Acute liver injury (ALI) serves as a critical precursor and major etiological factor in the progression and ultimate manifestation of various hepatic disorders. The prevention and treatment of ALI is still a serious global challenge. Given the limited therapeutic options for ALI, exploring novel targeted therapeutic agents becomes imperative. The potential therapeutic efficacy of inhibiting RIPK2 is highlighted, as it may provide significant benefits by attenuating the MAPK pathway and NF-κB signaling. Herein, we propose a CMD-OPT model, a two-stage molecular optimization tool for the rapid discovery of RIPK2 inhibitors with optimal properties. Compound RP20, which targets the ATP binding site, demonstrated excellent kinase specificity, ideal oral pharmacokinetics, and superior therapeutic effects in a model of APAP-induced ALI, positioning RP20 as a promising preclinical candidate. This marks the first application of RIPK2 inhibitors in ALI treatment, opening a novel therapeutic pathway for clinical applications. These results highlight the efficacy of the CMD-OPT model in producing lead compounds from known active molecules, showcasing its significant potential in drug discovery.

Objective:To quantitatively analyze the plaque components of carotid artery through energy spectrum computed tomography angiography(CTA),and to measure the blood flow perfusion in the blood-supply area of carotid artery through CT perfusion(CTP),so as to explore the relationship among plaque component,the degree of luminal stenosis and cerebral blood flow perfusion.Methods:A total of 68 patients with unilateral plaques of carotid artery and severe vascular stenosis who were screened and diagnosed by ultrasound and CTA in Xiyuan Hospital from December 2017 to July 2019 were selected,and all patients underwent CTA examination and CTP examination.North American symptomatic carotid endarterectomy test(NASCET)method was used to measure the degree of carotid stenosis.The GE AW 4.7 post-process workstation was used to conduct analyses of energy spectrum and cerebral perfusion for the plaque component.And then,the slope of energy spectrum curve and the effective atomic number were obtained.At the same time,the cerebral blood volume(CBV),cerebral blood flow(CBF),time to peak(TTP)and mean transit time(MTT)of contrast agent in blood-supplying area of anterior cerebral artery(ACA)and middle cerebral artery(MCA)at the side of lesion were measured.Results:A total of 68 measured plaques of 68 patients met the condition,including 44 vulnerable plaques(including lipid plaques and mixed plaques)and 24 stable plaques(fibrous plaques).The average slopes of the energy spectrum curves of vulnerable plaque and stable plaque were respectively 0.45±0.45 and 1.15±0.39,and the differences were significant(t=2.413,P<0.05).The averagely effective atomic numbers of vulnerable plaques and stable plaques were respectively 7.21±1.06 and 8.01±0.63,and the difference were significant(t=2.548,P<0.05).The average TTP values of the ACA at the side of lesion of vulnerable plaques and stable plaques were respectively(12.20±1.61)S and(13.59±2.79)S,and the difference was significant(t=-2.607,P<0.05).The mean MTT values of the ACA at the side of lesion of vulnerable plaques and stable plaques were respectively(5.07±1.66)S and(6.09±2.19)S,and the difference was significant(t=-2.177,P<0.05).The degree of vascular stenosis at the side of lesion was positively correlated with TTP and MTT in blood-supplying area of middle cerebral artery(MCA)at the side of lesion(r=0.537,0.465,P<0.05),and that was negatively correlated with CBF values in blood-supplying areas of ACA and MCA at the side of lesion(r=-0.281,-0.569,P<0.05),respectively.The slope of the energy spectrum curve of carotid plaque was positively correlated with the TTP values in blood-supplying areas of ACA and MCA at the side of lesion(r=0.242,0.246,P<0.05),respectively.Conclusion:CT spectral imaging can quantitatively analyze the displayed components of carotid atherosclerotic plaque,and the degree of vascular stenosis can affect the blood flow perfusion of cerebral tissue,and the delays of TTP and MTT are more easily caused by vulnerable plaque,and the TTP of them is more sensitivity.

Objective To explore the risk factors for bleeding at the puncture site after femoral artery puncture intervention.Methods A computerized retrieval of observation studies,including cross-sectional studies,case-control studies,and cohort studies,about the risk factors for bleeding at the puncture site after femoral artery puncture intervention from the databases of China National Knowledge Infrastructure(CNKI),Wanfang,VIP,China Biomedical Literature Service(CBM),PubMed,Medline,The Cochrane Library,EMbase and Web of Science was conducted.The retrieval time period was from the establishment of the database to December 31,2022.Newcastle-Ottawa scale(NOS)was used to evaluate the quality of the included studies,and RevMan5.3 software was used to make meta-analysis of the literature data.Results A total of 8 articles with a total sample size of 35 250 patients were included in this analysis.There were 1 410 patients in the postoperative bleeding group and 33 840 patients in the non-bleeding group.The results of the meta-analysis showed that the aged(OR=2.71,95％ CI=2.17-3.38),female(OR=4.26,95％ CI=1.08-16.89),hypertension(OR=2.48,95％CI=1.69-3.63),obesity(OR=2.33,95％ CI=1.59-3.42),use of thrombolytic agents,anticoagulants or platelet antagonists(OR=2.95,95％ CI=2.24-3.89),manual compression(OR=6.78,95％ CI=1.34-34.43)were the risk factors for the bleeding at the puncture site after femoral artery puncture intervention.Conclusion The aged,female,hypertension,obesity,use of thrombolytic agents,anticoagulants or platelet antagonists,and manual compression are the risk factors for the bleeding at the puncture site after femoral artery puncture intervention.(J Intervent Radiol,2024,33:314-320)

Objective:To understand the current status of the level of chronic disease prevention and treatment literacy and health anxiety among chronic disease residents, as well as the urban-rural differences, in order to provide a basis for improving the level of chronic disease prevention and treatment literacy among chronic disease residents.Methods:This was a cross-sectional study. From July to August 2022, a multi-stage random sampling method was adopted to select 201 rural residents with chronic diseases in one rural health center and 242 urban residents with chronic diseases in two community health service centers. General demographic characteristics questionnaire, Chronic Disease Prevention and Control Literacy Questionnaire and Short version of Health Anxiety Scale were used for questionnaire survey.Results:There were 93 males and 108 females with chronic diseases in 201 rural chronic disease residents, and the age range was 19-69 years. There were 116 males and 126 females with chronic diseases in 242 urban chronic disease residents, and the age range was 18-69 years old. The score of chronic disease prevention and control literacy of rural chronic disease residents (7.86 ± 2.25) was lower than that of urban chronic disease residents (8.55 ± 2.03). The score of health anxiety of rural chronic disease residents (13.69 ± 5.26) was higher than that of urban chronic disease residents (11.67 ± 5.95). Both differences were statistically significant ( t=-3.43, 3.79, both P<0.05). After controlling the general demographic data, the layered linear regression analysis of rural chronic disease residents and urban chronic disease residents showed that health anxiety can negatively affect rural chronic disease residents and urban chronic disease residents of chronic disease prevention and treatment literacy level ( β=-0.185, -0.129, both P<0.05). Conclusions:There are urban-rural differences in chronic disease prevention and treatment literacy and health anxiety of chronic disease residents in community. It is necessary to strengthen psychological construction among rural chronic disease residents in order to improve their chronic disease prevention and treatment literacy.

Objective:To investigate the effectiveness of preeclampsia risk prediction models based on maternal risk factors during the first trimester in a local population.Methods:This was a diagnostic study. Pregnant women who underwent prenatal examination in People′s Hospital of Rizhao from May 2019 to May 2022 and had risk factors for preeclampsia were enrolled at 11-13 +6 weeks gestation, and were divided into preterm preeclampsia group, term preeclampsia group and non-preeclampsia group according to the occurrence and the gestational week. Baseline clinical data were collected. The effectiveness of different models in predicting preeclampsia risk was evaluated using receiver operating characteristic (ROC) curves. Results:Among the 559 pregnant women enrolled, 78(14.0%) had preeclampsia, including 35(6.3%) with preterm preeclampsia (preterm preeclampsia group), 43 (7.7%) with term preeclampsia (term preeclampsia group), and 481 (86.0%) without preeclampsia (non-preeclampsia group).The most effective model for predicting preterm preeclampsia in the first trimester was maternal risk factor+mean arterial pressure (MAP)+serum placental growth factor (PLGF)+uterine artery pulse index (UTPI). The area under ROC curve was 0.805, and the sensitivity was 56.6% with a false-positive rate of 10%; the most effective model for predicting term preeclampsia and preeclampsia was maternal risk factor+MAP+UTPI. The area under ROC curve was 0.777, and the sensitivity was 52.6% and 53.5% with a false-positive rate of 10%.Conclusion:The combined predicting strategy for preterm preeclampsia based on maternal risk factors in the first trimester maybe effective among our population.

Objective:To investigate the molecular epidemiologic and clinical characteristics of norovirus (NoV) in hospitalized children with acute gastroenteritis (AGE) in Tianjin to provide theoretical basis for clinical diagnosis and treatment.Methods:Fecal specimens were collected from children with AGE in Tianjin Children′s Hospital from August 2017 to July 2020. NoV was detected by real-time fluorescence reverse transcription-polymerase chain reaction (RT-PCR). Partial sequence of the capsid protein VP1 of positive samples was amplified by conventional RT-PCR. The products were sent for sequencing and genotyping based on the sequence. As the same time, the clinical symptoms were compared among children infected with different NoV genotypes.Results:Among the 6 432 specimens, 1 703 (26.5%) were positive for NoV. Sequence analysis showed that 761 identified NoV strains could be divided into 7 genotypes. Genotypes GII.4, GII.3, GII.2, GII.17, GII.1, GII.13 and GII.6 accounted for 55.5% (422/761), 36.7% (279/761), 4.9% (37/761), 0.9% (7/761), 0.8% (6/761), 0.8% (6/761) and 0.5% (4/761), respectively. All of the GII.4 belonged to GII.4 Sydney 2012. There was also a significant difference in the seasonal distribution of children infected with GII.4 and other genotypes ( χ2=103.53, P<0.001). Children infected with GII.4 NoV were more likely to have diarrhea, vomiting and dehydration ( χ2=8.42, P=0.004; χ2=20.39, P<0.001; χ2=4.99, P=0.025). Conclusions:GII.4 and GII.3 were mainly genotypes of NoV infection in Tianjin from 2017 to 2020 and genotypes were diverse. In addition, children with GII.4 NoV were more likely to suffer from diarrhea, vomiting and dehydration.

Objective:To understand the pathogen infection and epidemiological characteristics of children with diarrhea in Tianjin.Methods:Stool samples from 1 466 children with diarrhea in Tianjin Children's Hospital from August 2017 to July 2018 were collected, and all samples were tested for five intestinal-related pathogens (norovirus, rotavirus, Clostridium difficile toxin, adenovirus, and astrovirus). Results:Among the 1 466 samples, 627 samples were positive for nucleic acid detection of intestinal pathogens, with a positive rate of 42.8%. The detection rate of norovirus was the highest (26.3%), followed by rotavirus (15.3%), Clostridium difficile toxin (4.6%), adenovirus (4.1%), and astrovirus (1.84%). The infection has obvious seasonality. The positive detection rates of the five pathogens were similar among children of different sexes, and only the positive detection rates of norovirus and rotavirus were statistically significant among different ages ( P<0.05). There were 110 cases of mixed infection, and the mixed infection of norovirus and rotavirus was the most common, with a total of 37 cases. Conclusions:The pathogen spectrum of infant infectious diarrhea in Tianjin is complex and diverse, and the main pathogens are norovirus and rotavirus.

Objective:To explore the mediating effect of adversity quotient between transition shock and work readiness among newly graduated nurses.Methods:This is a cross-sectional study. From May to June 2021, a total of 242 newly graduated nurses from three ClassⅢ Grade A hospitals in Shandong Province were selected as the research objects by the convenient sampling method. The general situation questionnaire, Transition Shock Scale of Newly Graduated Nurses (TSS-NGN) , The Adversity Response Profile (ARP) and Work Readiness Scale for Graduate Nurses (WRS-GN) were used to survey. Pearson correlation analysis was used to test the correlation between transition shock, adversity quotient and work readiness AMOS 23.0 was used to establish the structural equation model. A total of 242 nurses were investigated in this study. 228 valid questionnaires were collected, and the effective recovery rate was 94.21%.Results:Among 228 newly graduated nurses, the total scores of work readiness, transition shock and adversity quotient were respectively (279.04±47.73) , (81.43±22.22) and (132.39±15.00) . Transition shock was negatively correlated with adversity quotient and work readiness ( r=-0.307, -0.291; P<0.01) , and adversity quotient was positively correlated with work readiness ( r=0.339, P<0.01) . The results of structural equation modeling showed that adversity quotient partially mediated between transition shock and work readiness (β=-0.243, P<0.01) , and the mediating effect accounted for 38.76% of the total effect. Conclusions:The work readiness of newly graduated nurses is at the upper middle level. Clinical nursing managers should pay attention to cultivating the adversity quotient of newly graduated nurses, so as to reduce the negative effect of transition shock on their work readiness, in order to realize a good transition from school to clinical nursing work.

Objective:To investigate the clusters of COVID-19 associated with a market (market Y) in Haidian District, Beijing, and analyze the chain of transmission and provide reference for effective prevention and control of COVID-19.Methods:The investigation of field epidemiology and cluster epidemic was used to describe the distributions of all COVID-19 cases. The time sequence diagram of the cases, disease onset was drawn and transmission chains were analyzed. Real-time RT-PCR assay was conducted for SARS-CoV-2 nucleic acid test by using the respiratory samples of the cases.Results:The COVID-19 epidemic, originated from a wholesale farm produce market (market X) in Fengtai District, Beijing, was introduced by a marketer in the market Y who had exposed to market X, causing 8 clusters of 20 confirmed cases of COVID-19 and one asymptomatic case, including 8 men and 13 women, in market Y, surrounding communities, food plaza, companies,families and other places. The incidence peaked during June 10-14, 2020; the median age of the cases was 45 years, ranging from 5 years to 87 years. The initial symptoms of the cases included fever (10/20) and pharynx discomfort (7/20). The median of incubation period was 5 days ( IQR:3-8). The median of serial interval between primary case and secondary cases was 5 days with a secondary attack rate of 3.7%(20/538), and the secondary attack rate in household close-contacts was 14.0% (7/50). Conclusions:The clusters of COVID-19 associated with market Y were caused by several modes of transmission, including human-to-human, contaminated material-to-human, etc. The combined public-health response measures were effective to control the COVID-19 epidemic in Haidian district of Beijing.

Objective:To analyze the pathogenic bacteria and epidemiological characteristics in children with respiratory tract infection in Tianjin area.Methods:Retrospective case analysis was performed on 2 392 hospitalized children in the wards of respiratory diseases, intensive care unit and special care ward of Tianjin Children′s Hospital from June 2018 to May 2019. Thirteen pathogenic bacteria in deep sputum and bronchoalveolar lavage fluid samples were detected by loop-mediated isothermal amplification. The laboratory data and clinical characteristics of the infected children were analyzed, and the comparison between groups was performed by t test or χ 2 test. Results:Among 2 392 cases, 1 407 were males and 985 females. There was no significant difference in the detection rate between males and females (72.5% (1 020/1 407) vs.74.2% (731/985), χ 2=0.87, P=0.35). A total of 1 751 strains and 12 kinds of positive respiratory pathogens were detected, with a detection rate of 73.2%. Among them, 913 (38.2%) strains were Mycoplasma pneumoniae (MP), 514 (21.5%) were Streptococcus pneumoniae (Sp), 381 (15.9%) were Methicillin-resistant Staphylococcus aureus (MRSA) and 279 (11.7%) were Hemophilus influenzae (Hi). There was significant difference in the detection rate of pathogens among different age groups (χ2=83.67, P<0.01). The positive rate of alveolar lavage fluid group was higher than that of deep sputum fluid group [81.6% (614/752) vs. 69.3% (1 137/1 640), χ 2=39.89, P<0.01]. The length of hospital stay of children infected with different pathogens was significantly different (all P<0.01). There was significant difference in duration of fever among children infected with different pathogens (χ2=228.69,103.56, 3.96, 27.38,24.50,41.66, all P<0.05). There were 63 (7.7%) cases of atelectasis, 260 (31.9%) cases of pleurisy and 120 (14.7%) cases of pleural effusion in MP children. Children with Sma were most likely to involve the heart system (2/9), and children with Eco infection had a higher incidence of complications such as those of blood (3/19), urinary (2/19), digestive systems(4/19), systemic inflammatory response syndrome and sepsis (1/19). Conclusions:The main bacterial pathogens of respiratory tract infection in children in Tianjin were MP, Sp, MRSA and Hi. It is suggested that clinicians should not only pay attention to the respiratory symptoms of children, but also pay attention to the complications caused by bacterial pathogen infection, so as to prevent the deterioration of the disease and improve the prognosis.