Background/Aims: Metabolic dysfunction–associated steatotic liver disease (MASLD) is a chronic liver disease characterized by hepatic steatosis. Ubiquitin-specific protease 29 (USP29) plays pivotal roles in hepatic ischemiareperfusion injury and hepatocellular carcinoma, but its role in MASLD remains unexplored. Therefore, the aim of this study was to reveal the effects and underlying mechanisms of USP29 in MASLD progression. Methods: USP29 expression was assessed in liver samples from MASLD patients and mice. The role and molecular mechanism of USP29 in MASLD were assessed in high-fat diet-fed and high-fat/high-cholesterol diet-fed mice and palmitic acid and oleic acid treated hepatocytes. Results: USP29 protein levels were significantly reduced in mice and humans with MASLD. Hepatic steatosis, inflammation and fibrosis were significantly exacerbated by USP29 deletion and relieved by USP29 overexpression. Mechanistically, USP29 significantly activated the expression of genes related to fatty acid β-oxidation (FAO) under metabolic stimulation, directly interacted with long-chain acyl-CoA synthase 5 (ACSL5) and repressed ACSL5 degradation by increasing ACSL5 K48-linked deubiquitination. Moreover, the effect of USP29 on hepatocyte lipid accumulation and MASLD was dependent on ACSL5. Conclusions USP29 functions as a novel negative regulator of MASLD by stabilizing ACSL5 to promote FAO. The activation of the USP29-ACSL5 axis may represent a potential therapeutic strategy for MASLD.

Background/Aims: Metabolic dysfunction–associated steatotic liver disease (MASLD) is a chronic liver disease characterized by hepatic steatosis. Ubiquitin-specific protease 29 (USP29) plays pivotal roles in hepatic ischemiareperfusion injury and hepatocellular carcinoma, but its role in MASLD remains unexplored. Therefore, the aim of this study was to reveal the effects and underlying mechanisms of USP29 in MASLD progression. Methods: USP29 expression was assessed in liver samples from MASLD patients and mice. The role and molecular mechanism of USP29 in MASLD were assessed in high-fat diet-fed and high-fat/high-cholesterol diet-fed mice and palmitic acid and oleic acid treated hepatocytes. Results: USP29 protein levels were significantly reduced in mice and humans with MASLD. Hepatic steatosis, inflammation and fibrosis were significantly exacerbated by USP29 deletion and relieved by USP29 overexpression. Mechanistically, USP29 significantly activated the expression of genes related to fatty acid β-oxidation (FAO) under metabolic stimulation, directly interacted with long-chain acyl-CoA synthase 5 (ACSL5) and repressed ACSL5 degradation by increasing ACSL5 K48-linked deubiquitination. Moreover, the effect of USP29 on hepatocyte lipid accumulation and MASLD was dependent on ACSL5. Conclusions USP29 functions as a novel negative regulator of MASLD by stabilizing ACSL5 to promote FAO. The activation of the USP29-ACSL5 axis may represent a potential therapeutic strategy for MASLD.

Background/Aims: Metabolic dysfunction–associated steatotic liver disease (MASLD) is a chronic liver disease characterized by hepatic steatosis. Ubiquitin-specific protease 29 (USP29) plays pivotal roles in hepatic ischemiareperfusion injury and hepatocellular carcinoma, but its role in MASLD remains unexplored. Therefore, the aim of this study was to reveal the effects and underlying mechanisms of USP29 in MASLD progression. Methods: USP29 expression was assessed in liver samples from MASLD patients and mice. The role and molecular mechanism of USP29 in MASLD were assessed in high-fat diet-fed and high-fat/high-cholesterol diet-fed mice and palmitic acid and oleic acid treated hepatocytes. Results: USP29 protein levels were significantly reduced in mice and humans with MASLD. Hepatic steatosis, inflammation and fibrosis were significantly exacerbated by USP29 deletion and relieved by USP29 overexpression. Mechanistically, USP29 significantly activated the expression of genes related to fatty acid β-oxidation (FAO) under metabolic stimulation, directly interacted with long-chain acyl-CoA synthase 5 (ACSL5) and repressed ACSL5 degradation by increasing ACSL5 K48-linked deubiquitination. Moreover, the effect of USP29 on hepatocyte lipid accumulation and MASLD was dependent on ACSL5. Conclusions USP29 functions as a novel negative regulator of MASLD by stabilizing ACSL5 to promote FAO. The activation of the USP29-ACSL5 axis may represent a potential therapeutic strategy for MASLD.

AIM: To quantitatively evaluate the clinical characteristics of haze after transepithelial photorefractive keratectomy(TPRK)for astigmatism using corneal densitometry.METHODS:In this retrospective clinical study, a total of 74 patients(106 eyes)with astigmatism ≥1.25 D who underwent TPRK in our hospital from October 2022 to December 2024 were continuously collected. All of the study subjects were divided into transparent group(65 eyes)and haze group(41 eyes)based on whether haze occurred after surgery. Pentacam examination was performed before and after surgery, and corneal densitometry was recorded at the time points of preoperation, 1 mo postoperation in the transparent group and the most severe haze degree in the haze group. The collected corneal densitometry included the average densitometry of the entire corneal layer in the central 2 mm, 2-6 mm, and 6-10 mm areas, as well as the average densitometry of the entire layer of the corneal section in the center 6 mm of the astigmatism axis(astigmatism expressed in negative cylindrical form)and orthogonal axis(the axis perpendicular to the astigmatism axis), and the average densitometry of the entire layer of the corneal section in the nasal and temporal 2-6 mm areas of the astigmatism axis in the haze group of patients with regular astigmatism. The change in corneal densitometry after surgery compared with that before surgery was calculated.RESULTS:There was no statistically significant difference in baseline data such as gender, age, and spherical equivalent between the transparent group and the haze group(all P>0.05). The change in corneal densitometry in the 2-6 mm area of the haze group was greater than that in the transparent group(Z=-2.226, P=0.026), while there was no significant difference in the change of corneal densitometry in the central 2 mm and 6-10 mm areas between the two groups(both P>0.05). There was no significant difference in the change of corneal densitometry between the transparent group and haze group along the orthogonal axis(all P>0.05), while the change of corneal densitometry in the haze group along the astigmatism axis was greater than that in the transparent group(Z=-2.371, P=0.018). The temporal corneal densitometry of patients with regular astigmatism in the haze group after surgery was higher than that of the nasal side, and the change in corneal densitometry was also greater than that of the nasal side(Z=-4.288, P<0.001; Z=-4.043, P<0.001).CONCLUSION:Unlike spherical correction for myopia and hyperopia, haze after TPRK for astigmatism was mainly manifested in the peripheral cutting area of the astigmatism axis, and patients with regular astigmatism had a higher probability or severity of haze on the temporal side of the astigmatism axis than on the nasal side.

ObjectiveTo characterize the seasonal patterns of influenza in Kunming City, Yunnan Province before, during, and after the COVID-19 pandemic, and provide scientific evidence for optimizing influenza prevention and control strategies. MethodsInfluenza-like illness (ILI) and etiological surveillance data for influenza from the 14^th week of 2010 to the 13^th week of 2024 in Kunming City of Yunnan Province were collected. Harmonic regression models were constructed to analyze the epidemic characteristics and seasonal patterns of influenza before (2010/2011‒2019/2020 influenza seasons), during (2020/2021‒2022/2023 influenza seasons), and after (2023/2024 influenza season) the COVID-19 pandemic. ResultsBefore the COVID-19 pandemic, influenza in Kunming City mainly exhibited an annual cyclic pattern without a significant semi-annual periodicity, peaking from December to February of the next year, with an epidemic duration of 20‒30 weeks. During the pandemic, influenza seasonality shifted, with an increase in semi-annual periodicity and an approximate one month delay in annual peaks. However, after the pandemic, the annual amplitude of influenza increased compared with that before the pandemic, and the epidemic duration extended by about one month. Although the annual peak largely reverted to the pre-pandemic levels, the annual peaks for different influenza subtypes/lineages had not fully recovered. ConclusionInfluenza seasonality in Kunming City underwent substantial alterations following the COVID-19 pandemic and has not yet fully reverted to pre-pandemic levels. Continuous surveillance on different subtypes/lineages of influenza viruses remains essential, and prevention and control strategies should be adjusted and optimized in a timely manner based on current epidemic trends.

Objective To analyze micronucleus abnormalities in the peripheral blood lymphocytes of industrial radiation workers and the influencing factors, and to provide a reference for radiation protection. Methods The occupational health monitoring data of 661 industrial radiation workers were collected from the occupational health examination system of Gansu Provincial Center for Disease Control and Prevention. The abnormalities in the micronucleus of peripheral blood lymphocytes were analyzed. The influencing factors were identified by logistic regression. Results The micronucleus abnormality rate was 6.05% for the 661 industrial radiation workers. There was no significant difference in micronucleus abnormality rate between sexes (P > 0.05). Comparison of age groups showed that the rate of micronucleus abnormality increased with age, and workers over 50 years of age has the highest rate of micronucleus abnormalities (17.81%); there was a significant difference between age groups (P < 0.05). There was a significant difference in micronucleus abnormality rate between occupational categories (P < 0.05). There was a significant difference in micronucleus abnormality rate between groups with different years of work (P < 0.05). Logistic regression analysis showed that age and years of work were the risk factors for micronucleus abnormality rate (P < 0.05); age was an independent risk factor for micronucleus abnormality rate (P < 0.05). Conclusion The effect of low-dose ionizing radiation on micronucleus abnormality rate of industrial radiation workers is related to age and working years. Attention should be paid to occupational health monitoring of radiation workers, especially those with advanced age.

Objective:To explore the effects of Jianpi Bushen Jiedu Prescription on the proliferation and migration of hepatocellular carcinoma cells; To discuss its possible mechanism.Methods:Using human highly metastatic liver cancer cell line (HCCLM3) as the research object, they were randomly divided into control group and TCM group (100, 200, 400, 800, 1 600, 3 200 μg/ml Jianpi Bushen Jiedu Prescription) and Western medicine group (2.5, 5, 10, 20, 40 μmol/L sorafenib) using a random number table method. Cell viability was detected using cell counting reagent (CCK-8) method; HCCLM3 cells were divided into control group and TCM (Jianpi Bushen Jiedu Prescription 800 μg/ml) group and combined group (Jianpi Bushen Jiedu Prescription 800 μg/ml +sorafenib 20 μmol/L). Western blot method was used to detect the protein expressions of kinase/signaling transducer and transcriptional activator (JAK2/STAT3) pathway related proteins (p-JAK2, JAK2, p-STAT3, STAT3) in each group.Results:Compared with the control group, viability and mobility of HCCLM cell in TCM group and Western medicine group decreased ( P<0.01 or P<0.05); compared with the control group, the protein expressions of P-JAK2, JAK2, P-STAT3 and STAT3 in the TCM group and the combined group decreased ( P<0.05), and the JAK2 protein expression in the combined group was lower than that in the TCM group ( P<0.05). Conclusion:Jianpi Bushen Jiedu Prescription can inhibit the proliferation and migration of HCC cells by regulating JAK2/STAT3 pathway.

Objective To study the effective fraction and mechanism of Lycium barbarum leaves on improving learning and memory ability of subacute aging mice induced by D-galactose injection.Methods The model of subacute aging mice was developed by injection of D-galactose subcutaneously,and different extracts of Lycium barbarum leaves were prepared.The effects of the extracts of Lycium barbarum leaves on the learning and memory ability of model mice were evaluated by Y maze experiment and new object recognition experiment.The pathomorphological changes of hippocampus in mice were observed by hematoxylin-eosin and Nissl staining.The levels of brain-derived neurotrophic factor(BDNF),nerve growth factor(NGF),glial cell line-derived neurotrophic factor(GDNF),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),interferon-γ(IFN-γ)and interleukin-10(IL-10)in hippocampus of mice were detected by enzyme-linked immunosorbent assay.The activities of superoxide dismutase(SOD)and the contents of glutathione(GSH)and malondialdehyde(MDA)in hippocampus of mice were detected by related assay kits.Detection of apoptosis in the hippocampal region of mouse brain tissue using the TUNEL method.Western blotting analysis was used to detect the expressions of antioxidant proteins Nrf2,HO-1 and apoptotic proteins Caspase-3,Caspase-9 in hippocampus of mice.Results The water extraction part and 80%alcohol precipitation supernatant part of Lycium barbarum leaves significantly improved the learning and memory ability of model mice,improved the pathological damage of hippocampus in mice,increased the number of Nissl bodies in hippocampus of mice,and promoted the expression of neurotrophic factors BDNF,NGF and GDNF,and promoted the expression of neurotrophic factors BDNF,NGF and GDNF.Pro-inflammatory factors TNF-α,IL-1β and IFN-γ expression declines while anti-inflammatory factor IL-10 expression rises.The activity of SOD and the expression of GSH were increased,and the expression of MDA was decreased.Increase the expression of Nrf2 and HO-1 antioxidant proteins;reduce the expression of Caspase-3 and Caspase-9 apoptosis pathway proteins.Inhibition of apoptosis in the hippocampal region of mouse brain tissue using a model.Conclusion The water extracts and 80%alcohol precipitation supernatant extracts of Lycium barbarum leaves are the effective fractions of Lycium barbarum leaves to improve the learning and memory ability of D-galactose-induced subacute aging mice,and its mechanism might be related to the inhibition of neuronal apoptosis caused by oxidative stress and inflammation.

Objective Explore the impact of long-term blood glucose fluctuations and blood glucose control on the stroke incidence in patients with type 2 diabetes mellitus(T2DM).Methods An observa-tional cohort of patients with T2DM was established based on"Shanghai Community Chronic Disease Health Management Service Objects"on October 1st,2018.Follow-ups were conducted every three months,and fasting blood glucose(FBG)were tested at each visit.Basic epidemiological data were collected via the Shanghai Community Health Management Information Platform or survey questionnaires,and stroke incidents were gathered via the"Shanghai Cardio-Cerebrovascular Event Monitoring System".The first reported stroke incident within the observation period was considered.The observational deadline was December 31st,2021.Standard deviation of FBG was used to evaluate blood glucose fluctuation and FBG control rate was used to reflect blood glucose control status.Cox Proportional Hazards Model was utilized to analyze the impacts.Results The cumulative observation time was 91,826.1 person-years for the study,in which there were 1785 cases of stroke events observed,implying a cumulative incidence of 5.73%and incidence rate of 1943.9/100000 person-years.The mean number of follow-ups(10.29±3.07)per patient was recorded.The details of the stroke cases were as follows:transient ischemic attacks(n=111,6.22%),non-lacunar brain infarctions(n=754,42.24%),lacunar brain infarctions(n=798,44.71%),intracerebral hemorrhages(n=80,4.48%),non-intracerebral hemorrhages(n=8,0.45%),subarachnoid hemorrhages(n=12,0.67%),and unclassified strokes(n=22,1.23%).After excluding subjects with less than five follow-ups,the Cox Proportional Hazards Model suggested that increased standard deviation of FBG was an independent risk factor for the first stroke incident,and an increased blood glucose control rate was an independent protective factor.Both the standard deviation of FBG and the blood glucose control rate were not correlated with stroke recurrence.Conclusion Long-term blood glucose fluctuations and blood glucose control can predict the risk of a first stroke in patients with T2DM.The relationship between blood glucose fluctuations,blood glucose management,and stroke recurrence requires further studies.

Objective To investigate the effect of cinobufacini on inhibiting colorectal cancer metastasis by regula-ting the polarization of M2 macrophages.Methods THP-1 was induced into M0 type macrophages.The condi-tioned medium of HCT116 cells was collected to stimulate M0 type macrophages.The polarization of M2 type mac-rophages was observed by flow cytometry,real-time quantitative PCR and ELISA experiments.The conditioned me-dium of M0 type macrophages and HCT116-Mφ cells was collected to stimulate HCT116 cells.The ability of migra-tion and invasion was observed by wound healing assay and Transwell assay.The effect of cinobufacini on the via-bility of HCT116 cells was detected by CCK-8 assay.The conditioned medium of HCT116 and HCT116+cinobufa-cini was collected to stimulate M0 type macrophages.The polarization of M2 type macrophages was observed by flow cytometry,real-time quantitative PCR and ELISA experiments.The conditioned media of HCT116-Mφ cells and(HCT116+cinobufacini)-Mφ cells were collected to stimulate HCT116 cells.The changes of migration and inva-sion ability were observed by wound healing assay and Transwell assay.Results After stimulation of M0 type mac-rophages in HCT116 cell conditioned medium,the morphology of M0 macrophages turned into fusiform cells,the proportion of CD11b+CD206+cells increased,and the expression of M2 macrophage markers IL-10 and TGF-β in-creased.The migration and invasion ability of HCT116 cells were significantly enhanced after stimulation in the conditioned medium of HCT1 16-Mφ cells.After the addition of cinobufacini,not only the polarization proportion of M2 macrophages decreased,but also the metastatic effect mediated by M2 macrophages was inhibited.Conclusion HCT116 cells can induce the polarization of M2 macrophages,while cinobufacini can inhibit the tumor metastasis mediated by M2 macrophages by inhibiting the polarization of M2 macrophages.