CONCLUSION: BALF-NGS is a valuable tool for the rapid diagnosis of infections caused by difficult-to-culture bacteria. It played a decisive role in the early identification of F. necrophorum, enabling timely and targeted antibiotic intervention. Early diagnosis and appropriate treatment are crucial for the management of F. necrophorum pneumonia.

A rare case of scimitar syndrome with pulmonary arterial hypertension in an adult female.

Scimitar syndrome is a rare congenital anomaly characterized by partial or total anomalous pulmonary venous drainage of the right lung to the inferior vena cava. We report a case of a 67-year-old female who presented with cough and dyspnea and was diagnosed with scimitar syndrome and pulmonary arterial hypertension based on comprehensive imaging and hemodynamic evaluation. This case highlights the importance of considering scimitar syndrome as a cause of pulmonary hypertension even in adult patients.

5-methylcytosine RNA modification regulators-based patterns and features of immune microenvironment in acute myeloid leukemia.

Acute myeloid leukemia (AML) is a highly heterogeneous malignant disease of the blood cell. The current therapies for AML are unsatisfactory and the molecular mechanisms underlying AML are unclear. 5-methylcytosine (m5C) is an important posttranscriptional modification of mRNA, and is involved in the regulation of mRNA stability, translation, and other aspects of RNA metabolism. However, based on our knowledge of published literature, the role of the m5C regulators has not been explored in AML till date. In this study, we clarified the expression and gene variants of m5C regulators in AML and found that most m5C regulators were differentially expressed and correlated with disease prognosis. We also found that the methylation status of certain m5C regulators (e.g., DNMT3A, DNMT3B) affects the survival of AML patients. Two m5C modification subtypes, and high- and low-risk subgroups identified based on the expression of m5C regulators showed significant differences in the prognosis as well as immune cell infiltration. In addition, most of the m5C regulators were found to be correlated with miRNA expression in AML, as well as IC50 values of many drugs. The miRNA and GSVA analysis were used to identify the different miRNAs and KEGG or hallmark pathways between high- and low-risk subgroups. We also built a prognostic model based on m5C regulators, which was validated by two GSE databases. To verify the reliability of our analysis and conclusions, qPCR was used to identify the expressions of m5C regulators between normal and AML. In summary, we comprehensively explored the molecular characteristics of m5C regulators and built a prognostic model in AML. We proposed new mechanistic insights into the role of m5C in multiple databases and clinical data, which may pave novel ways for the development of therapeutic strategies.

CircGNB1 drives osteoarthritis pathogenesis by inducing oxidative stress in chondrocytes.

BACKGROUND: Circular RNAs (circRNAs) have risen to prominence as important regulators of biological processes. This study investigated whether circGNB1 functions as a competitive endogenous RNA to regulate the pathological process of oxidative stress in age-related osteoarthritis (OA). METHODS: The relationship between circGNB1 expression and oxidative stress/OA severity was determined in cartilages from OA patients at different ages. The biological roles of circGNB1 in oxidative stress and OA progression, and its downstream targets were determined using gain- and loss-of-function experiments in various biochemical assays in human chondrocytes (HCs). The in vivo effects of circGNB1 overexpression and knockdown were also determined using a destabilization of the medial meniscus (DMM) mouse model. RESULTS: Increased circGNB1 expression was detected in HCs under oxidative and inflammatory stress and in the cartilage of older individuals. Mechanistically, circGNB1 sponged miR-152-3p and thus blocked its interaction with its downstream mRNA target, ring finger protein 219 (RNF219), which in turn stabilized caveolin-1 (CAV1) by preventing its ubiquitination at the K47 residue. CircGNB1 inhibited IL-10 signalling by antagonizing miR-152-3p-mediated RNF219 and CAV1 inhibition. Consequently, circGNB1 overexpression promoted OA progression by enhancing catabolic factor expression and oxidative stress and by suppressing anabolic genes in vitro and in vivo. Furthermore, circGNB1 knockdown alleviated the severity of OA, whereas circGNB1 overexpression had the opposite effect in a DMM mouse model of OA. CONCLUSION: CircGNB1 regulated oxidative stress and OA progression via the miR-152-3p/RNF219/CAV1 axis. Modulating circGNB1 could be an effective strategy for treating OA.

Epidemiological Investigation of Pediatric Fractures-A Retrospective Cohort Study of 1129 Patients.

Background and Objectives: Fractures are common in pediatric trauma, and they are caused by a broad spectrum of factors. Only a few studies have discussed the mechanisms of injury and their relationships to different types of fractures. The most frequent type of fractures in different age groups remains unclear. Therefore, we aim to summarize the epidemiological characteristics of pediatric fractures in a medical center in Zhuhai, China from 2006 to 2021 and analyze the causes of fractures with the highest frequency in different age groups. Materials and Methods: We extracted the information from the Zhuhai Center for Maternal and Child Health Care of those under 14 years old who had fractures from 2006 to 2021. Results: We reviewed the information of 1145 children. The number of patients increased during the 15 years (p < 0.0001). The number of patients was significantly different between genders after Y2 (p = 0.014). In addition, more than two-thirds of patients (71.3%) had upper limb fractures, and all types of falls were the most common cause of fractures (83.6%). The incidence demonstrated an insignificant difference in age groups except for the fractures of humerus and radius. Moreover, we discovered that the prevalence of fall-related injuries decreased with age, while that of sports-related injuries increased with age. Conclusions: Our study demonstrates that the prevalence of fall-related injuries decreases with age, and that of sports-related injuries increases with age. Most patients have upper limb fractures, and all types of falls are the most common cause of fractures. Fracture types with the highest frequency differ in each age group. These findings might supplement current epidemiological knowledge of childhood fracture and provide references for decision-making in children's health policies.

A Combination of Ilizarov Frame, Externalized Locking Plate and Tibia Bridging for an Adult with Large Tibial Defect and Severe Varus Deformity Due to Chronic Osteomyelitis in Childhood: A Case Report.

Background: Various techniques have been reported to treat large, segmental tibial defects, such as autogenous bone graft, vascularized free fibula transfer and bone transport. We present a case of a 24-year-old male with a 17-year history of chronic osteomyelitis with obvious lower limb length discrepancy and severe varus deformity of the tibia secondary to osteomyelitis in childhood. Aim: The aim of this work is to provide an alternative choice for treating patients in developing countries with severe lower limb deformity caused by chronic osteomyelitis. Case Presentations: Without surgical intervention for a prolonged period of time, the patient was admitted in our institute for corrective surgery. Corrective surgery consisted of three stages: lengthening with Ilizarov frame, removal of Ilizarov frame and fixation with externalized locking plate, and removal of externalized locking plate. Tibia bridging was achieved at the distal and proximal junction. The range of motion (ROM) of the knee joint was nearly normal, but the stiffness of the ankle joint was noticeable. The remaining leg discrepancy of 0.1 cm required no application of a shoe lift. Moreover, the patient could engage in daily activities without noted limping. Conclusions: Distraction-compression osteogenesis using the Ilizarov apparatus is a powerful tool to lengthen the shortened long bone and adjust the deformity of the lower limbs. Externalized locking plates provide an alternative to the traditional bulky external fixator, as its low profile makes it more acceptable to patients without compromising axial and torsional stiffness. In all, a combination of Ilizarov frame, externalized locking plate and tibia bridging is an alternative for patients in similar conditions.

Efficacy and safety of platelet-rich plasma in the treatment of carpal tunnel syndrome: A network meta-analysis of different injection treatments.

Purpose: Carpal tunnel syndrome (CTS) is a common form of median nerve compression in the wrist caused by focal peripheral neuropathy. Platelet-rich plasma (PRP) therapy could improve the healing ability by exposing the injured tissues to high concentrations of autologous growth factors. Our study aims to compare all injective treatments for CTS and assess the efficacy and priority of PRP therapy. Methods: We searched Medline, Embase, Web of Science, Cochrane databases, and Clinicaltrial.gov until 17 October 2022. We only included data from randomized controlled trials (RCTs) that evaluated PRP injection therapy or drug injection therapy. The included RCTs measured at least one of the following three outcomes with validated instruments: in the visual analog scale (VAS), symptom severity scale (SSS), and functional status scale (FSS). Results: Overall, 19 studies with 1,066 patients were included in this study. We used the SUCRA rankings to determine the merits of various therapies. In all, 5% dextrose injections were the best treatment strategy for the VAS (MD -1.22, 95% CI -2.66 to 0.23; SUCRA = 79.2%), followed by triamcinolone (high-dose) injections (MD -0.69, 95% CI -2.11 to 0.73; SUCRA = 62.7%) and PRP injections (MD -0.39, 95% CI -1.67 to 0.89; SUCRA = 60.0%). In the SSS, the most effective intervention was hydroxyprogesterone injections (MD -0.62, 95% CI -1.09 to -0.16; SUCRA = 91.0%). The SUCRA ranking of PRP was second only to steroids and estrogen (MD -0.39, 95% CI -0.60 to -0.18; SUCRA = 60.8%). In the FSS, the best regimen strategy was hydroxyprogesterone injections (MD 0.12, 95% CI -0.30 to 0.54; SUCRA = 99.5%), followed by triamcinolone (low-dose) injections (MD -0.02, 95% CI -0.54 to 0.49; SUCRA = 87.4%) and PRP injections (MD -0.26, 95% CI -0.43 to -0.09; SUCRA = 77.1%). Conclusion: PRP is an alternative choice for CTS treatment. PRP injection is second only to steroids and estrogen in the treatment efficacy of CTS, with a wide indication and safe outcome.

Does Tranexamic Acid Reduce the Blood Loss in Various Surgeries? An Umbrella Review of State-of-the-Art Meta-Analysis.

Background: Tranexamic acid (TXA) has been applied in various types of surgery for hemostasis purposes. The efficacy and safety of TXA are still controversial in different surgeries. Guidelines for clinical application of TXA are needed. Materials and method: We systematically searched multiple medical databases for meta-analyses examining the efficacy and safety of TXA. Types of surgery included joint replacement surgery, other orthopedic surgeries, cardiac surgery, cerebral surgery, etc. Outcomes were blood loss, blood transfusion, adverse events, re-operation rate, operative time and length of hospital stay, hemoglobin (Hb) level, and coagulation function. Assessing the methodological quality of systematic reviews 2 (AMSTAR 2) and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) were used for quality assessment of the included meta-analyses. Overlapping reviews were evaluated by calculating the corrected covered area (CCA). Result: In all, we identified 47 meta-analyses, of which 44 of them were of "high" quality. A total of 319 outcomes were evaluated, in which 58 outcomes were assessed as "high" quality. TXA demonstrates significant hemostatic effects in various surgeries, with lower rates of blood transfusion and re-operation, shorter operative time and length of stay, and higher Hb levels. Besides, TXA does not increase the risk of death and vascular adverse events, but it is a risk factor for seizure (a neurological event) in cardiac surgery. Conclusion: Our study demonstrates that TXA has a general hemostatic effect with very few adverse events, which indicates TXA is the recommended medication to prevent excessive bleeding and reduce the blood transfusion rate. We also recommend different dosages of TXA for different types of adult surgery. However, we could not recommend a unified dosage for different surgeries due to the heterogeneity of the experimental design. Systematic Review Registration: clinicaltrials.gov/, identifier CRD42021240303.

Two-stage strategy for neglected Monteggia fracture in children: A retrospective study of 51 patients.

ABSTRACT: A neglected Monteggia fracture is defined as the fracture of the proximal ulna associated with radial head dislocation (RHD) without undergoing any treatment for 4 weeks or more after injury. One-stage operation of ulnar corrective osteotomy and open reduction of RHD might result in many complications. Therefore, a two-stage strategy, including ulnar osteotomy (UO) with or without annular ligament reconstruction (ALR), was adopted at our institute since 2010.We performed a retrospective review of 51 patients with neglected Monteggia fracture between January 2010 and January 2018. Patients with bilateral problems or concomitant injuries in the ipsilateral extremity were excluded. Radiological and clinical data were collected from Hospital Database and clinical visits. All patients were divided into 2 groups based on the status of the ALR: the UO alone (UO) group and the ALR group.There were 15 patients in the UO group and 36 patients in the ALR group. The age in the UO group (6.1 ±â€Š2.3, year) was significantly younger than the ALR group (9.8 ±â€Š2.8, year) (P < .001). Concerning the duration from initial injury to surgery, there was a significant difference between the UO group (8.6 ±â€Š3.2 months) and the ALR group (23.3 ±â€Š12.6 months, P < .001). Concerning the preoperative elbow function, there was no significant difference between the UO group (67.6 ±â€Š5.0) and the ALR group (66.6 ±â€Š4.4) according to the Mayo elbow performance score (MEPS) (P = .51). Concerning the postoperative parameters, including postoperative ROM of the joint, removal of external fixator (6.7 ±â€Š0.8, 6.9 ±â€Š0.9 weeks) (P = .55), lengthening (8.9 ±â€Š2.5, 10.3 ±â€Š2.5 mm) (P = .10) and MEPS (92.7 ±â€Š2.1, 91.6 ±â€Š2.1) (P = .08), there was no significant difference between the UO group and ALR group.Two-stage strategy is a reasonable choice for selected patients with long-lasting RHD with ulnar deformity.

Cyclin-Dependent Kinase 9 (CDK9) Inhibitor Atuveciclib Suppresses Intervertebral Disk Degeneration via the Inhibition of the NF-κB Signaling Pathway.

Intervertebral disk degeneration (IVDD) is a spinal disk condition caused by an inflammatory response induced by various proinflammatory cytokines, such as interleukin (IL)-1ß and tumor necrosis factor (TNF)-α. cyclin-dependent kinase 9 (CDK9) is a transcriptional regulator and potential therapeutic target for many diseases, especially in regulating the activation of primary inflammatory response genes. Our study investigated a highly selective CDK9 inhibitor, atuveciclib, which protects nucleus pulposus (NP) cells from proinflammatory stimuli-induced catabolism. The effects of CDK9 inhibition were determined in human and rat NP cells treated with IL-1ß in the presence or absence of atuveciclib or small interfering RNA target CDK9. Inhibition of CDK9 led to the attenuation of inflammatory response. In addition, rat intervertebral disk (IVD) explants were used to determine the role of CDK9 inhibition in extracellular matrix degradation. The rat IVDD model also proved that CDK9 inhibition attenuated IVDD, as validated using magnetic resonance imaging and immunohistochemistry. Taken together, CDK9 is a potential therapeutic target to prevent IVDD.

Circulating CD14+CD163+CD206+ M2 Monocytes Are Increased in Patients with Early Stage of Idiopathic Membranous Nephropathy.

AIM: To analyze changes in peripheral blood monocytes and their clinical significance in patients with early stage of idiopathic membranous nephropathy (IMN). METHODS: A total of 27 patients with early stage of IMN and 16 age- and sex-matched healthy controls (HCs) were recruited for the study. The monocyte subset counts in circulation were measured by flow cytometry, and serum interleukin- (IL-) 10 and IL-12 concentrations were tested by enzyme-linked immunosorbent assay. The potential association between clinical signs and monocyte subset counts was analyzed statistically. RESULTS: Compared with the HCs, the patients with early stage of IMN had higher counts of CD14+CD163+, CD14+CD163+CD206+, and CD14+CD163+CD206+CD115+ M2-like monocytes. The CD14+CD163+CD206+ M2-like cell counts and intracellular IL-10 concentrations in the monocytes were positively correlated with progression in proteinuria. The levels of serum IL-10 were significantly higher in early IMN patients than in the HCs. Furthermore, CD14+CD163+CD206+ M2-like cell counts in the patients with incipient IMN were also positively related with 24 h urinary albumin levels and the values of serum M-type phospholipase A2 receptor (PLA2R). CONCLUSION: CD14+CD163+CD206+ M2-like monocytes may contribute to the pathologic process in early-stage IMN and could serve as potential markers for evaluating the disease severity.