Urinary Frequency Research Articles

Patient-reported outcome measures for lupus nephritis: content validity of LupusQoL and FACIT-Fatigue

BackgroundLupus nephritis (LN), a severe organ manifestation of systemic lupus erythematosus (SLE), significantly impacts health-related quality of life (HRQoL). Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) and Lupus Quality of Life (LupusQoL) have been validated to measure HRQoL in SLE, but not specifically in LN. Patient-reported symptoms of LN are not well-reported. We assessed the content validity and relevance of these measures in evaluating patients with LN and their LN-related experiences.MethodsThis qualitative, interview-based study enrolled patients with LN from three US sites from a larger, retrospective survey study. The interview comprised an open-ended concept elicitation part and a more structured cognitive part. Concept elicitation was used to identify relevant themes describing the patients’ experiences. Patients were asked to describe their LN-related symptoms, the severity and impact of those symptoms and their satisfaction with treatment. A cognitive interview approach evaluated the appropriate understanding of the items, instructions, and response options and asked patients about their understanding of the FACIT-Fatigue or LupusQoL measures, their relevance to the condition, and any aspects of confusion or need for better clarity of the questionnaires. All interviews were recorded and transcribed. The concept elicitation data were coded, while the cognitive interview data were tabulated to present the participants’ responses next to the interview questions to support the evaluation of their understanding of the questionnaire items.ResultsOverall, 10 patients participated in FACIT-Fatigue and another 10 in LupusQoL interviews; 18 patients were female, 10 were Black (self-reported) and 17 were receiving maintenance treatment for LN with stable disease activity. When patients recalled their symptoms, 670 expressions of varying symptoms were reported. All patients described pain, discomfort, and energy-related symptoms. Urinary frequency and non-joint swelling were most frequently attributed to LN rather than SLE. Patients felt the questions asked in the FACIT-Fatigue and LupusQoL surveys were relevant to their LN experience.ConclusionsThe symptoms reported by patients with LN were consistent with symptoms reported by the overall SLE population. However, patients indicated that some symptoms of LN were more profound than symptoms of SLE alone, affecting a broad range of areas of daily life activity and resulting in a higher burden on their HRQoL. FACIT-Fatigue and LupusQoL demonstrated content relevance as meaningful tools for patients with LN. However, further quantitative data collection is needed to ensure that these patient-reported outcome tools demonstrate good measurement properties in an LN population.

Research on dynamic urine volume detection system based on smart flexible textile sensors

Urine leakage volume is an important indicator reflecting the severity of incontinence in patients. Currently, there are limited smart diapers capable of continuous dynamic monitoring of urine volume. This study developed two types of urine volume sensors, resistive and capacitive, which were integrated with traditional diapers to assess urine leakage levels: mild leakage (0–5 mL), moderate leakage (6–12 mL), and severe leakage (above 12 mL). Three patterns of resistive urine volume sensors were designed, and the results showed that the A pattern could accurately determine urine volume and frequency levels. Additionally, three electrode spacing designs were tested for the capacitive urine volume sensors. The results indicated that the sensor with a 1 cm electrode spacing could determine the urine volume range, with each 1 mL increase in urine causing a capacitance rise of approximately 1.5–1.8 pF, with an error of about ± 0.5 mL per increment. Both resistive and capacitive methods showed high accuracy in monitoring urine volume and frequency. This study validated the feasibility of smart flexible fabric sensors in detecting urine volume and frequency, providing a potential solution for better assessing and managing the condition of incontinence patients.

SETD2 regulates SLC family transporter-mediated sodium and glucose reabsorptions in renal tubule

A regulatory mechanism for SLC family transporters, critical transporters for sodium and glucose reabsorptions in renal tubule, is incompletely understood. Here, we report an important regulation of SLC family transporter by SETD2, a chromatin remodeling gene whose alterations have been found in a subset of kidney cancers. Kidney-specific inactivation of Setd2 resulted in hypovolemia with excessive urine excretion in mouse and interestingly, RNA-sequencing analysis of Setd2-deficient murine kidney exhibited decreased expressions of SLC family transporters, critical transporters for sodium and glucose reabsorptions in renal tubule. Importantly, inactivation of Setd2 in murine kidney displayed attenuated dapagliflozin-induced diuresis and glucose excretion, further supporting that SETD2 might regulate SLCfamily transporter-mediated sodium and glucose reabsorptions in renal tubule. These data uncover an important regulation of SLC family transporter by SETD2, which may illuminate a crosstalk between metabolism and epigenome in renal tubule.

Targeting NADPH Oxidase as an Approach for Diabetic Bladder Dysfunction.

Diabetic bladder dysfunction (DBD) is the most prevalent complication of diabetes mellitus (DM), affecting >50% of all patients. Currently, no specific treatment is available for this condition. In the early stages of DBD, patients typically complain of frequent urination and often have difficulty sensing when their bladders are full. Over time, bladder function deteriorates to a decompensated state in which incontinence develops. Based on studies of diabetic changes in the eye, kidney, heart, and nerves, it is now recognized that DM causes tissue damage by altering redox signaling in target organs. NADPH oxidase (NOX), whose sole function is the production of reactive oxygen species (ROS), plays a pivotal role in other well-known and bothersome diabetic complications. However, there is a substantial gap in understanding how NOX controls bladder function in health and the impact of NOX on DBD. The current review provides a thorough overview of the various NOX isoforms and their roles in bladder function and discusses the importance of further investigating the role of NOXs as a key contributor to DBD pathogenesis, either as a trigger and/or an effector and potentially as a target.

An Improved and Efficient Practical Process for the Synthesis of Enantiomerically Pure Solifenacin Succinate as an Antimuscarinic Agent

Background: Solifenacin succinate is an active pharmaceutical drug molecule that is extremely effective in treating overactive bladder symptoms, such as urine incontinence, urgency, and frequent urination. The free base is yellow oil, and the salt solifenacin succinate forms yellowish crystals that are extremely stable and effective. Solifenacin is a very active antagonist due to its potent muscarinic M3 receptor antagonist characteristics. Furthermore, solifenacin is effective in the treatment of bowel syndrome (IBS) by blocking M3 receptors and a broad spectrum of bowel dysfunction. Objective: The objective of this study was to develop a practical and highly efficient scalable synthesis of enantiomerically pure solifenacin as an antimuscarinic agent. Methods: In this work, the Zn(OTf)2 catalyst was used to develop a novel, environmentally benign, high-yielding, and robust protocol for the synthesis of enantiomerically pure solifenacin succinate. Results: The synthesis of enantiomerically pure solifenacin succinate was achieved in seven steps using commercially available phenylethylamine and benzoyl chloride as the starting materials. We carried out the reaction optimization by treatment of (S)-1-phenyl-3,4-dihydroisoquinoline-2(1H)- carbonyl chloride and (R)-(-)-3-Quinuclidinolin in the presence of Zn(OTf)2 catalyst. Furthermore, the solifenacin-free base was treated with succinic acid to afford its corresponding salt. The highlight of this protocol is the use of 20 mol% Zn(OTf)2 catalyst for the first time. The readily available starting materials, robustness, easy operation, high yield, and low cost make the approach more attractive and highly applicable. Conclusion: In summary, we developed a novel Zn(OTf)2-catalysed environmentally benign, highyielding, and robust protocol for the synthesis of enantiomerically pure solifenacin succinate. The proposed strategy is highly cost-effective and avoids the use of hazardous and unsafe sensitive, strong bases as well as tedious work-up procedures. Effective synthesis was achieved using readily available starting materials and reagents. Thus, the protocol is highly efficient, compatible, and commercially viable for the synthesis of important solifenacin products.

Multicenter, open label, randomized controlled superiority trial for availability to reduce nocturnal urination frequency: The TOP-STAR study.

Nocturia impairs the quality of life in patients with type 2 diabetes mellitus. Although sodium glucose co-transporter 2 inhibitors (SGLT2i) such as tofogliflozin increase urine volume, their impact on nocturia, in conjunction with dietary salt restriction, is less clear. This multicenter, open-label, randomized, parallel-group trial included 80 subjects with type 2 diabetes and nocturia. The patients were divided into two groups: one receiving tofogliflozin, the shortest half-life, without salt restriction, and the other receiving both tofogliflozin and dietary salt restriction. The primary endpoint was nocturia frequency at 12 weeks. The secondary outcomes included changes in daytime urination frequency, urine volume, and home blood pressure. At 12 weeks, there were no significant differences in nocturia changes between both groups. Nocturia frequency did not change in the tofogliflozin without salt restriction group from 1.5 ± 0.8 to 1.3 ± 1.1 times per night (P = 0.297), and significantly decreased from 1.6 ± 1.0 to 1.3 ± 0.7 times per night in the tofogliflozin and dietary salt restriction group (P = 0.049). There was a trend toward increased urine volume and frequency during the daytime in the group with salt restriction, indicating a time-shift effect of the short half-life tofogliflozin and salt restriction on urinary time. The frequency of nocturia after tofogliflozin did not increase. Tofogliflozin reduced nocturia when combined with salt restriction. Furthermore, daytime urine volume and frequency showed an increasing trend, suggesting a shift in urine production to daytime hours due to the short half-life of tofogliflozin. Dietary modifications can enhance the therapeutic benefits of tofogliflozin in managing nocturia in people with type 2 diabetes.

PDE5 inhibitor potentially improves polyuria and bladder storage and voiding dysfunctions in type 2 diabetic rats.

Bladder dysfunction associated with type 2 diabetes mellitus (T2DM) includes urine storage and voiding disorders. We examined pathological conditions of the bladder wall in a rat T2DM model and evaluated the effects of the phosphodiesterase-5 (PDE-5) inhibitor tadalafil. Male Otsuka Long-Evans Tokushima Fatty (OLETF) rats and Long-Evans Tokushima Otsuka (LETO) rats were used as the T2DM and control groups, respectively. Tadalafil was orally administered for 12 weeks. Micturition behavior was monitored using metabolic cages, and bladder function was evaluated by cystometry. Bladder blood flow was evaluated by laser speckle imaging, and an organ bath bladder distention test was used to measure adenosine triphosphate (ATP) release from the bladder urothelium. The expression levels of vesicular nucleotide transporter (VNUT), hypoxia markers, pro-inflammatory cytokines and growth factors in the bladder wall were measured using real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Bladder wall contractions in response to KCl and carbachol were monitored using bladder-strip tests. With aging, OLETF rats had higher micturition frequency and greater urine volume than LETO rats. Although bladder capacity was not significantly different, non-voiding bladder contraction occurred more frequently in OLETF rats than in LETO rats. Bladder blood flow was decreased and ATP release was increased with higher VNUT expression in OLETF rats than in LETO rats. These effects were suppressed by tadalafil administration, with accompanying decreased HIF-1α, 8-OHdG, IL-6, TNF-α, IGF-1, and bFGF expression. The impaired contractile responses of bladder strips to KCl and carbachol in OLETF rats with aging were restored by tadalafil administration. The T2DM rats had polyuria, increased ATP release induced by decreased bladder blood flow and impaired contractile function. PDE5 inhibition improved these changes and may prevent T2DM-associated urinary frequency and bladder storage and voiding dysfunctions.

Do sodium glucose co-transporter-2 (sglt-2) inhibitors affect lower urinary tract, sleep and quality of life in people with type 2 diabetes?

Aim: Sodium-glucose cotransporter-2 (SGLT-2) inhibitors are primarily preferred in patients with type 2 diabetes. The purpose of this paper was to elucidate the effects of SGLT-2 inhibitor use on patients' voiding habits, sleep, and quality of life. Materials and Methods: Our study involved patients with type 2 diabetes who had an SGLT2 inhibitor added to their current treatment. The frequency of day-night urination, lower urinary tract symptoms, sleep and quality of life were assessed both prior to initiation of the treatment and during subsequent 1st and 3rd months. Results: The study included 38 women and 34 men. At the third month after SGLT-2 inhibitor had been added, there was a significant decrease in HbA1c, triglyceride and microalbumin levels (p

Toxic and Metabolic Kidney Injury: Focus on Energy Drinks

Currently, energy drinks on the market are represented by medium and highly carbonated, as well as non-alcoholic and low-alcohol products. More than 500 brands producing energy drinks are registered in the world. Long-term abuse of energy drinks can lead to serious consequences. Kidney damage caused by energy drinks is becoming an urgent medical and social problem, since with prolonged use there is dependence on them, numbness of the limbs, palpitations, headaches and dizziness, pain in the precordial region, increased blood clotting, frequent urination, irritability, depression, insomnia, increased fatigue, anxiety, fear and convulsions. Widespread and uncontrolled use of energy drinks can cause social imbalance in society, decreased mental and physical performance, especially in adolescents. The toxic properties of energy drinks are manifested depending on the volume and composition, presentation, duration of intake, as well as concomitant disease. Availability, wide popularization through advertising in the media, insufficient awareness of young people about the harmful effects of energy drinks serves as a condition for the development of damage to internal organs when consuming them. The article presents data from scientific literature on the epidemiology of risk factors for the development and progression of chronic renal failure. Negative effects on human health with long-term abuse of energy drinks are discussed. The article presents the results of clinical observation of patient N., 31 years old, who developed a neo-oliguric variant of acute kidney injury against the background of long-term use of energy drinks. Laboratory testing revealed hyperglycemia, dyslipidemia, hypercreatininemia (blood creatinine 161.0 μmol/l) and hypercytokinemia due to an increase in the serum concentration of interleukin-6. The glomerular filtration rate (GFR) was at the level of 48 ml/min. Against the background of the therapy, kidney function was restored: blood creatinine 85.9 μmol/l, GFR increased to 116 ml/min.

Rare vesicourethral foreign body caused by sexual eccentricity - case report

BackgroundThere are many types of foreign bodies in the bladder and urethra. The most common way is to insert foreign bodies through the external urethra by oneself or by others. It is often seen in situations such as masturbation, mental disorder, curiosity, etc. This article discusses the clinical diagnosis and treatment methods and preventive measures for foreign bodies in the bladder and urethra caused by sexual fetishes.Case presentationThis article introduces a rare case. The patient was a 54-year-old male who inserted a thermometer into his urethra during masturbation and could not remove it. During the operation, we tried various methods to remove the thermometer many times, but due to the angle of the thermometer embedded in the bladder and urethra and the smooth tip of the thermometer, it could not be removed with foreign body forceps. Finally, a homemade negative pressure aspirator (consisting of a section of infusion tube and a 50 ml syringe) was used to completely remove the thermometer from the bladder and urethra. The Written informed consent was obtained from patient did not experience complications such as mercury leakage and bladder and urethral perforation. A telephone follow-up 4 months later showed that the patient urinated smoothly without discomfort such as frequent urination and urgency.DiscussionThere are many types of vesicourethral foreign bodies. When treating vesicourethral foreign bodies clinically, these can be removed through endoscopy, laparoscopy or open surgery according to the size, type and nature of the foreign bodies. At the same time, in order to effectively prevent the occurrence of bladder and urethra foreign bodies, sex education should be vigorously promoted.

A wireless, battery-free device for electrical neuromodulation of bladder contractions

Lower urinary tract dysfunction (LUTD) is a prevalent condition characterized by symptoms such as urinary frequency, urgency, incontinence, and difficulty in urination, which can significantly impair patient's quality of life and lead to severe physiological complications. Despite the availability of diverse treatment options, including pharmaceutical and behavioral therapies, these approaches are not without challenges. The objective of this study was to enhance treatment options for LUTD by developing a wireless, battery-free device for managing bladder contractions. We designed and validated a compact, fully implantable, battery-free pulse generator using the magnetic induction coupling mechanism of wireless power transmission. Weighing less than 0.2 g and with a volume of less than 0.1 cubic centimeters, this device enables precise stimulation of muscles or neurons at voltages ranging from 0 to 10 V. Wireless technology allows real-time adjustment of key stimulation parameters such as voltage, duration, frequency, pulse width, and pulse interval. Our findings demonstrate that the device effectively controlled bladder contractions in mice when used to stimulate the Major Pelvic Ganglion (MPG). Additionally, the device successfully managed micturition in mice with bilateral transection of the pudendal nerve. In conclusion, the development of this innovative wireless pulse generator provides a safer and more cost-effective alternative to conventional battery-powered neurostimulators for bladder control, addressing the limitations of such devices. We anticipate that this novel technology will play a pivotal role in the future of electrical stimulation therapies for voiding dysfunctions.

Bladder preservation with concurrent chemoradiotherapy for muscle-invasive bladder cancer: Retrospective comparison of three regimens.

The objectives of the study are to evaluate the oncological and functional outcomes of three bladder preservation regimens: radiotherapy alone (RT-alone group), concurrent chemoradiotherapy (CRT) using gemcitabine plus platinum (GP-RT group), and low-dose gemcitabine (LD-Gem-RT group) for muscle-invasive bladder cancer. The three oncological outcomes, bladder-intact distant metastasis-free survival (BI-DMFS), cancer-specific survival, and overall survival (OS), were compared among RT alone (n = 10), GP-RT (n = 16), and LD-Gem-RT (n = 11) groups. Treatment-related adverse events were evaluated against the Common Terminology Criteria for Adverse Events (version 5.0). In the LD-Gem-RT group, time-course changes in the domains and scales related to the quality of life were evaluated by utilizing three questionnaires. Age was significantly higher in the RT alone group (84 ± 7.2 years old) than in the GP-RT (74 ± 9.0) and LD-Gem-RT (75 ± 6.7) groups (P = 0.016). At a median follow-up of 26 months, the 2-year BI-DMFS rates were 80, 81, and 55% in the RT alone, GP-RT, and LD-Gem-RT groups, respectively, and the 2-year OS rates were 69, 62, and 81%, respectively. In the CRT groups, only the baseline CRP ≥ 1.0 mg/dL was associated with poor survival outcomes. Common early-onset adverse events included diarrhea, urinary frequency, and hematotoxicity. A questionnaire survey in the LD-Gem-RT group revealed patients experienced significant deterioration in the global health status/quality of life and the physical component summary score. We reported the oncological and functional outcomes of bladder preservation therapy using three different regimens, yielding acceptable outcomes.

The Pathomechanism and Current Treatments for Chronic Interstitial Cystitis and Bladder Pain Syndrome.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic and debilitating condition characterized by symptoms such as bladder pain, frequent urination, and nocturia. Pain is typically perceived in the lower abdomen, pelvic floor, or urethra, causing significant discomfort and impacting quality of life. Due to the similarity of its symptoms with those of overactive bladder and acute bacterial cystitis, patients often face misdiagnosis and delayed appropriate treatment. Hunner's (HIC) and non-Hunner's IC (NHIC), each with distinct clinical presentations, urothelial dysfunction, chronic inflammation, and central sensitization and thus multimodal symptomatic treatment approaches, may be the most common pathogeneses of IC/BPS. Treatment of IC/BPS should involve identifying the different clinical phenotypes and underlying pathophysiology causing clinical symptoms and developing strategies tailored to the patient's needs. This review discusses the roles of urine biomarkers, bladder inflammation, and glycosaminoglycans in the pathogenesis of IC/BPS. Various bladder treatment modalities are explored, including glycosaminoglycan replenishment, botulinum toxin A injection, platelet-rich plasma injection, low-energy shock waves, immunosuppression, and low-dose oral prednisolone. Pelvic floor muscle physiotherapy and bladder therapy combined with psychiatric consultation can help alleviate psychological stress and enhance the quality of life of patients with IC/BPS. Elucidating the pathological mechanisms and exploring diverse treatment options would help advance the care of individuals suffering from this challenging bladder condition.

Utilizing Bladder Diaries to Prevent Unnecessary Treatment in Patients With Storage Dysfunction: A Retrospective Study.

Introduction A frequency volume chart (FVC) or bladder diary (BD) is used to diagnose lower urinary tract symptoms and to determine the effectiveness of treatment. In outpatient practice, patients who use an FVC or BD may experience improvement in storage symptoms and not desire further treatment. The aim of this study was to determine the characteristics of patients who did not desire treatment after BD recording and to assess the changes in storage symptoms after BD recording. Methods This was a retrospective study. Patients who completed a three-day BD record were included. The patients were divided into two groups: those whose symptoms improved after using a BD and no longer desired treatment, and those who desired treatment. We compared endpoints including patient background, BD, Overactive Bladder Symptom Score (OABSS), and International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF) score. Results We recruited 79 patients. Four patients were excluded (two were minors and two due to cognitive impairment). Thus, 75 patients were included in the analysis. Of these, 27 (36.0%) did not desire treatment for storage symptoms after BD recording. Compared with the group of patients who desired treatment, those who did not desire treatment had significantly lower daytime and nighttime frequency and number of leaks recorded in their BD, and there were fewer patients with nocturia and habitual caffeine consumption. Baseline OABSSand ICIQ-UI SFscores were lower and there were no significant changes in storage symptoms after BD recording. The cut-off value for the baseline total score of OABSSthat did not desire treatment for storage symptoms after BD recording was 6 points. Conclusion In this study, 36.0% of patients no longer desired treatment for storage symptoms after using a BD. These patients initially exhibited a normal daily urinary frequency and mild storage symptoms. These findings suggest that among patients presenting to the outpatient clinic with storage symptoms, those with mild symptom severity and a total OABSSof 6 points or less may be able to avoid unnecessary treatment through BD recording.

Research Progress on the Mechanism of Chinese Herbal Compounds Treating Benign Prostatic Hyperplasia by Regulating Inflammatory Response

Benign prostatic hyperplasia (BPH) is one of the most common benign diseases in middle-aged and elderly men. Its main clinical manifestations are frequent urination, urgent urination, weak urine flow, other lower urinary tract symptoms, serious urinary retention, and urinary incontinence. Chinese herbal compounds are widely used in the clinical treatment of BPH with good efficacy and safety, reflecting the advantages of multi-target and multi-approach traditional Chinese medicine (TCM) treatment. There is usually a high level of inflammation in the affected area of BPH, and its persistence affects the whole body, causing multiple complications and accelerating the development of the disease. Inflammation can directly stimulate the proliferation of prostate cells and drive other pathological mechanisms to jointly promote the development of diseases, such as participating in oxidative stress, driving growth factor synthesis, destroying the imbalance between apoptosis and proliferation, and promoting fibrosis. To more fully elucidate the mechanism of action of Chinese herbal compounds in the treatment of BPH, this paper reviews the literature in recent years, beginning with basic research on the intervention of Chinese herbal compounds in BPH inflammation, to provide further ideas for relevant research on the prevention and treatment of BPH inflammation by TCM.

Caffeine consumption of medical students in Korea: amount and symptoms based on a 2023 survey.

To investigate the form and level of daily caffeine intake recommended above 400 mg in medical students expected to consume caffeinated beverages to enhance their performance. From May to June 2023, freshman through senior medical students at a medical school in Korea were administered a seven-item questionnaire designed to measure the amount of caffeine-containing foods consumed, the weekly interval between consumption, the reason for consumption, and the level of caffeine-induced symptoms experienced. Out of 443 students, 361 responded (81.5%). The most commonly consumed caffeine beverages were coffee (79.2%), followed by soda (33.2%), tea (27.4%), chocolate (25.2%), and energy drinks (20.5%). The estimated (average±standard deviation) daily intake was estimated to 274.6±276.5 mg, and they consumed caffeine on an average of 4.25±2.26 days per week. Students who consumed 400 mg or more of caffeine daily consumed 19.9%. The primary motivation for caffeine intake was "to improve academic performance" (60.9%) and "preferred food" (51.8%). Among the responders, 98% of them replied they had symptoms that could be caused by caffeine, in order of palpitations (47.4%), frequent urination (42.9%), anxiety (27.1%), indigestion (17.5%), and excitement (17.5%). A total of 45.7% reported two symptoms, and 24.7% reported three or more. Caffeinated beverage consumption was routine among current medical students, with 20% consuming more than the recommended daily amount. Most students experienced at least one caffeine-induced symptom, with two symptoms in half, suggesting the need for policy measures and warnings about caffeine-containing foods.

Diterpene glycosides from Fructus Rubi ameliorates benign prostatic hyperplasia in rats through the androgen and TGF-β/Smad signaling pathway

Fructus Rubi (FR), a food material with medicinal value, is used in traditional Chinese medicine (TCM) for treatment of various kidney-related problems, such as impotence, spermatorrhea, and frequent urination. It is also frequently used to produce diverse functional foods in China. The purpose of this research was to assess the therapeutic effects of FR diterpene glycosides on RWPE-1 epithelial cell (RWPE-1), a human normal prostatic epithelial cell, and benign prostate hyperplasia (BPH) rats, both of which had been exposed to dihydrotestosterone (DHT) and testosterone propionate (TP), respectively, and to investigate the mechanism of action. Target proteins that could stably bind to certain diterpene glycosides were screened through drug affinity responsive target stability combined with mass spectrometry (DARTS/MS). DHT-induced RWPE-1cells were used to detect drug activity. TP was subcutaneously injected to induce BPH in rats. The extract of diterpene glycosides from FR (FDS) was orally administered for 28 days. The DHT levels in the serum and prostate tissue of the rats were measured through enzyme-linked immunosorbent assay (ELISA), and to analyze cell proliferation and epithelial-mesenchymal transition (EMT), the protein expression of prostate-specific antigen (PSA), androgen receptor (AR), steroid 5α-reductase type 2 (SRD5A2), proliferating cell nuclear antigen (PCNA), S100 calcium-binding protein A2 (S100A2), transforming growth factor-β1 (TGF-β1), E-cadherin, vimentin, and Smad4 was determined through western blotting (WB), immunohistochemistry (IHC), or immunofluorescence (IF). FDS reduced the proliferation of DHT-induced RWPE-1cells. It also significantly inhibited rat prostate enlargement; decreased DHT levels in the serum and prostate tissue; inhibited the protein expression of AR, PSA, PCNA, S100A2, TGF-β1, E-cadherin, and Smad4; and increased the protein expression of E-cadherin. The present study is the first to report that diterpene glycosides isolated from FR inhibited BPH at the cellular level, regulated the proliferation of prostate cells through the androgen signaling pathway, and prevented EMT in the prostate through the S100A2-mediated TGF-β/Smad signaling pathway. These results indicate that FDS is a promising multitarget therapy for BPH.

Bladder Endometriosis: Symptoms and Pregnancy Outcomes

ObjectiveTo investigate the clinical features of bladder endometriosis and factors associated with urinary symptoms, pregnancy outcomes, and long-term effects of symptom relief and recurrence. DesignA single-center retrospective cohort study. SettingA tertiary referral hospital. ParticipantsForty-seven patients who were surgically confirmed to have bladder endometriosis at Peking Union Medical College Hospital between January 2012 and December 2023 were included in this study. InterventionsA retrospective study of the clinical and pathological features and reproductive outcomes in patients with bladder endometriosis. Measurements and Main ResultsAmong 47 patients with bladder endometriosis, 27 (57.4%) presented with urinary symptoms, including urinary frequency, urgency, dysuria, and hematuria. Patients with urinary symptoms were more likely to have previous cesarean sections (odds ratio [OR] 4.5, 95% confidence interval [CI] 1.1–19.2, p = .032) and experience dysmenorrhea compared to those without (p = .008, OR 5.3, 95% CI 1.5–18.8). Anterior compartment obliteration was another factor associated with urinary symptoms (OR 7.2, 95% CI 1.3–40.4, p = .016). Bladder lesions located within 1 cm of the ureteral orifice (OR 7.2, 95% CI 1.3–40.4, p = .020) and the deeper invasive layer of lesions (mucosal layer, OR 6.1, 95% CI 1.4–25.8, p = .009) were also found to be associated with symptoms. Regarding reproductive outcomes, 12 patients desired to conceive. Of the patients who desired pregnancy, 66.7% achieved pregnancy; 5 spontaneously and 3 after IVF treatment. The miscarriage rate among patients with bladder endometriosis was 25.0% in the age range of 27–40 years. Additionally, all patients experienced symptom relief after one year of follow-up. Only two patients experienced bladder endometriosis recurrence. ConclusionsPrevious cesarean section, dysmenorrhea, anterior compartment obliteration, lesion in the trigone, and mucosal layer invasion were identified as factors associated with urinary symptoms. Although some patients conceived successfully after surgery, disentangling the independent effect of bladder endometriosis on fertility remains challenging.

Feasibility and safety evaluation of ultra-remote robot-assisted laparoscopic hysterectomy

ObjectiveTo assess the safety and feasibility of ultra-remote robot-assisted laparoscopic hysterectomy using the Edge Multi-Port Endoscopic Surgical Robot MP1000 (Shenzhen Edge Medical Co., Ltd., Shenzhen, China) combined with 5G communication technology. MethodsA case of remote robot-assisted laparoscopic hysterectomy was successfully completed on May 2024 by using the Edge Multi-Port Endoscopic Surgical Robot MP1000 at Zhongnan Hospital of Wuhan University and the People's Liberation Army General Hospital, approximately 1, 200 ​km apart. The procedure was simultaneously broadcast during the 36th Annual Meeting of the International Society for Gynecologic Endoscopy in Conjuction with the Peking University Gynecologic Oncology Summit Forum. ResultsA 49-year-old female was hospitalized in the Department of Gynecology of Zhongnan Hospital of Wuhan University for frequent urination for half a year and increased menstrual flow for over a month. The patient was diagnosed with abnormal uterine bleeding caused by multiple uterine leiomyoma and endometrial polyps, combined with moderate anemia. There were no contraindications for surgery, and the patient had surgical indications. On May 2024, the patient underwent a 5G remote robot-assisted laparoscopic hysterectomy and bilateral salpingectomy under general anesthesia. The procedure was successful, with no surgical complications and no interruptions during the live broadcast. The intraoperative blood loss was approximately 20 ​mL, and the surgery lasted about 70 ​min. The bidirectional latency during the operation was around 19 ​ms, with no adverse events related to the robot or the network. The patient recovered well postoperatively and was discharged on the fourth day with no postoperative complications. ConclusionPreliminary findings indicate that ultra-remote robot-assisted laparoscopic hysterectomy is safe and feasible with the support of 5G communication technology. This surgery represents the first globally broadcast remote procedure in the field of gynecology, marking a new milestone in the stability and safety of China's remote medical technology. Remote robotic surgery is expected to be widely promoted in the future, providing services to patients in areas with limited medical resources.

Identification and Molecular Characterization of Clogmia (Telmatoscopus) albipunctatus (Drain Fly) Larva in a Rare Case of Urinary Myiasis in a Domestic Dog in India.

The study aimed to identify Clogmia (Telmatoscopus) albipunctata larva recovered from the urinary tract of a four-year-old female Siberian Husky dog in India using morphological assessment and molecular techniques. Larval specimen obtained from the dog urine underwent preliminary morphological assessments followed by polymerase chain reaction (PCR) to selectively amplify segments of the Cytochrome b (Cytb), NADH1 genes, and the tRNA-Ser gene within mitochondrial DNA. Species identification was achieved through sequence analysis of the amplified product and subsequent phylogenetic analysis. Larva recovered from dog urine underwent morphological examination, revealing notable features characteristic of Clogmia genus. The primers targeting the mitochondrial DNA gene region of fly larva, amplified a distinct product of approximately 788bp. Integration of morphological and molecular biology techniques confirmed the identification of the C. albipunctata larva in the dog urinary tract. This study elucidates the initial molecular evidence of C. albipunctata presence in a four-year-old female Siberian Husky dog exhibiting symptoms of haematuria and frequent micturition in India. It reveals an instance of a domestic dog in India contracting a C. albipunctata larva infection in its urinary tract, emphasizing the importance of clinical vigilance towards this infection.