Background China is a major coal producer and consumer country in the world. Coal workers' pneumoconiosis (CWP) is a primary factor endangering the occupational health of coal miners. Research on the disease burden of CWP and its changing trend is significant for disease prevention & control and associated policies. Objective To analyze the disease burden of CWP in China from 1990 to 2021 and its changing trend, and predict the disease burden from 2022 to 2035. Methods Using the Global Burden of Disease Study (GBD) database of 2021, numbers ofincident cases, prevalent cases, deaths, and disability-adjusted life years (DALYs) as well as crude and age-standardized rates of CWP in China were retrieved. Linear regression model was used to calculate the estimated annual percentage change (EAPC) of the age-standardized rates. Joinpoint regression model was used to analyze the temporal trend of disease burden and the disease burden of different sexes and age groups, and Bayesian age-period-cohort (BAPC) model was used to forecast the trend of CWP disease burden. Results In 1990, the incident, prevalent, and deaths cases of CWP in China were 3266, 18872, and 1561, respectively, and the DALYs of CWP were 44614.718 person-years. In 2021, the incident, prevalent, and deaths cases of CWP were 3446, 23975, and 1229, respectively, and the DALYs of CWP were 29610.754 person-years. From 1990 to 2021, the age-standardized incidence, prevalence, mortality, and DALYs rates of CWP in China all showed a downward trend, with the EAPCs of −3.121%, −2.532%, −4.018%, and −4.268%, respectively. The disease burden of CWP in China was mainly concentrated in the male population. The annual average percent change analysis indicated that each standardized rate showed a fluctuating downward trend in different periods. The BAPC model showed that from 2022 to 2035, the age-standardized rates of CWP in China would continue to decline steadily. In 2035, the age-standardized incidence, prevalence, mortality, and DALYs rates of CWP would be reduced to 0.10 per 100000, 0.74 per 100000, 0.03 per 100000, and 0.74 per 100000, respectively. Conclusion The disease burden contributed by CWP in China generally show a downward trend from 1990 to 2021, and it is expected that the age-standardized rates will continue to decline steadily from 2022 to 2035.

Gastric cancer is a high-incidence malignancy that poses a serious threat to public health in China, ranking among the top three cancers in both incidence and mortality. The majority of patients are diagnosed at an advanced stage, resulting in limited treatment options and poor prognosis. To address key challenges in gastric cancer diagnosis and treatment, a research team led by Professor Jiafu Ji at Peking University Cancer Hospital has focused on the project "Development and Dissemination of Precision Medicine Approaches in Gastric Cancer Management". Through a series of high-quality multicenter clinical studies, the team established a set of new international standards in perioperative treatment, individua-lized drug selection, intelligent noninvasive diagnostics, and novel immunotherapy strategies. These advances have significantly improved treatment efficacy and reduced surgical trauma, achieving key technological breakthroughs in diagnosis, therapy, and mechanistic understanding, and systematically enhancing outcomes for gastric cancer patients. The project ' s findings had a broad international impact, including hosting China ' s first International Gastric Cancer Congress. Through nationwide dissemination, they have promoted the development of precision diagnosis and treatment of gastric cancer as a discipline, and led the formulation of the National Health Commission's guidelines for gastric cancer diagnosis and treatment. In recognition of its achievements, the project was awarded the First Prize of the 2024 Chinese Medical Science and Technology Award.
Stomach Neoplasms/genetics* ; Humans ; Precision Medicine/methods* ; China ; Immunotherapy/methods*

Extensive epigenetic reprogramming involves in memory CD8+ T-cell differentiation. The elaborate epigenetic rewiring underlying the heterogeneous functional states of CD8+ T cells remains hidden. Here, we profile single-cell chromatin accessibility and map enhancer-promoter interactomes to characterize the differentiation trajectory of memory CD8+ T cells. We reveal that under distinct epigenetic regulations, the early activated CD8+ T cells divergently originated for short-lived effector and memory precursor effector cells. We also uncover a defined epigenetic rewiring leading to the conversion from effector memory to central memory cells during memory formation. Additionally, we illustrate chromatin regulatory mechanisms underlying long-lasting versus transient transcription regulation during memory differentiation. Finally, we confirm the essential roles of Sox4 and Nrf2 in developing memory precursor effector and effector memory cells, respectively, and validate cell state-specific enhancers in regulating Il7r using CRISPR-Cas9. Our data pave the way for understanding the mechanism underlying epigenetic memory formation in CD8+ T-cell differentiation.
CD8-Positive T-Lymphocytes/metabolism* ; Cell Differentiation ; Chromatin/immunology* ; Animals ; Mice ; Immunologic Memory ; Epigenesis, Genetic ; SOXC Transcription Factors/immunology* ; NF-E2-Related Factor 2/immunology* ; Mice, Inbred C57BL ; Gene Regulatory Networks ; Enhancer Elements, Genetic

Objective Exploring the mechanisms of Sanwu Huangqin Decoction in the treatment of liver tumors based on network pharmacology and molecular docking technologies and experimental observations.Methods TCMSP database was used to screen the effective compounds contained in Sanwu Huangqin decoction,Drug bank,Pharm mapper,Uniport,PubMed and other databases were used to obtain the action targets of Sanwu Huangqin decoction,gene cards and TCGA databases were used to obtain the related targets of hepatocellular carcinoma,and the"drug-disease"target genes were obtained after the intersection with the action targets of Sanwu Huangqin decoction,and the protein interaction network was constructed using string database,David and KEGG databases were used for go and KEGG enrichment analysis,Cytoscape software was used to build the corresponding network,and discovery studios software was used for molecular docking to verify the above network pharmacology related results.The effects of Sanwu Huangqin decoction on the proliferation,the metastasis and the expression of IL-6 of cancer cells were observed.Results 81 effective components and 10 key components of Sanwu Huangqin decoction,249 targets,1420 differential targets between tumor samples and normal samples were obtained,and 59 overlapping targets were obtained.Frequency analysis of protein interaction network:the potential mechanism of Sanwu Huangqin Decoction in treating hepatocellular carcinoma is related to ESR1,Myc,Jun,IL-6,MMP9,EGF,etc.Through GO and KEGG enrichment analysis,IL-17 signaling pathway,TNF signaling pathway,Toll like receptor signaling pathway may play important roles.The results of molecular docking showed that acacetin,wogonin,baicalein,oroxylin a,beta sitosterol,8-isoopenenyl-kaempferol,formononetin,luteolin,quercetin,and stigmastrol bound to IL-6 protein,which further confirmed the above results.Animal experiments showed that Sanwu Huangqin decoction could inhibit the tumor size and the pulmonary metastasis,and the content of IL-6 in cancer cells was decreased,which preliminarily verified the anti-tumor effects and mechanism of Sanwu Huangqin decoction.Conclusion In this study,we found that IL-6 was the key target of Sanwu Huangqin decoction by network pharmacology and molecular docking technology.Sanwu Huangqin decoction could reduce the content of IL-6 in tumor tissues to inhibit liver cancer in vivo.These results provided a theoretical basis for the application of Sanwu Huangqin decoction in the treatment of liver cancer.

Objective To identify the independent risk factors of cognitive impairment(CI)in patients with cerebral small vessel disease(CSVD)and construct a clinical prediction model.Methods Patients with CSVD who were hospitalized in the First Affiliated Hospital of Xi'an Jiaotong University from January 1,2017 to December 31,2022 were retrospectively enrolled,and were divided into a group with cognitive impairment(CSVD-CI group,n=83)and a group without cognitive impairment(CSVD-NCI group,n=164)according to the mini-mental state examination(MMSE).The influence factors of cognitive impairment were screened by logistic regression.The clinical prediction model of the nomogram was further developed based on the screened factors,and the efficacy of the model was tested.Results Compared with patients in the CSVD-NCI group,patients in the CSVD-CI group had higher neutrophil/lymphocyte ratio(NLR)(3.03±2.56 vs 2.33±1.34)and(1.58±0.27 vs 1.49±0.28),and a lower estimated glomerular filtration rate[eGFR:88.59±16.59 ml/(min·1.73m2)vs 94.02±12.45 ml/(min·1.73m2)],with significant differences(t=2.282,2.426,2.689,all P＜0.05).Compared with patients in the CSVD-NCI group,patients in the CSVD-CI group had lower proportion of males(43.4％vs 67.7％)and level of education(2.13±1.50 vs 2.86),and the differences were significant(x2=13.516,t=4.283,all P＜0.05).NLR(OR:1.20,95％CI:1.01～1.43),sex(OR:0.43,95％CI:0.24～0.79),eGFR(OR:0.97,95％CI:0.95～0.99)and education degree(OR:0.72,95％CI:0.57～0.91)were the impact factors for cognitive impairment in CSVD patients.The nomogram prediction model based on these four factors had good efficacy in predicting cognitive impairment(AUC=0.704,95％CI:0.633～0.766).Conclusion The nomogram constructed in this study has moderate accuracy and clinical utility in predicting the occurrence of cognitive impairment in CSVD patients.

Objective To investigate the genetic risk factors of deep vein thrombosis(DVT)after trauma.Methods In a nested case-control study,50 patients with DVT after traumatic lower extremity fractures and 50 patients without DVT were recruited.The two groups were matched with gender,age and fracture sites.Preoperative venography was performed to diagnose DVT in trauma patients.Genome wide association study(GWAS)was used to investigate the genetic risk factors for preoperative DVT after traumatic lower ex-tremity fractures.Genomic DNA in leukocytes from blood sample was extracted and used for GWAS.Results GWAS was conducted based on 2 662 single nucleotide variants(SNV)which were dispersed in 144 interested genes.Ten genes were found to have signifi-cant association with trauma-related DVT,including cofactors of hemostasis mechanism,i.e.,THBD,F5,SERPIND1 and ITGA2,the factors related to vitamin K-dependent(VKD)carboxylation,i.e.,GGCX and CALU,and the members of cytochrome P450 family,i.e.,CYP1A1,CYP3A4,CYP2C19 and CYP2B6.Conclusion DVT after trauma might be regulated by the cofactors of hemostasis mechanism,the factors related to VKD carboxylation and the members of cytochrome P450 family.The results of our study may provide reference and inspiration for genetic susceptibility of preoperative DVT after trauma.

Objective To analyze the current research application status and hotspots of nanoparticles in the treatment of non-small cell lung cancer (NSCLC) and predict the future development trend. Methods The Web of Science database was searched for literatures on nanoparticles use in the treatment of NSCLC from inception to November 2022. CiteSpace, VOSviewer and literature measurement analysis online platform (https://bibliometric.com/) were used for the visual analysis of the number of documents, source journals, authors, organizations, countries and keywords. Results A total of 742 English literatures were included. The results showed that the number of published literatures increased year by year from 2011 and reached the peak in 2020. Researches on nanoparticles and NSCLC treatment were mainly concentrated in China, the United States, India and Japan. China is a major research country in this field, but it lacked cooperation with other countries and related institutions. Among numerous research institutions, the Chinese Academy of Sciences was the authoritative and backbone force in this research field, with the number of published literatures ranking first and the research achievements outstanding. The keyword analysis found that "poly lactic-co-glycolic acid nanoparticles (PLGA NPs)" and "photothermal therapy" had become the latest breakout words since 2018. Moreover, the occurrence frequency of related keywords such as "drug delivery" increased significantly, indicating that the application of PLGA NPs in photothermal therapy might be the current research hotspot and future development trend of NSCLC treatment. Conclusion Currently, the domestic research on the treatment of nanoparticles and NSCLC is in a leading position in the world. The organic combination of nanoparticles with different materials and other NSCLC therapies is expected to improve the prognosis of NSCLC patients. In the future, attempts to develop nanoparticles with different sources and structures and combined with photothermal therapy for the treatment of NSCLC may become a research hotspot of nanoparticles in the treatment of NSCLC.

Objective:To investigate the clinical characteristics of choledocholithiasis com-bined with periampullary diverticulum and influencing factor for difficult cannulation of endoscopic retrograde cholangiopancreatography (ERCP).Methods:The retrospective case-control study was conducted. The clinical data of 1 920 patients who underwent ERCP for choledocholithiasis in 15 medical centers, including the First Hospital of Lanzhou University, et al, from July 2015 to December 2017 were collected. There were 915 males and 1 005 females, aged (63±16)years. Of 1 920 patients, there were 228 cases with periampullary diverticulum and 1 692 cases without periampullary diverticulum. Observation indicators: (1) clinical characteristics of patients with choledocholithiasis; (2) intraoperative and postoperative situations of patients undergoing ERCP for choledocholithiasis; (3) influencing factor analysis for difficult cannulation in patients undergoing ERCP for choledocholithiasis. Measurement data with normal distribution were represented as Mean±SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M(range) or M( Q1, Q3), and com-parison between groups was conducted using the Wilcoxon rank sum test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher exact probability. The Logistic regression model was used for univariate and multivariate analyses. Results:(1) Clinical characteristics of patients with choledocholithiasis. Age, body mass index, cases with complications as chronic obstructive pulmonary disease, diameter of common bile duct, cases with diameter of common bile duct as <8 mm, 8?12 mm, >12 mm, diameter of stone, cases with number of stones as single and multiple were (69±12)years, (23.3±3.0)kg/m 2, 16, (14±4)mm, 11, 95, 122, (12±4)mm, 89, 139 in patients with choledocholithiasis combined with periampullary diverticulum, versus (62±16)years, (23.8±2.8)kg/m 2, 67, (12±4)mm, 159, 892, 641, (10±4)mm, 817, 875 in patients with choledocholithiasis not combined with periampullary diver-ticulum, showing significant differences in the above indicators between the two groups ( t=?7.55, 2.45, χ2=4.54, t=?4.92, Z=4.66, t=?7.31, χ2=6.90, P<0.05). (2) Intraoperative and postoperative situations of patients undergoing ERCP for choledocholithiasis. The balloon expansion diameter, cases with intraoperative bleeding, cases with hemorrhage management of submucosal injection, hemostatic clip, spray hemostasis, electrocoagulation hemostasis and other treatment, cases with endoscopic plastic stent placement, cases with endoscopic nasal bile duct drainage, cases with mechanical lithotripsy, cases with stone complete clearing, cases with difficult cannulation, cases with delayed intubation, cases undergoing >5 times of cannulation attempts, cannulation time, X-ray exposure time, operation time were 10.0(range, 8.5?12.0)mm, 56, 6, 5, 43, 1, 1, 52, 177, 67, 201, 74, 38, 74, (7.4±3.1)minutes, (6±3)minutes, (46±19)minutes in patients with choledocholithiasis combined with periampullary diverticulum, versus 9.0(range, 8.0?11.0)mm, 243, 35, 14, 109, 73, 12, 230, 1 457, 167, 1 565, 395, 171, 395, (6.6±2.9)minutes, (6±5)minutes, (41±17)minutes in patients with choledocholithiasis not combined with periampullary diverticulum, showing significant differences in the above indicators between the two groups ( Z=6.31, χ2=15.90, 26.02, 13.61, 11.40, 71.51, 5.12, 9.04, 8.92, 9.04, t=?3.89, 2.67, ?3.61, P<0.05). (3) Influencing factor analysis for difficult cannulation in patients undergoing ERCP for choledocholithiasis. Results of multivariate analysis showed total bilirubin >30 umol/L, number of stones >1, combined with periampullary diverticulum were indepen-dent risk factors for difficult cannulation in patients with periampullary diverticulum who underwent ERCP for choledocholithiasis ( odds ratio=1.31, 1.48, 1.44, 95% confidence interval as 1.06?1.61, 1.20?1.84, 1.06?1.95, P<0.05). Results of further analysis showed that, of 1 920 patients undergoing ERCP for choledocholithiasis, the incidence of postoperative pancreatitis was 17.271%(81/469) and 8.132%(118/1 451) in the 469 cases with difficult cannulation and 1 451 cases without difficult cannula-tion, respectively, showing a significant difference between them ( χ2=31.86, P<0.05). In the 1 692 patients with choledocholithiasis not combined with periampullary diverticulum, the incidence of postopera-tive pancreatitis was 17.722%(70/395) and 8.250%(107/1 297) in 395 cases with difficult cannula-tion and 1 297 cases without difficult cannulation, respectively, showing a significant difference between them ( χ2=29.00, P<0.05). In the 228 patients with choledocholithiasis combined with peri-ampullary diverticulum, the incidence of postoperative pancreatitis was 14.865%(11/74) and 7.143%(11/154) in 74 cases with difficult cannulation and 154 cases without difficult cannulation, respectively, showing no significant difference between them ( χ2=3.42, P>0.05). Conclusions:Compared with patients with choledocholithiasis not combined with periampullary divertioulum, periampullary divertioulum often occurs in choledocholithiasis patients of elderly and low body mass index. The proportion of chronic obstructive pulmonary disease is high in choledocholithiasis patients with periampullary diverticulum, and the diameter of stone is large, the number of stone is more in these patients. Combined with periampullary diverticulum will increase the difficult of cannulation and the ratio of patient with mechanical lithotripsy, and reduce the ratio of patient with stone complete clearing without increasing postoperative complications of choledocholithiasis patients undergoing ERCP. Total bilirubin >30 μmol/L, number of stones >1, combined with periampullary diverticulum are independent risk factors for difficult cannulation in patients of periampullary diverticulum who underwent ERCP for choledocholithiasis.

With the development of information technology and the changes in people's lifestyle, E-health has become a new way for people to receive health services and has been widely applied in the prevention and control of HIV infection, including behavioral intervention, biomedical intervention, mental health intervention, improving access to health services and so on. This paper summarizes the application of E-health intervention in HIV prevention and control both at home and abroad to provide reference for the further optimization of planning and strategies of E-health intervention in HIV infection prevention.

Objective:To investigate the efficacy and safety of initial treatment with ibuprofen or paracetamol and rescue treatment with high-dose ibuprofen in preterm infants with haemodynamically significant patent ductus arteriosus (hsPDA).Methods:The preterm infants (gestational age ≤ 32 weeks) with hsPDA who were admitted to neonatal intensive care unit (NICU) of Xuzhou Central Hospital from October 2016 to November 2019 were enrolled in the study. A total of 110 eligible cases were included and randomly divided into three groups for initial treatment: 38 cases received oral ibuprofen 10 mg/kg, and 5 mg/kg after 24 h and 48 h (ibuprofen group), 37 cases received oral paracetamol 15 mg/kg, q.8.h for 3 d (paracetamol group) and 35 cases received oral injection water 1 ml/kg, and 0.5 ml/kg after 24 h and 48 h (conservative management group). The preterm infants who failed in the initial treatment were given high-dose ibuprofen for rescue treatment (oral ibuprofen 20mg/kg, and 10 mg/kg after 24 h and 48 h). Serum creatinine, cystatin C, glutamic-pyruvic transaminase (GPT), total bilirubin, fecal occult blood and urinary prostaglandin E 2 were measured; echocardiography and brain color Doppler ultrasonography examinations were performed before and after treatment. Urine output and complications were recorded. The data were analyzed by ANOVA, t-test, non-parametric test, chi-square test and Pearson correlation coefficient with SPSS 20.0 statistical software. Results:During initial treatment, the success rates of ibuprofen group and paracetamol group were higher than that of conservative management group [71.1% (27/38) and 70.3%(26/37) vs. 40.0% (14/35), P=0.008 and 0.010]. Thirty one patients, who failed in initial treatment, received rescue treatment (8, 7, 16 cases from ibuprofen, paracetamol and conservative groups, respectively). The success rate of rescue treatment with high-dose ibuprofen was 58.1% (18/31). During initial treatment, there were no significant differences in the incidence of oliguria, upper gastrointestinal bleeding, positive fecal occult blood tests, Ⅲ-Ⅳ grade intraventricular hemorrhage, and ≥Ⅱ stage necrotizing enterocolitis among the three groups (all P>0.05). There were no significant differences in the incidence of above complications between rescue treatment and initial treatment [6.5% (2/31) vs. 6.4%(7/110), 3.2%(1/31) vs. 4.5%(5/110), 12.9%(4/31) vs. 6.4%(7/110), 0 vs. 4.5%(5/110), 3.2%(1/31) vs. 1.8%(2/110), all P>0.05]. The changes of serum creatinine and GPT before and after treatment were not significant in all groups ( P>0.05). Serum cystatin C were increased in both ibuprofen group[(0.44±0.17)μmol/L] and paracetamol group [(0.18±0.09)μmol/L] after treatment ( t=-15.70, -14.64; P<0.001), and the increase in ibuprofen group was greater than that in paracetamol group ( P<0.001). Urinary prostaglandin E 2 were decreased in both ibuprofen group [(-11.63±3.70)ng/L] and paracetamol group[(-4.89±1.91)ng/L] after treatment ( t=15.57, 7.03; P<0.001), and the decrease in ibuprofen group was greater than that in paracetamol group ( P<0.001). Serum cystatin C was not significantly increased after high dose ibuprofen rescue treatment [(1.67±0.17)mg/L vs.(1.71±0.21)mg/L; t=-1.12, P=0.273]. Conclusion:Both initial treatment with ibuprofen or paracetamol and rescue treatment with high-dose ibuprofen can effectively promote hsPDA closure in preterm infants without increase of complications. However, renal function indexes such as urine output and serum cystatin C should be monitored. The high-dose ibuprofen is relatively safe, and can be used as one of rescue treatment.