AIM:This study aims to investigate the changes in the lactylation levels of mitsugumin 53(MG53)protein during myocardial ischemia/reperfusion(I/R)and to further explore the potential molecular mechanisms by which MG53 lactylation impacts myocardial cell injury resulting from I/R.METHODS:A myocardial I/R model was established in mice through ligation of the left anterior descending coronary artery followed by reperfusion.Simultaneous-ly,a hypoxia/reoxygenation(H/R)model of rat myocardial H9C2 cells was created in vitro.In the mouse model,TTC and HE staining were employed to assess myocardial ischemia and injury.The levels of creatine kinase and cardiac troponin I were quantified using ELISA,while MG53 expression was evaluated through immunofluorescence.In the in vitro cell model,CCK-8 assay and flow cytometry were utilized to measure cell viability and apoptosis level,respectively.The levels of MG53 protein,its lactylation,and ferroptosis-related proteins in both mouse myocardial tissue and in vitro rat cardiomyo-cytes were analyzed using immunoprecipitation and Western blot.Additionally,the levels of reactive oxygen species,fer-rous ion,lactate dehydrogenase and malondialdehyde in tissues and cells were measured using appropriate assay kits.RE-SULTS:In the I/R group,mouse myocardial tissue exhibited significant injury following cardiac I/R.The expression of MG53 protein was reduced,while the lactylation level of MG53 protein and the ferroptosis of myocardial cells were in-creased.In the in vitro cardiomyocyte experiments,H/R exposure resulted in decreased cell viability,increased apoptosis and ferroptosis levels,reduced MG53 protein expression,and increased MG53 lactylation level.Treatment with 2-deoxy-D-glucose(2-DG)improved cardiomyocyte viability,decreased apoptosis and ferroptosis levels,increased MG53 expres-sion,and lowered MG53 lactylation level.Furthermore,the addition of exogenous lactate significantly countered the ef-fects of 2-DG on cell viability and MG53 expression,and increased the cell apoptosis,ferroptosis and MG53 lactylation levels.CONCLUSION:During myocardial I/R,there is a down-regulation of MG53 protein expression accompanied by an increase in the lactylation level of MG53 protein.The elevation of MG53 lactylation may exacerbate myocardial I/R inju-ry by facilitating the ferroptosis of cardiomyocytes.

AIM:This study aims to investigate the changes in the lactylation levels of mitsugumin 53(MG53)protein during myocardial ischemia/reperfusion(I/R)and to further explore the potential molecular mechanisms by which MG53 lactylation impacts myocardial cell injury resulting from I/R.METHODS:A myocardial I/R model was established in mice through ligation of the left anterior descending coronary artery followed by reperfusion.Simultaneous-ly,a hypoxia/reoxygenation(H/R)model of rat myocardial H9C2 cells was created in vitro.In the mouse model,TTC and HE staining were employed to assess myocardial ischemia and injury.The levels of creatine kinase and cardiac troponin I were quantified using ELISA,while MG53 expression was evaluated through immunofluorescence.In the in vitro cell model,CCK-8 assay and flow cytometry were utilized to measure cell viability and apoptosis level,respectively.The levels of MG53 protein,its lactylation,and ferroptosis-related proteins in both mouse myocardial tissue and in vitro rat cardiomyo-cytes were analyzed using immunoprecipitation and Western blot.Additionally,the levels of reactive oxygen species,fer-rous ion,lactate dehydrogenase and malondialdehyde in tissues and cells were measured using appropriate assay kits.RE-SULTS:In the I/R group,mouse myocardial tissue exhibited significant injury following cardiac I/R.The expression of MG53 protein was reduced,while the lactylation level of MG53 protein and the ferroptosis of myocardial cells were in-creased.In the in vitro cardiomyocyte experiments,H/R exposure resulted in decreased cell viability,increased apoptosis and ferroptosis levels,reduced MG53 protein expression,and increased MG53 lactylation level.Treatment with 2-deoxy-D-glucose(2-DG)improved cardiomyocyte viability,decreased apoptosis and ferroptosis levels,increased MG53 expres-sion,and lowered MG53 lactylation level.Furthermore,the addition of exogenous lactate significantly countered the ef-fects of 2-DG on cell viability and MG53 expression,and increased the cell apoptosis,ferroptosis and MG53 lactylation levels.CONCLUSION:During myocardial I/R,there is a down-regulation of MG53 protein expression accompanied by an increase in the lactylation level of MG53 protein.The elevation of MG53 lactylation may exacerbate myocardial I/R inju-ry by facilitating the ferroptosis of cardiomyocytes.

ObjectiveTo determine the current status and characteristics of tuberculosis （TB） registration and treatment in Kashgar， and to provide scientific evidence for targeted prevention and control measures in future. MethodsKashgar registered TB cases information in 2011 to 2020 was exported from the National Tuberculosis Management Information System. Descriptive epidemiological analysis was conducted using Stata 12.0. ResultsFrom 2011 to 2020， number of Kashgar registered TB patients showed rising trend， followed by a falling one. Average proportion of annual decline in registered TB incidence was 40.48% from 2018 to 2020. From 2011 to 2016， number of registered TB patients in women was always higher than that in men， with a gender ratio （male ： female） of about 0.90. In 2017， the gender ratio was 1.00. From 2018 to 2020， the gender ratios were 1.05， 1.20， and 1.12， respectively. Moreover， number of registered TB cases increased with age （χ²=547.79， P<0.001）. Proportion of registered TB cases was relatively large in Shache County （16.43%‒23.64%）， Yengisar County （9.51%‒13.87%） ， Kashgar City （8.11%‒11.40%）， Yecheng County （6.98%‒13.40%） and Bachu County（4.92%‒16.65%）. Proportion of recurrent TB cases in Kashgar had increased to 27.29%， 20.77% and 28.39% in 2018， 2019 and 2020， respectively. Multivariate analysis showed that age， drug resistance， calendar year and etiological diagnosis were significantly correlated with the proportion of recurrent cases （all P<0.05）. ConclusionSince 2018， TB incidence has decreased significantly due to the increasing efforts for identification and treatment of TB cases. However， Kashgar remains facing a high TB incidence. TB cases that are elderly， drug-resistant and positive for pathogen are susceptible to recurrent treatment. In future， targeted prevention and control measures should be improved for these groups.

The binding mechanism between pefloxacin mesylate (PM) and transferrin (Tf) was explored using spectral experiment combined with molecular modeling techniques. The binding parameters and thermodynamic functions of PM-Tf solution system were measured at different temperatures. The effect of PM on molecular conformation of Tf was investigated and the interaction mechanism was also discussed. The results showed that dynamic quenching mechanism occurs with PM binding to Tf. The value of binding distances (r) is low, which indicates the occurrence of energy transfer. The drug had conformational effect on Tf, which resulted in changes of hydrophobic environment of the binding domain in Tf. According to the obtained thermodynamic parameters, the main interaction force between PM and Tf is attributed to hydrophobic bonding. The results of molecular modeling revealed that hydrophobic and hydrogen bonds are main binding forces in the PM-Tf system. These results were in accordance with spectral experiments. The research results have given a better theoretical reference for the study of pharmacological mechanism between protein and quinolone.

A combination of spectral experiment and molecular modeling techniques has been used to characterize the binding mechanism between an active component 5-hydroxymethyl-furfural (5-HMF) of traditional Chinese medicine and human serum albumin (HSA) or bovine serum albumin (BSA). The interaction mechanism of 5-HMF binding with HSA/BSA is analyzed. Although the drug can bind with HSA/BSA to form stable complexes, there are some differences in the bond strength. The values of binding distances (r) are different and low, which indicated the occurrence of energy transfer. The drug had conformational effect on HSA/BSA, which resulted in different changes of hydrophobic environment of the binding domain in HSA/BSA. The 'phase diagram' of fluorescence revealed that the changes on the conformational pattern of proteins have been affected by drug conformed to the "all-or-none" pattern. The interactions between drug and protein influenced by Co(II) were also discussed. Its effects acting on 5-HMF-HSA/BSA interactions are different. The computational modeling method was used to study the interaction between 5-HMF and HSA/BSA. The results of molecular model studies revealed that the binding modes for drug-serum albumin systems are mainly hydrophobic interactions and hydrogen bonding. These results are in accordance with spectral results. The research results have given a better theoretical reference for the study of pharmacological mechanism of 5-hydroxymethyl-furfural.