Background::An evidence gap still exists regarding the efficacy and safety of tegoprazan in patients with erosive esophagitis (EE) in China. This study aimed to verify the efficacy and safety of tegoprazan vs. esomeprazole in patients with EE in China. Methods::This study was a multicenter, randomized, double-blind, parallel, active-controlled, non-inferiority phase III trial of patients with EE randomized 1:1 to tegoprazan 50 mg/day vs. esomeprazole 40 mg/day. This study was conducted in 32 sites between October 24, 2018 and October 18, 2019. The primary endpoint was the cumulative endoscopic healing rate at week 8. The secondary endpoint included endoscopic healing rate at week 4, changes in the reflux disease questionnaire (RDQ) and gastroesophageal reflux disease health-related quality of life (GERD-HRQL) scores, and symptom improvement. Results::A total of 261 patients were randomized: 132 to the tegoprazan group and 129 to the esomeprazole group. The cumulative endoscopic healing rate at 8 weeks in the tegoprazan group was non-inferior to that of the esomeprazole group (91.1% vs. 92.8%, difference: -1.7%, 95% confidence interval [CI]: -8.5%, 5.0%, P = 0.008). There were no statistically significant differences in the changes in RDQ (total, severity, and frequency) and GERD-HRQL scores between the two groups (all P >0.05). The percentages of days without symptoms, including daytime and nighttime symptoms based on patients' diaries, were similar between the two groups (all P >0.05). In the tegoprazan and esomeprazole groups, 71.5% (93/130) and 61.7% (79/128) of the participants reported adverse events (AEs), 2.3% and 0 experienced serious AEs, while 70.0% and 60.2% had treatment-emergent AEs, respectively. Conclusion::Tegoprazan 50 mg/day demonstrated non-inferior efficacy in healing EE, symptom improvement, and quality of life, and it has similar tolerability compared with esomeprazole 40 mg/day.

Background::An evidence gap still exists regarding the efficacy and safety of tegoprazan in patients with erosive esophagitis (EE) in China. This study aimed to verify the efficacy and safety of tegoprazan vs. esomeprazole in patients with EE in China. Methods::This study was a multicenter, randomized, double-blind, parallel, active-controlled, non-inferiority phase III trial of patients with EE randomized 1:1 to tegoprazan 50 mg/day vs. esomeprazole 40 mg/day. This study was conducted in 32 sites between October 24, 2018 and October 18, 2019. The primary endpoint was the cumulative endoscopic healing rate at week 8. The secondary endpoint included endoscopic healing rate at week 4, changes in the reflux disease questionnaire (RDQ) and gastroesophageal reflux disease health-related quality of life (GERD-HRQL) scores, and symptom improvement. Results::A total of 261 patients were randomized: 132 to the tegoprazan group and 129 to the esomeprazole group. The cumulative endoscopic healing rate at 8 weeks in the tegoprazan group was non-inferior to that of the esomeprazole group (91.1% vs. 92.8%, difference: -1.7%, 95% confidence interval [CI]: -8.5%, 5.0%, P = 0.008). There were no statistically significant differences in the changes in RDQ (total, severity, and frequency) and GERD-HRQL scores between the two groups (all P >0.05). The percentages of days without symptoms, including daytime and nighttime symptoms based on patients' diaries, were similar between the two groups (all P >0.05). In the tegoprazan and esomeprazole groups, 71.5% (93/130) and 61.7% (79/128) of the participants reported adverse events (AEs), 2.3% and 0 experienced serious AEs, while 70.0% and 60.2% had treatment-emergent AEs, respectively. Conclusion::Tegoprazan 50 mg/day demonstrated non-inferior efficacy in healing EE, symptom improvement, and quality of life, and it has similar tolerability compared with esomeprazole 40 mg/day.

Objective:To evaluate the predictive value of anthropometric indicators in predicting cardiovascular risk in the population with metabolic syndrome(MS).Methods:A cross-sectional study was used to analyze the correlation between anthropometric measures and cardiovascular risk in subjects with MS. Cardiometabolic risk was assessed with cardiometabolic risk index(CMRI). Receiver operating characteristic(ROC) curve analysis was used to assess the predictive power of anthropometric measures for cardiometabolic risk.Results:(1) The anthropometric measures [body mass index(BMI), waist-hip ratio(WHR), waist-to-height ratio(WtHR), body fat percentage(BFP), visceral fat index(VFI), conicity index(CI), a body shape index(ABSI), body roundness index(BRI), abdominal volume index(AVI)] in the MS group were significantly higher than those in the non-MS group( P<0.05). Moreover, there were significant differences in CMRI score and vascular risk between the two groups( P<0.05). (2) Logistic regression analysis showed that the cardiovascular risk was increased with the increases of BMI, VFI, WHR, WtHR, CI, BRI, and AVI after adjusting for confounding factors in the overall population, the non-MS population, and the MS population( P<0.05). (3) In the ROC analysis, the AUC values of BMI, VFI, and AVI were 0.767, 0.734, and 0.770 in the overall population; 0.844, 0.816, and 0.795 in the non-MS population; 0.701, 0.666, and 0.702 in the MS population, respectively. For the overall population and non-MS population, the optimal cut points of BMI to diagnose high cardiovascular risk were 26.04 kg/m 2 and 24.36 kg/m 2; the optimal cut points of VFI were 10.25 and 9.75; the optimal cut points of AVI were 17.3 cm 2 and 15.53 cm 2, respectively. In the MS population, the optimal cut point as a predictor of high cardiovascular risk in young and middle-aged men with MS was 27.63 kg/m 2, and the optimal cut point of AVI in women was 18.08 cm 2. Conclusion:BMI, VFI, and AVI can be used as predictors of cardiovascular risk in the general population. BMI can be used as a predicator of high cardiovascular risk in young and middle-age men with MS. AVI can be used as a predicator of high cardiovascular risk in women with MS.

Corneal confocal microscopy (CCM) is a non-invasive, simple and rapid visual corneal imaging technique, which can directly conduct real-time collection and quantitative analysis of corneal nerve fibers. Studies have shown that CCM can be used in the diagnosis and prognosis evaluation of degenerative diseases, demyelinating diseases, degenerative diseases and other types of diseases of the central nervous system. In this paper, the recent advance in CCM in neurological diseases is summarized to provide new ideas for their diagnosis and prognosis evaluation.

Corneal confocal microscopy (CCM) is an in vivo corneal imaging technique, which can directly quantify corneal nerve fibers in real time. It has the characteristics of non-invasive, objective and high sensitivity. CCM can not only be used for the diagnosis and treatment evaluation of corneal diseases, but also plays an important role in the diagnosis and prognosis evaluation of some peripheral and central nervous system diseases, such as diabetes peripheral neuropathy and Parkinson's disease. In addition, the changes of corneal nerve fibers can indirectly reflect the severity of ischemic cerebrovascular disease, and it is expected to become a noninvasive bioimaging marker of ischemic cerebrovascular disease. This article reviews CCM and its application in ischemic cerebrovascular disease, in order to provide better means for early diagnosis and prognosis evaluation of ischemic cerebrovascular disease.

Objective: By implementing the best practice of bedtime and position after diagnostic adult lumbar puncture,we hope to establish a scientific and standardized nursing routine for lumbar puncture, shorten the bed-rest time after lumbar puncture, and improve the comfort of patients. Methods: By reviewing literatures related to positions after adult lumbar puncture and post-dural puncture headache, six best practice were concluded. By combining the best evidence and the clinical circumstances, the evidenced-based criteria were established and then applied in the Neurology Department. Results: After two rounds of reviews, the results showed that except the 93.3% compliance with the new evidence, all other four criteria had 100% complacence. Comparing before and after applying the evidence, there was no statistically significant difference for the occurrence of post-dural puncture headache or dizziness(P>0.05), there was a statistically significant reduction of back pain from 28.3%(30/106) to 15.1%(18/119)(χ² value was 5.799, P<0.05) when the evidence was applied. Conclusions The best practice shows that patients needn′t lie on bed for 4 to 6 hours after lumbar puncture, the occurrence of back pain is lowered and the comfort level of the patient is improved in those who rest with pillow or activities.

Objective To evaluate therapeutic effects of bone marrow mesenchymal stem cells(MSC)derived exosomes on alcohol-induced liver injury.Methods Eighteen male C57BL/6 mice aged 6 to 8 week were randomly divided into control group,model group and exosomes group,with 6 mice in each group.The mice in the model group and the exosomes group were fed with Lieber-DeCarli ad libitum diet(Dyets Inc.)for 4 weeks,followed by gavage a bolus of ethanol at day 26,27 and 28.The mice in the control group matched the alcohol-derived calories with dextran-maltose.Meanwhile,the mice in exosomes group were injected with MSC-exosomes via the tail vein at day 14 and 26.After the experiment,serum levels of alanine aminotransferase(ALT)and aspartate aminotransaminase(AST)were detected,and the pathological changes of liver tissues were observed.The expressions of nuclear factor erythroid 2-related factor 2(Nrf-2),heme oxygenase-1(HO-1),CD63,CD81,TSG101 and Cytochrome C were analyzed by Western blot,and mRNA levels of Nrf-2,HO-1,interleukin(IL)-10 and IL-17 were analyzed by real-time polymerase chain reaction(RT-PCR).The commercial kits were used to detect serum IL-10,IL-17 levels and liver tissue malondialdehyde(MDA),glutathione(GSH),superoxide dismutase(SOD)oxidative stress indicators.The numbers of regulatory T cell(Treg)and help T(Th)17 cells in the liver were analyzed by flow cytometry.One-way analysis of variance was used for comparison between groups.Results MSC-exosomes expressed positive markers CD63,CD81 and TSG101,but did not express the negative markers Cytochrome C.The serum ALT and AST levels in model group were(87.3±25.1)U/L and(223.2±43.5)U/L,respectively,while those in exosomes group were(47.7±12.0)U/L and(128.2±33.6)U/L,respectively.The differences between the two groups were both statistically significant(F=12.818 and 12.226,respectively,both P<0.05).Compared with control group,the SOD activity and GSH level in the model group significantly decreased with statistically significant differences(F=4.245 and 24.074,respectively,both P <0.05).Lieber-DeCarli ethanol feeding significantly increased intrahepatic MDA level in the model mice,which was reversed by MSC-exosomes supplementation,and the difference was statistically significant(F=36.675,P <0.05).Compared with control group,the intrahepatic protein expressions of Nrf-2 and HO-1 in model group were significantly decreased,while the expressions in exosomes group were obviously increased.The differences were statistically significant(F=33.623 and 14.960,respectively,both P <0.05).The expression trends of Nrf-2 and HO-1 mRNA were the same as those of protein expressions(F=20.784 and 276.336,respectively,both P <0.05).The proportions of liver Treg/Th17 in the control group,model group and exosomes group were 4.3±0.9,0.4±0.2,and 3.4±0.5,respectively.The differences among groups were statistically significant(F=64.227,P <0.05).Compared with control group,the serum protein and intrahepatic gene expression of IL-17 in the model group were significantly increased,which were reversed by MSC-exosomes treatment.The differences were statistically significant(F=15.581 and 40.095,respectively,both P<0.05).Serum IL-10 protein levels and intrahepatic IL-10 gene expression were significantly decreased after Lieber-DeCarli ethanol feeding,which were lower than the exosomes group.The differences were statistically significant(F=98.268 and 153.743,respectively,both P <0.05).Conclusions MSC-exosomes transplantation may relieve alcohol-induced liver injury.The mechanism could involve reduction of oxidative stress in the liver via regulating Nrf-2/HO-1 and normalizing the balance of Treg and Th17 cells.

Genetically encoded Ca(2+) indicators (GECI) are important for the measurement of Ca(2+) in vivo. GCaMP2, a widely-used GECI, has recently been iteratively improved. Among the improved variants, GCaMP3 exhibits significantly better fluorescent intensity. In this study, we developed a new GECI called GCaMPJ and determined the crystal structures of GCaMP3 and GCaMPJ. GCaMPJ has a 1.5-fold increase in fluorescence and 1.3-fold increase in calcium affinity over GCaMP3. Upon Ca(2+) binding, GCaMP3 exhibits both monomeric and dimeric forms. The structural superposition of these two forms reveals the role of Arg-376 in improving monomer performance. However, GCaMPJ seldom forms dimers under conditions similar to GCaMP3. St ructural and mutagenesis studies on Tyr-380 confirmed its importance in blocking the cpEGFP β-barrel holes. Our study proposes an efficient tool for mapping Ca(2+) signals in intact organs to facilitate the further improvement of GCaMP sensors.
Calcium ; chemistry ; metabolism ; Calmodulin ; chemistry ; genetics ; metabolism ; Crystallography, X-Ray ; Dimerization ; Green Fluorescent Proteins ; chemistry ; genetics ; metabolism ; Histidine ; chemistry ; genetics ; metabolism ; Hydrogen-Ion Concentration ; Myosin-Light-Chain Kinase ; chemistry ; genetics ; metabolism ; Peptide Fragments ; chemistry ; genetics ; metabolism ; Protein Structure, Tertiary ; Recombinant Fusion Proteins ; biosynthesis ; chemistry ; genetics

Previous studies have indicated that ERp44 inhibits inositol 1,4,5-trisphosphate (IP(3))-induced Ca(2+) release (IICR) via IP(3)R(1), but the mechanism remains largely unexplored. Using extracellular ATP to induce intracellular calcium transient as an IICR model, Ca(2+) image, pull down assay, and Western blotting experiments were carried out in the present study. We found that extracellular ATP induced calcium transient via IP(3)Rs (IICR) and the IICR were markedly decreased in ERp44 overexpressed Hela cells. The inhibitory effect of C160S/C212S but not C29S/T396A/ΔT(331-377) mutants of ERp44 on IICR were significantly decreased compared with ERp44. However, the binding capacity of ERp44 to L3V domain of IP(3)R(1) (1L3V) was enhanced by ERp44 C160S/C212S mutation. Taken together, these results suggest that the mutants of ERp44, C160/C212, can more tightly bind to IP(3)R(1) but exhibit a weak inhibition of IP(3)R(1) channel activity in Hela cells.
Adenosine Triphosphate ; pharmacology ; Amino Acid Substitution ; Biological Transport ; drug effects ; physiology ; Blotting, Western ; Calcium ; metabolism ; Calcium Signaling ; drug effects ; physiology ; HeLa Cells ; Humans ; Immunoprecipitation ; Inositol 1,4,5-Trisphosphate ; metabolism ; Inositol 1,4,5-Trisphosphate Receptors ; physiology ; Membrane Potentials ; drug effects ; physiology ; Membrane Proteins ; genetics ; metabolism ; Microscopy, Confocal ; Molecular Chaperones ; genetics ; metabolism ; Mutation ; Plasmids ; Transfection

OBJECTIVE To study the change and significance of TNF-? and IL-18 in the Acinetobacter baumannii sepsis. METHODS Sixty male SD rats were divided into 6 groups. The first group was normal control group. The second to sixth groups were sepsis groups which were killed at 4h,16h,24h,48h,72h after injecting A. baumannii through intraperitoneal injection to make sepsis model. The level of TNF-? and IL-18 in the serum of rats was measured by enzyme linked immunosorbent assay (ELISA). RESULTS The level of TNF-? in the serum increased markedly in the sepsis groups (P