1.Mechanism of action of remifentanil in alleviating lung ischemia-reperfusion injury in rats by modulating HIF-1α/NLRP3 pathway to inhibit cell pyroptosis
Lifang ZHAO ; Jiangong YANG ; Mingyong LI ; Kun SHAO ; Changli SHEN ; Jiajie LI ; Hong ZHU ; Liangchao QU
Acta Universitatis Medicinalis Anhui 2026;61(3):395-401
ObjectiveTo investigate the mechanism of action of remifentanil (RMZL) in alleviating lung ischemia-reperfusion injury (LIRI) in rats by inhibiting pyroptosis through modulating hypoxia inducible factor-1α (HIF-1α)/NOD-like receptor thermal protein domain associated protein 3 (NLRP3) pathway. MethodsRats were stochastically assigned into Control group, LIRI group, RMZL low-dose group, RMZL medium-dose group, RMZL high-dose group, and RMZL high-dose+HIF-1α activator dimethyloxallyl glycine (DMOG) group, with 18 rats in each group. Rats in Control group only had their left pulmonary hilum free and did not undergo ischemia-reperfusion treatment. Except for the Control group, LIRI models were constructed in all other groups. Rats in LIRI group were intraperitoneally injected with an equal amount of physiological saline 15 minutes before constructing LIRI model; rats in Control group were intraperitoneally injected with an equal amount of physiological saline 15 minutes before freeing left pulmonary hilum; rats in other groups were intraperitoneally injected with corresponding dose of drug 15 minutes before constructing LIRI model. The wet/dry weight ratio of lungs was calculated. HE staining was used to study lung tissue pathology. Immunofluorescence staining was used to detect the relative fluorescence intensity of gasdermin D (GSDMD) and NLRP3 double positive cells in lung tissue. ELISA was used to detect interleukin-1β and IL-18 in lung tissue. Western blot was used to detect HIF-1α, NLRP3, cysteine-aspartic protease-1 (Cleaved caspase-1), and gasdermin D-N (GSDMD-N) proteins in lung tissue. ResultsCompared to the Control group, the LIRI group showed disordered alveolar structure, thickened alveolar septa, and abundant inflammatory cell infiltration in rats. The lung wet/dry weight ratio, relative fluorescence intensity of GSDMD and NLRP3 double positive cells in lung tissue, IL-1β, IL-18 levels, and HIF-1α, NLRP3, Cleaved caspase-1, and GSDMD-N proteins increased (P0.05). For the LIRI group, rats in the RMZL low, medium, and high-dose groups displayed attenuated alveolar septal thickening and reduced inflammatory cell infiltration. The lung wet/dry weight ratio, relative fluorescence intensity of GSDMD and NLRP3 double positive cells in lung tissue, IL-1β, IL-18 levels, and HIF-1α, NLRP3, Cleaved caspase-1, and GSDMD-N proteins declined, and the RMZL high-dose group showed the most prominent trend (P0.05). Compared with the RMZL high-dose group, rats in the RMZL high-dose+DMOG group exhibited thickened alveolar septa and more inflammatory cell infiltration, along with increased lung wet/dry weight ratio, relative fluorescence intensity of GSDMD and NLRP3 double positive cells in lung tissue, levels of IL-1β and IL-18, and protein expression of HIF-1α, NLRP3, Cleaved caspase-1, and GSDMD-N (P0.05). ConclusionRMZL may inhibit pyroptosis in LIRI rats by suppressing HIF-1α/NLRP3 pathway.
2.The Implications of the Health Service System Construction in the Macao Special Administrative Region for the Mainland
Yanchun ZHANG ; Lifang ZHANG ; Ge GAN ; Hongming ZHU
Chinese Health Economics 2025;44(6):105-108
Objective:To review the health service system,personnel salary system and service model in Macao Special Administrative Region(Macao),and analyze the reference significance for the of the tightly-knit medical alliance construction.Methods:On-site visits were conducted to 2 hospitals,3 community health service centers and 1 nursing home in Macao.Interviews and focus group discussions were held with key informants.Literature review was carried out at the same time.Qualitative and quantitative analysis methods were used to analyze the collected data.Results:Macao has clearly defined the functional positioning of public hospitals and primary healthcare institutions,and has given full play to the supplementary role of private medical institutions,establishing a grid-based medical and health service system with clear division of labor and public-private cooperation.Macao has implemented a strict system of first diagnosis in primary health care and two-way referral,providing high-quality and efficient medical and health services to community residents.Macao has institutionalized the salary system for medical personnel,with only a small income gap between different types of institutions and personnel,establishing a homogenized high-level medical and health salary system.Conclusion:The mainland should strengthen the financial protection,and promote the coordinated management of staff,funds and properties.Institutionalize the income and responsibility system for medical personnel,and narrow the income gap between different types of institutions and personnel,strengthen the functional positioning of primary health care and services for key populations,and promote first diagnosis in primary health care and two-way referral.
3.Epidemiological characteristics of clustered vomiting and diarrhea outbreaks in Minhang District of Shanghai from 2018 to 2023
Zhiyin XU ; Lifang ZHAO ; Minhui ZHU ; Long CHEN ; Wanli CHEN ; Weibing WANG ; Yaxu ZHENG ; Xiaohua LIU
Shanghai Journal of Preventive Medicine 2025;37(9):737-741
ObjectiveTo analyze the epidemiological characteristics of clustered vomiting and diarrhea outbreaks in Minhang District of Shanghai, to identify the influencing factors of outbreak scale and duration of epidemic, and to provide scientific evidence for further strengthening surveillance early-warning efforts in key settings and for optimizing prevention and control measures. MethodsThe data for describing epidemiological characteristics of clustered vomitting and diarrhea outbreaks in Minhang District from 2018 to 2023 were collected, multivariable logistic regression models were applied to analyze the influencing factors for epidemic scale,and Spearman rank correlation analyses were applied to analyze the factors duration. ResultsA total of 136 clustered vomiting and diarrhea outbreaks were reported in Minhang District from 2018 to 2023, all occurring in school settings, with an overall attack rate of 0.90%. The outbreaks exhibited distinct seasonality, predominantly occurring from October to December (43.38%) and March to May (32.35%). The primary settings were preschools (45.59%) and elementary schools (44.12%), with students accounted for the majority of cases (99.48%). The predominant clinical manifestation was vomiting (90.44%), with person-to-person contact being the primary transmission route (98.53%). Norovirus genogroup Ⅱ was identified as the main pathogen (71.32%). Standardized terminal disinfection of outbreak sites (OR=0.39, 95%CI=0.20‒0.74) and effective isolation of affected classes (OR=0.23, 95%CI=0.09‒0.57) were significant protective factors for reducing outbreak scale. Both response time (r=0.64, P<0.001) and the number of case generations (r=0.71, P<0.001) showed positive correlations with outbreak duration. ConclusionSchools are the key settings for the prevention and control of clustered vomiting and diarrhea outbreaks in Minhang District, with peak occurring in autumn and spring. Early detection, timely reporting, and prompt response to outbreaks are crucial. Strengthening school-based surveillance systems and standardizing outbreak management protocols are of particular importance.
4.Redox-responsive nanoparticles reversing non-small cell lung cancer multidrug resistance via dual mechanisms
Feng ZHU ; Chaoting FU ; Yazhou WANG ; Zheng KUANG ; Lifang YIN
Journal of China Pharmaceutical University 2025;56(6):729-736
A redox-responsive hyaluronic acid-vitamin E polyethylene glycol succinate nanoparticle loaded with paclitaxel (HA-SS-TPGS@PTX) was designed to investigate its mechanism for overcoming multidrug resistance (MDR) in non-small cell lung cancer (NSCLC) in vitro. HA-SS-TPGS@PTX nanoparticles were prepared using an emulsion-ultrasonication method. Techniques such as flow cytometry and confocal laser scanning microscopy (CLSM) were employed to study their effects on apoptosis induction, mitochondrial function, and the regulation of P-glycoprotein (P-gp) expression in PTX-resistant lung cancer cells (A549/T). Results showed that HA-SS-TPGS@PTX nanoparticles significantly inhibited the proliferation of A549/T cells in vitro, with an IC50 of 1.35 μg/mL. The nanoparticles entered the cells via CD44 receptor-mediated endocytosis. The high intracellular concentration of glutathione (GSH) triggered the release of PTX and TPGS, which subsequently induced a decrease in mitochondrial membrane potential, leading to apoptosis. Meanwhile, HA-SS-TPGS@PTX also inhibited P-gp expression and ATP consumption, thereby blocking drug efflux. The design of HA-SS-TPGS@PTX provides a new strategy for overcoming MDR in NSCLC.
5.Study on the Correlation between TCM Syndrome Types of Diabetic Nephropathy Complicated with Atherosclerosis and WLR,PLR,MLR
Xiao'ou ZHU ; Bijia ZHAO ; Lifang CHEN
Journal of Zhejiang Chinese Medical University 2025;49(9):1157-1162
[Objective]To investigate the correlation between traditional Chinese Medicine(TCM)syndrome types in patients with diabetic nephropathy(DN)and leukocyte lymphocyte ratio(WLR),platelet/lymphocyte ratio(PLR),monocyte lymphocyte ratio(MLR).[Methods]A total of 227 patients with DN and AS were included in this study to analyze the changes of WLR,PLR,MLR,carotid intima-medial thickness(IMT)and the levels of WLR,PLR and MLR under different TCM syndrome types.Logistic analysis and receiver operating characteristic(ROC)curves were used to evaluate the application value of WLR,PLR and MLR in predicting the severity and prognosis of DN complicated with AS.[Results]Among the TCM syndrome types in patients with DN and AS,Qi and Yin deficiency syndrome accounted for the highest proportion,followed by spleen and kidney Yang deficiency syndrome,Yin and Yang deficiency syndrome,and turbidity and stasis obstruction syndrome.The levels of WLR,PLR,and MLR in patients with DN and AS from high to low were turbidity and stasis obstruction syndrome,Yin and Yang deficiency syndrome,spleen and kidney Yang deficiency syndrome,and Qi and Yin deficiency syndrome.WLR,PLR,MLR were positively correlated with IMT(P<0.05).Logistic analysis showed that the levels of WLR,PLR and MLR were correlated with the severity of DN and AS.ROC curve analysis indicated WLR,PLR,MLR had high value in evaluating the prognosis of DN combined with AS(P<0.05).[Conclusion]WLR,PLR and MLR are expected to be potential biological indicators for microscopic syndrome differentiation and prognosis evaluation of DN combined with AS in TCM.
6.Assessment of consistency between coronal architectural distortion in three-dimensional ultrasonography and full-field digital mammography
Yanjuan TAN ; Anqian HUANG ; Lifang YU ; Luoxi ZHU ; Lingyun BAO
Chinese Journal of Ultrasonography 2025;34(3):225-231
Objective:To evaluate the consistency between architectural distortion(AD)observed on coronal images in three-dimensional ultrasonography(3D-US)and full-field digital mammography(FFDM),and to analyze the influencing factors of the presence of AD on 3D-US coronal images.Methods:A retrospective study was conducted on 96 female patients(97 lesions)with AD identified via FFDM that examined at Affiliated Hangzhou First People's Hospital,School of Medicine,Westlake University from January 2019 to December 2021,all of which with corresponding 3D-US results. Kappa analysis was used to assess the consistency between AD on 3D-US and FFDM.The differences of the lesion characteristics on FFDM(glandular density,presence of calcifications,and degree of distortion),3D-US features(number of lesions,presence of mass or non-mass lesions,and skipping sign in coronal images),clinical pathological characteristics(age,location,and pathology)between groups with AD and without AD in 3D-US were compared. Multivariate Logistic regression was used to identify the influencing factors.Results:Among the FFDM-identified AD lesions,62(63.92%,62/97)lesions showed AD on 3D-US coronal images,including 30 malignant lesions(48.39%,30/62);35(36.08%,35/97)lesions without AD on 3D-US,in which 4(11.43%,4/35)were malignant. The consistency of distortion degree between FFDM and 3D-US was moderate(Kappa=0.455, P<0.001),with no statistically significant difference( χ2=2.882, P=0.143). The probability of malignancy was higher in typical AD compared to atypical AD. The comparisons of age,location,number of lesions,presence of skipping sign in 3D-US,breast density,and presence of calcification in the lesion showed no statistically significant differences between the groups with and without AD(all P >0.05).The pathological results of malignancy,presence of lesions in 3D-US(mass and non-mass lesions),and the degree of distortion in FFDM showed statistically significant differences(all P < 0.05). The multivariate Logistic regression analysis indicated that there were no independent risk factors for the appearance of AD in 3D-US(all P > 0.05). Conclusions:In breast FFDM AD lesions,the incidence of 3D-US coronal plane AD was 63.92%,and the consistency between the degree of distortion in FFDM and 3D-US was moderate. The probability of malignancy is higher with typical AD. Pathological malignancy,presence of lesions in 3D-US(both mass and non-mass lesions),and typical AD in FFDM are more likely to correspond with AD in the coronal.
7.Configuration-based analysis of improvement paths for professional commitment among master of nursing specialist degree students: a fsQCA approach
Tianyan WANG ; Kaiyun ZHOU ; Juanjuan ZHOU ; Yuelan ZHU ; Meimei ZHANG ; Qianqian ZHANG ; Lifang FAN ; Hui ZHOU
Chinese Journal of Modern Nursing 2025;31(29):4055-4060
Objective:To explore the configurational factors influencing the professional commitment of Master of Nursing Specialist (MNS) students and identify effective paths to enhance their professional commitment.Methods:A convenience sample of MNS students from six hospitals in Jiangsu Province, Shanghai City, and Anhui Province was surveyed between December 2023 and October 2024. Data were collected using a general information questionnaire, the Nurses' Professional Commitment Scale (NPCS), the Connor-Davidson Resilience Scale (CD-RISC-10), the Multidimentional Perceived Social Support (MSPSS), and the Vocational Outcome Expectation Scale (VOE-R). Fuzzy-set Qualitative Comparative Analysis (fsQCA) was used to explore the configurational influences on professional commitment.Results:A total of 332 questionnaires were distributed, and 302 valid responses were obtained (effective response rate: 90.1%). The mean NPCS score among respondents was (89.30±22.42), indicating a upper-middle level of professional commitment. The fsQCA results revealed that the frequency of night shift rotation was a necessary condition affecting professional commitment. A total of three distinct configurations (paths) were identified that can enhance the professional commitment of MNS students.Conclusions:The professional commitment of MNS students is influenced by multiple interacting factors. It is recommended that hospitals, universities, and nursing educators develop targeted interventions based on these identified configurations to improve professional commitment.
8.Application of three-level task-driven teaching based on motivational regulation strategy in training nurse interns in the Department of Clinical Psychology
Lifang JIN ; Qiwen BIAN ; Fei SHAO ; Linlin JIN ; Meng LAI ; Junpeng ZHU
Chinese Journal of Medical Education Research 2025;24(6):848-852
Objective:To explore the application of three-level task-driven teaching based on motivational regulation strategy in training nurse interns in the Department of Clinical Psychology.Methods:This study included 80 nurse interns in the Department of Clinical Psychology at Zhejiang Provincial People's Hospital between June 2021 and May 2024 as research subjects. They were divided into a control group ( n=40) and an experimental group ( n=40). The control group received traditional teaching, while the experimental group received three-level task-driven teaching based on motivational regulation strategy, covering basic knowledge mastery, practical operation improvement, and comprehensive ability enhancement. Through scenario guidance and simulation exercises, the intrinsic motivation of nurse interns was stimulated. The assessment scores, self-learning ability, teaching quality, and recognition of teaching were compared between the two groups of nurse interns. Results:After teaching, the experimental group scored higher than the control group on theoretical assessment [(86.05±5.86) vs. (74.35±4.72)] and operational skill assessment [(88.18±5.67) vs. (82.65±6.09)] ( P<0.001). The total score and scores of various dimensions of teaching quality were higher in the experimental group compared to those in the control group ( P<0.001). After teaching, the total score and scores of various dimensions of self-learning ability of both groups were higher than those before teaching, and the scores were higher in the experimental group than in the control group ( P<0.05). Conclusions:The three-level task-driven teaching based on motivational regulation strategy can significantly improve the assessment scores, self-learning abilities, and teaching quality of nurse interns in the Department of Clinical Psychology. Additionally, this method can enhance their recognition of nursing internship teaching. This teaching method is worth promoting.
9.Analysis of Hearing Loss in Offspring Mice with Chronic Intrauterine Hypoxia
Rifu WEI ; Liwen CHEN ; Ping LIU ; Zhongshou ZHU ; Lifang GUO ; Xiaomei ZENG
Journal of Audiology and Speech Pathology 2025;33(1):62-65
Objective To study the effects and the possible mechanism of the hearing loss of offspring mice with chronic intrauterine hypoxia.Methods Ten healthy SD pregnant mice with SPF level were selected to establish an intrauterine hypoxia model as the hypoxia group,while another ten healthy SD pregnant mice without hypoxia treatment were selected as the control group.Arterial blood gas analysis was performed on pregnant mice and audi-tory brainstem response(ABR)testing was performed on their offspring after birth,and the results of each group were compared.Results The PaO2 and SaO2 of the hypoxic group were significantly lower than those of in the con-trol group.The hearing loss rate and wave Ⅲ response threshold of the offspring mice of the hypoxia group were significantly higher than those of in the control group at 21 and 56 days,but over time,the hearing loss rate and wave Ⅲ response threshold of the hypoxia group improved compared to before.Although some offspring mice in the hypoxic group at 21 day and 56 day had normal Ⅲ wave response thresholds,their wave Ⅱ and Ⅲ latency,as well as the latency between Ⅰ-Ⅱ,Ⅱ-Ⅲ,and Ⅰ-Ⅲ,were still significantly higher,while the amplitude of wave Ⅲ and the ratio of Ⅲ/Ⅰ were significantly lower than those of in the control group during the same period.For hypoxic off-spring mice with abnormal wave Ⅲ response threshold at 21 days and normal wave Ⅲ response threshold at 56 days,the latency of waves Ⅱ and Ⅲ,as well as the latency between Ⅰ-Ⅱ,Ⅱ-Ⅲ,and Ⅰ-Ⅲ were significantly higher,while the amplitude of wave Ⅲ and the ratio of Ⅲ/Ⅰ were significantly lower than those of in the control group and hypoxic group with normal wave Ⅲ response thresholds at 21 days and 56 days.The hearing loss of offspring mice in the hypoxia group was mainly bilateral.Conclusion Chronic intrauterine hypoxia can lead to varying degrees of hearing loss,but this type of hearing loss has a certain degree of retrogression in the early stages,and the body can undergo limited developmental compensation and repair.
10.Effect of TCF1+CD8+T cells on prognosis of nasopharyngeal carcinoma patients undergoing immunotherapy
Lifang WEI ; Shuyan ZHAO ; Qingshan ZHU ; Xinsen WANG
Chinese Journal of Immunology 2025;41(7):1610-1615
Objective:To investigate the effect of TCF1+CD8+T cells on the prognosis of nasopharyngeal carcinoma(NPC)pa-tients undergoing immunotherapy.Methods:A retrospective study was conducted on 108 NPC patients admitted to Anyang Cancer Hospital from January 2018 to April 2020.Pathological findings and clinical data were collected,and multiple immunofluorescence staining was utilized to detect TCF1+CD8+T cell levels in tumor tissue.Cell counts and the proportion of positive cells were measured,and the optimal cut-off value was determined using a time-dependent receiver operating characteristic(ROC)curve.Patients were clas-sified into high expression group and low expression group according to the cut-off value.The general information and survival status were compared between two groups,and univariate and multivariate Cox regression analysis were performed to screen the influencing factors of patient prognosis.Results:The optimal cut-off value was determined using ROC curve.A cut-off value of 0.34%for TCF1+CD8+T cell area under the curve(AUC)=0.653 resulted in a sensitivity of 73.5%and a specificity of 43.7%.Based on the opti-mal cut-off value,33 patients with TCF1+CD8+T cell beyond 0.34%were included in high expression group,and the remaining 75 pa-tients were included in low expression group.The proportion of TCF1+CD8+T cells was(0.43±0.09)%in high expression group and(0.21±0.08)%in low expression group.Comparison of general data yielded that the gender,age,body mass index(BMI),clinical stage,and pathological classification showed no statistical difference between two groups(P>0.05),while the percentage of patients with T stage of T3 and T4,N stage of N2 and N3,and M stage of M1 in high expression group were smaller than that in low expression group(P<0.05).The 24-month survival rate was 81.82%(27/33)in high expression group and 74.67%(56/75)in low expression group,with no statistical difference between two groups(χ2=0.658 8,P=0.417 0).Univariate and multivariate Cox regression analysis found that T stage,N stage and M stage were independent risk factors affecting the prognosis of patients,and TCF1+CD8+T expression was a protective factor.ROC curve indicated that the AUC,sensitivity and specificity of TCF1+CD8+T expression in predicting death of NPC patients undergoing immunotherapy was 0.674,69.7%and 65.3%,while the AUC,sensitivity and specificity of TCF1+CD8+T ex-pression combined with TNM stage in predicting death was 0.809,75.8%and 84.0%,respectively.Conclusion:NPC patients with higher proportion of TCF1+CD8+T cells and lower TNM stage have higher 24-month survival rate after immunotherapy,and the above parameters are of great predictive value for patient prognosis.

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