OBJECTIVE To provide reference for rational clinical use of immune checkpoint inhibitor （ICI）. METHODS Electronic medical record information of patients who received ICI treatment from January 1st 2020 to December 31st 2023 at a certain hospital was collected. Patients were divided into thyroid immune-related adverse event （irAE） group （subdivided into clinical hypothyroidism， clinical hyperthyroidism， subclinical hypothyroidism， and subclinical hyperthyroidism subgroups） and non- thyroid irAE group based on whether they experienced immune-induced thyroid irAE. Univariate and multivariate Logistic regression analyses were employed to analyze the influencing factors of ICI-related thyroid adverse events. RESULTS A total of 382 patients who received ICI treatment were included， with 137 cases in the thyroid irAE group （accounting for 35.9%） and 245 cases in the non-thyroid irAE group （accounting for 64.1%）. Multivariate Logistic regression analysis， following univariate screening， revealed that ICI combined with radiotherapy was positively associated with the occurrence of thyroid irAE [odds ratio （OR）＝2.157， 95% confidence interval （CI） （1.144， 4.066）， P＜0.05]， while lung squamous cell carcinoma was negatively associated with the occurrence of thyroid irAE [OR＝0.600， 95%CI （0.369， 0.975）， P＜0.05]. Among various thyroid irAE， nasopharyngeal malignancy was positively associated with the occurrence of immune-related clinical hyperthyroidism [OR＝4.678， 95%CI （1.149， 19.042）， P＜0.05]； ICI combined with radiotherapy [OR＝2.622， 95%CI （1.227， 5.603）， P＜0.05] and lung adenocarcinoma [OR＝2.013， 95%CI （1.078， 3.759）， P＜0.05] were positively associated with the occurrence of immune-related subclinical hyperthyroidism. Age was negatively associated with the occurrence of immune-related clinical hypothyroidism [OR＝0.944， 95%CI （0.896， 0.995）， P＜0.05]； age [OR＝0.963， 95%CI （0.932， 0.994）， P＜0.05] and ICI combined with chemotherapy [OR＝0.332， 95%CI （0.137， 0.802）， P＜0.05] were negatively associated with the occurrence of immune-related subclinical hypothyroidism. CONCLUSIONS Among patients receiving ICI treatment， younger patients are more prone to thyroid irAE. Patients receiving ICI combined with chemotherapy are less likely to experience subclinical hypothyroidism， while ICI combined with radiotherapy significantly increases the risk of thyroid adverse events.

OBJECTIVE To study the immunotherapeutic effect of chimeric virus-like particles(VLPs) based on hepatitis E virus(HEV) against human papillomavirus type 16(HPV 16) tumor. METHODS HPV16 E7 was inserted into the p239 protein of HEV to form the recombinant chimeric protein p239-HPV16 E7. The constructed recombinant protein was expressed by Escherichia coli, purified, and then refolded, and the protein was detected by electron microscopy and dynamic light scattering to confirm size and shape. Then, the C57B/L mice were immunized with the protein grain, and the lymphocyte differentiation of mouse spleen was detected by flow cytometry and enzyme-linked immune spot immunoassay; in addition, TC-1 tumor cells were used to construct tumor models in C57B/L mice to evaluate the anti-tumor immune effect of protein particles in mice. RESULTS After refold in vitro, the structure of chimeric protein was observed under electron microscopy, and the size of particle was 22.80 nm. The obtained protein particles induced favorable specific cellular immune response in C57B/L mice. Compared with the control group, the proportions of CD3+/CD4+ and CD3+/CD8+ in spleen lymphocytes of experimental groups were significantly different(P＜0.05), and effector T cells secreting IFN-γ interferon were also increased remarkably. At the same time, the obtained protein particles could effectively inhibit the growth of tumor cells in TC-1 tumor-bearing mice, and the mice did not die during the experimental period, while the tumors in the control mice grew rapidly and all died after 6 weeks. CONCLUSION Chimeric protein p239-HPV16E7 which was expressed in prokaryotes can form virus-like particles and effectively induce anti-tumor immunity against HPV16.

Background In recent years, the incidence of metabolic syndrome (MS) is increasing significantly in China. Some studies have found that temperature is related to single metabolic index, but there is a lack of research on associated mechanism and identifying path of the influence of temperature on MS. Objective Based on the data of Guangdong Province, to investigate the effect of temperature on MS and its pathway. Methods A total of 8524 residents were enrolled by multi-stage random sampling from October 2015 to January 2016 in Guangdong. Basic characteristics, behavioral characteristics, health status, and physical activity level were obtained through questionnaires and physical examinations, and meteorological data were obtained from meteorological monitoring sites. We matched individual data both with the temperature data of the physical examination day and of a lag of 14 d. A generalized additive model was used to explore the exposure-effect relationship between temperature and MS and its indexes, calculate effect values, and explore the effects of single-day lag temperature. Based on the literature and the results of generalized additive model analysis, a path analysis was conducted to explore the pathways of temperature influencing MS. Results The association between daily average temperature on the current day or lag 14 day and MS risk was not statistically significant. When daily average temperature increased by 1 ℃, the change values of fasting blood-glucose (FBG), systolic blood pressure (SBP), diastolic blood pressure (DBP), and high density lipoprotein cholesterol (HDL-C) were −0.033 (95%CI: −0.040-−0.026) mmol·L⁻¹, −0.662 (95%CI: −0.741-−0.583) mmHg, −0.277 (95%CI: −0.323-−0.230) mmHg, and −0.005 (95%CI: −0.007-−0.004) mmol·L⁻¹ respectively. The effects of average daily temperature on FBG, blood pressure, HDL-C, and waist circumference lasted until lag 14 day. The effects of daily average temperature on SBP and DBP were the largest on the current day. Daily average temperature of current day had direct and indirect effects on FBG and SBP. Temperature had an indirect effect on TG, and the intermediate variables were waist circumference and FBG, with an indirect effect value of −0.011 (95%CI: −0.020-−0.002). The indirect effects of daily average temperature on SBP, FBG, and TG were weak. Conclusion There is no significant correlation between temperature and risk of MS, and daily average temperature of current day could significantly affected blood pressure and FBG with a lag effect. Daily average temperature of current day has indirect effects on FBG and TG.

Objective:To investigate the postoperative changes in levels of 25-hydroxy vitamin D (25-[OH]D], parathyroid hormone (PTH) and other relevant biomarkers in obese patients receiving metabolic surgery and analyze the dynamic changes in relevant biomarkers in the short term (after 3-6 months) and the long term (after 12-24 months).Methods:A total of 96 obese patients who underwent metabolic surgery and received follow-up examinations from January 2018 to January 2020 were included. Baseline and postoperative data were collected, including anthropometric data (height, weight, neck circumference, waistline and hipline) and laboratory test results (fasting glucose, glycated hemoglobin, 25-[OH)D, PTH, serum calcium and serum phosphorus). Body mass index (BMI) and waist-hip ratio were calculated. The anthropometric data were analyzed by repeated measures analysis of variance and laboratory data were compared between groups using t test and Kruskal-Wallis test. Results:96 patients (33 males and 63 females) were included, of whom 49 were complicated with diabetes. Prior to surgery, 79 (79.17%) of the patients had 25-(OH)D deficiency (< 20 μg/L), 16 (16.67%) had 25-(OH)D insufficiency (≥ 20 μg/L and < 30 μg/L) and 23 (23.96%) had high PTH levels (> 70 ng/L). After the surgery, 25-(OH)D level was transiently increased in the short term ( P = 0.01) but declined thereafter in the long term ( P < 0.01) to levels lower than baseline ( P = 0.023). Long-term PTH level was higher than baseline ( P = 0.012), with 11 patients showing PTH levels higher than normal (> 70 ng/L). Serum phosphorus level was increased in both the short term and the long term ( P < 0.01). Conclusions:Obese patients have 25-(OH)D deficiency/insufficiency before metabolic surgery and experience further decrease in the long term after surgery, despite a transient increase. Secondary increase in PTH level occurs in some of the patients after surgery. Long-term nutritional supplements and comprehensive nutritional management play important roles in postoperative management of obese patient.

Objective:To investigate the value of minimal residual disease (MRD) in prediction of prognosis in acute lymphoblastic leukemia (ALL) patients with or above complete remission 2 (CR2) underwent.Methods:A retrospective analysis was performed on 201 ALL patients who received allogeneic stem cell transplantation (allo-SCT) and pretransplant disease status ≥CR2 in Peking University People′s Hospital from January 2009 to December 2018. MRD was measured by multi-parameter flow cytometry at 1 month before transplantation and 1 month, 2 months, 3 months, 4 months, 6 months, 9 months or 12 months after transplantation. To investigate the influence of dynamic changes of MRD before and after transplantation on prognosis.Results:201 ALL patients, including 126 males and 75 females, with a median age of 18 years. The 3-year cumulative incidence of relapse (CIR), non-relapse mortality (NRM), leukemia-free survival (LFS) and overall survival (OS) of all cases were 34%, 16%, 50%, and 56%, respectively. Positive pre-SCT MRD patients with higher 3-year CIR (47% vs 26%, P=0.003), lower 3-year LFS (40% vs 55%, P=0.047) and OS (42% vs 60%, P=0.065) than those with negative one. Subjects with positive post-MRD had higher 3-year CIR (73% vs 22%, P<0.001) and lower 3-year LFS (28% vs 56%, P=0.005) and OS (32% vs 60%, P=0.040) compared with those with negative one. Multivariate analysis showed that both pre-MRD and post-MRD were associated with higher CIR ( HR=1.823, P=0.018; HR=3.474, P<0.001), lower LFS ( HR=1.779, P=0.007; HR=2.185, P=0.001) and OS ( HR=1.609, P=0.034; HR=1.970, P=0.001). Negative pre-and post-SCT MRD group had lower 3-year CIR (17%, 42%, 82%; P<0.001) and higher 3-year LFS (61%, 44%, 18%; P<0.001) and OS (63%, 47%, 27%; P<0.001) compared with those unrisen post-SCT MRD group, and increased post-SCT MRD group. Multivariate analysis showed that pre-and post-SCT MRD dynamics were associated with CIR, LFS and OS ( P<0.01 for all) independently. The pre-and post-SCT MRD dynamics could better distinguish CIR (C=0.669) from that of pre-SCT MRD (C=0.587) and post-SCT MRD (C=0.629). Conclusion:Our data suggest that pre-SCT MRD, post-SCT MRD and the dynamic peri-SCT MRD could be used to predict transplant outcome of ALLpatients with or above CR2 who underwent allo-SCT.

Objective:To explore the relationship between anti-human leukocyte antigen (HLA) antibodies and transplant outcomes in patients with hematological diseases who underwent matched sibling donor transplantation (MSDT).Methods:A retrospective analysis was conducted in 168 patients with hematological diseases who received MSDT in Peking University People's Hospital from March 2015 to November 2017. All patients received detection of anti-HLA antibodies before transplantation, and the correlation between anti-HLA antibodies and transplant outcomes such as hematopoietic cells implantation, blood product transfusion and prognosis after transplantation were analyzed.Results:Among the 168 patients, 28 (16.7%) were positive for anti-HLA class Ⅰ or class Ⅱ antibodies, and 14 (8.3%) were positive for both anti-HLA class Ⅰ and class Ⅱ antibodies. All patients received neutrophil engraftment, 164 patients (97.9%) received platelet engraftment. Univariate analysis showed that there were no effects of anti-HLA antibodies on neutrophil engraftment and engraftment time, platelet engraftment and engraftment time, the volume of red cell transfusion, the volume of platelet transfusion, overall survival (OS) rate, disease free survival (DFS) rate and transplant-related mortality (TRM) in patients with hematological diseases underwent MSDT (all P > 0.05). Multivariate analysis showed that platelet engraftment was associated with better OS ( HR=0.065, 95% CI 0.017-0.252, P < 0.01), better DFS ( HR=0.083, 95% CI 0.024-0.289, P < 0.01) and lower TRM ( HR=0.094, 95% CI 0.014-0.626, P=0.015). Conclusion:Anti-HLA antibodies have no effect on transplant outcomes of patients with hematological diseases who have received MSDT.

Objective To evaluate the accuracy of different anatomic landmark methods in determining the size of nasopharyngeal airway.Methods Fifty-two patients of both sexes,aged 16-60 yr,of American Society of Anesthesiologists physical status Ⅰ to Ⅲ,with body mass index of 18-30 kg/m2,scheduled for elective awake craniotomy for supratentorial tumors under sedation-awake-sedation anesthesia,were included.For each patient,the distance from the apex of nose to the right tragus (NT),distance from apex of nose to the right mandibular angle (NM),and thyro-mental distance (TM) were measured and marked on a transnasal tube correspondingly.The patients were placed in supine position without pillow,topical anesthesia (nasal mucosal surface) was performed with 2％ lidocaine,and patients were sedated with midazo1am,propofol and dexmedetomidine.When Observer's Assessment of Alertness/Sedation Scale score was 2 or 3 points,the tube was transnasally inserted to each marked depth.When the three marked depths mentioned above were reached,the positions of the tube's tip were checked using a fiberoptic bronchoscope and recorded as:above epiglottis (the tip of the tube was placed between the epiglottis and the free edge of soft palate) or below epiglottis (the tip of the tube placed at or beyond the epiglottis).Results When the depth reached the NT mark,the tube's tip was above epiglottis in 14 cases (27％),and the tube's tip was below epiglottis in 38 cases (73％).When the depth reached the NM mark,the tube's tip was above epiglottis in 31 cases (60％),and the tube's tip was below epiglottis in 21 cases (40％).When the depth reached the TM mark,the tube's tip was above epiglottis in 52 cases (100％).Compared with the NM and NT methods,the TM method had a higher probability with the tube's tip above epiglottis when used to determine the depth of insertion (P＜0.01).Conclusion TM anatomic landmark method provides higher accuracy in determining the size of nasopharyngeal airway.

Objective To evaluate the efficacy and safety of heated gel mattress(HGM) for prevention of heat loss on preterm infants with hypothermia during the transport systematically and objectively. Methods Systematic searches on PubMed, EMBASE, Cochrane Library, Web of Science CBM,CNKI,Wanfang and VIP were performed for randomized controlled trials or quasi-randomized control trials which explored the effects of HGM on prevention of hypothermia in premature infants relative to conventional alternatives. Studies were screened according to inclusion and exclusion criteria,extracting data and assessing quality. Then, Meta-analysis and trial sequential analysis were performed by using RevMan 5.3 and TSA v0.9 software developed at the Copenhagen Clinical Trials Center in Denmark, independently. Results This systematic review included 10 studies which comprised 7 randomized controlled trials and 3 quasi-randomized control trials, encompassing 773 patients. The results of Meta-analysis showed that in HGM group admission temperature on neonatal intensive care unit (standardized mean difference was 0.63, 95% confidence interval was 0.40-0.87, P=0.00), incidence of hypothermia (relative risk was 0.73, 95% confidence interval was 0.57-0.93, P=0.01) and hyperthermia (relative risk was 1.82, 95% confidence interval was 1.31-2.54, P=0.00) compared with the control group had significantly statistical difference;however, there was no significant difference in admission temperature on EM or TWM group, mortality, sepsis, retinopathy of prematurity, intraventricular hemorrhage III/IV between two groups. TSA confirmed that the pooled results of admission temperature on NICU and hyperthermia were stable and reliable; but the combination of low-temperature incidence and mortality indicators suggested that the sample size was insufficient. Conclusions HGM is an effective rewarming intervention that can improve body temperature of hypothermic preterm infants during transport, reduce the incidence of hypothermia but not decrease the incidence of morbidity and complications. However, it is recommended that clinical monitoring of body temperature should be performed dynamically to decrease the potential risk of high fever and complications. In addition, due to the limitation of quantity and quality of included studies, its cost-effectiveness and far-reaching influence on long-term follow-up outcomes need further evaluation through clinical multicenter, large sample, high-quality research.

Objective The present study was to investigate the feasibility of use of high resolution magnetic reso?nance vessel wall imaging(HR-VWI)in evaluation of intracranial aneurysms. Methods We prospectively collected data from patients who had intracranial aneurysms and received HR-VWI scan before surgical treatment or conservative treatment. Aneurysms were divided into ruptured group (n=12) and unruptured group (n=88). Aneurysm site, size, neck, aspect ratio(AR), daughter sac and aneurysmal wall enhancement scale were analyzed in both groups. Univariate and multivariate Logistic regression were performed to evaluate the risk factors of aneurysm rupture. Subgroup analysis was also performed to study symptomatic and asymptomatic unruptured aneurysms. Results Aneurysm size(t=2.187,P=0.031),AR(t=3.164,P=0.002),incidence of daughter sac(P=0.012) and aneurysmal wall enhancement scale(P<0.001)were higher in ruptured aneurysm group. Multivariate Logistic regression showed that aneurysmal wall enhance?ment scale was the only independent risk factor of ruptured aneurysms(P=0.002). Subgroup analysis showed aneurysm wall enhancement scale(P<0.001) and AR(t=3.939,P<0.001) were higher in symptomatic unruptured aneurysms. Conclusion Aneurysm wall enhancement on HR-VWI is more frequently seen in ruptured aneurysms and symptomatic unruptured aneurysms. Histological study is needed for better understanding of the mechanism of aneurysm wall enhance?ment.

OBJECTIVETo assess the association of VKORC1 gene -1639G/A polymorphism with atrial fibrillation (AF) in ethnic Uygurs and Hans from Xinjiang.

METHODSThe above polymorphism was detected among 100 Uygur and 102 Han AF patients and 103 Uygur and 111 Han subjects that have no AF with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.

RESULTSA statistically significant difference was detected between the patient and control groups of Uygur origin in terms of genotypic and allelic frequencies (P<0.05). Logistic regression analysis also indicated the -1639G/A polymorphism as an independent risk factor for AF in Uygur population (OR=2.085, 95% CI: 1.067-4.072, P=0.031). No similar statistical difference was found between the patient and control groups of Han origin (P>0.05).

CONCLUSIONThe -1639G/A polymorphism of VKORC1 gene is associated with AF in the Uygur population but not in Hans.

Adult ; Aged ; Asian Continental Ancestry Group ; ethnology ; genetics ; Atrial Fibrillation ; ethnology ; genetics ; Base Sequence ; China ; ethnology ; Female ; Humans ; Male ; Middle Aged ; Molecular Sequence Data ; Polymorphism, Single Nucleotide ; Vitamin K Epoxide Reductases ; genetics