Objective:To investigate the role of the CD38/p53/ME1 axis in regulating T cell mitochondrial function and senescence during HIV infection.Methods:The expression of CD38 on T cells was examined in HIV-infected individuals receiving antiretroviral therapy(ART), untreated HIV-infected individuals, and HIV-negative healthy controls. Flow cytometry was used to compare senescence markers and mitochondrial function between CD38 + and CD38 - T cells. Malic enzyme 1(ME1) mRNA levels were measured by qRT-PCR in T cells treated with the CD38 inhibitor 78c. Mitochondrial function and senescence were assessed in T cells treated with an ME1 inhibitor. The regulatory mechanism of CD38-mediated ME1 downregulation was further explored. Results:Compared to healthy controls, T cells from HIV-infected individuals exhibited significantly elevated CD38 expression, which persisted despite ART. CD38 + T cells showed increased senescence (CD28 -CD57 + subset) and mitochondrial dysfunction[depolarization and reactive oxygen species(ROS) accumulation]. CD38 inhibition upregulated ME1 mRNA level ( P<0.05). ME1 suppression led to mitochondrial impairment (reduced membrane potential and elevated ROS) and senescence in T cells. Mechanistically, CD38 depletion increased NAD + levels and SIRT1 activity, while SIRT1/p53 inhibition rescued ME1 expression, suggesting CD38 regulates ME1 via the NAD + /SIRT1/p53 axis. Conclusions:The CD38/p53/ME1 axis drives T cell senescence in HIV infection by disrupting mitochondrial function. Targeting this pathway may ameliorate CD38-associated T cell dysfunction and immune aging.

Objective:To investigate the role of the CD38/p53/ME1 axis in regulating T cell mitochondrial function and senescence during HIV infection.Methods:The expression of CD38 on T cells was examined in HIV-infected individuals receiving antiretroviral therapy(ART), untreated HIV-infected individuals, and HIV-negative healthy controls. Flow cytometry was used to compare senescence markers and mitochondrial function between CD38 + and CD38 - T cells. Malic enzyme 1(ME1) mRNA levels were measured by qRT-PCR in T cells treated with the CD38 inhibitor 78c. Mitochondrial function and senescence were assessed in T cells treated with an ME1 inhibitor. The regulatory mechanism of CD38-mediated ME1 downregulation was further explored. Results:Compared to healthy controls, T cells from HIV-infected individuals exhibited significantly elevated CD38 expression, which persisted despite ART. CD38 + T cells showed increased senescence (CD28 -CD57 + subset) and mitochondrial dysfunction[depolarization and reactive oxygen species(ROS) accumulation]. CD38 inhibition upregulated ME1 mRNA level ( P<0.05). ME1 suppression led to mitochondrial impairment (reduced membrane potential and elevated ROS) and senescence in T cells. Mechanistically, CD38 depletion increased NAD + levels and SIRT1 activity, while SIRT1/p53 inhibition rescued ME1 expression, suggesting CD38 regulates ME1 via the NAD + /SIRT1/p53 axis. Conclusions:The CD38/p53/ME1 axis drives T cell senescence in HIV infection by disrupting mitochondrial function. Targeting this pathway may ameliorate CD38-associated T cell dysfunction and immune aging.

Objective To investigate the long-term incidence of in-stent stenosis(ISS)in patients with intracranial aneurysms receiving pipeline embolization device(PED)who showed no ISS at short-to-medium term follow-up examination.Methods The clinical data of patients,who received PED treatment at the Department of Neurointervention,First Affiliated Hospital of Zhengzhou University of China between April 2015 and June 2022,were retrospectively collected.The patients with intracranial aneurysms,who showed no ISS at the initial follow-up with DS A and completed＞12 months long-term follow-up check after treatment at the same hospital,were screened out,and their relevant clinical data and imaging materials were collected.The incidence of ISS occurring in postoperative＞12 months long-term follow-up was calculated.The ISS was defined as a＞25％lumen loss of the parent artery when compared with its lumen size measured immediately after PED implantation.Results A total of 57 patients with 61 aneurysms were enrolled in this study,and a total of 68 PEDs were implanted.Forty-one(67.21％)aneurysms were treated by PED implantation only,and 20(32.79％)aneurysms by PED plus spring coils.The median initial follow-up time was 184.0 days(119.0,212.5).At postoperative＞12 months long-term follow-up visit,DSA was employed for 35(57.38％)aneurysms,CTA was adopted for 22(36.07％)aneurysms,and 3D-SPACE sequence MR scan was performed in 4(6.56％)aneurysms.The median follow-up time was 538.0 days(407.5,678.0),and the incidence of ISS was 0％.No ISS-related neurological symptoms occurred in all patients.Conclusion In treating intracranial aneurysms with PED,the postoperative incidence of ISS is low.No ISS is found during the short-term follow-up period,and long-term follow-up results tend to indicate that no ISS events have occurred.

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

Abstract: Objective　To analyze the genotype of carbapenemase resistance genes and their genetic homology in multidrug-resistant Acinetobacter baumannii, and to provide a theoretical basis for guiding the rational use of antibiotics and controlling the prevalence of nosocomial infections. Methods A total of 83 multidrug-resistant Acinetobacter baumannii isolated from patients in the intensive care unit (ICU) and environmental specimens in the Sixth People's Hospital of Nantong from July 2020 to December 2021 were collected. The bacteria were identified and subjected to drug sensitivity tests using the BioMérieux DL96-Ⅱ automatic bacterial identification susceptibility system. The carbapenemase-related drug resistance gene types were detected using the polymerase chain reaction (PCR) method, and clones were analyzed by pulsed field gel electrophoresis (PFGE). Results The types of 83 ICU Acinetobacter baumannii specimens include sputum (43 strains), broncholavage fluid (20 strains), and surfaces of objects such as ventilators (20 strains). The resistance rates of all strains to imipenem, tetracycline, gentamicin, amikacin and ciprofloxacin were 100%, 32.5%, 38.6%, 41.0% and 77.1% respecitively, while the resistance rates to others such as ticarcillin and clavulanate were greater than 95%. All strains carried were detected to carry OXA-23 and OXA-51 genes, while OXA-24, OXA-58, IMP-1, VIM, IMP-4, SIM and NDM-1 resistance genes were all negative. PFGE homology analysis confirmed that 83 strains of Acinetobacter baumannii, with counts of 12, 18, 12, 13, 10, 6, 7, 5 respectively, mainly A, B, C, D, E clones, the rest were sporadic clones. Conclusions The carbapenem resistant Acinetobacter baumannii isolated from our ICU are widely drug-resistant to commonly used antimicrobial drugs, with B clone strain being the major prevalent strain. Carrying OXA-23 and OXA-51 genes may be an important reason for the resistance of Acinetobacter baumannii to carbapenem antibiotics in our ICU. Rational use of antimicrobial drugs, enhanced monitoring of bacterial resistance, and effective control of the generation and further spread of drug-resistant strains should be emphasized.

Objective To explore the association of (cardiometabolic index , CMI ) and ( lipid accumulation product , LAP ) with the prevalence of hypertension in adults in Pingshan District, Shenzhen, and to evaluate the predictive value of CMI and LAP for the prevalence of hypertension. Methods A cross-sectional survey was conducted, in which 1000 permanent residents aged 18-69 years in Pingshan District, Shenzhen were randomly selected as survey subjects. The data were collected using questionnaires, physical measurements and blood tests, and the relationship between CMI, LAP and hypertension prevalence was analyzed using logistic regression models. Results A total of 987 subjects were included in the analysis, including 471 (47.72%) males and 516 (52.28%) females, with an average age of 40.9 ± 11.1 years. Subjects of different genders were divided into groups Q1 to Q4 according to quartiles of CMI and LAP, and the prevalence of hypertension increased with increasing levels of CMI and LAP in both men and women (P for trend < 0.001). Logistic regression analysis revealed that after adjusting for variables such as age and occupation, the OR for hypertension was 1.251 (1.025-1.526) and 1.685 (1.001-2.836) for men and women, respectively, for each standard deviation increase in CMI; the OR for hypertension was 3.519 (1.343-9.222) for men in the Q4 group, compared to the CMI subgroup Q1. For each standard deviation increase in LAP, the ORs for hypertension were 1.355 (1.089-1.686) and 1.825 (1.023-3.254) for men and women, respectively; compared to LAP subgroup Q1, the ORs for hypertension in the male Q3 and Q4 groups were 2.554 (1.103-5.909) and 5.322 (2.393-11.834), while the OR for hypertension in the female Q4 group was 2.906 (1.096-7.703). ROC analysis revealed that the area under the curve (AUC) for CMI, LAP, and BMI was 0.671, 0.704, and 0.702 for males, and 0.660, 0.722, and 0.697 for females, respectively. The AUC for LAP was greater than that for CMI for different genders (P < 0.01). Conclusion The greater the CMI and LAP values in adults in Pingshan District, Shenzhen , the higher the prevalence of hypertension. CMI and LAP have certain values in predicting the prevalence of hypertension.

【Objective】 To explore the relationship between chronic comorbidity and the physical and mental health of relatives of elderly people during the nursing home confinement, and to analyze the mediating effects of perceived stress and intolerance of uncertainty in this context. 【Methods】 A total of 568 family members of elderly people in nine elderly institutions in Shaanxi Province were selected. The survey included the short version of the Perceived Stress Scale, Intolerance of Uncertainty Scale, and The World Health Organization-5 Well-being Index. The data were analyzed with Stata for correlation and mediation effects. 【Results】 ① The comorbidities of chronic diseases was positively correlated with the perceived stress (r=0.16, P<0.001) and intolerance of uncertainty (r=0.11, P=0.006) of the family members, but negatively correlated with the physical and mental health of the family members (r=-0.13, P=0.002). ② The mediating effect of perceived stress between chronic disease co-morbidity and physical and mental health of family members in older adults was -0.023, accounting for 18.8% of the total effect; the mediating effect of intolerance of uncertainty between chronic disease co-morbidity and physical and mental health of family members in older adults was -0.041, accounting for 33.5% of the total effect. 【Conclusion】 During closed management in a nursing facility, the physical and mental health of family members of older adults with chronic co-morbidities is poorer than that of family members of non-chronic co-morbidities. And it can lead to a decline in physical and mental health of family members through increased perceived stress and intolerance of uncertainty.

Objective:To compare the differences in the prevalence of mild micro-hepatic encephalopathy (MHE) among patients with cirrhosis by using the psychometric hepatic encephalopathy score (PHES) and the Stroop smartphone application (Encephal App) test.Methods:This prospective, multi-center, real-world study was initiated by the National Clinical Medical Research Center for Infectious Diseases and the Portal Hypertension Alliance and registered with International ClinicalTrials.gov (NCT05140837). 354 cases of cirrhosis were enrolled in 19 hospitals across the country. PHES (including digital connection tests A and B, digital symbol tests, trajectory drawing tests, and serial management tests) and the Stroop test were conducted in all of them. PHES was differentiated using standard diagnostic criteria established by the two studies in China and South Korea. The Stroop test was evaluated based on the criteria of the research and development team. The impact of different diagnostic standards or methods on the incidence of MHE in patients with cirrhosis was analyzed. Data between groups were differentiated using the t-test, Mann-Whitney U test, and χ2 test. A kappa test was used to compare the consistency between groups. Results:After PHES, the prevalence of MHE among 354 cases of cirrhosis was 78.53% and 15.25%, respectively, based on Chinese research standards and Korean research normal value standards. However, the prevalence of MHE was 56.78% based on the Stroop test, and the differences in pairwise comparisons among the three groups were statistically significant (kappa = -0.064, P < 0.001). Stratified analysis revealed that the MHE prevalence in three groups of patients with Child-Pugh classes A, B, and C was 74.14%, 83.33%, and 88.24%, respectively, according to the normal value standards of Chinese researchers, while the MHE prevalence rates in three groups of patients with Child-Pugh classes A, B, and C were 8.29%, 23.53%, and 38.24%, respectively, according to the normal value standards of Korean researchers. Furthermore, the prevalence rates of MHE in the three groups of patients with Child-Pugh grades A, B, and C were 52.68%, 58.82%, and 73.53%, respectively, according to the Stroop test standard. However, among the results of each diagnostic standard, the prevalence of MHE showed an increasing trend with an increasing Child-Pugh grade. Further comparison demonstrated that the scores obtained by the number connection test A and the number symbol test were consistent according to the normal value standards of the two studies in China and South Korea ( Z = -0.982, -1.702; P = 0.326, 0.089), while the other three sub-tests had significant differences ( P < 0.001). Conclusion:The prevalence rate of MHE in the cirrhotic population is high, but the prevalence of MHE obtained by using different diagnostic criteria or methods varies greatly. Therefore, in line with the current changes in demographics and disease spectrum, it is necessary to enroll a larger sample size of a healthy population as a control. Moreover, the establishment of more reliable diagnostic scoring criteria will serve as a basis for obtaining accurate MHE incidence and formulating diagnosis and treatment strategies in cirrhotic populations.

Sudden sensorineural hearing loss (SSNHL) refers to the sudden and unexplained sensorineural hearing loss within 72 h and a decrease in hearing of ≥30 dB affecting at least 3 consecutive frequencies. It is one of the common emergencies in neurology and otolaryngology. Early etiological evaluation and systematic and targeted treatment are very important for delaying the progression of SSNHL and restoring hearing. Recent studies have shown that SSNHL overlaps with vascular risk factors of ischemic stroke, and may predict the risk of ischemic stroke. SSNHL may be one of the clinical manifestation and even the prodromal symptoms of ischemic stroke, especially the infarction of the blood supply area of the anterior inferior cerebellar artery or its branch internal auditory artery. Although these factors can not fully reveal the relationship between SSNHL and ischemic stroke, they are enough to warn clinicians that they should consider the possibility of ischemic stroke when receiving patients with SSNHL. Screening of vascular risk factors for patients with SSNHL as early as possible is helpful to avoid the risk of recurrence of ischemic stroke.

Objective : To analyze the status and influencing factors of the intention of people aged 18 to 25 years to primary medical institutions and their satisfaction for health services in Zhejiang Province, so as to provide basis for the improvement of health services in primary medical institutions. Methods: During November and December in 2019,the 18-25 year-old people in Zhejiang Province were recruited to investigate the general information, intention to seek medical advice and satisfaction for health services in primary medical institutions through WeChat. Logistic regression was performed to analyze the influencing factors of the intention and the satisfaction. Importance matrix was used to analyze the key drivers of the satisfaction. Results: Among the 620 people surveyed, with a response rate of 93.37%, 142 (22.90%) chose primary medical institutions for advice. Actually 516 (83.23%) people went to primary medical institutions last year, and 384 ( 74.42% ) of them were satisfied with the health services. The results of multivariate logistic regression analysis showed that the people aged 18-25 years who were under the new rural cooperative medical care system ( OR=3.062, 95%CI: 1.745-5.373 ) and who had records in community health centers ( OR=0.547, 95%CI: 0.308-0.970 ) were more likely to go to primary medical institutions for medical advice; the ability of doctors ( OR=1.478, 95%CI:1.168-1.871 ) ,the drug notification by medical staff ( OR=1.308, 95%CI: 1.065-1.606 ) , routine examination items ( OR=1.523, 95%CI: 1.227-1.889 ) , the ways of payment ( OR=1.168, 95%CI: 1.017-1.340 ) , the comfort of environment ( OR=1.785, 95%CI: 1.437-2.219 ) and the bulletin boards of health knowledge ( OR=1.302, 95%CI: 1.086-1.561 ) were associated with the satisfaction. The results of importance matrix analysis showed that the ability of doctors and routine examination items were the priorities to improve, followed by the drug notification by medical staff; the comfort of environment had competitive advantages; the ways of payment and the bulletin boards of health knowledge needed to be further analyzed. Conclusions The 18-25-year-old people in Zhejiang Province were less intended to seek medical advice in primary medical institutions, which was associated with the type of medical insurance and records in community health centers. They were satisfied with the health services, the ability of doctors and routine examination items were the key drivers.