Aim To investigate the effect of cumulative non-high density lipoprotein cholesterol/high density lip-oprotein cholesterol(non-HDLC/HDLC)exposure on atherosclerotic cardiovascular disease(ASCVD).Methods A prospective cohort study was conducted.A total of 50 777 employees of Kailuan Group who participated in three physical examinations in 2006-2007,2008-2009 and 2010-2011 were selected as the study subjects.Groups were divided into Q1,Q2,Q3 and Q4 according to the cumulative non-HDLC/HDLC exposure quartiles.Kaplan-Meier curve was used to calculate the cumulative incidence of ASCVD in different cumulative non-HDLC/HDLC groups,and Log-rank test was used to compare the differences among groups.Cox proportional risk model was used to analyze the effect of cumulative non-HDLC/HDLC exposure on ASCVD.Results The average follow-up was(10.19±2.21)years,and 5 003 new cases of ASCVD occurred.The cumulative incidence of ASCVD in groups Q1 to Q4 was 6.49％,8.71％,10.86％and 14.85％,respectively(Log-rank P＜0.01).Multivariate Cox regression analysis showed that compared with group Q1,the HR(95％CI)of ASCVD in groups Q2,Q3 and Q4 were 1.13(1.03～1.24),1.18(1.07～1.29),1.22(1.12～1.34),respectively;the HR(95％CI)of myocardial infarction were 1.15(0.87～1.53),1.44(1.10～1.88),1.67(1.29～2.17),respectively;the HR(95％CI)of revascularization were 1.21(0.99～1.49),1.31(1.07～1.60)and 1.49(1.22～1.81),respectively;the HR(95％CI)of ischemic stroke were 1.17(1.03～1.32),1.17(1.04～1.33)and 1.21(1.06～1.37),respectively;but the above association was not found when heart failure and atrial fibrillation were used as the outcome events.The restricted cubic spline showed that cumulative non-HDLC/HDLC values were line-arly associated with the risk of ASCVD.Conclusion Cumulative non-HDLC/HDLC exposure was positively associated with the risk of ASCVD.

In recent years，the prevalence of asthma in children has been on the rise，affecting children's physical and mental health and placing a burden on families and society. As the in-depth study of asthma phenotypes and endotypes progresses，targeted therapy for asthma has become a new treatment strategy. Dupilumab，a drug targeting IL-4 and IL-13，is used treating patients with uncontrolled moderate-to-severe type 2 asthma. It has been approved for use in children aged 6-11 years with moderate-to-severe asthma in the United States and Europe，but there are fewer reports on the treatment of type 2 asthma in children in China. Therefore，this article aims to review the research progress of Dupilumab in the treatment of type 2 asthma in children，in order to provide reference for the clinical treatment of asthma in children.

Aim To investigate the effect of cumulative non-high density lipoprotein cholesterol/high density lip-oprotein cholesterol(non-HDLC/HDLC)exposure on atherosclerotic cardiovascular disease(ASCVD).Methods A prospective cohort study was conducted.A total of 50 777 employees of Kailuan Group who participated in three physical examinations in 2006-2007,2008-2009 and 2010-2011 were selected as the study subjects.Groups were divided into Q1,Q2,Q3 and Q4 according to the cumulative non-HDLC/HDLC exposure quartiles.Kaplan-Meier curve was used to calculate the cumulative incidence of ASCVD in different cumulative non-HDLC/HDLC groups,and Log-rank test was used to compare the differences among groups.Cox proportional risk model was used to analyze the effect of cumulative non-HDLC/HDLC exposure on ASCVD.Results The average follow-up was(10.19±2.21)years,and 5 003 new cases of ASCVD occurred.The cumulative incidence of ASCVD in groups Q1 to Q4 was 6.49％,8.71％,10.86％and 14.85％,respectively(Log-rank P＜0.01).Multivariate Cox regression analysis showed that compared with group Q1,the HR(95％CI)of ASCVD in groups Q2,Q3 and Q4 were 1.13(1.03～1.24),1.18(1.07～1.29),1.22(1.12～1.34),respectively;the HR(95％CI)of myocardial infarction were 1.15(0.87～1.53),1.44(1.10～1.88),1.67(1.29～2.17),respectively;the HR(95％CI)of revascularization were 1.21(0.99～1.49),1.31(1.07～1.60)and 1.49(1.22～1.81),respectively;the HR(95％CI)of ischemic stroke were 1.17(1.03～1.32),1.17(1.04～1.33)and 1.21(1.06～1.37),respectively;but the above association was not found when heart failure and atrial fibrillation were used as the outcome events.The restricted cubic spline showed that cumulative non-HDLC/HDLC values were line-arly associated with the risk of ASCVD.Conclusion Cumulative non-HDLC/HDLC exposure was positively associated with the risk of ASCVD.

Objective:To investigate the impact of non-high-density lipoprotein cholesterol (non-HDL-C) level on major adverse cardiovascular and cerebrovascular events (MACCE) and all-cause mortality in the Kailuan Study cohort undergoing revascularization.Methods:This is a prospective cohort study, with participants from the Kailuan Study cohort who participated in physical examinations from 2006 to 2020 and received revascularization therapy for the first time. According to the level of non-HDL-C, the study subjects were divided into 3 groups:<2.6 mmol/L group, 2.6-<3.4 mmol/L group, and≥3.4 mmol/L group. Annual follow-up was performed, and the endpoint events were MACCE and all-cause mortality. Cox proportional regression model was implemented to estimate the impact on MACCE and all-cause mortality associated with the different non-HDL-C groups. The partial distributed risk model was used to analyze the impact of different non-HDL-C levels on MACCE event subtypes, and death was regarded as a competitive event. The restricted cubic spline regression model was used to explore the dose-response relationship between non-HDL-C level and all-cause mortality, MACCE and its subtypes.Results:A total of 2 252 subjects were enrolled in the study, including 2 019 males (89.65%), aged (62.8±8.3) years, the follow-up time was 5.72 (3.18, 8.46) years. There were 384 cases(17.05%) of MACCE and 157 cases(6.97%) of all-cause mortality. Compared with patients with non-HDL-C≥3.4 mmol/L, patients with non-HDL-C<2.6 mmol/L were associated with a 38% reduced risk of MACCE after revascularization [ HR=0.62(95% CI: 0.48-0.80)]. Every 1 mmol/L decrease in non-HDL-C was associated with a 20% reduction in the risk of MACCE [ HR=0.80(95% CI: 0.73-0.88)]. The results of restricted cubic spline also showed that non-HDL-C levels after revascularization therapy were positively correlated with MACCE events (overall association P<0.001, non-linear association P=0.808). For all-cause mortality, compared to the non-HDL-C≥3.4 mmol/L group, the HR for all-cause mortality after revascularization in non-HDL-C<2.6 mmol/L group was 0.67(95% CI: 0.46-1.01). Every 1 mmol/L decrease in non-HDL-C was associated with a 15% reduction in the risk of all-cause mortality [ HR=0.85(95% CI: 0.73-0.99)]. The restricted cubic spline results showed a linear association between non-HDL-C levels after revascularization therapy and the risk of all-cause mortality (overall association P=0.039, non-linear association P=0.174). Conclusion:The decrease in non-HDL-C levels after revascularization were significantly associated with a reduced risk of MACCE and all-cause mortality.

Objective:To analyze the immunology-related risk factors for short-term prognosis in patients with demyelinating diseases of central nervous system, and to evaluate their predictive value.Methods:From January 2012 to October 2022 in Beijing Tiantan Hospital of Capital Medical University and General Hospital of Tianjin Medical University, the clinical data of 362 patients with demyelinating diseases of central nervous system were analyzed, including neuromyelitis optic spectrum disease (NMOSD) 181 cases, multiple sclerosis (MS) 129 cases, anti-myelin oligodendrocyte glycoprotein antibody associated disease (MOGAD) 38 cases, acute disseminated encephalomyelopathy (ADEM) 14 cases. According to the expanded disability status scale (EDSS) score at discharge, the patients were divided into good prognosis group (EDSS≤3 scores, 267 cases) and poor prognosis group (EDSS>3 scores, 95 cases). The clinical data, admission severity (admission EDSS score), treatment, autoantibodies and immunoglobulin level and serum inflammatory factor level were compared between two groups. Multivariate Logistic regression was used to analyze the independent risk factors of short-term prognosis in patients with demyelinating diseases of central nervous system; and the predictive efficacy was evaluated by receiver operating characteristic (ROC) curve.Results:Compared with the good prognosis group, the admission EDSS score in the poor prognosis group was significantly higher: 2.5 (1.5) scores vs. 6.5 (3.5) scores. The positive rates of autoimmune disease-related antibody, systemic autoantibody, anti-nuclear antibody, anti-extractable nuclear antigen antibody, thyroid peroxidase antibody and thyroid globulin antibody were significantly higher: 89.5% (85/95) vs. 59.6% (159/267), 75.8% (72/95) vs. 52.1% (139/267), 65.3% (62/95) vs. 38.6% (103/267), 42.1% (40/95) vs. 23.2% (62/267), 40.0% (38/95) vs. 19.1% (51/267) and 42.1% (40/95) vs. 19.9% (53/267). The serum IgM was significantly lower: 0.84 (0.78) g/L vs. 1.00 (0.75) g/L. The serum tumor necrosis factor-α, interleukin-2 receptor and cerebrospinal fluid IgG were significantly higher: 8 055 (3 118) pg/L vs. 6 830 (3 515) pg/L, 348 (175) kU/L vs. 314 (146) kU/L and 47.50 (46.50) g/L vs. 33.00 (24.00) g/L. And there were statistical differences ( P<0.01 or <0.05). Multivariate Logistic regression analysis result showed that the admission EDSS score and anti-nuclear antibody positive were the independent risk factors of short-term prognosis in patients with demyelinating diseases of central nervous system ( OR = 5.034 and 6.942, 95% CI 3.289 to 7.705 and 2.250 to 21.422, P<0.01). ROC curve analysis result showed that the area under the curve of anti-nuclear antibody positive combined with admission EDSS score predicted the short-term prognosis in patients with demyelinating diseases of central nervous system was 0.972, with a sensitivity of 90.5%, and a specificity of 92.5%. Conclusions:The admission EDSS score and anti-nuclear antibody positive are the independent risk factors for poor prognosis in patients with demyelinating diseases of central nervous system. And the combination of two indexes can better predict the short-term prognosis.

Objective:To analyze the influencing factors, prevention and treatment strategy of short-term poor prognosis of continuous lumbar cistern external drainage after aneurysms subarachnoid hemorrhage (aSAH).Methods:Used retrospective research method, the clinical data of 300 patients with aSAH combined with continuous lumbar cistern external drainage treated in Sanya Central Hospital (Hainan Third People′s Hospital) from March 2019 to March 2021 were selected as the training set. In addition, the clinical data of 144 patients with aSAH with continuous lumbar cistern external drainage treated in Sanya Central Hospital (Hainan Third People′s Hospital) from March 2017 to May 2019 were selected as the verification set. According to the results of postoperative follow-up, the patients in the training set were divided into two groups: good prognosis group ( n=208) and poor prognosis group ( n=92). The demographic characteristics, past history, Hunt-Hess grade, modified Fisher grade, location of responsible aneurysm, postoperative complications, bone flap decompression and lumbar cistern drainage were compared between the two groups. The independent risk factors for prognosis of aSAH patients undergoing continuous lumbar cistern external drainage were screened by Cox proportional hazard regression model, and these factors were included and XGboost model was established. The prediction model was validated internally and externally in the training set and verification set: AUROC(C-index) was used to verify the model differentiation; GiViTI calibration band and Hosmer-Lemeshow test were used to verify the model calibration; DCA curve was used to verify the clinical validity of the model. Results:Hunt-Hess grade, modified Fisher grade, drainage duration, average daily drainage volume, shunt-dependent hydrocephalus, aneurysm rebleeding, cerebral vasospasm and delayed cerebral ischemia were independent risk factors for poor prognosis in patients with aSAH who underwent continuous lumbar cistern external drainage( P<0.05). The XGboost model was successfully established by incorporating the above independent risk factors, and the internal and external verification of the XGboost model was carried out in the training set and verification set, respectively, the area under the curve of receiver operating characteristic was 0.882(95% CI: 0.820-0.955) and 0.878(95% CI: 0.774-0.928) respectively, and the model differentiation was good; the 80%-90% confidence interval of the GiViTI calibration curve did not cross the 45° angle bisector ( P>0.05). In the Hosmer-Lemeshow goodness-of-fit test, the P value were 0.581 and 0.716, respectively. The threshold probability value in the DCA curve was 30.4%. The clinical net benefit rate of the training set and verification set were 31% and 34%, respectively, indicating that the prediction model was clinically effective. Conclusions:The independent risk factors for poor prognosis of aSAH patients undergoing continuous lumbar cistern drainage are Hunt-Hess grade, modified Fisher grade, cerebral vasospasm, delayed cerebral ischemia and shunt-dependent hydrocephalus. The XGboost model constructed in this study can effectively predict the prognosis of patients with aSAH undergoing continuous lumbar cistern drainage, and provide reference for the formulation of follow-up treatment plans.

Cervical cancer is a common malignant tumor of female reproductive system. The treatment of cervical cancer is based on surgery and radiotherapy (or concurrent chemoradiation). Lower extremity lymphedema (LEL) is a frequent complication after cervical cancer treatment, which significantly affects the quality of life of patients. Both pelvic surgery and radiation for cervical cancer can lead to LEL. The risk factors for LEL are complicated and involving characteristics regarding patient (age, comorbidities, lifestyle, etc.), tumor [International Federation of gynecology and Obstetrics (FIGO) stage, lymph node metastasis, etc.], and treatment (number of resected lymph nodes, removal of circumflex iliac nodes, adjuvant therapy, etc.). Comprehensive measures are proposed to prevent cervical cancer patients from LEL, and further investigations in terms of effectiveness are warranted.

Objective: To detect the expression of GREM1 gene in gastric cancer cells, investigate its effects on the biological characteristics of gastric cancer cells and evaluate its application value in the diagnosis and prognosis of gastric cancer. Methods: The expression difference of GREM1 in gastric cancer tissues and adjacent normal tissues was analyzed by the database, and the correlation of GREM1 expression levels with the prognosis of gastric cancer patients was evaluated. The expression levels of GREM1 protein in gastric cancer cell lines were detected by western blot. After GREM1 gene in AGS cells was silenced, its effects on the proliferation, migration, epithelial-mesenchymal transition (EMT) and Wnt/β-catenin pathway of AGS cells were detected by the colony formation assay, Transwell and Western blot, respectively. Results: Kaplan-Meier analysis showed that the patients with high expression of GREM1 gene had low overall survival (OS) and progression-free survival (PFS). The expression level of GREM1 protein in AGS cells was the highest in all gastric cancer cell lines (1.967 ± 0.056). The analysis of colony formation assay, Transwell and Western blot showed that the silencing of GREM1 gene could decrease the proliferation and migration of gastric cancer cells (t=22.00; t=29.60; P＜0.01), increase the expression of E-cadherin (t=10.65, P＜0.01), and decrease the expressions of ZEB1 and MMP2 (t=10.74; t=13.67; P＜0.01) and the expressions of β-catenin, Cyclin D1, c-myc, p-GSK3β and PCNA in the Wnt/β-catenin pathway (t=12.65; t=16.21; t=8.74; t=7.75; t=8.42; P＜0.01). Conclusion GREM1 may induce EMT by activating the Wnt/β-catenin pathway, [JP2]and promote the metastasis and growth of tumors, which may be used as a new molecular diagnostic and prognostic marker for gastric cancer.

Objective To investigate the inhibitory effects of aloin on the growth of Staphylococcus aureus and its virulence factors α-hemolysin in vitro.Methods Broth dilution was used to measure the minimum inhibitory concentration (MIC) of water-soluble aloin on S.aureus.Agar drilling method was used to observe the size of inhibition zone of aloin for S.aureus.Plasma coagulase test was used to detect the changes of S.aureus coagulase and absorbance was measured to detect the changes of hemolytic activity when S.aureus was exposed to aloin.Real time PCR was used to detect the effects of aloin on the expressions of hla and agrA mRNA.Results The soluble aloin inhibited the growth of S.aureus in a dose-dependent manner.The inhibition zone diameter of a standard strain of S.aureus (ATCC 25923) was 21.5 mm with MIC of 12.5 mg/mL and 17 mm for the clinical isolate SA1.5 with MIC of 15 mg/mL.After treated with soluble aloin,the coagulase titers of ATCC 25923 were 16,4 and 2 for 1/2 MIC,1 MIC and 2 MIC respectively compared with titer 32 of the control group without soluble aloin.The expression of α-hemolysin of S.aureus ATCC 25923 was down-regulated by soluble aloin and the hemolytic activity of S.aureus ATCC 25923 with 1/2 MIC,1 MIC and 2 MIC groups were (77.4 ±3.41) ％,(42.2 ± 2.4) ％ and (38.7 ± 2.4) ％ respectively.The expression levels of hla were 0.020 3 (0.019 6,0.028 8),0.011 6(0.010 6,0.013 1) and 0.033 7(0.020 2,0.042 9) respectively in the 1/2 MIC,1 MIC and 2 MIC group respectively,and there were significant differences among the three groups (H =16.807,P ＜ 0.05).The expression levels of agrA was 0.074 6 (0.066 2,0.098 2),0.020 8 (0.012 2,0.032 6) and 0.021 3 (0.010 2,0.029 6) in the 1/2 MIC,1 MIC and 2 MIC group respectively,and there were significant differences among the three groups (H =16.320,P ＜ 0.05).Conclusion Aloin may inhibit the growth of S.aureus and could effectively inhibit the expression of α-hemolysin.

Objective To investigate the difference between Han nationality residents and the Hani nationality residents in southern Yunnan about the effects of stroke risk factors on cerebral vascular hemodynamic indicators.Methods In the cohort crowds,Hani nationality outpatient patients were selected as the Hani nationality group,the Han nationality outpatient patients with the same gender and similar age were randomly selected as the Han nationality group with the ratio of nearly 1 ∶ 3.The risk factors of stroke and the differences of the hemodynamic indicators were compared between the two groups.Results The dyslipidemia proportion of the Hani nationality group was lower than that of the Han nationality group [48 cases (11.5 ％) vs.257 cases (17.5 ％),x2 =8.867,P =0.003],and the drinking proportion of the Hani nationality group was higher than that of the Han nationality group [79 cases (18.9％) vs.214 cases(14.6％),x2 =4.498,P =0.034],the other risk factors exposure rates had no statistically significant differences between the two groups (all P ＞ 0.05).The ratio of numbers of cerebral vascular hemodynamic indicators below 75 points(optimum truncation points) in the Hani nationality group and the Han nationality group were 30.3％ and 31.9％,respectively,the proportion of the two groups of integral value distribution had statistically significant difference (x2 =12.614,P ＜ 0.01);Vmean (left:t =0.632,P =0.527;right:t =0.642,P =0.532),Vmin (left:t =-0.349,P =0.727;right:t =-0.540,P =0.589),Wv(left:t =0.297,P =0.767;right:t =1.119,P =0.263),Zcv(left:t =0.297,P =0.767;right:t =1.247,P =0.213),Rv(left:t =0.837,P =0.403;right:t =1.222,P =0.222),DR(left:t =0.720,P =0.482;right:t =0.396,P =0.692),Cp(left:t =0.614,P =0.539;right:t =1.486,P =0.138) and other indicators of the two groups had no statistically significant differences.Conclusion The Hani nationality residents'stroke risk factors and CVHI integral distribution in different age groups are different from Han people in southern Yunnan.