Metabolic associated fatty liver disease （MAFLD） is the most prevalent chronic liver disease worldwide， and its progression is closely associated with the development of liver fibrosis， liver cirrhosis， and even hepatocellular carcinoma. However， there is still a lack of effective therapies for MAFLD in clinical practice. Telomere is the protective structure at the end of chromosomes， and telomere shortening and functional impairment have been identified as one of the key factors regulating the pathological progression of MAFLD. This article systematically reviews the core mechanism of action of telomere regulation in MAFLD， including its molecular functions in nucleotide metabolism， oxidative stress， and epigenetic regulation， as well as its pathological effect in hepatocytes and hepatic stellate cells. In addition， this article explores the clinical prospects of telomeres as biomarkers and therapeutic targets for MAFLD， in order to provide a theoretical reference for improving the precise diagnosis and treatment system of MAFLD.

Objective:To explore the efficacy of intensive repetitive transcranial magnetic stimulation (irTMS) in treatment-resistant depression (TRD) and its impact on cognitive function and systemic immune-inflammation index (SII).Methods:Forty-eight TRD patients were divided into observation group and control group using random number table method, with 24 patients in each group. The observation group was treated with irTMS, and the stimulation site was the left dorsolateral prefrontal lobe. The stimulation intensity was 110% of the motor threshold, and the stimulation frequency was 15 Hz. The stimulation interval was 26 s, and 3 000 pulses were stimulated each time. Stimulating 5 times per day, with an interval of 50 min, and continuous treatment for 5 days. The total stimulation amount for 5 days was 75 000 pulses. The control group was treated with pseudo stimulation. Before treatment (T0), 5 days after treatment (T1), and 1 month after treatment (T2), 17-item Hamilton depression scale (HAMD-17) was used to assess depressive mood. Evaluating cognitive function using the Wisconsin card sorting test.A fully automated blood cell analyzer was used to detect platelet count (PLT), neutrophil count (NC), and lymphocyte count (LC), calculate the systemic immune inflammation index (SII), SII=PLT × NC/LC. Statistical analysis was conducted using SPSS 20.0 software. The comparison between two sets of repeated measurement data was performed using repeated measurement analysis of variance.Simple effect analysis was performed if the interaction effect was significant.Pearson analysis was used for correlation testing.Results:The interaction effect between the time and group of HAMD-17 scores was significant ( F=121.784, P<0.05). The results of simple effects analysis showed that the HAMD-17 scores of the observation group at T1 and T2 ((12.07±4.08) and (14.78±4.99), respectively) were lower than those of the control group ((23.78±5.87) and (24.67±7.00), P<0.05). The treatment response rate and remission rate of the observation group at T1 were higher than those of the control group ( χ2=4.090, 7.378, both P<0.05).The treatment response rate and remission rate of the observation group at T2 were higher than those of the control group ( χ2=4.463, 4.547, both P<0.05). The time and group interaction effects of the percentage of correct response and conceptualization level in the Wisconsin card sorting test were significant ( F=30.087, 20.004, P<0.05). The results of simple effects analysis showed that the percentage of correct response and conceptualization level in the observation group at T1 and T2 were higher than those in the control group (all P<0.05). The time and group interaction effect of SII was significant ( F=8.173, P<0.05). The results of simple effects analysis showed that there was no statistically significant difference in SII between the two groups at T0 ( P>0.05). The SII at T1 and T2 in the observation group was lower than that in the control group ( P<0.05). In the observation group, the changes in SII from T2 to T0 was positively correlated with the change in HAMD-17 scores ( r=0.527, P<0.05), and negatively correlated with the percentage of correct responses to the Wisconsin card sorting test ( r=-0.412, P<0.05) and the percentage of conceptualization level ( r=-0.411, P<0.05). Conclusion:irTMS is effective in treating TRD and can improve patients' cognitive function and immune inflammation damage.

Objective:To explore the efficacy of intensive repetitive transcranial magnetic stimulation (irTMS) in treatment-resistant depression (TRD) and its impact on cognitive function and systemic immune-inflammation index (SII).Methods:Forty-eight TRD patients were divided into observation group and control group using random number table method, with 24 patients in each group. The observation group was treated with irTMS, and the stimulation site was the left dorsolateral prefrontal lobe. The stimulation intensity was 110% of the motor threshold, and the stimulation frequency was 15 Hz. The stimulation interval was 26 s, and 3 000 pulses were stimulated each time. Stimulating 5 times per day, with an interval of 50 min, and continuous treatment for 5 days. The total stimulation amount for 5 days was 75 000 pulses. The control group was treated with pseudo stimulation. Before treatment (T0), 5 days after treatment (T1), and 1 month after treatment (T2), 17-item Hamilton depression scale (HAMD-17) was used to assess depressive mood. Evaluating cognitive function using the Wisconsin card sorting test.A fully automated blood cell analyzer was used to detect platelet count (PLT), neutrophil count (NC), and lymphocyte count (LC), calculate the systemic immune inflammation index (SII), SII=PLT × NC/LC. Statistical analysis was conducted using SPSS 20.0 software. The comparison between two sets of repeated measurement data was performed using repeated measurement analysis of variance.Simple effect analysis was performed if the interaction effect was significant.Pearson analysis was used for correlation testing.Results:The interaction effect between the time and group of HAMD-17 scores was significant ( F=121.784, P<0.05). The results of simple effects analysis showed that the HAMD-17 scores of the observation group at T1 and T2 ((12.07±4.08) and (14.78±4.99), respectively) were lower than those of the control group ((23.78±5.87) and (24.67±7.00), P<0.05). The treatment response rate and remission rate of the observation group at T1 were higher than those of the control group ( χ2=4.090, 7.378, both P<0.05).The treatment response rate and remission rate of the observation group at T2 were higher than those of the control group ( χ2=4.463, 4.547, both P<0.05). The time and group interaction effects of the percentage of correct response and conceptualization level in the Wisconsin card sorting test were significant ( F=30.087, 20.004, P<0.05). The results of simple effects analysis showed that the percentage of correct response and conceptualization level in the observation group at T1 and T2 were higher than those in the control group (all P<0.05). The time and group interaction effect of SII was significant ( F=8.173, P<0.05). The results of simple effects analysis showed that there was no statistically significant difference in SII between the two groups at T0 ( P>0.05). The SII at T1 and T2 in the observation group was lower than that in the control group ( P<0.05). In the observation group, the changes in SII from T2 to T0 was positively correlated with the change in HAMD-17 scores ( r=0.527, P<0.05), and negatively correlated with the percentage of correct responses to the Wisconsin card sorting test ( r=-0.412, P<0.05) and the percentage of conceptualization level ( r=-0.411, P<0.05). Conclusion:irTMS is effective in treating TRD and can improve patients' cognitive function and immune inflammation damage.

Objective To investigate the interference of varying degrees of lipemia on serum lithium(Li)measurement using the phosphatase method and explore effective mitigation strategies.Methods A pooled sample of severe lipemic serum without lithium was collected and concentrated to obtain lipemic serum concentrate.A pooled serum sample from patients with normal lipid levels taking lithium carbonate was used for triglyceride(TG)interference experiments.Additionally,28 serum samples from patients not taking lithium carbonate were collected.Based on the results of TG interference experiments,the maximum TG concentration that did not interfere with serum lithium measurement was determined as the target concentration for dilution,and the corresponding dilution factor was calculated.Lithium solution was added to each sample to determine the theoretical lithium concentration.Samples were divided into three groups and analyzed using direct detection,physiological saline dilution,and high-speed centrifugation(13 000 r/min,10 min).The results obtained from different methods were compared.Results Lipemic serum with TG concentrations>4.77mmol/L interfered with lithium measurement by the phosphatase method.The physiological saline dilution method showed the largest deviation(t=10.87,P<0.000 1)and significant differences from theoretical values,making it unsuitable for accurate measurement.In contrast,the high-speed centrifugation method provided results closest to the theoretical values(t=2.97,P=0.036 9)with higher accuracy.Although the direct detection method was highly correlated with the high-speed centrifugation method(r=0.976 5,P<0.000 1),with a significant mean difference remained(t=5.37,P<0.000 1).Conclusion For lipemic serum samples with TG concentrations>4.77mmol/L,the physiological saline dilution method should be avoided due to its inaccuracy.High-speed centrifugation effectively removes lipemic interference,yielding results closer to theoretical values,and is recommended as the optimized method for serum lithium measurement in lipemic samples.

The ribosomal protein S11(RPS11)from Enterococcus faecalis is was heterologously ex-pressed using the Pichia pastoris system.The RPS11 gene sequence was optimized to match the yeast codon preference,and the recombinant expression vector pPIC9K-RPS11 was constructed.Electroporation was used to transform the vector into the Pichia pastoris GS115 strain,and high-copy recombinant strains were selected through G418 resistance screening.Protein expression was induced with methanol,and the expression was verified by SDS-PAGE.The recombinant protein was applied in a mouse melanoma treatment model to evaluate its therapeutic effects.The results showed that the recombinant expression vector pPIC9K-RPS11 successfully expressed the target protein with an approximate molecular weight of 14 kDa in Pichia pastoris.The optimal fermenta-tion conditions were determined to be an induction temperature of 30 ℃,induction time of 72 h,and methanol concentration of 1％.Analysis using a mouse peritoneal macrophage trained immuni-ty model revealed that recombinant RPS11 possessed biological activity capable of inducing trained immunity.Additionally,therapeutic experiments in a mouse melanoma model demonstrated that recombinant RPS11 significantly inhibited tumor growth.These findings suggest that the recombi-nant RPS11 secreted by Pichia pastoris not only possesses biological activity in inducing trained immunity but also inhibits tumor cell growth in a mouse melanoma model,providing theoretical support for the heterologous expression and potential applications of recombinant RPS11.

Geraniin, a polyphenol derived from the fruit peel of Nephelium lappaceum L., has been shown to possess anti-inflammatory and antioxidant properties in the cardiovascular system. The present study explored whether geraniin could protect against an isoproterenol (ISO)-induced cardiac hypertrophy model. Mice in the ISO group received an intraperitoneal injection of ISO (5 mg/kg) once daily for 9 days, and the administration group were injected with ISO after 5 days of treatment with geraniin or spironolactone. Potential therapeutic effects and related mechanisms analysed by anatomical coefficients, histopathology, blood biochemical indices, reverse transcription-PCR and immunoblotting. Geraniin decreased the cardiac pathologic remodeling and myocardial fibrosis induced by ISO, as evidenced by the modifications to anatomical coefficients, as well as the reduction in collagen I/III á1mRNA and protein expression and cross-sectional area in hypertrophic cardiac tissue. In addition, geraniin treatment reduced ISO-induced increase in the mRNA and protein expression levels of interleukin (IL)-6, IL-1β and tumor necrosis factor-α, whereas ISO-induced IL-10 showed the opposite behaviour in hypertrophic cardiac tissue.Further analysis showed that geraniin partially reversed the ISO-induced increase in malondialdehyde and nitric oxide, and the ISO-induced decrease in glutathione, superoxide dismutase and glutathione. Furthermore, it suppressed the ISO-induced cellular apoptosis of hypertrophic cardiac tissue, as evidenced by the decrease in Bcell lymphoma-2 (Bcl-2)-associated X/caspase-3/caspase-9 expression, increase in Bcl-2 expression, and decrease in TdT-mediated dUTP nick-end labeling-positive cells.These findings suggest that geraniin can attenuate ISO-induced cardiac hypertrophy by inhibiting inflammation, oxidative stress and cellular apoptosis.

Geraniin, a polyphenol derived from the fruit peel of Nephelium lappaceum L., has been shown to possess anti-inflammatory and antioxidant properties in the cardiovascular system. The present study explored whether geraniin could protect against an isoproterenol (ISO)-induced cardiac hypertrophy model. Mice in the ISO group received an intraperitoneal injection of ISO (5 mg/kg) once daily for 9 days, and the administration group were injected with ISO after 5 days of treatment with geraniin or spironolactone. Potential therapeutic effects and related mechanisms analysed by anatomical coefficients, histopathology, blood biochemical indices, reverse transcription-PCR and immunoblotting. Geraniin decreased the cardiac pathologic remodeling and myocardial fibrosis induced by ISO, as evidenced by the modifications to anatomical coefficients, as well as the reduction in collagen I/III á1mRNA and protein expression and cross-sectional area in hypertrophic cardiac tissue. In addition, geraniin treatment reduced ISO-induced increase in the mRNA and protein expression levels of interleukin (IL)-6, IL-1β and tumor necrosis factor-α, whereas ISO-induced IL-10 showed the opposite behaviour in hypertrophic cardiac tissue.Further analysis showed that geraniin partially reversed the ISO-induced increase in malondialdehyde and nitric oxide, and the ISO-induced decrease in glutathione, superoxide dismutase and glutathione. Furthermore, it suppressed the ISO-induced cellular apoptosis of hypertrophic cardiac tissue, as evidenced by the decrease in Bcell lymphoma-2 (Bcl-2)-associated X/caspase-3/caspase-9 expression, increase in Bcl-2 expression, and decrease in TdT-mediated dUTP nick-end labeling-positive cells.These findings suggest that geraniin can attenuate ISO-induced cardiac hypertrophy by inhibiting inflammation, oxidative stress and cellular apoptosis.

Geraniin, a polyphenol derived from the fruit peel of Nephelium lappaceum L., has been shown to possess anti-inflammatory and antioxidant properties in the cardiovascular system. The present study explored whether geraniin could protect against an isoproterenol (ISO)-induced cardiac hypertrophy model. Mice in the ISO group received an intraperitoneal injection of ISO (5 mg/kg) once daily for 9 days, and the administration group were injected with ISO after 5 days of treatment with geraniin or spironolactone. Potential therapeutic effects and related mechanisms analysed by anatomical coefficients, histopathology, blood biochemical indices, reverse transcription-PCR and immunoblotting. Geraniin decreased the cardiac pathologic remodeling and myocardial fibrosis induced by ISO, as evidenced by the modifications to anatomical coefficients, as well as the reduction in collagen I/III á1mRNA and protein expression and cross-sectional area in hypertrophic cardiac tissue. In addition, geraniin treatment reduced ISO-induced increase in the mRNA and protein expression levels of interleukin (IL)-6, IL-1β and tumor necrosis factor-α, whereas ISO-induced IL-10 showed the opposite behaviour in hypertrophic cardiac tissue.Further analysis showed that geraniin partially reversed the ISO-induced increase in malondialdehyde and nitric oxide, and the ISO-induced decrease in glutathione, superoxide dismutase and glutathione. Furthermore, it suppressed the ISO-induced cellular apoptosis of hypertrophic cardiac tissue, as evidenced by the decrease in Bcell lymphoma-2 (Bcl-2)-associated X/caspase-3/caspase-9 expression, increase in Bcl-2 expression, and decrease in TdT-mediated dUTP nick-end labeling-positive cells.These findings suggest that geraniin can attenuate ISO-induced cardiac hypertrophy by inhibiting inflammation, oxidative stress and cellular apoptosis.

Geraniin, a polyphenol derived from the fruit peel of Nephelium lappaceum L., has been shown to possess anti-inflammatory and antioxidant properties in the cardiovascular system. The present study explored whether geraniin could protect against an isoproterenol (ISO)-induced cardiac hypertrophy model. Mice in the ISO group received an intraperitoneal injection of ISO (5 mg/kg) once daily for 9 days, and the administration group were injected with ISO after 5 days of treatment with geraniin or spironolactone. Potential therapeutic effects and related mechanisms analysed by anatomical coefficients, histopathology, blood biochemical indices, reverse transcription-PCR and immunoblotting. Geraniin decreased the cardiac pathologic remodeling and myocardial fibrosis induced by ISO, as evidenced by the modifications to anatomical coefficients, as well as the reduction in collagen I/III á1mRNA and protein expression and cross-sectional area in hypertrophic cardiac tissue. In addition, geraniin treatment reduced ISO-induced increase in the mRNA and protein expression levels of interleukin (IL)-6, IL-1β and tumor necrosis factor-α, whereas ISO-induced IL-10 showed the opposite behaviour in hypertrophic cardiac tissue.Further analysis showed that geraniin partially reversed the ISO-induced increase in malondialdehyde and nitric oxide, and the ISO-induced decrease in glutathione, superoxide dismutase and glutathione. Furthermore, it suppressed the ISO-induced cellular apoptosis of hypertrophic cardiac tissue, as evidenced by the decrease in Bcell lymphoma-2 (Bcl-2)-associated X/caspase-3/caspase-9 expression, increase in Bcl-2 expression, and decrease in TdT-mediated dUTP nick-end labeling-positive cells.These findings suggest that geraniin can attenuate ISO-induced cardiac hypertrophy by inhibiting inflammation, oxidative stress and cellular apoptosis.

Geraniin, a polyphenol derived from the fruit peel of Nephelium lappaceum L., has been shown to possess anti-inflammatory and antioxidant properties in the cardiovascular system. The present study explored whether geraniin could protect against an isoproterenol (ISO)-induced cardiac hypertrophy model. Mice in the ISO group received an intraperitoneal injection of ISO (5 mg/kg) once daily for 9 days, and the administration group were injected with ISO after 5 days of treatment with geraniin or spironolactone. Potential therapeutic effects and related mechanisms analysed by anatomical coefficients, histopathology, blood biochemical indices, reverse transcription-PCR and immunoblotting. Geraniin decreased the cardiac pathologic remodeling and myocardial fibrosis induced by ISO, as evidenced by the modifications to anatomical coefficients, as well as the reduction in collagen I/III á1mRNA and protein expression and cross-sectional area in hypertrophic cardiac tissue. In addition, geraniin treatment reduced ISO-induced increase in the mRNA and protein expression levels of interleukin (IL)-6, IL-1β and tumor necrosis factor-α, whereas ISO-induced IL-10 showed the opposite behaviour in hypertrophic cardiac tissue.Further analysis showed that geraniin partially reversed the ISO-induced increase in malondialdehyde and nitric oxide, and the ISO-induced decrease in glutathione, superoxide dismutase and glutathione. Furthermore, it suppressed the ISO-induced cellular apoptosis of hypertrophic cardiac tissue, as evidenced by the decrease in Bcell lymphoma-2 (Bcl-2)-associated X/caspase-3/caspase-9 expression, increase in Bcl-2 expression, and decrease in TdT-mediated dUTP nick-end labeling-positive cells.These findings suggest that geraniin can attenuate ISO-induced cardiac hypertrophy by inhibiting inflammation, oxidative stress and cellular apoptosis.