Ulcerative colitis （UC）， which is characterized by a complex and multifactorial etiology， remains one of the challenging disorders in the international field of digestive system diseases. In recent years， rectal administration preparations have made rapid progress in UC therapeutic applications. This study systematically reviews the dosage forms， mechanisms of action， and clinical applications of rectally-administered preparations for the treatment of UC. It is found that suppositories are the most commonly used dosage forms for rectal administration. The newer suppositories have the advantages of high bioavailability and good stability. Enemas can retain the drug in the intestine as much as possible to achieve the effects of diluting intestinal toxins， cleansing the bowel， and reducing inflammation. Gels can achieve a drug-sustained-release effect and effectively improve intestinal mucosal damage. The mechanism of action of this type of preparation is mainly to inhibit inflammatory cell infiltration， regulate intestinal microbial homeostasis， and increase the expression of tight-junction proteins， so as to play anti-inflammatory， regulate the intestinal bacterial flora， repair the intestinal mucosa， and other efficacies. The diversity of rectal administration forms provides a wide range of choices for the clinical treatment of UC， such as Mesalazine suppositories， Lianshao enemas， and temperature- sensitive gels loaded with drugs for UC.

Studies on specific transient receptor potential melastatin 2 (TRPM2) channel inhibitors can deepen our understanding of the pathological mechanism of related diseases, and allow discovery of novel, effective targets and drugs for therapy. The development of TRPM2 channel inhibitors can be broadly classified into four categories with distinct characteristics: reutilization and structural modification of homologous ion channel modulators to produce a diverse array of TRPM2 channel inhibitors with strong inhibitory effects; TRPM2 channel inhibitors based on channel gating mechanism with high specificity; inhibitors identified through high-throughput screening with novel chemical structures; inhibitors developed from natural antioxidants with higher safety. In recent years, the application of computer-aided drug design has significantly accelerated the development of TRPM2 channel inhibitors. Several promising compounds such as ZA18, A1 and D9 have been discovered, and it is expected that more potent and selective TRPM2 channel inhibitor scaffolds will be discovered in the future. This article reviews the advances on the studies of TRPM2 channel inhibitors, aiming to provide insights for further research and clinical application of TRPM2 channel inhibitors.
TRPM Cation Channels/antagonists & inhibitors* ; Humans ; Drug Design

BACKGROUND: The presence of fibrosis is a criterion for subtype classification in the newly updated hypersensitivity pneumonitis (HP) guidelines. The present study aimed to summarize differences in clinical characteristics and prognosis of non-fibrotic hypersensitivity pneumonitis (NFHP) and fibrotic hypersensitivity pneumonitis (FHP) and explore factors associated with the presence of fibrosis. METHODS: In this prospective cohort study, patients diagnosed with HP through a multidisciplinary discussion were enrolled. Collected data included demographic and clinical characteristics, laboratory findings, and radiologic and histopathological features. Logistic regression analyses were performed to explore factors related to the presence of fibrosis. RESULTS: A total of 202 patients with HP were enrolled, including 87 (43.1%) NFHP patients and 115 (56.9%) FHP patients. Patients with FHP were older and more frequently presented with dyspnea, crackles, and digital clubbing than patients with NFHP. Serum levels of carcinoembryonic antigen, carbohydrate antigen 125, carbohydrate antigen 153, gastrin-releasing peptide precursor, squamous cell carcinoma antigen, and antigen cytokeratin 21-1, and count of bronchoalveolar lavage (BAL) eosinophils were higher in the FHP group than in the NFHP group. BAL lymphocytosis was present in both groups, but less pronounced in the FHP group. Multivariable regression analyses revealed that older age, <20% of lymphocyte in BAL, and ≥1.75% of eosinophil in BAL were risk factors for the development of FHP. Twelve patients developed adverse outcomes, with a median survival time of 12.5 months, all of whom had FHP. CONCLUSIONS Older age, <20% of lymphocyte in BAL, and ≥1.75% of eosinophil in BAL were risk factors associated with the development of FHP. Prognosis of patients with NFHP was better than that of patients with FHP. These results may provide insights into the mechanisms of fibrosis in HP.
Humans ; Bronchoalveolar Lavage Fluid ; Prospective Studies ; Alveolitis, Extrinsic Allergic/diagnosis* ; Fibrosis ; Carbohydrates

Objective:In this study, a simple and easy diagnostic index of sarcopenia based on computed tomography (CT) images, linear skeletal muscle index (LSMI), was proposed and its diagnostic efficiency was verified.Methods:From April 2013 to September 2017, patients with cirrhotic gastroesophageal varices were selected from the Department of Gastroenterology, Zhongshan Hospital, Fudan University. The SMI of the third lumbar lower than 50 cm 2/m 2 in male and 39 cm 2/m 2 in female was defined as sarcopenia. The sensitivity, specificity, positive predictive value, negative predictive value, Youden index and receiver operating characteristic (ROC) curve were used to evaluate the diagnostic efficacy of LSMI in patients with cirrhotic gastroesophageal varices. Results:A total of 115 patients with cirrhotic gastroesophageal varices were finally recruited. All participants were randomly divided into modeling group ( n=58) and validation group ( n=57). In the modeling group, the area under the ROC curve of LSMI was 0.913(95% CI:0.84-0.986, P<0.001) in total population, 0.895(95% CI:0.793-0.997, P<0.001) in male and 0.917(95% CI:0.782-1.000, P<0.008) in female. The cut-off value of LSMI was 24.114 cm 2/m 2 in male and 22.54 cm 2/m 2 in female. According to the diagnostic cut-off value of the modeling group, the area under the ROC curve of LSMI was 0.846(95% CI:0.737-0.954, P<0.001) in the validation group. The sensitivity, specificity, positive predictive value, negative predictive value and Youden index were 88.5%, 80.6%, 79.3%, 89.3% and 0.691, respectively. Conclusions:48.7% of patients with cirrhosis of esophageal and gastric varices have sarcopenia. LSMI is a simple and convenient method for diagnosis of sarcopenia in patients with liver cirrhosis.

Objective:To discuss the effects of transjugular intrahepatic portosystemic shunt (TIPS) procedure on hemodynamics in cirrhotic patients.Methods:A total of 23 cirrhotic patients for TIPS insertion were enrolled from January 2018 to October 2018. Serum N-terminal pro-B-type natriuretic peptide (NT-proBNP), transthoracic echocardiography and non-invasive cardiac output measurement based on impedance cardiogram were carried out before and 24h, 1 month, 6 months after TIPS in order to observe cardiac function and hemodynamic changes after TIPS.Results:Significant increases in right atrial area [(17.2±4.0) cm 2 vs. (15.0±3.4) cm 2, P<0.05], right ventricular area [(15.1±3.8) cm 2 vs. (13.7±3.5) cm 2, P<0.05] and left ventricular volume [(97.4±21.5) ml vs. (91.1±22.7) ml, P<0.05] were observed 24 h after TIPS. These changes were accompanied with significant reduction in collapsible index of inferior vena cava [(20.7± 8.1)% vs. (28.6±11.3)%, P<0.01] and elevation in pulmonary arterial systolic pressure [(36.0±8.4) mmHg (1 mmHg=0.133 kPa) vs. (31.8±5.4) mmHg, P<0.01]. There also existed significantly elevated serum NT-proBNP [(551.2±325.1) ng/L vs. (124.2±94.4) ng/L, P<0.01], cardiac output [(5.82±0.96) L/min vs. (5.12±1.28) L/min, P<0.01], cardiac index [(3.47±0.64) L·min -1·m -2 vs. (3.05±0.78) L·min -1·m -2, P<0.01], early diastolic filling rate [(59.0±14.3)% vs. (54.5±11.0)%, P<0.05], and reduced systemic vascular resistance index (SVRi) [(1 798.4±357.3) dyne·s·cm -5·m -2 vs. (2 195.7±508.7) dyne·s·cm -5·m -2, P<0.01] 24 h after TIPS. At the end of 6-month follow-up, all these parameters, but not SVRi, returned towards baseline values. Moreover, peak early to late diastolic tissue velocity ratio at the level of lateral mitral annulus (E′/A′) was significantly higher at the end of 6-month follow-up than that at baseline (1.06±0.32 vs. 0.90±0.45, P<0.05). Neither the right ventricular fractional area changes nor the left ventricular ejection fractions during the follow-up period were different from those at baseline ( P>0.05). Conclusion:Cirrhotic patients who had no cardiovascular pathologies had adequate adaptation and good compensation ability to reach a new hemodynamic homeostasis for the increased volume load after TIPS insertion.

Objective: To predict the efficacy of endoscopic tissue adhesives in the treatment of gastric varices in patients with liver cirrhosis by Nomogram model. Methods: From August 2014 to September 2017, 158 patients with liver cirrhosis caused esophagogastric variceal bleeding and received endoscopic tissue adhesives treatment at Zhongshan Hospital, Fudan University were collected. All patients were followed for 12 months. The primary outcome was rebleeding. The factors of rebleeding after endoscopic treatment of esophagogastric varices were analyzed. Nomogram prognostic model was developed and compared with Child-Pugh grading, computed tomography angiography (CTA) and hepatic venous pressure gradient (HVPG) in prognostic accuracy in rebleeding after endoscopic treatment in liver cirrhosis caused esophagogastric varices. Univariate and multivaricate Cox regression analysis, Kaplan-Meier curve and log-rank test were performed for statistical analysis. Results: During the follow-up, rebleading occurred in 18 cases (11.4%), 37 cases (23.4%) and 49 cases (31.0%) at 2, 6, and 12 months after endoscopic treatment. The results of univariate Cox regression analysis showed the risk factors of rebleeding after endoscopic treatment of gastric varices included gender, alcoholic liver cirrhosis, diabetes mellitus, Child-Pugh grade (Grade A vs. B or C), extraluminal vessels on CTA (presence vs. absence) HVPG (<16 mmHg vs. ≥16 mmHg, 1 mmHg = 0.133 kPa), extensive portal embolism, esophageal varices, type 2 gastric varices, injection points of tissue adhesive (≤3 points vs. > 3 points), injection volume of tissue adhesive (≤ 3 mL vs. > 3 mL) (hazard ratio (HR)=0.575, 2.018, 1.562, 3.433, 2.945, 1.859, 2.743, 0.324, 1.840, 1.477, and 1.716; 95% confidence interval (CI) 0.305 to 1.084, 0.902 to 4.514, 1.753 to 6.724, 1.663 to 5.217, 1.012 to 3.415, 0.852 to 8.830, 0.079 to 1.335, 1.012 to 3.317, 0.839 to 2.602, and 0.935 to 3.152; all P<0.2). The results of multivariate Cox regression analysis indicated that Child-Pugh grade, extraluminal vessels by CTA, and HVPG (HR = 2.095, 95% CI 1.099 to 3.995, P = 0.025) were all independent risk factors of rebleeding after endoscopic treatment of gastric varices (HR=2.665, 2.886, and 2.095; 95% CI 1.339 to 5.300, 1.580 to 5.271, and 1.099 to 3.995; all P<0.05). Kaplan-Meier curves showed that Child-Pugh grade (Grade A vs. B or C), extraluminal vessels on CTA (presence or absent) and HVPG (<16 mmHg vs. ≥16 mmHg) could effectively predict cumulative non-rebleeding rate in one year after endoscopic treatment of gastric varices, and the differences were statistically significant (all P<0.05). Receiver operataring characteristic curve analysis demonstrated that the predictive value of the model combined with Child-Pugh grade, extraluminal vessels on CTA and HVPG was higher than that of Child-Pugh grade and HVPG (AUC=0.746, 0.673 and 0.585; 95% CI 0.662 to 0.829, 0.583 to 0.762, and 0.486 to 0.683; P<0.01, P=0.001 and P=0.089, respectively). Patients were divided into low, medium, and high-risk groups according to the 25th and 75th percentiles of the Nomogram score. The results showed that Nomogram model could effectively distinguish high-risk groups of rebleeding after endoscopic treatment of gastric varices, and the difference was statistically significant (P <0.01). Conclusions Extraluminal vessels on CTA, HVPG and Child-Pugh grade are independent prognostic evaluation indexes of rebleeding after endoscopic treatment of gastric varices. The predictive accuracy of Nomogram model based on these three prognostic factors may be better than Child-Pugh grade and HVPG.

Objective To investigate the influence of gravity levels on lower limb motions during human walking. Methods A suspended microgravity simulation system was designed for the experiment. Kinetic parameters from lower limb joints of twelve volunteers during walking were measured by the motion capture system and 3D force plate under simulated Mars gravity (1/3 G), lunar gravity (1/6 G) and earth gravity (1 G). Results Under simulated Mars and lunar gravity, the ranges of motion (ROMs) of hip and knee joints in sagittal plane significantly decreased (P＜0.01) while the ROMs of ankle joints obviously increased (P＜0.05). The ROMs of hip, knee and ankle joints in sagittal plane under earth gravity were 45.2°, 67.7°, 32.5°, respectively, while the ROMs of hip, knee and ankle joints under lunar gravity were 25.1°, 50.8°, 42.4°, respectively. In addition, the force and torque of lower limb joints in sagittal plane under lower gravity also decreased significantly (P＜0.01). Conclusions The results obtained by this study were almost the same as the research findings obtained by using treadmill. Astronauts can use the treadmill and microgravity simulation system for walking exercises under lunar gravity on the earth.

BACKGROUND/AIMS: Gastroesophageal variceal hemorrhage is a common complication of portal hypertension. Endoscopic therapy is currently recommended for preventing gastroesophageal variceal rebleed. However, the rate of variceal rebleed and its associated mortality remain concerning. This study is aimed at differentiating patient response to endoscopic therapy based on endoscopic ultrasound (EUS) findings. METHODS: One-hundred seventy patients previously treated with repeat endoscopic therapy for secondary prophylaxis were enrolled and classified into two groups based on treatment response. Prior to consolidation therapy, all patients received an EUS examination to observe for extraluminal phenomena. All available follow-up endoscopic examination records were retrieved to validate study results. RESULTS: Of the 170 subjects, 106 were poor responders, while 64 were good responders. The presence of para-gastric, gastric perforating, and esophageal perforating veins was associated with poor patient response (p < 0.001). The odds ratio for para-gastric veins was 5.374. Follow-up endoscopic findings for poor responders with incomplete variceal obliteration was closely correlated with the presence of para-gastric veins (p=0.002). CONCLUSIONS: The presence of para-gastric veins is a characteristic of poor response to endoscopic therapy for treating gastroesophageal varices. Early identification of this subgroup necessitates a change in course of treatment to improve overall patient outcome.
Cyanoacrylates ; Endosonography ; Esophageal and Gastric Varices ; Follow-Up Studies ; Hemorrhage ; Humans ; Hypertension, Portal ; Mortality ; Odds Ratio ; Risk Assessment ; Ultrasonography* ; Varicose Veins* ; Veins

Objective:To analyze the trend relevant factors leading to death and their patterns over a 10-year period in inpatients with connective tissue diseases (CTDs).Methods:All clinical data about death in inpatients with CTDs were retrospectively reviewed between 2005 and 2014 at the Department of Rheumatology and Immunology in Xiangya Hospital of Central South University.Results:In the 10-year time period,the overall hospital mortality was 15.689‰.The disease itself accounted for 44.71% of the total causes of death,infection accounted for 42.94%,and comorbidities accounted for 12.35%.The constituent ratio of deaths and the average hospital mortality caused by the disease itself declined gradually year by year,and the constituent ratio of deaths caused by infection and comorbidities increased gradually year by year (P<0.05).In 2013-2014,infection was the leading cause of death,which accounted for 51.06%.The survival time for CTDs inpatients with interstitial lung disease (ILD) was shorter than that of CTDs inpatients without ILD,and even the risk of death was 1.722 times of the latter.The proportion of deaths caused by the disease itself was the highest in systemic sclerosis and systemic lupus erythematosus,that by infection was the highest in idiopathic inflammatory myopathy (IIM),and that by comorbidities was the highest in rheumatoid arthritis.Conclusion:The proportion of deaths and the hospital mortality in CTDs inpatients caused by the disease itself show a declining trend,while the proportion of deaths caused by infection and comorbidities increase.CTDs patients with ILD have shorter survival time and an increase in risk of death.