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.

OBJECTIVES: To investigate the clinical features and prognosis of children with non-Down-syndrome-related acute megakaryoblastic leukemia (non-DS-AMKL). METHODS: A retrospective analysis was conducted on the medical data of 17 children with non-DS-AMKL who were admitted to Children's Hospital of The First Affiliated Hospital of Zhengzhou University from January 2013 to December 2023, and their clinical features, treatment, and prognosis were summarized. RESULTS: Among the 17 children with non-DS-AMKL, there were 8 boys and 9 girls. Fourteen patients had an onset age of less than 36 months, with a median age of 21 months (range:13-145 months). Immunophenotyping results showed that 16 children were positive for CD61 and 13 were positive for CD41. The karyotype analysis was performed on 16 children, with normal karyotype in 6 children and abnormal karyotype in 9 children, among whom 5 had complex karyotype and 1 had no mitotic figure. Detected fusion genes included EVI1, NUP98-KDM5A, KDM5A-MIS18BP1, C22orf34-BRD1, WT1, and MLL-AF9. Genetic alterations included TET2, D7S486 deletion (suggesting 7q-), CSF1R deletion, and PIM1. All 17 children received chemotherapy, among whom 16 (94%) achieved complete remission after one course of induction therapy, and 1 child underwent hematopoietic stem cell transplantation (HSCT) and remained alive and disease-free. Of all children, 7 experienced recurrence, among whom 1 child received HSCT and died of graft-versus-host disease. At the last follow-up, six patients remained alive and disease-free. CONCLUSIONS Non-DS-AMKL primarily occurs in children between 1 and 3 years of age. The patients with this disorder have a high incidence rate of chromosomal abnormalities, with complex karyotypes in most patients. Some patients harbor fusion genes or gene mutations. Although the initial remission rate is high, the long-term survival rate remains low.
Humans ; Male ; Female ; Leukemia, Megakaryoblastic, Acute/etiology* ; Child, Preschool ; Infant ; Child ; Retrospective Studies ; Prognosis ; Down Syndrome/complications*

Objective:To investigate the current status of the implementation of home-based phototherapy (HBPT) in patients with vitiligo, and to analyze management needs among patients receiving HBPT.Methods:A questionnaire survey was conducted on the application of HBPT among patients with vitiligo who visited the outpatient clinic of the Hospital for Skin Diseases, Chinese Academy of Medical Sciences from December 2021 to November 2022. Additionally, the popularization and usage of HBPT as well as needs of patient management were investigated and analyzed in these vitiligo patients.Results:A total of 496 valid questionnaires were collected from 496 patients with vitiligo (241 males [48.5%] and 255 females [51.5%]) . Their ages at visit ranged from 2 to 67 (30.87 ± 12.36) years. The most commonly affected sites were the head and face (52.2%) , followed by hair (32.1%) , hands and feet (31.4%) , trunk (30.2%) , limbs (24.3%) , neck (19.5%) , and perineum (9.9%) . Among the participants, 320 (64.5%) were currently using or had used HBPT, and 352 (70.8%) expressed a willingness to learn more about HBPT usage guidelines and health education. Regarding the repigmentation outcomes after HBPT: among 312 patients, 54 (17.3%) reported complete recovery, 64 (20.5%) were markedly improved, 142 (45.5%) experienced improvement, and 52 (16.7%) showed no response. Adverse reactions occurred in 223 patients (71.5%) , of whom 28 (9.0%) experienced severe adverse reactions. The most desired guiding information was the adjustment method for phototherapy dosage and treatment duration (184/352, 52.3%) ; the most effective way to receive health education information was through verbal education by medical staff (177/352, 50.3%) .Conclusion:For vitiligo patients who were willing to accept and use HBPT, the most desired guiding information was the adjustment method for phototherapy dosage and treatment duration, and verbal health education by medical staff appeared to be the main way to obtain health education information.

Objective To establish a stable,reliable,and clinically relevant porcine model of endotoxin-induced acute respiratory distress syndrome(ARDS).Methods Ten 8-month-old male Bama minipigs were deeply sedated,followed by invasive mechanical ventilation and electrocardiographic monitoring.Lipopolysaccharide(LPS)was intravenously pumped at 600 μg/(kg·h)for 3 hours,then maintained at 15 μg/(kg·h)thereafter.Dynamic monitoring was performed at five time points after LPS injection(LPS 0,1,3,5,and 8 h),including arterial blood gas analysis and chest computed tomography(CT)scans.Pathological examination of lung tissues obtained via bronchoscopic biopsy(HE staining and transmission electron microscopy)was conducted.These indicators were comprehensively used to evaluate the success of the animal model.Results At 5 hours after LPS administration,8 minipigs developed symptoms such as skin cyanosis,elevated body temperature,and respiratory distress.The oxygenation index decreased to<300 mmHg.Chest CT scans showed diffuse pulmonary infiltrates.Histopathology revealed alveolar edema and hyaline membrane formation.Transmission electron microscopy demonstrated disruption of pulmonary blood-air barrier,depletion of lamellar bodies in type Ⅱ pneumocytes,inflammatory cell infiltration,and exudation of plasma proteins and fibrin.Compared with LPS 0 h,at LPS 8 h,the oxygenation index and arterial blood pH were significantly decreased(P<0.001),while blood lactic acid and serum potassium were significantly increased(P<0.05);serum calcium and base excess were significantly decreased(P<0.05),and the lung injury score based on HE-stained lung sections was significantly increased(P<0.01).Conclusion The porcine ARDS model established by continuous LPS injection can dynamically simulate the pathophysiological characteristics and typical pathological manifestations of clinical septic ARDS,making it an effective tool to study the pathogenesis,prevention,and treatment strategies of septic ARDS.

Purpose To investigate the sex differences of white matter damage in Alzheimer's disease(AD)and their association with cognitive impairment.Materials and Methods This retrospective study included 88 AD patients(48 females),71 amnestic mild cognitive impairment(aMCI)patients(39 females),and 95 healthy controls(63 females)recruited from the Memory Disorder Clinic at the First Affiliated Hospital of Anhui Medical University from September 2017 to July 2024.High-resolution three-dimensional T1 structure images and diffusion tensor imaging images were all obtained from each participant.The mean diffusivity(MD)and fractional anisotropy(FA)values of each white matter region were obtained,and the two-way ANOVA analysis was conducted to investigate brain regions with interaction effects between groups and sexes,those brain regions were then chosen as regions of interest for further correlation analysis with a series of cognitive scale scores.Results In terms of FA values,the right posterior corona radiata,right anterior limb of the internal capsule and left corticospinal tract showed interaction between sexes and cognitive groups(F=4.764,3.812,5.937,all P<0.05).The FA value of AD group was significantly lower than that of healthy control and aMCI group(all P<0.05),but there was no significant difference between healthy control and aMCI group(except the right anterior limb of the internal capsule,P=0.018).In AD group,FA values were significantly higher in women than in men in the previously described brain regions(all P<0.05),while there was no significant difference in FA values between male and female in healthy control and aMCI groups(except the left corticospinal tract,P<0.001).In terms of MD values,the right anterior limb of the internal capsule,right superior corona radiata and left external capsule showed interaction effect between sexes and cognitive groups(F=8.581,3.680,7.218,all P<0.05).The MD value of AD group was significantly higher than that of aMCI group(P<0.001),and aMCI group was higher than that of healthy control group(all P<0.05).In AD group,the MD values in the above brain regions were significantly higher in males than those in females(all P<0.01),while no significant difference was found between males and females in healthy control and aMCI groups(except for the left external capsule,P<0.05).For correlation analysis,the AD group was dimidiated into two groups by sex,the scores of the Montreal cognitive assessment,the Mini Mental state examination and the verbal fluency test of the female patient group were positively correlated with the FA values of the right posterior corona radiate(r=0.372,P=0.009;r=0.345,P=0.016;r=0.383,P=0.007),while the Mini Mental state examination and the verbal fluency test scores of female AD patient group were negatively correlated with the MD values of the right superior corona radiata(r=-0.360,P=0.012;r=-0.360,P=0.003).Conclusion Compared to the healthy control and MCI groups,white matter damage in AD patients shows sex differences and is associated with general cognitive and language functions impairment in female AD patients.

BACKGROUND:Formononetin is an isoflavonoid compound widely found in red clover,astragalus,and chickweed,which has the ability to inhibit oxidative stress,inflammatory factor release,and apoptosis. OBJECTIVE:To investigate the effect of formononetin on interleukin-1β-induced chondrocyte injury and its mechanism. METHODS:(1) Cartilage tissues from patients with osteoarthritis and patients with simple meniscus injury were collected,and real-time quantitative PCR was used to detect miR-135b-5p expression. (2) Human chondrocytes were cultured in vitro,and then divided them into nine groups:cells in normal control group were cultured for 48 hours with no treatment;cells in interleukin-1β group were treated with interleukin-1β for 48 hours;cells in interleukin-1β+low-dose formononetin group were treated with 25 μmol/L formononetin for 24 hours followed by treatment with interleukin-1β for 48 hours;cells in interleukin-1β+middle-dose formononetin group were treated with 50 μmol/L formononetin for 24 hours followed by treatment with interleukin-1β for 48 hours;cells in interleukin-1β+high-dose formononetin group were treated with 100 μmol/L formononetin for 24 hours followed by treatment with interleukin-1β for 48 hours;cells in interleukin-1β+miR NC group were treated with miR NC for 6 hours followed by treatment with interleukin-1β for 48 hours;cells in interleukin-1β+miR-135b-5p group were treated with miR-135b-5p mimics for 6 hours followed by treatment with interleukin-1β for 48 hours;cells in interleukin-1β+high dose formononetin+anti-miR-NC group were treated with anti-miR-NC for 6 hours,then treated with 100 μmol/L formononetin for 24 hours,and finally treate with interleukin-1β for 48 hours;cells in interleukin-1β+high-dose formononetin+anti-miR-135b-5p group were treated with anti-miR-135b-5p for 6 hours,the treated with 100 μmol/L formononetin for 24 hours,and finally treated with interleukin-1β for 48 hours. Relevant tests are performed after treatment. RESULTS AND CONCLUSION:The expression level of miR-135b-5p in cartilage tissue of patients with osteoarthritis was significantly lower than that of patients with simple meniscus injury (P<0.05). Compared with the normal control group,the expression level of miR-135b-5p,proliferative ability,activity of superoxid dismutase,and expression levels of collagenase Ⅱ protein and Bcl-2 protein in chondrocytes were lower in the interleukin-1β group (P<0.05),while apoptotic rate,lactate dehydrogenase activity,malondialdehyde level,levels of proinflammatory factors,and expression levels of matrix metalloproteinase-13 protein and Bax protein were higher in the interleukin-1β group (P<0.05). Formononetin inhibited chondrocyte damage caused by interleukin-1β in a concentration-dependent manner. Transfection of miR-135b-5p mimics elevated miR-135b-5p expression in the interleukin-1β group and inhibited chondrocyte damage induced by interleukin-1β;transfection of anti-miR-135b-5p decreased miR-135b-5p expression in the interleukin-1β+high-dose formononetin group and inhibited the effect of formononetin on chondrocytes. To conclude,the protective effect of formononetin on chondrocyte injury induced by interleukin-1β may be related to the regulation of miR-135b-5p expression.

Objective:To investigate the current status of the implementation of home-based phototherapy (HBPT) in patients with vitiligo, and to analyze management needs among patients receiving HBPT.Methods:A questionnaire survey was conducted on the application of HBPT among patients with vitiligo who visited the outpatient clinic of the Hospital for Skin Diseases, Chinese Academy of Medical Sciences from December 2021 to November 2022. Additionally, the popularization and usage of HBPT as well as needs of patient management were investigated and analyzed in these vitiligo patients.Results:A total of 496 valid questionnaires were collected from 496 patients with vitiligo (241 males [48.5%] and 255 females [51.5%]) . Their ages at visit ranged from 2 to 67 (30.87 ± 12.36) years. The most commonly affected sites were the head and face (52.2%) , followed by hair (32.1%) , hands and feet (31.4%) , trunk (30.2%) , limbs (24.3%) , neck (19.5%) , and perineum (9.9%) . Among the participants, 320 (64.5%) were currently using or had used HBPT, and 352 (70.8%) expressed a willingness to learn more about HBPT usage guidelines and health education. Regarding the repigmentation outcomes after HBPT: among 312 patients, 54 (17.3%) reported complete recovery, 64 (20.5%) were markedly improved, 142 (45.5%) experienced improvement, and 52 (16.7%) showed no response. Adverse reactions occurred in 223 patients (71.5%) , of whom 28 (9.0%) experienced severe adverse reactions. The most desired guiding information was the adjustment method for phototherapy dosage and treatment duration (184/352, 52.3%) ; the most effective way to receive health education information was through verbal education by medical staff (177/352, 50.3%) .Conclusion:For vitiligo patients who were willing to accept and use HBPT, the most desired guiding information was the adjustment method for phototherapy dosage and treatment duration, and verbal health education by medical staff appeared to be the main way to obtain health education information.

Purpose To investigate the sex differences of white matter damage in Alzheimer's disease(AD)and their association with cognitive impairment.Materials and Methods This retrospective study included 88 AD patients(48 females),71 amnestic mild cognitive impairment(aMCI)patients(39 females),and 95 healthy controls(63 females)recruited from the Memory Disorder Clinic at the First Affiliated Hospital of Anhui Medical University from September 2017 to July 2024.High-resolution three-dimensional T1 structure images and diffusion tensor imaging images were all obtained from each participant.The mean diffusivity(MD)and fractional anisotropy(FA)values of each white matter region were obtained,and the two-way ANOVA analysis was conducted to investigate brain regions with interaction effects between groups and sexes,those brain regions were then chosen as regions of interest for further correlation analysis with a series of cognitive scale scores.Results In terms of FA values,the right posterior corona radiata,right anterior limb of the internal capsule and left corticospinal tract showed interaction between sexes and cognitive groups(F=4.764,3.812,5.937,all P<0.05).The FA value of AD group was significantly lower than that of healthy control and aMCI group(all P<0.05),but there was no significant difference between healthy control and aMCI group(except the right anterior limb of the internal capsule,P=0.018).In AD group,FA values were significantly higher in women than in men in the previously described brain regions(all P<0.05),while there was no significant difference in FA values between male and female in healthy control and aMCI groups(except the left corticospinal tract,P<0.001).In terms of MD values,the right anterior limb of the internal capsule,right superior corona radiata and left external capsule showed interaction effect between sexes and cognitive groups(F=8.581,3.680,7.218,all P<0.05).The MD value of AD group was significantly higher than that of aMCI group(P<0.001),and aMCI group was higher than that of healthy control group(all P<0.05).In AD group,the MD values in the above brain regions were significantly higher in males than those in females(all P<0.01),while no significant difference was found between males and females in healthy control and aMCI groups(except for the left external capsule,P<0.05).For correlation analysis,the AD group was dimidiated into two groups by sex,the scores of the Montreal cognitive assessment,the Mini Mental state examination and the verbal fluency test of the female patient group were positively correlated with the FA values of the right posterior corona radiate(r=0.372,P=0.009;r=0.345,P=0.016;r=0.383,P=0.007),while the Mini Mental state examination and the verbal fluency test scores of female AD patient group were negatively correlated with the MD values of the right superior corona radiata(r=-0.360,P=0.012;r=-0.360,P=0.003).Conclusion Compared to the healthy control and MCI groups,white matter damage in AD patients shows sex differences and is associated with general cognitive and language functions impairment in female AD patients.

BACKGROUND:Formononetin is an isoflavonoid compound widely found in red clover,astragalus,and chickweed,which has the ability to inhibit oxidative stress,inflammatory factor release,and apoptosis. OBJECTIVE:To investigate the effect of formononetin on interleukin-1β-induced chondrocyte injury and its mechanism. METHODS:(1) Cartilage tissues from patients with osteoarthritis and patients with simple meniscus injury were collected,and real-time quantitative PCR was used to detect miR-135b-5p expression. (2) Human chondrocytes were cultured in vitro,and then divided them into nine groups:cells in normal control group were cultured for 48 hours with no treatment;cells in interleukin-1β group were treated with interleukin-1β for 48 hours;cells in interleukin-1β+low-dose formononetin group were treated with 25 μmol/L formononetin for 24 hours followed by treatment with interleukin-1β for 48 hours;cells in interleukin-1β+middle-dose formononetin group were treated with 50 μmol/L formononetin for 24 hours followed by treatment with interleukin-1β for 48 hours;cells in interleukin-1β+high-dose formononetin group were treated with 100 μmol/L formononetin for 24 hours followed by treatment with interleukin-1β for 48 hours;cells in interleukin-1β+miR NC group were treated with miR NC for 6 hours followed by treatment with interleukin-1β for 48 hours;cells in interleukin-1β+miR-135b-5p group were treated with miR-135b-5p mimics for 6 hours followed by treatment with interleukin-1β for 48 hours;cells in interleukin-1β+high dose formononetin+anti-miR-NC group were treated with anti-miR-NC for 6 hours,then treated with 100 μmol/L formononetin for 24 hours,and finally treate with interleukin-1β for 48 hours;cells in interleukin-1β+high-dose formononetin+anti-miR-135b-5p group were treated with anti-miR-135b-5p for 6 hours,the treated with 100 μmol/L formononetin for 24 hours,and finally treated with interleukin-1β for 48 hours. Relevant tests are performed after treatment. RESULTS AND CONCLUSION:The expression level of miR-135b-5p in cartilage tissue of patients with osteoarthritis was significantly lower than that of patients with simple meniscus injury (P<0.05). Compared with the normal control group,the expression level of miR-135b-5p,proliferative ability,activity of superoxid dismutase,and expression levels of collagenase Ⅱ protein and Bcl-2 protein in chondrocytes were lower in the interleukin-1β group (P<0.05),while apoptotic rate,lactate dehydrogenase activity,malondialdehyde level,levels of proinflammatory factors,and expression levels of matrix metalloproteinase-13 protein and Bax protein were higher in the interleukin-1β group (P<0.05). Formononetin inhibited chondrocyte damage caused by interleukin-1β in a concentration-dependent manner. Transfection of miR-135b-5p mimics elevated miR-135b-5p expression in the interleukin-1β group and inhibited chondrocyte damage induced by interleukin-1β;transfection of anti-miR-135b-5p decreased miR-135b-5p expression in the interleukin-1β+high-dose formononetin group and inhibited the effect of formononetin on chondrocytes. To conclude,the protective effect of formononetin on chondrocyte injury induced by interleukin-1β may be related to the regulation of miR-135b-5p expression.

OBJECTIVE To investigate the effects of borneol on pharmacodynamic and pharmacokinetic effects of Corydalis saxicola total alkaloids in depression model rats.METHODS Thirty male SD rats were divided into blank control group,negative control group,positive control group (fluoxetine 10 mg/kg,i.g.),single drug group (C.saxicola total alkaloids 210 mg/kg,i.g.) and combined drug group (C.saxicola total alkaloids 210 mg/kg+borneol 50 mg/kg,i.g.) according to the random number table method,with 6 rats in each group.By lipopolysaccharide (LPS) induction modeling,except blank control group (no model and no administration) received intraperitoneal injection of the same amount of normal saline,the rats in the other groups were intraperitoneally injected with LPS once a day to establish a rat model of depression.After 1 week of modeling,each administration group was given relevant drug intragastrically according to the corresponding dose,and blank control group and negative control group (without drug treatment) were administered intragastrically with an equal volume of solvent to dissolve the drug;continued modeling while administering the drug.After two weeks of continuous administration,the effects of C.saxicola total alkaloids versus the combination of C.saxicola total alkaloids and borneol on the behavior of depressed rats were tested by behavioral experiments;the levels of tumor necrosis factor-α,interleukin-1β and interleukin-6 in rats were determined;the histopathological changes of the hippocampus of rats were observed.Blood sample was collected from the orbit at different time points after administration on the 15th day,and the upper plasma was obtained.Ultra-performance liquid chromatography-triple quadrupole tandem mass spectrometry was established for the simultaneous determination of dehydrocarvedine,tetrahydropalmatine,coptisine,palmatine,jatrorrhizine,berberine,berberrubine and epiberberine in rat plasma.The average plasma concentration-time curve was depicted,the area under the curve (AUC) was calculated,and the pharmacokinetic parameters were analyzed by DAS 3.2.2 software.RESULTS Compared with blank control group,the negative control group had a decrease in body mass and sugar water preference rate,a decrease in the total distance of open field,a prolonged swimming immobility time,and a increased in the expression of inflammatory factors in serum (P<0.05);compared with negative control group,the single drug group and the combined drug group increased the preference rate of sugar water,increased the total distance of open field,shortened the time of swimming immobility,and decreased the expression of inflammatory factors in serum (P<0.05).There was no significant difference in the above indicators between the single drug group and the combined drug group in rats (P>0.05).Pharmacokinetic results showed that compared with single drug group,AUC0-t of coptisine,AUC0-t,AUC0-∞,tmax and cmax of jatrorrhizine,AUC0-t,AUC0-∞,t1/2 and cmax of berberrubine,and AUC0-t of epiberberine,cmax of dehydrocarvedine,cmax of palmatine were significantly increased in combined drug group,but there was no significant difference,indicating that borneol didn't have a significant effect on the efficacy of Corydalis saxicola nigra at this dose.CONCLUSIONS Both C.saxicola total alkaloids alone and in combination with borneol can improve depression-like behavior in depression model rats,reduce serum inflammatory cytokine levels,and protect hippocampal neurons.Compared with the use of Corydalis saxicola base alone,the combination with borneol do not show significant pharmacodynamic differences,bu can improve the absorption of coptisine,jatrorrhizine in model rats.