Objective:To investigate the association between serum uric acid,pulmonary function and airflow obstruction in Chinese Taiwan healthy subjects.Methods:All the cross-sectional analysis was performed in the population over 40 years old using the physical examination data of Chinese Taiwan MJ Health Resource Center between 1996 and 2016 stratification by gender.The correlation analyses between serum uric acid were done and multivariate Logistic regression analysis was used to explore the effect of serum uric acid on airflow obstruction.Results:A total of 35 465 people were included in the study,in-cluding 16 411 men and 19 054 women.Among them,the serum uric acid concentration of men was higher than that of women,and the serum uric acid concentration of the people with airflow obstruction was higher than that of the people without airflow obstruction.There was a negative correlation between serum uric acid level and the forced expiratory volume in one second(FEV1)and the force vital capacity(FVC)in women(P＜0.05),but in men the correlation didn't exist(P＞0.05).After adjusting for age,education,smoking status,drinking status,work strength,body mass index,history of cough,his-tory of hypertension,history of diabetes,history of dyslipidemia,white blood cells and blood albumin,the airflow obstruction in women was more likely to exist with the serum uric acid elevated(OR=1.12,95％CI:1.02-1.22,P＜0.05).The results showed that women with hyperuricemia were more likely to have airflow obstruction than those without hyperuricemia(OR=1.36,95％CI:1.06-1.75,P＜0.05).There was no correlation between serum uric acid concentration and airflow obstruction in men(OR=1.04,95％CI:0.96-1.13,P＞0.05),also the hyperuricemia and airflow obstruction(OR=1.12,95％CI:0.89-1.39,P＞0.05).Conclusion:There is a negative correlation between serum uric acid and FEV1 and FVC in relatively healthy women,and there is an association between elevated serum uric acid and airflow obstruction in women,but not in men.Further prospective studies are needed to explore whether high serum uric acid level can increase the risk of airflow obstruction.

Objective:Diabetic retinopathy (DR) has been reported as the leading cause of blindness among diabetic adults, which is closely related to poor quality of life and increased burden of disability. This study aimed to aggregate the optimally available evidence on modifiable risks of DR.Methods:Until June 2023, PubMed, Cochrane Library, CNKI, and Wanfang databases were used to retrieve Meta-analysis about various risk factors for DR, and Meta-analysis were analyzed and summarized. R 4.3.2 software was used for each Meta-analytic association to calculate the effect size, 95% CI, heterogeneity, small-study effects, excess significance bias, and 95% prediction intervals. The credibility of significant evidence was graded. Results:We captured 23 eligible papers (72 associations) covering a wide range of medication use, concomitant diseases, daily intervention, biomarkers, lifestyle, and physical measurement index. Among them, higher HbA1c variability ( RR=1.45, 95% CI: 1.26-1.66) and urine microalbumin positive ( OR=2.44, 95% CI: 1.99-2.97) were convincing (grade Ⅰ) evidence, and insulin use ( RR=3.48, 95% CI: 2.14-5.67) was highly suggestive (grade Ⅱ) evidence. Moreover, hypertension ( OR=2.03, 95% CI: 1.06-3.97), poor glycemic control ( OR=4.35, 95% CI: 1.47-12.85), positive macroalbuminuria ( OR=8.42, 95% CI: 3.52-20.15), long sleep duration ( OR=2.05, 95% CI: 1.37-3.05), vitamin D deficiency ( OR=2.02, 95% CI: 1.17-3.50), periodontitis ( OR=4.51, 95% CI: 1.76-11.55) were the main risk factors for DR. Intensive blood pressure intervention ( RR=0.78, 95% CI: 0.65-0.94), dietary control ( OR=0.64, 95% CI: 0.47-0.89) and moderate intensity physical activity ( RR=0.76, 95% CI: 0.59-0.97) yielded significant protective associations with DR. Conclusions:Intensive blood pressure glycemic control, and a healthy lifestyle pattern could reduce the risk of DR. This study provides the evidence to identify high-risk populations and recommends rational treatment options and healthy living interventions.

Objective To explore the construction and practice of an intelligent prevention and treatment system for venous thromboembolism (VTE) in grassroots hospitals. Methods Based on relevant guidelines and expert consensuses on VTE prevention and treatment, domestic and foreign literature was reviewed. A research and development team composed of clinical experts in VTE prevention and treatment, medical and nursing quality management experts, and information engineers conducted investigations and research in surrounding grassroots hospitals. Through evidence-based research and surveys, the team identified relevant business needs, user needs, and functional requirements of grassroots hospitals, and finally formulated a detailed design plan. The main program of system was written in Java. The interface obtained data from the hospital's data platform through Webservice and view interfaces. To prevent issues of repeated data extraction when multiple applications perform time tasks to assess the same patient during later server usage and expansion, the XXL-JOB distributed task scheduling platform was adopted to handle VTE assessments by medical staff. Results After the clinical application of the intelligent VTE prevention and treatment system, the bleeding risk assessment rate increased from 26.20% at the initial system launch in January 2023 to 83.04% by the end of 2023. In January 2023, the implementation rates of mechanical prevention, pharmacological prevention, and combined prevention for medium-to-high-risk VTE patients were 21.39%, 16.39%, and 5.26%, respectively, which increased to 51.75%, 25.50%, and 25.65% in December 2023. Conclusion The VTE prevention and treatment software system developed by grassroots hospitals can improve development efficiency, enhance the clinical practicality of the system, reduce the workload of medical staff, promote standardization and normalization in VTE prevention and treatment, strengthen closed-loop management of medical quality for VTE as a single disease, and effectively improve the prevention and treatment capabilities and levels of VTE within hospitals.

Hydrogen peroxide (H2O2) plays a significant role in regulating a variety of biological processes. Dys-regulation of H2O2 can lead to various diseases. Although numerous fluorescent imaging probes for H2O2 have been reported, the development of H2O2 ratiometric fluorescent probe with large Stokes shift re-mains rather limited. Such probes have shown distinct advantages, such as minimized interference from environment and improved signal-to noise ratio. In this work, we reported a new pyrene-based com-pound Py-VPB as H2O2 fluorescent probe in vitro. The probe demonstrated ratiometric detection behavior, large Stokes shift and large emission shift. In addition, the probe showed high sensitivity and selectivity towards H2O2 in vitro. Based on these excellent properties, we successfully applied Py-VPB to the visualization of exogenous and endogenous H2O2 in living cells. Cell imaging study also showed that our probe was localized in the mitochondria. We envision that the probe can provide a useful tool for unmasking the biological roles of mitochondrial H2O2 in living systems.

Objective To establish the key question list for the development of evidencebased guideline in China according to the content and limitation of current evidence-based guidelines around the world.Methods First,we introduced the evidence-based guidelines in detail which met the criteria based on World Health Organization guideline development handbook and then formulated the draft list of key questions for the development of evidence-based guidelines.At last,the Delphi method was used to determine the list of key questions in developing evidence-based guidelines of colorectal cancer screening.Results Totally,34 questionnaires were collected,with experts from clinical and epidemiological fields.The average experts' authority coefficient was 0.81,indicating a high degree of authority.The concentration of opinions on all items in the questionnaire was relatively high,with the full score ratio greater than 75％ and the coefficient of variation less than 0.3.The list of key questions on evidence-based guidelines for colorectal cancer screening has been divided into six parts:epidemiological problems,risk classification,screening age,screening tools,implementation and selection of steering group members,which covers the issues that need to be considered in the development of evidence-based colorectal cancer screening guidelines in China.Conclusion The key question list for evidence-based guideline development in our study can be applied to the development of evidence-based guidelines for colorectal cancer screening in the future,as well as the development of evidence-based guidelines for other cancer screening in China.

Objective:The objective of the study was systematically summarized the current status of the hepatocellular carcinoma (HCC) screening guidelines, and evaluated the HCC screening guidelines according to the authoritative framework of cancer screening guidelines of authoritative institutions, which provided important value for the formulation of HCC screening evidence-based guidelines.Methods:Literature search was conducted in multiple databases from their inception dates to January 3, 2019. In addition, we sought relevant websites further was searched to identify potentially eligible studies. Two reviewers independently screened literature and extracted data. Qualitative description of the basic information, recommendations of HCC screening, source of evidence and update progress of the HCC screening guidelines was conducted.Results:At present, there were no independent HCC screening guidelines worldwide. There were only 17 clinical practice HCC guidelines briefly provided the recommendation of HCC screening. Current HCC screening guidelines only recommended screening for high-risk groups of HCC. All guidelines have identified patients with chronic hepatitis B, hepatitis C and cirrhosis as high-risk groups for HCC. Most of guidelines recommended screening intervals was 6 months. The latest guidelines in Europe and the United States recommended ultrasound for screening HCC. The combination of ultrasound and AFP was recommended in the Asian guidelines. Currently, HCC screening guidelines mainly recommended screening strategies based on factors such as risk of HCC, accuracy of screening modality, screening cost, etc.. The key factors such as screening efficacy and safety have not yet been considered comprehensively. Conclusions:There were no independent HCC screening guidelines worldwide. Only some clinical practice HCC guidelines briefly mentioned HCC screening. Currently, the guidelines only recommend screening for high-risk groups of HCC, with a screening interval of 6 months. There are differences in screening modalities recommended by European, American and Asian guidelines for screening HCC. It is suggested that the relevant institutions should formulate the evidence-based HCC screening guidelines by referring to the theoretical framework of other authoritative other cancer screening guidelines.

This paper introduces the conducting systematic reviews and Meta-analyses of observational studies of etiology (COSMOS-E) and illustrates the critical issues of COSMOS-E with a published systematic review. This document provides researchers with guidance on all steps in systematic reviews of observational studies of etiology, from shaping the research question, defining exposure and outcomes, to assessing the risk of bias and statistical analysis.

Objective:To investigate the clinicopathological and molecular characteristics of pulmonary enteric adenocarcinoma (PEAC).Methods:The clinical and pathological data of 19 cases of PEAC in the Affiliated Cancer Hospital of Zhengzhou University were retrospectively collected from 2015 to 2019. Immunohistochemistry (IHC) was used to detect the relevant immunophenotypes, amplification refractory mutation system (ARMS) and fluorescence in situ hybridization (FISH) were used to detect the expression of EGFR, KRAS and ALK genes. The patients were followed up, and the relevant literature was reviewed and analyzed.Results:There were 19 cases, including 10 males and 9 females, with a mean age of 58 years (range 33-71 years). Microscopically, the tumors showed moderately to highly differentiated adenoid and/or papillary growth patterns. The tumor cells were highly columnar and sometimes showed pseudostratification. Inflammatory necrosis and scattered nuclear fragmentation were seen in some glandular lumens. IHC showed variable expression of CK7 (19/19), TTF1 (8/19), Napsin A (6/19), villin (17/19), CK20 (16/19) and CDX2 (10/19). Molecular testing showed KRAS mutation in nine cases (9/19), EGFR mutation in one case (1/19), and positive ALK split signal in one case (1/19). In the literature, the reported mutation rate of KRAS in PEAC was much higher than that of EGFR and ALK. All 19 cases underwent surgical resection and 11 cases were subjected to chemotherapy or radiotherapy.Conclusions:PEAC is a rare variant of invasive pulmonary adenocarcinoma, and has similar histological and cytological features to that of colorectal adenocarcinoma. However, detailed medical history, histologic heterogeneity, an IHC combination of CK7 +/villin + and high KRAS mutation rate are the key points of diagnosis. The prognosis needs long-term follow-up and big data statistics.

Objective: To understand the consistency of ALK Ventana-D5F3 immunohistochemistry (IHC) interpretation in Chinese lung adenocarcinoma among histopathologists from different hospitals, and to recommend solution for the problems found during the interpretation of ALK IHC in real world, with the aim of the precise selection of patients who can benefit from ALK targeted therapy. Methods: This was a multicenter and retrospective study. A total of 109 lung adenocarcinoma cases with ALK Ventana-D5F3 IHC staining were collected from 31 lung cancer centers in RATICAL research group from January to June in 2018. All cases were scanned into digital imaging with Ventana iSCANcoreo Digital Slide Scanning System and scored by 31 histopathologists from different centers according to ALK binary (positive or negative) interpretation based on its manufacturer′s protocol. The cases with high inconsistency rate were further analyzed using FISH/RT-PCR/NGS. Results: There were 49 ALK positive cases and 60 ALK negative cases, confirmed by re-evaluation by the specialist panel. Two cases (No. 2302 and No.2701) scored as positive by local hospitals were rescored as negative, and were confirmed to be negative by RT-PCR/FISH/NGS. The false interpretation rate of these two cases was 58.1% (18/31) and 48.4% (15/31), respectively. Six out of 31 (19.4%) pathologists got 100% accuracy. The minimum consistency between every two pathologists was 75.8%.At least one pathologist gave negative judgement (false negative) or positive judgement (false positive) in the 49 positive or 60 negative cases, accounted for 26.5% (13/49), 41.7% (25/60), respectively, with at least one uncertainty interpretation accounted for 31.2% (34/109). Conclusion There are certain heterogeneities and misclassifications in the real world interpretation of ALK-D5F3 IHC test, which need to be guided by the oncoming expert consensus based on the real world data.

Objective: To investigate the level of interleukin-6 (IL-6) and the effect of valproic acid(VPA) administration on IL-6 promoter methylation, further to explore the epigenetic mechanism in febrile seizures. Methods: Sprague-Dawley (SD) rats (21 day) were randomly divided into control group (n=12) and febrile seizure (FS) group (n=12), and seizures were generated using hot bath methods and evaluated by racine score and electroencephalogram (EEG). The IL-6 protein and mRNA levels were detected using ELISA and quantitative reverse transcription polymerase chain reaction (qRT-PCR), respectively.Rat C6 cell line was cultured and randomly divided into control, VPA(0.2 mol/L), hyperthermia(43.5 ℃, 1 h), hyperthermia (43.5 ℃, 1 h)+VPA (0.2 mol/L) groups.The methylation status of IL-6 promoter in FS rats and the effect of VPA on IL-6 methylation in C6 cell line were examined by bisulfite sequencing polymerase chain reaction (BSP) to determine the epigenetic regulation of IL-6 level in FS. Results: Racine score and EEG results showed that the frequency and amplitude of neuronal discharge increased after hot water bath in rats, and the latency of convulsion was shorter.The expression levels of IL-6 mRNA and protein were significantly increased in Fs group compared with those in control group(mRNA: Control: 0.98±0.34; FS: 2.85±0.39, P<0.05; Protein: Control: (2 824.33±169.20)pg/ml; FS: (3 514.58±86.4)pg/ml, P<0.01). The methylation of IL-6 promoter in FS group (84% (21/25)) was lower than that in control group (100% (25/25)) (P<0.05). A significant increase in methylation of IL-6 promoter was observed in C6 cell line from VPA combined with hyperthermia (96% (24/25)) but no change was showed in that from VPA alone (100% (25/25)) compared with that from control(100% (25/25)). Conclusion IL-6 level is up-regulated in FS rats, and the hypomethylation or demethylation of the IL-6 promoter region might increase the IL-6 level.VPA administration can elevate its methylation level, which provides a strong experimental basis for the future study of the epigenetic mechanism in FS.