[Objective] To analyze the characteristics of HLA-A, HLA-B, HLA-DRB1, HLA-C, HLA-DQB1 and HLA-DPB1 allele polymorphisms among cord blood donors in Guangdong population. [Methods] According to HLA high resolution genotyping data of 32 717 samples of cord blood donors from Guangdong Cord Blood Bank from January 2009 to December 2023, the allele frequencies were calculated by direct counting and the haplotype frequencies were calculated by using Arlequin software 3.5.2.2. [Results] A total of 102 HLA-A alleles, 160 HLA-B alleles and 96 HLA-DRB1 alleles were detected in 32 717 samples. Among them, 46 HLA-DPB1 alleles were detected in 5 377 samples, and 66 HLA-C alleles and 35 HLA-DQB1 alleles were detected in 13 310 samples. The most common alleles were HLA-A^*11∶01 (28.96%), HLA-B^*40∶01 (15.23%), HLA-DRB1^*09∶01 (15.72%), HLA-C^*01∶02 (19.40%), HLA-DQB1^*03∶01 (20.85%) and HLA-DPB1^*05∶01 (40.79%). The most common 3 loci haplotype and 6 loci haplotype were HLA-A^*02∶07-B^*46∶01-DRB1^*09∶01 (1.55%), HLA-C^*07∶02-DQB1^*03∶01-DPB1^*05∶01 (1.77%), HLA-DRB1^*09∶01-DQB1^*03∶03-DPB1^*05∶01 (3.31%) and HLA-A^*02∶07-B^*46∶01-C^*01∶02-DRB1^*09∶01-DQB1^*03∶03-DPB1^*05∶01 (0.30%). [Conclusion] In this study, the allele and haplotype frequencies of HLA-A, HLA-B, HLA-DRB1, HLA-C, HLA-DQB1 and HLA-DPB1 were obtained in the cord blood donors in Guangdong, which can provide important reference data for HLA gene related research and the selection of donors for clinical application.

Objective To construct a theoretical model of venous thromboembolism(VTE)risk perception in pregnant women,so as to provide a scientific basis for promoting pregnant women to form a correct risk perception of VTE and actively take preventive behaviors.Methods A qualitative research approach guided by the procedural grounded theoiy was adopted.Data were collected by a semi-structured deep interview on 18 pregnant women who received prenatal examination in the outpatient department of a tertiary A obstetrics and gynecology hospital in Nanjing from June to July 2023,and the data were analyzed by three-level coding and continuous comparison method.Results The VTE risk perception of pregnant women was affected by 6 factors including social coupling system,self health status,life behavior habits,knowledge on disease,compliance behavior and emotional stimulation.Pregnant women perceived VTE risk from 3 aspects:threats to maternal and child safety,increased family economic burden and increased time cost,impact on social roles.Thus,3 health behavior decisions were formed,including taking preventive behaviors,overcoming implementation barriers,and seeking knowledge behaviors,in order to reduce their own risk of VTE,and prevent the occurrence of VTE.Conclusion The theoretical model of VTE risk perception of pregnant women can guide medical staff to comprehensively consider the influencing factors of VTE risk perception of pregnant women,optimize the form and content of VTE health education,give pregnant women individualized and sustainable VTE prevention guidance,and strengthen pregnant women's perception of VTE risk and the benefits of preventive behavior,so as to actively take the correct health behavior decisions.

Objective To investigate the genetic association between nonalcoholic fatty liver disease(NAFLD)and type 2 diabetes mellitus(T2DM)using bidirectional two-sample Mendelian randomization(MR),as well as the causal relationship between NAFLD and T2DM across different body mass index(BMI)categories.Methods The data were derived from genome-wide association studies conducted in European populations,with a sample size of 32 941 cases for NAFLD,312 646 cases for T2DM,and 681 275 cases for BMI.The univariate and multivariate MR methods were used to assess the bidirectional causal relationship between NAFLD and T2DM in the general population and across different BMI subtypes.The methods of inverse-variance weighting,MR-Egger regression,constrained maximum likelihood and model averaging,and weighted median were used to conduct the MR analysis,and MR-Pleiotropy Residual Sum and Outlier,radial MR,the MR-Egger intercept method,and the Cochrane Q test were used for sensitivity analysis.Results The univariate MR analysis revealed a bidirectional causal relationship between NAFLD and T2DM in the general population(forward analysis:odds ratio[OR]=9.75,95%confidence interval[CI]:2.57-37.00,P＜0.001;reverse analysis:OR=1.01,95%CI:1.00-1.01,P＜0.01).After adjustment for BMI,the multivariate MR analysis showed that the causal relationship between NAFLD and T2DM remained significant in the general population(OR=33.12,95%CI:7.57-144.95,P＜0.000 1).The subgroup analysis showed a causal relationship between NAFLD and T2DM across all BMI subtypes(lean subgroup:OR=12.19,95%CI:3.35-44.40,P＜0.001;overweight subgroup:OR=4.30,95%CI:1.69-10.92,P＜0.01;obese subgroup:OR=1.67,95%CI:1.14-2.44,P＜0.01).Conclusion This study reveals the causal relationship between NAFLD and T2DM in the general population of NAFLD and across different BMI subtypes from a genetic perspective.

Various c-mesenchymal-to-epithelial transition (c-MET) inhibitors are effective in the treatment of non-small cell lung cancer; however, the inevitable drug resistance remains a challenge, limiting their clinical efficacy. Therefore, novel strategies targeting c-MET are urgently required. Herein, through rational structure optimization, we obtained novel exceptionally potent and orally active c-MET proteolysis targeting chimeras (PROTACs) namely D10 and D15 based on thalidomide and tepotinib. D10 and D15 inhibited cell growth with low nanomolar IC₅₀ values and achieved picomolar DC₅₀ values and >99% of maximum degradation (D_max) in EBC-1 and Hs746T cells. Mechanistically, D10 and D15 dramatically induced cell apoptosis, G1 cell cycle arrest and inhibited cell migration and invasion. Notably, intraperitoneal administration of D10 and D15 significantly inhibited tumor growth in the EBC-1 xenograft model and oral administration of D15 induced approximately complete tumor suppression in the Hs746T xenograft model with well-tolerated dose-schedules. Furthermore, D10 and D15 exerted significant anti-tumor effect in cells with c-MET^Y1230H and c-MET^D1228N mutations, which are resistant to tepotinib in clinic. These findings demonstrated that D10 and D15 could serve as candidates for the treatment of tumors with MET alterations.

Objective:To explore the mediating roles of rumination and avoidance coping between information anxiety and suicidal ideation.Methods:In March 2022, a total of 896 college students were surveyed by the information anxiety scale(IAS), ruminative responses scale(RRS), coping style questionnaire(CSQ)and self-rating idea of suicidal ideation scale(SIOSS). The ANOVA analysis, Pearson correlation analysis and mediating effect analysis were performed by the SPSS 22.0 software.Results:The detection rate of suicidal ideation among college students was 9.15%(82/896). The information anxiety score was(73.84±17.29), the rumination score was(47.73±12.16), the avoidance coping score was(3.76±2.52), and the suicidal ideation score was(5.41±4.09). Information anxiety was significantly positively correlated with rumination, avoidance coping and suicidal ideation( r=0.49, 0.36, 0.37, all P<0.05). Rumination was significantly positively correlated with avoidance coping and suicidal ideation( r=0.42, 0.59, both P<0.05). There was a significantly positive correlation between avoidance coping and suicidal ideation( r=0.45, P<0.05). Information anxiety affected suicidal ideation of college students through four paths.The direct effect value of information anxiety on suicidal ideation was 0.06, accounting for 16.67% of the total effect. The effect values of the separate mediating effect of rumination and avoid coping were 0.22 and 0.04, and accounting for 61.11% and 11.11% of the total effect respectively. The chain mediating effect value of rumination and avoid coping was 0.04, accounting for 11.11% of the total effect. Conclusion:Information anxiety can directly affect suicidal ideation of college students and indirectly affect suicidal ideation through rumination and avoidance coping.

Objective:To investigate the effects of rifaximin treatment outcomes on complications and 24-week survival rate in cirrhotic patients with refractory type ascites.Methods:A retrospective cohort study was conducted on 62 cases with refractory ascites, and were divided into rifaximin treatment group (42 cases) and control group (20 cases) according to the actual treatment conditions. Rifaximin treatment group patients were administered oral rifaximin-α 200 mg four times daily for 24 consecutive weeks, and the other treatments were basically the same in both groups. Fasting body weight, ascites, complications and survival rate between the two groups were observed. Measurement data of the two groups using t-test, Mann-Whitney U test, and repeated measures analysis of variance were compared. χ2 test or Fisher's exact test were used to compare the enumeration data between the two groups. Kaplan-meier survival analysis was used to compare the survival rates. Results:At 24-week of rifaximin treatment, patients average body weight was reduced by 3.2 kg and the average ascites depth was reduced by 4.5 cm with B-ultrasound measurement, while in the control group at 24-week, the average body weight was reduced by 1.1 kg and the average ascites depth was reduced by 2.1 cm with B-ultrasound measurement, and the differences between the two groups were statistically significant ( F=4.972, P=0.035; F=5.288, P=0.027). Hepatic encephalopathy incidence of grade II or above, hospitalization rates due to exacerbation of ascites, and spontaneous bacterial peritonitis were significantly lower in the rifaximin treatment group than those in the control group (2.4% vs. 20.0%, χ2=5.295, P=0.021; 11.9% vs. 50.0%, χ2=10.221, P=0.001; 7.1% vs. 25.0%, χ2=3.844, P=0.050). The 24-week survival rate was 83.3% in the rifaximin treatment group and 60.0% in the control group, P=0.039. Conclusion:Rifaximin treatment can significantly improve ascites symptoms, reduce the incidence of cirrhosis complications and improve the 24-week survival rate in cirrhotic patients with refractory type ascites.

Objective:To explore the relationship between insulin resistance, glucose and lipid metabolism related molecules and colorectal polyps.Methods:A total of 262 healthy people who underwent colonoscopy in Shandong cancer hospital from June 2019 to September 2020 were selected. The levels of serum vascular cell adhesion molecule-1 (VCAM-1), fibroblast growth factor 19 (FGF19), insulin like growth factor (IGF-1), fasting blood glucose and fasting blood insulin were detected by enzyme-linked immunosorbent assay (ELISA). Insulin resistance index (HOMA-IR) was calculated, and the influencing factors of occurrence, pathological type, size and number of polyps were analyzed.Results:Among 262 cases, 116 cases were polyp free, 113 cases were adenomatous polyp and 33 cases were inflammatory polyp. HOMA-IR, VCAM-1 and FGF19 in polyp group were 2.904±1.754, (334.415±139.573) ng/ml and (135.865±98.470) pg/ml, respectively, which were higher than 2.369±1.306, (302.480±99.946) ng/ml and(110.694±76.044) ng/ml in non-polyp group, respectively ( P<0.05). Multivariate Logistic regression analysis showed that the gender ( OR=4.269, 95% CI: 1.963-9.405) and FGF19 (77.0-131.4 pg/ml: OR=2.385, 95% CI: 1.155-4.926) were independent factors of colorectal polyps. The gender ( OR=3.799, 95% CI: 1.650-8.748) and FGF19 (77.0-131.4 pg/ml: OR=2.290, 95% CI: 1.072-4.891) were independent factors of colorectal adenomatous polyps. The gender( OR=6.725, 95% CI: 1.853-24.410) and fasting plasma glucose (≥6.5 mmol/L: OR=0.047, 95% CI: 0.009-0.245) were independent factors of colorectal inflammatory polyps. The gender ( OR=3.539, 95% CI: 1.293-9.689) was an independent factor for the occurrence of single polyp. The gender ( OR=5.063, 95% CI: 2.048-12.515), FGF19 (77.0-131.4 pg/ml: OR=2.502, 95% CI: 1.102-5.681), fasting plasma glucose (≥6.5 mmol/L: OR=0.282, 95% CI: 0.095-0.839) were independent factors of multiple polyps. The gender ( OR=3.416, 95% CI: 1.134-10.289) and fasting insulin (≥9.4 μU/ml: OR=9.480, 95% CI: 1.485-60.521) were independent risk factors for colorectal polyps<0.5 cm. The gender ( OR=3.151, 95% CI: 1.244-7.984) and fasting plasma glucose (≥6.5 mmol/L: OR=0.310, 95% CI: 0.102-0.941) were independent risk factors for colorectal polyps with the size of 0.5-0.9 cm. The gender ( OR=22.649, 95% CI: 4.154-123.485), age (55 to 64 years old: OR=4.473, 95% CI: 1.070-18.704; ≥65 years old: OR=5.815, 95% CI: 1.300-26.009), BMI (≥28 kg/m 2: OR=5.310, 95% CI: 1.224-23.032) and FGF19 (77.0-131.4 pg/ml: OR=7.474, 95% CI: 1.903-29.351) were independent factors for colorectal polyps with size ≥ 1.0 cm. Gender stratification analysis showed that FGF19 was an independent factor for the occurrence of male polyps (77.0-131.4 pg/ml: OR=6.109, 95% CI: 1.688-22.104) and adenomas (77.0-131.4 pg/ml: OR=6.401, 95% CI: 1.717-23.864). The age (55 to 64 years old: OR=3.783, 95% CI: 1.052-13.611) and VCAM-1 (≥352.8 ng/ml: OR=4.341, 95% CI: 1.142-16.493) were independent risk factors of female polyps. The age (55 to 64 years old: OR=5.743, 95% CI: 1.205-27.362, ≥65 years old: OR=6.885, 95% CI: 1.143-41.467), VCAM-1 (≥352.8 ng/ml: OR=6.313, 95% CI: 1.415-28.159) and IGF-1 (≥7.6 ng/ml: OR=5.621, 95% CI: 1.069-29.543) were independent factors of female adenoma. Conclusions:The occurrences of colorectal polyps and adenomatous polyps are related to insulin resistance and glucose and lipid metabolism. Serum FGF19 is an independent influencing factor for the occurrence of colorectal polyps and adenomatous polyps, and is a potential serological diagnostic marker and therapeutic target for colorectal polyps and adenomatous polyps.

Objective:To explore the relationship between insulin resistance, glucose and lipid metabolism related molecules and colorectal polyps.Methods:A total of 262 healthy people who underwent colonoscopy in Shandong cancer hospital from June 2019 to September 2020 were selected. The levels of serum vascular cell adhesion molecule-1 (VCAM-1), fibroblast growth factor 19 (FGF19), insulin like growth factor (IGF-1), fasting blood glucose and fasting blood insulin were detected by enzyme-linked immunosorbent assay (ELISA). Insulin resistance index (HOMA-IR) was calculated, and the influencing factors of occurrence, pathological type, size and number of polyps were analyzed.Results:Among 262 cases, 116 cases were polyp free, 113 cases were adenomatous polyp and 33 cases were inflammatory polyp. HOMA-IR, VCAM-1 and FGF19 in polyp group were 2.904±1.754, (334.415±139.573) ng/ml and (135.865±98.470) pg/ml, respectively, which were higher than 2.369±1.306, (302.480±99.946) ng/ml and(110.694±76.044) ng/ml in non-polyp group, respectively ( P<0.05). Multivariate Logistic regression analysis showed that the gender ( OR=4.269, 95% CI: 1.963-9.405) and FGF19 (77.0-131.4 pg/ml: OR=2.385, 95% CI: 1.155-4.926) were independent factors of colorectal polyps. The gender ( OR=3.799, 95% CI: 1.650-8.748) and FGF19 (77.0-131.4 pg/ml: OR=2.290, 95% CI: 1.072-4.891) were independent factors of colorectal adenomatous polyps. The gender( OR=6.725, 95% CI: 1.853-24.410) and fasting plasma glucose (≥6.5 mmol/L: OR=0.047, 95% CI: 0.009-0.245) were independent factors of colorectal inflammatory polyps. The gender ( OR=3.539, 95% CI: 1.293-9.689) was an independent factor for the occurrence of single polyp. The gender ( OR=5.063, 95% CI: 2.048-12.515), FGF19 (77.0-131.4 pg/ml: OR=2.502, 95% CI: 1.102-5.681), fasting plasma glucose (≥6.5 mmol/L: OR=0.282, 95% CI: 0.095-0.839) were independent factors of multiple polyps. The gender ( OR=3.416, 95% CI: 1.134-10.289) and fasting insulin (≥9.4 μU/ml: OR=9.480, 95% CI: 1.485-60.521) were independent risk factors for colorectal polyps<0.5 cm. The gender ( OR=3.151, 95% CI: 1.244-7.984) and fasting plasma glucose (≥6.5 mmol/L: OR=0.310, 95% CI: 0.102-0.941) were independent risk factors for colorectal polyps with the size of 0.5-0.9 cm. The gender ( OR=22.649, 95% CI: 4.154-123.485), age (55 to 64 years old: OR=4.473, 95% CI: 1.070-18.704; ≥65 years old: OR=5.815, 95% CI: 1.300-26.009), BMI (≥28 kg/m 2: OR=5.310, 95% CI: 1.224-23.032) and FGF19 (77.0-131.4 pg/ml: OR=7.474, 95% CI: 1.903-29.351) were independent factors for colorectal polyps with size ≥ 1.0 cm. Gender stratification analysis showed that FGF19 was an independent factor for the occurrence of male polyps (77.0-131.4 pg/ml: OR=6.109, 95% CI: 1.688-22.104) and adenomas (77.0-131.4 pg/ml: OR=6.401, 95% CI: 1.717-23.864). The age (55 to 64 years old: OR=3.783, 95% CI: 1.052-13.611) and VCAM-1 (≥352.8 ng/ml: OR=4.341, 95% CI: 1.142-16.493) were independent risk factors of female polyps. The age (55 to 64 years old: OR=5.743, 95% CI: 1.205-27.362, ≥65 years old: OR=6.885, 95% CI: 1.143-41.467), VCAM-1 (≥352.8 ng/ml: OR=6.313, 95% CI: 1.415-28.159) and IGF-1 (≥7.6 ng/ml: OR=5.621, 95% CI: 1.069-29.543) were independent factors of female adenoma. Conclusions:The occurrences of colorectal polyps and adenomatous polyps are related to insulin resistance and glucose and lipid metabolism. Serum FGF19 is an independent influencing factor for the occurrence of colorectal polyps and adenomatous polyps, and is a potential serological diagnostic marker and therapeutic target for colorectal polyps and adenomatous polyps.

OBJECTIVE：To evaluate guidelines f or health technology assessment （HTA）at home and abroad ，and to provide reference for scientific formulation of HTA guidelines in China. METHODS ：Databases including PubMed ，Embase，Guidenlines International Network and 83 official websites from 26 countries governments and academic organizations were searched to collect HTA guidelines from inception to April 2020. Two reviewers independently screened literature and extracted data ，including basic characteristics， content of guideline and assessment content. Then a descriptive analysis was conducted. RESULTS & CONCLUSIONS：A total of 19 guidelines published during 2001 to 2018 were included ，7 guidelines（36.8％）were published in 2015-2020；in addition to 1 guideline from WHO ，14 guidelines （73.7％）were published in Europeand ，2 guidelines（10.5％） in North America and 1 guideline each from South America and Asia （5.3％）. There were 11 guidelines（57.9％）developed by academic organizations and 8 guidelines（42.1％）by health administration ；11 guidelines（57.9％）were evidence-based ，while the others weren ’t evidence- based （42.1％）. The purpose ，content and object of assessment are demonstrated in 19 guidelines；18 guidelines specified the assessment method （94.7％），and 16 guidelines（84.2％）defined the subject of assessment ；14 guidelines （73.7％）specified the HTA assessment process ；12 guidelines（63.3％）mentioned the conflict of interest in HTA assessment process；7 guidelines（36.8％）mentioned the application of assessment results. There are some differences in the formulation methods and contents of HTA guidelines in foreign countries ，but the core contents ar e basically the same. At present ，there is a lack of HTA guidelines in China. We can refer to foreign guidelines，and establish applicable HTA guidelines which aresuitable for national conditions ，so as to provide scientific guidance for HTA research.

OBJECTIVE： To systematically evaluate the efficacy and safety of Clonidine tansdermal patch for child tic disorders in children， and to provide evidence-based reference for clinical treatment. METHODS： Retrieved from Medline， Embase， Cochrane library， CNKI， VIP， CBM and Wanfang database， randomized controlled trials （RCTs） about Clonidine tansdermal patch （trial group） versus other therapies （control group， including placebo group， thiopride group， haloperidol group） for child tic disorders were collected from datbase estallishment to July 2018. The literatures met inclusion criteria were summarized. After quality evaluation with Cochrane system evaluation manual 5.1.0， Meta-analysis of reduction rate （amount） of YGTSS， the incidence of ADR and response rate was performed by using Rev Man 5.3 statistical software. Descriptive analysis was performed on indicators of groups that were unable to perform Meta-analysis. RESULTS： A total of 8 RCTs involving 1 320 patients were included. Among them， 2 RCTs involved placebo in control group； 2 RCTs involved thiopride， 3 RCTs involved haloperidol， and 1 RCT involved thiopride and haloperidol. Results of Meta-analysis showed that reduction rate of YGTSS in trial group were significantly higher than haloperidol group [MD＝21.94， 95％CI（21.03， 22.86）， P＜0.001]， but there was no statistical significance compared with thiopride group [MD＝10.66， 95％CI（－15.68， 37.00）， P＝0.43]. The incidence of adverse events （mainly including skin itching， redness， dry mouth， dizziness， decreased blood pressure， abnormal electrocardiogram） in trial group were significantly lower than thiopride group [OR＝0.42， 95％CI（0.22， 0.82）， P＝0.01] and haloperidol group [OR＝0.17， 95％CI（0.09， 0.32）， P＜0.001]， but there was no statistical significance compared with placebo group [OR＝0.61， 95％CI（0.29， 1.29）， P＝0.20]. There was no statistical significance in response rate of trial group compared with thiopride group [OR＝1.29，95％CI（0.38， 4.39）， P＝0.69] and haloperidol group [OR＝1.63， 95％CI（0.89， 2.96）， P＝0.11]. The results of descriptive analysis showed that reduction rate （amount） of YGTSS in trial group was significantly higher than that of placebo group （P＜0.05）， and response rate of trial group was significantly higher than that of placebo group （P＜0.01）. CONCLUSIONS： For child tic disorders in children， Clonidine tansdermal patch is better than placebo and haloperidol in reduction rate （amount） of YGTSS， and is similar to thiopride. Response rate of Clonidine tansdermal patch is better than that of placebo， and is similar to those of thiopride and haloperidol. The safety of Clonidine tansdermal patch is better than those of thiopride and haloperidol， and is similar to that of placebo.