Objective To quantitatively assess the exposure-response association between exposure to heatwave and sudden death, estimate the attributable excess deaths, and identify potential vulnerable subgroups. Methods A time-stratified case-crossover study was conducted among residents who died from sudden death in Jiangsu Province, China between 2015 and 2021. Heatwave events in Jiangsu Province, defined using varying relative temperature thresholds and durations, were identified using temperature data from the China Meteorological Administration Land Data Assimilation System (CLDAS V2.0). Individual heatwave exposure was assessed based on each subject's residential address. The exposure-response association between heatwave and sudden death was evaluated using conditional logistic regression model combined with a Distributed Lag Nonlinear Model(DLNM). Heatwave-attributable excess deaths were estimated. Stratified analyses by sex and age were performed to assess potential effect modifications. Results Under all definitions, exposure to heatwave was significantly associated with an increased risk of sudden death, and the risk increased with the intensity of heatwave. Using the P95_3d definition (temperature exceeding the 95th percentile for ≥3 consecutive days), heatwave was significantlyassociated with a 56% increased risk of sudden death (95% CI: 31%, 86%). The population-attributable fraction of sudden death due to heatwave exposure was 1.45% (95% CI: 0.97%, 1.90%). Stratified analyses indicated no statistically significant differences in the association between heatwave exposure and sudden death across age or sex subgroups. Conclusion Heatwave exposure was associated with an increased risk of sudden death. Reducing heatwave exposure during summer may help lower the occurrence of sudden death.

Objective: To prepare the erythrocyte-liposome drug delivery system to enhance the therapeutic effect of drugs on tumors and inhibit tumor metastasis. Methods: This study prepared and characterized paclitaxel (PTX)-plerixafor (AMD3100) liposomes (Lips), developed the erythrocyte-liposome drug delivery system, and evaluated its targeting efficiency and therapeutic efficacy through a series of in vitro cellular and in vivo animal experiments. Results: The particle size of PTX-AMD-Lips was (186.4±0.83) nm. Drug encapsulation efficiency of PTX-AMD-Lips was (75.50±5.27)% for PTX and (88.31±2.45)% for AMD. The Binding efficiency between RBC and liposomes in the drug delivery system was (69.93±2.55)%. Vitro cellular experiments revealed that PTX-AMD-Lips significantly inhibited tumor cell migration. In vivo animal experiments, the erythrocyte-liposome drug delivery system significantly increased drug accumulation in the lungs. At the experimental endpoint, the quantitative fluorescence signal of tumor size measured (4.04±0.44)×10 for the PTX-Lips group, and (5.14±3.40)×10 for the RBC-PTX-AMD-Lips group. Conclusion: The erythrocyte-liposome drug delivery system could enhance the lung-specific targeting capability of liposomes, kill tumor cells and suppress further metastasis effectively.

Objective: To verify the inhibitory effect of a carbon monoxide hemoglobin-based oxygen carrier (CO-HBOC) on the fibrotic process in mice with idiopathic pulmonary fibrosis (IPF), clarify its efficacy difference compared with hemoglobin-based oxygen carriers (HBOCs), and elucidate its mechanism of action via proteomic analysis. Methods: CO-HBOC was prepared using gas loading technology. An IPF mouse model was established and the mice were randomly divided into a normal saline control group, an HBOC treatment group, and a CO-HBOC treatment group. The fibrotic area percentage was analyzed using Micro-CT; the degree of inflammatory infiltration and fibrosis in lung tissue was assessed by pathological section staining (e.g., HE and Masson staining); and differentially expressed proteins in lung tissue of IPF mice after CO-HBOC treatment were screened using proteomic technology. Results: Micro-CT results showed that the mean fibrotic area percentage in the CO-HBOC treatment group on day 21 was (8.89±0.98)%, which was better than that of the HBOC group (16.5±1.732)% and the normal saline group (30.75±6.45)% (P<0.05). HE and Masson staining results showed that the CO-HBOC group had reduced inflammatory cell infiltration and significantly decreased collagen fiber deposition in lung tissue, with a mean pathological score of 3.33±0.58, which was lower than that of the normal saline control group (8.33±1.53)(P<0.05); the mean collagen-positive area percentage was (3.33±1.53)%, significantly lower than that of the normal saline control group (14.00±3.61)% (P<0.05). Proteomic analysis identified 330 differentially expressed proteins, which were mainly enriched in inflammatory response regulatory pathways (such as the complement and coagulation cascades), and the expression changes of complement proteins may be the core target of CO-HBOC's anti-fibrotic effects. Conclusion: CO-HBOC can inhibit inflammatory responses and regulate fibrosis-related signaling pathways, there-by effectively inhibiting the fibrotic process in IPF mice, with superior efficacy to HBOC. Its mechanism of action involves the regulation of complement cascade-related signaling pathways and complement protein expression, providing an experimental and theoretical basis for targeted therapy of IPF.

Objective: To enhance the ability of nanoparticles to target and bind tumor cells by constructing a neutrophil hitchhiking system based on hyaluronic acid (HA)-modified dual-drug loaded lipid nanoparticles. Methods: Lipid nanoparticles (LNPs) were prepared using microfluidic technology, and the nitrogen/phosphate (N/P) ratio, flow rate ratio, and drug-to-lipid ratio were optimized. HA-modified LNPs (HA-LNPs) were prepared and characterized. The interaction between the nanoparticles and tumor cells was evaluated through in vitro cell experiments. Results: The optimal preparation conditions for LNPs are N/P=8, flow rate ratio=5, and drug-to-lipid ratio=1∶30 (w∶w). HA-LNPs has a particle size of (177.28±2.41) nm, a polydispersity index (PDI) of 0.198±0.10, and an siRNA encapsulation efficiency of (91.37±0.47)%. The optimal binding rate with neutrophils was (98.64±2.34)%. Conclusion: An HA-modified dual-drug loaded lipid nanoparticle-neutrophil hitchhiking system was successfully constructed, enhancing the synergistic anti-tumor activity of the nanomedicine and the uptake of nanoparticles by tumor cells, providing a novel delivery strategy for targeted therapy of bone marrow tumors.

Objective To construct a medical consumables selection indicator system based on analytic hierarchy process(AHP)and fuzzy cluster method.Methods Firstly,a medical consumables selection indicator system was established preliminarily with the literature research results and actual situation of hospital consumables management;secondly,13 experts in related fields were selected to execute two rounds of online questionnaires,the expert weights were determined with AHP,the importance of each selection indicator was scored by the expert evaluation method and fuzzy cluster method,and consistency analysis was carried out on the two rounds of expert evaluation results;finally,the final medical consumables selection indicator system was built with the 100-point scale.Results The constructed medical consumables selection indicator system was composed of 5 primary indicators,12 secondary indicators and 38 tertiary indicators.The primary indicators included consumables quality,clinical demand,cost-effectiveness,supply capacity and after-sales service,with the percentage-based scores being 27,25,14,26 and 8,respectively.Conclusion The medical consumables selection indicator system based on AHP and fuzzy cluster method with high reliability provides effective and reliable references for medical institutions to select medical consumables.

Objective To evaluate the efficacy and safety of enteric-coated metformin hydrochloride capsules(Junlida?)in patients with T2DM and poor glycemic control under lifestyle interventions.Methods In this study,419 patients with T2DM were recruited from 15 research centers from July 2020 to March 2022,and randomly divided into observation(Obs)group(n=209)and control group(Con,n=210)using a multicenter,randomized,double-blind,non-inferiority trial design.Patients in the Obs group were treated with enteric-coated Metformin hydrochloride capsules(Junlida?),and patients in the Con group were treated with Metformin hydrochloride tablets(Glucophage?).The optimal effective dose of 2 g/d was achieved within 4 weeks,and the reasonable dose was maintained until the end of treatment.The treatment period was 24 weeks.HbA1c and its compliance rate,FPG,and body weight were compared between the two groups in full analysis set(FAS)and protocol set(PPS).Safety and adverse events(AE)were evaluated in safety set(SS).Results A total of 414 participants were randomized(207 cases in Obs group and 207 cases in Con group).414 cases in FAS population(207 cases in Obs group and 207 cases in Con group),and 328 cases in PPS population(164 cases in Obs group and 164 cases in Con group),and 414 cases in SS population(207 cases in Obs group and 207 cases in Con group).After treatment,HbA1c,FPG and body weight were lower in both groups(P<0.05)in FAS and PPS.HbA1c compliance rate was not significantly different between the two groups in FAS and PPS(P>0.05).The results of non-inferiority test showed that the lower limit was>-0.4%in both FAS(-0.154,95%CI-0.384～0.069)and PPS(-0.139,95%CI-0.390～0.112),and the Obs group reached non-inferiority end point.The achievement rate,compliance rate,safety index and incidence of AE were not significantly different between the two groups(P>0.05).Conclusions Junlida? demonstrated non-inferiority to Glucophage? in glycemic control and can be safely and effectively used in patients with diabetes.

Objective To investigate the correlation of serum leucine-rich alpha-2 glycoprotein-1(LRG1)and Thiol levels with autoimmune antibodies and renal injury in patients with systemic lupus erythematosus nephritis(SLEN).Methods 80 SLEN patients(SLEN group)and 80 simple SLE patients(non-SLEN group)admitted to the Department of Nephrology at Qingdao Eighth People's Hospital and the Department of Rheumatology and Immunology at Affiliated Hospital of Qingdao University from January 2021 to December 2023 were selected.An enzyme-linked immunosorbent assay(ELISA)was used to detect serum LRG1 levels,while a colorimetric assay was used to detect serum Thiol levels.Pearson/Spearman correlation analysis was used to investigate the correlation between serum LRG1 and Thiol levels,autoimmune antibodies,and renal function indicators in SLEN patients.The diagnostic value of serum LRG1 and Thiol levels in SLEN was analyzed using receiver characteristic curves.Results The serum LRG1(26.00±8.76 μg/ml)and Scr(98.03±49.71μmol/L)in the SLEN group were higher than those in the non-SLEN group(16.71±5.51μg/ml,73.85±33.51μmol/L),and Thiol(80.69±36.90μmol/L)was lower than those in the non-SLEN group(131.49±45.34μmol/L),the differences were statistically significant(t=8.026,3.608,7.772,all P<0.001).Pearson/Spearman correlation analysis showed that serum LRG1 in SLEN patients was positively correlated with anti-double-stranded deoxyribonucleic acid(dsDNA)antibody,anti-complement 1q(C1q)antibody,anti-Smith antibody,serum creatinine(Scr),24-hour urine protein(r=0.226～0.637,all P<0.05),and negatively correlated with estimated glomerular filtration rate(eGFR)(r=-0.633,P<0.05).Serum Thiol was negatively correlated with anti-dsDNA antibodies,anti C1q antibodies,anti-Smith antibodies,Scr and 24-hour urine protein(r=-0.612～-0.256,all P<0.05),and positively correlated with eGFR(r=0.614,P<0.05).The AUC(95%CI)of serum LRG1 combined with Thiol levels for diagnosing of SLEN was 0.907(0.851～0.947),which was higher than that of serum LRG1 and Thiol alone at 0.802(0.731～0.860)and 0.808(0.738～0.866),and the differences were statistically significant(Z=3.450,3.749,all P<0.05).Conclusion Elevated serum LRG1 levels and decreased Thiol levels in SLEN patients were closely related to positive expression of autoimmune antibodies and renal dysfunction.Combined detection of serum LRG1 and Thiols can provide reference for the diagnosis of SLEN.

AIM To study the chemical constituents from the water fraction of rhizoma of Smilax trinervula Miq.and their biological activities.METHODS Polyamide,silica gel,Sephadex LH-20,ODS and semi-preparative HPLC were used for isolation and purification,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The antitumor activities were determined by MTT mothod,and the inhibitory activities on α-glucosidase were determined by PNPG method.RESULTS Eleven compounds were isolated and identified as tyrosine(1),uridine(2),2-(2',3',4'-trihydroxybutyl)-6-(2",3",4"-trihydroxybutyl)-pyrazine(3),2-(1',2',3',4'-tetrahydroxybutyl)-6-(2",3",4"-trihydroxybutyl)-pyrazine(4),2-(1',2',3',4'-tetrahydroxybutyl)-5-(2",3",4"-trihydroxybutyl)-pyrazine(5),uracil(6),2-(1',2',3',4'-tetrahydroxybutyl)-5-(1",2",3",4"-tetrahydroxybutyl)-pyrazine(7),dioscin(8),shikimic acid(9),pyrazine(10),3,4-dihydroxyphenyethyl alcohol 8-O-β-D-glycopyranoside(11).The IC50 values of compounds 8 to human breast cancer cell MCF-7 was(2.36±0.26)μg/mL,and the IC50 values of compounds 3-5 and 7 to α-glucosidase were(1.54±0.15)-(10.53±0.38)μg/mL.CONCLUSION Compounds 1-7,10 are isolated from Smilax genus for the first time,and compound 9,11 are first isolated from this plant.Compound 8 has anti-tumor activity,and compounds 3-5,7 have α-glucosidase inhibitory activities.

Objective:To explore the correlation between the post-traumatic stress disorder(PTSD)level and postoperative fear disease progression and quality of life in patients undergoing laparoscopic myomectomy,and to analyze the related factors affecting the occurrence of PTSD in patients.Methods:120 patients who underwent laparoscopic myomectomy in Ruijin People's Hospital from April 2022 to April 2024 were selected,the PTSD occurrence was assessed with the Civilian version of PTSD checklist-civilian version(PCL-C)1 month after operation,and the progression of fear of Disease was assessed with the fear of progression questionnaire-short form(FoP-Q-SF),the quality of life was assessed with uterine fibroid symptoms and health-related quality of life questionnaire(UFS-QOL).The correlation between PTSD level and postoperative fear disease progression and quality of life in patients undergoing laparoscopic myomectomy was analyzed,and the factors of PTSD in patients undergoing laparoscopic myomectomy were analyzed by multivariate Logistic regression.Results:PTSD scores of in patients undergoing laparoscopic myomectomy was(36.93±5.69)score,fear of disease progression was(26.00±1.66)score,quality of life was(54.27±4.82)score.The total score of PCL-C was positively correlated with the total score of FoP-Q-SF,and negatively correlated with the total score of UFS-QOL(P＜0.05).The patients were divided into PTSD group(n=30)and non-PTSD group(n=90)according to whether or not occurrence of PTSD at 1 month after operation.Univariate analysis showed that,there were significant differences in age,education level,family income,number of fibroids,operation time and preoperative anxiety level between the PTSD group and the non-PTSD group(P＜0.05).Multivariate Logistic regression analysis showed that age ≥35 years old,operation time ≥90 min,preoperative anxiety level of moderate to severe,and increased total score of FoP-Q-SF were independent risk factors for PTSD in patients undergoing laparoscopic myomectomy(P＜0.05),and increased total score of UFS-QOL were protective factors(P＜0.05).Conclusion:The PTSD level in patients undergoing laparoscopic myomectomy is positively correlated with fear disease progression and negatively correlated with quality of life.Age,operation time,preoperative anxiety,fear disease progression and quality of life were the factors that influenced the occurrence of PTSD.

Jiaxing city is one of the pilot cities for the Long-term Care Insurance(LTCI)policy in Zhejiang Province.This study examines the current implementation status of Jiaxing's LTCI policy in terms of financing(including financing targets,channels,methods,and standards)and benefit payments(including payment forms,contents,standards,and levels).It summarizes the experiences and challenges encountered during the pilot process.Currently,Jiaxing's LTCI policy has undergone continuous improvement in financing and benefit payment mechanisms.The financing targets now cover both urban and rural residents,and the coverage has expanded from individuals with severe disabilities to include those with severe dementia.The benefit content has been refined,with the introduction of a detailed service project directory and service pricing.For the future,it is recommended to expand the coverage to individuals with moderate disabilities,based on the fund's capacity and sustainability,and to differentiate benefit standards according to the severity of disability.Furthermore,it is suggested to strengthen the responsibilities of employers and individuals,diversify financing channels,and gradually explore an independent financing mechanism for LTCI.A combination of fixed-amount and proportional financing methods should be considered,alongside factors such as intergenerational equity and population aging trends,to establish a scientific and dynamic premium adjustment mechanism.