Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent cause of chronic liver disease worldwide, and its intricate pathogenesis presents challenges in the development of new drugs. As a common way of post-translational modification, acetylation regulates protein stability, enzyme activity, and subcellular localization, occurring extensively in MASLD-associated processes such as lipid metabolism, inflammatory response, and oxidative stress. In this paper, we comprehensively review the mechanism of acetylation in MASLD, analyze the expression levels of acetylases in liver tissues of MASLD patients from the gene expression omnibus (GEO), discuss the changes in relevant enzyme expression and mechanisms in animal models, and further explore the feasibility of targeting acetylation for MASLD treatment, in the hope of offering a new perspective for advancing drug discovery in the field of MASLD.

An LC-MS method with natural isotope abundance correction and a ¹H NMR relative quantitative method were established to determine the deuterium incorporation of donafenib tosilate, a new deuterated drug molecule. First, the peak areas of isotopic impurities (non-deuterated and incompletely deuterated impurities) and deuterated drug were recorded through the single ion monitoring (SIM) mode of the established LC-MS method and then corrected in terms of the natural isotope abundance offered by ChemDraw soft, removing the nature isotope interference from ¹³C, ³⁷Cl, etc. The corrected areas were subsequently used to calculate mol% of isotopologues (D₀, D₁, D₂, D₃) and Atom% D, namely, deuterium incorporation. In addition, a ¹H qNMR experiment was conducted with the aromatic proton at δ 8.63 and the residual proton of isotopic impurities at δ 2.79 as quantitative peaks. The mixture of DMSO-d₆ and D₂O (10∶1) was employed as the solvent to change the spin-coupling between the residual proton and active hydrogen so that the residual proton could be measured as the single peak, and the sensitivity was greatly improved. The acquisition parameters were also optimized, and Atom% ¹H and the deuterium incorporation were then calculated. The two methods were applied to samples of three commercial batches, and the testing results were almost consistent. Both methods proved accurate, sensitive, fast and independent of standard substances and accurate weighing, which could be applied to the determination of the deuterium incorporation of donafenib tosilate and provide a reference for other deuterated drugs.

Objective To explore the protective mechanism of RNA binding protein LIN28 on diabetic nephropathy(DN).Methods LIN28 was overexpressed or knocked down by adenovirus in HEK 293T cells.The gene and functional signaling pathway significantly changed after overexpression of LIN28 were obtained through RNA Seq transcriptome sequencing and bioinformatics analysis.HEK 293T cells were divided into the Control group,the Treatment group,the Adv-LIN28-OE+D-ribose group and the Adv-LIN28-NC+D-ribose group in in vitro LIN28 overexpression studies.And HEK 293T cells were divided into the Control group,the Treatment group,the Adv-shRNA LIN28+D-ribose group and the Adv-shRNA NT+D-ribose group in in vitro LIN28 knockdown studies.ELISA was used to detect the levels of human advanced glycation end products(AGEs)of cells supernatants in the above groups.Western blot was used to detect the expression levels of RAGE,NF-κB and MMP-2 of cells in the above groups.Results The results of RNA-Seq transcriptome sequencing,GO analysis and KEGG analysis showed that overexpression of LIN28 resulted in a significant down-regulation of AGE-RAGE signaling pathway in HEK 293T cells(P<0.05).The results of ELISA showed that compared with the Control group,the cell in the Treatment group produced a large amount of AGEs(P<0.05);compared with the Treatment group,the AGEs level of cells in the Adv-LIN28-OE+D-ribose group was significantly decreased(P<0.05),while the AGEs level of cells in the Adv-shRNA LIN28+D-ribose group was increased(P>0.05).The results of Western blot showed that compared with the Control group,the expression levels of RAGE,NF-κB and MMP-2 of cells in the Treatment group were significantly increased(P<0.05);compared with the Treatment group,the expression levels of RAGE,NF-κB and MMP-2 of cells in the Adv-LIN28-OE+D-ribose group were significantly decreased(P<0.05),while the expression levels of RAGE,NF-κB and MMP-2 of cells in the Adv-shRNA LIN28+D-ribose group were significantly increased(P>0.05).Conclusion Overexpression of LIN28 by adenovirus at the cellular level in vitro can lead to significant differential expression of thousands of genes.In particular,it can inhibit the diabetes and complications-related AGE-RAGE signaling pathway,which is critical in the progression of DN disease,and play a role in protecting DN.

Non-alcoholic fatty liver disease (NAFLD) has become a major public health hazard threatening human health worldwide.Yet, due to its complex pathogenesis, new drug development is difficult, with still insufficient clinical medication.Palmitoylation is a universal posttranslational modification of proteins catalyzed by palmitoyltransferase, affecting their stability, membrane localization and function.Recent studies have shown that palmitoylation is closely associated with NAFLD.This review summarizes the mechanisms of palmitoylation in NAFLD and analyzes the expression levels of the palmitoyltransferase family in liver tissues of NAFLD patients from GEO database, aiming to provide important clues to explore new mechanisms for NAFLD.

Objective:To analyze the risk factors of bronchopulmonary dysplasia(BPD)in very preterm infants(VPI), and to provide scientific basis for the prevention and treatment of BPD in VPI.Methods:A prospective multicenter study was designed to collect the clinical data of VPI in department of neonatology of 28 hospitals in 7 regions from September 2019 to December 2020.According to the continuous oxygen dependence at 28 days after birth, VPI were divided into non BPD group and BPD group, and the risk factors of BPD in VPI were analyzed.Results:A total of 2 514 cases of VPI including 1 364 cases without BPD and 1 150 cases with BPD were enrolled.The incidence of BPD was 45.7%.The smaller the gestational age and weight, the higher the incidence of BPD( P<0.001). Compared with non BPD group, the average birth age, weight and cesarean section rate in BPD group were lower, and the incidence of male infants, small for gestational age and 5-minute apgar score≤7 were higher( P<0.01). In BPD group, the incidences of neonatal respiratory distress syndrome(NRDS), hemodynamically significant patent ductus arteriosus, retinopathy of prematurity, feeding intolerance, extrauterine growth restriction, grade Ⅲ~Ⅳ intracranial hemorrhage, anemia, early-onset and late-onset sepsis, nosocomial infection, parenteral nutrition-associated cholestasis were higher( P<0.05), the use of pulmonary surfactant(PS), postnatal hormone exposure, anemia and blood transfusion were also higher, and the time of invasive and non-invasive mechanical ventilation, oxygen use and total hospital stay were longer( P<0.001). The time of starting enteral nutrition, cumulative fasting days, days of reaching total enteral nutrition, days of continuous parenteral nutrition, days of reaching 110 kcal/(kg·d) total calorie, days of reaching 110 kcal/(kg·d) oral calorie were longer and the breastfeeding rate was lower in BPD group than those in non BPD group( P<0.001). The cumulative doses of amino acid and fat emulsion during the first week of hospitalization were higher in BPD group( P<0.001). Multivariate Logistic regression analysis showed that NRDS, invasive mechanical ventilation, age of reaching total enteral nutrition, anemia and blood transfusion were the independent risk factors for BPD in VPI, and older gestational age was the protective factor for BPD. Conclusion:Strengthening perinatal management, avoiding premature delivery and severe NRDS, shortening the time of invasive mechanical ventilation, paying attention to enteral nutrition management, reaching whole intestinal feeding as soon as possible, and strictly mastering the indications of blood transfusion are very important to reduce the incidence of BPD in VPI.

Objective: To examine the association of body mass index (BMI) and waist circumference (WC) with frailty among oldest-old adults in China. Methods: A total of 7 987 people aged 80 years and older (oldest-old) who participated in the Chinese Longitudinal Healthy Longevity Survey (CLHLS) in 2017-2018 were included. Information on demographic characteristics, behavior pattern, diet, activities of daily living, cognitive function, health status, disease condition were collected by questionnaire and physical examination. Generalized linear mixed model and restricted cubic splines (RCS) were used to analyze the association of BMI and WC with frailty. Results: The mean age of all participants was 91.7 years, and their mean BMI and WC were (21.3±3.5) kg/m² and (82.9±10.5) cm, respectively. The proportion of male was 42.3% (3 377/7 987), and the proportion of people with frailty was 33.7% (2 664/7 987). After controlling confounding factors, compared with T₂ (19.1-22.1 kg/m²) of BMI, the OR (95%CI) of the female T₁ (<19.1 kg/m²) and T₃ (≥22.2 kg/m²) group was 1.39 (1.17-1.65) and 1.27 (1.07-1.52), respectively. Compared with T₂ (77-85 cm) of WC, the OR (95%CI) of female T₁ (<77 cm) and T₃ (≥86 cm) group was 1.20 (1.01-1.42) and 1.10 (0.93-1.31), respectively. The results of multiple linear regression model with restrictive cubic spline showed that there was a non-linear association of BMI and WC with frailty in female. Conclusion: There is a U-shaped association of BMI and WC with frailty in female participants.
Adult ; Male ; Female ; Humans ; Aged, 80 and over ; Waist Circumference ; Body Mass Index ; Frailty/epidemiology* ; Activities of Daily Living ; China/epidemiology* ; Risk Factors

To investigate the relationship between serum uric acid to creatinine ratio (SUA/Cr) and metabolic syndrome (MS) and other indexes on physical examination population in Nantong area. Using the method of cross-sectional study, 8 148 physical examiners in the physical examination center of the Affiliated Hospital of Nantong University from January 2017 to April 2020 were used as the research objects, and the clinical data and serum biochemical indicators such as smoking and alcohol addiction, physical examination and so on were collected. According to the standard diagnosis of MS of Diabetes Society of Chinese Medical Association, the patients were grouped according to the quartile of SUA/Cr and the clinical data of each group were compared. Pearson correlation analysis and logistic regression analysis were used to explore the correlation between SUA/Cr and clinical indicators and the relationship between SUA/Cr and the risk of MS. The results showed that UA and SUA/Cr were the lowest in normal metabolism group, followed by abnormal metabolism group and the highest in MS group, The difference between the two groups was statistically significant (H=919.21 and 629.34, P<0.001). According to the SUA/Cr quartile, the population was divided into four groups. After adjusting for gender, age, smoking history and drinking history, SUA/Cr in group Q₁ was positively correlated with BMI and TG (r=0.061 and 0.080, P<0.05), but negatively correlated with HDL-C (r=-0.057, P<0.05). Multivariate logistic regression results showed that after adjusting for age, sex, smoking history and drinking history, the risk of MS for BMI, SBP, DBP, FBG, TG, HDL-C and SUA/Cr [OR (95%CI)] were: 1.44 (1.41-1.47), 1.07 (1.06-1.07), 1.10 (1.10-1.11), 1.83 (1.73-1.92), 1.89 (1.79-1.99), 0.08 (0.06-0.10) and 1.54 (1.47-1.62). Compared with SUA/Cr group Q₁, the risk of MS in group Q₂, Q₃ and Q₄ increased by 75%, 162% and 346%, respectively. In conclusion, there was an independent positive correlation between SUA/Cr and MS risk in Nantong area.
Humans ; Metabolic Syndrome/epidemiology* ; Creatinine ; Uric Acid ; Cross-Sectional Studies ; Physical Examination ; Risk Factors

Objective: To explore the effects and mechanism of water-soluble chitosan hydrogel on infected full-thickness skin defect wounds in diabetic mice. Methods: The experimental research method was adopted. The control hydrogel composed of polyvinyl alcohol and gelatin, and the water-soluble chitosan hydrogel composed of the aforementioned two materials and water-soluble chitosan were prepared by the cyclic freeze-thaw method. The fluidity of the two dressings in test tube before and after the first freeze-thawing was generally observed, and the difference in appearance of the final state of two dressings in 12-well plates were compared. According to random number table (the same grouping method below), the cell strains of L929 and HaCaT were both divided into water-soluble chitosan hydrogel group and control hydrogel group, respectively. After adding corresponding dressings and culturing for 24 h, the cell proliferation activity was measured using cell counting kit 8. Rabbit blood erythrocyte suspensions were divided into normal saline group, polyethylene glycol octyl phenyl ether (Triton X-100) group, water-soluble chitosan hydrogel group, and control hydrogel group, which were treated accordingly and incubated for 1 hour, and then the hemolysis degree of erythrocyte was detected by a microplate reader. Twenty-four female db/db mice aged 11-14 weeks were selected, and full-thickness skin defect wounds on their backs were inflicted and inoculated with the methicillin-resistant Staphylococcus aureus (MRSA), 72 h later, the mice were divided into blank control group, sulfadiazine silver hydrogel group, control hydrogel group, and water-soluble chitosan hydrogel group, which were treated accordingly. On post injury day (PID) 0 (immediately), 7, 14, and 21, the healing of the wound was observed. On PID 14 and 21, the wound healing rate was calculated. On PID 14, MRSA concentration in wounds was determined. On PID 21, the wounds were histologically analyzed by hematoxylin and eosin staining; the expression of CD31 in the wounds was detected by immunofluorescence method, and its positive percentage was calculated. Raw264.7 cells were taken and divided into interleukin-4 (IL-4) group, blank control group, control hydrogel group, and water-soluble chitosan hydrogel group, which were treated accordingly. At 48 h of culture, the percentages of CD206 positive cells were detected by flow cytometry. The number of samples was all 3. Data were statistically analyzed with independent sample t test, one-way analysis of variance, analysis of variance for repeated measurement, least significant difference test, and Dunnett T3 test. Results: Two dressings in test tube had certain fluidity before freeze-thawing and formed semi-solid gels after freeze-thawing for once. The final forms of two dressings in 12-well plates were basically stable and translucent sheets, with little difference in transparency. At 24 h of culture, the cell proliferation activities of L929 and HaCaT in water-soluble chitosan hydrogel group were significantly higher than those in control hydrogel group (with t values of 6.37 and 7.50, respectively, P<0.01). At 1 h of incubation, the hemolysis degree of erythrocyte in water-soluble chitosan hydrogel group was significantly lower than that in Triton X-100 group (P<0.01), but similar to that in normal saline group and control hydrogel group (P>0.05). On PID 0, the traumatic conditions of mice in the 4 groups were similar. On PID 7, more yellowish exudates were observed inside the wound in blank control group and control hydrogel group, while a small amount of exudates were observed in the wound in sulfadiazine silver hydrogel group and water-soluble chitosan hydrogel group. On PID 14, the wounds in blank control group and control hydrogel group were dry and crusted without obvious epithelial coverage; in sulfadiazine silver hydrogel group, the scabs fell off and purulent exudate was visible on the wound; in water-soluble chitosan hydrogel group, the base of wound was light red and obvious epithelial coverage could be observed on the wound. On PID 14, the wound healing rate in water-soluble chitosan hydrogel group was significantly higher than that in the other 3 groups (all P<0.01). On PID 21, the wound in water-soluble chitosan hydrogel group was completely closed, while the wounds in the other 3 groups were not completely healed; the wound healing rate in water-soluble chitosan hydrogel group was significantly higher than that in the other 3 groups (all P<0.01). On PID 14, the concentration of MRSA in the wound in water-soluble chitosan hydrogel group was significantly lower than that in blank control group (P<0.01), but similar to that in control hydrogel group and sulfadiazine silver hydrogel group (P>0.05). On PID 21, the new epidermis was severely damaged in blank control group; the epidermis on the wound in control hydrogel group also had a large area of defect; complete new epidermis had not yet being formed on the wound in sulfadiazine silver hydrogel group; the wound in water-soluble chitosan hydrogel group was not only completely covered by the new epidermis, the basal cells of the new epidermis were also regularly aligned. On PID 21, the percentage of CD31 positivity in the wound in water-soluble chitosan hydrogel group was (2.19±0.35)%, which was significantly higher than (0.18±0.05)% in blank control group, (0.23±0.06)% in control hydrogel group, and (0.62±0.25)% in sulfadiazine silver hydrogel group, all P<0.01. At 48 h of culture, the percentage of CD206 positive Raw264.7 cells in water-soluble chitosan hydrogel group was lower than that in IL-4 group (P>0.01) but significantly higher than that in blank control group and control hydrogel group (P<0.05 or P<0.01). Conclusions: The water-soluble chitosan hydrogel has good biosafety and can induce higher level of macrophage M2 polarization than control hydrogel without water-soluble chitosan, so it can enhance the repair effect of MRSA-infected full-thickness skin defect wounds in diabetic mice and promote rapid wound healing.
Mice ; Female ; Animals ; Rabbits ; Interleukin-4 ; Hydrogels/pharmacology* ; Wound Healing ; Chitosan/pharmacology* ; Diabetes Mellitus, Experimental ; Water ; Methicillin-Resistant Staphylococcus aureus ; Gelatin ; Polyvinyl Alcohol ; Hemolysis ; Saline Solution ; Eosine Yellowish-(YS) ; Hematoxylin ; Octoxynol ; Silver ; Phenyl Ethers ; Sulfadiazine

Objective We used standardized patients to evaluate the accuracy and explore the influencing factors of the diagnosis of unstable angina pectoris and type 2 diabetes by primary healthcare providers in Sichuan rural areas,aiming to provide a scientific basis for improving the diagnosis accuracy of primary healthcare providers for the two chronic diseases. Methods A multi-stage stratified random cluster sampling method was adopted to select 100 villages from 50 townships in 5 districts/counties in Zigong city,Sichuan province. General and internal medicine practioners who were on duty on the survey day were enrolled in the survey.Two rounds of data collection were conducted.In the first round,the basic information of providers from township health centers and village clinics was collected.One month after the the first survey,standardized patients were used to collect the information related to the diagnosis of unstable angina pectoris and type 2 diabetes by rural primary providers.Logistic regression was carried out to analyze the factors influencing the diagnosis accuracy. Results A total of 172 rural primary healthcare providers were enrolled in the survey,who completed 186 standardized patient visits and showed the correct diagnosis rate of 48.39%.Specifically,the correct diagnosis rates of unstable angina pectoris and type 2 diabetes were 18.68%(17/91) and 76.84%(73/95),respectively.The providers with medical practitioner qualifications were more likely to make correct diagnosis(OR=4.857,95%CI=1.076-21.933, P=0.040).The providers who involved more necessary consultation and examination items in the diagnosis process had higher probability of correct diagnosis(OR=1.627,95%CI=1.065-2.485, P=0.024).Additionally,the providers were more likely to make a correct diagnosis for type 2 diabetes than for unstable angina pectoris(OR=6.306,95%CI=3.611-11.013, P<0.001). Conclusions The overall diagnosis accuracy of unstable angina pectoris and type 2 diabetes was relatively low among primary healthcare providers in Sichuan rural areas.The training of diagnosis process can be taken as a key for improving providers' practice ability so as to increase the diagnosis accuracy of chronic diseases.
Angina, Unstable ; China ; Chronic Disease ; Diabetes Mellitus, Type 2/diagnosis* ; Health Personnel ; Humans ; Primary Health Care ; Surveys and Questionnaires

Objective To understand the growth and dietary diversity status of children in multi-ethnic areas of Sichuan province,and to explore the associations of dietary diversity with growth and development indicators. Methods Children of 18-36 months old and their primary caregivers were selected with multi-stage cluster random sampling method from rural areas of Han,Tibetan,and Yi ethnic groups in Sichuan province. The sociodemographic information of children and their caregivers was collected using self-designed questionnaire.The dietary diversity score(DDS)was calculated according to the criteria in the Guidelines for Measuring Household and Individual Dietary Diversity released by the Food and Agriculture Organization of the United Nations.The body height(length)and body weight of each child were measured by standard equipment for anthropological measurement,and the height for age Z score(HAZ),weight for age Z score(WAZ),and weight for height Z score(WHZ) were calculated.Multivariate linear regression was performed to analyze the relationship between dietary diversity and growth indicators of children. Results A total of 1092 children were enrolled in this study,and the prevalence of stunting(HAZ<-2),underweight(WAZ<-2),and wasting(WHZ<-2)was 21.1%,4.9%,and 2.5%,respectively.The children had the mean DDS of 4.8±1.7,and 45.3% of children had poor dietary diversity(DDS≤4).The children of Han ethnic group(5.8±1.4)had higher DDS than those of Tibetan ethnic group(4.9±1.6)and Yi ethnic group(3.9±1.6)(P<0.001).The results of multivariate linear regression indicated that DDS was positively correlated with HAZ(β=0.206,95%CI=0.158-0.254,P<0.001)after adjustment of sex,age,birth weight,preterm birth,and parental body height.After further adjustment of family fixed assets,ethnic group,caregiver's type,and caregiver's education background,the correlation between DDS and HAZ remained significant(β=0.077,95%CI=0.026-0.128, P=0.003). Conclusions The children in the multi-ethnic rural areas of Sichuan province showed troublesome growth and development status and low dietary diversity,which were conspicuously different between ethnic groups,especially in the rural areas of Yi ethnic group.The dietary diversity was positively associated with HAZ.It is recommended to carry out nutrition and health education according to the local dietary characteristics and thus improve the growth and development of children in multi-ethnic rural areas in Sichuan.
Child ; Child, Preschool ; China/epidemiology* ; Ethnicity ; Female ; Growth and Development ; Humans ; Infant ; Infant, Newborn ; Nutritional Status ; Pregnancy ; Premature Birth ; Rural Population