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.

In clinical, manually scoring by technician is the major method for sleep arousal detection. This method is time-consuming and subjective. This study aimed to achieve an end-to-end sleep-arousal events detection by constructing a convolutional neural network based on multi-scale convolutional layers and self-attention mechanism, and using 1 min single-channel electroencephalogram (EEG) signals as its input. Compared with the performance of the baseline model, the results of the proposed method showed that the mean area under the precision-recall curve and area under the receiver operating characteristic were both improved by 7%. Furthermore, we also compared the effects of single modality and multi-modality on the performance of the proposed model. The results revealed the power of single-channel EEG signals in automatic sleep arousal detection. However, the simple combination of multi-modality signals may be counterproductive to the improvement of model performance. Finally, we also explored the scalability of the proposed model and transferred the model into the automated sleep staging task in the same dataset. The average accuracy of 73% also suggested the power of the proposed method in task transferring. This study provides a potential solution for the development of portable sleep monitoring and paves a way for the automatic sleep data analysis using the transfer learning method.
Sleep ; Sleep Stages ; Arousal ; Data Analysis ; Electroencephalography

Background: and Purpose This study aimed to determine the changes in cerebral blood flow (CBF) in patients who received different durations of hemodialysis (HD) using arterial spin labeling magnetic resonance imaging. Methods: The study included 46 patients who received HD and 24 demographically similar healthy controls (HCs). Patients who received HD were divided into three subgroups based on its duration: HD-1 (n=15, dialysis duration ≤24 months), HD-2 (n=16, dialysis duration >24 and ≤72 months), and HD-3 (n=15, dialysis duration ≥73 months). All subjects completed the Mini Mental State Examination and Montreal Cognitive Assessment tests, and the patients who received HD underwent laboratory tests. Group-level differences in the global and regional CBFs between patients who received HD and HCs were assessed. Correlation analysis was performed to evaluate the associations among CBF, clinical variables, and cognitive function. Results: Compared with HCs, global and regional CBFs were significantly increased in the HD-1 and HD-2 groups (p<0.05), but there was no significant difference in the HD-3 group (p>0.05). However, compared with the HD-1 group, the HD-3 group had significantly decreased global and regional CBFs (p<0.05). The cognitive function was worse in patients who received long-term HD than in HCs. Increased dialysis duration and hemoglobin level were predictive risk factors for decreased CBF in patients who received long-term HD. Conclusions Patients who received long-term HD with normal CBF had worse cognitive function, which may be related to increased dialysis duration.

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.

Inhibition of human epidermal growth factor receptor 2 mediated cell signaling pathway is an important therapeutic strategy for HER2-positive cancers. Although monoclonal antibodies are currently used as marketed drugs, their large molecular weight, high cost of production and susceptibility to proteolysis could be a hurdle for long-term application. In this study, we reported a strategy for the development of artificial antibody based on

Objective: To investigate the optimal duration of pegylated-alpha interferon (Peg-INFα) combined with ribavirin (RBV) in treating chronic hepatitis C infection in human immunodeficiency virus (HIV)-infected patients. Methods: A multicenter prospective study was conducted. The study subjects were divided into two groups; HIV/HCV co-infections (Group A, n = 158) and control with HCV-monoinfections (Group B, n = 60). All recruited patients received standard Peg-INFα plus RBV therapy. Group A was divided into 3 subgroups according to CD4⁺ cell counts: A1 subgroup, 79 cases, CD4⁺ counts > 350 cells /μl, who received anti-HCV before combination antiretroviral therapy(cART); A2 subgroup, 45 cases, CD4⁺ counts between 200 and 350 cells/μl, who did not start anti-HCV until they could tolerate cART well; A3 subgroup, 34 cases, CD4⁺ counts < 200 cells /μl, cART was administered first, and anti-HCV therapy was started when CD4⁺ counts > 200 cells/μl. The anti-HCV efficacy of two groups and 3 subgroups were compared. Statistical analysis for normal distribution and homogeneity of variance data was calculated by t-test and the counting data was analyzed by χ ² test. The Mann-Whitney U test was used for non-normal data. A one-way analysis of variance (ANOVA) was used for the comparison of multiple groups, followed by SNK method. Multiple independent samples were used for non-parametric tests. Results: There was no significant difference in age and baseline HCV RNA levels between groups and subgroups (P > 0.05). By an intent-to-treat (ITT) analysis, in Group A, the ratio of complete early virological response (cEVR) rate was 75.3% (119/158), the ratio of end of treatment virological response (eTVR) rate was 68.4% (108/158), and the ratio of sustained virological response (SVR) rate was 48.7% (77/158); in Group B, the ratio of cEVR rate was 93.3% (56/60), the ratio of eTVR rate was 90.0% (54/60), and the ratio of SVR rate was 71.7% (43/60); The therapeutic index of Group A were lower than those of Group B (P≤0.05). By per-protocol (PP) analysis, the ratio of cEVR rate in Group A [75.2% (88/112)] was still lower than that in Group B [93.3% (56/60)], but no significant differences were found in the ratio of eTVR rate and SVR rate between 2 groups (P > 0.05). Comparing the efficacy of subgroups (A1, A2 and A3) by ITT analysis, the ratios of cEVR rate were respectively 78.5% (62/79), 75.6% (34/45) and 67.6% (23/34); the ratios of eTVR rate were respectively 68.4%(54/79), 80.0%(36/45)and 52.9%(18/34); and the ratios of SVR rate were respectively 41.8%(33/79), 64.4%(29/45)and 44.1%(15/34). The ratio of eTVR in subgroup A2 was obviously higher than that in subgroup A3 and the ratio of SVR in subgroup A2 was statistically higher than that of subgroup A1(P≤0.05). However, by PP analysis, no significant differences of the therapeutic indexes were found among the respective subgroups (P > 0.05). Conclusion HIV-HCV co-infected patients would have better anti-HCV efficacy with Peg-INFα-2a plus RBV than HCV- monoinfected patients. The best time for initiating anti-HCV therapy in HIV-HCV co-infected patients is when CD4⁺ counts 200 cells/ μl.

Objective To explore the diagnostic value of Talaromyces marneffei (T.marneffei)-specific mannose glycoprotein Mp1p antigen for T.marneffei infection in acquired immune deficiency syndrome (AIDS) patients.Methods All cases were recruited in this study from January 2012 to June 2015 in Guangzhou No.8 People′s Hospital, including 184 AIDS patients with T.marneffei infection confirmatively diagnosed by culture, and 205 controls including 176 AIDS patients without T.marneffei infection and 29 health controls.Double antibody sandwich enzyme linked immunosorbent assay and fluoroimmunoassay combined with double-antibody sandwich were both utilized to detect serum Mp1p antigen levels, and their sensitivity and specificity for diagnosing T.marneffei infection in patients with AIDS were analyzed.x2 test and t test were used for statistical analysis.Results The ratio of males to females and age of the study group were both comparable to those of the control group (x2=0.019, P=0.889;t=1.810,P=0.07, respecitvley).The sensitivities of double antibody sandwich enzyme linked immunosorbent assay and fluoroimmunoassay combined with double-antibody sandwich were 82.07%(151/184) and 83.15%(153/184), respectively (x2=0.076, P=0.783).The specificities were 93.17%(191/205) and 92.68%(190/205), respectively (x2=0.037, P=0.847).The accuracy values were 87.92%(342/389) and 88.17%(343/389), respectively (x2=0.012, P=0.912).The false positive rates were 6.83%(14/205) and 7.32%(15/205), respectively.The false negative rates were 17.93%(33/184) and 16.85%(31/184), respectively (x2=0.049, P=0.829).The positive predictive values were 91.52%(151/165) and 91.07%(153/168), respectively (x2=0.021, P=0.886).The negative predictive values were 85.27%(191/224) and 85.97%(190/221), respectively (x2=0.045, P=0.832).The Kappa values were 0.83 and 0.80, respectively.Conclusion Detection of serum Mp1p antigen of T.marneffei possesses high specificity and sensitivity, which may be utilized for rapid and early diagnosis of T.marneffei infection in patients with AIDS.

Objective To investigate the prevalence and characteristics of non-nucleoside reverse transcriptase inhibitors (NNRTIs)resistance-related gene mutations among the AIDS patients with virological suppression failure in Guangdong Province 2015.Methods Plasma samples from AIDS patients receiving highly active antiretroviral therapy for more than one year with viral loads > 1000 copies/mL from Guangdong province (except Shenzhen)were collected from January to December 2015.Total 612 HIV-1 gene fragments were amplified from plasma samples using self-developed lab method.Sub-genotypes were determined by phylogenetic tree according to the sequences,NNRTIs resistance-related mutations were determined in Stanford University HIV-1 Drug Resistance Database. The NNRTIs-resistance, the relationships of NNRTIs resistance-related mutations with baseline CD4 +T lymphocyte counts,transmission routes,antiviral regimens and HIV-1 genotypes were analyzed.SPSS 17.0 software was used to analyze the data.Results In 612 patients with virological suppression failure,the main NNRTIs resistance-related mutations were K103 (26.80%),Y181 (14.71 %),V179 (13.73%),G190 (11 .44%) and V106 (10.62%).The susceptibility rate of 310 patients (50.65%)to NNRTIs had changed,the highly resistant rate to nevirapine was 49.51 %,which was higher than that of efavirenz (43.14%),etravirine (5.56%) and rilpivirine (12.25%),respectively,and the differences were statistically significant (χ2 =5.00,296.3 and 198.0,all P <0.05).The incidence rate of drug resistance in patients with baseline CD4 +T lymphocyte counts >200 cells/μL was lower than that in those with baseline CD4 +T lymphocyte counts <200 cells/μL (χ2 =17.93,P <0.01 );the incidence rate of drug resistance was lower in intravenous drug abusers than that of sexually transmitted patients (χ2 =44.21 ,P <0.01 );while the incidence of drug resistance in patients receiving NVP-containing regimens was higher than that in those receiving EFV-containing regimens (χ2 =8.93,P <0.01 ),and the incidence rate was higher in patients with CRF01 _AE than that in those with CRF07_BC and CRF08 _BC (χ2 =8.46 and 8.47,P <0.01 ).Conclusions The results suggest that compliance education and follow-up should be strengthened in patients with high baseline CD4 +T lymphocyte counts and intravenous drug users,and patients with liver diseases should avoid using drugs containing NVP regimens.

Objective To evaluate the efficacy and safety of HLA identical and haploidentical related allogeneic hematopoietic stem cell trans?plantation in the treatment of acute myeloid leukemia(AML)and myelodysplastic syndrome(MDS). Methods A total of 21 patients with AML and 8 patients with MDS who underwent allogeneic hematopoietic stem cell transplantation in our hospital from April 2011 to April 2016 were ana?lyzed retrospectively,including 16 cases of HLA?identical allogeneic HSCT,10 cases of haploidentical allogeneic HSCT,and 3 cases of syngeneic HSCT. BUCY2 or TBI plus CY ± chemotherapeutic agents was the regular conditioning regimen. No graft versus host disease(GVHD)prophylax?is was required for syngeneic HSCT,but cyclosporine in combination with methotraxate was essential for allogeneic HSCT,cyclosporine,methotrax?ate,antithymocyte globulin,mycophenolate mofetil and glucosteroids for haploidentical HSCT. Results All patients achieved fully donor?originat?ed hematopoiesis. Two patients died of severe acute GVHD within 100 days post HSCT. Acute GVHD with gradeⅡ?Ⅳoccurred in 23.1%(6/26) patients,chronic GVHD in 50%patients,therapy and relapse?relevant mortality was 4/29(13.8%)and 6/29(20.7%)cases within a median follow?up of 23(1?60)months,respectively. Two?year overall survival and leukemia free survival rates are 68.09%( 95%CI:45.77%?82.78%)and 60.22%(95%CI:38.19%?76.55%),respectively. High risk AML is still the main challenge to long?term leukemia free survival. Conclusion HLA identical and haploidentical allogeneic HSCT for AML and MDS is safe ,effective and feasible. Minimal residual disease monitoring and pre?ventative as well as preemptive intervention is necessary for improving prognosis of high risk AML.

ObjectiveTo observe andanalyze the clinical efficacy of needle knife treatment for knee meniscus injury from improving knee biomechanical balance and to provide a therapeutic basis and method for clinical practice.MethodOne hundred patients (112 knees) with knee meniscus injury meeting the inclusion criteria were allocated, in order of visits, to observation and control groups, 50 cases each. They were treated with a needle knife and an injection of sodium hyaluronate injectio into knee joint cavity, respectively. Changes in the indices were observed and assessed in the two groups by recording the plantar pressure analysis score and the knee function score before and after treatment and at follow-up. The clinical therapeutic effects were evaluated in the two groups.ResultThemaximum load, time integral difference value and load ratio around the knee joint decreased significantly in both observation and control groups after treatment and at follow-up (P<0.05). The regulating effect on knee joint force balance was better in theneedle knife group than in the control group (P<0.05). The improving effect on knee joint function was significantly better in the observation group than in the control group (P<0.01). The excellence rate was significantly higher in the observation groupthan in the control group after treatment and at follow-up (P<0.05).ConclusionNeedle knife treatment restores the function of the knee joint by loosing focal soft tissues around the knee joint, improving knee joint load imbalance and correcting the mechanical equilibrium around the knee joint in patient with knee meniscus injury. It has a definite curative effect on the disease.