ObjectiveTo investigate the association between noninvasive liver fibrosis markers and carotid plaque （CP） in patients with lean metabolic dysfunction-associated fatty liver disease （MAFLD）， and to provide a basis for screening high-risk populations. MethodsA total of 957 patients with lean MAFLD who underwent physical examination in Subei People’s Hospital from January 2021 to June 2023 was enrolled as the observation cohort， with the presence or absence of CP as the outcome， and fibrosis-4 （FIB-4） index and nonalcoholic fatty liver disease fibrosis score （NFS） were used to assess liver fibrosis degree. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between two groups. The multivariate logistic regression analysis， the restricted cubic spline analysis， the receiver operating characteristic curve， and the mediation effect analysis were used to investigate the association between liver fibrosis degree and CP. ResultsThe prevalence rate of CP was 36.6% in the lean MAFLD population. Compared with the non-CP group（n=607）， the CP group （n=350） had a significantly higher proportion of male patients， a significantly higher proportion of patients with smoking/diabetes/hypertension， and significantly higher levels of age， creatinine， blood urea nitrogen， triglycerides， fasting blood glucose， aspartate aminotransferase， aspartate aminotransferase/alanine aminotransferase ratio， NFS， and FIB-4 index， as well as significantly lower levels of platelet count and albumin （all P<0.05）. The multivariate logistic regression analysis showed that after adjustment for confounding factors， FIB-4 index （odds ratio［OR］=2.979， 95% confidence interval［CI］：2.141 — 4.219， P<0.001） and NFS （OR=1.747， 95%CI： 1.499 — 2.046， P<0.001） were positively correlated with CP. Both FIB-4 index and NFS had a good value in predicting CP. Hypertension had a significant indirect effect on the prevalence rate of CP through its impact on liver fibrosis markers， and its mediating effect accounted for 39.5% — 40.8% of the total effect （P<0.001）. ConclusionIn patients with lean MAFLD， NFS and FIB-4 index are significantly positively correlated with the prevalence rate of CP， and they can be used as potential epidemiological predictive indicators. Liver fibrosis markers may play a mediating role in the association between hypertension and CP. Interventions targeting hypertension and liver fibrosis markers may help to prevent and delay the progression of CP.

ObjectiveTo investigate the association of liver fibrosis scores and inflammation markers with gallstones in patients with metabolic dysfunction-associated fatty liver disease （MAFLD）， as well as the mediating role of liver fibrosis scores in the relationship between inflammation markers and gallstones. MethodsA total of 14 567 patients who received physical examination and were diagnosed with MAFLD in Subei People’s Hospital from January 2014 to June 2023 were enrolled in this study， and according to the results of abdominal color Doppler ultrasound， they were divided into gallstone group with 1 724 patients and non-gallstone group with 12 843 patients. Related clinical data were collected from all patients， including demographic data， medical history， family history， physical examination， Color Doppler ultrasound， and biochemical parameters. The biomarkers associated with metabolic disorders and insulin resistance included triglyceride-glucose index （TyG）， TyG-body mass index （BMI） index， atherogenic index of plasma （AIP）， and non-high-density lipoprotein cholesterol-to-high-density lipoprotein cholesterol ratio （NHHR）； the biomarkers associated with inflammation and nutritional status included neutrophil-to-lymphocyte ratio （NLR）， neutrophil percentage-to-albumin ratio （NPAR）， and monocyte-to-lymphocyte ratio （MLR）； the biomarkers for assessing liver fibrosis degree and liver function included albumin-bilirubin （ALBI） score， NAFLD fibrosis score （NFS）， fibrosis-4 （FIB-4） index， and aspartate aminotransferase-to-platelet ratio index （APRI）. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， while the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between two groups. Multivariate Logistic regression analysis， restricted cubic spline analysis， and mediating effect analysis were used to assess the association of liver fibrosis markers and inflammation markers with the risk of gallstones. ResultsThe prevalence rate of gallstones was 11.8% among the MAFLD patients. There were significant differences between the gallstone group and the non-gallstone group in sex， age， smoking history， diabetes， hypertension， lymphocytes， platelets， glucose， albumin， serum uric acid， alanine aminotransferase， aspartate aminotransferase， red blood cell， NLR， NPAR， MLR， NFS， FIB-4 index， and ALBI score （all P<0.05）. The multivariate Logistic regression analysis showed that NLR （odds ratio ［OR］=1.091， 95% confidence interval ［CI］： 1.028　—　1.160， P<0.05）， NPAR （OR=1.073， 95%CI： 1.042　—　1.105， P<0.05）， MLR （OR=1.142， 95%CI： 1.057　—　1.232， P<0.05）， NFS （OR=1.239， 95%CI： 1.190　—　1.291， P<0.05）， and FIB-4 index （OR=1.326， 95%CI： 1.241　—　1.417， P<0.05） were influencing factors for the prevalence rate of gallstones. The restricted cubic spline analysis showed a significant non-linear association between NFS/FIB-4 index and the risk of gallstone （non-linear P<0.05）. The mediating effect analysis further showed that the association of NLR， MLR， and NPAR with gallstones was partially mediated by NFS or FIB-4 index， with a mediating effect accounting for 36.79%、28.09%、29.67% and 18.31%、17.70、11.57%， respectively. ConclusionNFS and FIB-4 index have a non-linear association with the prevalence rate of gallstones in MAFLD patients， and they also mediate the association of NLR， NPAR， and MLR with the risk of gallstone.

Background: High-mobility group box protein 1 (HMGB1) is a chromatin-binding protein involved in arthritis, ischemia, sepsis, atherosclerosis, neurodegenerative disorders, meningitis, and cancer. HMGB1 exhibits dual roles in cancer, acting as either a tumor suppressor or oncoprotein depending on context. Objective: This research aimed to elucidate HMGB1’s functional significance in cutaneous squamous cell carcinoma (cSCC). Methods: We overexpressed HMGB1 in cSCC cell lines using recombinant adenovirus and examined its effects on cell proliferation, colony formation, and cell migration. Results: Immunohistochemical analysis revealed elevated HMGB1 expression levels in cSCC tissue relative to normal epidermis. To assess the influence of HMGB1, we employed recombinant adenoviruses expressing HMGB1 to transduce SCC cell lines (SCC12 and SCC13). Enhanced HMGB1 expression significantly promoted cellular proliferation and colony formation capacity.Notably, HMGB1 overexpression elevated the levels of proliferation regulators, including P63, SOX2, CDK4 and CDK6. Furthermore, HMGB1 overexpression substantially enhanced tumor invasiveness, accompanied by upregulation of epithelial-mesenchymal transition (EMT) biomarkers. Mechanistically, overexpression of HMGB1 enhanced transforming growth factor-β signaling by increasing phosphorylation of SMAD2/3, the key mediators of EMT. Conclusion These data imply that HMGB1 acts as a tumor-promoting factor in cSCC.

ObjectiveHepatocellular carcinoma (HCC) represents 90% of all primary liver cancers. The main risk factors associated with HCC include viral hepatitis (B and/or C), alcohol abuse, and metabolic dysfunction-associated steatotic liver disease (MASLD), which progressively advance to liver fibrosis, cirrhosis, and ultimately evolve into HCC. Surgical resection represents the most effective treatment for HCC, while recent advances in immunotherapy, including immune checkpoint inhibitors and adoptive cell therapies, have provided improved treatment prospects for patients with unresectable HCC. However, the complex metabolic heterogeneity of HCC limits the therapeutic efficacy. Metabolic intermediates acyl-CoA not only provide energy and substrates for numerous biochemical reactions but also serve as donors for protein lysine acylation, a major class of post-translational modification (PTM). Therefore, a deeper understanding of the molecular mechanisms underlying protein lysine acylation and hepatocarcinogenesis is urgently needed. MethodsThe levels of protein lysine acylation and silence information regulator 5 (SIRT5) expression levels in clinical HCC samples were analyzed by Western blot. Quantitative malonylome and succinylome of HCC samples were analyzed by antibody-based affinity enrichment coupled with tandem mass spectrometry. The proliferation of HCC cells was analyzed with Cell Counting Kit-8 (CCK-8) assays, the apoptosis was quantified by Annexin V-FITC/propidium iodide (PI) staining coupled with flow cytometry, and the ability of cells to migrate was assayed by Transwell assays. The enzymatic activity of glutathione S-transferase Mu 1 (GSTM1) was quantified. Transgenic mice with hepatic overexpression of SIRT5 were constructed using CRISPR-Cas9, and primary hepatocarcinogenesis was induced by administration of diethylnitrosamine. ResultsWestern blot analysis indicated that the expression level of SIRT5 was elevated in clinical samples from HCC patients, and the levels of lysine malonylation, glutarylation, and succinylation were significantly reduced in HCC tissues. Knockout of SIRT5 in MHCC-97H and MHCC-97L hepatoma cells suppressed cell proliferation, and increased the percentage of apoptotic cells significantly. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the differentially malonylome and succinylome of HCC samples revealed significant enrichment in two major classes of biological processes: core energy metabolism (e.g., glycolysis/gluconeogenesis, tricarboxylic acid metabolic process, fatty acid beta oxidation) and detoxification and oxidative stress response (e.g., response to toxic substance, chemical carcinogenesis, reactive oxygen species (ROS)). SIRT5 removes malonylation from lysine residues in GSTM1 and restores its detoxification activity, which is crucial for the survival of hepatocytes under stressed conditions. More importantly, in vivo experiment indicated that hepatic-specific overexpression of SIRT5 in mice accelerated diethylnitrosamine-induced liver fibrosis and hepatocarcinogenesis, indicating the critical role of SIRT5 in HCC progression. ConclusionThis study highlights the previously unrecognized SIRT5-GSTM1 axis as a key regulator in hepatocarcinogenesis, and suggests a potential target for the treatment of patients with HCC.

Objective To investigate the relationship between the radial-ulnar ratio,lateral lunate angle of radius and height loss of radius after palmar locking plate internal fixation for distal radius fractures.Methods A total of 158 patients with distal radius fractures treated with palmar locking plate internal fixation in our hospital from March 2020 to September 2023 were selected.According to the height of radius loss after operation,the patients were divided into non-radius loss group(41 cases,<2 mm),mild to moderate radius loss group(32 cases,2 to 5 mm)and severe radius loss group(85 cases,>5 mm),and the clinical data of patients in the three groups were compared.Multivariate Logistic regression analysis was used to analyze the risk factors affecting height loss of radius.Locally weighted scatterplot smoothing(LOWESS)method was used to analyze the two-dimensional curve relationship of continuous variables.Restricted cubic spline(RCS)and threshold effect were used to analyze the relationship between the radial-ulnar ratio,lateral lunate angle of radius and height loss of radius after operation.Results The age of patients in the severe radius loss group was significantly higher than those in the non-radius loss group and the mild to moderate radius loss group(P<0.05),and the age of patients in the mild to moderate radius loss group was significantly higher than that in the non-radius loss group(P<0.05).Female patients and patients with osteoporosis and fracture type C were more likely to have height loss of radius(P<0.05).There were significant differences in patient-rated wrist evaluation(PRWE)score,disabilities of the arm,shoulder and hand(DASH)score,dorsal extension,palmar curvature,ulnar deviation,radial deviation,radial-ulnar ratio,and lateral lunate angle of radius of patients at 3 and 6 months after operation among three groups(P<0.001).The first prediction model based on age,gender,osteoporosis,fracture type,PRWE score,DASH score,dorsal extension,palmar curvature,ulnar deviation,and radial deviation and the second prediction model based on age,gender,osteoporosis,fracture type,PRWE score,DASH score,dorsal extension,palmar curvature,ulnar deviation,radial deviation,radial-ulnar ratio,and lateral lunate angle of radius were subjected to Hosmer-Lemeshow test showed good goodness of fit.LOWESS analysis showed that age,PRWE score,DASH score,dorsal extension,palmar curvature,ulnar deviation,radial deviation,radial-ulnar ratio,and lateral lunate angle of radius had a certain nonlinear relationship with the height loss of radius.RCS and threshold effect analysis showed that the probability of postoperative radius loss increased with the increase of radial-ulnar ratio in patients with distal radius fractures and radial-ulnar ratio≥13.254(P<0.001).The probability of postoperative radius loss decreased with the increase of the lateral lunate angle of radius in patients with distal radius fractures and lateral lunate angle of radius≤11.068°(P<0.001).Conclusion There was a positive correlation between the radial-ulnar ratio and the height loss of radius,and a negative correlation between the lateral lunate angle of radius and the height loss of radius after palmar locking plate internal fixation for distal radius fractures.

Objective To investigate the effect of long non-coding RNA(lncRNA)potassium voltage-gated channel subfamily Q member 1 overlapping transcript 1(KCNQ1OT1)on oxidative glucose deprivation/reoxygenation(OGD/R)-induced microglia injury through regulating the miR-145-5p/Rho-associated coiled-coil forming protein kinase 1(ROCK1)axis.Methods Microglia N9 were divided into the control group(normal culture),the OGD/R group(OGD/R-induced injury),the sh-NC group(transfected with sh-NC after OGD/R-induced injury),the sh-KCNQ1OT1 group(transfected with sh-KCNQ1OT1 after OGD/R-induced injury),the sh-KCNQ1OT1+inhibitor NC group(co-transfected with sh-KCNQ1OT1 and inhibitor NC after OGD/R-induced injury),and the sh-KCNQ1OT1+miR-145-5p inhibitor group(co-transfected with sh-KCNQ1OT1 and miR-145-5p inhibitor after OGD/R-induced injury).RT-qPCR was applied to detect the expression of lncRNA KCNQ1OT1,miR-145-5p,and ROCK1 mRNA in cells.The expression of ROCK1 protein was detected by Western blot.CCK-8 was applied to detect the cell proliferation.Flow cytometry was applied to detect cell apoptosis.ELISA was applied to detect the levels of interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),and interleukin-6(IL-6)in cells.The action sites of miR-145-5p with lncRNA KCNQ1OT1 and ROCK1 were predicted by bioinformatics website,and their targeting relationships were verified by dual-luciferase reporter assay.Results Compared with the control group,the expression of lncRNA KCNQ1OT1,the expression of ROCK1 mRNA and protein,the apoptosis rate,and the levels of IL-6,TNF-α,and IL-1β in cells were all increased,and the level of miR-145-5p and cell survival rate were all decreased in the OGD/R group(P<0.05).Compared with the OGD/R group and the sh-NC group,the expression of lncRNA KCNQ1OT1,the expression of ROCK1 mRNA and protein,the apoptosis rate,and the levels of IL-6,TNF-α,and IL-1β in cells were all decreased,and the level of miR-145-5p and cell survival rate were all increased in the sh-KCNQ1OT1 group,with significant differences(P<0.05).Compared with the sh-KCNQ1OT1+inhibitor NC group,the expression of ROCK1 mRNA and protein,the apoptosis rate,and the levels of IL-6,TNF-α,and IL-1β in cells were all increased,and the expression of miR-145-5p and cell survival rate were all decreased in the sh-KCNQ1OT1+miR-145-5p inhibitor group,with significant differences(P<0.05).Bioinformatics website showed that miR-145-5p had targeted action sites with lncRNA KCNQ1OT1 and ROCK1,and dual-luciferase reporter assay confirmed that miR-145-5p had targeting relationships with lncRNA KCNQ1OT1 and ROCK1(P<0.05).Conclusion Silencing lncRNA KCNQ1OT1 can alleviate OGD/R-induced microglia injury via upregulating the expression of miR-145-5p and targeting the down-regulation of ROCK1 expression.

Objective To explore the effects of different education and examination methods on the examination results during the screening/evaluation of patent foramen ovale by contrast-enhanced transcranial Doppler(cTCD).Methods Patients who underwent cTCD screening/evaluation for patent foramen ovale in our hospital from May 2023 to February 2024 were retrospectively selected as the research subjects.The patients were divided into the observation group and the control group according to different education and examination methods during the peri-examination period.Patients who received video education,modified Valsalva maneuver,and injection of contrast agent with 20 mL syringe were included into the observation group,and patients who received artificial education,Valsalva maneuver,and injection of contrast agent with 10 mL syringe were included into the control group.The positive detection rate of patent foramen ovale,right-to-left shunt microbubble grading during Valsalva/modified Valsalva maneuver,systolic blood flow velocity,pulsatility index(PI),resistive index(RI),examination duration,total physician-patient communication time,whether occlusion surgery was performed,and patient satisfaction were compared between the two groups.Results The positive detection rate of patent foramen ovale by cTCD(82.93%vs.95.92%),the detection rate of the maximum amout(grade Ⅲ)of microbubbles(39.02%vs.61.22%),the total physician-patient communication time during the peri-examination period[11.30(10.00,14.00)minutes vs.8.23(7.00,10.00)minutes],the rate of occlusion surgery(48.78%vs.73.47%),and the total patient satisfaction(80.49%vs.91.84%)showed statistically significant differences between the control group and the observation group(P<0.05).Additionally,the receiver operating characteristic(ROC)curve analysis showed that the area under the curve(AUC)for diagnosing patent foramen ovale were 0.718 in the control group and 0.855 in the observation group.Conclusion Peri-examination interventions such as video education,modified Valsalva maneuver,and injection of contrast agent with 20 mL syringe can improve the positive detection rate of patent foramen ovale,reduce ineffective physician-patient communication,and improve patient satisfaction.

To construct a recombinant fowl adenovirus 4(FAdV-4)expressing the Cap protein of goose astrovirus genotype 2(GoAstV-2),the expression cassette of Cap gene was inserted into the natural 1 966 bp deletion region of the FAdV-4 genome in the infectious clone p15A-cm-FAdV4-HNJZ.The resulted recombinant plasmid p15A-cm-FAdV4-HNJZ-Cap/GoAstV-2 was linearized with restriction enzyme and transfected into chicken hepatoma cell line(LMH)to rescue the recombinant FAdV-4 expressing the Cap protein of GoAstV-2,rF Ad V4-Cap/GoAstV-2.After 15 passages in LMH cells,the recombinant rFAdV4-Cap/GoAstV-2 was identified by PCR using primers flanking the insertion site of the Cap gene expression cassette and using viral genome DNA extracted from rFAdV4-Cap/GoAstV-2 infected LMH cells as template.LMH cells were in-fected with 15th passage rFAdV4-Cap/GoAstV-2 and indirect immunofluorescence was performed with a polyclonal antibody against Cap protein as the primary antibody.Western blot was carried out with lysates of rFAdV4-Cap/GoAstV-2 infected LMH cells.The in vitro replication dynamic of the 15th passage of the rFAdV4-Cap/GoAstV-2 was also investigated in LMH cells.The results demonstrated that the Cap gene of GoAstV-2 was presented in the genome of the recombinant vi-rus rF AdV4-Cap/Go Ast V-2,and could be expressed stably.The prepared recombinant virus in this study will lay a foundation for developing inactivated bivalent vaccine candidate against co-in-fection of FAdV-4 and GoAstV-2 in goose.

[Purpose]To analyze cancer incidence and mortality in Liaoning cancer registration areas from 2016 to 2020 and the trends from 2006 to 2020.[Methods]Cancer data in cancer registra-tion areas in Liaoning Province from 2016 to 2020 were collected.The incidence and mortality,age-standardized rate,cumulative rate(0～74 years old),and age-specific rate were calculated.Age-standardized incidence and mortality rate were calculated by the Chinese standard popula-tion(ASIRC,ASMRC)and Segi world standard population(ASIRW,ASMRW).Joinpoint software was applied to analyze the trends of incidence and mortality.[Results]From 2016 to 2020,the crude incidence rate of cancer in Liaoning cancer registration areas was 422.30/105,the ASIRC and ASIRW were 215.67/105 and 209.52/105.The ASIRC was higher in urban areas(225.00/105)than that in rural areas(190.15/105),and higher in male(221.47/105)than that in female(213.03/105).The crude mortality rate was 254.22/105,the ASMRC and ASMRW were 113.26/105 and 112.91/105.The ASMRC in urban areas(113.12/105)was the same as that in rural areas(113.01/105),and higher in male(146.86/105)than that in female(83.46/105).The ASIRW of lung cancer was 46.13/105,and the ASMRW was 32.04/105,both ranking the first of all cancers.From 2006 to 2020,the crude incidence,ASIRC and ASIRW in urban areas showed an increasing trend(AAPC=3.921％,t=16.222,P＜0.05;AAPC=0.823％,t=2.409,P＜0.05;AAPC=0.875％,t=2.933,P＜0.05).The crude incidence,ASIRC and ASIRW in urban female were all rising(AAPC=4.151％,t=15.888,P＜0.05;AAPC=1.597％,t=4.819,P＜0.05;AAPC=1.514％,t=4.752,P＜0.05).During the same period,the cancer mortality in urban areas showed an increasing trend(AAPC=3.175％,t=14.745,P＜0.05),and the ASMRW showed a decreasing trend(AAPC=-0.908％,t=-2.273,P＜0.05).The crude mor-tality of both men and women showed an increasing trend(AAPC=3.010％,t=6.032,P＜0.05;AAPC=2.820％,t=5.921,P＜0.05),while the crude mortality and ASMRW for female showed a significant downward trend(AAPC=-1.487％,t=-2.437,P＜0.05;AAPC=-2.680％,t=-2.246,P＜0.05).From 2016 to 2020,the crude incidence,ASIRC and ASIRW in rural areas showed no significant change;however,the crude incidence in male was increasing(AAPC=2.025％,t=3.853,P＜0.05).In the same period,the crude mortality rate in rural areas increased(AAPC=3.577％,t=9.377,P＜0.05),while there was no significant change in the ASMRC and ASMRW.The crude mortality of both men and women showed an increasing trend(AAPC=3.377％,t=10.615,P＜0.05;AAPC=3.978％,t=7.245,P＜0.05),while there was no significant change in ASMRC and ASMRW.[Conclusion]The cancer burden in Liaoning from 2016 to 2020 was higher than the average level in China,can-cer prevention and control should be further strengthened in the provice.

Objective To conduct a bibliometric analysis of relevant literature on liver failure caused by viral hepatitis from the past five years,and to help researchers understand the current status and hotspots in this field,and to provide insights into future research trends.Methods Based on the Science Citation Index Expanded(SCI-Expanded)data from Web of Science Core Collection,visualization analysis and mapping were conducted through VOSviewer and CiteSpace software to generate visual representations of international research collaboration networks,keyword co-occurrence clustering,and keyword bursts.Results From 2019 to 2023,a total of 873 relevant literature were included,with a total citation frequency of 7 364 and an average citation frequency of 8.44.Among them,China had the highest number of publications(458 articles,52.46%)and had the most cooperation with the United States.The research hotspots of viral hepatitis induced liver failure were mainly divided into three categories:basic and clinical research on liver failure caused by non-hepatitis B virus(HBV),the pathogenesis of HBV related liver failure,and treatment and prediction models of liver failure.The keyword time overlay map and burst map showed that the research hotspots had gradually shifted from the prevention and control of new infections to the treatment and prognosis assessment of patients with chronic infection.Conclusion China is a major international research entity in liver failure caused by viral hepatitis and actively participates in international scientific collaborations.The research hotspots on liver failure caused by viral hepatitis have gradually shifted from preventing viral hepatitis infections and expanding treatment options to the treatment of chronic infection patients and prognostic prediction.