Objective To investigate the correlation between arterial stiffness(AS)and incident chronic kidney disease(CKD)among the elderly individuals taking health checkup.Methods A retrospective study was conducted on 857 elderly individuals without CKD at baseline who taking physical exams in our medical center from December 2009 to May 2021.Their clinical and labora-tory data were collected.Brachial-ankle pulse wave velocity(baPWV)was used to assess the se-verity of AS,and then the subjects were divided into normal elasticity group(201 cases),and moderate(490 cases)and severe AS group(166 cases).Kaplan-Meier curves were plotted to dis-play cumulative incidence rates of incident CKD across different AS groups.Restricted cubic splines(RCS)and Cox regression models were applied to analyze the correlation of baPWV and incident CKD risk.Results The severe AS group had significantly advanced age,greater ratio of hypertension,larger waist circumference,higher HR,SBP and DBP,increased urinary albumin/creatinine ratio(UACR),elevated levels of TG and fasting blood glucose,and baPWV than the normal elasticity group(P＜0.05).During the follow-up period,37 participants developed CKD.The incidence of CKD was obviously higher in the severe AS group than the normal arterial elas-ticity group(9.04％vs 3.48％).RCS analysis revealed a U-shaped relationship between baPWV and incident CKD risk.When baPWV ≥1 400 cm/s,each standard deviation increase in baPWV indicates the risk of incident CKD increasing by 71％(HR=1.71,95％CI:1.30-2.25,P＜0.01).Regardless of adjustment for covariates or not,baPWV remained positive correlation with inci-dent CKD risk(P＜0.05).Conclusion Among the elderly individuals undergoing health check-up,increased AS severity is significantly associated with higher risk of incident CKD when baP-WV ≥1400 cm/s.

Objective:To explore differences in the efficacy and safety of ruxolitinib in patients with myelofibrosis by age and to identify prognostic factors by analyzing clinical features and characteristics of chromosomes and gene mutations.Methods:This study retrospectively analyzed 188 patients with myelofibrosis who received ruxolitinib in the Department of Hematology, Qilu Hospital, Shandong University from January 1, 2017, to July 1, 2024. According to age at diagnosis, the patients were divided into the middle-aged group (≤55 years), young elderly group (56-65 years), and elderly group (>65 years). Clinical features, the characteristics of chromosomes and gene mutations, and the efficacy and safety of ruxolitinib treatment were compared across the three age groups. Independent factors influencing overall survival were identified through Cox proportional risk regression analysis.Results:Before treatment, the elderly group had more underlying comorbidities, a heavier symptom burden, higher leukocyte count, higher proportion and frequency of JAK2 mutations, and lower proportion of CALR mutations. The incidence of nondriver gene mutations was significantly higher in the young elderly group. After ruxolitinib treatment, the degree of reduction in spleen size did not differ significantly among the three groups. The length of the palpable spleen below the left costal margin reduced by more than 50% from baseline in 50.9% (27/53) of the patients in the middle-aged group, 43.5% (27/62) in the young elderly group, and 45.5% (20/44) in the elderly group ( P=0.720). No significant difference was observed among the three groups in the degree of reduction in Myeloproliferative Neoplasm Symptom Assessment Form (10-item version) score ( P=0.153), with a reduction in total symptom score by more than 50% achieved by 54.0% (27/50), 60.3% (41/68), and 66.7% (34/51) of the patients from the three groups, respectively ( P=0.429). The most common hematological adverse events were anemia and thrombocytopenia, while the most common nonhematological adverse events were electrolyte disturbance, elevated transaminase activity, and pulmonary infection. Multivariate analysis indicated that in ruxolitinib-treated patients with myelofibrosis, poor overall survival was independently predicted by increased age, reduced hemoglobin, percentage of bone marrow blasts ≥ 1%, absence of JAK2 mutations, chromosomal abnormalities, ≥2 high-molecular-risk mutations, and TP53 mutations. Conclusions:Patients with myelofibrosis stratified by age exhibited heterogeneous clinical features and gene mutation profiles but similar efficacy of ruxolitinib treatment and occurrence of adverse events.

Objective To explore the relationship of metabolic comorbidities and insulin resistance(IR)with chronic kidney disease(CKD)among elderly individuals undergoing health exam.Methods A cross-sectional observational study was conducted on 8358 older adults who took health exam in Chinese PLA General Hospital between December 2009 and May 2021.According to the guidelines for CKD diagnostic criteria,they were divided into CKD group(983 cases)and non-CKD(7375 cases).Clinical data was collected,and the eGDR was calculated.Quasi-Bayesian method was used for causal mediation analysis.Results The prevalence of metabolic comorbidi-ties including hypertension,CHD,DM,hyperlipidemia,and hyperuricemia was significantly higher in the CKD group than the non-CKD group(P＜0.01).The eGDR was obviously lower in the CKD group than the non-CKD group[6.88±2.09 mg/(kg·min)vs 8.41±2.12 mg/(kg·min),P＜0.01].Logistic regression analysis revealed that,without adjusting covariates,each 1-unit increase in eGDR was associated with a 29％reduction in the risk of developing CKD(OR=0.714,95％CI:0.691-0.738,P＜0.01),and after adjusting covariates,eGDR remained signifi-cantly negatively association with the risk of CKD(P＜0.01).Mediation analysis indicated that DM and brachial-ankle pulse wave velocity accounted for the highest proportions of the mediating effect in the relationship between eGDR and CKD(14.2％and 12.5％,respectively).Conclusion In the elderly population undergoing health exam,reduced insulin sensitivity is significantly asso-ciated with the development of CKD.Diabetes and arteriosclerosis exert mediating effect in this association.

Objective To investigate the correlation between arterial stiffness(AS)and incident chronic kidney disease(CKD)among the elderly individuals taking health checkup.Methods A retrospective study was conducted on 857 elderly individuals without CKD at baseline who taking physical exams in our medical center from December 2009 to May 2021.Their clinical and labora-tory data were collected.Brachial-ankle pulse wave velocity(baPWV)was used to assess the se-verity of AS,and then the subjects were divided into normal elasticity group(201 cases),and moderate(490 cases)and severe AS group(166 cases).Kaplan-Meier curves were plotted to dis-play cumulative incidence rates of incident CKD across different AS groups.Restricted cubic splines(RCS)and Cox regression models were applied to analyze the correlation of baPWV and incident CKD risk.Results The severe AS group had significantly advanced age,greater ratio of hypertension,larger waist circumference,higher HR,SBP and DBP,increased urinary albumin/creatinine ratio(UACR),elevated levels of TG and fasting blood glucose,and baPWV than the normal elasticity group(P＜0.05).During the follow-up period,37 participants developed CKD.The incidence of CKD was obviously higher in the severe AS group than the normal arterial elas-ticity group(9.04％vs 3.48％).RCS analysis revealed a U-shaped relationship between baPWV and incident CKD risk.When baPWV ≥1 400 cm/s,each standard deviation increase in baPWV indicates the risk of incident CKD increasing by 71％(HR=1.71,95％CI:1.30-2.25,P＜0.01).Regardless of adjustment for covariates or not,baPWV remained positive correlation with inci-dent CKD risk(P＜0.05).Conclusion Among the elderly individuals undergoing health check-up,increased AS severity is significantly associated with higher risk of incident CKD when baP-WV ≥1400 cm/s.

Objective To explore the relationship of metabolic comorbidities and insulin resistance(IR)with chronic kidney disease(CKD)among elderly individuals undergoing health exam.Methods A cross-sectional observational study was conducted on 8358 older adults who took health exam in Chinese PLA General Hospital between December 2009 and May 2021.According to the guidelines for CKD diagnostic criteria,they were divided into CKD group(983 cases)and non-CKD(7375 cases).Clinical data was collected,and the eGDR was calculated.Quasi-Bayesian method was used for causal mediation analysis.Results The prevalence of metabolic comorbidi-ties including hypertension,CHD,DM,hyperlipidemia,and hyperuricemia was significantly higher in the CKD group than the non-CKD group(P＜0.01).The eGDR was obviously lower in the CKD group than the non-CKD group[6.88±2.09 mg/(kg·min)vs 8.41±2.12 mg/(kg·min),P＜0.01].Logistic regression analysis revealed that,without adjusting covariates,each 1-unit increase in eGDR was associated with a 29％reduction in the risk of developing CKD(OR=0.714,95％CI:0.691-0.738,P＜0.01),and after adjusting covariates,eGDR remained signifi-cantly negatively association with the risk of CKD(P＜0.01).Mediation analysis indicated that DM and brachial-ankle pulse wave velocity accounted for the highest proportions of the mediating effect in the relationship between eGDR and CKD(14.2％and 12.5％,respectively).Conclusion In the elderly population undergoing health exam,reduced insulin sensitivity is significantly asso-ciated with the development of CKD.Diabetes and arteriosclerosis exert mediating effect in this association.

Objective:To explore differences in the efficacy and safety of ruxolitinib in patients with myelofibrosis by age and to identify prognostic factors by analyzing clinical features and characteristics of chromosomes and gene mutations.Methods:This study retrospectively analyzed 188 patients with myelofibrosis who received ruxolitinib in the Department of Hematology, Qilu Hospital, Shandong University from January 1, 2017, to July 1, 2024. According to age at diagnosis, the patients were divided into the middle-aged group (≤55 years), young elderly group (56-65 years), and elderly group (>65 years). Clinical features, the characteristics of chromosomes and gene mutations, and the efficacy and safety of ruxolitinib treatment were compared across the three age groups. Independent factors influencing overall survival were identified through Cox proportional risk regression analysis.Results:Before treatment, the elderly group had more underlying comorbidities, a heavier symptom burden, higher leukocyte count, higher proportion and frequency of JAK2 mutations, and lower proportion of CALR mutations. The incidence of nondriver gene mutations was significantly higher in the young elderly group. After ruxolitinib treatment, the degree of reduction in spleen size did not differ significantly among the three groups. The length of the palpable spleen below the left costal margin reduced by more than 50% from baseline in 50.9% (27/53) of the patients in the middle-aged group, 43.5% (27/62) in the young elderly group, and 45.5% (20/44) in the elderly group ( P=0.720). No significant difference was observed among the three groups in the degree of reduction in Myeloproliferative Neoplasm Symptom Assessment Form (10-item version) score ( P=0.153), with a reduction in total symptom score by more than 50% achieved by 54.0% (27/50), 60.3% (41/68), and 66.7% (34/51) of the patients from the three groups, respectively ( P=0.429). The most common hematological adverse events were anemia and thrombocytopenia, while the most common nonhematological adverse events were electrolyte disturbance, elevated transaminase activity, and pulmonary infection. Multivariate analysis indicated that in ruxolitinib-treated patients with myelofibrosis, poor overall survival was independently predicted by increased age, reduced hemoglobin, percentage of bone marrow blasts ≥ 1%, absence of JAK2 mutations, chromosomal abnormalities, ≥2 high-molecular-risk mutations, and TP53 mutations. Conclusions:Patients with myelofibrosis stratified by age exhibited heterogeneous clinical features and gene mutation profiles but similar efficacy of ruxolitinib treatment and occurrence of adverse events.

OBJECTIVE: To evaluate the predictive value of plasma heparin-binding protein (HBP) combined with albumin (Alb) for predicting 28-day mortality in patients with sepsis. METHODS: The clinical data of patients with sepsis admitted to the emergency intensive care unit (EICU) of the People's Hospital of Shenzhen Baoan District from March 2020 to March 2024 were retrospectively analyzed. The study began at the time of the first diagnosis of sepsis upon EICU admission and ended upon patient death or at 28 days. The gender, age, length of stay in EICU, underlying diseases, and infection sites were recorded. Within 24 hours of sepsis diagnosis, blood culture results, white blood cell count (WBC), C-reactive protein (CRP), procalcitonin (PCT), blood lactate acid (Lac), HBP, Alb, sequential organ failure assessment (SOFA), acute physiology and chronic health evaluation II (APACHE II), mortality in emergency department sepsis score (MEDS), modified early warning score (MEWS), number of organ failures, use of vasopressors, application of mechanical ventilation, renal replacement therapy, and 28-day prognosis were recorded, the differences in these indicators between two groups were compared. Univariate and multivariate Logistic regression analyses were used to analyze the risk factors of 28-day mortality in patients with sepsis. Receiver operator characteristic curve (ROC curve) was drawn, and the area under the ROC curve (AUC) was calculated to evaluate the early predictive value of various risk factors for 28-day mortality in patients with sepsis. RESULTS: A total of 300 patients with sepsis were included, with 16 excluded, resulting in 284 patients being analyzed. Among them, 191 survived and 93 died within 28 days. There were no statistically significant differences between the two groups in terms of gender, age, underlying diseases, infection sites, blood culture positivity rate, number of organ failures, and length of stay in EICU. Univariate analysis showed that the rate of vasopressor use, the rate of mechanical ventilation, HBP, PCT, CRP, Lac, SOFA score, APACHE II score, MEDS score, and MEWS score were significantly higher in the death group than those in the survival group, while Alb was significantly lower in the death group than that in the survival group. Multivariate Logistic regression analysis showed that HBP and Alb were independent risk factors for predicting 28-day mortality in patients with sepsis [odds ratio (OR) and 95% confidence interval (95%CI) were 1.093 (0.989-1.128) and 1.174 (1.095-1.259), both P < 0.05]. ROC curve analysis showed that both HBP and Alb had certain predictive value for 28-day mortality in patients with sepsis [AUC and 95%CI were 0.820 (0.717-0.923) and 0.786 (0.682-0.890), both P < 0.05]. When the critical value of HBP was 117.50 μg/L, the sensitivity was 85.90%, and the specificity was 70.50%. When the critical value of Alb was 28.30 g/L, the sensitivity was 69.30%, and the specificity was 81.20%. When the two indexes were combined for diagnosis, the AUC was 0.881 (95%CI was 0.817-0.945, P < 0.001), the sensitivity was 92.70%, and the specificity was 76.80%. CONCLUSIONS HBP and Alb are independent risk factors for predicting 28-day mortality in patients with sepsis. The combined prediction efficiency of HBP and Alb for 28-day mortality in patients with sepsis is superior to a single indicator.
Humans ; Sepsis/diagnosis* ; Retrospective Studies ; Predictive Value of Tests ; Intensive Care Units ; Blood Proteins/analysis* ; Prognosis ; Antimicrobial Cationic Peptides/blood* ; APACHE ; Male ; Female ; Organ Dysfunction Scores ; ROC Curve ; Middle Aged ; C-Reactive Protein/analysis* ; Emergency Service, Hospital ; Aged ; Hospital Mortality ; Serum Albumin/analysis*

OBJECTIVE: Because of the limited number of studies and small sample sizes, whether metabolic syndrome (MS) leads to the occurrence and progression of osteoporosis and the possible underlying mechanisms require further investigation. This study aimed to investigate the association between MS and osteoporosis, along with its influencing factors. METHODS: This observational cross-sectional study included 139,470 individuals aged ≥ 18 years who underwent health examinations from September 2014 to March 2022. Based on bone mineral density (BMD) screening results, the participants were categorized into a suspected osteoporosis or non-osteoporosis group (control). Participants were further divided into those who met 0 MS criteria, 1 MS criterion, 2 MS criteria, and ≥ 3 MS criteria (MS group). Participants who had undergone health examinations at least twice formed the follow-up cohort; a self-matched analysis was performed on those with follow-up periods ≥ 5 years and unchanged MS grouping. RESULTS: Several examination indicators in the suspected osteoporosis group showed statistically significant differences compared with the control group. The proportion of suspected osteoporosis in the MS group was significantly increased compared with that in the 0 MS criteria group (odds ratio [ OR]: 1.215, Z = 29.11, P < 0.001, 95% confidence interval: 1.199-1.231). After adjusting for age, sex, smoking, and alcohol consumption, the 2 MS criteria group and MS group still had OR values > 1 ( P < 0.001). In the follow-up cohort, the proportion of suspected osteoporosis increased gradually with an increase in the number of MS criteria met at baseline and during each follow-up visit ( P < 0.05), with the highest proportion observed in the MS group. However, the proportion of suspected osteoporosis did not increase significantly over time in the different MS groups ( P > 0.05). In the follow-up cohort, the proportion of individuals transitioning from normal BMD to suspected osteoporosis was higher in the MS group after ≥ 5 years of follow-up compared with the group meeting 0 MS criteria (0.08% versus 1.15%, χ ² = 10.76, P = 0.001). There was no significant difference in BMD values for the 0 MS criteria group after 5 years ( P > 0.05), whereas the other three groups experienced a significant decrease in BMD values after 5 years ( P < 0.05). CONCLUSION MS is an independent risk factor for osteoporosis, and the effect of risk factors related to MS on osteoporosis may exceed that of aging alone. The specific mechanisms warrant further investigation.
Humans ; Osteoporosis/etiology* ; Female ; Male ; Metabolic Syndrome/complications* ; Middle Aged ; Cross-Sectional Studies ; China/epidemiology* ; Aged ; Adult ; Bone Density ; Risk Factors

We researched the mechanism of African swine fever virus (ASFV) protein E248R in regulating the cGAS-STING pathway. First, we verified via the dual-luciferase reporter assay system that E248R protein inhibited the secretion of IFN-β induced by cGAS-STING or HT-DNA in a dose-dependent manner. The relative quantitative PCR analysis indicated that the overexpression of E248R inhibited HT-DNA-induced transcription of IFN-b1, RANTES, IL-6, and TNF-α in PK-15 cells. Next, we found that E248R interacted with STING by co-immunoprecipitation assay and laser confocal microscopy. Finally, we demonstrated that E248R inhibited the expression of STING protein by using Western blotting. We demonstrated for the first time that the E248R protein of ASFV suppressed the host innate immune response via inhibiting STING expression. The results are pivotal in extending the understanding of the ASFV immune escape and can guide the design of vaccines against ASFV.
African Swine Fever Virus/genetics* ; Animals ; DNA ; Immunity, Innate ; Nucleotidyltransferases/metabolism* ; Signal Transduction ; Swine

Beh?et′s syndrome is a kind of chronic systemic vasculitis with involvement of multiple organs. Intestinal involvement of Beh?et′s syndrome is presently named as intestinal Beh?et′s syndrome. Recently, there is considering another kind of disease type with only typical intestinal ulcers. Since it is difficult to differentiate intestinal Beh?et′s syndrome from Crohn′s disease, intestinal tuberculosis, intestinal lymphoma, and intestinal manifestations of many other autoimmune diseases, and there is limited evidence for the therapy of intestinal Beh?et′s syndrome, proposing diagnosis and treatment recommendations for intestinal Beh?et′s syndrome through evidence-based judgment will be of great significance for clinical practice.