Epidemiological investigations and clinical studies have shown that inappropriate ambient temperatures (high and low temperatures) are the independent risk factors for ischemic stroke, but their underlying physiological mechanisms are not fully understood. This article systematically reviews the potential mechanisms by which inappropriate ambient temperatures promote the occurrence of ischemic stroke through multiple pathways, such as activating the sympathetic-renin-angiotensin system, inducing systemic inflammation and oxidative stress, damaging the integrity of the intestinal barrier and blood-brain barrier, and disrupting coagulation-fibrinolysis balance.

This study addresses the issue of disability risk among elderly individuals in the context of population aging. Through investigations conducted at 27 retirement cadre centers in Beijing and based on multidisciplinary team collaboration, a closed-loop health management service model was established, incorporating comprehensive geriatric assessment, personalized interventions, and dynamic follow-up. Preliminary implementation results demonstrate that this model can effectively identify high-risk elderly individuals, while improving both participation rates in interventions among the elderly and risk identification capabilities among healthcare professionals.

This study addresses the issue of disability risk among elderly individuals in the context of population aging. Through investigations conducted at 27 retirement cadre centers in Beijing and based on multidisciplinary team collaboration, a closed-loop health management service model was established, incorporating comprehensive geriatric assessment, personalized interventions, and dynamic follow-up. Preliminary implementation results demonstrate that this model can effectively identify high-risk elderly individuals, while improving both participation rates in interventions among the elderly and risk identification capabilities among healthcare professionals.

Bronchopulmonary dysplasia (BPD), characterized by impaired alveolarization and dysregulated vascularization, is a severe health burden for neonates worldwide. Hyperoxia induced acute lung injury is a major contributor to the progression and deterioration of BPD. An increasing number of animal studies have revealed that human umbilical cord blood derived mononuclear cells (hUCB-MNCs) infusion significantly attenuated the hyperoxia-induced acute lung injury through regeneration capacity. Currently, clinical application requires determination of the optimal dose and adjustment to good manufacturing practices. In this work, we comprehensively investigated the optimal dose of hUCB-MNCs in alleviating hyperoxia-induced lung injury in neonatal C57BL6/J mice. Mice with hyperoxia exposure were implanted with low (3×104cells/kg, Dl), middle (3×105 cells/kg, Dm) and high (3×106 cells/kg, Dh) dose of hUCB-MNCs at postnatal day 7. Three weeks after graft, characteristics exhibited in lungs including morphology, function and cytokine expression were thoroughly analyzed. Implantation of hUCB-MNCs sharply reverted the impaired lung architecture induced by hyperoxia exposure dose dependently as evidenced by indicated parameters. Attenuated expression of IL-1β concomitant with enhanced expression of IL-10 and IL-2 were shown in Dh inoculated groups, where Dl and Dm failed to restore the level of IL-10, IL-1β and IL-2. Significantly re-escalated marker of angiogenic marker VEGFA, CD31 in lung tissue were uniquely observed in Dh group. Mechanistically, our study revealed the appropriate dose of intravenous infusion of hUCB-MNCs in alleviating hyperoxia-induced lung injury through modulating reactive oxygen species response in neonatal mice.Therefore, a tight control of hUCB-MNCs density or levels of CB-MNC related products is of great significance.

Objective To investigate the regulatory role of nuclear factor erythroid 2-related factor 2(Nrf2)in the activation and polarization of microglia induced by methamphetamine(METH).Methods BV2 and HMC3 cells were studied in vitro and wild-type mice and Nrf2-knockout mice were studied in vivo.In vivo and in vitro toxicity models induced by METH were established,respectively.The activation and polarization of microglia in each group were examined using immunofluorescence and Western blot,respectively.Results METH treatment significantly increased the fluorescence level of inducible nitric oxide synthase(iNOS)in BV2 and HMC3 cells(P＜0.001),and significantly decreased the fluorescence level of Arginase1(Arg1)(P＜0.05,P＜0.01).METH exposure activated microglia in the cortex,increased expression levels of ionized calcium binding adaptor molecule-1(IBA1)and iNOS(P＜0.001,P＜0.05),and decreased the expression of Arg1(P＜0.01).The number of activated microglia was significantly increased after Nrf2 gene knockout(P＜0.01),compared with the WT METH group,while the expression levels of IBA1 and iNOS were also increased(P＜0.001,P＜0.01)and the expression level of Argl was decreased(P＜0.01).Conclusions Nrf2 plays an important role in regulating the activation and polarization of microglia induced by METH.Nrf2 may thus be a potential target for the treatment of neuroinflammation induced by METH.

Objective To investigate the regulatory role of nuclear factor erythroid 2-related factor 2(Nrf2)in the activation and polarization of microglia induced by methamphetamine(METH).Methods BV2 and HMC3 cells were studied in vitro and wild-type mice and Nrf2-knockout mice were studied in vivo.In vivo and in vitro toxicity models induced by METH were established,respectively.The activation and polarization of microglia in each group were examined using immunofluorescence and Western blot,respectively.Results METH treatment significantly increased the fluorescence level of inducible nitric oxide synthase(iNOS)in BV2 and HMC3 cells(P＜0.001),and significantly decreased the fluorescence level of Arginase1(Arg1)(P＜0.05,P＜0.01).METH exposure activated microglia in the cortex,increased expression levels of ionized calcium binding adaptor molecule-1(IBA1)and iNOS(P＜0.001,P＜0.05),and decreased the expression of Arg1(P＜0.01).The number of activated microglia was significantly increased after Nrf2 gene knockout(P＜0.01),compared with the WT METH group,while the expression levels of IBA1 and iNOS were also increased(P＜0.001,P＜0.01)and the expression level of Argl was decreased(P＜0.01).Conclusions Nrf2 plays an important role in regulating the activation and polarization of microglia induced by METH.Nrf2 may thus be a potential target for the treatment of neuroinflammation induced by METH.

Objective To determine the scores of patients with a confirmed diagnosis of drug-induced liver injury(DILI)using Roussel Uclaf Causality Assessment Method(RUCAM),Maria&Victorino assessment scale,and Revised Electronic Causality Assessment Method(RECAM),to compare the accuracy of the three scales in diagnosis,and to investigate their clinical significance in the diagnosis of DILI.Methods A total of 98 patients with a confirmed diagnosis of DILI who were hospitalized in Peking University First Hospital from January 2011 to December 2022 were enrolled,with liver biopsy results supporting DILI and a clear history of medication.Clinical data were collected from all subjects,and the above causality assessment scales were used for scoring.The chi-square test was used to analyze the diagnostic accuracy of the causality assessment scales,and the weighted kappa coefficient was used to analyze the consistency between the three scales.Results For all patients with DILI enrolled,RECAM had the highest accuracy,with a significant difference compared with RUCAM(χ2=5.667,P=0.017).RUCAM and RECAM had moderate consistency in diagnosis(κw=0.469),while RECAM and Maria&Victorino scale had poor consistency(κw=0.156).For the patients with acute DILI,RECAM,RUCAM,and Maria&Victorino scales had a diagnostic inconsistency rate of 3.7%,11.1%,and 42.6%,respectively;for the patients with hepatocellular type DILI,the three scales of a diagnostic inconsistency rate of 8.9%,21.4%,and 62.5%,respectively;for the patients with cholestasis type or mixed type DILI,the three scales of a diagnostic inconsistency rate of 10.0%,22.5%,and 47.5%,respectively.Conclusion The use of RECAM and RUCAM scales in acute DILI can improve diagnostic rate,and for hepatocellular type DILI and DILI with the clinical manifestation of cholestasis(cholestasis type DILI and mixed type DILI),the use of RECAM and RUCAM scales can also improve diagnostic rate.The selection of causality assessment scales with a relatively high accuracy based on the course and clinical classification of the disease may help to further improve clinical diagnostic rate.

Objective To explore the impact of δ-catenin expression level on resting-state brain function in breast cancer patients.Methods Totally 104 female breast cancer patients were prospectively enrolled and divided into δ-catenin high expression group(DH group,n=51)and δ-catenin low expression group(DL group,n=53)according to δ-catenin expression level,while 36 female healthy volunteers were selected as controls(control group).Neuropsychological tests were performed,and resting-state functional MRI(rs-fMRI)were acquired,then parameters of brain function,including amplitude of low frequency fluctuation(ALFF),fractional ALFF(fALFF),regional homogeneity(ReHo)and functional connectivity strength(FCS)of brain regions with differences among groups were obtained.Spearman correlation analysis was used to evaluate the correlations of function parameters of brain regions with general data and neuropsychological test scores.Results Significant differences of fALFF,ReHo and FCS values were found among 3 groups(familywise error rate[FWE]correction,all P＜0.05).fALFF value of left inferior temporal gyrus in DH and DL groups were both higher than that in control group(FWE correction,both P＜0.05),ReHo value of right inferior temporal gyrus in DH group,as well as of right middle temporal gyrus,right inferior temporal gyrus and right fusiform gyrus in DL group were all lower than that in control group(FWE correction,all P＜0.05),FSC value of left lenticular nucleus,left putamen,left fusiform gyrus,left calcarine fissure surrounding cortex and left inferior temporal gyrus in DH group were all higher than that in DL group(FWE correction,all P＜0.05),FSC value of left lenticular nucleus,left putamen,left fusiform gyrus and left calcarine fissure surrounding cortex in DH group were all higher than that in control group(FWE correction,all P＜0.05),while FSC value of left lingual gyrus,left lenticular nucleus and left putamen were both higher than that in control group(FWE correction,both P＜0.05).In brain regions with different fMRI indexes between DH group and DL group,FSC values were lowly positively correlated with CogPCA results(r=0.313,P＜0.05).In brain regions with different fMRI indexes between DH group and control group,fALFF value were lowly positively correlated with trail making test A(TMT A)and trail making test B(TMT B)(r=0.301,0.310,both P＜0.05),ReHo values were lowly negatively correlated with TMT B(r=-0.307,P＜0.05),FCS values were weakly/lowly positively correlated with TMT A and TMT B(r=0.282,0.309,both P＜0.05)and lowly negatively correlated with results of digital symbol substitution test(DSST)(r=-0.363,P＜0.05).In brain regions with different fMRI indexes between DL group and control group,fALFF values were weakly/lowly negatively correlated with results of mini mental state examination(MMSE),Montreal cognitive assessment(MoCA),auditory verbal learning test(AVLT)short-term memory and DSST(r=-0.399,-0.362,-0.344,-0.288,all P＜0.05).Conclusion The expression level of δ-catenin had certain impact on brain function of breast cancer patients,resulted in asymmetry changes of brain network in bilateral hemispheres,as well as memory loss through affecting left inferior temporal gyrus,left lenticular nucleus,left putamen and left fusiform gyrus.

Objective:To explore the value of multi-gene copy number variation (CNV) analysis in the clinical prognostic prediction of patients with multiple myeloma (MM).Methods:A retrospective case series study was conducted. The clinical data of 79 MM patients who were admitted to the Affiliated Cancer Hospital of Zhengzhou University from June 2016 to March 2023 were collected. The whole-genome CNV status was obtained by using whole-genome low depth sequencing (sWGS) of bone marrow blood cells. The outcomes of remission, minimal residual disease (MRD) turning negative, progression-free survival (PFS) and overall survival (OS) in patients with and without CNV were compared. The Cox proportional hazards model was used to analyze the influencing factors of PFS and OS.Results:Among the 79 patients with MM, 43 were males and 36 were females. The median age [ M ( Q1, Q3)] was 65 years old (55 years old, 71 years old). In the revised international staging system, there were 20, 51 and 8 cases in stage Ⅰ, Ⅱ and Ⅲ, respectively. The results of fluorescence in situ hybridization (FISH) were abnormal in 17 cases. CNV was detected in 55 patients (69.6%), and the abnormality of chromosome 1q (27 cases, 49.1%) was the most frequently detected, followed by the abnormality of chromosome 13 (26 cases, 47.3%), chromosome 6 (22 cases, 40.0%), chromosome 11 (19 cases, 34.5%), chromosome 8 (18 cases, 32.7%), chromosome 14 (14 cases, 25.5%), and chromosome 17 (11 cases, 20.0%). The ≥ very good partial remission rate in the detected CNV group was lower than that in the undetected CNV group [29.1% (16/55) vs. 45.8% (11/24)], but the difference was not statistically significant ( χ2 = 2.08, P = 0.149). The MRD negative conversion rate of detected CNV group was lower than that of undetected CNV group [21.8% (12/55) vs. 58.3% (14/24)], and the difference was statistically significant ( χ2 = 10.09, P = 0.001). Survival analysis showed that PFS in the detected CNV group was worse than in the undetected CNV group [median PFS time: 36.7 months (95% CI: 6.1-67.4 months) vs. not reached], and the difference between the two groups was statistically significant ( χ2 = 6.61, P = 0.010), while the difference in OS between the two groups was not statistically significant ( χ2 = 1.84, P = 0.175). There was no significant difference in PFS and OS between patients with 1 and ≥2 abnormal copy sequences (both P > 0.05). PFS of patients with CNV on chromosomes 1q, 17, 8, 11 and 13 was worse than that of patients without CNV at these sites (all P < 0.05), while there was no statistical difference in OS (all P > 0.05). Results of univariate analysis showed that lactate dehydrogenase (LDH) level was correlated with PFS and OS of patients (both P < 0.05), and CNV was correlated with PFS of patients (P = 0.010). Results of multivariate analysis showed that LDH > 250 U/L was an independent factor for poor PFS and OS of patients ( HR = 0.135, 95% CI: 0.019-0.983, P = 0.048; HR = 0.132, 95% CI: 0.018-0.951, P = 0.045). Conclusions:Multi-gene CNV analysis can assist in predicting the prognosis of MM patients, and it is more sensitive than traditional CNV detection methods such as FISH. Patients with CNV on chromosomes 1q, 17, 8, 11, and 13 have poor prognosis.

Objective:To explore the value of multi-gene copy number variation (CNV) analysis in the clinical prognostic prediction of patients with multiple myeloma (MM).Methods:A retrospective case series study was conducted. The clinical data of 79 MM patients who were admitted to the Affiliated Cancer Hospital of Zhengzhou University from June 2016 to March 2023 were collected. The whole-genome CNV status was obtained by using whole-genome low depth sequencing (sWGS) of bone marrow blood cells. The outcomes of remission, minimal residual disease (MRD) turning negative, progression-free survival (PFS) and overall survival (OS) in patients with and without CNV were compared. The Cox proportional hazards model was used to analyze the influencing factors of PFS and OS.Results:Among the 79 patients with MM, 43 were males and 36 were females. The median age [ M ( Q1, Q3)] was 65 years old (55 years old, 71 years old). In the revised international staging system, there were 20, 51 and 8 cases in stage Ⅰ, Ⅱ and Ⅲ, respectively. The results of fluorescence in situ hybridization (FISH) were abnormal in 17 cases. CNV was detected in 55 patients (69.6%), and the abnormality of chromosome 1q (27 cases, 49.1%) was the most frequently detected, followed by the abnormality of chromosome 13 (26 cases, 47.3%), chromosome 6 (22 cases, 40.0%), chromosome 11 (19 cases, 34.5%), chromosome 8 (18 cases, 32.7%), chromosome 14 (14 cases, 25.5%), and chromosome 17 (11 cases, 20.0%). The ≥ very good partial remission rate in the detected CNV group was lower than that in the undetected CNV group [29.1% (16/55) vs. 45.8% (11/24)], but the difference was not statistically significant ( χ2 = 2.08, P = 0.149). The MRD negative conversion rate of detected CNV group was lower than that of undetected CNV group [21.8% (12/55) vs. 58.3% (14/24)], and the difference was statistically significant ( χ2 = 10.09, P = 0.001). Survival analysis showed that PFS in the detected CNV group was worse than in the undetected CNV group [median PFS time: 36.7 months (95% CI: 6.1-67.4 months) vs. not reached], and the difference between the two groups was statistically significant ( χ2 = 6.61, P = 0.010), while the difference in OS between the two groups was not statistically significant ( χ2 = 1.84, P = 0.175). There was no significant difference in PFS and OS between patients with 1 and ≥2 abnormal copy sequences (both P > 0.05). PFS of patients with CNV on chromosomes 1q, 17, 8, 11 and 13 was worse than that of patients without CNV at these sites (all P < 0.05), while there was no statistical difference in OS (all P > 0.05). Results of univariate analysis showed that lactate dehydrogenase (LDH) level was correlated with PFS and OS of patients (both P < 0.05), and CNV was correlated with PFS of patients (P = 0.010). Results of multivariate analysis showed that LDH > 250 U/L was an independent factor for poor PFS and OS of patients ( HR = 0.135, 95% CI: 0.019-0.983, P = 0.048; HR = 0.132, 95% CI: 0.018-0.951, P = 0.045). Conclusions:Multi-gene CNV analysis can assist in predicting the prognosis of MM patients, and it is more sensitive than traditional CNV detection methods such as FISH. Patients with CNV on chromosomes 1q, 17, 8, 11, and 13 have poor prognosis.