Objective To investigate the clinical features of chronic hepatitis C(CHC)patients with hepatitis C virus genotype 3(HCV GT3)infection and the risk factors for disease progression.Methods A multicenter retrospective cohort study was conducted among 1 002 CHC patients from 11 clinical centers in Northwest China from December 2017 to November 2023,and according to their genotype,they were divided into GT1,GT2,GT3,and GT6 groups.Clinical features were compared between the patients with different genotypes.The one-way analysis of variance was used for comparison of normally distributed continuous data between groups,and the Scheffe test was used for further comparison between two groups.The Kruskal-Wallis H test was used for comparison of data with skewed distribution between groups;the chi-square test or Fisher test was used for comparison of categorical data between groups.The multivariate logistic regression analysis was used to explore the influencing factors for the progression of CHC to liver cirrhosis.Results In terms of the genotype,there were 427 patients with GT1 infection,242 with GT2 infection,299 with GT3 infection(210 patients with GT3a infection,87 with GT3b infection,and 2 with unclassified genotype),and 34 with GT6 infection.The patients with GT3 infection had a significantly younger age than those with GT1 infection(51.3±0.5 years vs 53.2±0.6 years,P<0.05)or GT2 infection(51.3±0.5 years vs 53.7±0.8 years,P<0.05),and for the patients with liver cirrhosis,the patients with GT3 infection had a significantly younger age than those with GT1 infection(52.1±0.5 years vs 59.4±0.9 years,P<0.001)or GT2 infection(52.1±0.5 years vs 58.1±1.1 years,P<0.001).Among the patients with GT3 infection,male patients accounted for 77.9%and the patients with liver cirrhosis accounted for 46.2%,which were significantly higher than those among the patients with GT1,GT2 or GT6 infection(all P<0.001).At baseline,the patients with GT3 infection had significantly higher levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)than those with GT1 or GT2 infection,significantly higher aspartate aminotransferase-to-platelet ratio index(APRI)and fibrosis-4(FIB4)than those with GT1,GT2 or GT6 infection,a significantly lower platelet count(PLT)than those with GT2 or GT6 infection,a significantly higher level of alpha-fetoprotein than those with GT2 or GT6 infection,and a significantly lower level of albumin(Alb)than those with GT6 infection(all P<0.05).There were no significant differences between the patients with GT3a infection and those with GT3b infection in age,sex,the proportion of patients with liver cirrhosis,comorbidities,HCV RNA quantification,PLT,ALT,AST,alkaline phosphatase,Alb,APRI,and FIB-4(all P>0.05).The multivariate logistic regression analysis showed that PLT≤150×109/L(odds ratio[OR]=10.72,95%confidence interval[CI]:5.76-35.86,P<0.001)and Alb≤35 g/L(OR=3.74,95%CI:1.22-11.45,P=0.021)were risk factors for liver cirrhosis.Conclusion Most CHC patients with GT3 infection are male in Northwest China,and compared with the patients with other genotypes,such patients tend to have a younger age of onset and higher degrees of liver inflammation activity and fibrosis.Low PLT and a low level of Alb are risk factors for progression to liver cirrhosis in CHC patients with GT3 infection.

Objective:To explore the correlation of cumulative atherogenic index of plasma (cumAIP) and cumulative atherosclerosis index (cumAI) with new-onset non-alcoholic fatty liver disease (NAFLD).Methods:From January 2017 to December 2023, 2 472 subjects who underwent health checkups at the Second Affiliated Hospital of Dalian Medical University for 3 consecutive years were enrolled. Triglyceride, total cholesterol, high density lipoprotein cholesterol and their measurement time intervals were used to calculate cumAIP and cumAI. The subjects were divided into Q1, Q2, Q3 and Q4 groups with the threshold values of 25th percentile, median and 75th percentile of the baseline atherogenic index of plasma (AIP) and atherosclerotic index (AI) subjects. Cox regression model was used to analyze the effects of cumAIP and cumAI on the new-onset NAFLD, restricted cubic spline was performed to analyze the nonlinear association between cumAIP and cumAI and new-onset NAFLD, and the clinical decision curve was used to compare the decision value of different indicators for NAFLD. Results:The risk of NAFLD gradually increased along with the increasing of cumAIP and cumAI. In the quartile groups of cumAIP, the incidence of Q1 to Q4 groups was 6.15%, 8.74%, 15.05%, and 25.08%, respectively. In the quartile groups of cumAI, the incidence of Q1 to Q4 groups was 5.99%, 11.17%, 15.21%, and 22.65%, respectively. After adjusting the confounding factors, the risk of new-onset NAFLD in the high-level group ( Q4) was higher than that in the low-level cumAIP group ( Q1) ( HR=3.15, 95% confidence interval (95% CI): 2.15 to 4.63, P<0.001) and the high-level cumAI group ( Q4) ( HR=2.74, 95% CI: 1.82 to 4.10, P<0.001). cumAIP and cumAI showed a significant nonlinear association with new-onset NAFLD ( χ2=119.15, 94.53; both P<0.001). The cumAIP had higher predictive value for NAFLD than the other cumulative lipid metrics and baseline AIP or AI. Conclusion:CumAIP and cumAI can be served as new predictive indicators of NAFLD, with a particular focus on the dynamic cumulative changes of AIP, which can achieve effective early screening for NAFLD.

Objective:Investigating the association of the systemic immune-inflammation index and the pan-inflammation index with incident non-alcoholic fatty liver disease (NAFLD).Methods:This retrospective cohort study included 42 891 participants who underwent at least two health examinations at the Second Affiliated Hospital of Dalian Medical University between 2014 and 2023. Based on their levels of the systemic immune inflammation index (SII) and the pan immune inflammation value (PIV), participants were respectively divided into four quartile groups (Q1 to Q4). Cox proportional hazards models were employed to analyze the association of different SII and PIV levels, as well as their quartile groups, with new onset NAFLD in the total population and across various subgroups. Restricted cubic splines were used to examine the dose response relationship between these inflammatory indices and incident NAFLD. Additionally, sensitivity analyses were conducted to confirm the robustness of the findings.Results:After adjusting for confounding factors, the natural logarithm-transformed lnSII ( HR=1.247, 95% CI: 1.184-1.314, P<0.001) and lnPIV ( HR=1.192, 95% CI: 1.148-1.238, P<0.001) were significantly positively associated with the risk of NAFLD. When the subjects were grouped by SII quartiles (Q1-Q4), compared with those in Q1, participants in Q2, Q3, and Q4 exhibited progressively higher risks of incident NAFLD:11.9% ( HR=1.119, 95% CI: 1.051-1.192, P<0.001), 17.1% ( HR=1.171, 95% CI: 1.100-1.248, P<0.001), and 29.1% ( HR=1.291, 95% CI: 1.211-1.377, P<0.001), respectively. Quartile analysis of PIV yielded similar trends: the risk of incident NAFLD increased for 10.4% ( HR=1.104, 95% CI: 1.034-1.179, P=0.003), 18.7% ( HR=1.187, 95% CI: 1.112-1.266, P<0.001), and 30.5% ( HR=1.305, 95% CI: 1.223-1.393, P<0.001) in Q2, Q3, and Q4 group respectively when compared to that in Q1 group. Subgroup analysis confirmed consistent associations of SII and PIV with elevated NAFLD risk across all subgroups. Conclusion:Elevated levels of SII and PIV are significantly associated with increased risk of NAFLD.

Objective:To investigate the effect of changes in metabolic syndrome status and persistence on carotid plaque risk.Methods:This retrospective cohort study analyzed individuals who underwent routine health check-ups at the health management center of the Second Affiliated Hospital of Dalian Medical University from 2014 to 2023. Participants with at least three carotid ultrasound records meeting the inclusion criteria were classified into 4 groups based on changes in metabolic status: persistently metabolic health, transitioning from metabolic health to unhealth, transitioning from metabolic unhealth to health, and persistently metabolic unhealth. The cumulative incidence of carotid plaque in these groups was compared. A Cox proportional risk model was used to evaluate the relationship between changes in metabolic syndrome status, the number of metabolic syndrome components, and the risk of carotid plaque development. Restricted cubic spline analysis was applied to explore the association between changes in individual metabolic syndrome components and carotid plaque risk.Results:Compared to the persistently metabolic health group, the persistent unhealth group had the highest risk of developing carotid plaque( HR=1.35, 95% CI 1.05-1.74, P=0.021), followed by those who transitioned from metabolic health to unhealth and those who improved from metabolic unhealth to health. Furthermore, the risk of carotid plaque increased progressively with the number of metabolic syndrome components. Restricted cubic spline analysis revealed a nonlinear relationship between fasting blood glucose change and carotid plaque risk, while systolic blood pressure, diastolic blood pressure, waist circumference, triglycerides, and high-density lipoprotein-cholesterol showed a linear dose-response relationship with carotid plaque. Conclusions:The change of metabolic syndrome is associated with the risk of developing carotid plaque, and maintaining metabolic health, recovering from metabolic syndrome, or minimizing the number of metabolic syndrome components may be effective strategies to prevent carotid plaque formation.

Objective To investigate the clinical features of chronic hepatitis C(CHC)patients with hepatitis C virus genotype 3(HCV GT3)infection and the risk factors for disease progression.Methods A multicenter retrospective cohort study was conducted among 1 002 CHC patients from 11 clinical centers in Northwest China from December 2017 to November 2023,and according to their genotype,they were divided into GT1,GT2,GT3,and GT6 groups.Clinical features were compared between the patients with different genotypes.The one-way analysis of variance was used for comparison of normally distributed continuous data between groups,and the Scheffe test was used for further comparison between two groups.The Kruskal-Wallis H test was used for comparison of data with skewed distribution between groups;the chi-square test or Fisher test was used for comparison of categorical data between groups.The multivariate logistic regression analysis was used to explore the influencing factors for the progression of CHC to liver cirrhosis.Results In terms of the genotype,there were 427 patients with GT1 infection,242 with GT2 infection,299 with GT3 infection(210 patients with GT3a infection,87 with GT3b infection,and 2 with unclassified genotype),and 34 with GT6 infection.The patients with GT3 infection had a significantly younger age than those with GT1 infection(51.3±0.5 years vs 53.2±0.6 years,P<0.05)or GT2 infection(51.3±0.5 years vs 53.7±0.8 years,P<0.05),and for the patients with liver cirrhosis,the patients with GT3 infection had a significantly younger age than those with GT1 infection(52.1±0.5 years vs 59.4±0.9 years,P<0.001)or GT2 infection(52.1±0.5 years vs 58.1±1.1 years,P<0.001).Among the patients with GT3 infection,male patients accounted for 77.9%and the patients with liver cirrhosis accounted for 46.2%,which were significantly higher than those among the patients with GT1,GT2 or GT6 infection(all P<0.001).At baseline,the patients with GT3 infection had significantly higher levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)than those with GT1 or GT2 infection,significantly higher aspartate aminotransferase-to-platelet ratio index(APRI)and fibrosis-4(FIB4)than those with GT1,GT2 or GT6 infection,a significantly lower platelet count(PLT)than those with GT2 or GT6 infection,a significantly higher level of alpha-fetoprotein than those with GT2 or GT6 infection,and a significantly lower level of albumin(Alb)than those with GT6 infection(all P<0.05).There were no significant differences between the patients with GT3a infection and those with GT3b infection in age,sex,the proportion of patients with liver cirrhosis,comorbidities,HCV RNA quantification,PLT,ALT,AST,alkaline phosphatase,Alb,APRI,and FIB-4(all P>0.05).The multivariate logistic regression analysis showed that PLT≤150×109/L(odds ratio[OR]=10.72,95%confidence interval[CI]:5.76-35.86,P<0.001)and Alb≤35 g/L(OR=3.74,95%CI:1.22-11.45,P=0.021)were risk factors for liver cirrhosis.Conclusion Most CHC patients with GT3 infection are male in Northwest China,and compared with the patients with other genotypes,such patients tend to have a younger age of onset and higher degrees of liver inflammation activity and fibrosis.Low PLT and a low level of Alb are risk factors for progression to liver cirrhosis in CHC patients with GT3 infection.

Objective:Investigating the association of the systemic immune-inflammation index and the pan-inflammation index with incident non-alcoholic fatty liver disease (NAFLD).Methods:This retrospective cohort study included 42 891 participants who underwent at least two health examinations at the Second Affiliated Hospital of Dalian Medical University between 2014 and 2023. Based on their levels of the systemic immune inflammation index (SII) and the pan immune inflammation value (PIV), participants were respectively divided into four quartile groups (Q1 to Q4). Cox proportional hazards models were employed to analyze the association of different SII and PIV levels, as well as their quartile groups, with new onset NAFLD in the total population and across various subgroups. Restricted cubic splines were used to examine the dose response relationship between these inflammatory indices and incident NAFLD. Additionally, sensitivity analyses were conducted to confirm the robustness of the findings.Results:After adjusting for confounding factors, the natural logarithm-transformed lnSII ( HR=1.247, 95% CI: 1.184-1.314, P<0.001) and lnPIV ( HR=1.192, 95% CI: 1.148-1.238, P<0.001) were significantly positively associated with the risk of NAFLD. When the subjects were grouped by SII quartiles (Q1-Q4), compared with those in Q1, participants in Q2, Q3, and Q4 exhibited progressively higher risks of incident NAFLD:11.9% ( HR=1.119, 95% CI: 1.051-1.192, P<0.001), 17.1% ( HR=1.171, 95% CI: 1.100-1.248, P<0.001), and 29.1% ( HR=1.291, 95% CI: 1.211-1.377, P<0.001), respectively. Quartile analysis of PIV yielded similar trends: the risk of incident NAFLD increased for 10.4% ( HR=1.104, 95% CI: 1.034-1.179, P=0.003), 18.7% ( HR=1.187, 95% CI: 1.112-1.266, P<0.001), and 30.5% ( HR=1.305, 95% CI: 1.223-1.393, P<0.001) in Q2, Q3, and Q4 group respectively when compared to that in Q1 group. Subgroup analysis confirmed consistent associations of SII and PIV with elevated NAFLD risk across all subgroups. Conclusion:Elevated levels of SII and PIV are significantly associated with increased risk of NAFLD.

Objective:To investigate the effect of changes in metabolic syndrome status and persistence on carotid plaque risk.Methods:This retrospective cohort study analyzed individuals who underwent routine health check-ups at the health management center of the Second Affiliated Hospital of Dalian Medical University from 2014 to 2023. Participants with at least three carotid ultrasound records meeting the inclusion criteria were classified into 4 groups based on changes in metabolic status: persistently metabolic health, transitioning from metabolic health to unhealth, transitioning from metabolic unhealth to health, and persistently metabolic unhealth. The cumulative incidence of carotid plaque in these groups was compared. A Cox proportional risk model was used to evaluate the relationship between changes in metabolic syndrome status, the number of metabolic syndrome components, and the risk of carotid plaque development. Restricted cubic spline analysis was applied to explore the association between changes in individual metabolic syndrome components and carotid plaque risk.Results:Compared to the persistently metabolic health group, the persistent unhealth group had the highest risk of developing carotid plaque( HR=1.35, 95% CI 1.05-1.74, P=0.021), followed by those who transitioned from metabolic health to unhealth and those who improved from metabolic unhealth to health. Furthermore, the risk of carotid plaque increased progressively with the number of metabolic syndrome components. Restricted cubic spline analysis revealed a nonlinear relationship between fasting blood glucose change and carotid plaque risk, while systolic blood pressure, diastolic blood pressure, waist circumference, triglycerides, and high-density lipoprotein-cholesterol showed a linear dose-response relationship with carotid plaque. Conclusions:The change of metabolic syndrome is associated with the risk of developing carotid plaque, and maintaining metabolic health, recovering from metabolic syndrome, or minimizing the number of metabolic syndrome components may be effective strategies to prevent carotid plaque formation.

Objective:To explore the correlation of cumulative atherogenic index of plasma (cumAIP) and cumulative atherosclerosis index (cumAI) with new-onset non-alcoholic fatty liver disease (NAFLD).Methods:From January 2017 to December 2023, 2 472 subjects who underwent health checkups at the Second Affiliated Hospital of Dalian Medical University for 3 consecutive years were enrolled. Triglyceride, total cholesterol, high density lipoprotein cholesterol and their measurement time intervals were used to calculate cumAIP and cumAI. The subjects were divided into Q1, Q2, Q3 and Q4 groups with the threshold values of 25th percentile, median and 75th percentile of the baseline atherogenic index of plasma (AIP) and atherosclerotic index (AI) subjects. Cox regression model was used to analyze the effects of cumAIP and cumAI on the new-onset NAFLD, restricted cubic spline was performed to analyze the nonlinear association between cumAIP and cumAI and new-onset NAFLD, and the clinical decision curve was used to compare the decision value of different indicators for NAFLD. Results:The risk of NAFLD gradually increased along with the increasing of cumAIP and cumAI. In the quartile groups of cumAIP, the incidence of Q1 to Q4 groups was 6.15%, 8.74%, 15.05%, and 25.08%, respectively. In the quartile groups of cumAI, the incidence of Q1 to Q4 groups was 5.99%, 11.17%, 15.21%, and 22.65%, respectively. After adjusting the confounding factors, the risk of new-onset NAFLD in the high-level group ( Q4) was higher than that in the low-level cumAIP group ( Q1) ( HR=3.15, 95% confidence interval (95% CI): 2.15 to 4.63, P<0.001) and the high-level cumAI group ( Q4) ( HR=2.74, 95% CI: 1.82 to 4.10, P<0.001). cumAIP and cumAI showed a significant nonlinear association with new-onset NAFLD ( χ2=119.15, 94.53; both P<0.001). The cumAIP had higher predictive value for NAFLD than the other cumulative lipid metrics and baseline AIP or AI. Conclusion:CumAIP and cumAI can be served as new predictive indicators of NAFLD, with a particular focus on the dynamic cumulative changes of AIP, which can achieve effective early screening for NAFLD.

Objective To investigate the role and mechanism of sine oculis homeobox 1(Six1),a nephrogenic transcription factor,in regulating injury repair after acute kidney injury(AKI).Methods C57BL/6J mice were inflicted with renal ischemia reperfusion(IR)injury to establish AKI model,and then the serum samples and kidney tissues were collected at days 1,2,and 3 after modeling.Serum creatinine(Cr)and blood urea nitrogen(BUN)levels were measured and renal morphology was observed with HE staining.The expression and distribution of nephrogenic molecules(Six1 and Pax2,etc.)and cell proliferation/migration genes(Cyclin A1,MMP9,etc.)were detected with RT-PCR,Western blotting,and immunofluorescence assay and immunohistochemical assay.The expression of apoptosis pathway(Bc12,Caspase3,etc.)and cell proliferation related molecules were evaluated in Six1 overexpression/knockout human epithelial cells(HK2)with CoCl2-induced injury.Additionally,after the adeno-associated viruses carrying Six1 overexpression vector were used to overexpress the molecule in the mice,the expression of Six1 and other related molecules were detected after IR injury modeling.Results After renal IR injury,Six1 was significantly activated in epithelial cells,the expression of nephrogenic and cell proliferation/migration molecules(Pax2,Cyclin A1,MMP9,etc.)was obviously up-regulated(P＜0.05),which was positively correlated with Six1 expression,while the proliferation/migration molecules(Ki67,MMP9)were also localized within the tubular epithelial cells.In cellular models of Six1 overexpression,the expression levels of nephrogenic and cell proliferation/migration molecules(Pax2,Cyclin A1,MMP9,etc.)were also notably up-regulated(P＜0.05).In the mice with renal overexpression of Six1,the nephrogenic molecules as well as anti-apoptotic ones(Six2,Pax2,Bc12,etc.)were up-regulated,while the expression of kidney injury-related molecule(Kim1)in kidneys was reduced in the renal tissues.While,in 2 d after IR injury,the anti-apoptotic gene(Bc12,Stat3)was significantly up-regulated(P＜0.05),and the apoptotic and injury molecules(Kim1,Caspase3)showed remarkable down-regulation(P＜0.05)in the mice with renal Six1 overexpression.Furthermore,CoCl2-inducion significantly decreased the cell proliferation rate in the Six1 knockoutgroup(TCMK1-Six1-/-)(P＜0.05)but increased the rate in the Six1 overexpression group(TCMK1-Six1)when compared to the control cells(P＜0.05).And,the expression of nephrogenic,anti-apoptotic pathways and cell proliferation/migration molecules(Pax2,Bc12,Cyclin A1,MMP9,etc.)were reduced in TCMK1-Six1-/-group,and apoptosis and kidney injury molecules(Caspase3,Kim1)were significantly down-regulated in TCMK1-Six1 group(P＜0.05).Conclusion Activation of Six1 after AKI can promote the proliferation/migration of renal tubular epithelial cells by up-regulating nephrogenic molecules and inducing anti-apoptotic pathway molecules,and then,participate in IR-induced renal injury repair.

The Qa-1 in mice is homologous to human leukocyte antigen E(HLA-E), and both of them belong to the non-classical major histocompatibility complex I b(MHC-I b) molecules. Qa-1 is capable of presenting self or exogenous antigen peptides to interact with two distinct receptors, namely T cell receptor (TCR) and natural killer cell group 2 member A (or C) (NKG2A/C), thus playing an important role in immune response and regulation. Qa-1-restricted regulatory CD8⁺ T cell (CD8⁺ Treg) is one of the most studied CD8⁺ Treg subgroups, which can maintain immune homeostasis and autoimmune tolerance by exerting immunosuppressive effects. Consequently, Qa-1-restricted CD8⁺Treg cells are closely associated with the occurrence and development of various clinical diseases, such as tumors, infections, autoimmune diseases, and transplant rejections. This paper provides a comprehensive review of the phenotypic characteristics, functional effects, regulatory mechanisms of Qa-1-restricted CD8⁺ Treg cells, as well as the latest research progresses of Qa-1-restricted CD8⁺ Treg cells involved in the pathogenesis of infectious diseases.
Humans ; Animals ; T-Lymphocytes, Regulatory/immunology* ; Histocompatibility Antigens Class I/immunology* ; CD8-Positive T-Lymphocytes/immunology* ; Communicable Diseases/immunology*