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Introduction Traumatic brain injury (TBI) is one of the prevalent critical illnesses encountered in clinical practice, often resulting in a spectrum of consciousness disorders among survivors. Prolonged states of impaired consciousness can significantly elevate the susceptibility to complications such as urinary tract infections and pulmonary issues, consequently leading to a compromised prognosis and substantially impacting the quality of life for affected individuals. Clinical studies have reported that median nerve electrical stimulation (MNES) may have a therapeutic effect in the treatment of disorders of consciousness (DOC). We plan to conduct a systematic review and meta-analysis to evaluate the efficacy and safety of MNES in the management of DOC subsequent to TBI.Methods and analysis We will conduct a comprehensive literature search in the following electronic databases: Web of Science, Embase, PubMed, Cochrane Library, China Biology Medicine, China National Knowledge Infrastructure, Wan Fang Database and Chinese Scientific Journal Database. The search will be performed from the inception of the databases until 30 September 2024. Furthermore, we will search for relevant ongoing trials in the International Clinical Trial Registry Platform, ClinicalTrials.gov and China Clinical Trial Registry. Grey literature will also be sourced from reputable sources like GreyNet International, Open Grey and Google Scholar. We will include eligible randomised controlled trials. The primary outcome of interest will be the assessment of consciousness disorder severity. To ensure rigour and consistency, two independent reviewers will screen the studies for inclusion, extract relevant data and assess the risk of bias. Any discrepancies will be resolved through discussion or consultation with a third reviewer. The quality of evidence will be evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation approach. Data synthesis and meta-analysis will be conducted using STATA 15.1 software.Ethics and dissemination This systematic review and meta-analysis do not involve the collection or use of any individual patient data, thereby obviating the necessity for ethical review. The research findings will be disseminated through publication in peer-reviewed scientific journals.PROSPERO registration number CRD42024533359.

Abstract Background It is widely accepted that there exist microbiota communities in urinary tract of healthy individuals. Imbalance in the urinary microbiome plays important roles in the development of various benign urological conditions including lower urinary track symptoms (LUTS) and overactive bladder (OAB). However, whether alteration in urinary microbiome exerts influence on the severity of OAB symptom has yet to be elucidated. The purpose of this study is to examine the correlation between urinary microbiome and the severity of OAB. Methods A total of 70 OAB patients were recruited to finish overactive bladder symptom score (OABSS) questionnaires. Catheterized urine samples were obtained for 16S rRNA gene sequencing. The species richness and evenness were evaluated by α diversity, and the difference in urinary microbiome between patients with mild or moderate/severe severity was evaluated by β diversity. The relationship between urinary microbiome and the severity of OAB symptom was evaluated using Pearson’s correlation analysis. Results Mild patients (OABSS ≤ 5, n = 17) had lower bacterial diversity (Simpson index, P = 0.024) and richness (Chao1, P = 0.023) than those with moderate/severe symptom (OABSS > 5, n = 53). Beta-diversity of urinary microbiome between two groups were significantly different. Furthermore, the score of OABSS was positively correlated with the richness index (Chao1, P = 0.002) and diversity index (Shannon index, P = 0.044) of urinary microbiome. Certain bacterial genera (e.g., Porphyromona and Prevotella) were significantly correlated with severity of OAB sub-symptoms. Conclusion This study demonstrated that urinary microbiome was intimately correlated with the severity of OAB symptom and the increase of the diversity and richness of urinary microbiome was accompanied by more severe OAB symptoms, indicating that urinary dysbiosis may play pivotal roles in the deterioration of functional bladder diseases.

Abstract Background Urogenital microbiota may be associated with the recurrence of bladder cancer, but the underlying mechanism remains unclear. The notion that microbiota can upregulate PD-L1 expression in certain epithelial tumors to promote immune escape has been demonstrated. Thus, we hypothesized that the urogenital microbiota may be involved in the recurrence and progression of non-muscle invasive bladder cancer (NMIBC) by upregulating the PD-L1 expression. To test this hypothesis, we investigated the relationship between urogenital microbial community and PD-L1 expression in male patients with NMIBC. Results 16S rRNA gene sequencing was performed to analyse the composition of urogenital microbiota, and the expression of PD-L1 in cancerous tissues was detected by immunohistochemistry. The subjects (aged 43–79 years) were divided into PD-L1-positive group (Group P, n = 9) and PD-L1-negative group (Group N, n = 19) respectively based on their PD-L1 immunohistochemical results. No statistically significant differences were found in the demographic characteristics between group P and N. We observed that group P exhibited higher species richness (based on Observed species and Ace index, both P < 0.05). Furthermore, subgroup analysis showed that the increase in number of PD-L1 positive cells was accompanied by increased richness of urogenital microbiota. Significantly different composition of urogenital microbiota was found between group P and group N (based on weighted Unifrac and unweighted Unifrac distances metric, both P < 0.05). Enrichment of some bacterial genera (e.g., Leptotrichia, Roseomonas, and Propionibacterium) and decrease of some bacterial genera (e.g., Prevotella and Massilia) were observed in group P as compared with group N. These findings indicated that these genera may affect the expression of PD-L1 through some mechanisms to be studied. Conclusion Our study provided for the first time an overview of the association between urogenital microbiota and PD-L1 expression in male patients with NMIBC, indicating that urogenital microbiota was an important determinant of PD-L1 expression in male NMIBC patients.

Abstract Background Lower urinary tract symptoms (LUTS) is the most common complication of diabetes. However, the underlying pathogenesis of cultured negative LUTS (cn-LUTS) in diabetic patients has not been well understood. Numerous evidence indicates that urinary dysbiosis is related to urologic disorders. We aim to study alterations of the urinary microbiota of cn-LUTS in type 2 diabetes (T2D) patients. Methods Female T2D patients and controls were recruited and requested to finish the American Urological Association Symptom Index. Mid-stream urine was collected for culturing and extracting DNA. Microbial diversity and composition were analyzed by targeting to 16S rDNA. Linear discriminant analysis effect size (LEfSe) was carried out to identify significantly different bacteria. Results 32 female T2D patients and 26 controls were enrolled. No significant differences in alpha diversity were observed between patients and controls. However, statistically decreased richness (ACE index and Chao 1 index, 85.52(13.75, 204.84) vs. 129.82(63.89, 280.30) and 83.86(11.00, 210.77) vs. 125.19(62.00, 251.77), P = 0.005; Observed Species, 76(10, 175) vs. 98(54, 234), P = 0.011) and decreased species diversity (Shannon index, 1.37(0.04, 3.48) vs. 2.09(0.98, 3.43), P = 0.033; Simpson index, 0.46 (0.06, 0.99) vs. 0.23(0.07, 0.64), P = 0.029) were shown in moderate-to-severe LUTS group and high Hemoglobin A1c group, respectively. A significant difference of beta diversity was found between T2D patients and controls and T2D patients with different severity of cn-LUTS as well as the different level of Hemoglobin A1c. LEfSe revealed that 10 genera (e.g., Escherichia-Shigella and Klebsiella) were increased and 7 genera were decreasing in T2D patients, 3 genera (e.g., Escherichia-Shigella and Campylobacter) were increased and 16 genera (e.g., Prevotella) were reduced in moderate-to-severe LUTS group, 2 genera (Escherichia-Shigella and Lactobacillus) were over-represented and 10 genera (e.g., Prevotella) were under-represented in high Hemoglobin A1c group. Finally, Hemoglobin A1c was found positively correlated with the total score of the American Urological Association Symptom Index (r = 0.509, P = 0.003). Conclusions Urinary dysbiosis may be related to cn-LUTS in female T2D patients. A better understanding of urinary microbiota in the development and progression of cn-LUTS in female T2D patients was necessary. The severity of cn-LUTS was correlated to hyperglycemia and chronic hyperglycemia might induce or promote cn-LUTS by influencing urinary microbiota.

Numerous studies indicate that resident microbiome exists in urine of healthy individuals and dysbiosis of the urobiome (urinary microbiome) may be associated with pathological conditions. This study was performed to characterize the alterations in urobiome and explore its implications of clinical outcome in male patients with bladder cancer. 62 male patients with bladder cancer and 19 non-neoplastic controls were recruited. The follow-up study cohort included 40 patients who were diagnosed with non-muscle invasive bladder cancer (NMIBC) and underwent transurethral resection of bladder tumor (TURBT). Mid-stream urine samples were collected from all the participants the day before cystoscopy. DNA was extracted from urine pellet samples and processed for high throughput 16S rRNA amplicon sequencing of the V4 region using Illumina MiSeq. Sequencing reads were filtered using QIIME and clustered using UPARSE. We found bacterial richness indices (Observed Species index, Chao1 index, Ace index; all P < 0.01) increased in cancer group when compared with non-neoplastic group, while there were no differences in Shannon and Simpson index between two groups. During a median follow-up time of 12 (5.25–25) months, 5/40 (12.5%)of the patients developed recurrence and no patient suffered from progression to muscle-invasive disease. Species diversity of the microbiome was significantly higher in the recurrence group compared with non-recurrence group in patients with NMIBC after TURBT. The LEfSe analysis demonstrated that 9 genera were increased (e.g., Micrococcus and Brachybacterium) in recurrence group. To our knowledge we report the relative comprehensive study to date of the male bladder cancer urinary microbiome and its relationship to pathogenesis and clinical outcomes. Given our preliminary data, additional studies evaluating the urine microbiome in relation to clinical outcomes are warranted to improve our understanding of tumor recurrence after TURBT.

Mounting evidence indicates that microbiome plays an important role in the development and progression of cancer. The dogma that urine in healthy individuals must be sterile has been overturned. Dysbiosis of the urinary microbiome has been revealed responsible for various urological disorders, including prostate cancer. The link between chronic inflammation, microbiome and solid tumors has been established for various neoplastic diseases. However, a detailed and comprehensive analysis of urinary microenvironment of bladder cancer has not been yet reported. We performed this study to characterize the potential urinary microbial community possibly associated with bladder cancer. Mid-stream urine was collected from 31 male patients with bladder cancer and 18 non-neoplastic controls. DNA was extracted from urine pellet samples and processed for high throughput 16S rRNA amplicon sequencing of the V4 region using Illumina MiSeq. Sequencing reads were filtered using QIIME and clustered using UPARSE. We observed increased bacterial richness (Observed Species, Chao 1 and Ace indexes; cancer vs. control; 120.0 vs. 56.0; 134.5 vs. 68.3; and 139.6 vs. 72.9, respectively), enrichment of some bacterial genera (e.g., Acinetobacter, Anaerococcus, and Sphingobacterium) and decrease of some bacterial genera (e.g., Serratia, Proteus, and Roseomonas) in cancer group when compared to non-cancer group. Significant difference in beta diversity was found between cancer and non-cancer group, among different risk level, but not among different tumor grade. Enrichment of Herbaspirillum, Porphyrobacter, and Bacteroides was observed in cancer patients with high risk of recurrence and progression, which means these genera maybe potential biomarkers for risk stratification. The PICRUSt showed that various functional pathways were enriched in cancer group, including Staphylococcus aureus infection, glycerolipid metabolism and retinol metabolism. To our knowledge, we performed the most comprehensive study to date to characterize the urinary microbiome associated with bladder cancer. A better understanding of the role of microbiome in the development and progression of bladder cancer could pave a new way for exploring new therapeutic options and biomarkers.