Background Amid global climate change, extreme environmental events are occurring more frequently, and it is imperative to investigate the impacts of combined exposure to fine particluate matter (PM_2.5) and cold spells (CS) on population mortality. Objective To analyze the association between sequential extreme PM_2.5-cold spell (EP-CS) events and non-accidental mortality among residents in Zigong City from 2016 to 2021. Methods Using time-series study design, meteorological data in Zigong were collected from the Zigong Meteorological Bureau for the period from January 1, 2016 to December 31, 2021, while daily non-accidental mortality data were obtained from the mortality surveillance system of the Zigong Center for Disease Control and Prevention. We adopted the percentile method to define extreme PM_2.5 events and cold spells. We analyzed the risk effect of EP-CS events on non-accidental mortality among residents in this city and explored the potential amplification of damage resulting from different patterns of consecutive extreme events by using distributed lag nonlinear model (DLNM). We also conducted stratified analyses based on age, gender, education level, and marital status. Results The EP-CS events demonstrated a significant impact on non-accidental mortality among the local residents, exhibiting a certain lagged effect. The effects on the overall residents lasted from lag0 (RR=1.030, 95%CI: 1.013, 1.048) to lag14 (RR=1.035, 95%CI: 1.019, 1.052). Notably, the effects were more pronounced among females, individuals aged 65 years and above, and those who were never married, divorced, or widowed. Different patterns of EP-CS events all associated with adverse effects, the health impact of EP-CS events was significantly greater than that of individual PM_2.5 pollution or CS events. The analysis of lag effects across different event patterns revealed that the overall effect of EP-CS events with shorter intervals (0–7 d) had a stronger effect compared to EP-CS with longer intervals (8–14 d), and the RR values of lag14 were 1.034 (95%CI: 1.015, 1.054) and 1.017 (95%CI: 1.007, 1.027), suggesting that the damaging effect of compound events occurring in the short term was more significant. Conclusion All sequential extreme EP-CS events have an impact on non-accidental mortality among residents in this city, with compound events demonstrating a stronger effect. Females, individuals aged ≥65 years, and those who were never married, divorced, or widowed are more sensitive to EP-CS events.

Objective To evaluate the subchronic systemic toxicity of disposable plasma virus-inactivated blood transfusion sets using hydroxyethyl starch(HES)130/0.4 sodium chloride injection as an extraction medium.Methods Firstly,40 Sprague Dawley(SD)rats including 20 male and 20 female ones were seleted and randomly enrolled into a sample group and a control group by sex,with 20 ones in each group.Secondly,instead of plasma HES 130/0.4 sodium chloride injection was used to leach disposable plasma virus-inactivated blood transfusion sets to prepare the test solution by simulating clinical application such as lighting,adsorption and filtration and storage.Finally,the test solution and HES 130/0.4 sodium chloride injection were injected into the tail vein of the SD rats at a dose of 20 mL/kg for 28 d in the sample group and in the control group respectively,and the subchronic systemic toxicity of disposable plasma virus-inactivated blood transfusion sets and the feasibility of using HES 130/0.4 sodium chloride injection as the extraction medium to assess their subchronic systemic toxicity were evaluated with clinical observation,body mass monitoring,clinical pathology examination,gross necropsy and histopathology examination.Results The sample group and control group had no significant differences in mortality rates,clinical observation results,body mass,gross necropsy results,hematological and coagulation examination results and organ weight(all P>0.05);blood biochemical examinations showed the male rats in the sample group had the cholesterol(CHO)values higher while the creatinine(CR)values lower than those in the control group,with the differences being statistically significant(both P<0.05)and the two indexes within the range of the laboratory's historical reference data,and other blood biochemical indexes were not significantly different(all P>0.05);the sample group had the spleen weight-to-body mass ratios of the female rates lower significantly than those in the control group(P<0.05),and the ratios of other organ weight to body mass had significant differences(all P>0.05);histopathology examination showed slight pathological changes in liver,spleen and kidney of female rats and in spleen and kidney of male rats in the sample group,and the female and male rats in the control group had similar pathological changes found in the sample group,which might be caused by HES metabolites.Conclusion Disposable plasma virus-inactivated blood transfusion sets prove to have no significant subchronic systemic toxicity,and its feasible to use HES 130/0.4 sodium chloride injection as the extraction medium to evaluate the subchronic systemic toxicity of disposable plasma virus-inactivated blood transfusion sets.[Chinese Medical Equipment Journal,2025,46(10):29-35]

Non-alcoholic fatty liver disease(NAFLD)is an increasingly serious chronic liver disease worldwide,with complex pathogenesis and many challenges in diagnosis and treatment.In recent years,genome-wide studies have revealed the important roles of epigenetic modifications in the development of NAFLD,especially the involvement of imprinted genes.The parental origin effect of NAFLD suggests that imprinted genes play a key role in its pathogenesis.The Dlk1-Dio3 gene cluster,as one of the largest clusters of imprinted genes,has become a focus of research because of its central role in embryonic devel-opment and metabolic regulation.This review explores the structure and function of the Dlk1-Dio3 gene cluster and its potential role in NAFLD pathogenesis.This gene cluster plays a key role in the"second strike"of NAFLD through a complex regulatory network that affects biological processes such as lipid me-tabolism,glucose metabolism,inflammatory response and oxidative stress in the liver.Specifically,DLK1 acts as a negative regulator,inhibiting adipocyte differentiation and thus reducing hepatic lipid ac-cumulation,while DIO3 promotes adipocyte differentiation and increases hepatic lipid accumulation by regulating thyroid hormone conversion.In addition,the Dlk1-Dio3 gene cluster regulates lipid metabolism by modulating multiple microRNAs(e.g.miR-370,miR-122,etc.).miR-370 exacerbates lipid accu-mulation by inhibiting CPT1α;miR-122 up-regulates SREBP-1c and promotes fatty acid synthesis;and miR-379/410 clusters increase lipid scavenging capacity by decreasing lipid accumulation.Long non-coding RNA MEG3 also plays an important role in NAFLD.meg3 promotes fatty acid oxidation and re-duces lipid droplet accumulation by up-regulating SIRT6,and attenuates lipid synthesis by inhibiting the Wnt/mTOR signaling pathway through binding to miR-21.In terms of insulin resistance,DLK1 inhibits gluconeogenesis and promotes fatty acid oxidation by activating the PI3K/Akt/mTOR pathway,thereby reducing hepatic lipid burden.DIO3,on the other hand,affects insulin sensitivity by regulating thyroid hormones and promotes the development of NAFLD.Meanwhile,the Dlk1-Dio3 gene cluster also plays an important role in regulating oxidative stress and inflammatory responses,and DLK1 attenuates hepatic oxi-dative stress injury by inhibiting inflammatory factor expression and activating antioxidant signaling.Taken together,the Dlk1-Dio3 gene cluster plays a multidimensional role in the occurrence and develop-ment of NAFLD,providing potential biomarkers and therapeutic targets.

Objective To systematically evaluate the effect of inspiratory muscle training(IMT)on weaning outcomes in patients with weaning failure.Methods Literatures in Chinese and English were retrieved from databases such as PubMed,Cochrane Library,Web of Science,Embase,CNKI,VIP,Wanfang data and CBM for researches on the effect of IMT in mechanical ventila-tion weaning failure,from the inception of the databases to October 22,2024.The methodological quality of the researches was evaluated with PEDro scale,and data were extracted for a systematic review.Results Nine randomized controlled trials were included,published between 2011 and 2023,from Brazil,China,the United States,Iran and Australia,with a total of 499 patients.The scores of the PEDro scale ranged five to eight.The population included patients with prolonged weaning,difficult weaning and tracheostomy.The IMT methods included threshold load training and tapered flow resistance training.The training intensity was 30%to 80%of maximal inspiratory pressure(MIP),and some researches did not set the training intensity based on MIP.The pro-gression of intensity varied widely across researches.The intervention frequency ranged from five to 30 breaths per set,with at least one minute rest between sets,two to six sets per session,one to two sessions per day,and five to seven days per week.The duration of the intervention ranged from successful weaning,one week after weaning,extubation,or four days to eight weeks.Regarding the efficacy of the intervention,IMT was not benefi-cial for the duration of mechanical ventilation and intensive care unit(ICU)length of stay on weaning failure pa-tients.However,the effect of IMT on weaning successful rates,duration of weaning,MIP and mortality was in-consistent.Conclusion IMT can not improve the duration of mechanical ventilation and ICU length of stay for weaning failure pa-tients,and there is still debate regarding its effect on successful rate of weaning,duration of weaning,MIP and mortality.

Objective:To analyze the association between inflammation-related dietary patterns and the risk for cognitive impairment in older adults aged ≥65 years in longevity areas in China by using reduced rank regression (RRR) analysis.Methods:This study used cross-sectional data from the 2021 Healthy Aging and Biomarkers Cohort Study, including the information about study participants' demographic characteristics, lifestyles, daily life activities, and disease histories. Dietary intake was obtained by using a simplified food frequency questionnaire. Cognitive impairment was evaluated based on the Mini-Mental State Examination Scale combined with years of education. Fasting venous blood samples were collected to detect inflammatory markers, especially high-sensitivity C-reactive protein (hs-CRP) and the platelet-to-lymphocyte ratio (PLR). RRR analysis was used to obtain inflammation-related dietary patterns using hs-CRP and PLR as response variables. Multivariate logistic regression model was used to analyze the association between dietary pattern score and the risk for cognitive impairment. Restricted cubic spline was used to explore the dose response relationship, and mediation analysis was used to quantify the mediating effects of hs-CRP and PLR.Results:Two dietary patterns were identified with RRR. The primary pattern was characterized by higher intakes of flour, red meat, and dairy products, and lower intake of fresh vegetables, explaining 6.84% of the variance in food intake and 0.50% of the variance in inflammatory markers. Compared with the T1 group, the T3 group had significantly higher risk for cognitive impairment ( OR=1.242, 95% CI: 1.034-1.491). Each one standard deviation increase in the dietary pattern score was associated with an 8.7% increase in the risk for cognitive impairment ( OR=1.087, 95% CI: 1.008-1.172), with a significant linear trend (overall-model P<0.001, non-linear P=0.295). Mediation analysis indicated that hs-CRP mediated 6.2% of the association between the dietary pattern and the risk for cognitive impairment. Conclusion:The inflammation- related dietary pattern characterized by higher consumption of flour, red meat, and dairy products and lower consumption of fresh vegetables is associated with an increased risk for cognitive impairment in older adults, and hs-CRP partially mediates this association.

Albendazole-glucan particles(ABZ-GPS)and abendazole(ABZ)were used to treat secondary alveolar echinococ-cosis in mice.The therapeutic effects of ABZ-GPS on alveolar echinococcosis in vivo were evaluated,and the feasibility of using glucan particles as anti-hydatid drug carriers was further verified.Mice with echinococcosis were randomly divided into an ABZ group,glucan nanoparticle(GP)group,ABZ-GPS group,and control group.After four courses of administration with a final concentration of 50 mg/mL,the therapeutic effects of ABZ-GPS were evaluated on the basis of imaging,histopathological changes,ultrastructure,and immunology.After ABZ-GPS and ABZ administration,clear liver lesion tissue necrosis and large numbers of infiltrating lymphocytes were observed.Significant differences in the average cyst wet weight(t=7.83,P＜0.05),were observed between the ABZ-GPS group and ABZ group.Imaging revealed that ABZ-GPs were targeted to liver tissue.Pa-thology and ultrastructure analyses demonstrated that the alveolar hydatid cells in the liver in the control group and GP group grew well,and the vesicles were large,filled with cystic fluid,and translucent or transparent;the cyst wall tension was high;no calcification was observed;the stratum corneum and germinal layer were clear;and more fertile capsules and different num-bers of protocephalospora were present in the liver.In the ABZ group,the capsular cavity collapsed,and showed partial necro-sis and lymphocyte infiltration.In the ABZ-GP group,the corneum and germinal layer of echinococcus vesicles were difficult to identify,and we observed bulbous necrosis,central calcification,fibrous tissue hyperplasia,inflammatory cell infiltration,coarser,shorter or absent microvilli of the germinal layer,nuclear shrinkage,dissolution or disappearance,clear expansion of cytoplasmic microtubules,and myelin-like or vacuole-like changes.Therefore,ABZ-GPs showed good targeting and killing ac-tivity in vivo in mice with secondary alveolar coccosis.

Chimeric antigen receptor(CAR)T cell therapy has made a major breakthrough in the treatment of hematological malignancies.However,more and more studies have shown that factors such as T-cell exhaustion,tumor antigen modulation,immunosuppressive tumor microenvironment,and CAR-T cell dysfunction can lead to relapse and CAR-T cell resistence in hematologic malignancies.Developing dual-targeted CAR-T cells,exploring new immune targets,blocking CAR-T cell exhaustion,combining CAR-T cells with other therapies,implementing bridging therapies,and designing novel immunotherapies may be strategies to address CAR-T cell resistance.This article reviews the mechanisms of resistance to CAR-T cell therapy in hematological malignancies and the corresponding coping strategies.

Aim To investigate the effect of Zhenwu decoction on inflammation,oxidative stress and apopto-sis of human glomerular epithelial cells(HGEC)in-duced by lipopolysaccharide(LPS)based on Nrf2/HO-1 signaling pathway,and to explore the underlying mechanism.Methods HGEC were treated with LPS(1.0 mg·L-1)for 24 h to construct an oxidative damage model.On this basis,2.5％,5％and 10％Zhenwu decoction-containing serum were added to the low,medium and high dose groups of Zhenwu decoc-tion,and a normal group was set up.The changes of cell activity were assessed by MTT method and LDH method.The contents of TNF-α,IL-6,IL-10,SOD,CAT,GSH-Px,ROS and MDA in each group were de-tected by ELISA.The apoptosis of each group was de-tected by flow cytometry.The mRNA and protein ex-pressions of Bax,Bcl-2,caspase-3,caspase-9 and Nrf2/HO-1 pathway were detected by RT-qPCR and Western blot,respectively.Results Compared to the normal group,the model group of HGEC exhibited increased levels of inflammatory cytokines,enhanced oxidative stress response and aggravated apoptosis;after inter-vention with various doses of Zhenwu decoction,the in-flammatory levels in HGEC were reduced,oxidative damage and apoptosis were effectively ameliorated,and the mRNA and protein expression levels of the Nrf2/HO-1 signaling pathway were upregulated.Conclu-sions Zhenwu decoction can protect HGEC from LPS-induced inflammation and oxidative damage and im-prove apoptosis.The mechanism may be related to the activation of Nrf2/HO-1 signaling pathway.

Aim To explore the mechanism of the syn-ergistic effect of the ferroptosis inducer erastin com-bined with shikonin in promoting ferroptosis in human hypertrophic scar fibroblasts(HSFBs).Methods Hypertrophic scar tissues provided by the General Hos-pital of Ningxia Medical University were collected,and HSFBs were extracted.HSFBs were identified by HE staining and immunofluorescence.The inhibitory rates of Era and SHK on HSFBs at different concentrations were detected by CCK-8 assay,and the IC50 value was calculated.CompuSyn software was used to calculate the co-use index(CI).Control group,Erastin(Era)group,shikonin(SHK)group and Era+SHK group were set up,and the number and morphological chan-ges of cells were observed after 24 hours of interven-tion.The ability of cell migration and invasion was de-tected by scratch test and Transwell test.The changes of malondialdehyde(MDA),total iron ion and reactive oxygen species(ROS)were detected by corresponding biochemical kits.The expressions of collagen I,α-SMA and GOT1,SLC7A11,GPX4 and FTH1 were detected by Western blot.Results The IC50 value of Era and SHK of primary HSFBs was 2.22 μmol·L-1 and 3.94μmol·L-1 respectively,which was used as the single drug concentration for subsequent experiments.The CompuSyn software was employed to calculate the CI value when the two drugs were used in combination,and the concentrations corresponding to CI=0.39597(Era:1.2 μmol·L-1+SHK:1.5 μmol·L-1)were selected as subsequent combination concentrations(Because when CI was equal to 0.395 97,the concen-tration of each drug was lower than the concentration of single drug,and the inhibition rate of combined drug was greater than 50％).Compared with the monother-apy group,the number of HSFBs in the SHK+Era group was significantly reduced,cell membrane showed breakage and vesiculation,cell wrinkling became smal-ler,and cytoplasm was concentrated.The migration and invasion ability of HSFBs in the SHK+Era group were obviously weakened(P＜0.05),and the expres-sion of fibrosis-related proteins collagen Ⅰ and α-SMA was reduced(P＜0.05);the contents of MDA,total i-ron ions,and ROS in HSFBs of the SHK+Era group increased(P＜0.05),and the protein expression lev-els of SLC7A11,GOT1,GPX4,and FTH1 further de-creased(P＜0.05).Conclusions Erastin in combi-nation with shikonin can synergistically inhibit the pro-liferation,migration and fibrosis levels of HSFBs.The mechanism may be that erastin enhances the inhibition of shikotin on GOT1,increases the levels of cellular i-ron ions,ROS,and lipid peroxides,thereby promoting ferroptosis in HSFBs.

Aim To identify the chemical components of Angelica sinensis(AS)and explore the mechanism of AS in activating blood circulation.Methods UP-LC-Q-TOF-MS was used to identify the chemical com-ponents of AS.The changes of syndrome and patholog-ical section of heart in rats were observed.Hemody-namics and proteomics were measured.Results A to-tal of 270 compounds were identified from AS.It showed that rats of Angelica sinensis group were greatly improved such as arched back,shrugged fur,huddled up and less mobile,purplish paws and tails,whitish ear margins and nasolabial lips,reduced drinking and feed-ing,and slow response to external stimuli;mildly disor-dered myocardial fibre arrangement,myofibre arrange-ment was tighter than that of model group,myocardial fibres were narrower and close to normal,and mild oe-dema,exudation,and inflammatory cell infiltration could be seen in the surrounding area;SAP was signif-icantly lower and LVSP was significantly higher in An-gelica sinensis group(P＜0.05).Proteomics showed that 62 differential proteins were screened in Angelica sinensis group compared to model,GO function were concentrated in the extracellular matrix,cytoskeletal proteins binding and protein hydrolysis negatively regu-lated.KEGG pathway were enriched in signalling path-ways such as complement and coagulation cascades,cellular focal adhesion,leukocyte transendothelial mi-gration and chemokine signalling pathways.Conclu-sions AS probably through the expression of proteins,which modulate the signalling pathways of the comple-ment and coagulation cascade reactions and the con-traction of vascular smooth muscle.