In the context of China's aging population, the issue of urinary incontinence among the elderly is becoming increasingly severe.Urinary incontinence not only significantly impacts patients' quality of life, but also imposes a substantial economic burden and psychological stress.This article explores the challenges and prospects of the early intervention of elderly urinary incontinence in China, including improving early diagnosis rates, enhancing patients' self-management abilities, and early screening and prevention for high-risk groups.With the advancement of technology and medical innovations, digital self-management tools offer new possibilities for managing urinary incontinence, helping patients to better control their condition, especially when medical resources are limited.Furthermore, this article calls for greater attention from all sectors of the society to address elderly urinary incontinence and promote the implementation of more systematic research and management strategies to improve the quality of life for China's elderly population.

Objective: In the global phase 3 Study 309/KEYNOTE-775 (NCT03517449) at the first interim analysis, lenvatinib+pembrolizumab significantly improved progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) versus treatment of physician’s choice chemotherapy (TPC) in patients with previously treated advanced/recurrent endometrial cancer (EC). This exploratory analysis evaluated outcomes in patients enrolled in East Asia at the time of prespecified final analysis. Methods: Women ≥18 years with histologically confirmed advanced, recurrent, or metastatic EC with progressive disease after 1 platinum-based chemotherapy (2 if 1 given in neoadjuvant/ adjuvant setting) were enrolled. Patients were randomized 1:1 to lenvatinib 20 mg orally once daily plus pembrolizumab 200 mg intravenously every 3 weeks (≤35 cycles) or TPC (doxorubicin or paclitaxel). Primary endpoints were PFS per RECIST v1.1 by blinded independent central review and OS. No alpha was assigned for this subgroup analysis. Results: Among 155 East Asian patients (lenvatinib+pembrolizumab, n=77; TPC, n=78), median follow-up time (data cutoff: March 1, 2022) was 34.3 (range, 25.1–43.0) months.Hazard ratios (HRs) with 95% confidence intervals (CIs) for PFS (lenvatinib+pembrolizumab vs. TPC) were 0.74 (0.49–1.10) and 0.64 (0.44–0.94) in the mismatch repair proficient (pMMR) and all-comer populations, respectively. HRs (95% CI) for OS were 0.68 (0.45–1.02) and 0.61 (0.41–0.90), respectively. ORRs were 36% with lenvatinib+pembrolizumab and 22% with TPC (pMMR) and 39% and 21%, respectively (all-comers). Treatment-related adverse events occurred in 97% and 96% (grade 3–5, 74% and 72%), respectively. Conclusion Lenvatinib+pembrolizumab provided clinically meaningful benefit with manageable safety compared with TPC, supporting its use in East Asian patients with previously treated advanced/recurrent EC.

Objective: In the global phase 3 Study 309/KEYNOTE-775 (NCT03517449) at the first interim analysis, lenvatinib+pembrolizumab significantly improved progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) versus treatment of physician’s choice chemotherapy (TPC) in patients with previously treated advanced/recurrent endometrial cancer (EC). This exploratory analysis evaluated outcomes in patients enrolled in East Asia at the time of prespecified final analysis. Methods: Women ≥18 years with histologically confirmed advanced, recurrent, or metastatic EC with progressive disease after 1 platinum-based chemotherapy (2 if 1 given in neoadjuvant/ adjuvant setting) were enrolled. Patients were randomized 1:1 to lenvatinib 20 mg orally once daily plus pembrolizumab 200 mg intravenously every 3 weeks (≤35 cycles) or TPC (doxorubicin or paclitaxel). Primary endpoints were PFS per RECIST v1.1 by blinded independent central review and OS. No alpha was assigned for this subgroup analysis. Results: Among 155 East Asian patients (lenvatinib+pembrolizumab, n=77; TPC, n=78), median follow-up time (data cutoff: March 1, 2022) was 34.3 (range, 25.1–43.0) months.Hazard ratios (HRs) with 95% confidence intervals (CIs) for PFS (lenvatinib+pembrolizumab vs. TPC) were 0.74 (0.49–1.10) and 0.64 (0.44–0.94) in the mismatch repair proficient (pMMR) and all-comer populations, respectively. HRs (95% CI) for OS were 0.68 (0.45–1.02) and 0.61 (0.41–0.90), respectively. ORRs were 36% with lenvatinib+pembrolizumab and 22% with TPC (pMMR) and 39% and 21%, respectively (all-comers). Treatment-related adverse events occurred in 97% and 96% (grade 3–5, 74% and 72%), respectively. Conclusion Lenvatinib+pembrolizumab provided clinically meaningful benefit with manageable safety compared with TPC, supporting its use in East Asian patients with previously treated advanced/recurrent EC.

Objective: In the global phase 3 Study 309/KEYNOTE-775 (NCT03517449) at the first interim analysis, lenvatinib+pembrolizumab significantly improved progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) versus treatment of physician’s choice chemotherapy (TPC) in patients with previously treated advanced/recurrent endometrial cancer (EC). This exploratory analysis evaluated outcomes in patients enrolled in East Asia at the time of prespecified final analysis. Methods: Women ≥18 years with histologically confirmed advanced, recurrent, or metastatic EC with progressive disease after 1 platinum-based chemotherapy (2 if 1 given in neoadjuvant/ adjuvant setting) were enrolled. Patients were randomized 1:1 to lenvatinib 20 mg orally once daily plus pembrolizumab 200 mg intravenously every 3 weeks (≤35 cycles) or TPC (doxorubicin or paclitaxel). Primary endpoints were PFS per RECIST v1.1 by blinded independent central review and OS. No alpha was assigned for this subgroup analysis. Results: Among 155 East Asian patients (lenvatinib+pembrolizumab, n=77; TPC, n=78), median follow-up time (data cutoff: March 1, 2022) was 34.3 (range, 25.1–43.0) months.Hazard ratios (HRs) with 95% confidence intervals (CIs) for PFS (lenvatinib+pembrolizumab vs. TPC) were 0.74 (0.49–1.10) and 0.64 (0.44–0.94) in the mismatch repair proficient (pMMR) and all-comer populations, respectively. HRs (95% CI) for OS were 0.68 (0.45–1.02) and 0.61 (0.41–0.90), respectively. ORRs were 36% with lenvatinib+pembrolizumab and 22% with TPC (pMMR) and 39% and 21%, respectively (all-comers). Treatment-related adverse events occurred in 97% and 96% (grade 3–5, 74% and 72%), respectively. Conclusion Lenvatinib+pembrolizumab provided clinically meaningful benefit with manageable safety compared with TPC, supporting its use in East Asian patients with previously treated advanced/recurrent EC.

OBJECTIVES: With the increase in aging population in China, elderly Crohn's disease (CD) patients need to receive more attention. This study aims to explore the clinical characteristics and disease process of elderly onset CD (EOCD) patients in a single center. METHODS: From January 2002 to January 2022, a total of 221 patients with CD from the Seventh Medical Center of Chinese PLA General Hospital were enrolled. According to the Montreal CD classification standard, the patients were further divided into 4 groups: an EOCD group (≥60 years old, n=25), a middle age onset CD (MOCD) group (40-59 years old, n=46), a young onset CD (YOCD) group (17-40 years old, n=131), and a childhood onset CD (COCD) group (6-16 years old, n=19). We compared the clinical characteristics and long-term prognosis among them. RESULTS: Females were predominant in the EOCD group (15/25, 60%). The number of people without smoking in the EOCD group (80%) was lower than that in COCD group (100%), higher than that in the YOCD group (70.2%) and the MOCD group (69.6%) (all P<0.05). Patients with perianal diseases at diagnosis were rare in the EOCD group (0%), lower than that in the COCD group (21.1%) and the YOVD group (19.8%) (all P<0.05). Stenosis was the most common disease behavior in the EOCD group (63.0%), significantly higher than that in the COCD group (15.8%), the YOCD group (36.6%) and the MOCD group (43.5%) (all P<0.05). The EOCD group was easier to be misdiagnosed as tumor (24%), higher than that in the COCD group (0%), the YOCD group (6.9%) and the MOCD group (19.6%) (all P<0.05). The EOCD group was prone to comorbidities (52%), and 20% of them were complicated with multiple comorbidities (P<0.05). During the follow-up, the all-cause mortality of EOCD was 12%, and the CD-related mortality was 8%, which was significantly higher than the other groups (all P<0.05). The use of immunosuppressants in the EOCD group (4.8%) was lower than that in the COCD group (12.8%), the YOCD group (16.8%) and the MOCD group (16.1%), but there was no statistical significance among the 4 groups (P=0.467). In addition, there was no significant difference in the rate of intestinal resection among the 4 groups (P=0.062). CONCLUSIONS In EOCD patients, females were predominant, smoking was less common, and they were prone to comorbidity. At the initial stage of diagnosis, it is easy to be misdiagnosed as tumor, and the disease behavior mainly showed stricture type, less complicated with perianal diseases. During the follow-up, all-cause mortality and CD-related mortality of EOCD patients were significantly higher than those of the non-elderly onset CD patients.
Female ; Middle Aged ; Humans ; Aged ; Child ; Adult ; Adolescent ; Young Adult ; Crohn Disease/epidemiology* ; Prognosis ; Constriction, Pathologic ; Aging ; Hospitals, General

Objective:To investigate associations between clinicopathological characteristics and mutations in susceptibility genes in cutaneous melanoma (CMM) .Methods:A total of 94 patients with confirmed CMM were collected from People′s Hospital of Xinjiang Uygur Autonomous Region from January to December in 2019, and their clinical and histopathological characteristics were retrospectively analyzed. In 48 paraffin-embedded melanoma tissue specimens, Sanger sequencing was performed to detect mutations in the BRAF, NRAS, c-KIT genes and the promoter region of human telomerase reverse transcriptase (hTERT) gene, and the association between gene mutations and clinicopathological characteristics was analyzed. Measurement data were compared using t test, and enumeration data were compared using chi-square test or Fisher′s exact test. Results:Among the 94 patients with CMM, there were 46 (48.9%) males and 48 (51.1%) females, with the age being 58.5 ± 16.0 years; 41 (43.6%) patients were of Han nationality, and 53 (56.4%) were of ethnic minorities. Skin lesions were located at the acral sites in 50 (53.2%) patients, including 27 (28.7%) of Han nationality; non-acral skin lesions occurred in 44 (46.8%) , including 14 (31.8%) of Han nationality; there was a significant difference in the nationality distribution between the acral CMM group and non-acral CMM group ( χ2 = 5.25, P = 0.022) . Histopathological examination showed CMM of Clark grades Ⅳ or Ⅴ in 41 (43.6%) cases, ulcers in 52 (55.3%) cases, and lymph node metastasis in 32 (34.04%) cases at the first clinic visit. Gene sequencing revealed BRAF gene mutations in 11 (22.9%) of 48 cases, including c.1799 T>A (p.V600E) , c.1790 T>A (p.L597Q) and c.1394 C>T (p.S465F) ; NRAS gene mutation c.182 A>G (p.Q61R) was identified in 5 (10.4%) cases; c-KIT gene mutations were identified in 6 (12.5%) cases, including c.1727 T>C (p.L576P) and c.1669 T>C (p.W557R) ; mutations in the promoter region of hTERT gene were identified in 7 (14.6%) cases, including 4 cases with a mutation at 124 bp upstream of the ATG start codon (C228T) and 3 cases with a mutation at 146 bp upstream of the ATG start codon (C250T) . Among 26 patients aged < 60 years, BRAF gene mutations were found in 9, and the incidence of BRAF gene mutations was significantly higher in the patients aged < 60 years than in those aged ≥ 60 years (2/22, P < 0.05) , but significantly lower in the patients with acral CMM (3/27) than in those with non-acral CMM (8/21, P < 0.05) ; the incidences of the NRAS, c-KIT and hTERT gene mutations were all significantly higher in the patients with lymph node metastases (3/10, 4/10, 4/10, respectively) than in those without (2/38, 2/38, 3/38, respectively, all P < 0.05) . Conclusion:CMM lesion locations significantly differed among different ethnic groups; the BRAF gene mutation was associated with the age of patients and lesion locations of CMM; NRAS, c-KIT gene mutations and hTERT promoter mutations were closely related to lymph node metastasis.

Objective:To evaluate the short-term efficacy of dual biologics combination therapy in the treatment of refractory Crohn′s disease (CD) .Methods:The clinical features, diagnosis and treatment of 5 cases of refractory CD treated with biologics dual-target therapy in the Seventh Medical Center of Chinese PLA General Hospital between January 26, 2020 and August 15, 2021 were retrospectively analyzed. The relevant literatures were reviewed and summarized by searching the articles on biologics dual-target therapy published in MEDLINE, EMBASE and Cochrane Library until August 2021.Results:Five patients with refractory CD were all male, aged 40.8 (23.0, 56.0) years, with disease course of 10.4 (6.0, 17.0) years, including 2 patients treated with infliximab (IFX) in combination with ustekinumab (UST) . Two patients treated with IFX in combination with vedolizumab (VDZ) and 1 patient treated with UST in combination with VDZ. Laboratory and colonoscopy examinations were performed 14 weeks after combination therapy in the VDZ containing group and 16 weeks after combination therapy in the VDZ free group. Results of examinations after treatment indicated that 1 case presented clinical remission, 3 cases presented clinical response and 3 cases presented endoscopic response. Combination therapy group with UST had better efficacy. None of the 5 patients had special adverse drug reactions during follow-up for six months after combined treatment. A total of 17 relevant reports were retrieved.Conclusion:Biologic dual-target therapy may be a short-term effective and safe treatment for refractory CD.

Objective:To evaluate the short-term efficacy of dual biologics combination therapy in the treatment of refractory Crohn′s disease (CD) .Methods:The clinical features, diagnosis and treatment of 5 cases of refractory CD treated with biologics dual-target therapy in the Seventh Medical Center of Chinese PLA General Hospital between January 26, 2020 and August 15, 2021 were retrospectively analyzed. The relevant literatures were reviewed and summarized by searching the articles on biologics dual-target therapy published in MEDLINE, EMBASE and Cochrane Library until August 2021.Results:Five patients with refractory CD were all male, aged 40.8 (23.0, 56.0) years, with disease course of 10.4 (6.0, 17.0) years, including 2 patients treated with infliximab (IFX) in combination with ustekinumab (UST) . Two patients treated with IFX in combination with vedolizumab (VDZ) and 1 patient treated with UST in combination with VDZ. Laboratory and colonoscopy examinations were performed 14 weeks after combination therapy in the VDZ containing group and 16 weeks after combination therapy in the VDZ free group. Results of examinations after treatment indicated that 1 case presented clinical remission, 3 cases presented clinical response and 3 cases presented endoscopic response. Combination therapy group with UST had better efficacy. None of the 5 patients had special adverse drug reactions during follow-up for six months after combined treatment. A total of 17 relevant reports were retrieved.Conclusion:Biologic dual-target therapy may be a short-term effective and safe treatment for refractory CD.

Objective:To prospectively follow up the patients with ileocecal inflammatory lesions, to explore the characteristics of Crohn′s disease(CD) at early stage, and to provide references for early diagnosis of CD.Methods:From January 2013 to December 2018, at Department of Gastroenterology, The Seventh Medical Center of PLA General Hospital, 232 patients with unexplained ileocecal inflammatory lesions under colonoscopy examination were enrolled, which were followed up for more than one year. Chi-square test and Fisher exact probability text were used to compare the patients with early CD, with non-specific enteritis and intestinal tuberculosis in abdominal symptoms (abdominal pain, diarrhea, abdominal distension, constipation, hematochezia, changes in bowel habits), accompanying symptoms (oral ulcer, arthralgia), the proportion of patients with elevated erythrocyte sedimentation rate (ESR) or elevated C-reactive protein (CRP) level, serum antineutrophilic cytoplasmic antibody (ANCA), anti-saccharomyces cerevisiae antibody (ASCA), tuberculosis infection of T cells spot test, positive rate of fecal occult blood, lesion size, morphology, involvement site under endoscopy and histopathological results. Multivariate binary logistic regression was used to analyze the related factors of early CD.Results:Among 232 patients, 155 were males and 77 were females, and the age of first diagnosis was (43.9±13.8) years old. The follow-up period (range) was 27 months (12 to 79 months). Twenty-nine cases (12.5%) were diagnosed as early CD, 45 cases (19.4%) were intestinal tuberculosis, 105 cases (45.3%) were non-specific enteritis, and 53 cases (22.8%) as undetermined. All of 29 patients with early CD had abdominal symptoms, which accounted for 16.9% (29/172) of 172 patients with ileoceccal inflammatory lesion as well as abdominal symptoms. In early CD patients, the proportions of patients with abdominal pain, elevated CRP level and ESR level, positive rate of ASCA, positive rate of tuberculosis infection T cells and percentage of patients with thickened intestinal wall were all higher than those in patients with non-specific enteritis (62.1%, 18/29 vs. 33.3%, 35/105; 13.8%, 4/29 vs. 0; 13.8%, 4/29 vs. 1.0%, 1/105; 24.1%, 7/29 vs. 1.0%, 1/105; 20.7%, 6/29 vs. 3.8%, 4/105; 95.7%, 22/23 vs. 0), and the proportion of patients without abdominal symptoms was lower than that of patients with non-specific enteritis (0 vs. 31.4%, 33/105). And the differences were statistically significant ( χ2=6.692, Fisher exact probability text, χ2=7.162, χ2=17.826, χ2=7.497, Fisher exact probability text, and Fisher exact probability text, all P<0.05). Early CD patients were more likely to have multiple lesion sites (55.2%, 16/29), and mainly deep ulcers (55.2%, 16/29) and ulcers with a long diameter of 5 to 10 mm (39.3%, 11/28). The lesions of non-specific enteritis were mostly confined to the end of ileum (75.2%, 79/105), which were mainly superficial ulcers (41.0%, 43/105) and ulcers with a long diameter less than 5 mm (69.0%, 49/71). The proportion of patients without abdominal symptoms and the positive rate of tuberculosis infection of T cells spot test of early CD patients were both lower than those of intestinal tuberculosis group (0 vs. 15.6%, 7/45 and 20.7%, 6/29 vs. 68.9%, 31/45). The positive rate of ASCA and the proportion of patients with thickened intestinal wall were higher than those of intestinal tuberculosis group (24.1%, 7/29 vs. 0 and 95.7%, 22/23 vs. 11/19), and the differences were statistically significant (Fisher exact probability text, χ2=13.713, Fisher exact probability text and χ2=6.710, all P<0.05). The results of multivariate binary logistic regression analysis showed that abdominal pain and positive ASCA were independent risk factors for early CD (odds ratio ( OR)=2.855, 95% confidence interval ( CI) 1.014 to 8.037, P=0.047; OR=10.033, 95% CI 2.274 to 44.250, P=0.002). Conclusions:Prospective follow-up for more than one year in patients with unexplained ileocecal inflammatory lesions can effectively identify and diagnose early CD. Ileocecal inflammatory lesions with abdominal symptoms are one of the early manifestations of CD. Abdominal pain and positive serum ASCA at the initial diagnosis are independent risk factors for early diagnosis of CD.

OBJECTIVE： To improve the quality of pediatric clinical trials， and establish the clinical trial training system for pediatric. METHODS： By consulting the literature， referring to the clinical research and training system of the United States and the European Union （mainly including initiators， training objects， training contents and time， training methods and assessment methods）， and combining with the characteristics of pediatric clinical trials in China， the pediatric clinical trial training system was built. RESULTS & CONCLUSIONS： The training system of clinical drug trials in the United States and the European Union is relatively perfect. Taking the United States as an example， clinical drug trials in the United States were initiated by the National Institutes of Health （NIH）， mainly for clinical researchers and other health technicians engaged in clinical research. The training contents included pharmacology， clinical research principle and practice， bioethics， etc. The training time was usually not indicated. The main methods included distance education and online network training， and assessment through online network examination. The author suggests that a collaborative network of pediatric clinical trials should be established in China. For clinical researchers， training courses should be developed at different levels （e.g. basic classes， promotion classes， advanced classes） and corresponding time should be set up （e.g. 2， 3， 4 d）. Various training methods should be set up （e.g. online， face-to-face， assignment， etc.） and assessment methods should changed （be changed to face-to-face assessment and formulate unified assessment criteria）. The training system of pediatric drug clinical trials in China can be gradually built and improved through the above ways.