Comparative genomics provides insights into the aquatic adaptations of mammals.

The ancestors of marine mammals once roamed the land and independently committed to an aquatic lifestyle. These macroevolutionary transitions have intrigued scientists for centuries. Here, we generated high-quality genome assemblies of 17 marine mammals (11 cetaceans and six pinnipeds), including eight assemblies at the chromosome level. Incorporating previously published data, we reconstructed the marine mammal phylogeny and population histories and identified numerous idiosyncratic and convergent genomic variations that possibly contributed to the transition from land to water in marine mammal lineages. Genes associated with the formation of blubber (NFIA), vascular development (SEMA3E), and heat production by brown adipose tissue (UCP1) had unique changes that may contribute to marine mammal thermoregulation. We also observed many lineage-specific changes in the marine mammals, including genes associated with deep diving and navigation. Our study advances understanding of the timing, pattern, and molecular changes associated with the evolution of mammalian lineages adapting to aquatic life.

Chronic high-sugar diet in adulthood protects Caenorhabditis elegans from 6-OHDA-induced dopaminergic neurodegeneration.

BACKGROUND: Diets high in saturated fat and sugar, termed "Western diets," have been associated with several negative health outcomes, including increased risk for neurodegenerative disease. Parkinson's disease (PD) is the second most prevalent neurodegenerative disease and is characterized by the progressive death of dopaminergic neurons in the brain. We build upon previous work characterizing the impact of high-sugar diets in Caenorhabditis elegans to mechanistically evaluate the relationship between high-sugar diets and dopaminergic neurodegeneration. RESULTS: Adult high-glucose and high-fructose diets, or exposure from day 1 to 5 of adulthood, led to increased lipid content, shorter lifespan, and decreased reproduction. However, in contrast to previous reports, we found that adult chronic high-glucose and high-fructose diets did not induce dopaminergic neurodegeneration alone and were protective from 6-hydroxydopamine (6-OHDA) induced degeneration. Neither sugar altered baseline electron transport chain function and both increased vulnerability to organism-wide ATP depletion when the electron transport chain was inhibited, arguing against energetic rescue as a basis for neuroprotection. The induction of oxidative stress by 6-OHDA is hypothesized to contribute to its pathology, and high-sugar diets prevented this increase in the soma of the dopaminergic neurons. However, we did not find increased expression of antioxidant enzymes or glutathione levels. Instead, we found evidence suggesting downregulation of the dopamine reuptake transporter dat-1 that could result in decreased 6-OHDA uptake. CONCLUSIONS: Our work uncovers a neuroprotective role for high-sugar diets, despite concomitant decreases in lifespan and reproduction. Our results support the broader finding that ATP depletion alone is insufficient to induce dopaminergic neurodegeneration, whereas increased neuronal oxidative stress may drive degeneration. Finally, our work highlights the importance of evaluating lifestyle by toxicant interactions.

Hologenome analysis reveals independent evolution to chemosymbiosis by deep-sea bivalves.

BACKGROUND: Bivalves have independently evolved a variety of symbiotic relationships with chemosynthetic bacteria. These relationships range from endo- to extracellular interactions, making them ideal for studies on symbiosis-related evolution. It is still unclear whether there are universal patterns to symbiosis across bivalves. Here, we investigate the hologenome of an extracellular symbiotic thyasirid clam that represents the early stages of symbiosis evolution. RESULTS: We present a hologenome of Conchocele bisecta (Bivalvia: Thyasiridae) collected from deep-sea hydrothermal vents with extracellular symbionts, along with related ultrastructural evidence and expression data. Based on ultrastructural and sequencing evidence, only one dominant Thioglobaceae bacteria was densely aggregated in the large bacterial chambers of C. bisecta, and the bacterial genome shows nutritional complementarity and immune interactions with the host. Overall, gene family expansions may contribute to the symbiosis-related phenotypic variations in different bivalves. For instance, convergent expansions of gaseous substrate transport families in the endosymbiotic bivalves are absent in C. bisecta. Compared to endosymbiotic relatives, the thyasirid genome exhibits large-scale expansion in phagocytosis, which may facilitate symbiont digestion and account for extracellular symbiotic phenotypes. We also reveal that distinct immune system evolution, including expansion in lipopolysaccharide scavenging and contraction of IAP (inhibitor of apoptosis protein), may contribute to the different manners of bacterial virulence resistance in C. bisecta. CONCLUSIONS: Thus, bivalves employ different pathways to adapt to the long-term co-existence with their bacterial symbionts, further highlighting the contribution of stochastic evolution to the independent gain of a symbiotic lifestyle in the lineage.

Predictive role of ferroptosis-related long non-coding RNAs in bladder cancer and their association with immune microenvironment and immunotherapy response.

BACKGROUND: We have previously reported that ferroptosis has an important role in bladder cancer development. In this study, we aimed to further explore the possible predictive ability of ferroptosis-related long non-coding RNAs (lncRNAs) in bladder cancer and their relation with immune microenvironment and immunotherapy response. MATERIALS AND METHODS: The ferroptosis-related lncRNAs were identified by Pearson's correlation analysis. The predictive lncRNA signature was developed by univariate and multivariate regression analyses. Only the main effects of independent variables in multivariate analysis were included in this signature. The TCGA dataset was defined as the training cohort and GEO was the validation cohort in this study. All samples were grouped into a high- or low-risk group depending on risk signature. The prognostic role of lncRNA signature was explored through survival analysis and receiver operating characteristic curve (ROC) analysis in both TCGA and GEO cohorts. Additionally, the independent prognostic ability of the lncRNA signature was confirmed by multivariate independent analysis. Furthermore, the relationship between lncRNAs and immune microenvironment as well as immunotherapy response in bladder cancers was studied. RESULTS: The Kaplan-Meier curves identified significantly poorer overall survival outcomes for high-risk groups in both TCGA (p < 0.001) and GEO (p < 0.001) cohorts. The area under the curve (AUC) during ROC analysis of 1, 3, and 5 years was 0.781 ± 0.046, 0.784 ± 0.027, and 0.817 ± 0.025, respectively, in the TCGA cohort and 0.665 ± 0.177, 0.719 ± 0.068, and 0.791 ± 0.055, respectively, in the GEO cohort. The multivariate independent analysis in TCGA cohort identified age (p = 0.003), stage (p < 0.001), and signature risk score (p < 0.001) as independent risk factors for overall survival. Furthermore, this study demonstrated a significant difference in infiltration levels of various immune cells between high- and low-risk groups. The high risk group tended to have a lower expression of proteins including PD1 (p < 0.01), PD-L1 (p < 0.01), CTLA-4 (p < 0.05), etc. corresponding to various immune checkpoints. Additionally, the immunotherapy trial confirmed that the high-risk group tended to have a poorer treatment response than the low-risk group (p < 0.001). CONCLUSIONS: The ferroptosis-related lncRNAs exhibited a good predictive capacity for overall survival in bladder cancer. Additionally, they could be utilized to reveal tumour-immune microenvironment and immunotherapy responses.

An effective N6-methyladenosine-related long non-coding RNA prognostic signature for predicting the prognosis of patients with bladder cancer.

BACKGROUND: Bladder cancer (BLCA) typically has a poor prognosis due to high relapse and metastasis rates. A growing body of evidence indicates that N6-methyladenosine (m6A) and long non-coding RNAs (lncRNAs) play crucial roles in the progression of BLCA and the treatment response of patients with BLCA. Therefore, we conducted a comprehensive RNA-seq analysis of BLCA using data from The Cancer Genome Atlas (TCGA) to establish an m6A-related lncRNA prognostic signature (m6A-RLPS) for BLCA. METHODS: Consensus clustering analysis was used to investigate clusters of BLCA patients with varying prognoses. The least absolute shrinkage and selection operator Cox regression were used to develop the m6A-RLPS. The ESTIMATE and CIBERSORT algorithms were used to evaluate the immune composition. RESULTS: A total of 745 m6A-related lncRNAs were identified using Pearson correlation analysis (|R| > 0.4, p < 0.001). Fifty-one prognostic m6A-related lncRNAs were screened using univariate Cox regression analysis. Through consensus clustering analysis, patients were divided into two clusters (clusters 1 and 2) with different overall survival rates and tumor stages based on the differential expression of the lncRNAs. Enrichment analysis demonstrated that terms related to tumor biological processes and immune-related activities were increased in patient cluster 2, which was more likely to exhibit low survival rates. Nine m6A-related prognostic lncRNAs were finally determined and subsequently used to construct the m6A-RLPS, which was verified to be an independent predictor of prognosis using univariate and multivariate Cox regression analyses. Further, a nomogram based on age, tumor stage, and the m6A-RLPS was generated and showed high accuracy and reliability with respect to predicting the survival outcomes of BLCA patients. The prognostic signature was found to be strongly correlated to tumor-infiltrating immune cells and immune checkpoint expression. CONCLUSIONS: We established a novel m6A-RLPS with a favorable prognostic value for patients with BLCA. We believe that this prognostic signature can provide new insights into the tumorigenesis of BLCA and predict the treatment response in patients with BLCA.

The impact of atrial fibrillation on outcomes in patients undergoing radical prostatectomy.

PURPOSE: To assess the role of atrial fibrillation (AF) on complicating inpatient outcomes of radical prostatectomy (RP). MATERIALS AND METHODS: We identified patients treated with RP during 2012-2014 within National Inpatient Sample (NIS) database. Length of stay, cost of hospitalization, and in-hospital complications were compared between patients with or without diagnosis of AF. Propensity score matching methods and multivariable regression analysis were used to adjust for potential confounders and a trend analysis was conducted. RESULTS: Patients with AF had a significantly longer hospital stay (coefficient 0.19, 95% CI 0.09-0.29, P < 0.001) and higher cost (coefficient 0.10, 95% CI 0.06-0.15, P < 0.001). Post-operative cardiac complications were significantly higher for patients with AF (OR 16.38, 95% CI 7.72-34.74, P < 0.001), while no differences were found in other complications between the two groups. Similar results were shown in propensity score matching methods. The cardiac complications after laparoscopic RP (OR: 37.71, 95% CI 1.85-768.73, P = 0.018) and open RP (OR: 16.78, 95% CI 1.41-199.51, P = 0.026) were significantly higher than robot-assisted RP (RARP) in patients with AF. The results of trend study indicated that postoperative cardiac complication rates showed a trend of decreasing year by year while the prevalence of AF was rising. CONCLUSIONS: Perioperative AF is associated with increased cardiac complications, longer hospital stay and higher cost in PCa patients undergoing RP. RARP may be a preferred choice for patients with AF. Attention should be paid to this special patient population. Reasonable pre-operative risk stratification and standardized management should be done to decrease perioperative complications.

DNA methylation-based classification and identification of bladder cancer prognosis-associated subgroups.

BACKGROUND: Bladder cancer (BCA) is the most common urinary tumor, but its pathogenesis is unclear, and the associated treatment strategy has rarely been updated. In recent years, a deeper understanding of tumor epigenetics has been gained, providing new opportunities for cancer detection and treatment. METHODS: We identified prognostic methylation sites based on DNA methylation profiles of BCA in the TCGA database and constructed a specific prognostic subgroup. RESULTS: Based on the consistent clustering of 402 CpGs, we identified seven subgroups that had a significant association with survival. The difference in DNA methylation levels was related to T stage, N stage, M stage, grade, sex, age, stage and prognosis. Finally, the prediction model was constructed using a Cox regression model and verified using the test dataset; the prognosis was consistent with that of the training set. CONCLUSIONS: The classification based on DNA methylation is closely related to the clinicopathological characteristics of BCA and determines the prognostic value of each epigenetic subtype. Therefore, our findings provide a basis for the development of DNA methylation subtype-specific therapeutic strategies for human bladder cancer.

Young age increases the risk of lymph-node metastasis in patients with muscle-invasive bladder urothelial carcinoma.

BACKGROUND: The risk of positive lymph nodes in patients with muscle-invasive bladder urothelial carcinoma (MIBC) can be used to guide treatment recommendations. However, little is known about the effect of age on lymph node positivity (LN+). This study aimed to evaluate the effect of age on LN+ in MIBC. METHODS: We analyzed patients with stage T2-T4 bladder urothelial carcinoma who had not received preoperative radiotherapy, had at least one lymph node examined, and underwent cystectomy between 1998 and 2015. The Cochran-Armitage trend test and logistic univariate and multivariate analyses were used to evaluate the effect of age on LN+ in all T stages. RESULTS: In total, 15,624 patients with MIBC were identified, including 747 patients aged ≤50 years (4.78%), 2614 patients aged 50-59 years (16.73%), 4914 patients aged 60-69 years (31.45%), 5225 patients aged 70-79 years old (33.44%), and 2124 patients aged > 80 years (13.59%). In T2-T4 staging, LN+ was negatively correlated with age. After adjustment for several covariates, multivariate logistic regression analysis revealed that age was an independent risk factor for LN+. CONCLUSIONS: In this large SEER analysis, Young patients with MIBC have a higher risk of lymph node metastasis. This finding is worthy of further study and may eventually affect the treatment decisions of young patients.

Sexual Functions in Women With Stress Urinary Incontinence After Mid-Urethral Sling Surgery: A Systematic Review and Meta-Analysis of Prospective Randomized and Non-Randomized Studies.

BACKGROUND: Stress urinary incontinence (SUI) is a common, distressing health issue which affects many women. Mid-urethral sling (MUS) surgeries are recommended as gold standard interventions, although evidence regarding their impact on female sexual function remains controversial. AIM: To provide high-quality evidence of the impact of MUS surgeries on sexual functions in women with SUI. METHODS: A systematic search of PubMed, Embase, and the Cochrane Library was conducted to identify studies assessing the effect of MUS treatments on sexual functions in women with SUI. The included studies were prospective randomized or non-randomized trials which assessed patients using 2 validated questionnaires, the Female Sexual Function Index (FSFI) and the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12). Pre- and postoperative data regarding sexual function were extracted. Meta-analysis of comparable data was performed using Review Manager (version 5.3) software. MAIN OUTCOME MEASURES: The relationship between MUS interventions and sexual functions was analyzed by pooling weighted mean differences (WMD) with 95% CI from studies which used either the FSFI or PISQ-12 questionnaires, before and after receiving surgical interventions. RESULTS: Of the 22 eligible studies, 13 utilized FSFI and 9 adopted the PISQ-12. Pooled analysis indicates that 6-month postoperative PISQ-12 scores were significantly higher than preoperative scores (WMD -3.31 points; 95% CI -5.32 to -1.30; P = .001). Similar results were found at the 12-month juncture (WMD -3.30 points; 95% CI -6.01 to -0.58; P = .02) and at 24 months (WMD -4.44 points; 95% CI -5.45 to -3.44; P < .00001). Likewise, pooled postoperative FSFI total scores were significantly higher than preoperative scores at 6 months (WMD -2.22 points; 95% CI -3.36 to -1.08; P = .00001) and 12 months (WMD -3.49 points; 95% CI -5.96 to -1.02; P = .006). Postoperative FSFI sub-scores also suggest that desire, arousal, orgasm, lubrication, satisfaction, and pain during sexual intercourse significantly improved postoperatively (all P < .05). Moreover, combined evidence highlighted a significant reduction in coital incontinence postoperatively (risk ratio 5.78; 95% CI 3.16-10.58; P < .00001). CLINICAL IMPLICATIONS: These assessment tools might be more appropriately used to create opportunities for counseling. STRENGTHS & LIMITATIONS: We encountered substantial heterogeneity and insufficient long term follow-up data. There is also a distinct lack of standards, in terms of data recording and reporting across this evidence base which adds to the problems with the PISQ-12 and FSFI which, even though validated, appear unsophisticated and not necessarily fit-for-purpose. CONCLUSION: This meta-analysis confirms that sexual functions do improve after MUS surgeries for women with SUI. Lai S, Diao T, Zhang W, et al. Sexual Functions in Women With Stress Urinary Incontinence After Mid-Urethral Sling Surgery: A Systematic Review and Meta-Analysis of Prospective Randomized and Non-Randomized Studies. J Sex Med 2020;17:1956-1970.

Analysis of the Correlation Between the Clinical Effect of Sacral Neuromodulation and Patient Age: A Retrospective Multicenter Study in China.

OBJECTIVES: This study aimed to evaluate whether patients stratified by age have the same level of benefits after a sacral neuromodulation (SNM) procedure for refractory lower urinary tract dysfunction. MATERIALS AND METHODS: This retrospective study comprised 211 patients with refractory lower urinary tract dysfunction who had been treated with SNM and recruited from multiple medical centers across China. Patients were grouped according to age: <40 (n = 58), 40-64 (n = 94), and > 64 (n = 59) years. Data were compared using voiding diaries and subjective scores pre-operatively, post-implantation of a stage I tined lead, and during a short-term follow-up period postimplantation of a stage II implanted pulse generator. RESULTS: In all groups, voiding diary data and subjective scores improved significantly over different periods. Residual urine improved in the 40-64 and > 64-year-old age groups. Quality of life scores improved in the <40-year-old age group. Voiding diary data among age groups varied at baseline; however, average urinary frequency did not differ at the last follow-up. Urgency and sexual life scores differed at baseline and these differences had resolved at the last follow-up. O'Leary-Sant and Pelvic Pain and Urgency/Frequency Symptoms Scale scores did not differ at baseline; however, significant differences were observed at the last follow-up. CONCLUSIONS: SNM success is unrelated to age, and age alone should not be considered a limiting factor in SNM. For older patients, an overactive bladder appears a better indication for SNM treatment; however, further studies are required to confirm this finding.

Regulation of Gap Junction Dynamics by UNC-44/ankyrin and UNC-33/CRMP through VAB-8 in C. elegans Neurons.

Gap junctions are present in both vertebrates and invertebrates from nematodes to mammals. Although the importance of gap junctions has been documented in many biological processes, the molecular mechanisms underlying gap junction dynamics remain unclear. Here, using the C. elegans PLM neurons as a model, we show that UNC-44/ankyrin acts upstream of UNC-33/CRMP in regulation of a potential kinesin VAB-8 to control gap junction dynamics, and loss-of-function in the UNC-44/UNC-33/VAB-8 pathway suppresses the turnover of gap junction channels. Therefore, we first show a signal pathway including ankyrin, CRMP, and kinesin in regulating gap junctions.

Impact of different color fiber sleeves on beam hazards of 532-nm laser and vaporization efficiency.

The 532-nm laser has become increasingly popular for the treatment of urologic diseases. However, laser beam will pose significant hazards for the health of surgeons. In order to reduce beam hazards during surgery, we compared the beam hazards of laser fiber with black sleeves to the traditional fiber with transparent sleeves, and the vaporization efficiency. A total of 18 porcine kidney specimens were vaporized in normal saline at a room temperature under 532-nm laser delivered through a 760-µm core diameter side firing fiber. Two groups were divided according to the color of fiber sleeves: the transparent and the black. Each group was then divided into another three subgroups by laser power: the 80 W group, the 120 W group, and the 160 W group. The beam hazard was evaluated by light intensity measured in a sector area at a distance of 0 m, 0.5 m, and 1 m from the irradiation center. The vaporization efficiency was measured by the vaporization groove depth under the working power of 80 W, 120 W, and 160 W with a working distance of 5 mm and irradiation time of 10 s. The light intensity measured in the black fiber sleeve group is significantly lower than that in the transparent one (P < 0.01), regardless of the measuring distance (0 m, 0.5 m, and 1.0 m) and laser power (80 W, 120 W, and 160 W). No statistical difference was found on the vaporization efficiency between the groups protected by fiber sleeves of different colors (transparent/black, p > 0.05). Compared to the traditional transparent fiber sleeves, more beam hazards will be reduced in the operative region with the protection of black fiber sleeves, especially those from the irradiation center. The vaporization efficiency is not affected by the color of fiber sleeves. Such findings may offer a completely new idea for the protection of surgeons in surgeries with 532-nm lasers.

Preliminary analysis of stimulation parameters for sacral neuromodulation in different indications: a multicenter retrospective cohort study from China.

BACKGROUND: Sacral neuromodulation (SNM) is an effective approach for treating lower urinary tract dysfunction (LUTD), and stimulation programming is essential for successful treatment. However, research on SNM programming for various indications is limited. Thus, the authors aimed to determine whether there were differences in the stimulation parameters for different SNM indications and the appropriate programming recommendations. MATERIALS AND METHODS: Clinical data were retrospectively collected from patients with LUTD who underwent SNM and completed internal pulse generator implantation. The parameters with the highest patient satisfaction or the most symptom improvement during the test period were considered optimal and used to set the programming after internal pulse generator implantation. RESULTS: After screening, 282 patients were enrolled and categorized into four groups based on the following indications: refractory overactive bladder (OAB) ( n =61), neurogenic lower urinary tract dysfunction (nLUTD) ( n =162), interstitial cystitis/painful bladder syndrome (IC/BPS) ( n =24), and idiopathic nonobstructive urinary retention (NOUR) ( n =35). When analyzing the optimal stimulus parameters, disparities in the stimulation amplitude and pulse frequency were noted among the four groups. The stimulation amplitude in the nLUTD group was higher than that in the idiopathic NOUR group ( P =0.013). Differences in pulse frequency were observed between the refractory OAB and nLUTD groups ( P <0.001) and between the refractory OAB and idiopathic NOUR groups ( P =0.001). No differences in the electrode configuration or pulse width settings existed among the four groups. CONCLUSIONS: The stimulation parameters for SNM varied among the different indications. For the initial programming of stage I, most patients are recommended to start with stimulation amplitudes below 2 V, although patients with nLUTD may benefit from higher amplitudes. A standard pulse width of 210 µs is recommended for all patients. However, for individuals experiencing nLUTD or idiopathic NOUR, the pulse frequency can begin above the standard 14 Hz but not exceed 50 Hz.

Remote programming in stage I sacral neuromodulation: a multicentre prospective feasibility study.

OBJECTIVE: Sacral neuromodulation (SNM) has emerged as an effective therapy for refractory lower urinary tract dysfunction (LUTD). Remote programming holds promise in addressing the time and economic burdens associated with outpatient programming, especially for patients in the observation period following Stage I implant surgery (where the lead is implanted first without the pulse generator). The study aimed to explore the effectiveness and patient satisfaction of remote programming for Stage I SNM patients, and analyze the benefits patients gain from remote programming. METHODS: This prospective study was conducted at multiple high-level clinical SNM centres in China. Patients requiring SNM implantation were enroled and divided into two groups based on patient preference: remote programming (RP) group and outpatient control (OC) group. Patient attitudes toward RP were assessed through questionnaires, and the degree of symptom improvement was compared between the two groups to explore the usability of RP. RESULTS: A total of 63 participants from 6 centres were included in the study, with 32 belonging to the RP group. The remote programming system presents a high level of usability (98%) and willingness (satisfaction rate: 96.83%) in result of questionnaire. RP showed a significant advantage in improving patients' score of ICSI/ICPI (medianΔICSI/ICPI RP vs. OC= -13.50 vs -2, P =0.015). And slightly ameliorate urinary symptoms such as pain (medianΔVAS RP vs. OC= -1 vs 0, P = 0.164) and urgency (medianΔOBASS -2.5 vs. -1, P = 0.,229), but the difference was not statistically significant. RP did not significantly impact the quality of life of patients ( P =0.113), so do the rate of phase-two conversion ( P = 0.926) or programming parameters. CONCLUSION: To the best of our knowledge, the presented study is the first multicenter research focusing on the remote programming of Stage I SNM patients. Through the clinical implementation and patient feedback, we demonstrate that remote programming is not inferior to in-person programming in terms of success rate, effectiveness, safety, and patient satisfaction.

Multi-disciplinary surgery for simultaneous resection of multiple tumors in a patient with newly diagnosed metastatic pheochromocytoma/paraganglioma.

Metastatic pheochromocytoma/paraganglioma (MPP) is a rare endocrine tumor that originates from extra-adrenal chromaffin cells such as the paraganglia cells of sympathetic and parasympathetic nerves. It usually causes multiple solid tumors and exhibits strong aggressiveness with poor prognosis, with a reported 5-year survival rate of less than 50%. Cases of brain and retroperitoneal metastases at the initial diagnosis have not yet been reported. We report a 41-year-old male patient initially diagnosed with MPP in the brain and retroperitoneum who underwent multi-disciplinary collaborative surgery and simultaneous removal of two tumors at our center. Postoperative pathology revealed infiltrative growth of a skull base tumor. The patient chose to receive the tyrosine kinase inhibitor sunitinib as a targeted treatment. A 3-month follow-up after surgery showed that the patient recovered well without signs of metastasis or recurrence. We present multi-disciplinary surgery under similar circumstances for enhanced treatment and postoperative management. The patient demonstrates a favorable prognosis during postoperative follow-up, indicating that simultaneous multidisciplinary surgery may offer greater benefits for MPP patients.

Application of the first rechargeable sacral neuromodulation system for treatment of neurogenic lower urinary tract dysfunction in China: a case report.

Neurogenic lower urinary tract dysfunction (NLUTD) is caused by nervous system lesions and characterized by impaired micturition and urinary incontinence. The goal of treatment is to manage these symptoms, improve quality of life, prevent urinary tract infections, and maintain urinary function. Pelvic floor muscle training and medication are commonly used for treating it. Sacral neuromodulation (SNM) has been used in the treatment of NLUTD for >20 years worldwide, and its effectiveness and safety have been verified. Several countries have begun using a rechargeable SNM system, whereas the current sacral SNM system used in China is non-rechargeable. A 29-year-old man with persistent voiding dysfunction for >20 years presented with progressive symptoms 1 year ago. He was admitted to our hospital in August 2022 for a rechargeable SNM system implantation. The patient underwent a video-urodynamic examination and the Short Form of a Urinary Quality of Life Questionnaire (SF-Qualiveen) before and 1 month after surgery. The video-urodynamic examination showed that the maximum bladder capacity significantly increased after surgery, bladder compliance improved, the phenomenon of uninhibited bladder contraction during filling decreased, and urine leakage was reduced. The SF-Qualiveen score showed the patient's quality of life significantly improved. To our knowledge, this is the first case of a rechargeable SNM system implantation in China, which shows that it is safe and effective. More clinical cases and long-term observation are still needed. In conclusion, a rechargeable SNM system has significance for health and the economy and has a broad clinical application prospect.

Chronic high-sugar diet in adulthood protects Caenorhabditis elegans from 6-OHDA induced dopaminergic neurodegeneration.

BACKGROUND: Diets high in saturated fat and sugar, termed western diets, have been associated with several negative health outcomes, including increased risk for neurodegenerative disease. Parkinson s Disease (PD) is the second most prevalent neurodegenerative disease and is characterized by the progressive death of dopaminergic neurons in the brain. We build upon previous work characterizing the impact of high sugar diets in Caenorhabditis elegans to mechanistically evaluate the relationship between high sugar diets and dopaminergic neurodegeneration. RESULTS: Non-developmental high glucose and fructose diets led to increased lipid content and shorter lifespan and decreased reproduction. However, in contrast to previous reports, we found that non-developmental chronic high-glucose and high-fructose diets did not induce dopaminergic neurodegeneration alone and were protective from 6-hydroxydopamine (6-OHDA) induced degeneration. Neither sugar altered baseline electron transport chain function, and both increased vulnerability to organism-wide ATP depletion when the electron transport chain was inhibited, arguing against energetic rescue as a basis for neuroprotection. The induction of oxidative stress by 6-OHDA is hypothesized to contribute to its pathology, and high sugar diets prevented this increase in the soma of the dopaminergic neurons. However, we did not find increased expression of antioxidant enzymes or glutathione levels. Instead, we found evidence suggesting alterations to dopamine transmission that could result in decreased 6-OHDA uptake. CONCLUSION: Our work uncovers a neuroprotective role for high sugar diets, despite concomitant decreases in lifespan and reproduction. Our results support the broader finding that ATP depletion alone is insufficient to induce dopaminergic neurodegeneration, whereas increased neuronal oxidative stress may drive degeneration. Finally, our work highlights the importance of evaluating lifestyle by toxicant interactions.

Sacral neuromodulation remote programming in patients with refractory lower urinary tract dysfunction: China's experience during the COVID-19 pandemic.

Objectives: Sacral neuromodulation is an effective, minimally invasive treatment for refractory lower urinary tract dysfunction. However, regular postoperative programming is crucial for the maintenance of the curative effects of electronic sacral stimulator devices. The outbreak of coronavirus disease 2019 (COVID-19) limited the ability of practitioners to perform traditional face-to-face programming of these stimulators. Therefore, this study aimed to evaluate the application of remote programming technology for sacral neuromodulation during the COVID-19 pandemic in China. Materials and methods: We retrospectively collected data including baseline and programming information of all patients with lower urinary tract dysfunction who underwent sacral neuromodulation remote programming in China after the outbreak of COVID-19 (i.e., December 2019). The patients also completed a self-designed telephone questionnaire on the subject. Results: A total of 51 patients from 16 centers were included. They underwent 180 total remote programming visits, and 118, 2, 25, and 54 voltage, current, pulse width, and frequency adjustments, respectively, were performed. Additionally, remote switching on and off was performed 8 times; impedance test, 54 times; and stimulation contact replacement, 25 times. The demand for remote programming was the highest during the first 6 months of sacral neuromodulation (average, 2.39 times per person). In total, 36 out of the 51 patients completed the questionnaire survey. Of these, all indicated that they chose remote programming to minimize unnecessary travel because they had been affected by COVID-19. The questionnaire also showed that remote programming could reduce the number of patient visits to the hospital, save time, reduce financial costs, and would be easy for patients to master. All surveyed patients indicated that they were satisfied with remote programming and were willing to recommend it to other patients. Conclusion: Remote programming for sacral neuromodulation is feasible, effective, safe, and highly recommended by patients with refractory lower urinary tract dysfunction. Remote programming technology has great development and application potential in the post-pandemic era.

m6A Methylation Patterns and Tumor Microenvironment Infiltration Characterization in Clear-Cell Renal Cell Carcinoma.

Increasing evidence suggests the essential regulation of RNA N6-methyladenosine (m6A) modification in carcinogenesis and immune response. Nevertheless, the potential impacts of these modifications on the tumor microenvironment (TME) immune cell infiltration characteristics in clear-cell renal cell carcinoma (ccRCC) remain unclear. Utilizing a consensus clustering algorithm, we determined three m6A modification patterns and identified three m6A-related gene clusters among 569 ccRCC samples, which were associated with different biological functions and clinical outcomes. Thereafter, the m6A score was constructed using m6A-associated signature genes to accurately exploit the m6A modification patterns within individual tumors. The m6A score was further demonstrated to be noticeably related to ccRCC prognosis. In addition, the m6A score was found to be strongly correlated with tumor mutational burden (TMB), microsatellite instability, immune infiltration, immune checkpoint expression, and immunotherapy response, which was also validated in the pan-cancer analyses. Our findings thoroughly elucidated that m6A modification contributes to tumor microenvironment immune-infiltrating characteristics and prognosis in ccRCC. Assessing the m6A modification patterns of individual patients with ccRCC will offer novel insights into TME infiltration and help develop more effective treatment strategies.

Acute effect of sacral neuromodulation on video-urodynamic parameters of neurogenic lower urinary tract dysfunction in a patient with vesicoureteral reflux: a case report.

Neurogenic lower urinary tract dysfunction (NLUTD) is a common urological disease that causes long-term complications and severely reduces patient's quality of life. Sacral neuromodulation has proven to be an effective treatment for NLUTD. However, most previous studies have focused mainly on the efficacy and safety of sacral neuromodulation in the treatment of NLUTD and less on the changes in urodynamic parameters in patients before and after sacral neuromodulation. This study aimed to evaluate the effect of short-term sacral neuromodulation on the results of video-urodynamic parameters in a 63-year-old woman with NLUTD with vesicoureteral reflux. The patient was admitted to the Department of Urology of Beijing Hospital in January 2021 and examined using video-urodynamics. In the same month, the patient underwent the first stage of sacral neuromodulation, with an experience period of 2 weeks. After the experience period ended, video-urodynamics was performed again in February 2021. By comparing the two video-urodynamic results, the effect of short-term sacral neuromodulation on the anatomy and physiology of the lower urinary tract was determined. After 2 weeks of sacral neuromodulation treatment, video-urodynamic parameter analysis showed that while the urine storage period of the patient significantly improved, the voiding period was not significantly changed. This was specifically reflected in the improvement of bladder compliance, safe capacity of the bladder, and significant reduction in vesicoureteral reflux. The improvement of the safe capacity of the bladder effectively helped the patient to control the number of intermittent catheterizations within an acceptable range, which greatly improved her quality of life. Therefore, the patient underwent permanent sacral neuromodulation implantation in February 2021. This study suggests that short-term sacral neuromodulation can significantly improve lower urinary tract function and reduce vesicoureteral reflux in patients with NLUTD with vesicoureteral reflux. In short, we believe that sacral neuromodulation may be a good choice for patients with NLUTD.