OBJECTIVE To evaluate the cost-effectiveness of cefiderocol versus best available therapy （BAT） or standard-of- care （SOC） for the treatment of confirmed or suspected carbapenem-resistant Gram-negative bacterial （CRGNB） serious infections from the perspective of the Chinese healthcare system， and to explore its reasonable pricing. METHODS A decision tree model was constructed based on data from two phase Ⅲ clinical trials （CREDIBLE-CR and GAME CHANGER） to simulate the cost- effectiveness of cefiderocol in two scenarios： salvage therapy for confirmed CRGNB infection （scenario 1） and empirical therapy for suspected CRGNB infection （scenario 2）. The primary outcome measure was the incremental cost-effectiveness ratio （ICER）. The willingness-to-pay （WTP） was set at 1 to 3 times China’s per capita GDP in 2024. To verify the robustness of the results， one- way and probabilistic sensitivity analyses were conducted， and based on these， a reasonable price range for cefiderocol in the Chinese market was explored. RESULTS The results for scenario 1 showed that the clinical cure rate in the cefiderocol group was higher than that in the BAT group （47.50% vs. 34.21%）， but its ICER was 415 065.03 yuan per cured case， exceeding three times China’s GDP per capita. Scenario 2 revealed that the ICER for cefiderocol relative to SOC was as high as 1 362 446.16 yuan per cured case， far exceeding the WTP. Sensitivity analysis indicated that the treatment duration and price of cefiderocol were key factors affecting its cost-effectiveness. In the two scenarios described above， the unit price of cefiderocol must fall below 683.47 and 242.00 yuan/g， respectively， to be considered cost-effective. CONCLUSIONS Based on the current market price， cefiderocol lacks sufficient cost-effectiveness for treating confirmed or suspected CRGNB serious infections within China’s healthcare system. To improve its accessibility， price negotiations or a tiered medical insurance payment strategy are required.

OBJECTIVE To evaluate the efficacy， safety and cost-effectiveness of serplulimab as a first-line treatment of small- cell lung cancer （SCLC）， and provide an evidence-based basis for drug selection in hospitals. METHODS Rapid health technology assessment was adopted； PubMed， Cochrane Library， Embase， CNKI， Wanfang， VIP and official websites of domestic and international health technology assessment agencies were systematically searched from the inception to Oct. 2024. Two reviewers independently screened the literature， assessed the quality of included studies and carried out the qualitative analysis according to the inclusion and exclusion criteria. RESULTS A total of 13 systematic reviews/meta-analyses and 9 economic studies were included， and the literature quality was generally good. In terms of effectiveness， compared with chemotherapy alone， serplulimab combined with chemotherapy significantly improved progression-free survival， overall survival， and objective response rate in patients with SCLC. In terms of safety， serplulimab combined with chemotherapy showed no significant difference in the incidence of ≥3 grade adverse events compared with chemotherapy alone in the treatment of SCLC， indicating a good safety profile； compared with combination therapies involving other immunosuppressive agents， the incidence rate of adverse events was also lower. In terms of cost-effectiveness， compared with chemotherapy alone， serplulimab combined with chemotherapy is not cost- effective， which may be related to the high price of serplulimab. CONCLUSIONS Serplulimab is effective and safe in the treatment of SCLC， but has no obvious advantage in terms of cost-effectiveness.

Objective:To analyze the growth characteristics of different genotypes of Japanese encephalitis virus (JEV) in different cell lines, and to provide scientific basis for the selection of cell lines in the study of JEV.Methods:BHK-21, Vero, C6/36, PK-15, DF-1, N2a, SH-sy5y and MDCK cell lines were selected. The proliferation ability of genotype 1 (NX1889 strain), genotype 3 (P3 strain) and genotype 5 (XZ0934 strain) JEV in these cell lines was evaluated by plaque assay and RT-qPCR.Results:Significant cytopathogenic effects (CPE) were observed in BHK-21, Vero, C6/36, DF-1, N2a and PK-15 cell lines across all three JEV genotypes. However, no significant differences in CPE characteristics were observed within the same cell line. SH-sy5y and MDCK cell lines did not show significant CPE, but virus proliferation was detected in SH-sy5y cell line, while MDCK cell line were found to be insensitive to JEV. No significant difference was observed in the proliferation curves of G1, G3 and G5 JEV in BHK-21, Vero and SH-sy5y cell lines. In C6/36 and PK-15 cell lines, the titer of G1 JEV was higher than that of G3 and G5. In DF-1 cell line, G5 demonstrated a higher titer than the other two genotypes, whereas in N2a cell line, G5 showed a lower titer than the other two.Conclusions:There are differences in the proliferation of three different genotypes of JEV in different cell lines, which can provide reference for the study of JEV in different directions.

Objective:To establish a rapid method for the detection of varicella-zoster virus (VZV) by recombinase-aid amplification (RAA).Methods:The whole genome sequences of VZV were downloaded from the global shared database for comparison and analysis. Specific primers and probe were designed for the four conserved genes respectively and the optimal combination was selected. The optimal reaction system was selected through the concentration gradient of primers and probes, and a fluorescence RAA detection method was established. The sensitivity of the method was evaluated with VZV positive plasmid standard and clinical samples with gradient dilution, the repeatability of the method was evaluated with the lowest detectable limit concentration of positive plasmid standard, and the specificity of other viral nucleic acid method was evaluated. At the same time, this method and quantitative real-time PCR (qPCR) were used to detect clinical samples and the result were compared.Results:The optimal combination of primer pair F2/R2 and probe P2 targeting open reading frame (ORF) 28 gene was selected. Considering the cost factor, the optimal primer concentration was set at 500 nmol/L and the optimal probe concentration was 280 nmol/L. The minimum detection limit was 10 1 copies/μL, and the minimum clinical positive samples with a Ct value of 36.027 could be detected, and the result of repeated experiments were consistent. The method has no cross-reaction with other viral nucleic acids. The detection rate of clinical positive samples was 93.33%, which was almost identical to that of qPCR. Conclusions:This method is simple to operate with high sensitivity, strong specificity, low requirements for experimental conditions, visual detection result, and can detect VZV nucleic acid in samples within 20 minutes, which is a rapid VZV detection method that can be considered for clinical use for detection.

Objective:To explore the value of multiparametric ultrasonography consisting of gray-scale ultrasound(US), color Doppler flow imaging (CDFI), real-time strain elastography(RTE), and contrast-enhanced ultrasound(CEUS) in the differential diagnosis of testicular lesions.Methods:Forty patients (40 lesions) detected by ultrasonography examination at the Ultrasound Medical Center of Lanzhou University Second Hospital from June 2020 to June 2022 were retrospectively analyzed, and further the CDFI, CEUS and RTE were performed. The presence of vascularization in the lesion was determined by CDFI and CEUS, avascular lesions were defined as benign, vascularization lesions were defined as malignant. The lesion tissue elasticity was assessed by real-time strain elastography, tissue stiffness was encoded as red(soft), green(intermediate), and blue(hard), and the hard lesions were defined as malignant, soft lesions were defined as benign. All lesions were subjected to pathological histologic examination after surgical resection or puncture biopsy as a reference standard. The correct classification rate, sensitivity, specificity and likelihood ratio of the multiparametric ultrasonography imaging for the diagnosis of benign and malignant testicular lesions were analyzed by ROC.Results:Of 40 testicular lesions, 24 (60.0%) were benign and 16 (40.0%) were malignant. The sensitivity of CDFI, CEUS and RTE in the diagnosis of testicular lesions was 0.875, 1.000 and 1.000, and the specificity was 0.833, 0.750 and 0.708, respectively. The correct classification rate was 85.0%, 85.0% and 82.5%, and the positive likelihood ratio was 5.24, 4.00 and 4.42, respectively. AUC was 0.781, 0.802, 0.771, respectively. By combining RTE and CDFI, a sensitivity of 1.000 and specificity of 0.875 and correct classification rate of 92.8% and positive likelihood ratio of 8.00 and AUC of 0.915 ( P<0.001) were achieved in differentiating testicular lesions. And combining RTE and CEUS, achieved sensitivity of 1.000 and specificity of 0.917 and correct classification rate of 95.0% and positive likelihood ratio of 12.0 and AUC of 0.958( P<0.001). Conclusions:Multiparametric US is of great value in the differential diagnosis of benign and malignant testicular lesions.

Abstract： Objective　To elucidate the antigenic antibody reaction of recombinant expression of non-structural protein 1 (NS1) of Japanese encephalitis (JE) virus with various mosquito-borne flaviviruses, including JE virus, and the antigenic antibody reaction of serum samples of patients infected with JE virus in acute stage. Methods　In this study, Escherichia coli prokaryotic expression vector (pET) system was used to recombinant express Japanese encephalitis virus NS1 gene. Western Blot assay was performed to detect the antibody responses of the recombinantly expressed protein against a variety of mosquito-transmitted flaviviruses, including JE virus, as well as antigen-antibody reactions of serum from patients with acute JE virus infection. Results　The NS1 gene expression product of JE virus (P3 strain) was in the form of an inclusion body, and the denatured and renatured expression product was displayed as a single band in the denatured gel (polyacrylamide gel electrophoresis, PAGE), with a molecular weight of about 45 000. The results of further antigen-antibody analysis showed that the antigen/antibody hybridization reaction of the expression product with polyclonal or monoclonal antibody of JE virus (mosquito isolates, encephalitis isolates) and serum samples of patients with acute JE virus infection could be completely consistent. The recombinant product showed negative antigen/antibody hybridization reactions with mosquito-transmitted flaviviruses, such as dengue virus and yellow fever virus polyclonal antibodies, but positive reactions with polyclonal antibodies to West Nile virus and Murray Valley encephalitis virus. Conclusions　In this study, the recombinant expression of the NS1 protein of JE virus was successfully obtained, and the antigen/antibody reaction between the recombinant protein and samples of patients infected with mosquito-borne flavivirus and JE virus was analyzed. The study results provide important basic data for elucidating the antigen-antibody reaction between the NS1 protein of JE virus and mosquito-borne flavivirus. The recombinant expression protein obtained in this study provides an important material basis for further research on the function of JE virus NS1 protein.

Objective:To develop a suitable scale for assessing the public health safety literacy in residents in China.Methods:The initial scale of Chinese public health safety literacy was developed through theoretical conceptualization, item pooling, field verifying and item inclusion and exclusion. Then the initial scale was converted into an electronic questionnaire. A total of 2 809 residents from 4 provinces were randomly selected for field testing. Classical test theory (CTT) and item response theory (IRT) were used for item reduction. SPSS 23.0 was used for exploratory factor analysis (EFA) and unidimensional testing. Package R 4.1.1 ltm and mirt were used for the analysis of the psychometric properties of items and generate the ICC, IIC and TIF.Results:The initial scale had 30 items (B1-B30), and the test took 9.8 s to complete one item averagely. According to the CTT, B2 was deleted due to coefficient of total correlation (CITC) <0.3 and the item-dimension correlation coefficient (IDCC) <0.4. B23 was deleted due to CITC<0.3, IDCC<0.4 and difficulty index ( W) <0.2. B30 was deleted due to CITC<0.3 and W<0.2. The total Cronbach's α of the scale was 0.923 after deletion. EFA indicated that 14 items should be deleted due to lower factor loadings <0.7. EFA was conducted for remaining 13 items and 2 common factors were extracted, the factor loadings of all items were >0.7, the accumulated variance contribution of the 2 common factors was 63.361%, and the total Cronbach's α was 0.891, showing unidimensionality, IRT was used to test the remaining items. B14 and B20 were deleted due to discrimination coefficient ( a) <0.3, difficulty threshold coefficient ( b) ?[-3,3], the small amount of information and the flat, crowded, non-monotonic ICC, and IIC. Finally, the Cronbach's α of the 11-itemed scale was 0.936 with TLI=0.97, CFI=0.99, and RMSEA =0.03. Conclusion:The final scale has good reliability, validity, discrimination, difficulty level and feasibility, and can be applied for the rapid assessment of public health safety literacy in China.

Objective:To establish a real-time fluorescent quantitative TaqMan reverse transcription polymerase chain reaction (Real-time RT-PCR) detection method for Wuxiang virus (WUXV).Methods:All gene sequences of WUXV were downloaded from GenBank, and multi-sequence alignment analysis was performed using Mega-X. Primers and probes designed for the highly conservative region of S-segment genes were selected to evaluate the specificity, sensitivity and stability of detection reactions.Results:The established method can specifically detect WUXV and does not cross-react with various arboviruses. The lowest detection limit was 1 pfu/ml. The inter-batch variation coefficients of repeated detection cycle threshold ( Ct) of the same sample were all less than 1.00%. TaqMan RT-PCR was used to detect 30 batches of sandflies nucleic acid samples, and 7 of them showed positive amplification curve of WUXV. Conclusions:TaqMan RT-PCR with high sensitivity, specificity and repeatability has been successfully established, which can be used to screen large quantities of samples of WUXV.

Objective:To explore the application value of CT pulmonary function imaging in patients with Coronavirus Disease 2019 (COVID-19) in the convalescent phase.Methods:The COVID-19 patients who were clinically cured and discharged from Union Hospital, Tongji Medical College, Huazhong University of Science and Technology were prospectively collected from January to April 2020. Clinical pulmonary function tests (PFTs) and CT pulmonary function imaging were performed 3 months after discharge. The Philips IntelliSpace Portal image post-processing workstation was used to obtain the paired inspiratory-expiratory CT quantitative indexes of the whole lung, left lung, right lung and five lobes. The patients were divided into two groups according to whether residual lesions remain in inspiratory CT images: non-residual lesion group and residual lesion group. The chi-square test was used to compare the differences in the PFT results between groups; the Mann-Whitney U test was used to compare the differences in PFT indexes [forced expiratory volume in the first second as percentage of predicted value (FEV 1%), FEV 1/forced vital capacity (FEV 1/FVC), total lung capacity as percentage of predicted value (TLC%), FVC%] and the differences in quantitative CT indexes [lung volume (LV), mean lung density (MLD), volume change in inspiratory phase and expiratory phase (?LV)] between groups. Multiple linear regression was used to analyze the relationship between CT pulmonary function imaging and PFT indexes of convalescent COVID-19 patients. Results:Of the 90 patients with COVID-19, 35 were males and 55 were females; 45 were included in the non-residual lesion group and 45 were included in the residual lesion group. Fifty-three patients had clinical pulmonary dysfunction 3 months after discharge, including 22 patients in the non-residual lesion group and 31 patients in the residual lesion group. In patients with residual disease, left lower lobe and right lower lobe LV, left lower lobe and right lower lobe ?LV in the inspiratory and expiratory phase were smaller than those without residual disease; whole lung, left lung, right lung, left upper lobe, left lower lobe and right lower lobe MLD in the inspiratory phase and left lower lobe and right lower lobe MLD in the expiratory phase were greater than those without residual disease ( P<0.05). Since there was no significant difference in FEV 1/FVC and FVC% between residual and non-residual lesion groups ( P>0.05), FEV 1/FVC and FVC% of two groups were combined. Multiple linear regression analysis showed FEV 1/FVC=91.765-0.016×LV in-right middle lobe+0.014×MLD ex-left lower lobe ( R2=0.200, P<0.001), FVC%=-184.122-0.358×MLD in-right lung-0.024×?LV left upper lobe ( R2=0.261, P<0.001). There was significant difference in TLC% between residual and non-residual lesion groups ( P<0.05), so multiple linear regression analysis was performed both in the two groups. In the non-residual lesion group, TLC%=80.645+0.031×LV ex-right lower lobe ( R2=0.132, P<0.001); In the residual lesion group, TLC%=-110.237-0.163×MLD in-right upper lobe-0.098×MLD ex-left upper lobe -0.025×LV ex-right lower lobe ( R2=0.473, P<0.001). Conclusion:CT pulmonary function imaging can quantitatively analyze the whole lung, unilateral lung and lobulated lung, thus reflecting the regional pulmonary function, providing more valuable diagnostic information for the assessment of pulmonary function in convalescent patients with COVID-19.

Background: Porcine circovirus type 2 (PCV2) is an important infectious pathogen implicated in porcine circovirus-associated diseases (PCVAD), which has caused significant economic losses in the pig industry worldwide. Objectives: A suitable viral vector-mediated gene transfer platform for the expression of the capsid protein (Cap) is an attractive strategy. Methods: In the present study, a recombinant adeno-associated virus 8 (rAAV8) vector was constructed to encode Cap (Cap-rAAV) in vitro and in vitro after gene transfer. Results: The obtained results showed that Cap could be expressed in HEK293T cells and BABL/c mice. The results of lymphocytes proliferative, as well as immunoglobulin G (IgG) 2a and interferon-γ showed strong cellular immune responses induced by Cap-rAAV. The enzyme-linked immunosorbent assay titers obtained and the IgG1 and interleukin-4 levels showed that humoral immune responses were also induced by Cap-rAAV. Altogether, these results demonstrated that the rAAV8 vaccine Cap-rAAV can induce strong cellular and humoral immune responses, indicating a potential rAAV8 vaccine against PCV2. Conclusions The injection of rAAV8 encoding PCV2 Cap genes into muscle tissue can ensure long-term, continuous, and systemic expression.