Metabolic dysfunction-associated steatotic liver disease (MASLD), the most prevalent chronic liver condition globally, lacks adequate and effective therapeutic remedies in clinical practice. Recent studies have increasingly highlighted the close connection between the ubiquitin-proteasome system (UPS) and the progression of MASLD. This relationship is crucial for understanding the disease's underlying mechanism. As a sophisticated process, the UPS govern protein stability and function, maintaining protein homeostasis, thus influencing a multitude of elements and biological events of eukaryotic cells. It comprises four enzyme families, namely, ubiquitin-activating enzymes (E1), ubiquitin-conjugating enzymes (E2), ubiquitin-protein ligases (E3), and deubiquitinating enzymes (DUBs). This review aims to delve into the array of pathways and therapeutic targets implicated in the ubiquitination within the pathogenesis of MASLD. Therefore, this review unveils the role of ubiquitination in MASLD while spotlighting potential therapeutic targets within the context of this disease.

BACKGROUND:Percutaneous kyphoplasty was a common surgical procedure for the treatment of osteoporotic vertebral compression fracture.However,there was no research to confirm whether percutaneous kyphoplasty could effectively correct the local kyphoplasty of the spine in patients over 80 years old with osteoporotic vertebral compression fracture.OBJECTIVE:To investigate the effect of percutaneous kyphoplasty on local kyphosis in super-aging patients with osteoporotic vertebral compression fracture.METHODS:Single-segment osteoporotic vertebral compression fracture patients treated with percutaneous kyphoplasty at the Department of Spinal Surgery,Peking University People's Hospital,from March 2016 to August 2022,were selected as the research cohort,and the follow-up data of patients in hospital and out-patient were collected.According to patients'age,patients were divided into the advanced age group(60-79 years old,n=126)and the super-aged group(＞80 years old,n=52).According to gender,body mass index,basic diseases(hypertension,diabetes,and cardiovascular diseases),fracture segments and the presence or absence of preoperative intravertebral cleft,the two groups of patients were matched 1:2 by propensity score matching.The lumbar CT values,injection amount of bone cement,preoperative and postoperative vertebral height,preoperative collapse rate of the vertebral body,preoperative and postoperative Cobb angle,recovery rate of Cobb angle,distance between the bone cement and anterior edge of the vertebral body,sagittal position of cement filling,contact between the bone cement and endplate,distance between the bone cement and vertebral endplates,bone cement distribution score,bone cement leakage,and vertebral refracture were compared between the two groups.RESULTS AND CONCLUSION:(1)After matching the propensity score,115 patients were included,with 71 patients in the advanced age group and 44 patients in the super-aged group.There was no statistically significant difference in baseline data,including gender,body mass index,hypertension ratio,diabetes ratio,cardiovascular disease ratio,fracture section,and preoperative intravertebral cleft,between the two groups(P＞0.05).The postoperative Cobb angle of the super-aged patients was significantly smaller than that of the elderly patients(P＜0.05).There was no significant difference in lumbar CT values,injection amount of bone cement,preoperative and postoperative vertebral height,preoperative collapse rate of the vertebral body,preoperative Cobb angle,recovery rate of Cobb angle,postoperative distance between the bone cement and anterior edge of the vertebral body,sagittal position of cement filling,contact between the bone cement and endplate,distance between the bone cement and vertebral endplates,bone cement distribution score,bone cement leakage,and vertebral refracture ratio between the two groups(P＞0.05).(2)These findings indicate that percutaneous kyphoplasty can effectively correct local kyphosis of the spine in super-aging patients with osteoporotic vertebral compression fractures.

In February 2025, a local cluster outbreak caused by the D8 genotype Measles virus (MV) was first discovered in Henan Province. Epidemiological investigations and laboratory testing were conducted, including the collection of serum and throat swabs for MV IgM antibody and nucleic acid detection, virus isolation and genetic homology analysis. Measures such as close contact tracing, vaccination rate assessment and supplementary immunization activities were implemented, successfully preventing broader community transmission. A total of three cases were reported during the outbreak, including one imported-related adolescent and two secondary local adult cases. All cases presented with typical symptoms such as fever and rash. Both adult cases were complicated by pneumonia, with one case developing into severe pneumonia. MV genotyping showed that the two secondary cases were both the D8 genotype, with the viral sequences being completely homologous to the Kazakhstan strain. Among the close contacts, 98.2% were adults, and 142 individuals received emergency vaccination.

In February 2025, a local cluster outbreak caused by the D8 genotype Measles virus (MV) was first discovered in Henan Province. Epidemiological investigations and laboratory testing were conducted, including the collection of serum and throat swabs for MV IgM antibody and nucleic acid detection, virus isolation and genetic homology analysis. Measures such as close contact tracing, vaccination rate assessment and supplementary immunization activities were implemented, successfully preventing broader community transmission. A total of three cases were reported during the outbreak, including one imported-related adolescent and two secondary local adult cases. All cases presented with typical symptoms such as fever and rash. Both adult cases were complicated by pneumonia, with one case developing into severe pneumonia. MV genotyping showed that the two secondary cases were both the D8 genotype, with the viral sequences being completely homologous to the Kazakhstan strain. Among the close contacts, 98.2% were adults, and 142 individuals received emergency vaccination.

BACKGROUND:Percutaneous kyphoplasty was a common surgical procedure for the treatment of osteoporotic vertebral compression fracture.However,there was no research to confirm whether percutaneous kyphoplasty could effectively correct the local kyphoplasty of the spine in patients over 80 years old with osteoporotic vertebral compression fracture.OBJECTIVE:To investigate the effect of percutaneous kyphoplasty on local kyphosis in super-aging patients with osteoporotic vertebral compression fracture.METHODS:Single-segment osteoporotic vertebral compression fracture patients treated with percutaneous kyphoplasty at the Department of Spinal Surgery,Peking University People's Hospital,from March 2016 to August 2022,were selected as the research cohort,and the follow-up data of patients in hospital and out-patient were collected.According to patients'age,patients were divided into the advanced age group(60-79 years old,n=126)and the super-aged group(＞80 years old,n=52).According to gender,body mass index,basic diseases(hypertension,diabetes,and cardiovascular diseases),fracture segments and the presence or absence of preoperative intravertebral cleft,the two groups of patients were matched 1:2 by propensity score matching.The lumbar CT values,injection amount of bone cement,preoperative and postoperative vertebral height,preoperative collapse rate of the vertebral body,preoperative and postoperative Cobb angle,recovery rate of Cobb angle,distance between the bone cement and anterior edge of the vertebral body,sagittal position of cement filling,contact between the bone cement and endplate,distance between the bone cement and vertebral endplates,bone cement distribution score,bone cement leakage,and vertebral refracture were compared between the two groups.RESULTS AND CONCLUSION:(1)After matching the propensity score,115 patients were included,with 71 patients in the advanced age group and 44 patients in the super-aged group.There was no statistically significant difference in baseline data,including gender,body mass index,hypertension ratio,diabetes ratio,cardiovascular disease ratio,fracture section,and preoperative intravertebral cleft,between the two groups(P＞0.05).The postoperative Cobb angle of the super-aged patients was significantly smaller than that of the elderly patients(P＜0.05).There was no significant difference in lumbar CT values,injection amount of bone cement,preoperative and postoperative vertebral height,preoperative collapse rate of the vertebral body,preoperative Cobb angle,recovery rate of Cobb angle,postoperative distance between the bone cement and anterior edge of the vertebral body,sagittal position of cement filling,contact between the bone cement and endplate,distance between the bone cement and vertebral endplates,bone cement distribution score,bone cement leakage,and vertebral refracture ratio between the two groups(P＞0.05).(2)These findings indicate that percutaneous kyphoplasty can effectively correct local kyphosis of the spine in super-aging patients with osteoporotic vertebral compression fractures.

DNMT3A encodes a DNA methyltransferase involved in development, cell differentiation, and gene transcription, which is mutated and aberrant-expressed in cancers. Here, we revealed that loss of DNMT3A promotes malignant phenotypes in lung cancer. Based on the epigenetic inhibitor library synthetic lethal screening, we found that small-molecule HDAC6 inhibitors selectively killed DNMT3A-defective NSCLC cells. Knockdown of HDAC6 by siRNAs reduced cell growth and induced apoptosis in DNMT3A-defective NSCLC cells. However, sensitive cells became resistant when DNMT3A was rescued. Furthermore, the selectivity to HDAC6 inhibition was recapitulated in mice, where an HDAC6 inhibitor retarded tumor growth established from DNMT3A-defective but not DNMT3A parental NSCLC cells. Mechanistically, DNMT3A loss resulted in the upregulation of HDAC6 through decreasing its promoter CpG methylation and enhancing transcription factor RUNX1 binding. Notably, our results indicated that HIF-1 pathway was activated in DNMT3A-defective cells whereas inactivated by HDAC6 inhibition. Knockout of HIF-1 contributed to the elimination of synthetic lethality between DNMT3A and HDAC6. Interestingly, HIF-1 pathway inhibitors could mimic the selective efficacy of HDAC6 inhibition in DNMT3A-defective cells. These results demonstrated HDAC6 as a HIF-1-dependent vulnerability of DNMT3A-defective cancers. Together, our findings identify HDAC6 as a potential HIF-1-dependent therapeutic target for the treatment of DNMT3A-defective cancers like NSCLC.

Objective To study the feasibility of using morphological changes of bronchioles and lymph nodes in rats for estimating the postmortem interval(PMI).Methods Thirty-five 8-week-old male SD rats were sacrificed by cervical dislocation and placed in a constant temperature and humidity box.Lung tissues of 5 rats were extracted at each time point within 24 hours after death for routine HE and PHH3 immunohistochemical staining.Image J was used to measure mucosal area,extramucosal area,luminal area of small bronchi,Then calculate the ratio of mucosal area to luminal area,extramucosal area to extramucosal,extramucosal area to mucosal area.imageJIHCprofiler was used to measure the positive degree of PHH3 immunohistochemical staining in lymph node nuclei,and the above calculation results and the positive degree of PHH3 staining were statistically analyzed by GraphPad Prism 9.5.Results The ratio of mucosal area to lumen area showed an overall downward trend with the increase of PMI(0h was statistically different compared with 18h and 24h,P<0.05).The ratio of extramucosal to lumen area and extramucosal to mucosa area showed an upward trend with the increase of PMI(0h was statistically different from other time points,P<0.05),the positive degree of PHH3 immunohistochemical staining was significantly decreased at 24 h after death(P<0.05).Conclusion The morphological changes of pulmonary bronchiole and lymph nodes showed a certain regularity within 24h after death,which was helpful to infer the early PMI,lymph node nucleus PHH3 was expected to be a critical index to distinguish early and late PMI.

Objective To study the feasibility of using morphological changes of bronchioles and lymph nodes in rats for estimating the postmortem interval(PMI).Methods Thirty-five 8-week-old male SD rats were sacrificed by cervical dislocation and placed in a constant temperature and humidity box.Lung tissues of 5 rats were extracted at each time point within 24 hours after death for routine HE and PHH3 immunohistochemical staining.Image J was used to measure mucosal area,extramucosal area,luminal area of small bronchi,Then calculate the ratio of mucosal area to luminal area,extramucosal area to extramucosal,extramucosal area to mucosal area.imageJIHCprofiler was used to measure the positive degree of PHH3 immunohistochemical staining in lymph node nuclei,and the above calculation results and the positive degree of PHH3 staining were statistically analyzed by GraphPad Prism 9.5.Results The ratio of mucosal area to lumen area showed an overall downward trend with the increase of PMI(0h was statistically different compared with 18h and 24h,P<0.05).The ratio of extramucosal to lumen area and extramucosal to mucosa area showed an upward trend with the increase of PMI(0h was statistically different from other time points,P<0.05),the positive degree of PHH3 immunohistochemical staining was significantly decreased at 24 h after death(P<0.05).Conclusion The morphological changes of pulmonary bronchiole and lymph nodes showed a certain regularity within 24h after death,which was helpful to infer the early PMI,lymph node nucleus PHH3 was expected to be a critical index to distinguish early and late PMI.

Humans ; COVID-19 ; Consensus ; SARS-CoV-2 ; China

Objective:To investigate the incidence and risk factors of human cytomegalovirus (HCMV) reactivation in immunocompetent severe pneumonia patients with mechanical ventilation and their effects on clinical outcomes.Methods:A prospective observational study was conducted. Forty-eight immunocompetent patients requiring invasive mechanical ventilation due to severe pneumonia in the department of critical care medicine of the First Affiliated Hospital of Guangzhou Medical University from June 30th, 2017 to July 1st, 2018 were enrolled. Meanwhile, all cases were followed up until 90 days after inclusion and were required to quantitatively detect HCMV DNA in serum at regular weekly intervals until 28 days after transferring to intensive care unit (ICU). Patients were divided into HCMV reactivation group (≥5×10 5 copies/L) and non-reactivation group (<5×10 5 copies/L) based on HCMV DNA at any time point within 28 days. Demographic data, basic indicators, respiratory indicators, disease severity scores, laboratory indicators, complication and clinical outcomes of the two groups were collected and analyzed. Multivariate Logistic regression analysis was performed to screen independent risk factors for HCMV reactivation. Results:All 48 subjects were tested positive for HCMV immunoglobulin G (IgG), so HCMV seropositive rate was 100%. HCMV reactivation occurred in 10 patients within 28 days after admission to ICU, and the reactivation incidence of HCMV was 20.83%. There was no significant difference in gender, age, body mass index (BMI), underling disease reasons for ICU transfer (except sepsis), basic vital signs, disease severity scores, or laboratory findings including infection, immune, blood routine, liver, kidney and circulatory indicators except neutrophils count (NEU), hypersensitivity C-reactive protein(hs-CRP), hemoglobin (Hb), blood urea nitrogen (BUN), N-terminal pro-brain natriuretic peptide (NT-proBNP) between the two groups. The height (cm: 160±6 vs. 166±8), body weight (kg: 49.4±11.2 vs. 57.6±10.5), Hb (g/L: 87±18 vs. 104±24) in HCMV reactivation group were significantly lower than non-reactivation group, as well as NEU [×10 9/L:12.7 (9.9, 22.5) vs. 8.9 (6.2, 13.8)], hs-CRP [mg/L: 115.5 (85.2, 136.6) vs. 39.9 (17.5, 130.2)], BUN [mmol/L:13.7 (8.9, 21.5) vs. 7.1 (4.9, 10.5)] and NT-proBNP [ng/L: 6 751 (2 222, 25 449) vs. 1 469 (419, 4 571)] within 24 hours of admission to ICU. The prevalence of sepsis [60.0% (6/10) vs. 15.8% (6/38)], blood transfusion [100.0% (10/10) vs. 60.5% (23/38)], hospitalization expense [ten thousand yuan: 35.7 (25.3, 67.1) vs. 15.2 (10.4, 22.0)], 90-day all-cause mortality [70.0% (7/10) vs. 21.1% (8/38)], length of ICU stay [days: 26 (16, 66) vs. 14 (9, 19)], the duration of mechanical ventilation [days: 26 (19, 66) vs. 13 (8, 18)] in HCMV reactivation group were significantly higher than non-reactivation group, and there were significant statistical differences between the two groups (all P < 0.05). Logistic regression analysis showed that sepsis was an independent risk factor for HCMV reactivation in immunocompetent mechanical ventilation severe pneumonia patients with mechanical ventilation [odds ratio ( OR) = 9.35, 95% confidence interval (95% CI) was 1.72-50.86, P = 0.010]. Conclusions:HCMV infection is very common in immunocompetent severe pneumonia patients on mechanical ventilation and incidence of HCMV reactivation is high. Moreover, HCMV reactivation could adversely affect clinical prognoses, and sepsis may be a risk factor for HCMV reactivation.