Background:Recurrence after stone removal is common in patients with choledocholithiasis.Recent studies have indicated that dysbiosis in gut microbiota plays an important role in the formation of cholesterol gallstones.Aims:To explore the effect of probiotics supplementation on serum lipopolysaccharide(LPS)and the indicators of bile acid metabolism in patients with a high risk of cholesterol gallstone formation.Methods:Sixty choledocholithiasis patients undergoing ERCP lithotomy were recruited at the First Affiliated Hospital of Shihezi University from June 2021 to June 2023.Bile and stool samples were collected for bacterial culture.Then the patients were randomly allocated into two groups:patients in control group received conventional supportive therapy after calculus removal,while those in probiotics intervention group were given oral bifid triple viable enteric capsule 420 mg,twice a day for 6 months based on conventional therapy.Changes in serum levels of LPS,the cell wall component of Gram-negative bacteria,fibroblast growth factor 19(FGF19),the key molecule in bile acid metabolism,and cholesterol 7α-hydroxylase(CYP7A1),the rate-limiting enzyme of bile acid synthesis,were determined and compared between the two groups.Results:Escherichia coli and Klebsiella pneumoniae were the main pathogens in bile and stool of patients with choledocholithiasis.Six months after ERCP lithotomy,the serum levels of LPS and FGF19 were decreased,and the serum level of CYP7A1 was increased in both groups(all P<0.05),especially in probiotics intervention group(all P<0.05).Conclusions:Oral probiotics supplementation can reduce the serum LPS level and modulate the canonical pathway of enterohepatic circulation of bile acids--farnesoid X receptor(FXR)-FGF19 pathway in high-risk patients of cholesterol gallstone formation.These alterations reduce the cholesterol supersaturation in bile and inhibit the probability of cholesterol gallstone formation.

Hypertension is one of the main factors leading to cardiovascular death.The number of cardiovascular patients were about 330 million in China,and 245 million among them were suffering from hypertensive in 2021.The rates of treatment and control of hypertension were less than 45.8%from 1991 to 2018.Therefore,it is of great clinical significance and social value to carry out hypertension related research.Animal models of hypertension are important tools to explore the pathogenesis of hypertension and evaluate the development of antihypertensive agents.At present,there are many ways to establish animal models of hypertension,by consulting and sorting out the relevant papers of animal models of hypertension at home and abroad,the author summarized and discussed the replication methods,principles,features and applications of commonly used animal models from four aspects,such as genetics,surgical induction,environmental induction and pharmaceuticals induction,in order to provide a reference for the selection and establishment of more scientific animal models of hypertension and lay the foundation for the combined treatment of hypertension with Chinese and Western medicine.

Objective:To construct an automatic recognition system for PD patients with freezing of gait (FOG) based on mobile phone videos by recording the gait videos of PD patients with FOG.Methods:Forty-nine PD patients with FOG, admitted to our hospital from December 2020 to May 2021, were chosen in our study. Their clinical data were collected. The processes of these patients accepted "3-meter-round trip" and "3-meter-round trip through narrow (0.6 m)" were recorded and 87 valid gait videos were extracted. Position signals of key points in the video were extracted, and featured data were extracted after signal preprocessing. From the featured data, action recognition model, straight FOG recognition model and turn FOG recognition model were established respectively, and finally end-to-end FOG recognition model was formed. Leave-one-subject-out (LOSO) method was used to evaluate the performance of the above models.Results:A total of 22 066 non-FOG window samples and 3815 FOG window samples were obtained from 87 valid videos, which constituted the training sample pool of this study. LOSO method showed that the motion recognition model enjoyed 83.27% sensitivity, 91.38% specificity, and 89.28% accuracy; the straight FOG recognition model enjoyed 57.69% sensitivity and 88.12% specificity; the turn FOG recognition model enjoyed 61.54% sensitivity and specificity 98.72%; and the end-to-end FOG recognition model enjoyed 85.71% sensitivity and 75.73% specificity.Conclusion:The automatic recognition system for PD patients with FOG based on mobile phone videos has relatively high sensitivity and specificity, which can realize remote assessment and is convenient for screening and follow-up of PD patients with FOG.

Chitinase has a wide industrial application prospect. For example, it can degrade shrimp shells, crab shells and other crustacean waste into high value-added chitooligosaccharides. However, the low catalytic efficiency of chitinase greatly limits the production of chitooligosaccharides. In previous study, the we expressed a chitinase Chisb with high catalytic efficiency and studied its enzymatic properties. In order to further improve the catalytic efficiency of Chisb, with R13NprB-C-SP-H as the parent, here error-prone PCR was used to construct random mutant library to conduct directed evolution of chitinase Chisb. Two mutants C43D and E336R were obtained with 96-well plate primary screening and shaker-screening, and their enzymatic properties were also studied. The optimum temperature of C43D and E336R was 55 °C, and the optimum pH of C43D was 5.0, while that of E336R was 9.0. The catalytic efficiency of C43D and E336R was 1.35 times and 1.57 times higher than that of control. The chitooligosaccharide concentration of E336R and C43D was 2.53 g/L and 2.06 g/L, improved by 2.84 times and 2.31 times compared with the control (0.89 g/L), respectively. In addition, the substrate conversion rate of mutants E336R and C43D was 84.3% and 68.7%, improved by 54.6% and 39% compared with the control (29.7%), respectively. In summary, the study indicates that random mutation introduced by error-prone PCR can effectively improve the catalytic efficiency of chitinase Chisb. The positive mutants with higher catalytic efficiency obtained in the above study and their enzymatic property analysis have important research significance and application value for the biosynthesis of chitooligosaccharides.
Biocatalysis ; Chitin ; analogs & derivatives ; Chitinases ; Hydrogen-Ion Concentration ; Polymerase Chain Reaction

BACKGROUND: Rheumatoid arthritis (RA), a chronic systemic autoimmune disease, is characterized by synovitis and progressive damage to the bone and cartilage of the joints, leading to disability and reduced quality of life. This study was a randomized clinical trial comparing the outcomes between withdrawal and dose reduction of tofacitinib in patients with RA who achieved sustained disease control. METHODS: The study was designed as a multicenter, open-label, randomized controlled trial. Eligible patients who were taking tofacitinib (5 mg twice daily) and had achieved sustained RA remission or low disease activity (disease activity score in 28 joints [DAS28] ≤3.2) for at least 3 months were enrolled at six centers in Shanghai, China. Patients were randomly assigned (1:1:1) to one of three treatment groups: continuation of tofacitinib (5 mg twice daily); reduction in tofacitinib dose (5 mg daily); and withdrawal of tofacitinib. Efficacy and safety were assessed up to 6 months. RESULTS: Overall, 122 eligible patients were enrolled, with 41 in the continuation group, 42 in the dose-reduction group, and 39 in the withdrawal group. After 6 months, the percentage of patients with a DAS28-erythrocyte sedimentation rate (ESR) of <3.2 was significantly lower in the withdrawal group than that in the reduction and continuation groups (20.5%, 64.3%, and 95.1%, respectively; P  < 0.0001 for both comparisons). The average flare-free time was 5.8 months for the continuation group, 4.7 months for the dose reduction group, and 2.4 months for the withdrawal group. CONCLUSION: Withdrawal of tofacitinib in patients with RA with stable disease control resulted in a rapid and significant loss of efficacy, while standard or reduced doses of tofacitinib maintained a favorable state. TRIAL REGISTRATION Chictr.org, ChiCTR2000039799.
Humans ; Quality of Life ; China ; Arthritis, Rheumatoid/drug therapy* ; Piperidines/therapeutic use* ; Treatment Outcome ; Antirheumatic Agents/therapeutic use* ; Pyrroles/therapeutic use*