Association between ABO genotypes and risk of dementia and neuroimaging markers: roles of sex and APOE status.

Background: Whether the relationships between ABO blood genotypes (AA, AO, BB, BO, AB, and OO) and dementia are modified by gender and APOE status has been unclear. Methods: We used data from the UK Biobank, a population-based cohort study of 487,425 individuals. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI) between ABO genotypes and risk of dementia. Multivariable linear regression models were used to estimate the relationship between ABO genotypes and MRI-based brain indices. Results: Overall, 487,425 participants were included at baseline. After 34 million person-years follow up, 7,548 patients developed all-cause dementia. Before stratifying by sex and APOE status, compared to OO genotype, BB genotype was associated with increased risk of all-cause dementia (1.36, 1.03-1.80) and other types dementia (1.65, 1.20-2.28). After stratifying by sex, only in males, BB genotype was associated with higher risk of all-cause dementia (1.44, 1.02-2.09) and other types of dementia (1.95, 1.30-2.93). AB genotype in males was also associated with increased AD (1.34, 1.04-1.72). After further stratifying by APOE e4 status, BB genotype with two APOE e4 alleles showed even stronger association with all-cause dementia 4.29 (1.57, 11.72) and other types dementia (5.49, 1.70-17.69) in males. Also in males, AA genotype with one APOE e4 was associated with increased risks of all-cause dementia (1.27, 1.04-1.55), AD (1.45, 1.09-1.94) and other types dementia (1.40, 1.08-1.81). Linear regression models showed that in both sexes with APOE e4, AA genotype was associated with reduced total grey matter volume. Conclusion: Sex and APOE e4 carrier status modified the association between ABO genotypes and risk of dementia. In males, BB genotype was consistently associated with increased risk of dementia, especially in those with two APOE e4 alleles. Also, in males with one APOE e4, AA genotype might be linked to higher risk of dementia.

Deletion of Nrf2 induced severe oxidative stress and apoptosis in mice model of diabetic bladder dysfunction.

The nuclear factor erythroid 2-related factor 2 (Nrf2) pathway has been confirmed as a therapeutic target for type 2 diabetes mellitus (T2DM), however few studies revealed its effect in diabetic bladder dysfunction (DBD). Herein, we reported a Nrf2 deletion diabetic mouse model induced by 8-week high-fat diet feeding combined with streptozocin (STZ) injection in Nrf2 knockout mice. Besides, wild-type mice (WT) were used as control group, wild-type mice with high-fat diet feeding and STZ injection as diabetic group (WT-T2DM), and Nrf2 knockout mice as Nrf2 deletion group (KO). The pathophysiological indexes and bladder morphology showed typical pathological features of diabetic bladder dysfunction in Nrf2 knockout diabetic mouse mice (KO-T2DM). ELISA results showed that advanced glycation end products (AGEs), ROS and malondialdehyde (MDA) levels in bladder was were up-regulated in both WT-T2DM and KO-T2DM group, while superoxide dismutase (SOD) and glutathione (GSH) levels decreased in these two groups. Compared with WT-T2DM group, western blot analysis of the bladder showed down-regulated expression of NQO1 and HO-1 in KO-T2DM group. However, apoptosis, marked by Caspase3 and bax/bcl-2 ratio, was increased in KO-T2DM group. Neurotrophic factor (NGF) was significantly decreased in DBD model, and even much lower in KO-T2DM group. Collectively, our findings demonstrated that deletion of Nrf2 lead to severe oxidative stress, apoptosis, and lower level of neurotrophic factor, and provided the first set of experimental evidence, in a mouse model, to support Nrf2 as a promising target for DBD.

Z-DNA binding protein 1 orchestrates innate immunity and inflammatory cell death.

Innate immunity is not only the first line of host defense against microbial infections but is also crucial for the host responses against a variety of noxious stimuli. Z-DNA binding protein 1 (ZBP1) is a cytosolic nucleic acid sensor that can induce inflammatory cell death in both immune and nonimmune cells upon sensing of incursive virus-derived Z-form nucleic acids and self-nucleic acids via its Zα domain. Mechanistically, aberrantly expressed or activated ZBP1 induced by pathogens or noxious stimuli enables recruitment of TANK binding kinase 1 (TBK1), interferon regulatory factor 3 (IRF3), receptor-interacting serine/threonine-protein kinase 1 (RIPK1) and RIPK3 to drive type I interferon (IFN-I) responses and activation of nuclear factor kappa B (NF-κB) signaling. Meanwhile, ZBP1 promotes the assembly of ZBP1- and absent in melanoma 2 (AIM2)-PANoptosome, which ultimately triggers PANoptosis through caspase 3-mediated apoptosis, mixed lineage kinase domain like pseudokinase (MLKL)-mediated necroptosis, and gasdermin D (GSDMD)-mediated pyroptosis. In response to damaged mitochondrial DNA, ZBP1 can interact with cyclic GMP-AMP synthase to augment IFN-I responses but inhibits toll like receptor 9-mediated inflammatory responses. This review summarizes the structure and expression pattern of ZBP1, discusses its roles in human diseases through immune-dependent (e.g., the production of IFN-I and pro-inflammatory cytokines) and -independent (e.g., the activation of cell death) functions, and highlights the attractive prospect of manipulating ZBP1 as a promising therapeutic target in diseases.

Z-nucleic acid sensor ZBP1 in sterile inflammation.

Z-DNA binding protein 1 (ZBP1), a cytosolic nucleic acid sensor for Z-form nucleic acids (Z-NA), can detect both exogenous and endogenous nucleic acids. Upon sensing of self Z-NA or exposure to diverse noxious stimuli, ZBP1 regulates inflammation by activating nuclear factor kappa B and interferon regulating factor 3 signaling pathways. In addition, ZBP1 promotes the assembly of ZBP1 PANoptosome, which initiates caspase 3-mediated apoptosis, mixed lineage kinase domain like pseudokinase (MLKL)-mediated necroptosis, and gasdermin D (GSDMD)-mediated pyroptosis (PANoptosis), leading to the release of various damage-associated molecular patterns. Thereby, ZBP1 is implicated in the development and progression of diverse sterile inflammatory diseases. This review outlines the expression, structure, and function of ZBP1, along with its dual roles in controlling inflammation and cell death to orchestrate innate immunity in sterile inflammation, especially autoimmune diseases, and cancers. ZBP1 has emerged as an attractive therapeutic target for various sterile inflammatory diseases.

Upregulation of PTPN1 aggravates endotoxemia-induced cardiac dysfunction through inhibiting mitophagy.

OBJECTIVES: To investigate the role of protein tyrosine phosphatase non-receptor type 1 (PTPN1) in mitophagy during sepsis and its underlying mechanisms and determine the therapeutic potential of PTPN1 inhibitors in endotoxemia-induced cardiac dysfunction. METHODS: A mouse model of endotoxemia was established by administering an intraperitoneal injection of lipopolysaccharide (LPS). The therapeutic effect of targeting PTPN1 was evaluated using its inhibitor Claramine (CLA). Mitochondrial structure and function as well as the expression of mitophagy-related proteins were evaluated. Rat H9c2 cardiomyocytes were exposed to mouse RAW264.7 macrophage-derived conditioned medium. Cryptotanshinone, a specific p-STAT3 (Y705) inhibitor, was used to confirm the role of STAT3 in PTPN1-mediated mitophagy following LPS exposure. Electrophoretic mobility shift and dual luciferase reporter assays were performed to discern the mechanisms by which STAT3 regulated the expression of PINK1 and PRKN. RESULTS: CLA alleviated LPS-induced myocardial damage, cardiac dysfunction, and mitochondrial injury and dysfunction in the mouse heart. PTPN1 upregulation exacerbated LPS-induced mitochondrial injury and dysfunction in H9c2 cardiomyocytes, but inhibited LPS-induced mitophagy. LPS promoted the interaction between PTPN1 and STAT3 and reduced STAT3 phosphorylation at Tyr705 (Y705), which was required to inhibit mitophagy by PTPN1. Upon LPS stimulation, PTPN1 negatively regulated the transcription of PINK1 and PRKN through dephosphorylation of STAT3 at Y705. STAT3 regulated the transcription of PINK1 and PRKN by binding to STAT3-responsive elements in their promoters. CONCLUSION: PTPN1 upregulation aggravates endotoxemia-induced cardiac dysfunction by impeding mitophagy through dephosphorylation of STAT3 at Y705 and negative regulation of PINK1 and PRKN transcription.

Serpina3n/serpina3 alleviates cyclophosphamide-induced interstitial cystitis by activating the Wnt/ß-catenin signal.

BACKGROUND/OBJECTIVE: Serpina3n/Serpina3 has been identified to be implicated in inflammatory diseases, but its role in interstitial cystitis/bladder pain syndrome (IC/BPS) remains unknown. Here, we aimed to reveal serpina3n/serpina3 role in IC/BPS in vivo and in vitro. METHODS: The IC/BPS model in mice was induced by intraperitoneal injection of 150 mg/kg of cyclophosphamide (CYP). HE and toluidine blue staining were used for histology assessment. Serpina3n/serpina3 expression in the bladder tissues from IC/BPS patients and mouse models were determined by qPCR, immunohistochemistry and western blotting. XAV-939 treatment was applied to inhibit ß-catenin activation. Serpina3 role in modulating the growth and apoptosis of HBlEpCs, a human primary bladder epithelial cell line, was assessed by CCK-8 and flow cytometry assays. RESULTS: Serpina3n/serpina3 expression was decreased in both human and mice bladder tissues with IC/BPS. Upregulation of serpina3n significantly alleviated CYP-induced bladder injury, with decreased mast cells and pro-inflammatory factor levels, including IL-1ß, IL-6, and TNF-α, while increased IL-10 level. In addition, serpina3 overexpression inhibited the apoptosis of HBlEpCs, and increased cell growth. In mechanism, we found that serpina3 overexpression promoted the activation of wnt/ß-catenin signaling. And, the inhibition of wnt/ß-catenin signaling with XAV-939 abolished serpina3n/serpina3 role in protecting bladder tissues from CYP-induced cystitis, as well as inhibiting HBlEpC apoptosis. CONCLUSION: Serpina3n/serpina3 expression was decreased in IC/BPS. Overexpression of serpina3n could alleviate CYP-induced IC/BPS by activating the Wnt/ß-catenin signal. This study may provide a new therapeutic strategy for IC/BPS.

Adjustable continence therapy (proACT) for the treatment of male stress urinary incontinence post-prostatectomy: a systematic review and meta-analysis (2023 update).

PURPOSE: Stress urinary incontinence (SUI) is a key factor for post-prostatectomy (RP) quality of life. Current international guidelines struggle to find the adequate place for each kind of surgeries. The aim of this systematic review and meta-analysis considering updated evidence is to assess the efficacy and safety of proACT in treating male patients with post-RP SUI. METHODS: A review of the literature was performed by searching the PubMed database. We narrowed included studies with adult male patients with SUI; outcomes included pads or pad weight per day and quality of life (QOL) questionnaires, as well as safety outcomes. RESULTS: 18 studies involving 1570 patients mean age of 68.8 (EC 2.1) were included. The mean follow-up reported was 34.7 months (EC 17.7; median 38.5; range 1-128 months). An average of 60.7% (EC 27) and 40.4% of patients suffered from mild-to-moderate and severe incontinence, respectively. The overall dryness rate was 55.1% (EC 19.3) while respecting the definition of 0-1 pads per day, and the mean dryness rate was 53% (EC 0.2). The mean overall complication rate was 31.2% (EC 18.3%), including an explantation rate of 26.5% (EC 15.3) and a reoperation rate of 22.7% (EC 8.7). The methodological quality of the 18 studies was very heterogeneous. CONCLUSION: Implantation of proACT adjustable balloons is a minimally invasive technique that provides medium outcomes (53%) with a strict definition of dryness (0-1 PPD) and important complication rate (31.2%). Past of irradiation is a negative predictive factor for incontinence.

The application of "S.I.S" technique improves long-term continence after robotic radical prostatectomy.

AIMS: To propose a novel S.I.S technique during the robotic-assisted radical prostatectomy (RARP), encompassing pubourethral suspension, posterior wall intensification, and bladder neck stripping, and to present functional and oncological outcomes with a special focus on long-term continence. METHODS: From January 1, 2018, to December 31, 2019, consecutive patients who underwent RARP were retrospectively investigated and separated into the S.I.S group and the conventional group. Preoperative patient characteristics, tumor status, and perioperative parameters were collected, followed by the assessment of self-reported status on continence, using an International Consultation on Incontinence Modular Questionnaire-urinary incontinence short form (ICIQ-UI-SF). Statistical comparisons were performed on variables between the two surgery groups, and multivariate logistic regression analysis was used to determine predictive factors for postoperative incontinence severity. RESULTS: A total of 602 subjects were analyzed with a median follow-up of 24 months. There was no significant difference regarding baseline characteristics and perioperative parameters, except for a more advanced tumor stage in the S.I.S group. The application of the S.I.S technique did not jeopardize the positive surgical margin rate at the bladder neck or long-term tumor control. Notably, the patient-reported degree of incontinence was significantly reduced with the assistance of S.I.S technique, as evidenced by the diminished severe-to-very severe cases. On multivariate analysis, both preoperative body mass index and use of S.I.S modification were independent predictive factors for the long-term incontinence severity. CONCLUSIONS: The application of S.I.S technique during RARP is feasible and superior compare with the conventional approach, with a significantly alleviated long-term incontinence severity, without compromising cancer control.

The machine learning model based on trajectory analysis of ribonucleic acid test results predicts the necessity of quarantine in recurrently positive patients with SARS-CoV-2 infection.

Background: SARS-CoV-2 patients re-experiencing positive nucleic acid test results after recovery is a concerning phenomenon. Current pandemic prevention strategy demands the quarantine of all recurrently positive patients. This study provided evidence on whether quarantine is required in those patients, and predictive algorithms to detect subjects with infectious possibility. Methods: This observational study recruited recurrently positive patients who were admitted to our shelter hospital between May 12 and June 10, 2022. The demographic and epidemiologic data was collected, and nucleic acid tests were performed daily. virus isolation was done in randomly selected cases. The group-based trajectory model was developed based on the cycle threshold (Ct) value variations. Machine learning models were validated for prediction accuracy. Results: Among the 494 subjects, 72.04% were asymptomatic, and 23.08% had a Ct value under 30 at recurrence. Two trajectories were identified with either rapid (92.24%) or delayed (7.76%) recovery of Ct values. The latter had significantly higher incidence of comorbidities; lower Ct value at recurrence; more persistent cough; and more frequently reported close contacts infection compared with those recovered rapidly. However, negative virus isolation was reported in all selected samples. Our predictive model can efficiently discriminate those with delayed Ct value recovery and infectious potentials. Conclusion: Quarantine seems to be unnecessary for the majority of re-positive patients who may have low transmission risks. Our predictive algorithm can screen out the suspiciously infectious individuals for quarantine. These findings may assist the enaction of SARS-CoV-2 pandemic prevention strategies regarding recurrently positive patients in the future.

The detection of urinary viruses is associated with aggravated symptoms and altered bacteriome in female with overactive bladder.

Although it is known that changes in bacterial components of the urinary microbiome are associated with overactive bladder (OAB), the specific role of viruses is still insufficiently investigated. The aim of the present study is to evaluate the role of urinary viruses in woman with OAB, and analyze the potential relationship between viruses, bacteria and disease. Catheterized urine samples were collected from 55 women with OAB and 18 control individuals. OAB patients fulfilling the following criteria were considered eligible for this study: female, 18 years of age or older; presented with classic OAB symptoms defined by the International Continence Society; and OAB Symptom Score (OABSS) total score ≥ 3 points and question 3 (urgency) score ≥ 2 points. Based on results of metagenomic next-generation sequencing (mNGS), all participants were divided into virus-infected and virus-uninfected groups for analysis. The results of mNGS showed that the diversity of the OAB group was lower than that of the control group when focused on bacterial sequences, which was consistent with our previous study. According to the questionnaire filled out by the patients, OABSS and 8-item OAB questionnaire, female OAB patients who had viruses detected in their urine had more severe symptoms. In parallel, John Cunningham virus (mainly subtype 7 and subtype 2) was the most frequently detected virus in urine. Correlation analysis indicated that risk factors for virus infection in OAB patients include age, habit of holding urine and pelvic surgery history. Given our preliminary data, viral infection can aggravate OAB severity and affect the composition of bacterial. Further research is required to explain how viral infections can aggravate OAB patient symptoms and cause bacterial changes.

A retrospective study of Pupingqinghua prescription versus Lianhuaqingwen in Chinese participants infected with SARS-CoV-2 Omicron variants.

Background: Coronavirus disease (COVID-19) seriously endangers global public health. Pupingqinghua prescription (PPQH) is an herbal formula from traditional Chinese medicine used for treatment of SARS-CoV-2 infection. This study aims to evaluate the clinical efficacy and safety of PPQH in Chinese participants infected with the SARS-CoV-2 Omicron variant. Methods: A total of 873 SARS-CoV-2 (Omicron)-infected patients were included. Among them, the patients were divided into the PPQH group (653 cases) and LHQW group (220 cases) according to different medications. The effectiveness indicators (hematological indicators, Ct values of novel Coronavirus nucleic acid tests, and viral load-shedding time) and safety indicators (liver and kidney function and adverse events) were analyzed. Results: There was no significant difference in baseline characteristics between the PPQH group and the LHQW group, except the gender; After the treatment, the levels of IL-5, IL-6, IL-10, NK cells, and INF-α of the patients in the PPQH group showed a downward trend (p < 0.05); The viral load shedding time was 5.0 (5.0, 7.0) in the PPQH group and 5.0 (4.0, 7.0) in the LHQW group; both PPQH and LHQW can shorten the duration of symptoms of fever, cough, and sore throat. The re-positive rate of COVID-19 test was 1.5 % in the PPQH group and 2.3 % in the LHQW group. In terms of safety, the levels of γ-GTT decreased significantly (p < 0.01); gastrointestinal reaction was the primary adverse reaction, and the reaction rate was 4.7 % in the PPQH group and 9.5 % in the LHQW group. Conclusion: PPQH can shorten the length of hospital stay and improve clinical symptoms of patients with SARS-COV-2 (Omicron), and it also has a good safety profile.

Potential role of oxidative stress in the pathogenesis of diabetic bladder dysfunction.

Diabetes mellitus is a chronic metabolic disease, posing a considerable threat to global public health. Treating systemic comorbidities has been one of the greatest clinical challenges in the management of diabetes. Diabetic bladder dysfunction, characterized by detrusor overactivity during the early stage of the disease and detrusor underactivity during the late stage, is a common urological complication of diabetes. Oxidative stress is thought to trigger hyperglycaemia-dependent tissue damage in multiple organs; thus, a growing body of literature has suggested a possible link between functional changes in urothelium, muscle and the corresponding innervations. Improved understanding of the mechanisms of oxidative stress could lead to the development of novel therapeutics to restore the redox equilibrium and scavenge excessive free radicals to normalize bladder function in patients with diabetes.

Can the nucleic acid Ct value of discharged patients infected with SARS-CoV-2 Omicron variant be 35?--A retrospective study on fluctuation of nucleic acid Ct values in SNIEC mobile cabin hospital.

Objective: To explore the meaning of cycle threshold (Ct) value fluctuation and the appropriateness of setting the discharge Ct value to 35, which is the current standard in Chinese guidelines. Method: A retrospective study was conducted on 95 patients with Ct value fluctuation (Ct value below 35 on day 3; group A) and 97 patients with a normal discharge process (control; group B). Their clinical characteristics and follow-up data were collected. Results: (1) There was no significant difference between the groups in age, gender distribution, number of vaccinations, initial ORF-Ct value, and initial N-Ct value. The proportion of patients complicated with chronic internal disorders, respiratory symptoms, and abnormal chest radiology in group A was significantly higher than that in group B. (2) Between the two groups, there was no significant difference in the ORF-Ct or N-Ct value on day 1, but the ORF-Ct and N-Ct values of group B on days 2 to 4 were significantly higher than those of group A. (3) There was no significant difference between the groups in the ORF-Ct value at discharge, but there was a significant difference in the N-Ct value at discharge. Seven days after discharge, almost 100% of the patients had been cured. The mean negative conversion interval of nucleic acid of the patients in group A was 14.5 ± 4.6 days, which was longer than that of the patients in group B (11.8 ± 4 days). (4) Logistic regression analysis showed that the ORF-Ct value on day 2 was the key factor influencing the Ct value fluctuation. Conclusion: The fluctuation of Ct value is only a normal phenomenon in the recovery period of the disease, and there is no need for excessive intervention. It is reasonable to set the Ct value of the discharge standard to 35 and retest the nucleic acid on the 10th day after discharge for patients with underlying diseases or symptoms.

The characteristics and risk factors of healthcare-seeking men with lower urinary tract symptoms in China: Initial report from the POInT group.

AIMS: To investigate the clinical characteristics of health care-seeking men presenting with lower urinary tract symptoms (LUTS) in China and to reveal risk factors for symptom severity. METHODS: This multicenter, hospital-based, cross-sectional study recruited 1477 eligible male subjects, who were at least 45 years, seeking health care at 9 participating hospitals across the mainland China. The general medical information and subjective symptoms were recorded, followed by the measurement of prostate volume, urodynamic indices, and laboratory tests for kidney function, plus glucose/lipid metabolism. Univariate and multivariate linear regression were employed for the detection of risk factors for symptom severity. RESULTS: The proportion of mild, moderate, and severe LUTS was 14.6%, 32.6%, and 52.8%, respectively, with 62.2% reporting the triple combination of storage, voiding, and postmicturition symptoms. Median prostate volume was 44.6 ml, and 71.1% were experiencing comorbidities. Thirteen independent risk factors for LUTS severity were identified, namely, nocturnal voiding episodes and the presence of straining and weak steam; the triple combination of symptom subtypes; general and nocturia quality of life; Qmax and bladder outlet obstruction index; and numbers of comorbidities, hypertension, estimated glomerular filtration rate, and cholesterol and glycosylated hemoglobin. CONCLUSIONS: The majority of health care-seeking LUTS men present with moderate-to-severe and overlapping symptoms, with a high prevalence of both lower urinary tract dysfunction and systemic comorbidities. The evidence from both urological and nonurological independent risk factors demonstrate the multifactorial nature of LUTS, for which a multidisciplinary management is essential.

The Clinical Features and Predictive Factors of Nocturnal Enuresis in Adult Women.

OBJECTIVE: Our current knowledge on nocturnal enuresis (NE) in adults is scarce due to its uncommon nature. The present study was designed to investigate symptom characteristics and risk factors of NE in adult women to improve the current clinical understanding and management of this rare disease. METHODS: Over a 3-year period, we enrolled 70 adult women who complained of bedwetting, with a frequency of at least once per week and a symptom duration of 3 months or longer. Patients were excluded if they had known pregnancy, current urinary tract infection, untreated malignancies, anatomical abnormalities, and irregular sleep cycle. The International Consultation on Incontinence Modular Questionnaire-female lower urinary tract symptoms and bladder diary were employed to appraise lower urinary tract symptoms and voiding behavior. Urodynamics was performed to assess the bladder function. A linear regression analysis was applied to determine potential risk factors for NE frequency. RESULTS: Among the recruited subjects, comorbidities and lower urinary tract symptoms were frequently reported. On bladder diary, patients commonly presented with nocturnal polyuria (NP), reduced nocturnal voided volumes (RNVVs), or both. Urodynamics revealed multiple dysfunctions, namely, detrusor overactivity (DO), urodynamic stress incontinence (USI), reduced compliance, bladder outlet obstruction, detrusor underactivity (DU), and simultaneous DO and DU. Patients with more frequent NE (≥4/week) demonstrated markedly increased body mass index, more comorbid conditions, worse incontinence symptoms, NP or NP plus RNVVs, reduced compliance, and poorer voiding possibly owing to DU. Whereas, RNVVs alone and worse overactive bladder-related parameters were associated with milder NE. Multivariate analysis indicated that frequency/urgency quality of life, incontinence symptom, NP + RNVVs, poor flow, increased bladder sensation, USI, and simultaneous detrusor overactivity plus DU were independent risk factors for NE severity. CONCLUSION: NE in adult women may have both urological and non-urological pathophysiology. Imbalanced circadian urine production, jeopardized continence mechanisms, overactive bladder, and DU-induced poor voiding are major factors that contribute to the pathogenesis of NE in adult women. Focused treatments on restoring these functions should be individually considered.

[Diagnosis and treatment of 12 cases of sexual activity-related hematuria: Experience and literature review].

OBJECTIVE: To summarize and analyze the experience in the diagnosis and treatment of sexual activity-related hematuria. METHODS: A retrospective analysis was conducted on 12 cases of sexual activity-related hematuria treated in Changhai Hospital from October 2015 to April 2019. The patients ranged in age between 31 and 59 years, with a disease course of 2 weeks to 25 years, 6 complaining of urethral bleeding at penile erection and another 6 hematuria immediately after ejaculation, including 2 accompanied by hemospermia. All the patients underwent urethroscopy and cauterization of the lesioned urethral mucosa with the electric excision ring or holmium laser. In addition, one of the patients received seminal tract endoscopic exploration and seminal vesicle irrigation, and another one seminal tract endoscopy and transurethral resection of the prostate. RESULTS: All the patients were diagnosed with posterior urethral varicosity, one accompanied with bulbar and posterior urethral varicosity, one with seminal vesiculitis, and still another with BPH. The patients were followed up for 3－45 (mean 23.5) months, during which the symptoms of sexual activity-related hematuria disappeared in 11 cases, with smooth urination and no recurrence, and post-ejaculation hematuria developed in one case at 2 and 10 months postoperatively but never again thereafter. No complications, such as epididymitis, urethral stricture and ED, were observed in any of the patients. CONCLUSIONS: Urethral varicosity should be first considered in patients with painless hematuria immediately after penile erection or sexual activity though other conditions such as seminal vesicle bleeding can also be taken into account. Urethroscopy combined with seminal tract endoscopy is effective in the diagnosis and treatment of sexual activity-related hematuria.

Combined Treatment With CCR1-Overexpressing Mesenchymal Stem Cells and CCL7 Enhances Engraftment and Promotes the Recovery of Simulated Birth Injury-Induced Stress Urinary Incontinence in Rats.

Objective: To observe whether urethral injection of chemokine (c-c motif) ligand 7 (CCL7) and overexpressing CC receptor 1 (CCR1) in mesenchymal stem cells (MSCs) can promote their homing and engraftment to the injured tissue, and improve the recovery of simulated birth injury-induced stress urinary incontinence (SUI) in rats. Methods: Female rats underwent a dual injury consisting of vaginal distension (VD) and pudendal nerve crush (PNC) to induce SUI. Bone marrow-derived MSCs were transduced with lentivirus carrying CCR1 (MSC-CCR1) and green fluorescent protein (GFP). Forty virgin Sprague-Dawley rats were evenly distributed into four groups: sham SUI + MSC-CCR1+CCL7, SUI + MSCs, SUI + MSC-CCR1, and SUI + MSC-CCR1+CCL7 group. The engrafted MSCs in urethra were quantified. Another three groups of rats, including sham SUI + sham MSC-CCR1+CCL7 treatment, SUI + sham MSC-CCR1+CCL7 treatment, and SUI + MSC-CCR1+CCL7 treatment group, were used to evaluate the functional recovery by testing external urethral sphincter electromyography (EUS EMG), pudendal nerve motor branch potentials (PNMBP), and leak point pressure (LPP) 1 week after injury and injection. Urethra and vagina were harvested for histological examination. Results: The SUI + MSC-CCR1+CCL7 group received intravenous injection of CCR1-overexpressing MSCs and local injection of CCL7 after simulated birth injury had the most engraftment of MSCs to the injured tissues and best functional recovery from SUI compared to other groups. Histological examination showed a partial repair in the SUI + MSC-CCR1+CCL7 group. Conclusions: Our study demonstrated combined treatment with CCR1-overexpressing MSCs and CCL7 can increase engraftment of MSCs and promote the functional recovery of simulated birth trauma-induced SUI in rats, which could be a new therapeutic strategy for SUI.

The clinical features and predictive factors of nocturnal enuresis in adult men.

OBJECTIVES: To characterise the clinical features and to discover predictive factors of adult males with nocturnal enuresis (NE). PATIENTS AND METHODS: A total of 43 eligible adult male patients (mean age was 57.8 years) were recruited prospectively over a 2-year period. After documentation of medical history, lower urinary tract symptoms (LUTS) were assessed using the International Consultation on Incontinence Modular Questionnaire-male LUTS (ICIQ-MLUTS), and a 3-day ICIQ-bladder diary (ICIQ-BD). Video-urodynamic studies (VUDS) were conducted conforming to the International Continence Society standards. Univariate and multivariate linear regressions were performed to determine potential predictive factors. RESULTS: Patients with NE had a variety of LUTS and had a high incidence of obesity and comorbidities. On the ICIQ-BD, NE was associated with nocturnal polyuria (NP), reduced nocturnal bladder capacity (NBC), or a combination of both. Subgroup analysis indicated that patients with more frequent NE had: higher body mass index (BMI); more comorbidities; reduced daytime urinary frequency and urgency quality of life (QoL) sub-scores; and increased stress urinary incontinence (SUI) and nocturnal bedwetting sub-scores. Patients with reduced NBC only, had fewer NE episodes, while patients with NP, or with both NP and reduced NBC were more likely have frequent NE. Multivariate analysis confirmed that: BMI; neurogenic causes; sub-scores of SUI QoL and bedwetting domain; the presence of reduced NBC, and both NP and reduced NBC; and bladder outlet obstruction, were all independent predictive factors for the severity of NE. CONCLUSIONS: NE n the adult male should be systemically assessed and treated, as obesity, neurogenic disorders, excessive urine production, bladder storage and emptying dysfunctions are risk factors. Bladder diaries and VUDS provide valuable information on potential pathophysiological causes, which could assist clinical evaluation and selection of focussed treatment.

Learning Curve for the Tension-Free Vaginal Tape-Obturator Procedure for Female Stress Urinary Incontinence: A Prospective Single-Surgeon Study.

Objective: To evaluate the learning curve in an untrained resident surgeon for the initial case series of tension-free vaginal tape-obturator (TVT-O) to treat stress urinary incontinence. Materials and Methods: A retrospective observational study was conducted in Changhai Hospital, Shanghai, China, between March 2014 and June 2018. All consecutive women included were treated by the TVT-O procedure performed by one surgeon working under the supervision of an expert surgeon. Clinical features, estimated blood loss, operative time, postoperative hospital stay, total hospital stay, adverse events, and subjective and objective cure rates were recorded. Learning curve patterns were estimated to determine the number of cases to reach a plateau using the moving average method. Results: In total, 188 patients were included for analysis. Patients ranged from 39 to 91 years, with the average age of 57.5 ± 9.7 years. The mean operative time was 32.0 minutes (range 20-60). Operative time and blood loss decreased with increase in the level of expertise, whereas postoperative hospital stay and total hospital stay were not influenced by the number of procedures performed. The number of cases required to reach a plateau was ∼30. Objective cure rate and subjective cure rate were achieved in 88.7% and 88.2% at 12 months, respectively. Groin pain was the most common postoperation complication, which continued to be present in 11.7% patients at 12 months after surgery. Conclusions: The TVT-O procedure showed encouraging objective and subjective outcomes and low complication rates, even at the initial stage of the learning curve. Thirty cases were required for a naïve resident surgeon to learn TVT-O procedures. However, long-term outcome and complications caused by the synthetic sling still need further follow-up.

Current status and progression of lower urinary tract symptoms in Chinese male patients: the protocol and rationale for a nationwide, hospital-based, prospective, multicentre study.

INTRODUCTION: It has become increasingly evident that the male lower urinary tract symptoms (LUTS) may not only be caused by abnormalities in one or more components of the lower urinary tract, but also be secondary to a range of systemic disorders. The primary aim of this study is to evaluate the features of urological and systemic disorders among middle-aged and elderly male LUTS patients in China. The second aim is to investigate the changes of both conditions after interventions through a 2-year prospective follow-up. METHODS AND ANALYSIS: This nationwide, hospital-based, multicentre cohort study was designed and initiated by the Prostatic Obstruction Investigation Team which is an international multidisciplinary academic group focusing on the management of male LUTS. An expectation of 11 500 eligible subjects from 23 authorised urological centres across the mainland of China will be recruited with a baseline assessment and data collection. Subsequently, subjects will undergo a follow-up for 24 months having been prescribed with oral medications or after being selected for prostate surgery based on the standard practice of each institution as well as the clinician's own experience. All statistical analysis will be performed using SAS V.9.4 and R package. ETHICS AND DISSEMINATION: This study has received ethical approval from the Ethics Committee Boards of Shanghai Changhai Hospital (CHEC2017-244). The results will be reported at scientific conferences and be published on peer-reviewed journals. TRIAL REGISTRATION: NCT03394651.