Natural History and Longitudinal Outcomes of Patients with Mild-to-Moderate Ulcerative Proctitis or Ulcerative Proctosigmoiditis: A Single-Center, Retrospective Study.

BACKGROUND: Ulcerative proctitis (UP) and ulcerative proctosigmoiditis (UPS) are special forms of ulcerative colitis. The disease burdens of UP and UPS are increasing. However, the natural history and prognosis of patients with mild-to-moderate UP or UPS have been poorly studied. AIMS: The aim of this study is to evaluate the characteristics, short-term and long-term outcomes of patients with mild-to-moderate UP or UPS followed at a single center over a period of 3 years. METHODS: A retrospective study of patients with UP and UPS followed at a single center from 2021 to 2023 was performed. After scanning for inclusion and exclusion criteria, patient demographics and clinical data were collected. Disease severity was accessed by Myao endoscopy scores and ulcerative colitis endoscopic index of severity. Endoscopic improvement was defined as decreased scores at the last follow-up. Disease extension was defined as endoscopic evidence of a greater extent of disease at the last follow-up. RESULTS: A total of 414 patients were included for evaluation, of which 292 patients (70.53%) were at mild disease stage, and 122 patients (29.47%) had moderate diseases. At the last follow-up, 315 patients (76.09%) showed endoscopic improvement, and 247 patients (59.66%) showed endoscopic remission. An overall extension rate of 11.11% was observed at the last follow-up. Subgroup analysis revealed a better prognosis in younger patients. The disease extension rate was higher in moderate group and symptomatic patients. CONCLUSION: Promising outcomes were observed in patients with mild-to-moderate ulcerative proctitis or ulcerative proctosigmoiditis. Disease severity and symptoms are correlated with the risk of extension.

The Potential Role of Female Sex Hormones in Patients With Inflammatory Bowel Disease: A 2-Sample Mendelian Randomization Study.

INTRODUCTION: An association between female sex hormones and inflammatory bowel disease (IBD) has been reported in epidemiological studies. However, a solid causal relationship has not been established. Therefore, we performed a 2-sample Mendelian randomization (MR) study to explore the causal association between genetically predicted female sex hormone exposure, especially estrogen, and IBD. METHODS: Genetic variants for female sex hormone exposure (ovulatory function, reproductive function, oral contraceptive pills, and hormone replacement therapy) were obtained from genome-wide association studies. Summary statistics for IBD were derived from the International Inflammatory Bowel Disease Genetics Consortium. We applied inverse variance weighted (IVW), MR-Egger, and weighted median (WM) methods in this MR study. Heterogeneity, horizontal pleiotropy, and sensitivity analyses were conducted to confirm the accuracy and robustness of our results. RESULTS: Our study found that genetically predicted age at menarche was associated with an increased risk of Crohn's disease (odds ratio [OR] IVW 1.235, 95% confidence interval [CI] 1.028-1.484, P = 0.024), genetically predicted age of the last used hormone replacement therapy was associated with an increased risk of ulcerative colitis (OR WM 1.636, 95% CI 1.011-2.648, P = 0.045), and genetically predicted number of live births was related to a decreased risk of Crohn's disease (OR IVW 0.583, 95% CI 0.373-0.912, P = 0.018). DISCUSSION: This study provided evidence for a link between female sex hormone exposure, especially estrogen, and IBD. Further investigations are needed to explore the causal effect of estrogen on IBD activity and the underlying mechanism of estrogen in IBD.

Whole body vibration training promotes proprioceptive pathway for the treatment of stress urinary incontinence in rats.

Background: Stress urinary incontinence (SUI) is the most ubiquitous form of urinary incontinence in women. The therapeutic management of patients with SUI is challenging. The aim of this study is to evaluate the efficacy of whole body vibration training (WBVT) for SUI. Methods: Thirty-five female rats were randomly divided into a sham group (Sham group, n=5), SUI + WBVT group (n=15) and SUI + whole body rest group (SUI + WBR group, n=15). The SUI + WBVT group was trained as follows: frequency 30 Hz, amplitude four mm, one min/repeat, four min rest, repeated 10 times, five days/week. After the intervention, five rats were taken on the 7th, 14th and 21st day to observe the urodynamic changes, levator ani muscle and dorsal root ganglia (DRG) morphology, and to observe the expression of neurotrophic factor-3/tyrosine protein kinase C (NT-3/TrkC) by Western blot. Results: The urodynamic results showed that the difference in bladder leak point pressure/abdominal leak point pressure (BLPP/ALPP) between the Sham group and the SUI + WBR group was statistically significant (P<0.001) on 7th day, indicating successful modeling. The BLPP/ALPP of the SUI + WBVT group and the SUI + WBR group improved on 7th, 14th, and 21st day, and the BLPP/ALPP of SUI + WBVT group was higher than the SUI + WBR group. Compared with the Sham group, pathological changes appeared in the muscle shuttles in the SUI + WBVT group and SUI + WBR group. Western blot showed a gradual up-regulation of NT-3/TrkC. Conclusions: WBVT can be used to treat SUI by affecting the expression of NT-3/TrkC, improving the structural morphology of the proprioceptors, and restoring the urinary control function. This study provides evidence for the clinical practice of WBVT. Future studies could further refine the behavioral and electrophysiological aspects of the assessment.

Global burden and trends in female premenstrual syndrome study during 1990-2019.

PURPOSE: Premenstrual syndrome (PMS) is prevalent worldwide and considered a crucial issue regarding women's health. In the present study, the Global Burden of Disease (GBD) Study 2019 dataset was utilized to assess the distributional trends in PMS burden and prevalence in regional, national, and sociodemographic index (SDI) categories. METHODS: The analytical methods and approaches used in the 2019 GBD study were adopted to investigate the incidence rates and disability-adjusted life years (DALY) related to PMS in 204 countries or regions. Age-standardized incidence rates (ASIR), 95% uncertainty intervals (95% UI), and annual percentage changes (EAPC) were calculated from the data. RESULTS: The global incidence and disability-adjusted life years of PMS exhibited a declining trend in the year 2019. Regions with medium-low SDI had the greatest burden of PMS, with the regions of South Asia (ASR = 7337.9 per 10,000) exhibiting the greatest Age-standardized incidence rates, while the high-income North American states presented the fastest upward trends in Age-standardized disability-adjusted life year rates. At the national level, 107 nations exhibited a decreasing trend in PMS incidence ASR, while 97 nations exhibited an increasing trend, with the United States presenting the greatest increase. CONCLUSIONS: The present study highlighted that even though the global PMS incidence and disability-adjusted life years have decreased from the year 1990 to 2019, PMS remains a prevalent health concern for women worldwide. While addressing preventive measures and treatment, it is also important to consider the regional and national differences in PMS to develop further effective and targeted health policies.

Pelvic floor dysfunction after colorectal cancer treatment is related to physical and psychological health and body image: A cross-sectional study.

PURPOSE: Pelvic floor dysfunction (PFD) often occurs in patients with colorectal cancer (CRC), which can affect their quality of life. However, the precise factors that related to PFD in CRC patients remain elusive. The main objective of this study was to identify the variables associated with PFD following CRC treatment and establish a foundation for the development of a tailored rehabilitation plan specific to this population. METHODS: The classification of 149 patients with CRC was conducted according to the type of medical treatment they underwent. PFD was evaluated using the Urogenital Distress Inventory 6 (UDI-6) and Colorectal-Anal Distress Inventory 8 (CRADI-8) questionnaires. The study employed the Short form 36 health survey (SF-36) and Body Image Scale (BIS) to evaluate physical and psychological health as well as body image disorders. The connection between PFD and independent variables was determined through logistic regression analyses. RESULTS: Of all patients, more than 50% reported experiencing dysfunction, with the highest proportion observed in the PRT (primary radiotherapy) group. The LRR/RR (robotic-assisted colorectal resection or laparoscopic colorectal resection) group revealed a significant association between high BMI (Body Mass Index) and alcohol consumption with PFD. Moreover, in the PRT group, PFD was correlated with poorer physical condition (OR = 0.94, 95% CI = [0.88-1.00]). CONCLUSIONS: PFD is a commonly complained-about issue among patients with CRC. Early intervention targeted towards these factors may aid in the alleviation of associated distress and contribute towards the individualization of CRC rehabilitation programs, consequently improving the quality of life for patients.

Risk Factors Related to Polyp Miss Rate of Short-Term Repeated Colonoscopy.

BACKGROUND: Colonoscopy is regarded as the gold standard for colorectal cancer screening and surveillance. However, previous studies have reported large numbers of polyps were missed during routine colonoscopy. AIMS: To evaluate polyp miss rate in short-term repeated colonoscopy and explore the related risk factors. METHODS: A total of 3695 patients and 12,412 polyps were included in our studies. We calculated the miss rate for polyps of different sizes, pathologies, morphologies and locations, and patients of different characteristics. Univariate and multivariate logistic regression analyses were performed to evaluate risk factors related to miss rate. RESULTS: The polyp miss rate was 26.3% and the adenoma miss rate was 22.4% in our study. The advanced adenoma miss rate was 11.0% and the proportion of missed advanced adenomas in missed adenomas sized > 5 mm was up to 22.8%. Polyps sized < 5 mm had a significantly higher miss rate. The miss rate of pedunculated polyps was lower than that of flat or sessile polyps. Polyps in the right colon were prone to be missed than that in the left colon. For older men, current smokers, individuals with multiple polyps detected in the first colonoscopy, the risk of missing polyps was significantly higher. CONCLUSION: Nearly a quarter of polyps were missed during routine colonoscopy. Diminutive, flat, sessile, and right-side colon polyps were at higher risk of missing. The risk of missing polyps was higher in older men, current smokers, and individuals with multiple polyps detected in the first colonoscopy than their counterparts.

Platelet-rich Plasma Promotes Restoration of the Anterior Vaginal Wall for the Treatment of Pelvic Floor Dysfunction in Rats.

STUDY OBJECTIVE: To determine the efficacy of using platelet-rich plasma (PRP) for vaginal wall repair in rats with vaginal wall impairment induced by vaginal distension (VD). DESIGN: A single-blind, randomized study. SETTING: A certified animal research facility. ANIMALS: Twenty-four female Sprague Dawley rats. INTERVENTIONS: Female Sprague Dawley rats were divided into sham (n = 8), VD (n = 8), and VD + PRP (n = 8) groups. Vaginal tissues from the VD group were dissected at 28-day post injury. VD + PRP rats received vaginal PRP injections on the 1st, 7th, 14th, and 21st day after VD and sacrificed on the 28th day. MEASUREMENTS AND MAIN RESULTS: Urodynamic tests were performed in all rats. Immunohistochemistry was used to evaluate matrix metalloprotease-2 (MMP-2) and matrix metalloprotease-9 (MMP-9). Masson's staining was used to evaluate collagen fibers and calculate collagen volume fraction. Collagen fiber damage was confirmed in the VD group, evidenced by thinner and sparse distribution of collagen fibers, with significantly higher MMP-2 and MMP-9 expression than the sham group (p <.05). The collagen fiber damage in the vaginal wall likely led to pelvic floor dysfunction (PFD), evidenced by significantly decreased bladder leak-point pressure (p <.01) and abdominal leak-point pressure (p <.01) in the VD group compared with the sham group. After completion of the PRP treatment, a significantly higher collagen volume fraction (p <.01) and significantly increased bladder leak-point pressure (p <.05) and abdominal leak-point pressure (p <.01) were achieved in the VD + PRP compared with the VD group, thus indicating repair of the vaginal wall and improvement of PFD. CONCLUSION: PRP injections facilitate the regeneration of vaginal wall tissue, particularly collagen fiber, after VD, leading to functional improvement of PFD. Findings support the feasibility of using PRP as a novel treatment for PFD.

Treatment with platelet-rich plasma attenuates proprioceptor abnormalities in a rat model of postpartum stress urinary incontinence.

INTRODUCTION AND HYPOTHESIS: Stress urinary incontinence (SUI) is the most prevalent form of urinary incontinence, and vaginal delivery is a major risk factor for developing SUI. We evaluated the hypothesis that applying the autologous platelet rich plasma (PRP) to the pelvic floor muscles via injection affects expression of proprioceptors and improves postpartum stress urinary incontinence (PSUI) in rats. METHODS: Virgin female Sprague-Dawley rats were divided into control (n = 10) and experimental group(n = 20). Vaginal dilation was used to establish PSUI, and the rats in the experimental group were further divided into the PSUI group (n = 10) and PSUI+PRP group (n = 10). Pelvic floor muscles from rats in the PSUI+PRP group were positioned under ultrasound guidance for PRP injection. The morphology and number of pelvic floor muscle spindles were assessed using H&E staining, proprioceptors evaluated by gold chloride staining, and changes in the expression of neurotrophin-3 (NT-3) and skeletal myosin MY-32 determined by immunohistochemistry. RESULTS: After 28 days,bladder leak point pressure (BLPP) and abdominal leaking-urine point pressure (ALPP) in rats with PSUI were significantly lower than in control animals (P<0.01). Both BLPP and ALPP increased significantly in the PSUI+PRP group (P<0.01). Compared with the control group, muscle spindle morphology and structure in the PSUI and PSUI+PRP groups had different pathological changes,with higher variations in the PSUI group. The positive signals for NT-3/MY-32 expression in control rats were higher than those from PSUI or PSUI+PRP groups, however, the expression for NT-3/MY-32 in PSUI+PRP animals was higher than that seen in the PSUI group (P < 0.01). CONCLUSIONS: PSUI rats have an abnormal expression of pelvic proprioceptors, which affect proprioceptive function, and further the contractibility of pelvic floor muscles. A PRP injection may restore the sensory function of pelvic proprioceptors, thus improving urine leakage in PSUI rats.

The safety and efficacy of peroral endoscopic cardial constriction in gastroesophageal reflux disease.

BACKGROUND AND AIM: Gastroesophageal reflux disease (GERD) is one of the most common digestive disorders, which seriously affects the quality of life and brings a heavy burden to the medical care. Peroral endoscopic cardial constriction (PECC) can narrow the cardia through mucosal ligation to alleviate acid reflux symptoms. This study aims to assess the clinical efficacy of PECC. METHODS: This was a retrospective case series including patients diagnosed with GERD and undergoing PECC from September 2019 to July 2021. GERD-Q questionnaire and GERD-QOL questionnaire were applied to evaluate the symptom severity and the impact of life because of GERD. RESULTS: A total of 16 patients were included in our study. The mean GERD-Q score was 10.94 ± 2.11 before PECC, while 5.38 ± 3.90 after PECC. The mean GERD-QOL score was 43.60 ± 16.94 before PECC, while 73.65 ± 22.08 after PECC. 62.5% of patients were satisfied with the symptom control and no serious complications were reported in our study. CONCLUSIONS: PECC is an efficient and safe minimally invasive endoscopic intervention for GERD. It can significantly improve GERD-related symptoms and quality of life.

Validation of a Chinese version for the global Pelvic Floor Bother Questionnaire.

PURPOSE: The Pelvic Floor Bother Questionnaire (PFBQ) is a self-administered instrument for determining pelvic floor dysfunction (PFD). The PFBQ was validated in English, but lately in other languages. However, a Chinese version has not been established. Thus, we aimed at validating a Chinese PFBQ version. METHODS: We used a translation-back method to develop a PFBQ Chinese version and validated in 102 women, 51 with at least one PFD symptom participated in the patient group, and 51 without PFD in the control group. Construct validity was assessed by comparing groups and a content validity index (CVI) determined. For test-retest reliability, participants completed the questionnaire twice within 1-week interval and the interclass correlation coefficient (ICC) was determined. Internal consistency was calculated using Cronbach's statistics. RESULTS: Missing information after applying the translated PFBQ did not exceed 4% of any questions. Total scores between control and PFD women were significantly different (2.94 ± 1.84 vs. 10.29 ± 6.64; P < 0.001). The CVI for all items ranged from 0.800 to 1.000, and a good reliability was corroborated (α = 0.677, ICC = 0.938). CONCLUSION: The Chinese PFBQ version is a valid and reliable tool to identify the existence and severity of bothersome symptoms in Chinese women with PFD.

Transforming a toxic drug into an efficacious nanomedicine using a lipoprodrug strategy for the treatment of patient-derived melanoma xenografts.

Despite the progress made with the recent clinical use of the anticancer compound cabazitaxel, the efficacy in patients remains unsatisfactory, largely due to the high in vivo toxicity of the agent. Therefore, strategies that achieve favorable outcomes and good safety profiles will greatly expand the repertoire of this potent agent. Here, we propose a combinatorial strategy to reform the cabazitaxel agent and the use of sequential supramolecular nanoassembly with liposomal compositions to assemble a prodrug-formulated liposome, termed lipoprodrug, for safe and effective drug delivery. Reconstructing cabazitaxel with a polyunsaturated fatty acid (i.e., docosahexaenoic acid) via a hydrolyzable ester bond confers the generated prodrug with the ability to be readily integrated into the lipid bilayer of liposomes for systemic administration. The resulting lipoprodrug scaffold showed significantly sustained drug release profiles and improved pharmacokinetics in rats as well as a reduction in systemic toxicity in vivo. Notably, the lipoprodrug outperformed free cabazitaxel in terms of in vivo therapeutic efficacy in multiple separate tumor xenograft-bearing mouse models, one of which was a patient-derived xenograft model. Surprisingly, the lipoprodrug was able to reduce tumor invasiveness and reprogram the tumor immunosuppressive microenvironment by proinflammatory macrophage polarization. Our findings validate this lipoprodrug approach as a simple yet effective strategy for transforming the highly toxic cabazitaxel agent into an efficacious nanomedicine with excellent in vivo tolerability. This approach could also be applied to rescue other drugs or drug candidates that have failed in clinical trials due to poor pharmacokinetic properties or unacceptable toxicity in patients.