Objective To investigate the clinical efficacy and safety of nivolumab(PD-1 inhibitor)in combination with lenvatinib and FOLFOX regimen[5-fluorouracil(5-FU),oxaliplatin(L-OHP),and calcium folinate(LV)]in the treatment of intermediate and advanced hepatocellular carcinoma(HCC)via hepatic arterial infusion chemotherapy(HAIC).Methods A total of 160 patients with intermediate and advanced HCC admitted to the Second Affiliated Hospital of Guilin Medical University from January 2021 to January 2023 were randomly divided into the control group and the observation group,with 80 patients in each group,using a random number table.The control group received once-daily oral lenvatinib and intravenous carrizumab infusions for 12 weeks as part of transcatheter arterial chemoembolization(TACE)therapy.The observation group was administered with FOLFOX regimen via HAIC chemotherapy,plus intravenous infusion of carrizumab for 12 weeks and once-daily oral lenvatinib.All the patients were followed up regularly.The clinical efficacy was evaluated using the mRECIST criteria.The objective response rate(ORR),disease control rate(DCR),overall survival(OS),progression-free survival(PFS),and incidence of adverse reactions were compared between the two groups.Results There were no significant differences in the objective response rate and incidence of adverse reactions between the groups.The disease control rate,overall survival,and progression-free survival in the observation group were significantly higher than those in the control group(P<0.05).Conclusions The FOLFOX-HAIC regimen in combination with nivolumab and lenvatinib is safe and effective for the treatment of intermediate and advanced HCC,without adverse reactions.It can prolong the overall survival and progression-free survival,and improve the patient's quality of life.

Objective To investigate the application value of Revolution CT dual-low technique coronary angiography in coronary heart disease.Methods One hundred patients with suspected coronary heart disease were retrospectively selected and randomly divided into control group and observation group,who all were examined by Revolution CT.In the control group(50 cases),the tube voltage was 120 kV,the contrast agent iohexol was 350 mg I/mL,and the dose of contrast agent was 1 mL/kg.In the observation group(50 cases),the tube voltage was 100 kV,the contrast agent iohexol was 350 mg I/mL,and the dose of contrast agent was 0.8 mL/kg.All patients underwent coronary digital subtraction angiography(DSA)examination at the same time.The image quality(subjective and objective evaluation indexes)and radiation dose of the two groups were compared,the diagnostic value of the two methods for coronary artery stenosis was compared,and the diagnostic consistency with coronary DSA between the two methods were compared using the Kappa test,as well as the typical coronary images of the two groups were analyzed.Results There were no significant differences in the sub-jective image quality grade and excellence rate between the observation group and the control group(P＞0.05).The CT value and noise of the observation group were higher than those of the control group(P＜0.05).There were no statistically significant differ-ences in the signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)of the right coronary proximal and the left coronary main trunk between the two groups(P＞0.05).Compared with the control group,the volume CT dose index(CTDIvol),dose length product(DLP),and effective dose(ED)were lower in the observation group(P＜0.05).Compared with the results of coronary DSA,the positive predictive value,negative predictive value,sensitivity,specificity and accuracy of the two methods were＞80％,while there was no significant difference between the two groups(P＞0.05).The Kappa value of the observation group versus coronary DSA diagnosis was 0.871,the Kappa value of the control group ver-sus coronary DSA diagnosis was 0.889,and the consistency of both methods versus coronary DSA diagnosis was good.Conclusion Revolution CT dual-low technigue coronary angiography has good diagnostic value for coronary heart disease and can significantly reduce the radiation dose while ensuring image quality.

Objective:To explore the association of human betaine-homocysteine methyltransferase ( BHMT) and BHMT2 gene polymorphisms with non-syndromic congenital heart disease (CHD). Methods:A hospital-based case-control study was conducted, in which children with CHD who attended Hunan Children′s Hospital from January 2018 to May 2019 were enrolled as the case group, and children without any congenital deformity who attended the hospital during the same period were enrolled as the control group on a 1∶1 basis. A self-administered questionnaire survey was performed to collect information about the study subjects and their mothers, and then venous blood samples were collected from the subjects to detect BHMT and BHMT2 gene polymorphisms. Logistic regression analyses were used to evaluate the association of BHMT and BHMT2 gene polymorphisms and their haplotypes with CHD. Crossover analyses and logistic regression were used to explore the gene-gene and gene-environment interactions. Results:The case and control group both enrolled 620 children. The multivariate logistic regression showed that BHMT gene polymorphisms at rs3733890 (AA vs. GG: OR=3.476, Q FDR<0.001; GA vs. GG: OR=1.525, Q FDR=0.036), at rs1915706 (CC vs. TT: OR=3.464, Q FDR<0.001) and at rs1316753 (GG vs. CC: OR=1.875, Q FDR=0.020) increased the risk of CHD. Children with haplotype of A-G-A had an increased risk of CHD ( OR=1.468, 95% CI: 1.222-1.762). Interaction analysis showed that a statistically significant positive interaction between rs3733890 and rs1915706 on both additive ( RERI=0.628, 95% CI: 0.298-0.958) and multiplicative ( OR=3.754, 95% CI: 1.875-7.519) scales. Gene-environment interactions were found between the BHMT gene with secondhand smoke exposure before pregnancy and in early pregnancy, tea consumption before pregnancy and in early pregnancy, alcohol consumption before pregnancy, and folic acid supplementation before or during pregnancy. Conclusion:BHMT gene rs3733890, rs1915706 and rs1316753 polymorphisms may be associated with the risk of CHD. In addition, there is an association of cooperative interaction between rs3733890 and rs1915706 on both additive and multiplicative scales with the risk of CHD, and the BHMT gene interacts with multiple environmental factors.

Objective To analyze and clarify the concept of intrinsic capacity of the elderly.Methods We searched studies on intrinsic capacity of the elderly from websites and databases,including PubMed,Cochrane Library,Web of Science,Embase,CINAHL,China Biomedical Literature Service System databases,CNKI,WanFang databases and VIP.We selected relevant papers from the inception of databases to July 2023 according to inclusion criteria.Rodgers evolutionary method of concept analysis was used.Results A total of 30 articles were retrieved.4 attributes were identified on intrinsic capacity,including:guided by the goal of achieving healthy aging,inherent physiological reserve capacity of individuals,rich and interactive dimensions,and a dynamic and reversible development trajectory.Its prerequisites include demographic factors,socio-economic factors,health-related charac-teristics,external environment,and other factors;post effects include early identification of declining intrinsic abilities in the elderly and timely adoption of targeted intervention measures,which are of great significance for improving the quality of life of the elderly and promoting healthy aging.The decline in intrinsic capabilities is closely related to various adverse health outcomes,posing a serious threat to the health status of the elderly.Conclusion The concept attributes of intrinsic capacity were identified by concept analysis method.In the future,research and clinical practice should be carried out based on the concept of intrinsic capacity.

Objective:To explore the association of human betaine-homocysteine methyltransferase ( BHMT) and BHMT2 gene polymorphisms with non-syndromic congenital heart disease (CHD). Methods:A hospital-based case-control study was conducted, in which children with CHD who attended Hunan Children′s Hospital from January 2018 to May 2019 were enrolled as the case group, and children without any congenital deformity who attended the hospital during the same period were enrolled as the control group on a 1∶1 basis. A self-administered questionnaire survey was performed to collect information about the study subjects and their mothers, and then venous blood samples were collected from the subjects to detect BHMT and BHMT2 gene polymorphisms. Logistic regression analyses were used to evaluate the association of BHMT and BHMT2 gene polymorphisms and their haplotypes with CHD. Crossover analyses and logistic regression were used to explore the gene-gene and gene-environment interactions. Results:The case and control group both enrolled 620 children. The multivariate logistic regression showed that BHMT gene polymorphisms at rs3733890 (AA vs. GG: OR=3.476, Q FDR<0.001; GA vs. GG: OR=1.525, Q FDR=0.036), at rs1915706 (CC vs. TT: OR=3.464, Q FDR<0.001) and at rs1316753 (GG vs. CC: OR=1.875, Q FDR=0.020) increased the risk of CHD. Children with haplotype of A-G-A had an increased risk of CHD ( OR=1.468, 95% CI: 1.222-1.762). Interaction analysis showed that a statistically significant positive interaction between rs3733890 and rs1915706 on both additive ( RERI=0.628, 95% CI: 0.298-0.958) and multiplicative ( OR=3.754, 95% CI: 1.875-7.519) scales. Gene-environment interactions were found between the BHMT gene with secondhand smoke exposure before pregnancy and in early pregnancy, tea consumption before pregnancy and in early pregnancy, alcohol consumption before pregnancy, and folic acid supplementation before or during pregnancy. Conclusion:BHMT gene rs3733890, rs1915706 and rs1316753 polymorphisms may be associated with the risk of CHD. In addition, there is an association of cooperative interaction between rs3733890 and rs1915706 on both additive and multiplicative scales with the risk of CHD, and the BHMT gene interacts with multiple environmental factors.

In recent years, the artificial intelligence machine learning and deep learning technology have made leap progress. Using clinical decision support system for auxiliary diagnosis and treatment is the inevitable developing trend of wisdom medical. Clinicians tend to ignore the interpretability of models while pursuing its high accuracy, which leads to the lack of trust of users and hamper the application of clinical decision support system. From the perspective of explainable artificial intelligence, the authors make some preliminary exploration on the construction of clinical decision support system in the field of liver disease. While pursuing high accuracy of the model, the data governance techniques, intrinsic interpretability models, post-hoc visualization of complex models, design of human-computer interactions, providing knowledge map based on clinical guidelines and data sources are used to endow the system with interpretability.

Objective : To investigate the effect of adeno⁃associated virus ( AAV) delivery of short hairpin RNA ( shRNA) against the Ptger3 gene in the lateral parabrachial nucleus (LPB) on the fever induced by microinjection of prostaglandin E2 (PGE2 ) into the LPB and the intraperitoneal injection of lipopolysaccharide (LPS) . Methods: AAV2⁃shRNA⁃Ptger3(EP3) ⅣEGFP ( shRNA⁃EP3) and AAV2⁃ CMV⁃ EGFP ( shRNA⁃control) viruses were constructed and transfected the rat LPB by stereotaxic injection. Four weeks later, the transfection efficiency of AAV viruses was observed by fluorescence microscopy , and the knockdown efficiency was determined by real⁃time PCR of EP3 receptor mRNA on the LPB. The effects of microinjection of saline or PGE2 in the LPB or intraperitoneal injection of LPS on body temperature (Tcore ) and energy expenditure (EE) of shRNA⁃control group and shRNA⁃EP3 group were monitored using an animal monitoring system with temperature telemetry. Results : AAV virus transfecnificant difference in basal body temperature between shRNA⁃control group and shRNA⁃EP3 group. Tcore and EE were briefly and slightly increased after microinjection of saline in the LPB , but there was no significant difference between the two groups. Compared with the shRNA⁃control group , the febrile response induced by LPB PGE2 was attenuated in the shRNA⁃EP3 group (P < 0. 05) . Furthermore , the knockdown of EP3 receptor of LPB also attenuated the LPS⁃induced fever, and the Tcore 5. 5 h post⁃LPS in the shRNA⁃EP3 rats increased compared with the baseline (P < 0. 05) , which was lower than that in the shRNA⁃control rats ( P < 0. 01) . Conclusion EP3 receptor knockdown in LPB attenuates the febrile response induced by microinjection of PGE2 in the LPB and intraperitoneal injection of LPS , suggesting that EP3 receptors of LPB mediate the pyrogenic action of LPB PGE2 and partly participate in LPS⁃induced fever.

Objective:To analyze the epidemic characteristics of Cornona virus disease 2019 (COVID-19) in Wangkui County, Heilongjiang Province, and to provide a reference for optimizing epidemic prevention and control strategies.Methods:The epidemic characteristics of COVID-19 in Wangkui County, Heilongjiang Province in January 2021 were analyzed by applying the national infectious disease report system and information management system of Heilongjiang Provincial Center for Disease Control and Prevention, the public health emergency report management information system, the epidemiological investigation report of the Heilongjiang Provincial Center for Disease Control and Prevention and Suihua Municipal Certer for Disease Control and Prevention, and the epidemic information publicly released by the Health Commission of Heilongjiang Province.Results:From January 9 to February 5, 2021, 804 cases infected with Cornona virus were reported in Wangkui County, with an infection rate of 280.29/100 000. The epidemic affected 20 districts and counties in 6 cities, including Suihua, Harbin, Mudanjiang, Qiqihar, Yichun and Daqing. The sex ratio of male to female was 1.08 ∶ 1.00 (418 ∶ 386), the age ranged from 3 months to 93 years old, and the median age was 50 years old. The proportion of confirmed cases and asymptomatic infection was 1.23 ∶ 1.00 (444 ∶ 360), there were significant differences in gender, age and occupation between them ( P < 0.05). There were 314 places where the aggregation epidemic occurred, with family aggregation as the main way (300 households, 95.54%). The places with the highert average number of cases were banquets (25.75 cases/place) and grocery stores/chess and card rooms (16.00 cases/place). Conclusions:In January 2021, the epidemic of COVID-19 in Wangkui County is a typical outbreak in rural areas of North China. The main reasons for the rapid spread of the epidemic are a large number of gathering activities, frequent contact of personnel in confined spaces and other factors.

Objective:To compare the differences of event-related potential P300 and serum fibroblast growth factor 22 (FGF22) levels in cognitive impairment patients with first-episode and recurrent depression, and analyze the relations of each index with cognitive function and serum inflammatory factors.Methods:From June 2020 to April 2021, 45 cognitive impairment patients with first-episode depression (first-episode group) and 42 cognitive impairment patients with recurrent depression (recurrence group) were selected from our hospital. P300 examination was performed and serum FGF22, interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) levels were measured by enzyme-linked immunosorbent experiment (ELISA). The differences in clinical data, P300 examination results, and serum FGF22, IL-6 and TNF-α levels were compared between the two groups. The correlations of P300 amplitude and latency and serum FGF22 level with Montreal Cognitive Assessment (MoCA) scores and IL-6 and TNF-α levels were analyzed.Results:As compared with the first-episode group, the recurrence group had significantly decreased MoCA scores, P300 amplitude and serum FGF22 level, and statistically increased P300 latency and IL-6 and TNF-α levels ( P<0.05). Correlation analysis showed that P300 amplitude and serum FGF22 level were positively correlated with MoCA scores, and negatively correlated with IL-6 and TNF-α levels ( P<0.05); P300 latency was negatively correlated with MoCA scores, and positively correlated with IL-6 and TNF-α levels ( P<0.05). Conclusion:P300 amplitude and latency and serum FGF22 level are different between cognitive impairment patients with first-episode and recurrent depression, and they are correlated with the cognitive function and serum inflammatory factors.

Objective:To explore the value of aspartate aminotransferase(AST)and platelet (PLT)ratio index(APRI)in the prognosis of liver transplantation(LT)for hepatocellular carcinoma and establish a nomogram model for evaluating its clinical application potential.Methods:From January 2015 to December 2019, retrospective review was conducted for clinical data of LT for hepatocellular carcinoma(HCC)at First Affiliated Hospital of Zhejiang University School of Medicine and Shulan(Hangzhou)Hospital(601 cases). They were randomized into two groups of modeling (399 cases)and validation(202 cases)and then divided into low and high APRI groups according to the APRI value at Month 1 post-transplantation. The independent risk factors of recurrence and prognosis post-LT were screened in modeling group using univariate and multivariate Cox regression analyses and were further used for constructing a nomogram prediction model. The receiver operating characteristic curve(ROC)and survival curve were utilized for verifying the accuracy of nomogram prediction model.Results:Univariate and multivariate Cox regression analyses revealed that independent risk factors for the prognosis of HCC-LT included cold ischemic time(CIT) >8 h, beyond Hangzhou criteria, surgical bleeding volume >1 000 ml and APRI >1.5. The AUC of HCC-LT recurrence prediction model was 0.734(95%CI: 0.681~0.787)and 0.749(95%CI: 0.671~0.817)in modeling and validation groups; the AUC of HCC-LT mortality prediction model was 0.735(95%CI: 0.679~0.790)and 0.758(95%CI: 0.682~0.834)in modeling and validation groups.Conclusions:APRI>1.5 is an independent risk factor for postoperative recurrence and mortality after HCC-LT. The nomogram prediction model based upon CIT, Hangzhou criteria, intraoperative bleeding volume and APRI can effectively predict the recurrence and overall survival of LT for HCC.