Objective:To understand the negative conversion of syphilis-specific antibody in follow-up in 0-18 months-old children born to pregnant women with syphilis in China in 2021 and analyze the related factors.Methods:The basic information of pregnant women with syphilis and follow-up information of their children in 2021 were extracted from the National Management Information System for the Prevention of mother-to-child transmission of HIV, syphilis and Hepatitis B. The logistic regression model was used to analyze related factors of negative conversion of syphilis-specific antibody.Results:In 2021, a total of 34 201 children was delivered by syphilis-infected pregnant women, and 23 592 (68.98%) children were included in this study. Negative conversion of syphilis-specific antibody occurred in 21 076 (89.34%) children, but not in 2 516 (10.66%) children. Multivariate logistic regression analysis identified several factors associated with a higher probability of the negative conversion of syphilis-specific antibody: prophylactic benzathine penicillin injection at birth (a OR=1.35,95% CI:1.10-1.65), mother's age 26-30 years (a OR=1.22,95% CI:1.01-1.46), 36-40 years (a OR=1.34, 95% CI:1.09-1.64), other ethnic groups (a OR=1.19,95% CI:1.04-1.36), non-syphilis-specific antibody titers less than 1∶8 during pregnancy (a OR=1.56,95% CI:1.37-1.78), penicillin treatment (a OR=1.56,95% CI:1.23-1.98) and standardized treatment (a OR=1.21,95% CI:1.11-1.32). Conclusions:In 2021,the level of syphilitic-specific antibody negative conversion in follow-up in children born to pregnant women with syphilis was high in China. According to the factors associated with syphilis-specific antibody negative conversion, it is necessary to develop the follow-up strategies for the children born to pregnant women.

Objective:To understand the negative conversion of syphilis-specific antibody in follow-up in 0-18 months-old children born to pregnant women with syphilis in China in 2021 and analyze the related factors.Methods:The basic information of pregnant women with syphilis and follow-up information of their children in 2021 were extracted from the National Management Information System for the Prevention of mother-to-child transmission of HIV, syphilis and Hepatitis B. The logistic regression model was used to analyze related factors of negative conversion of syphilis-specific antibody.Results:In 2021, a total of 34 201 children was delivered by syphilis-infected pregnant women, and 23 592 (68.98%) children were included in this study. Negative conversion of syphilis-specific antibody occurred in 21 076 (89.34%) children, but not in 2 516 (10.66%) children. Multivariate logistic regression analysis identified several factors associated with a higher probability of the negative conversion of syphilis-specific antibody: prophylactic benzathine penicillin injection at birth (a OR=1.35,95% CI:1.10-1.65), mother's age 26-30 years (a OR=1.22,95% CI:1.01-1.46), 36-40 years (a OR=1.34, 95% CI:1.09-1.64), other ethnic groups (a OR=1.19,95% CI:1.04-1.36), non-syphilis-specific antibody titers less than 1∶8 during pregnancy (a OR=1.56,95% CI:1.37-1.78), penicillin treatment (a OR=1.56,95% CI:1.23-1.98) and standardized treatment (a OR=1.21,95% CI:1.11-1.32). Conclusions:In 2021,the level of syphilitic-specific antibody negative conversion in follow-up in children born to pregnant women with syphilis was high in China. According to the factors associated with syphilis-specific antibody negative conversion, it is necessary to develop the follow-up strategies for the children born to pregnant women.

Objective:To construct a nanoparticle vaccine displaying the prefusion F (preF) protein of respiratory syncytial virus (RSV) using the I53-50 protein nanoparticle platform, and to systematically evaluate its immunogenicity and protective efficacy.Methods:The RSV preF trimer antigen was genetically fused to I53-50A and assembled in vitro with I53-50B to form preF-I53-50 nanoparticles, theoretically displaying 20 preF antigens per particle. The structure and purity were characterized by size-exclusion chromatography, SDS-PAGE, and negative-stain electron microscopy. BALB/c mice were intramuscularly immunized with varying doses (1 μg or 5 μg) of preF antigen or an equimolar amount of preF-I53-50 nanoparticles. Humoral immunity, B-cell responses, and protective efficacy were assessed following intranasal viral challenge.Results:The preF-I53-50 nanoparticles self-assembled into spherical structures (50-60 nm in diameter) with uniformly arrayed antigens. The nanoparticle vaccine enhanced RSV-specific IgG1 and IgG2a antibody responses, promoting a Th1-biased immune profile. At equimolar preF doses, the neutralizing antibody titers induced by 1 μg and 5 μg nanoparticle formulations were 2.8-fold and 2.3-fold higher, respectively, than those elicited by preF alone ( P<0.05). Notably, even the low-dose nanoparticle group outperformed the high-dose preF group (1.6-fold increase). Viral challenge experiments demonstrated that preF-I53-50 effectively suppressed pulmonary viral replication, mitigated pathological damage, and induced stronger germinal center and memory B-cell responses, suggesting enhanced B-cell affinity maturation and long-term immune memory. Conclusion:The preF-I53-50 vaccine improves the immunogenicity and protective efficacy of RSV preF through multivalent antigen display.

Objective:To investigate the safety of Holmium laser enucleation of the prostate (HoLEP) and bipolar plasma resection of prostate (BPRP) in the treatment of large volume benign prostatic hyperplasia (LV-BPH), and to analyze their long-term follow-up results.Methods:Two hundred patients of LV-BPH admitted to Cangzhou Hospital of Integrated TCM-WM·Hebei from January 2022 to January 2024 were retrospectively selected and divided into BPRP group and HoLEP group according to different treatment methods, with 100 cases in each group. Patients in BPRP group were treated with BPRP, and patients in HoLEP group were treated with HoLEP. The clinical data, perioperative indicators, postoperative complications and long-term follow-up results were compared between groups. Measurement data were expressed as mean±standard deviation ( ± s), paired sample t-test was used for intra-group comparison, covariance analysis or independent sample t-test was used for inter-group comparison, and analysis of variance of repeated measurement data was used for multi-time node comparison. Count data were expressed as the cases and percentage, and Chi-square test was used for comparison between groups. Results:The operation time [(31.46±13.47) min vs (40.25±15.33) min], clearance time [(28.14±12.94) min vs (37.16±13.15) min] and the decrease in hemoglobin [(5.14±1.93) g/L vs (7.92±2.45) g/L] of patients in the HoLEP group were lower than those in the BPRP group, and the clearance efficiency [(1.58±0.19) g/min vs (1.30±0.10) g/min] was higher than that in the BPRP group, and the differences were statistically significant ( P<0.05). The incidence of postoperative hematuria (1.00% vs 8.00%) in HoLEP group was lower than that in BPRP group, and the difference was statistically significant ( P<0.05). There were no statistically significant differences in the incidence of other complications and total complications except hematuria between BPRP group and HoLEP group ( P>0.05). The results of covariance analysis showed that there were no statistically significant differences in serum sodium, prostate specific antigen (PSA) levels, maximum urine flow rate (Qmax), postvoid residual urine (PVR), international prostate symptom score (IPSS) and quality of life (QOL) score at different time points after the operation ( P>0.05). The analysis of variance of repeated measurement data showed that the group effects of the above indexes were F=0.91, 0.52, 1.30, 0.40, 0.02, 0.63, respectively, all P>0.05, and the time effects were F=18.57, 104.31, 814.68, 1 106.64, 1 894.37, 555.31, respectively, all P<0.001, and the interaction effects were F=2.79, 0.75, 1.22, 1.20, 0.02, 0.72, respectively, all P>0.05. Conclusions:The application of HoLEP and BPRP in LV-BPH patients are beneficial to improve prostate symptoms and quality of life, with equal safety and effectiveness. However, compared with BPRP, HoLEP applied to LV-BPH patients has the advantages of short operation time, high clearance efficiency, small decrease of hemoglobin and low risk of postoperative hematuria.

Objective:To construct a nanoparticle vaccine displaying the prefusion F (preF) protein of respiratory syncytial virus (RSV) using the I53-50 protein nanoparticle platform, and to systematically evaluate its immunogenicity and protective efficacy.Methods:The RSV preF trimer antigen was genetically fused to I53-50A and assembled in vitro with I53-50B to form preF-I53-50 nanoparticles, theoretically displaying 20 preF antigens per particle. The structure and purity were characterized by size-exclusion chromatography, SDS-PAGE, and negative-stain electron microscopy. BALB/c mice were intramuscularly immunized with varying doses (1 μg or 5 μg) of preF antigen or an equimolar amount of preF-I53-50 nanoparticles. Humoral immunity, B-cell responses, and protective efficacy were assessed following intranasal viral challenge.Results:The preF-I53-50 nanoparticles self-assembled into spherical structures (50-60 nm in diameter) with uniformly arrayed antigens. The nanoparticle vaccine enhanced RSV-specific IgG1 and IgG2a antibody responses, promoting a Th1-biased immune profile. At equimolar preF doses, the neutralizing antibody titers induced by 1 μg and 5 μg nanoparticle formulations were 2.8-fold and 2.3-fold higher, respectively, than those elicited by preF alone ( P<0.05). Notably, even the low-dose nanoparticle group outperformed the high-dose preF group (1.6-fold increase). Viral challenge experiments demonstrated that preF-I53-50 effectively suppressed pulmonary viral replication, mitigated pathological damage, and induced stronger germinal center and memory B-cell responses, suggesting enhanced B-cell affinity maturation and long-term immune memory. Conclusion:The preF-I53-50 vaccine improves the immunogenicity and protective efficacy of RSV preF through multivalent antigen display.

OBJECTIVE To investigate the current status of quality management of cold chain medicines in direct-to-patient(DTP)pharmacies and propose measures for pre-emptive risk management,providing references for the quality risk management of cold chain medicines.METHODS Based on the requirements of national regulations,a survey was conducted on the quality management of cold chain medicines in DTP pharmacies of J Province from November 2023 to February 2024,focusing on the receipt,storage,distribution,and delivery processes,using questionnaires,telephone interviews,and on-site visits.Common quality management issues in the operation of cold chain medicines were identified,and the causes of these issues were analyzed to propose feasible pre-emptive risk management measures.RESULTS&CONCLUSIONS A total of 122 DTP pharmacies participated in the questionnaire survey,and personnel from 30 DTP pharmacies participated in on-site and telephone interviews.Typical problems were identified in some DTP pharmacies,including insufficient personnel allocation or training,incomplete or inadequate implementation of quality system documentation,inadequate provision or management of cold chain facilities and equipment,and non-compliant storage and distribution of cold chain medicines.These issues posed certain risks to the quality management of cold chain medicines.It is recommended that DTP pharmacies strengthen personnel allocation and training,improve quality system documentation,enhance the provision and management of facilities and equipment,standardize storage and transportation operations,and strengthen supervision and assessment as pre-emptive measures.In addition,all sectors of society should also collaborate in governance from the perspective of ensuring the safety of cold chain drug storage and transportation,in order to mitigate the risk of quality and safety issues during the distribution of cold chain drugs and guarantee the safe and effective use of medications for patients.

At present,there are policies for hepatitis B testing in 89.8%of countries and regions around the world.In 2022,the global hepatitis B vaccine birth dose coverage reached 45%,while the third-dose coverage reached 85%.Approximately 3%of pregnant women with high viral loads have received antiviral therapy,and the prevalence rate of HBsAg is about 0.7%among children aged≤5 years.While significant progress has been made in various countries towards eliminating mother-to-child transmission of hepatitis B virus(HBV),there are still large gaps across countries and numerous challenges.There are differences in the prevalence of hepatitis B,vaccination,and access to antiviral drugs across the globe,and in addition,the factors such as insufficient laboratory testing capacity and difficulties in ensuring sustained access to treatment among pregnant and parturient women with HBV infection pose obstacles to eliminating the mother-to-child transmission of HBV.

Objective:To construct a nomogram for predicting unfavorable prognosis at 6 months after moderate and severe traumatic brain injury (msTBI) and validate its predictive effectiveness.Methods:A retrospective cohort study was conducted to analyze the clinical data of 387 patients with msTBI who were admitted to 904th Hospital of the Joint Logistic Support Force of PLA from January 2020 to December 2022, including 265 males and 122 females, aged 6-97 years [58(47, 68)years]. According to the Glasgow outcome scale (GOS) score at 6 months after injury, the patients were divided into favorable prognosis group (GOS 4-5 points, n=201) and unfavorable prognosis group (GOS 1-3 points, n=186). The clinical characteristics, imaging manifestations, and laboratory test results of the two groups on admission were recorded. Univariate analysis was applied to evaluate the correlation between the aforementioned indicators and the unfavorable prognosis of the msTBI patients at 6 months after injury. Receiver operating characteristic (ROC) curves of single variable and the correlation heatmap among continuous variables were plotted. Lasso regression was used to select variables and multivariate Logistic regression analysis was used to determine independent predictive factors so as to construct Logistic regression equation and plot the nomogram. The internal verification was carried out by means of random and non-random split of data. In random split, the data were divided randomly with a ratio of 6∶4 into training group ( n=232) and verification group ( n=155). In non-random split, the patients admitted from January 2020 to December 2021 were assigned to the training group ( n=260), while those admitted from January 2022 to December 2022 to the verification group ( n=127). Area under the curve (AUC) was used to evaluate the predictive ability of the model in the training group and verification group, calibration curve and Hosmer-Lemeshow (H-L) test to evaluate its goodness of fit, and decision curve analysis (DCA) to evaluate its clinical applicability. The influence of inclusion of neutrophil-to-lymphocyte ratio (NLR) model on the warning effectiveness of poor prognosis was analyzed in comparison with the model without inclusion of NLR. Results:Univariate analysis showed that there was a certain correlation between age, length of hospital stay, Glasgow coma scale (GCS), American Society of Anesthesiologists Physical Status (ASA-PS) classification, Injury severity score (ISS), prehospital tracheal intubation, hypotension, hypoxia, pupillary responsiveness, midline shift, basilar cisterna status, traumatic subarachnoid hemorrhage (tSAH), D-Dimer, prothrombin time activity (PTA), glucose, hemoglobin, K +, Cl -, Ca 2+, HCO -, creatinine, albumin, lactic acid, platelet, lymphocyte, systemic immune-inflammation index (SII), NLR, lymphocyte-to-monocyte ratio (LMR) and unfavorable prognosis of msTBI patients at 6 months after injury ( P<0.05 or 0.01). The ROC curve of single variable showed that GCS (AUC=0.82), ISS (AUC=0.81), pupillary responsiveness (AUC=0.76), basal cistern status (AUC=0.73) and NLR (AUC=0.73) had good predictive validity. The results of the correlation heatmap showed that there was a significant correlation and collinearity among the continuous variables, while no collinearity was found between ISS and NLR. Fourteen potential predictors selected by Lasso regression were included in multivariate Logistic regression analysis and its results showed that age ( OR=0.86, 95% CI 1.38, 5.19), GCS 6-8 points ( OR=3.13, 95% CI 1.06, 9.27), GCS 3-5 points ( OR=12.36, 95% CI 2.81, 54.27), ISS ( OR=3.68, 95% CI 1.38, 9.80), pupillary responsiveness ( OR=2.45, 95% CI 0.85, 7.07), and NLR ( OR=2.62, 95% CI 1.52, 4.51) were identified as the independent risk factors for unfavorable prognosis of msTBI patients at 6 months after injury ( P<0.05 or 0.01). The multivariate Logistic regression equation was Logit [P/(1-P)]=0.066×"age"+ 1.474×"GCS 6-8"+2.357×"GCS 3-5"+0.066×"ISS"+0.965×"absence of pupillary light reflex"+0.194×"NLR"-10.704. In the internal verification of random split of data, the AUC value of the model was 0.93 (95% CI 0.89, 0.96) in the training group and 0.93 (95% CI 0.89, 0.97) in the verification group. In the internal verification of non-random split, the AUC value was 0.94 (95% CI 0.91, 0.97) in the training group and 0.93 (95% CI 0.89, 0.97) in the verification group. The calibration curve and H-L test showed that the model had good calibration ability ( P>0.5). The results of DCA showed that the application of the nomogram would increase the net benefit of the patients (risk threshold probability of 0.0-0.8). Compared with the conventional model (AUC=0.90), inclusion of NLR model (AUC=0.93) enhanced the warning effectiveness. Conclusions:Age, GCS, ISS, pupillary responsiveness and NLR are independent risk factors affecting unfavorable prognosis in msTBI patients at 6 months after injury, based on which the nomogram constructed can better predict the clinical outcome of msTBI patients.

Objective:To establish a Plaque-reduction Neutralization Test (PRNT) for the detection of neutralizing antibody titers of Human Respiratory Syncytial Virus (HRSV) and optimize the conditions for preliminary application.Methods:The CHO expression system was used to produce palivizumab monoclonal antibody (palivizumab) and the influencing factors such as cell type, cell culture duration, fixation and permeabilization protocols, and blocking agents. The reproducibility of the method was verified and its correlation was verified with conventional PRNT. Finally, the optimized PRNT assay was further used to determine neutralizing antibody titers against HRSV subtypes A and B in BALB/c mouse serum (immunized by intramuscular injection of HRSV fusion proteins).Results:Palivizumab was expressed at approximately 50 mg/L. The optimal working conditions for PRNT were as follows: culturing HEp-2 cells for 2 days, fixing with 4% (V/V) paraformaldehyde at room temperature for 15 min followed by 0.2% (V/V) Triton X-100 permeabilization for 15 minutes as the optimal fixation-permeabilization and removing the blocking step. The overall coefficient of variation (CV) for the reproducibility validation of this method was <15%, showing a good linear relationship with the conventional PRNT. The Spearman correlation coefficient r s was 0.983. This method was used to detect neutralizing antibody titers in mouse sera against HRSV subtype A strain long and subtype B strain 9320, and the fusion proteins combined with AlOH and CpG adjuvant induced the highest neutralizing antibody titers in mice. Conclusion:The HRSV neutralizing antibody assay established in this study is rapid, reproducible, high-throughput, and can be used to detect neutralizing antibodies to HRSV subtypes A and B.

Objective:To establish a Plaque-reduction Neutralization Test (PRNT) for the detection of neutralizing antibody titers of Human Respiratory Syncytial Virus (HRSV) and optimize the conditions for preliminary application.Methods:The CHO expression system was used to produce palivizumab monoclonal antibody (palivizumab) and the influencing factors such as cell type, cell culture duration, fixation and permeabilization protocols, and blocking agents. The reproducibility of the method was verified and its correlation was verified with conventional PRNT. Finally, the optimized PRNT assay was further used to determine neutralizing antibody titers against HRSV subtypes A and B in BALB/c mouse serum (immunized by intramuscular injection of HRSV fusion proteins).Results:Palivizumab was expressed at approximately 50 mg/L. The optimal working conditions for PRNT were as follows: culturing HEp-2 cells for 2 days, fixing with 4% (V/V) paraformaldehyde at room temperature for 15 min followed by 0.2% (V/V) Triton X-100 permeabilization for 15 minutes as the optimal fixation-permeabilization and removing the blocking step. The overall coefficient of variation (CV) for the reproducibility validation of this method was <15%, showing a good linear relationship with the conventional PRNT. The Spearman correlation coefficient r s was 0.983. This method was used to detect neutralizing antibody titers in mouse sera against HRSV subtype A strain long and subtype B strain 9320, and the fusion proteins combined with AlOH and CpG adjuvant induced the highest neutralizing antibody titers in mice. Conclusion:The HRSV neutralizing antibody assay established in this study is rapid, reproducible, high-throughput, and can be used to detect neutralizing antibodies to HRSV subtypes A and B.