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 effectiveness and feasibility of whole exome sequencing (WES), as a molecular diagnosis technique, for adult patients with genetic diseases.Methods:The present retrospective analysis included 445 adult patients (ages 18-80 years) with suspected genetic diseases who underwent whole exome sequencing (WES) from August 2021 to December 2022. The pathogenicity classification of each variant was assessed in accordance with the recommendations developed by the American Society of Medical Genetics and Genomics.Results:The overall positive rate of WES among adult patients with suspected genetic diseases was 28.08% (125/445). The highest positive rate was observed in the age group of 41-50 years (34.33%, 23/67). Among the diagnosed genetic diseases, those affecting the cardiovascular system (63.16%, 84/133), nervous system (18.05%, 24/133), and endocrine system (13.53%, 18/133) ranked as the top three. The most common genetic diseases identified through WES in adult patients were hypertrophic cardiomyopathy (18.80%, 25/133), dilated cardiomyopathy (16.54%, 22/133), Marfan syndrome (15.04%, 20/133), epilepsy (9.02%, 12/133), and familial hypercholesterolemia (4.51%, 6/133). The main causative genes identified included FBN1 (14.29%, 19/133), MYBPC3 (9.02%, 12/133), MYH7 (9.02%, 12/133), LDLR (3.76%, 5/133), TTN (3.76%, 5/133), and TNNI3 (3.01%, 4/133).Conclusion:Applying the WES technique in clinical practice can improve the diagnostic rate of adult genetic diseases, especially in adult patients with suspected genetic conditions involving the cardiovascular system, nervous system, and endocrine system.

Objective To investigate the correlation of human epididymis protein 4(HE4)with proteinuria in patients with type 2 diabetes mellitus(T2DM).Methods A total of 147 T2DM patients from January 2020 to July 2023 in Jiujiang NO.l People's Hospital were enrolled in observation group.According to the severity of proteinuria,observation group was divided into three groups:Normal albuminuria group(101 cases),microalbuminuria group(25 cases),and massive albuminuria group(21 cases).50 healthy examinees with gender and age matching during the same period were selected as control group.HE4 levels and clinical indicators in each group were compared and analyzed.Correlation between HE4 and proteinuria was analyzed by using univariate and multivariate linear regression.Results The correlation network diagram reveals that HE4 functions was a pivotal node linking serum albumin,urinary microalbumin,urinary microalbumin-to-creatinine ratio(UACR),and renal function biomarkers.Compared to control group,HE4 levels significantly elevated in observation group(P＜0.01).Both univariate and multivariate linear regression analysis demonstrate a positive correlation between HE4 and UACR.Logistic regression analysis shew that after adjusting for confounding factors including age,gender,estimated glomerular filtration rate(eGFR),albumin(ALB),blood urea nitrogen(BUN),serum creatinine(SCr),uric acid(UA),lactate dehydrogenase(LDH)etc.elevated HE4 levels was a risk factor for proteinuria(OR=1.110,95％CI:1.005-1.226).Conclusion Elevated HE4 levels in patients with T2DM is positivly correlated with UACR.Increase its level increases the risk of proteinuria in T2DM patients.

Objective:To analyze the nutritional status of elderly inpatients using Global Leadership Initiative on Malnutrition (GLIM) criteria.Methods:A total of 5 236 elderly patients (aged 65 years or older) who were hospitalized at the West China Hospital, Sichuan University from March 2021 to March 2022 were included. The nutritional status was analyzed using the GLIM diagnostic criteria for malnutrition.Results:The rate of patients at nutritional risk was 30.29%, and the incidence of malnutrition as per GLIM criteria was 15.64%. The levels of hemoglobin, albumin, triglycerides, and cholesterol, and body mass index of the malnutrition group were lower compared with the non-malnutrition group, and the differences were statistically significant ( P<0.05). The non-malnutrition group had significantly shorter hospital stay and lower hospitalization costs compared with the malnutrition group ( P<0.001). Conclusions:The GLIM criteria is suitable for evaluating the nutritional status in elderly inpatients. The incidence of malnutrition in elderly inpatients is relatively high, which deserves attention in clinical management.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To construct a predictive model based on preoperative heat shock protein 90 alpha (HSP90 alpha) and lymphocyte count/monocyte ratio (LMR), for prediction of the textbook outcome (TO) of intrahepatic cholangiocarcinoma after surgery, and evaluate the predictive value of the model.Methods:Retrospective analysis of data from 210 patients with intrahepatic cholangiocarcinoma admitted to Chengde Central Hospital from January 2022 to December 2023, including 122 males and 88 females, aged (61.3±5.5) years. The patients were randomly divided into a training set (147 cases) and a validation set (63 cases) according to a ratio of 7: 3. According to whether the patients achieved TO after surgery, the patients in the training set were divided into a TO group ( n=39) and a non-TO group ( n=108). The conditions of tumor length < 5 cm, lymph node metastasis, large vessel invasion, preoperative HSP90α decrease, and preoperative LMR increase were compared between the two groups. Based on the training set, univariate and multivariate logistic regression were used to analyze the influencing factors of postoperative TO in patients with intrahepatic cholangiocarcinoma. Based on multi-factor results, R 4.3.0 software was used to construct a prediction model for TO. The model was evaluated by receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DSA). Results:Multivariate logistic regression analysis showed that the tumor diameter < 5 cm ( OR=1.917, 95% CI: 1.104-4.024), no lymph node metastasis ( OR=2.489, 95% CI: 1.030-3.619), and no invasion of large vessels ( OR=2.565, 95% CI: 2.097-5.093), the decrease of HSP90α before surgery ( OR=3.161, 95% CI: 2.536-5.358), and the increase of LMR before surgery ( OR=2.088, 95% CI: 1.454-4.262) were the influencing factors for patients TO achieve postoperative TO (all P<0.05). A correlation nomogram model was built based on the above indicators. The area under the curve of the model predicting the postoperative TO of the patients in the training set and the test set were 0.875 (95% CI: 0.782-0.938) and 0.860 (95% CI: 0.767-0.912), respectively, indicating good predictive value of the model. The calibration curve was basically consistent with the standard curve, indicating that the model has good consistency and accuracy. DCA results showed that the models had good clinical net benefit in the threshold probability range of 0.1~0.8. Conclusion:The nomogram model based on perioperative HSP90α and LMR has good accuracy and clinical applicability in predicting the possibility of achieving TO after surgery for cholangiocarcinoma, which can provide a reference for clinical treatment.

From October 2021 to February 2023, we retrospectively analyzed the clinical and laboratory data of six patients (three male and three female, median age: 54 years, age range: 29-73 years) with mast cell leukemia (MCL) diagnosed in the First Affiliated Hospital of Soochow University (The Mastocytosis Collaborative Network of China). All patients had acute MCL, with at least one C-finding present. The main clinical presentations were hypoalbuminemia ( n=4), fatigue ( n=3), fever ( n=2), abdominal discomfort ( n=2), osteolytic lesions ( n=2), dizziness ( n=1), skin flushing ( n=1), and weight loss ( n=1). Splenomegaly and lymphadenopathy were noted in six and three patients, respectively. Six patients were strongly positive for CD117, five were positive for CD30 and CD25, and four were positive for CD2. Four patients had a normal karyotype and two patients had an abnormal karyotype. Gene mutations were detected in 4/6 cases. The median serum tryptase level was 24.9 (range: 20.1-171.9) μg/L. Two patients were treated with venetoclax and azacitidine for induction (one patient achieved partial remission by combination with afatinib, while there was no remission after combination with dasatinib in the other patient). Two patients did not achieve complete remission despite treatment with cladribine and imatinib, respectively. One patient treated with interferon combined with glucocorticoids was lost to follow-up, and one patient abandoned treatment. The follow-up time ranged from 1.1 to 21.7 months. Three patients died and two survived. Overall, MCL is a rare subtype of systemic mastocytosis with heterogeneous clinical course, and these patients have poor outcome. A better understanding of the clinical characteristics, treatment, and prognosis of MCL is urgently needed.

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.