Objective:To explore the clinical characteristics and outcomes of type 2 autoimmune pancreatitis (AIP) and compare with type 1 AIP.Methods:Clinical data of the patients diagnosed with type 2 AIP by the International Consensus on diagnostic criteria of AIP at Peking Union Medical College Hospital from January 2001 to December 2022 were retrospectively analyzed, and type 1 AIP patients diagnosed in Peking Union Medical College Hospital from January 1985 to December 2016 were collected as controls. The clinical symptoms, treatments and follow-ups were analyzed.Results:A total of 25 patients with type 2 AIP were included, of which 16 cases (64.0%) were pathologically confirmed cases (13 cases by endoscopic ultrasound puncture, 2 cases by surgery, and 1 case by interventional puncture), and 9 cases (36.0%) were suspected. The average age of onset was 40 years old. Most patients ( n=23, 92.0%) had abdominal pain along with emaciation to a various degree. Among them, 3 cases primarily presented as acute pancreatitis. Two cases were diagnosed after surgery for pancreatic masses. Eighteen cases were complicated with inflammatory bowel disease, including 16 cases with ulcerative colitis, one case with Crohn's disease, and one case with indeterminate colitis. All patients had typical imaging manifestations, including 13 cases (52.0%) with diffuse pancreatic enlargement, 12 cases (48.0%) with focal or multifocal pancreatic lesions, and 5 cases (20.0%) with simultaneous focal pancreatic masses and diffuse enlargement. All patients had normal serum IgG4 levels, anti-neutropil cytoplasmic antibodies (ANCA) positivity rate was 35.3% (6/17), and anti-nuclear antibody (ANA) positivity rate was 29.2% (7/24). Two surgical patients recovered well after surgery, and the other patients all achieved clinical and imaging relief after hormone therapy, and no recurrence was seen during follow-up. Compared with type 1 AIP, type 2 AIP had younger onset age, main manifestation as abdominal pain without jaundice, rare involvement with extra-pancreatic organs, the lesions mainly located in the intestine and normal IgG4 level with statistically significant differences. The recurrence rate of type 2 AIP was lower than that of type 1 AIP (0 vs 16%). Conclusions:Type 2 AIP has different clinical characteristics from type 1 AIP. Due to the lack of specific serum markers, the diagnosis is more difficult. It responds well to glucocorticoids and has a low recurrence rate.

Background::Erosive esophagitis (EE) is a gastroesophageal reflux disease characterized by mucosal breaks in the esophagus. Proton pump inhibitors are widely used as maintenance therapy for EE, but many patients still relapse. In this trial, we evaluated the noninferiority of vonoprazan vs. lansoprazole as maintenance therapy in patients with healed EE. Methods::We performed a double-blind, double-dummy, multicenter, phase 3 clinical trial among non-Japanese Asian adults with endoscopically confirmed healed EE from April 2015 to February 2019. Patients from China, South Korea, and Malaysia were randomized to vonoprazan 10 mg or 20 mg once daily or lansoprazole 15 mg once daily for 24 weeks. The primary endpoint was endoscopically confirmed EE recurrence rate over 24 weeks with a noninferiority margin of 10% using a two-sided 95% confidence interval (CI). Treatment-emergent adverse events (TEAEs) were recorded.Results::Among 703 patients, EE recurrence was observed in 24/181 (13.3%) and 21/171 (12.3%) patients receiving vonoprazan 10 mg or 20 mg, respectively, and 47/184 (25.5%) patients receiving lansoprazole (differences: -12.3% [95% CI, -20.3% to-4.3%] and -13.3% [95% CI, -21.3% to -5.3%], respectively), meeting the primary endpoint of noninferiority to lansoprazole in preventing EE recurrence at 24 weeks. Evidence of superiority (upper bound of 95% CI <0%) was also observed. At 12 weeks, endoscopically confirmed EE recurrence was observed in 5/18, 2/20, and 7/20 of patients receiving vonoprazan 10 mg, vonoprazan 20 mg, and lansoprazole, respectively. TEAEs were experienced by 66.8% (157/235), 69.0% (156/226), and 65.3% (158/242) of patients receiving vonoprazan 10 mg, vonoprazan 20 mg, and lansoprazole, respectively. The most common TEAE was upper respiratory tract infection in 12.8% (30/235) and 12.8% (29/226) patients in vonoprazan 10 mg and 20 mg groups, respectively and 8.7% (21/242) patients in lansoprazole group.Conclusion::Vonoprazan maintenance therapy was well-tolerated and noninferior to lansoprazole for preventing EE recurrence in Asian patients with healed EE.Trial Registration::https://clinicaltrials.gov; NCT02388737.

Ulcerative colitis(UC)is a chronic and prolonged condition spanning multiple disciplines.Standardized diagnostics and treatment are paramount for enhancing the therapeutic efficacy and improving the prognosis of UC.In the last a couple of years,substantial progress has been achieved in both basic and clinical research on UC in our country.The integration of novel diagnostic and therapeutic paradigms,new treatment modalities,have necessitated the update of consensus on UC management,offering imperative,evidence-based guidelines for health providers.This guideline,collaboratively developed by the Inflammatory Bowel Disease Group of Chinese Society of Gastroenterology,Chinese Medical Association,and the Inflammatory Bowel Disease Quality Control Center of China,incorporates the latest international consensus,domestic research findings,and practical considerations,as an update based on the 2018 Chinese consensus on diagnosis and treatment in inflammatory bowel disease.The formulation of this guideline aims to reflect the latest concepts and research findings in the clinical diagnosis and treatment of UC,providing standardized guidance for the clinical management of UC.

Benign prostatic hyperplasia(BPH)is one of the major chronic complications of type 2 diabetes mellitus(T2DM),and sex steroid hormones are common risk factors for the occurrence of T2DM and BPH.The profiles of sex steroid hormones are simultaneously quantified by LC-MS/MS in the clinical serum of patients,including simple BPH patients,newly diagnosed T2DM patients,T2DM complicated with BPH patients and matched healthy individuals.The G protein-coupled estrogen receptor(GPER)inhibitor G15,GPER knockdown lentivirus,the YAP1 inhibitor verteporfin,YAP1 knockdown/overexpression lentivirus,targeted metabolomics analysis,and Co-IP assays are used to investigate the molecular mechanisms of the disrupted sex steroid hormones homeostasis in the pathological process of T2DM complicated with BPH.The homeostasis of sex steroid hormone is disrupted in the serum of patients,accompanying with the proliferated prostatic epithelial cells(PECs).The sex steroid hormone metabolic profiles of T2DM patients complicated with BPH have the greatest degrees of separation from those of healthy individuals.Elevated 17β-estradiol(E2)is the key contributor to the disrupted sex steroid hormone homeostasis,and is significantly positively related to the clinical characteristics of T2DM patients complicated with BPH.Activating GPER by E2 via Hippo-YAP1 signaling exacerbates high glucose(HG)-induced PECs prolifer-ation through the formation of the YAP1-TEAD4 heterodimer.Knockdown or inhibition of GPER-mediated Hippo-YAP1 signaling suppresses PECs proliferation in HG and E2 co-treated BPH-1 cells.The anti-proliferative effects of verteporfin,an inhibitor of YAP1,are blocked by YAP1 overexpression in HG and E2 co-treated BPH-1 cells.Inactivating E2/GPER/Hippo/YAP1 signaling may be effective at delaying the progression of T2DM complicated with BPH by inhibiting PECs proliferation.

Objective:To explore the differences in dynamic spontaneous brain activity in individuals with subjective cognitive decline (SCD) and its correlation with spatial navigation ability in SCD subjects.Methods:A total of 72 SCD subjects(SCD group) and 67 normal controls (NC group) matched for age, gender and education level were recruited from September 2020 to February 2023 at the Affiliated Drum Tower Hospital, Medical School of Nanjing University. All participants underwent resting-state functional magnetic resonance imaging (rs-fMRI) examinations, spatial navigation tests and cognitive function assessments. The rs-fMRI time series were segmented using a sliding time window method, and statistical analyses were carried out using SPSS 26.0 software to compare the differences in the dynamic amplitude of low frequency fluctuation (dALFF) between the two groups. Correlation analysis was conducted between dALFF values in different brain regions and scale scores and spatial navigation tests.Results:Compared with the NC group, the dALFF variability in the right precuneus(0.119±0.021, 0.130±0.031) and left cuneus(0.143±0.034, 0.156±0.032) in SCD group decreased ( t=-3.41, -3.12, P<0.05, FDR corrected), and the dALFF variability in the right middle occipital gyrus(0.146±0.023, 0.137±0.020) and right angular gyrus(0.148±0.025, 0.139±0.026) increased ( t=4.51, 3.36, both P<0.05, FDR corrected). The temporal variability of dALFF in the right precuneus in SCD group was negatively correlated with egocentric spatial navigation ( r=-0.341, P=0.025), delayed allocentric spatial navigation ( r=-0.286, P=0.035) and memory function ( r=-0.332, P=0.009). The temporal variability of dALFF in the left middle occipital gyrus was positively correlated with language function ( r=0.339, P=0.015) and visuospatial function ( r=0.343, P=0.008) in SCD group. Conclusions:The temporal variability of dALFF in the right precuneus and the left middle occipital gyrus may be the neurobiological basis of cognitive decline and spatial navigation impairment in SCD subjects, and it can be used as a potential imaging marker for early identification of SCD patients.

Background/Aims: Crohn’s disease (CD) has a progressive nature and commonly perianal involvement. The aim of this study is to assess the prevalence, surgical treatment, and outcome of perianal fistulizing CD with associated risk factors in a large Chinese cohort. Methods: Hospitalized patients diagnosed with CD in our center were consecutively enrolled between January 2000 and December 2018. Transition of disease behavior was classified according to the presence or absence of penetrating behavior (B3 in the Montreal classification) at diagnosis and at a median follow-up of 102 months. Results: A total of 504 patients were included, of whom 207 (41.1%) were classified as B3 and 348 (69.0%) as L2/3 at follow-up. Transition of behavior to B3 was observed in 86 patients (17.1%). The incidence of perianal fistulizing lesions was 10.9% at 10 years with a final prevalence of 27.0% (n = 136) at the end of follow-up. Multivariate Cox regression identified independent risks of perianal fistulizing lesions for persistent B3 (hazard ratio, 4.72; 95% confidence interval, 1.91–11.66) and behavior transition of progressed to B3 (hazard ratio, 9.90; 95% confidence interval, 4.60–21.33). Perianal surgical treatments were performed in 104 patients (20.6%). Thirty-six cases (7.1%) were refractory, and it is independently associated with behavior of persistent B3 (P= 0.011). Conclusions Perianal fistulizing lesions occurred frequently in Chinese CD patients. Its incidence and refractory outcome were closely associated with the penetrating CD behavior. An additional risk of perianal fistulizing lesions was indicated for CD patients with behavior of progressing to B3, suggesting further attention.

Humans ; Fecal Microbiota Transplantation ; Colitis, Ulcerative/therapy* ; Donor Selection ; Feces ; Gastrointestinal Microbiome ; Treatment Outcome

BackgroundDue to the COVID-19 pandemic， both teenagers' studies and personal life are critically affected， which has resulted in a variety of mental health problems. In this regard， scholars at home and abroad have carried out a large number of research concerning adolescent mental health， of which there still exists a lack of systematic combing and review. ObjectiveTo understand the status and development trend of research on adolescent mental health during the COVID-19 pandemic at home and abroad， and to grasp the current research hotspots and trends in this field， so as to provide references for relevant research and practice in the post-epidemic era. MethodsOn October 30， 2022， we searched through China Knowledge Network Infrastructure （CNKI） and Web of Science database， and the publishing time of articles to be retrieved was limited between December 1， 2019 and October 30， 2022. Excel and CiteSpace were used to perform visual analysis on these articles in terms of number， author， institution， country and keywords of the articles. ResultsA total of 7 608 articles were included. At home and abroad， the number of papers related to adolescent mental health generally increased at first and then decreased under the pandemic situation. Compared with foreign countries， the connection and cooperation among domestic scholars and institutions was not close enough. The top three countries in the number of English literature published were the United States， Britain and China， and those in intermediary center were Tunis， Cameroon and Anguilla. The parent-child relationship and mental health of teenagers during were much concerned by scholars both at home and abroad. With the passage of time， researchers at home and abroad had shifted their focus from only negative factors to positive factors. ConclusionChinese scholars or institutions need to strengthen more domestic and international exchanges and cooperation. Scholars from different countries can carry out cross-cultural study on research topics of common concern， and continue to explore the positive psychological changes of teenagers in the post-epidemic era.［Funded by National Social Science Foundation 2020 Education Youth Project of 13th Five-Year Plan （number， CHA200259）］

Coronavirus disease 2019 (COVID-19) has become a worldwide pandemic. During the rapid spread time, it is a great challenge for patients with inflammatory bowel disease (IBD) who use immunosuppressive drugs from vaccination and drug application. This article is intended to supplement and revise the recommendations of the Inflammatory Bowel Disease Group of the Chinese Society of Gastroenterology in 2020 on the "Management of patients with inflammatory bowel disease during epidemic of novel coronavirus pneumonia", mainly including the treatment and vaccination of IBD patients complicated with COVID-19. It is expected to guide clinicians in drug use, vaccination of IBD patients at an appropriate time, also help patients getting through the epidemic period of COVID-19.

Age-dependent loss of skeletal muscle mass and function is a feature of sarcopenia, and increases the risk of many aging-related metabolic diseases. Here, we report phenotypic and single-nucleus transcriptomic analyses of non-human primate skeletal muscle aging. A higher transcriptional fluctuation was observed in myonuclei relative to other interstitial cell types, indicating a higher susceptibility of skeletal muscle fiber to aging. We found a downregulation of FOXO3 in aged primate skeletal muscle, and identified FOXO3 as a hub transcription factor maintaining skeletal muscle homeostasis. Through the establishment of a complementary experimental pipeline based on a human pluripotent stem cell-derived myotube model, we revealed that silence of FOXO3 accelerates human myotube senescence, whereas genetic activation of endogenous FOXO3 alleviates human myotube aging. Altogether, based on a combination of monkey skeletal muscle and human myotube aging research models, we unraveled the pivotal role of the FOXO3 in safeguarding primate skeletal muscle from aging, providing a comprehensive resource for the development of clinical diagnosis and targeted therapeutic interventions against human skeletal muscle aging and the onset of sarcopenia along with aging-related disorders.
Animals ; Humans ; Sarcopenia/metabolism* ; Forkhead Box Protein O3/metabolism* ; Muscle, Skeletal/metabolism* ; Aging/metabolism* ; Primates/metabolism*