Preliminary analysis of stimulation parameters for sacral neuromodulation in different indications: A multi-center 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, we 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 (IPG) 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 IPG 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 non-obstructive 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.

Development and validation of a nomogram based on geriatric nutritional risk index for predicting prognosis and postoperative complications in surgical patients with upper urinary tract urothelial carcinoma.

BACKGROUND: This study aimed to evaluate the potential role of the Geriatric Nutritional Risk Index (GNRI) in predicting oncological outcomes and postoperative complications in UTUC patients undergoing radical nephroureterectomy (RNU) and to develop a nomogram incorporating GNRI to predict outcomes. METHODS: A retrospective analysis was performed on 458 consecutive patients who underwent RNU in our center. According to nutritional scores, patients were divided into the following groups: low GNRI (GNRI ≤ 98) and high GNRI (GNRI > 98). Univariable and multivariable logistic regression were performed to investigate the role of GNRI in predicting the perioperative complications. The survival was compared with Kaplan - Meier curve, and test by log-rank tests. Risk factors associated with cancer-specific survival (CSS) and overall survival (OS) were evaluated using Cox proportional hazards regression model and were integrated into a nomogram for individualized risk prediction. The calibration and discrimination ability of the model were evaluated by concordance index (C-index) and risk group stratification. RESULTS: When compared with high GNRI, low GNRI had significantly lower survival (CSS, p < 0.001; OS, p < 0.001). Across all patients, multivariable analyses revealed that low GNRI was an independent prognostic factor (CSS, p = 0.007; OS, p = 0.005). Nomograms for 1-, 3-, and 5 years of CSS and OS had good performance. Patients can be stratified into different groups based on the nomogram, with significant differences in OS and CSS. Further, GNRI was also found to be an independent risk factor for postoperative complications. The complication - prediction nomogram based on GNRI was also internally validated and showed good performance. CONCLUSIONS: The GNRI score is an independent predictor for the prognosis and postoperative complications of UTUC following RNU. This study presented a nomogram incorporating preoperative GNRI that might be used as a convenient tool to facilitate the preoperative individualized prediction of short- and long-term outcomes for patients with UTUC.

Systematic oxidative stress indices predicts prognosis in patients with urothelial carcinoma of the upper urinary tract after radical nephroureterectomy.

BACKGROUND: Oxidative stress plays an important role in the occurrence and development of malignancy. However, the relationship between oxidative stress and upper urinary tract urothelial carcinoma (UTUC) prognosis remains elusive. This study aimed to evaluate the prognostic value of systematic oxidative stress indices as a predictor of patient outcomes in UTUC after radical nephroureterectomy. METHODS: Clinical data for 483 patients with UTUC who underwent radical nephroureterectomy were analyzed. Patients were categorized according to an optimal value of systematic oxidative stress indices (SOSIs), including fibrinogen (Fib), gamma-glutamyl transpeptidase (γ-GGT), creatinine (CRE), lactate dehydrogenase (LDH) and albumin (ALB). Kaplan-Meier analyses were used to investigate associations of SOSIs with overall survival (OS) and progression-free survival (PFS). Moreover, associations between SOSIs and OS and PFS were assessed with univariate and multivariate analyses. RESULTS: High values of Fib, γ-GGT, CRE, and LDH, and low values of ALB were associated with reduced OS. SOSIs status correlated with age, tumor site, surgical approach, hydronephrosis, tumor size, T stage, and lymph node status. The Kaplan-Meier survival analysis showed a significant discriminatory ability for death and progression risks in the two groups based on SOSIs. Multivariate Cox proportional hazards models showed that SOSIs were an independent prognostic indicator for OS (p = 0.007) and PFS (p = 0.021). SOSIs and clinical variables were selected to establish a nomogram for OS. The 1-, 3-, and 5-year AUC values were 0.77, 0.78, and 0.81, respectively. Calibration curves of the nomogram showed high consistencies between the predicted and observed survival probability. Decision curve analysis curves showed that the nomogram could well predict the 1-year, 3-year, and 5-year OS. CONCLUSIONS: SOSIs are an independent unfavorable predictor of OS and PFS in patients diagnosed with UTUC undergoing RNU. Therefore, incorporating SOSIs into currently available clinical parameters may improve clinical decision-making.

A simplified frailty index and nomogram to predict the postoperative complications and survival in older patients with upper urinary tract urothelial carcinoma.

Purpose: This study was designed to investigate the clinical value of a simplified five-item frailty index (sFI) for predicting short- and long-term outcomes in older patients with upper urinary tract urothelial carcinoma (UTUC) patients after radical nephroureterectomy (RNU). Method: This retrospective study included 333 patients (aged ≥65 years) with UTUC. Patients were classified into five groups: 0, 1, 2, 3, and 3+, according to sFI score. The variable importance and minimum depth methods were used to screen for significant variables, and univariable and multivariable logistic regression models applied to investigated the relationships between significant variables and postoperative complications. Survival differences between groups were analyzed using Kaplan-Meier plots and log-rank tests. Cox proportional hazards regression was used to evaluate risk factors associated with overall survival (OS) and cancer-specific survival (CSS). Further, we developed a nomogram based on clinicopathological features and the sFI. The area under the curve (AUC), Harrel's concordance index (C-index), calibration curve, and decision curve analysis (DCA) were used to evaluate the nomogram. Result: Of 333 cases identified, 31.2% experienced a Clavien-Dindo grade of 2 or greater complication. Random forest-logistic regression modeling showed that sFI significantly influenced the incidence of postoperative complications in older patients (AUC= 0.756). Compared with patients with low sFI score, those with high sFI scores had significantly lower OS and CSS (p < 0.001). Across all patients, the random survival forest-Cox regression model revealed that sFI score was an independent prognostic factor for OS and CSS, with AUC values of 0.815 and 0.823 for predicting 3-year OS and CSS, respectively. The nomogram developed was clinically valuable and had good ability to discriminate abilities for high-risk patients. Further, we developed a survival risk classification system that divided all patients into high-, moderate-, and low-risk groups based on total nomogram points for each patient. Conclusion: A simple five-item frailty index may be considered a prognostic factor for the prognosis and postoperative complications of UTUC following RNU. By using this predictive model, clinicians may increase their accuracy in predicting complications and prognosis and improve preoperative decision-making.

FOXP2 confers oncogenic effects in prostate cancer.

Identification oncogenes is fundamental to revealing the molecular basis of cancer. Here, we found that FOXP2 is overexpressed in human prostate cancer cells and prostate tumors, but its expression is absent in normal prostate epithelial cells and low in benign prostatic hyperplasia. FOXP2 is a FOX transcription factor family member and tightly associated with vocal development. To date, little is known regarding the link of FOXP2 to prostate cancer. We observed that high FOXP2 expression and frequent amplification are significantly associated with high Gleason score. Ectopic expression of FOXP2 induces malignant transformation of mouse NIH3T3 fibroblasts and human prostate epithelial cell RWPE-1. Conversely, FOXP2 knockdown suppresses the proliferation of prostate cancer cells. Transgenic overexpression of FOXP2 in the mouse prostate causes prostatic intraepithelial neoplasia. Overexpression of FOXP2 aberrantly activates oncogenic MET signaling and inhibition of MET signaling effectively reverts the FOXP2-induced oncogenic phenotype. CUT&Tag assay identified FOXP2-binding sites located in MET and its associated gene HGF. Additionally, the novel recurrent FOXP2-CPED1 fusion identified in prostate tumors results in high expression of truncated FOXP2, which exhibit a similar capacity for malignant transformation. Together, our data indicate that FOXP2 is involved in tumorigenicity of prostate.

Identifying possible hub genes and biological mechanisms shared between bladder cancer and inflammatory bowel disease using machine learning and integrated bioinformatics.

BACKGROUND: Recent studies have shown that inflammatory bowel disease (IBD) is associated with bladder cancer (BC) incidence. But there is still a lack of understanding regarding its pathogenesis. Thus, this study aimed to identify potential hub genes and their important pathways and pathological mechanisms of interactions between IBD and BC using bioinformatics methods. METHODS: The data from Gene Expression Omnibus (GEO) and the cancer genome atlas (TCGA) were analyzed to screen common differentially expressed genes (DEGs) between IBD and BC. The "clusterProfiler" package was used to analyze GO term and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment in DEGs. After that, we conducted a weighted gene co-expression network analysis (WGCNA) on these DEGs to determine the vital modules and genes significantly related to BC. Protein-protein interaction (PPI) networks was used to identify hub genes. Further, the hub genes were used to develop a prognostic signature by Cox analysis. The validity of the ten hub DEGs was tested using three classification algorithms. Finally, we analyzed the microRNAs (miRNA)-mRNA, transcription factors (TFs)-mRNA regulatory network. RESULTS: Positive regulation of organelle fission, chromosomal region, tubulin binding, and cell cycle signaling pathway were the major enriched pathways for the common DEGs. PPI networks identified three hub proteins (AURKB, CDK1, and CCNA2) with high connectivity. Three machine-learning classification algorithms based on ten hub genes performed well for IBD and BC (accuracy > 0.80). The robust predictive model based on the ten hub genes could accurately classify BC cases with various clinical outcomes. Based on the gene-TFs and gene-miRNAs network construction, 9 TFs and 6 miRNAs were identified as potential critical TFs and miRNAs. There are 13 drugs that interact with the hub gene based on gene-drug interaction analysis. CONCLUSIONS: This study explored common gene signatures and the potential pathogenesis of IBD and BC. We revealed that an unbalanced immune response, cell cycle pathway, and neutrophil infiltration might be the common pathogenesis of IBD and BC. Molecular mechanisms for the treatment of IBD and CC still require further investigation.

Current prevalence, changes, and determinants of breastfeeding practice in China: data from cross-sectional national household health services surveys in 2013 and 2018.

BACKGROUND: The World Health Organization and the government of China have made many efforts to improve breastfeeding practices. The evidence of breastfeeding practices over the past decade in China is limited. The current study aimed to describe the current prevalence, variation trends, and determinants of breastfeeding practices in China using data from the National Household Health Service Surveys (NHHSS) in 2013 and 2018. METHODS: Women who had at least one live birth in the five years from the 2013 NHHSS numbered 10,544, and 12,766 women from the 2018 NHHSS were included in the current study. The rates of breastfeeding, early initiation of breastfeeding within the first hour after birth, exclusive breastfeeding for at least six months since birth, and continued breastfeeding accompanied by adequate complementary feeding for over two years were measured. Logistic regressions were performed to study the associations between breastfeeding practices and maternal-based, healthcare-based, and infant-based characteristics. RESULTS: In the 2018 survey, the rates of practiced any breastfeeding, early initiation of breastfeeding within the first hour after birth, exclusive breastfeeding for at least six months, and continued breastfeeding for over two years were 91.50%, 28.16%, 47.90%, and 4.78%, respectively, showing significant improvements compared to the 2013 survey period. Women who received high education, were from a household with high incomes, had more than one child, and had more antenatal and postnatal visits, were more likely to practice breastfeeding and initiate it within the first hour, but they were less likely to breastfeed the infants for two years. Births by caesarean section and low birthweight were associated with worse breastfeeding practices. CONCLUSIONS: The rates of practicing breastfeeding and exclusive breastfeeding for six months or more in China improved over the past decades, suggesting improved awareness and knowledge of breastfeeding among women. However, individual and social factors may impact practices of early initiation and continued breastfeeding. Strengthening breastfeeding support from family, community, and health professionals (e.g., family member engagement, friendly work environment, and professional consultation, etc.) during the postpartum and infant period may improve women's confidence in breastfeeding practices.

Characterization of the male-specific region containing the candidate sex-determining gene in Amur catfish (Silurus asotus) using third-generation- and pool-sequencing data.

Amur catfish (Silurus asotus) is an ecologically and economically important fish species in Asia. Here, we assembled the female and male Amur catfish genomes, with genome sizes of 757.15 and 755.44 Mb, respectively, at the chromosome level using nanopore and Hi-C technologies. Consistent with the known diploid chromosome count, both genomes contained 29 chromosome-size scaffolds covering 98.80 and 98.73 % of the complete haplotypic assembly with scaffold N50 of 28.87 and 27.29 Mb, respectively. The female (n = 40) and male (n = 40) pools were re-sequenced. Comparative analysis of sequencing and re-sequencing data from both sexes confirmed the presence of an XX/XY sex determination system in Amur catfish and revealed Chr5 as the sex chromosome containing an approximately 400 kb Y-specific region (MSY). Gene annotation revealed a male-specific duplicate of amhr2, namely amhr2y, in MSY, which is male-specific in different wild populations and expressed only in the testes. Amur catfish shared partially syntenic MSY and amhr2y genes with the southern catfish (S. meridionalis, Chr24), which were located on different chromosomes. High sequence divergence between amhr2y and amhr2 and high sequence similarity with amhr2y were observed in both species. These results indicate the common origin of the sex-determining (SD) gene and transition of amhr2y in the two Silurus species. Accumulation of repetitive elements in the MSY of both species may be the main driver of the transition of amhr2y. Overall, our study provides valuable catfish genomic resources. Moreover, determination of amhr2y as the candidate SD gene in Amur catfish provides another example of amhr2 as the SD gene in fish.

[Cloning and expression analysis of U6 promoters in Panax quinquefolius].

The U6 promoter is an important element driving sgRNA transcription in the CRISPR/Cas9 system. Seven PqU6 promo-ter sequences were cloned from the gDNA of Panax quinquefolium, and the transcriptional activation ability of the seven promoters was studied. In this study, seven PqU6 promoter sequences with a length of about 1 300 bp were cloned from the adventitious roots of P. quinquefolium cultivated for 5 weeks. Bioinformatics tools were used to analyze the sequence characteristics of PqU6 promoters, and the fusion expression vectors of GUS gene driven by PqU6-P were constructed. Tobacco leaves were transformed by Agrobacterium tumefaciens-mediated method for activity detection. The seven PqU6 promoters were truncated from the 5'-end to reach 283, 287, 279, 289, 295, 289, and 283 bp, respectively. The vectors for detection of promoter activity were constructed with GUS as a reported gene and used to transform P. quinquefolium callus and tobacco leaves. The results showed that seven PqU6 promoter sequences(PqU6-1P to PqU6-7P) were cloned from the gDNA of P. quinquefolium, with the length ranged from 1 246 bp to 1 308 bp. Sequence comparison results showed that the seven PqU6 promoter sequences and the AtU6-P promoter all had USE and TATA boxes, which are essential elements affecting the transcriptional activity of the U6 promoter. The results of GUS staining and enzyme activity test showed that all the seven PqU6 promoters had transcriptional activity. The PqU6-7P with a length of 1 269 bp had the highest transcriptional activity, 1.31 times that of the positive control P-35S. When the seven PqU6 promoters were truncated from the 5'-end(PqU6-1PA to PqU6-7PA), their transcriptional activities were different in tobacco leaves and P. quinquefolium callus. The transcriptional activity of PqU6-7PA promoter(283 bp) was 1.59 times that of AtU6-P promoter(292 bp) when the recipient material was P. quinquefolium callus. The findings provide more ideal endogenous U6 promoters for CRISPR/Cas9 technology in ginseng and other medicinal plants.

Impact of a novel immune and nutritional score on prognosis in patients with upper urinary tract urothelial carcinoma following radical nephroureterectomy.

BACKGROUND: This study aimed to evaluate the clinical significance of a novel immune and nutritional score combining prognostic values of the controlling nutritional status (CONUT) score and prognostic immune and nutritional index (PINI) on long-term outcomes in patients with upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy (RNU). METHODS: This study analyzed 437 consecutive patients with UTUC treated by RNU. Restricted cubic splines were used to visualize the relation of PINI with Survival in patients with UTUC. The PINI was stratified into low- (1) and high-PINI (0) categories. The CONUT score was divided into three groups: Normal (1), Light (2), and Moderate/severe (3). Subsequently, patients were grouped according to CONUT-PINI score (CPS) (CPS group 1; CPS group 2; CPS group 3; and CPS group 4). Survival curves were plotted using the Kaplan-Meier method and log-rank test. The Cox proportional hazards regression model was used to determine the risk factors associated with overall Survival (OS) and cancer-specific Survival (CSS). By comprising independent prognostic factors, a predictive nomogram was constructed. RESULTS: PINI and CONUT score were identified as independent prognostic factors for OS and CSS. Kaplan-Meier survival analysis showed that the high CPS group was associated with worse OS and CSS than the low CPS group. Multivariate Cox regression and competing risk analyses showed that CPS, LVI, T stage, margin, and pN were independent factors associated with OS and CSS. Based on these five significant factors, we constructed a prognostic model for predicting clinical outcomes. The receiver operating characteristic curve indicated that the model had excellent predictive abilities for survival. The C-index of this model for OS and CSS were 0.773, and 0.789, respectively. The nomogram for OS and CSS showed good discrimination and calibration. Decision curve analysis (DCA) showed that this nomogram has a higher net benefit. CONCLUSION: The CPS combined the prognostic capacity of PINI and CONUT score and was able to predict patient outcomes in our cohort of UTUC patients. We have developed a nomogram to facilitate the clinical use of the CPS and provide accurate estimates of survival for individuals.

Prognostic models for upper urinary tract urothelial carcinoma patients after radical nephroureterectomy based on a novel systemic immune-inflammation score with machine learning.

PURPOSE: This study aimed to evaluate the clinical significance of a novel systemic immune-inflammation score (SIIS) to predict oncological outcomes in upper urinary tract urothelial carcinoma(UTUC) after radical nephroureterectomy(RNU). METHOD: The clinical data of 483 patients with nonmetastatic UTUC underwent surgery in our center were analyzed. Five inflammation-related biomarkers were screened in the Lasso-Cox model and then aggregated to generate the SIIS based on the regression coefficients. Overall survival (OS) was assessed using Kaplan-Meier analyses. The Cox proportional hazards regression and random survival forest model were adopted to build the prognostic model. Then we established an effective nomogram for UTUC after RNU based on SIIS. The discrimination and calibration of the nomogram were evaluated using the concordance index (C-index), area under the time-dependent receiver operating characteristic curve (time-dependent AUC), and calibration curves. Decision curve analysis (DCA) was used to assess the net benefits of the nomogram at different threshold probabilities. RESULT: According to the median value SIIS computed by the lasso Cox model, the high-risk group had worse OS (p<0.0001) than low risk-group. Variables with a minimum depth greater than the depth threshold or negative variable importance were excluded, and the remaining six variables were included in the model. The area under the ROC curve (AUROC) of the Cox and random survival forest models were 0.801 and 0.872 for OS at five years, respectively. Multivariate Cox analysis showed that elevated SIIS was significantly associated with poorer OS (p<0.001). In terms of predicting overall survival, a nomogram that considered the SIIS and clinical prognostic factors performed better than the AJCC staging. CONCLUSION: The pretreatment levels of SIIS were an independent predictor of prognosis in upper urinary tract urothelial carcinoma after RNU. Therefore, incorporating SIIS into currently available clinical parameters helps predict the long-term survival of UTUC.

Development of a real-time loop-mediated isothermal amplification method for monitoring Pseudomonas lurida in raw milk throughout the year of pasture.

Introduction: The psychrophilic bacterium Pseudomonas lurida (P. lurida) and its thermostable alkaline proteases can seriously damage raw milk quality. Methods: In this study, specific primers were designed for P. lurida's gyrB and aprX genes, and a real-time loop-mediated isothermal amplification (RealAmp) rapid detection method was developed for the early monitoring of P. lurida and its proteases in raw milk. A phylogenetic tree of the gyrB and aprX genes of P. lurida was constructed to analyze the homology of the design sequence of the RealAmp primer. The DNA of 2 strains of P. lurida and 44 strains of non-P. lurida were detected via RealAmp to analyze the specificity of the primer. Results: It was found that aprX-positive proteases were produced by P. lurida-positive strains only when Pseudomonas fluorescens was negative. The dissociation temperatures of gyrB and aprX in the RealAmp-amplified products were approximately 85.0°C and 90.0°C, respectively. Moreover, DNA was detected through a 10-fold dilution of P. lurida in a pure bacterial solution and artificially contaminated skimmed milk. The limit of detection of P. lurida DNA copy number in the pure bacterial solution was 8.6 copies/µL and that in the 10% skimmed milk was 5.5 copies/µL. Further, 144 raw milk samples throughout the year from three farms in Hebei province were analyzed using RealAmp. The highest detection rate of P. lurida was 56% in the first and third quarters, and that of proteases was 36% in the second quarter. The detection rates of P. lurida and its proteases were the highest in samples collected from pasture 2 (52 and 46%, respectively), and the ability of P. lurida to produce proteases reached 88%. Discussion: In conclusion, RealAmp established an early and rapid method for the detection of P. lurida and its proteases in raw milk samples, allowing the identification and control of contamination sources in a timely manner to ensure the quality of milk and dairy products.

Application of Nanocellulose-Based Aerogels in Bone Tissue Engineering: Current Trends and Outlooks.

The complex or compromised bone defects caused by osteomyelitis, malignant tumors, metastatic tumors, skeletal abnormalities, and systemic diseases are difficult to be self-repaired, leading to a non-union fracture. With the increasing demands of bone transplantation, more and more attention has been paid to artificial bone substitutes. As biopolymer-based aerogel materials, nanocellulose aerogels have been widely utilized in bone tissue engineering. More importantly, nanocellulose aerogels not only mimic the structure of the extracellular matrix but could also deliver drugs and bioactive molecules to promote tissue healing and growth. Here, we reviewed the most recent literature about nanocellulose-based aerogels, summarized the preparation, modification, composite fabrication, and applications of nanocellulose-based aerogels in bone tissue engineering, as well as giving special focus to the current limitations and future opportunities of nanocellulose aerogels for bone tissue engineering.

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.

Immunogenic Cell Death Associated Molecular Patterns and the Dual Role of IL17RA in Interstitial Cystitis/Bladder Pain Syndrome.

The unclear etiology and pathogenesis of interstitial cystitis/bladder pain syndrome (IC/BPS) are responsible for the lack of effective treatment and the poor patient prognosis. Various studies show that chronic inflammation and immune responses are important factors contributing to the pathogenesis of IC/BPS. The process of immunogenic cell death (ICD) involves both the immune response and inflammatory process, and the involvement of ICD in IC/BPS pathogenesis has not been explored. Two IC/BPS transcriptome datasets collected from the Gene Expression Omnibus (GEO) database were used to identify distinct ICD-associated molecular patterns (IAMPs). IAMPs and IC/BPS subtypes were found to be related. The inflammatory immune microenvironments (IIME) in different IAMPs were studied. The potential mechanism by which the interleukin 17 receptor A (IL17RA) influences IC/BPS was examined using in vitro assays. The expression of ICD-related genes (IRGs) was upregulated in IC/BPS bladders, compared with normal bladders. Disease prediction models, based on differentially expressed IRGs, could accurately predict IC/BPS. The IC/BPS patients had two distinct IAMPs, each with its own subtype and clinical features and association with remodeling IIME. IL17RA, a well-established IC/BPS bladder biomarker, mediates both the inflammatory insult and the protective responses. In summary, the current study identified different IAMPs in IC/BPS, which may be involved in the pathogenesis of IC/BPS by remodeling the IIME. The chronic inflammatory process in IC/BPS may be prolonged by IL17RA, which could mediate both pro- and anti-inflammatory responses. The IL17RA-associated pathway may play a significant role in the development of IC/BPS and can be used as a therapeutic target.

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.