OBJECTIVE From the perspective of China’s healthcare system， to evaluate the cost-effectiveness of tislelizumab in patients with locally advanced or metastatic squamous or non-squamous non-small cell lung cancer （NSCLC） whose disease progresses or is intolerable after receiving platinum-containing dual chemotherapy in the past. METHODS Rationale-303 research data were used to construct a partitioned survival model. The model period was set to be 21 days and simulated to 120 months. Using quality-adjusted life year （QALY） as a health output index， the incremental cost-effectiveness ratio （ICER） was calculated by discounting cost and health output with a discount rate of 5%. Single-factor sensitivity analysis and probability sensitivity analysis were performed to verify the robustness of the basic analysis results. RESULTS Cost-utility analysis results showed that the ICER of tislelizumab group was 65 653.52 yuan/QALY， compared with docetaxel group. This means that the regimen of tislelizumab was more cost-effective than the docetaxel regimen when the willingness-to-pay threshold （WTP） was 3 times China’s gross domestic product （GDP） per capita in 2023 （268 200 yuan/QALY）. The results of single-factor sensitivity analysis showed that the three parameters that had a greater impact on ICER were the prices of tislelizumab， docetaxel and pemetrexed. The results of the probabilistic sensitivity analysis showed that the probabilities of the above two treatment regimens being cost-effective were both 50% when the WTP threshold was approximately 65 000 yuan/QALY. The probability of tislelizumab regimen being cost- effective was 100% when the WTP threshold was ≥134 000 yuan/QALY. CONCLUSIONS From the perspective of China’s healthcare system， when taking 3 times China’s GDP per capita in 2023 as the WTP threshold， tislelizumab is cost-effective for patients with locally advanced or metastatic squamous or non-squamous NSCLC after receiving platinum-containing dual chemotherapy in the past， compared with docetaxel.

BACKGROUND: The potential impact of pre-existing coronary artery stenosis (CAS) on right ventricular (RV) function during acute pulmonary embolism (PE) episodes remains underexplored. This study aimed to investigate the association between pre-existing CAS and RV dysfunction in patients with acute PE. METHODS: In this multicenter, case-control study, 89 cases and 176 controls matched for age were enrolled at three study centers (Peking Union Medical College Hospital, Fuwai Hospital, and the Second Affiliated Hospital of Harbin Medical University) from January 2016 to December 2020. The cases were patients with acute PE with CAS, and the controls were patients with acute PE without CAS. Coronary artery assessment was performed using coronary computed tomographic angiography. CAS was defined as ≥50% stenosis of the lumen diameter in any coronary vessel >2.0 mm in diameter. Conditional logistic regression analysis was used to evaluate the association between CAS and RV dysfunction. RESULTS: The percentages of RV dysfunction (19.1% [17/89] vs. 44.6% [78/176], P <0.001) and elevated systolic pulmonary artery pressure (sPAP) (19.3% [17/89] vs. 39.5% [68/176], P = 0.001) were significantly lower in the case group than those in the control group. In the multivariable logistic regression model, CAS was independently and negatively associated with RV dysfunction (adjusted odds ratio [OR]: 0.367; 95% confidence interval [CI]: 0.185-0.728; P = 0.004), and elevated sPAP (OR: 0.490; 95% CI: 0.252-0.980; P = 0.035), respectively. CONCLUSIONS Pre-existing CAS was significantly and negatively associated with RV dysfunction and elevated sPAP in patients with acute PE. This finding provides new insights into RV dysfunction in patients with acute PE with pre-existing CAS.
Humans ; Pulmonary Embolism/complications* ; Case-Control Studies ; Male ; Ventricular Dysfunction, Right/physiopathology* ; Female ; Middle Aged ; Aged ; Coronary Stenosis/complications* ; Logistic Models ; Adult

Objective To investigate the epidemiological characteristics and mutation spectrum of monogenic diseases in Chinese population through a large-scale,multicenter carrier screening.Methods This study was conducted among a total of 33 104 participants(16 610 females)from 12 clinical centers across China.Carrier status for 223 genes was analyzed using high-throughput sequencing and different PCR methods.Results The overall combined carrier frequency was 55.58%for 197 autosomal genes and 1.84%for 26 X-linked genes in these participants.Among the 16 669 families,874 at-risk couples(5.24%)were identified.Specifically,584 couples(3.50%)were at risk for autosomal genes,306(1.84%)for X-linked genes,and 16 for both autosomal and X-linked genes.The most frequently detected autosomal at-risk genes included GJB2(autosomal recessive deafness type 1A,393 couples),HBA1/HBA2(α-thalassemia,36 couples),PAH(phenylketonuria,14 couples),and SMN1(spinal muscular atrophy,14 couples).The most frequently detected X-linked at-risk genes were G6PD(G6PD deficiency,236 couples),DMD(Duchenne muscular dystrophy,23 couples),and FMR1(fragile X syndrome,17 couples).After excluding GJB2 c.109G>A,the detection rate of at-risk couples was 3.91%(651/16 669),which was lowered to 1.72%(287/16 669)after further excluding G6PD.The theoretical incidence rate of severe monogenic birth defects was approximately 4.35‰(72.5/16 669).Screening for a battery of the top 22 most frequent genes in the at-risk couples could detect over 95%of at-risk couples,while screening for the top 54 genes further increased the detection rate to over 99%.Conclusion This study reveals the carrier frequencies of 223 monogenic genetic disorders in the Chinese population and provides evidence for carrier screening strategy development and panel design tailored to the Chinese population.In carrier testing,genetic counseling for specific genes or gene variants can be challenging,and the couples need to be informed of these difficulties before testing and provided with options for not screening these genes or gene variants.

Objective To investigate the association of triglyceride-glucose index(TyG)with non-alcoholic fatty liver disease(NAFLD)and its diagnostic value for NAFLD in non-obese individuals.Methods We retrospectively collected the data of non-obese individuals(BMI<25 kg/m2)undergoing routine health examination at Second Affiliated Hospital of Xi'an Jiaotong University between May,2020 and December,2023,who all received abdominal ultrasound examination for NAFLD screening.The nonlinear relationship between TyG and non-obese NAFLD was explored using restricted cubic splines(RCS),and LASSO regression was used for variable screening;the correlation between TyG and NAFLD risk was analyzed using multivariate logistic regression.The diagnostic value of TyG for non-obese NAFLD was assessed using receiver-operating characteristic(ROC)curves and sensitivity analysis.Results A total of 3723 non-obese subjects were enrolled in this study,including 432(11.6%)patients with NAFLD.Compared with the healthy individuals,the patients with NAFLD had significant elevations of systolic and diastolic blood pressures,total cholesterol,triglycerides,LDL-C,blood uric acid,fasting blood glucose,and TyG index and a decreased HDL-C level(P<0.05).Multivariate logistic regression revealed that for each one-unit increase of TyG,the risk of non-obese NAFLD increased by 2.2 folds(OR=3.22,95%CI:2.53-4.12,P<0.001).Compared with a TyG index in the lowest quartile Q1,a TyG index in the Q2,Q3 and Q4 quartiles was associated with an increased risk of NAFLD by 1.52 folds(OR=2.52,95%CI:1.20-5.95),3.56 folds(OR=4.56,95%CI:2.28-10.46),and 8.66-folds(OR=9.66,95%CI:4.83-22.18),respectively.The RCS curve demonstrated a significant linear correlation between TyG index and non-obese NALFD risk(P for nonlinear=0.019).For diagnosing non-obese NALFD,TyG index had an area under ROC curve of 0.819 with a sensitivity of 78.0%and a specificity of 71.2%.Conclusion An increase of TyG index is correlated with increased risks of NAFLD in non-obese individuals and can serve as an indicator for screening early NAFLD in healthy individuals.

Objective To explore the mechanism of electroacupuncture pretreatment(EP)for relieving post-stroke spasticity in rats.Methods Eighteen rats were randomized equally into sham-operated group,middle cerebral artery occlusion(MCAO)group,and MCAO+EP group.In MCAO+EP group,the rats received electroacupuncture at the acupoints Qubin and Baihui for 3 consecutive days prior to MCAO.Neurological deficits and cognitive function of the rats were evaluated,and pathologies in the hippocampus were examined using HE,Nissl,and TUNEL staining.The expressions of IL-4,IL-6,TNF-α,and TMAO in the brain tissues were detected with ELISA,and the mRNA and protein expression levels of NF-κB p65,NLRP3,caspase-3,and caspase-9 were determined with qRT-PCR,Western blotting,and immunohistochemistry.Results The rats receiving MCAO had significantly increased neurological deficit scores and showed increased muscle tension,number of apoptotic neurons,and expressions of IL-6,TNF-α,NF-κB p65,NLRP3,caspase-3 and caspase-9 in the hippocampus and significantly reduced length of time for new object recognition.Microscopically,the cells in the hippocampus of the MCAO rats showed uneven and loosened arrangement and unclear cell boundaries.In contrast,the rats in I/R+EP group showed significantly lowered neurological deficit scores and dystonia rating scores,reduced cell apoptosis,lowered hippocampal expressions of IL-6,TNF-α,caspase-3,caspase-9,and NF-κB p65,increased time for new object recognition,tightly arranged and uniformly stained hippocampal cells with clear boundaries,with also an increased number of active neurons and enhanced expression of IL-4 in the hippocampus.Conclusion EP alleviates post-stroke spasticity in rats by inhibiting inflammatory responses and hippocampal neuronal apoptosis mediated by the NF-κB/NLRP3 signaling pathway.

Objective:To systematically evaluate the qualitative research on the practical experience of hospice care among medical staff in nursing homes, and to provide a reference basis for the implementation of hospice care services in nursing homes.Methods:The qualitative research on the practical experience of hospice care among medical staff in nursing homes was searched from databases including the Web of Science, PubMed, Cochrane Library, Embase, CINAHL, China National Knowledge Infrastructure, China Biology Medicine disc, Wanfang Data and VIP Database. The retrieval period was from the establishment of the database to March 21, 2024. The quality evaluation standards for qualitative research of the Australian Joanna Briggs Institute Evidence-Based Health Care Center were used to evaluate the quality of the literature. The results were integrated by the method of aggregative integration.Results:A total of 15 studies were included, and 47 clear research results were extracted, summarized into 11 categories, and 4 integrated results were obtained: the palliative care work responsibilities of medical staff; the emotional experience of medical staff in practice; coping with negative experience and gaining personal growth;the practical dilemmas faced by nursing homes when implementing hospice care.Conclusions:Nursing homes face multiple obstacles and challenges in the process of providing hospice care services. It is recommended that future research should focus on improving the policy system of hospice care in nursing homes, building a support system for hospice care services, and promoting the development and practice of death literacy among the public, so as to promote the healthy and long-term development of hospice care services in nursing homes.

Objective:Exploring the dilemmas faced by adolescents with type 1 diabetes mellitus in self-management during the transition to adult healthcare, to inform healthcare professionals in the delivery of transitional care interventions.Methods:Using descriptive qualitative research methods, in-depth interviews were conducted from August to December 2023 to adolescents with type 1 diabetes mellitus (selected by objective sampling) who met the inclusion and exclusion criteria in the Department of Endocrinology of the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine and the Shenzhen Children′s Hospital, and the data were analysed inductively using directed content analysis.Results:A total of 12 adolescents with type 1 diabetes mellitus were included for interview, 6 males and 6 females, aged 12-18 years. The self-management dilemmas for adolescents with type 1 diabetes in the transition to adult healthcare can be summarised into 4 themes and 10 sub-themes: disease management dilemmas (weak awareness of disease management, insufficient disease-related knowledge and competence, low adherence to disease management, and restriction of daily activities), role adaptation difficulties (lack of perceived transition to the healthcare role, difficulty in transitioning to the family role, and maladaptation to the social role), negative emotions Inadequate social support system (lack of school support, limited accessibility of social organisations, insufficient socio-economic support).Conclusions:Adolescents with type 1 diabetes mellitus face multiple dilemmas in disease self-management during the transition to adult healthcare, and healthcare professionals should pay attention to transition self-management education, improve patients′ awareness of transition self-management and their ability to participate in it, formulate a transition preparation plan, build an emotional support network, and improve the social security system, so as to help juvenile patients with type 1 diabetes master the method of self-management and make a successful transition to adulthood.

Objective To investigate the epidemiological characteristics and mutation spectrum of monogenic diseases in Chinese population through a large-scale,multicenter carrier screening.Methods This study was conducted among a total of 33 104 participants(16 610 females)from 12 clinical centers across China.Carrier status for 223 genes was analyzed using high-throughput sequencing and different PCR methods.Results The overall combined carrier frequency was 55.58%for 197 autosomal genes and 1.84%for 26 X-linked genes in these participants.Among the 16 669 families,874 at-risk couples(5.24%)were identified.Specifically,584 couples(3.50%)were at risk for autosomal genes,306(1.84%)for X-linked genes,and 16 for both autosomal and X-linked genes.The most frequently detected autosomal at-risk genes included GJB2(autosomal recessive deafness type 1A,393 couples),HBA1/HBA2(α-thalassemia,36 couples),PAH(phenylketonuria,14 couples),and SMN1(spinal muscular atrophy,14 couples).The most frequently detected X-linked at-risk genes were G6PD(G6PD deficiency,236 couples),DMD(Duchenne muscular dystrophy,23 couples),and FMR1(fragile X syndrome,17 couples).After excluding GJB2 c.109G>A,the detection rate of at-risk couples was 3.91%(651/16 669),which was lowered to 1.72%(287/16 669)after further excluding G6PD.The theoretical incidence rate of severe monogenic birth defects was approximately 4.35‰(72.5/16 669).Screening for a battery of the top 22 most frequent genes in the at-risk couples could detect over 95%of at-risk couples,while screening for the top 54 genes further increased the detection rate to over 99%.Conclusion This study reveals the carrier frequencies of 223 monogenic genetic disorders in the Chinese population and provides evidence for carrier screening strategy development and panel design tailored to the Chinese population.In carrier testing,genetic counseling for specific genes or gene variants can be challenging,and the couples need to be informed of these difficulties before testing and provided with options for not screening these genes or gene variants.

Objective To investigate the association of triglyceride-glucose index(TyG)with non-alcoholic fatty liver disease(NAFLD)and its diagnostic value for NAFLD in non-obese individuals.Methods We retrospectively collected the data of non-obese individuals(BMI<25 kg/m2)undergoing routine health examination at Second Affiliated Hospital of Xi'an Jiaotong University between May,2020 and December,2023,who all received abdominal ultrasound examination for NAFLD screening.The nonlinear relationship between TyG and non-obese NAFLD was explored using restricted cubic splines(RCS),and LASSO regression was used for variable screening;the correlation between TyG and NAFLD risk was analyzed using multivariate logistic regression.The diagnostic value of TyG for non-obese NAFLD was assessed using receiver-operating characteristic(ROC)curves and sensitivity analysis.Results A total of 3723 non-obese subjects were enrolled in this study,including 432(11.6%)patients with NAFLD.Compared with the healthy individuals,the patients with NAFLD had significant elevations of systolic and diastolic blood pressures,total cholesterol,triglycerides,LDL-C,blood uric acid,fasting blood glucose,and TyG index and a decreased HDL-C level(P<0.05).Multivariate logistic regression revealed that for each one-unit increase of TyG,the risk of non-obese NAFLD increased by 2.2 folds(OR=3.22,95%CI:2.53-4.12,P<0.001).Compared with a TyG index in the lowest quartile Q1,a TyG index in the Q2,Q3 and Q4 quartiles was associated with an increased risk of NAFLD by 1.52 folds(OR=2.52,95%CI:1.20-5.95),3.56 folds(OR=4.56,95%CI:2.28-10.46),and 8.66-folds(OR=9.66,95%CI:4.83-22.18),respectively.The RCS curve demonstrated a significant linear correlation between TyG index and non-obese NALFD risk(P for nonlinear=0.019).For diagnosing non-obese NALFD,TyG index had an area under ROC curve of 0.819 with a sensitivity of 78.0%and a specificity of 71.2%.Conclusion An increase of TyG index is correlated with increased risks of NAFLD in non-obese individuals and can serve as an indicator for screening early NAFLD in healthy individuals.

Objective To explore the mechanism of electroacupuncture pretreatment(EP)for relieving post-stroke spasticity in rats.Methods Eighteen rats were randomized equally into sham-operated group,middle cerebral artery occlusion(MCAO)group,and MCAO+EP group.In MCAO+EP group,the rats received electroacupuncture at the acupoints Qubin and Baihui for 3 consecutive days prior to MCAO.Neurological deficits and cognitive function of the rats were evaluated,and pathologies in the hippocampus were examined using HE,Nissl,and TUNEL staining.The expressions of IL-4,IL-6,TNF-α,and TMAO in the brain tissues were detected with ELISA,and the mRNA and protein expression levels of NF-κB p65,NLRP3,caspase-3,and caspase-9 were determined with qRT-PCR,Western blotting,and immunohistochemistry.Results The rats receiving MCAO had significantly increased neurological deficit scores and showed increased muscle tension,number of apoptotic neurons,and expressions of IL-6,TNF-α,NF-κB p65,NLRP3,caspase-3 and caspase-9 in the hippocampus and significantly reduced length of time for new object recognition.Microscopically,the cells in the hippocampus of the MCAO rats showed uneven and loosened arrangement and unclear cell boundaries.In contrast,the rats in I/R+EP group showed significantly lowered neurological deficit scores and dystonia rating scores,reduced cell apoptosis,lowered hippocampal expressions of IL-6,TNF-α,caspase-3,caspase-9,and NF-κB p65,increased time for new object recognition,tightly arranged and uniformly stained hippocampal cells with clear boundaries,with also an increased number of active neurons and enhanced expression of IL-4 in the hippocampus.Conclusion EP alleviates post-stroke spasticity in rats by inhibiting inflammatory responses and hippocampal neuronal apoptosis mediated by the NF-κB/NLRP3 signaling pathway.