ObjectiveTo investigate the recurrence of ischemic stroke (IS) and to analyze the association between four indices of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) and the risk of IS recurrence by analyzing the follow-up data related to IS in the community-based natural population of Songjiang District, Shanghai, so as to provide a scientific basis for improving the prognosis of stroke patients in the community and controlling IS recurrence. MethodsA prospective follow-up study was conducted among the IS patients in the community-based cohort population, collecting data about patient’s age, gender, disease history, biochemical indicators, and etc. Cox regression model and restricted cubic spline model were used to analyze the relationship between different levels of plasma lipids and the recurrence of IS in these patients. ResultsA total of 1 368 patients with IS were included. The total follow-up duration was 7 171.46 person-years, with a median follow-up time of 6.24 years. There were 420 cases of IS recurrence, resulting in a cumulative recurrence rate of 30.70%. The results of multivariate Cox regression analysis showed that the recurrence risk of IS was reduced when the baseline TC and LDL-C levels of IS patients were in the ranges of 4.65‒5.67 mmol·L^-1 and 2.52‒3.46 mmol·L^-1, respectively. The results of restricted cubic spline analysis showed a U-shaped relationship between baseline TC and LDL-C levels and the recurrence risk in IS patients. ConclusionThe cumulative recurrence rate of patients with IS in the community of Songjiang District in Shanghai is high, and the levels of TC and LDL-C at baseline survey are correlated with the recurrence of IS in these patients. It is suggested to pay more attention to the levels of LDL-C and TC in patients with IS, so as to improve the prognosis.

Objective:To analyze the mediating effect of cardiovascular health status (CVH) on the association between educational level and cardiovascular disease (CVD).Methods:The participants were from Shanghai Suburban Adult Cohort and Biobank, and questionnaire survey, physical examination, blood biochemistry were conducted from 2016 to 2020 for baseline information collection, and follow up was conducted until March 31, 2024 based on the medical data, CVD incidence data and death surveillance data at different levels. The associations of educational level, CVH and time to CVD onset of the study population were analyzed using the accelerated failure time model to analyze the mediating effects of CVH, health behaviors, and health factors in the association of educational level and time to CVD onset. The mediating effects of educational level, gender, and age moderated associations were also analyzed.Results:A total of 57 312 participants were included, with 2 780 new cases of CVD during a median follow-up of 6.71 (6.71-6.72) years, and a mean incidence density of 7.77/1 000 person-years (95% CI: 7.48/1 000 person-years -8.06/1 000 person-years). In total, the less educational level and the lower CVH, the higher CVD incidence density ( P<0.05). The results of accelerated failure time models showed that the time ratio for CVD-free survival was 1.15 (95% CI: 1.06-1.24) and 1.33 (95% CI: 1.10-1.60) for moderate and high educational level, respectively. The results of the mediation effect analysis showed that the association between moderate and high educational level and time to CVD onset was 29.60% (20.50%-50.00%) and 36.10% (23.80%-59.00%), 9.97% (5.07%-20.00%) and 13.84% (6.84%-29.00%), 15.24% (9.64%-27.00%) and 17.55% (11.58%-33.00%) of mediators mediated by CVH, health behaviors, health factors, respectively. Among them, there was an exposure-mediated interaction of educational level and a positive moderating effect of age. Conclusion:CVH, health behaviors and health factors had a proportionate mediating effect in the association between educational level and risk of CVD development.

Our research reveals the critical role of the suprachiasmatic nucleus (SCN) vasoactive intestinal peptide (VIP) neurons in mediating light-induced transient forgetting. Acute exposure to bright light selectively impairs trace fear memory by activating VIP neurons in the SCN, as demonstrated by increased c-Fos expression and Ca²⁺ recording. This effect can be replicated and reversed through optogenetic and chemogenetic manipulations of SCN VIP neurons. Furthermore, we identify the SCN → PVT (paraventricular nucleus of the thalamus) VIP neuronal circuitry as essential in this process. These findings establish a novel role for SCN VIP neurons in modulating memory accessibility in response to environmental light cues, extending their known function beyond circadian regulation and revealing a mechanism for transient forgetting.
Animals ; Vasoactive Intestinal Peptide/metabolism* ; Male ; Mice ; Neurons/metabolism* ; Suprachiasmatic Nucleus/physiology* ; Light ; Mice, Inbred C57BL ; Memory/physiology* ; Fear/physiology* ; Suprachiasmatic Nucleus Neurons/metabolism* ; Optogenetics ; Proto-Oncogene Proteins c-fos/metabolism*

Objective:To analyze the mediating effect of cardiovascular health status (CVH) on the association between educational level and cardiovascular disease (CVD).Methods:The participants were from Shanghai Suburban Adult Cohort and Biobank, and questionnaire survey, physical examination, blood biochemistry were conducted from 2016 to 2020 for baseline information collection, and follow up was conducted until March 31, 2024 based on the medical data, CVD incidence data and death surveillance data at different levels. The associations of educational level, CVH and time to CVD onset of the study population were analyzed using the accelerated failure time model to analyze the mediating effects of CVH, health behaviors, and health factors in the association of educational level and time to CVD onset. The mediating effects of educational level, gender, and age moderated associations were also analyzed.Results:A total of 57 312 participants were included, with 2 780 new cases of CVD during a median follow-up of 6.71 (6.71-6.72) years, and a mean incidence density of 7.77/1 000 person-years (95% CI: 7.48/1 000 person-years -8.06/1 000 person-years). In total, the less educational level and the lower CVH, the higher CVD incidence density ( P<0.05). The results of accelerated failure time models showed that the time ratio for CVD-free survival was 1.15 (95% CI: 1.06-1.24) and 1.33 (95% CI: 1.10-1.60) for moderate and high educational level, respectively. The results of the mediation effect analysis showed that the association between moderate and high educational level and time to CVD onset was 29.60% (20.50%-50.00%) and 36.10% (23.80%-59.00%), 9.97% (5.07%-20.00%) and 13.84% (6.84%-29.00%), 15.24% (9.64%-27.00%) and 17.55% (11.58%-33.00%) of mediators mediated by CVH, health behaviors, health factors, respectively. Among them, there was an exposure-mediated interaction of educational level and a positive moderating effect of age. Conclusion:CVH, health behaviors and health factors had a proportionate mediating effect in the association between educational level and risk of CVD development.

ObjectiveTo describe different non-alcoholic fatty liver disease （NAFLD） outcomes among community inhabitants， and further to explore the correlation between bio-indicator level variance and the outcomes. MethodsPhysical indicators （height， weight， waist circumstances， hip circumstances， blood pressure， etc）， biochemical indicators ［fasting plasma glucose， HbA1c， serum triglycerides（TG）， serum total cholesterol（TC）， low-density lipoprotein cholesterol（LDL-C）， high-density lipoprotein cholesterol（HDL-C）， liver related transaminase， etc］ and clinical imaging （B-scan ultrasonography） were collected during the follow-up from the Songjiang Natural Population Sub-cohort. The identification of NAFLD was supported by the definition criteria from Guidelines for the diagnosis and treatment of non⁃alcoholic fatty liver disease. Paired t-test and multifactorial logistic regression model were used to compare the difference between the indicator level of the subjects from different outcome subgroups and to further analyze the correlation between these indicator variance and different NAFLD outcomes. ResultsDuring a median follow-up time of 2.94 years， 12 076 subjects were involved. The cumulative NAFLD incidence and remission rate were 21.57% and 31.15%， respectively. The proportion of subjects who still had NAFLD was 27.96%. Among subjects with newly-developed NAFLD， indicators including blood pressure， BMI， fasting plasma glucose， and plasma lipid level increased， while in the remission subgroup， blood pressure， BMI（WHR）， waist-hip ratio（WHR）， and TG level were significantly decreased. Increased level of systolic pressure， WHR， BMI， HbA1c， and LDL-C might be the risk factors to the occurrence of NAFLD. While decreased level of WHR， BMI， TC and LDL-C level and elevated HDL-C level were likely to be the influencing factors of NAFLD remission process. ConclusionThe NAFLD morbidity in the community inhabitants is relatively high. BMI， WHR， fasting plasma sugar and plama lipid level variance may act as the influencing factors towards different NAFLD outcomes.

Objective:To explore the efficacy of ixazomib combination treatment therapies for multiple myeloma (MM), and the influencing factors of prognosis.Methods:The clinical data of 80 MM patients admitted to Yancheng Third People's Hospital from January 2020 to January 2022 were retrospectively analyzed. All patients received 3 courses of ixazomib combination treatment therapies (28 d was 1 course). All combination treatment therapies included ID group (ixazomib + dexamethasone, 11 cases) and ID + immunomodulator group (ixazomib + dexamethasone + lenalidomide/thalidomide, 50 cases), ID + other chemotherapy drugs group (ixazzomib + dexamethasone + doxorubicin liposome/cyclophosphamide/bendamustine, 19 cases). The clinical efficacy of patients in different treatment regimens was compared, and the prognosis was followed up and recorded. The clinical characteristics between the survival and the dead patients were compared. Cox proportional risk model was used to make multivariate analysis of the overall survival of MM patients receiving ixazomib combination therapies.Results:The treatment was effective in 9 cases (81.82%) of the ID group, 32 cases (64.00%) of the ID + immunomodulator group, and 9 cases (47.37%) of the ID + other chemotherapy drugs group. There was no statistically significant difference in the effectiveness rate of 3 ixazomib combination regimens ( χ2 = 0.62, P = 0.432). All patients were followed up for 5 to 20 months, with an average follow-up time of (15±4) months. There were statistically significant differences in immunoglobulin type, Durie-Salmon stage, early treatment line and therapeutic efficacy between the survival group (49 cases) and the death group (31 cases) (all P < 0.05). Multivariate Cox regression analysis showed that the clinical effectiveness (effectiveness vs. ineffectiveness: OR = 0.242, 95% CI 0.103-0.567, P = 0.001) and the previous first-line treatment (the first-line vs. the other lines: OR = 0.577, 95% CI 0.452-0.736, P < 0.001) were independent protective factors for the overall survival of MM. Conclusions:The 3 ixazomib combination therapies have a certain efficacy in the treatment of MM; ID regimen has the best clinical efficacy and survival. The clinical effectiveness and the previous first-line treatment are independent protective factors for the survival of MM.

Abdomen/diagnostic imaging* ; Artificial Intelligence ; Body Composition ; Magnetic Resonance Imaging ; Practice Guidelines as Topic

Objective:To explore the risk factors of linezolid-induced thrombocytopenia (LIT) and evaluate their predictive value.Methods:Medical records of hospital acquired pneumonia (HAP) patients who admitted in Suzhou Municipal Hospital from July 2019 to October 2021 and received linezolid were collected and retrospectively analyzed. Clinical data including general information, comorbidities, linezolid application, laboratory test results, and trough concentration of linezolid was extracted. Patients were divided into LIT group and non-LIT group according to the occurrence of LIT. Clinical characteristics were compared between the 2 groups; risk factors of LIT in patients with HAP were analyzed using a binary logistic regression model, and the odds ratio ( OR) and its 95% confidence interval ( CI) were calculated; the predictive value of the risk factors for LIT were evaluated using receiver operating characteristic (ROC) curve. Results:A total of 74 patients were included in the study, including 55 males and 19 females, aged 82 (73, 88) years. LIT occurred in 25 patients (33.8%). Compared with the non-LIT group, the age and trough concentration of linezolid in patients in the LIT group were higher [88 (81, 92) years vs. 79(70, 86) years, P=0.001; (19.6±10.3) mg/L vs. (9.8±6.4) mg/L, P<0.001], and the baseline platelet count and baseline creatinine clearance rate were lower [181(162, 212) ×10 9/L vs. 229 (169, 289) ×10 9/L, P=0.025; 31(19, 44) ml/(min·1.73 m 2) vs. 46 (27, 65) ml/(min·1.73 m 2), P=0.018]. Binary logistic regression analysis showed that the lower baseline creatinine clearance rate ( OR=0.974, 95 %CI: 0.951-0.998, P=0.035) and higher trough concentration of linezolid ( OR=1.156, 95 %CI: 1.059-1.261, P=0.001) were independent risk factors for LIT in HAP patients. ROC curve analysis showed that the threshold of the age, trough concentration of linezolid, baseline platelet count, and baseline creatinine clearance rate were 87 years (sensitivity 56.0%, specificity 83.7%), 15.4 mg/L (sensitivity 64.0%, specificity 87.8%), 189×10 9/L (sensitivity 67.3%, specificity 68.0%), and 45 ml/(min·1.73 m 2) (sensitivity 53.1%, specificity 80.0%), respectively. Patients were respectively divided into 2 groups according to the thresholds and the incidences of LIT were compared. The results showed that the incidences of LIT in patients with age and trough concentration of linezolid exceeding the thresholds and in patients with baseline plate count and baseline creatinine clearance rate lower than or equal to the thresholds were significantly higher than those in the other patients (all P<0.01). Conclusions:Baseline creatinine clearance rate, trough concentration of linezolid, age, and plate count are risk factors for LIT in HAP patients and their thresholds are 45 ml/(min·1.73 m 2), 15.4 mg/L, 87 years, and 189×10 9/L, respectively. These risk factors have good predictive value for the occurrence of LIT.

Objective:To explore the risk factors of linezolid-induced thrombocytopenia (LIT) and evaluate their predictive value.Methods:Medical records of hospital acquired pneumonia (HAP) patients who admitted in Suzhou Municipal Hospital from July 2019 to October 2021 and received linezolid were collected and retrospectively analyzed. Clinical data including general information, comorbidities, linezolid application, laboratory test results, and trough concentration of linezolid was extracted. Patients were divided into LIT group and non-LIT group according to the occurrence of LIT. Clinical characteristics were compared between the 2 groups; risk factors of LIT in patients with HAP were analyzed using a binary logistic regression model, and the odds ratio ( OR) and its 95% confidence interval ( CI) were calculated; the predictive value of the risk factors for LIT were evaluated using receiver operating characteristic (ROC) curve. Results:A total of 74 patients were included in the study, including 55 males and 19 females, aged 82 (73, 88) years. LIT occurred in 25 patients (33.8%). Compared with the non-LIT group, the age and trough concentration of linezolid in patients in the LIT group were higher [88 (81, 92) years vs. 79(70, 86) years, P=0.001; (19.6±10.3) mg/L vs. (9.8±6.4) mg/L, P<0.001], and the baseline platelet count and baseline creatinine clearance rate were lower [181(162, 212) ×10 9/L vs. 229 (169, 289) ×10 9/L, P=0.025; 31(19, 44) ml/(min·1.73 m 2) vs. 46 (27, 65) ml/(min·1.73 m 2), P=0.018]. Binary logistic regression analysis showed that the lower baseline creatinine clearance rate ( OR=0.974, 95 %CI: 0.951-0.998, P=0.035) and higher trough concentration of linezolid ( OR=1.156, 95 %CI: 1.059-1.261, P=0.001) were independent risk factors for LIT in HAP patients. ROC curve analysis showed that the threshold of the age, trough concentration of linezolid, baseline platelet count, and baseline creatinine clearance rate were 87 years (sensitivity 56.0%, specificity 83.7%), 15.4 mg/L (sensitivity 64.0%, specificity 87.8%), 189×10 9/L (sensitivity 67.3%, specificity 68.0%), and 45 ml/(min·1.73 m 2) (sensitivity 53.1%, specificity 80.0%), respectively. Patients were respectively divided into 2 groups according to the thresholds and the incidences of LIT were compared. The results showed that the incidences of LIT in patients with age and trough concentration of linezolid exceeding the thresholds and in patients with baseline plate count and baseline creatinine clearance rate lower than or equal to the thresholds were significantly higher than those in the other patients (all P<0.01). Conclusions:Baseline creatinine clearance rate, trough concentration of linezolid, age, and plate count are risk factors for LIT in HAP patients and their thresholds are 45 ml/(min·1.73 m 2), 15.4 mg/L, 87 years, and 189×10 9/L, respectively. These risk factors have good predictive value for the occurrence of LIT.

OBJECTIVE：To study the effects of augmented renal clearance （ARC）on blood trough concentration of patients receiving high-dose regimen of teicoplanin. METHODS ：Patients who received high-dose regimen of teicoplanin in the ICU were prospectively collected from the Affiliated Suzhou Hospital of Nanjing Medical University/Suzhou Municipal Hospital during Jul. 2018-Jun. 2020. They were divided into ARC group and normal renal function group according to corrected creatinine clearance. The dosage regimen of teicoplanin in the two groups were loading dose of 600 mg，q12 h×3 doses，maintenance dose of 6-10 mg/kg，qd，and the dosage was adjusted in combination with creatinine clearance rate and blood trough concentration. The trough concentration of blood samples which were collected 30 min before the 4th and 8th-10th dosage of teicoplanin were determined by HPLC. Trough concentration ，clinical efficacy ，Gram-positive bacterial clearance rate and the occurrence of ADR were compared between 2 groups. RESULTS ：A total of 56 patients were included and divided into ARC group （18 cases）and normal renal function group （38 cases）. ARC group had younger age （P＜0.001）and lower serum albumin level （P＝0.025）than normal renal function group. The trough concentrations before administration of the 4th and 8th-10th dosage in ARC group were lower than normal renal function group （P＝0.034；P＝0.035）. The trough concentrations in the ARC group and normal renal function group before 8th-10th dosage were all higher than 30 min before the 4th dosage （P＝0.003；P＜0.001）. The clinical efficacy rate and the clearance rate of Gram-positive bacteria in ARC group were 77.8％ and 76.2％，which were lower than those of the normal renal function group ，but there was no statistical difference （P＝0.195；P＝0.223）. There was no liver function damage ，hemocytopenia and allergic reaction in both groups ，but in the normal renal function group ，the causal relationship between acute renal damage and teicoplanin was assessed as “very likely ”in one patient. CONCLUSIONS ：ARC patients are younger ，most of them have hypoproteinemia，and the blood trough concentrations of teicoplanin in high-dose regimen are significantly lower than those of normal renal function patients. For critical ill ARC patients ，it is advisable to increase the loading dose of teicoplanin to make the trough concentration reach the target concentration range quickly.