OBJECTIVE To evaluate the cost-effectiveness of toripalimab combined with paclitaxel （albumin binding type） in the treatment of metastatic or recurrent triple-negative breast cancer （TNBC）. METHODS Based on the data of TORCHLIGHT clinical trial， a three-state partitioned survival model including progression-free survival， disease progression， and death was established. The simulation cycle was 21 days， the study duration was 10 years， and the discount rate was 5%. Using quality- adjusted life year （QALY） and cost as output indicators， a cost-effectiveness analysis method was adopted to calculate the incremental cost-effectiveness ratio （ICER） of toripalimab combined with paclitaxel （albumin binding type） versus placebo combined with paclitaxel （albumin binding type）. Using three times the per capita gross domestic product （GDP） of China in 2023 as the willingness-to-pay（WTP） threshold（268 074 yuan/QALY）， the cost-effectiveness of the above two regimens was evaluated， and the sensitivity analysis was conducted. RESULTS ICER of toripalimab combined with paclitaxel （albumin binding type） versus placebo combined with paclitaxel （albumin binding type） in the treatment of Chinese metastatic or recurrent TNBC patients was 176 347.17 yuan/QALY， which was lower than the WTP threshold set in this study， demonstrating the cost-effectiveness of this regimen. The results of the single-factor sensitivity analysis showed that the parameters such as the cost of toripalimab， discount rate， and utility value of the progression-free survival state had a great impact on the ICER. The results of the probabilistic sensitivity analysis indicated that the results of the basic analysis were robust. CONCLUSIONS When three times the per capita GDP of China in 2023 is used as the WTP threshold， compared with the regimen of placebo combined with paclitaxel （albumin binding type）， toripalimab combined with paclitaxel （albumin binding type） is cost-effective in the treatment of metastatic or recurrent TNBC.

Objective:To analyze the prevalence and clinical features of respiratory syncytial virus (RSV) in Chengde city.Methods:From August 2022 to June 2023, throat swabs and clinical data of 478 hospitalized children with respiratory tract infection in the Chengde Central Hospital were collected. Real-time quantitative PCR was used to detect the molecular epidemiology of RSV-A and RSV-B subtypes and analyze the clinical features of patients with RSV infection.Results:Among the hospitalized children, 67.57% (323/478) tested positive for RSV. The outbreak of RSV infection was caused by RSV-A subtype. The peaks of RSV-A infection occurred from November to December, 2022 and May to June, 2023. There were 86.07% (278/323) of the RSV-A-positive cases had mixed infection with other pathogens, primarily bacterial pathogens with Streptococcus pneumoniae being the most common, followed by Klebsiella pneumoniae. Influenza virus A was the most common viral pathogens causing mixed infection. The level of lactate dehydrogenase was higher in the patients with single RSV-A infection than in those with mixed infection ( Z=2.396, P=0.017), and higher than the normal upper limit. Compared with the single infection group, the mixed infection group had higher white blood cell count ( Z=2.417, P=0.016), neutrophil ratio ( Z=3.218, P=0.001), C-reactive protein level ( Z=1.998, P=0.046) and creatinine level ( Z=2.107, P=0.035), and lower lymphocyte ratio ( Z=3.205, P=0.001), but they were all within the normal range. There were no significant differences in the clinical features between RSV-A-positive patients co-infected with bacteria or other viruses (all P>0.05). Conclusions:RSV-A is the leading cause of respiratory tract infection in children in Chengde from 2022 to 2023, and often co-detected with bacteria. The mixed infection with other respiratory pathogens is related to the clinical features of patients with RSV-A infection.

Objective:To explore the association between frailty index (FI) and the risk for cardiovascular disease (CVD) in adults in Inner Mongolia Autonomous Region, and provide new evidence for the prevention of CVD in adults in Inner Mongolia Autonomous Region.Methods:The FI was constructed by using the data from a prospective cohort with a sample size of 25 055 individuals in 6 years of follow-up, and the prevalence of frailty in adults in Inner Mongolia Autonomous Region was described by the FI, and Cox proportional hazard regression model was used to evaluate the association between the FI and the incidence of CVD in adults in Inner Mongolia Autonomous Region.Results:The FI of the study population was 0.24±0.09. The population in the pre-frail (FI: 0.21-0.27) and frail (FI≥0.28) phases had increased risk for CVD compared to non-frail (FI≤0.20) population [pre-frail: hazard ratio ( HR)=1.232, 95% CI: 1.127-1.347; frail phase: HR=1.418, 95% CI:1.299-1.548]. For every 0.10 increase in FI, the risk for cardiovascular disease increased by 20.3% ( HR=1.203,95% CI:1.156-1.252). Conclusions:In this study, we constructed a FI, which can suggest the risk for CVD. As the increase of frailty degree, the risk for CVD increases.

  Objective  To summarize the clinical manifestations, pathological features and gene mutation diversity of Blau syndrome/early-onset sarcoidosis.  Methods  We collected general data, clinical manifestations, and auxiliary examination results from 8 patients who were diagnosed of Blau syndrome/early-onset sarcoidosis and treated in our hospital from January 2011 to December 2022, and then summarized and analyzed their characteristics and diversity.  Results  Among the 8 patients, 4 were males and 4 were females. The onset age was 3 to 8 months old. Rash was the first symptom in 7 patients(87.5%). 6 patients(75.0%) had papules and erythema.3 cases(37.5%) had arthritis. 2 cases(25.0%) had uveitis and other eye inflammation. 4 cases (50.0%) also showed intermittent fever. 3 cases (37.5%) showed symptoms in nerve and respiratory system, and hypertension respectively. The skin histopathology of 8 patients showed non-caseous granuloma formation. In laboratory detection, CRP and TNF-α were significantly increased before treatment, while IL-6, IL-8, TNF-α and IL-2 receptor(IL-2R) were significantly decreased in 5 patients after glucocorticoid therapy. The results of genetic testing showed that 4 of the 7 patients had p.R334W(c.1000C > T) mutation, 1 had p.H313R(c.938A > G) and p.R471C(c.1411C > T)double mutation, and 1 had p.476_477del (c.1427_1429delcct).  Conclusions  Blau syndrome/early-onset sarcoidosis has significant features in clinical manifestations, histopathology and gene mutation, but it also has diversity.

ObjectiveThis study aimed to investigate the HIV genotypic subtypes and molecular transmission clusters among men who have sex with men （MSM） with newly reported HIV infections in Dehong Dai and Jingpo Autonomous Prefecture （Dehong Prefecture）， Yunnan Province， China， between 2010 and 2019. The study aimed to identify potential high-risk transmitters and provide reference data for screening， management， and intervention of infection sources. MethodsPlasma samples from newly reported HIV-positive MSM individuals in Dehong Prefecture between 2010 and 2019 were collected. The viral pol gene fragments were amplified， sequenced， and genotyped. Genetic distances （GD） between pairwise sequences were analyzed and calculated. MEGA 7.0 and Gephi were used for phylogenetic and molecular transmission network analysis. ResultsA total of 159 newly reported HIV infections among MSM were included in the study， with successful genotyping of 100 cases. Nine HIV-1 subtypes were identified， with the most prevalent being CRF01_AE subtype （52%）， followed by CRF07_BC subtype （31%）， CRF55_01B subtype （10%）， and others （7%）. Cluster analysis revealed a total network access rate of 67%， forming three transmission clusters. CRF01_AE subtype formed two transmission clusters with 38 and 3 infected individuals， while CRF07_BC subtypes formed one transmission cluster with 26 infected individuals. The transmission network within the CRF01_AE clusters exhibited a more complex relationship. Significant differences in educational level were observed between the two main transmission clusters. ConclusionThe predominant HIV subtypes among newly reported MSM cases in Dehong Prefecture between 2010 and 2019 were CRF01_AE and CRF07_BC. Significant cultural differences are observed between the main transmission clusters. Continued monitoring of genotypic subtypes and targeted interventions within transmission clusters are warranted.

Abstract: This research aimed to explore the application of the combination of region growth and U-Net in the retinal vessel segmentation system, retinal vessels were automatically segmented through the developed system. This research provides doctors with accurate information on changes in the retinal blood vessel structure, which will improve the efficiency of diagnosis and treatment. Methods: Combined with U-Net network and region growth, the pre-processed retinal blood vessels were automatically segmented, and the algorithms were integrated into the retinal blood vessel segmentation system through the design of controls. Results: The average values of blood vessel segmentation performance indexes— accuracy, sensitivity, and specificity were 0.977 7, 0.768 4, and 0.982 1, respectively, and regional iterative growth could improve the segmentation effect of fine retinal blood vessels. Conclusion The system has the characteristics of simple interface and convenient operation.It realizes automatic retinal blood vessel segmentation with high precision and visualization, provides an effective application platform for doctors to observe the changes of retinal vascular structure, and also provides a thinking direction for doctors to judge the nature of lesions.

Objective: To understand knowledge, attitude and behavior toward Coronavirus disease 2019 (COVID 19) among middle school students in Wuhan, in the phase of normalized control and prevention of COVID 19, so as to provide evidence for further health education. Methods: In January 2021, cluster random sampling method was used to select one middle school from Hongshan and Dongxihu District, as well as Donghu high tech zone, respectively. By using the "questionnaire star" platform, questionnaire QR code were sent to students through QQ or wechat by schools. A total of 4 531 middle school students were investigated. Results: Preventive knowledge and behavior rate was 71.5% (3 238) and 56.0% (2 537), respectively. Preventive behaviors towards COVD 19 was reported in 56.0% (2 537) of participants. Students with parents as health care workers reported higher preventive behaviors(P<0.05).Girls had a higher rate of possession of health knowledge for prevention and control than boys. Compared with "essentially no concern about the epidemic","students with less concern about the epidemic" and "those with similar concern as 2020" were more likely to have higher awareness of health knowledge for prevention and control. Compared with the first-year junior middle school students, high school students were less likely to have the rates of knowledge for prevention and control health [OR(95%CI）=1.24（1.09-1.43）,2.56(1.54-4.25),3.30(1.99-5.48),0.49(0.39-0.62),0.45(0.36-0.57),0.63(0.46-0.88)].In terms of health behavior rate, middle school students whose mothers are undergraduates, whose incomes were more than 8 001-15 000 and 15 000 yuan, "whose attention to epidemic situation has declined" , "whose attention is the same as that in 2020" , "who did not plan to study medicine before" , "who are determined to study medicine, and who plan to study medicine more firmly after epidemic situation " were more likely to have health behavior,[OR(95%CI)=1.29(1.04-1.60),1.39（1.07-1.82）,1.74(1.32-2.29),1.77(1.06-2.96),3.47(2.08-5.81)] ,The grade-2 high middle school students had lower probability of preventing and controlling health behaviors [OR(95%CI)=0.74(0.60-0.90)](P<0.05). Preventive knowledge and behaviors towards COVID 19 are mainly from school education, communication with parents and mobile learning. Conclusion Preventive knowledge and behaviors towards COVID 19 among Wuhan middle school students are needed to be improved and targeted health education should be implemented accordingly.

Objective:To investigate the predictive value of 3-hour post-endoscopic retrograde cholangiopancreatography (ERCP) serum amylase and lipase levels for postoperative pancreatitis (PEP).Methods:Clinical data of patients who underwent ERCP from June 2017 to December 2018 in our hospital were retrospectively analyzed. Risk factors of PEP were examined with univariate and multivariate analysis. Receiver operator characteristic (ROC) curve for 3-h postoperative serum amylase and lipase was generated and the optimal cut-off levels for PEP prediction were calculated.Results:A total of 491 patients were enrolled in this study, and 29 patients developed PEP. Compared with the uncomplicated group, female gender [75.9% (22/29) vs. 49.1% (227/462)], pancreatogram [65.5% (19/29) vs. 32.0% (148/462)], pancreatic duct cannulation [27.6% (8/29) vs. 11.7% (54/462)] and coronary heart disease [17.2% (5/29) vs. 4.5% (21/462)] accounted for a significant higher proportion in PEP group (χ 2=7.79, 13.63, 6.25, 6.42, all P<0.05), while logistic regression analysis revealed that only pancreatic duct cannulation was an independent risk factor ( OR=3.574, 95 %CI: 1.315-9.713, P<0.05). Areas under the ROC curve of serum amylase and lipase at 3 h were 0.897 (95 %CI: 0.842-0.951, P<0.01) and 0.915 (95 %CI: 0.881-0.948, P<0.01), respectively ( Z=0.550, P>0.05). For amylase, ideal sensitivity(93.1%) and specificity(93.3%) could be obtained as cut-off levels>1.0 and 3.0 times the upper limit reference (ULR), respectively. Correspondingly, as cut-off levels for lipase>2.5 and 6.0 times the ULR, the sensitivity was 93.1% and specificity was 91.3%, respectively. Conclusion:Three-hour postoperative serum amylase and lipase are both ideal indicators for predicting PEP with similar clinical value.

Objective To study the effect of amino acid site variation of HIV-1 Nef protein on its inhibition of neuronal autophagy and explore the mechanism of Nef protein-induced central nervous system injury.Methods HIV-1 nef genes were amplified and cloned from the temporal cortex (TC) of the central nervous system in 1 case of HIV-associated dementia (HAD) H and 1 case of non-HAD AIDS patient N.The amino acid sequences were aligned by NCBI BLAST tools and MEGA6.0 software to study the variation of amino acid sites.The eukaryotic expression vectors pEGFP-N1-nef derived from H-TC and N-TC were constructed and transfected into U87 cells to observe green fluorescence.At the same time,the expression of Nef protein,LC3-Ⅱ and p62 protein in U87 cells were detected by Western blot,and the effects of different sources of Nef on autophagy of U87 cells were analyzed.Results The nef genes were amplified by PCR and clone vectors pMD-19T-nef of H-TC and N-TC were successfully constructed.The sequencing confirmed that they were HIV-1B subtypes.The amino acid sequence analysis showed that there were differences between H-TC and N-TC key amino acid sites.The recombinant plasmid pEGFP-N1-nefwas successfully constructed and expressed Nef protein in U87 cells.Western blot analysis showed that the expression of LC3-Ⅱ protein was significantly different among groups (F =11.764,P =0.001).There was no significant difference in the expression of LC3-Ⅱ between cell control and plasmid control(P=0.169).The content of LC3-Ⅱ was low in the two groups of cells,which could not be detected by Western blot.The expression of LC3-Ⅱ in H-TC,N-TC and positive control CQ group increased,compared with blank control or blank vector.The difference was statistically significant (P=0.017,P=0.039,P=0.031),and the expression of LC3-Ⅱ in H-TC group was higher than that in N-TC group (P =0.023);the expression of p62 protein in H-TC,N-TC and positive control CQ group was higher than that in blank control or blank vector group,but there was no significant difference between groups (F=2.049,P =0.163).Conclusions HIV-1 Nef amino acid sites in the central nervous system of patients with HAD and non-HAD were different,and their effects on autophagy of U87 cells were different.The expression of LC3-Ⅱ,an autophagic marker protein,was more strongly induced by Nef from H-TC.

OBJECTIVETo investigate the association between maternal serum neutrophil-lymphocyte ratio (NLR) and placental inflammatory response (PIR) in late pregnancy.

METHODSWe retrospectively analyzed the clinical and follow-up data of 478 pregnant women undergoing routine prenatal examination and delivery in our hospital in the year 2016. According to the placental pathological results, the women were divided into PIR group (238 cases) and control group (240 cases). The levels of serum inflammatory makers including leukocytes, neutrophils, lymphocytes, C-reactive protein (CRP) and NLR were compared between the two groups to analyze the association of these markers with PIR. Multivariate analysis was performed to identify the independent risk factors of PIR. Logistic regression model was established and the area under the receiver operating characteristic curve (ROC) was used for analyzing the prognostic value of these makers in late pregnancy.

RESULTSThe areas under the curve (AUC) of leukocytes, neutrophils, lymphocytes, CRP and NLR were 0.698 (95%: 0.485-0.766), 0.716 (95%: 0.453-0.783), 0.329 (95%: 0.228-0.431), 0.725 (95%: 0.677-0.765) and 0.801 (95%: 0.742-0.856), respectively. After adjusting the confounders, multivariate logistic regression analysis showed that preterm labor (OR=2.446, 95%: 1.003-4.590), premature rupture of membranes (OR=2.304, 95%: 1.049-4.161), NLR > 7 (OR=3.268, 95%: 2.071-6.920), and CRP > 15 mg/L (OR=2.137, 95%: 1.412-8.236) were independent risk factors for PIR.

CONCLUSIONSAn increased NLR in late pregnancy can serve as an effective indicator for predicting the risk of PIR.