Owing to the increasing incidence and prevalence of inflammatory bowel disease (IBD) worldwide, effective and safe treatments for IBD are urgently needed. Hydrogen sulfide (H₂S) is an endogenous gasotransmitter and plays an important role in inflammation. To date, H₂S-releasing agents are viewed as potential anti-inflammatory drugs. The slow-releasing H₂S donor 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione (ADT-OH), known as a potent therapeutic with chemopreventive and cytoprotective properties, has received attention recently. Here, we reported its anti-inflammatory effects on dextran sodium sulfate (DSS)-induced acute (7 days) and chronic (30 days) colitis. We found that ADT-OH effectively reduced the DSS-colitis clinical score and reversed the inflammation-induced shortening of colon length. Moreover, ADT-OH reduced intestinal inflammation by suppressing the nuclear factor kappa-B pathway. In vivo and in vitro results showed that ADT-OH decreased intestinal permeability by increasing the expression of zonula occludens-1 and occludin and blocking increases in myosin II regulatory light chain phosphorylation and epithelial myosin light chain kinase protein expression levels. In addition, ADT-OH restored intestinal microbiota dysbiosis characterized by the significantly increased abundance of Muribaculaceae and Alistipes and markedly decreased abundance of Helicobacter, Mucispirillum, Parasutterella, and Desulfovibrio. Transplanting ADT-OH-modulated microbiota can alleviate DSS-induced colitis and negatively regulate the expression of local and systemic proinflammatory cytokines. Collectively, ADT-OH is safe without any short-term (5 days) or long-term (30 days) toxicological adverse effects and can be used as an alternative therapeutic agent for IBD treatment.
Humans ; Mice ; Animals ; Gastrointestinal Microbiome ; Intestinal Barrier Function ; Mice, Inbred C57BL ; Colitis/metabolism* ; Inflammatory Bowel Diseases/drug therapy* ; Inflammation ; Anti-Inflammatory Agents/pharmacology* ; Disease Models, Animal

Objective To compare clinical and pathological features between autoimmune hepatitis (AIH) patients with positive and negative autoantibodies, and to summarize the experience in diagnosis. Methods A retrospective analysis was performed for the patients who attended Beijing Ditan Hospital from January 2010 to August 2021 and were diagnosed with AIH by liver histopathology, and according to the presence or absence of autoantibodies, they were divided into positive autoantibody group and negative autoantibody group. The two groups were compared in terms of biochemical parameters, immunological features, histopathological features, disease stage, and clinical symptoms and signs. The t -test or the Mann-Whitney U test was used for comparison of continuous data between groups, and the chi-square test or the Fisher's exact test was used for comparison of categorical data. Results A total of 110 patients were enrolled, among whom 78 (71%) had positive autoantibodies and 32 (29%) had negative autoantibodies. Anti-nuclear antibody (ANA), anti-mitochondrial antibody (AMA), and anti-smooth muscle antibody (ASMA) were the main autoantibodies detected, and of all 110 patients, 74 (67.27%) had positive ANA, 1 (0.91%) had positive AMA, 5 (4.55%) had positive ASMA, and 14 (12.73%) had positive anti-Ro-52 antibody. As for clinical and immunological features, compared with the positive autoantibody group, the negative autoantibody group had significantly lower incidence rates of jaundice of the skin and sclera (21.90% vs 50.00%, χ 2 =7.377, P =0.007) and poor appetite (18.80% vs 41.00%, χ 2 =4.979, P =0.026) and significantly lower median levels of direct bilirubin [7.30(4.05~12.10) μmol/L vs 16.80(6.48~69.75) μmol/L, Z =-2.304, P =0.021], IgG [16.40(13.15~18.05) g/L vs 20.30(16.00~27.15) g/L, Z =-2.715, P =0.007], and GLo [30.60(26.00~34.90) g/L vs 37.30(30.50~42.50) g/L, Z =-3.356, P =0.001]. In terms of liver histopathology, compared with the negative autoantibody group, the positive autoantibody group had a significantly higher proportion of patients with lymphocyte infiltration (91.03% vs 68.75%, χ 2 =6.997, P =0.008) and plasma cell infiltration (82.05% vs 50.00%, χ 2 =11.572, P =0.001); compared with the ANA-negative patients, the ANA-positive patients had significantly higher inflammation grade (G1-G4) (9.46%/16.22%/44.59%/29.73% vs 5.56%/27.78%/63.89%/2.78%, Z =-2.179, P =0.029) and fibrosis degree (S1-S4) (37.84%/25.68%/32.43%/4.05% vs 13.89%/41.67%/30.56%/13.89%, Z =-0.082, P =0.037). Conclusion Compared with AIH patients with positive autoantibodies, AIH patients with negative autoantibodies are mostly in the early stage of the disease and tend to have a low level of IgG, with a relatively high rate of missed diagnosis in clinical practice. Early and active liver biopsy is of particular importance.

PURPOSE: . The present study compared the accuracy between digital and conventional implant impressions. MATERIALS AND METHODS: . The experimental models were divided into six groups depending on the implant location and the scanning span. Digital impressions were captured using the intraoral optical scanner TRIOS (3Shape, Copenhagen, Denmark). Conventional impressions were taken with the monophase impression material based on addition-cured silicones, Honigum-Mono (DMG, Hamburg, Germany). A highprecision laboratory scanner D900 (3Shape, Copenhagen, Denmark) was used to obtain digital data of resin models and stone casts. Surface tessellation language (STL) datasets from scanner were imported into the analysis software Geomagic Qualify 14 (3D Systems, Rock Hill, SC, USA), and scan body deviations were determined through two-dimensional and three-dimensional analyses. Each scan body was measured five times. The Sidak t test was used to analyze the experimental data. RESULTS: . Implant position and scanning distance affected the impression accuracy. For a unilateral arch implant and the mandible models with two implants, no significant difference was observed in the accuracy between the digital and conventional implant impressions on scan bodies; however, the corresponding differences for trans-arch implants and mandible with six implants were extremely significant (P <.001). CONCLUSION . For short-span scanning, the accuracy of digital and conventional implant impressions did not differ significantly. For long-span scanning, the precision of digital impressions was significantly inferior to that of the traditional impressions.

Objective:To evaluate the etiological diagnosis value of soft bronchoscopy in children with laryngeal stridor.Methods:The clinical data of 402 children with laryngeal stridor wheezing were retrospectively analyzed, which examined by soft bronchoscopy in Anhui Provincial Children′s Hospital from January 2016 to January 2019.Results:A total of 402 cases of laryngeal stridor were diagnosed by soft bronchoscopy, 317(78.8%) cases were diagnosed as congenital airway dysplasia, including 200(49.7%)cases of congenital laryngeal chondromalacia, which including 132 cases of single laryngeal chondromalacia and 68 cases with other respiratory tract dysplasia, and 117(29.1%) cases of respiratory dysplasia other than laryngeal chondromalacia; 46(11.5%) cases of laryngitis; 28(7.0%) cases of airway acquired stenosis and 11 (2.7%)cases of foreign body.Among 402 cases of children with laryngeal stridor who were diagnosed according to clinical feature, combined with chest X-ray, chest CT, CT angiography and color Doppler echocardiography as well as other imaging data, 335(83.3%) cases were congenital laryngeal chondromalacia, 16(4.0%) cases were other respiratory tract dysplasia (including six cases of subglottic and tracheal stenosis, five cases of laryngeal space occupying lesions, four cases of tracheobronchial malformation, and one case of subglottic hemangioma), 35 (8.7%)cases of laryngitis, acquired airway stenosis in 15 cases including 13 cases of congenital heart disease, one case of pulmonary artery sling, one case of mediastinal cyst, and one case of foreign body.Congenital laryngeal chondromalacia, other causes of respiratory dysplasia and foreign body detected by flexible bronchoscopy were not consistent with clinical examination( P<0.05). Conclusion:Congenital laryngeal chondromalacia is the main cause of laryngeal stridor, but it is often associated with other airway dysplasia.Soft bronchoscopy can provides etiological diagnosis for children with laryngeal stridor wheezing, especially in the diagnosis of respiratory tract dysplasia and airway foreign body.

Objective:To investigate the distribution characteristics and related factors of HBsAb in infants born to women with chronic hepatitis B virus (HBV) infection.Methods:A total of 605 infants born to women with chronic HBV infection who met the requirements for inclusion were selected as the subjects. Information about the mother′s previous HBV infection, biochemical indicators during pregnancy, pregnancy complications, information about delivery, and hepatitis B test result after birth were collected. HBsAg and HBsAb at the age of 1 year were determined, and HBsAg and HBsAb at the age of 7 months were retrospectively collected. The factors influencing HBsAb in infants were analyzed by ordered logistic regression.Results:In 605 infants, the infection rate was about 1%. Among them, 6 infants were positive for HBsAg and HBV DNA at 7 months and 1 year of age. Uninfected infants were divided into groups according to HBsAb titers. The result showed that there were significant differences in prothrombin activity (PTA) ( χ2=11.17, P=0.01), positive rate of HBeAg ( χ2=7.87, P=0.049) and HBsAg positive rate at birth ( χ2=10.52, P=0.02) among different groups. Multivariate ordered Logistic regression analysis showed that HBsAg negative at birth was an independent protective factor for HBsAb at 7 months of age ( OR=1.564, 95% CI 1.092-2.239, P=0.015). Logistic regression analysis of HBsAb at 1 year of age showed maternal gestational diabetes mellitus ( OR=1.578, 95% CI 1.126-2.210, P=0.008), infant enhanced immunization ( OR=81.207, 95% CI 31.202-211.352, P < 0.001) and antibody level at 7 months of age ( OR=42.123, 95% CI 22.824-77.739, P < 0.001) were independently associated with HBsAb at 1 year of age. Conclusions:HBsAg negative in venous blood at birth was an independent protective factor for HBsAb at 7 months of age, and enhanced immunization was an independent protective factor for HBsAb at 1 year of age.

Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disease affecting the upper and lower motor neurons. It is characterized by progressive muscle weakness, atrophy and ultimate death due to dysphagia and dyspnea. There are many causes of ALS, among which the genetic factors show great relevance. Imbalance of protein homeostasis in neurons, prion-like proliferation and propagation of abnormal proteins, mitochondrial dysfunction, glutamate mediated excitotoxicity, and intraneuronal substance transport disorders are recognized as the pathogenesis.The study on gene mutation related to pathogenesis will bridge the molecular and cellular research of ALS, which can deepen the understanding of the occurrence and development of ALS and the role of gene mutation in ALS, and provide new ideas and enlightenment for the treatment of ALS.
Amyotrophic Lateral Sclerosis/genetics* ; Humans ; Motor Neurons ; Mutation ; Neurodegenerative Diseases ; Proteins

OBJECTIVE: To investigate the differentially expressed proteins in the cerebrospinal fluid (CSF) of patients with amyotrophic lateral sclerosis (ALS) at the proteomics level using tandem mass spectrometry label (TMT) technique and explore the pathogenic mechanism and related pathways of ALS. METHODS: Between November, 2017 and April, 2018, 5 patients with medulla oblongata onset ALS and 5 patients with limb onset ALS were selected from the Departments of Neurology of 928 Hospital of Army Joint Logistics Support Force of PLA and Xiangya Hospital of Central South University, with 5 patients with migraine and low intracranial pressure headache serving as the healthy controls.CSF samples were obtained from all the participants, and the differentially expressed proteins in the CSF were identified using tandem mass spectrometry (TMT) technique with bioinformatics analysis. RESULTS: A total of 1530 proteins were identified and quantified in the CSF samples.The expression of 48 proteins was up-regulated and 6 proteins were down-regulated in medulla oblongata onset ALS patients; 16 proteins were up-regulated and 19 were down-regulated in limb onset ALS patients.GO analysis showed that these proteins, which were distributed both within and outside the cells, were involved in cell physiological process, single organ process and biological regulation and had binding function, catalytic activity, and receptor activity.KEGG pathway analysis showed that the up-regulated proteins in the CSF from patients with medulla oblongata onset ALS participated in 3 pathways involving the lysosomes, metabolism, and measles.The down-regulated proteins in the CSF from patients with limb onset ALS participated in 7 pathways involving the complement and coagulation cascade, infection and herpes simplex infection, and all the pathways contained complement components. CONCLUSIONS The CSF samples of ALS patients with medullary onset and limb onset have differentially expressed proteins.The lysosomal pathway is involved in the occurrence and progression of ALS with medullary onset, and the immune responses are involved in the occurrence and progression of ALS with limb onset.
Amyotrophic Lateral Sclerosis ; Biomarkers ; Cerebrospinal Fluid ; Humans ; Proteome ; Proteomics ; Tandem Mass Spectrometry

To investigate the clinical features, auxiliary examination and characteristics for anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis and its concomitant seizure.
 Methods: A total of 20 patients diagnosed as anti-NMDAR encephalitis were enrolled from January 2016 to September 2018 in Xiangya Hospital. The data including the clinical features, auxiliary examination, characteristics of seizure, treatment and prognosis were collected. The discharged patients were followed up for half a year.
 Results: The initial symptom in patients with anti-NMDAR encephalitis were mainly psychiatric symptom and seizure. Most of the EEG result were diffused slow waves. The mainly type of seizure in patients with anti-NMDAR encephalitis showed generalized tonic-clonic seizure. Patients occurred consciousness during the onset of the disease. MRI showed that patients with temporal lobe were more inclined to occur seizure than patients with anti-NMDAR encephalitis (P<0.05). After standardized treatment, 20 patients showed a significant improvement in modified Rankin Scale (mRS) scores and the seizure was under control within half a year. 
 Conclusion: Patients with temporal lobe affected in MRI should pay attention to the possibility of seizure occurrence. Anti-epileptic drugs and immunotherapy should be used promptly in patient with seizure. After standardized treatment, the prognosis of patients will be mostly good.
Anti-N-Methyl-D-Aspartate Receptor Encephalitis ; Humans ; Immunotherapy ; Magnetic Resonance Imaging ; Receptors, N-Methyl-D-Aspartate ; Seizures

Objective To investigate the risk factors of death in patients with syncope. Methods Clinical data of 516 patients experienced syncope admitted from June 2010 to June 2016 were analyzed retrospectively. Factors including gender, age, history of hypertension, diabetes mellitus, hyperlipidemia, smoking history, drinking history, and etiology of syncope (cardiogenic syncope, neuroreflex syncope, orthostatic hypotension, orthostatic syncope, unexplained syncope, and syncope caused by other special diseases) were analyzed as likely risk factors of death within 30 days after syncope happened. After adding the derived variables (over 22 new factors), analyses were done to investigate independent risk factors of death for patients with syncope. Results This study included 321 male (62.2％) and 195 females (37.8％), with mean age of (62.23±19.69) years. Logistic regression analyses showed that age (OR=1.033, 95％ confidence interval (95％CI):1.008-1.058, P =0.008 8),cardiac syncope (OR=19.704,95％CI:5.894-5.875,P＜0.01) were independent risk factors of death within 30 days after syncope occurred. Multiple-variate analysis with derived variables showed that cardiac syncope (OR=11.487, 95％CI:4.938-26.721,P＜0.01),age and age derived variables (OR=1.000, 95％CI:1.000-1.000,P=0.000 8),age and cardiogenic syncope derivative variables (OR=1.033, 95％CI:1.022-1.044, P＜0.01) were independent risk factors for death within 30 days after syncope. Conclusion Age and cardiogenic syncope were independent risk factors for death within 30 days after syncope occurred. And a derivative factor of age, and interactivity between age and cardiac syncope were independent risk factors of death in patients with syncope.

To explore the role of the mutations G38R and D40G of Annexin A11 (ANXA11) in the onset of amyotrophic lateral sclerosis (ALS).
 Methods: The plasmids expressing ANXA11 wild type protein, ANXA11 G38R protein and ANXA11 D40G protein were constructed, respectively. The recombinant plasmids were then transfected into HEK293 cells respectively followed by cycloheximide (CHX) treatment for 0, 2, 4 and 8 h. The protein expressions of ANXA11 wild type, ANXA11 G38R and ANXA11 D40G mutations were determined by Western blot. Gray analysis by Image J was performed to compare the half-life of each protein. The NSC-34 cell lines constantly expressing ANXA11 wild type protein, ANXA11 G38R protein and ANXA11 D40G protein were established. The cells were treated with NP-40 lysis buffer to examine the protein solubility by Western blot.
 Results: Both ANXA11 G38R protein and ANXA11 D40G protein showed a shorter half-life than ANXA11 wild type protein (P<0.05), while there was no difference between ANXA11 G38R protein and ANXA11 D40G protein (P>0.05). There was no visible insoluble substance in the NP-40 lysates for ANXA11 wild type protein, ANXA11 G38R protein and ANXA11 D40G protein.
 Conclusion: G38R and D40G mutations reduce the stability of ANXA11 protein. G38R and D40G mutations do not alter ANXA11 solubility.
Amyotrophic Lateral Sclerosis ; genetics ; metabolism ; Annexins ; chemistry ; genetics ; metabolism ; HEK293 Cells ; Humans ; Mutation ; Plasmids ; genetics ; Protein Stability ; Solubility ; Transfection