Objective: To systematically analyze the confirmatory positivity of different combinations of HBsAg screening results in blood testing, providing data to support the optimization of blood donor eligibility management. Methods: A retrospective analysis was conducted on blood screening data from 174 266 voluntary blood donor samples at the Chongqing Blood Center between October 2021 and September 2022. Samples with inconsistent results between the two HBsAg enzymelinked immunosorbent assays (ELISA) and individual donor nucleic acid testing (NAT) were confirmed using an electrochemiluminescence immunoassay (ECLIA) and a neutralization test. The detection efficacy of four different HBsAg ELISA reagents was compared using the HBsAg-confirmed positive samples. Results: A total of 767(0.44%) HBV-reactive (HB-sAg and/or HBV DNA reactive) samples were detected. Among them, 344 samples with discordant serological and NAT results were collected, of which 64(18.6%) were confirmed positive by neutralization test. Additionally, 5 samples that were neutralization-negative but double-reactive for HBsAg and HBV DNA were confirmed as positive according to FDA guidance, resulting in a total of 69(20.1%) confirmed HBsAg-positive samples. There were significant differences in the neutralization test confirmation rates among different screening result categories (P<0.05): The group with dual HBsAg reagent reactivity (double reactive) & NAT-negative had the highest confirmation rate (96.9%, 31/32); the group reactive to only reagent 2 (single reactive) had a rate of 25.7% (29/113); while the confirmation rates for samples reactive to only reagent 1 and samples with isolated HBV DNA positivity were extremely low [0(0/34) and 2.4%(4/165), respectively]. The four commercial reagents showed significant differences in their ability to detect confirmed positive samples that were initially single reactive (P<0.05). Conclusion: Given the performance variations among HBsAg screening reagents, thorough performance verification is essential before implementation. When NAT is negative, dual HBsAg reactivity in screening can serve as a basis for confirming infection and directly deferring blood donors. However, confirming infection in donors with single HBsAg reactivity is more challenging, necessitating supplementary tests to rule out infection risk.

Objective To analyze the impact of medical guidance games combined with special-ized nursing on treatment compliance and clinical symptoms in preschool children with pneumonia.Methods A total of 113 preschool children with pneumonia admitted to Beijing Daxing District Peo-ple's Hospital from February 2023 to June 2024 were selected as research subjects and randomly di-vided into control group(n=56)and observation group(n=57).The control group received routine nursing,while the observation group received medical guidance games combined with specialized nursing on the basis of the control group.Treatment compliance,improvement time of clinical symp-toms,and psychological states were compared between the two groups.Results The total treatment compliance rate in the observation group was 98.2％,which was higher than 89.3％in the control group,and the difference was statistically significant(P＜0.05).The disappearance times of symp-toms such as cough,expectoration,dyspnea,and fever in the observation group were all shorter than those in the control group(P＜0.05).After intervention,the scores of the Children's Medical Fear Scale(CMFS)and the Screen for Child Anxiety Related Emotional Disorders(SCARED)in the ob-servation group were both lower than those in the control group(P＜0.05).Conclusion Medical guidance games combined with specialized nursing can improve treatment compliance in preschool children with pneumonia,shorten their recovery time,help alleviate negative emotions such as medi-cal fear and anxiety,and promote disease recovery.

Objectives:The ORION-18 study has demonstrated that inclisiran can significantly reduce low-density lipoprotein cholesterol(LDL-C)and has good safety in Asian atherosclerotic cardiovascular disease(ASCVD)patients or ASCVD high-risk population.This subgroup analysis aims to further evaluate the efficacy and safety of inclisiran in Chinese mainland population.Methods:ORION-18 study is a multi-center,randomized,double-blind,placebo-controlled,phase Ⅲ clinical trial among Asian subjects,Chinese mainland subgroup included 232 ASCVD patients or ASCVD high-risk subjects who had already been treated with diet control and maximum tolerated doses of statins treatment(with or without other lipid-lowering treatments)but still had elevated LDL-C levels.Subjects were randomized in a 1:1 ratio to the inclisiran group and the placebo group(n=116 each),and received 300 mg of inclisiran or placebo respectively on day 0,90 and 270.The primary endpoint was the percentage change in LDL-C from baseline to day 330.The secondary endpoints included the time-adjusted percentage change and absolute change in LDL-C from baseline after day 90 and up to day 360,the absolute change in LDL-C from baseline to day 330,and the percentage changes from baseline to day 330 in proprotein convertase subtilisin/kexin type 9(PCSK9),total cholesterol,apolipoprotein B(ApoB),non-high-density lipoprotein cholesterol(non-HDL-C).Other secondary endpoints included the proportion of participants reaching LDL-C levels of<1.8 mmol/L at day 330,the proportion of participants with≥50%LDL-C reduction from baseline to day 330 and the proportion of participants who attained global lipid targets(the LDL-C target was<1.4 mmol/L for ASCVD patients and<1.8 mmol/L for ASCVD high-risk subjects)at day 330.Safety endpoints included adverse events during treatment,aboratory test abnormalities during treatment,serious adverse events,and assessed their severity and relation to treatment.Results:The inclisiran group showed a placebo-corrected percentage change in LDL-C from baseline to day 330 of-61.16%,and an absolute change of-1.73 mmol/L(both P<0.0001).Compared to the placebo group,the inclisiran group's time-adjusted percentage change in LDL-C from baseline between day 90 and day 360 was-58.51%,and an absolute change of was-1.64 mmol/L(both P<0.0001).At day 330,reductions from baseline were observed in the inclisiran group for PCSK9,total cholesterol,ApoB,non-HDL-C,with placebo-corrected percentage changes of-77.44%,-35.65%,-43.43%,-50.90%(all P<0.0001),respectively.At day 330,79.6%(74/93)of patients in the inclisiran group and 7.8%(6/77)in the placebo group achieved LDL-C levels<1.8 mmol/L,69.9%(65/93)of patients in the inclisiran group and 0%(0/77)in the placebo group achieved≥50%LDL-C reduction from baseline,66.7%(62/93)of patients in the inclisiran group and 2.6%(2/77)in the placebo group achieved their global LDL-C targets.The safety profile of inclisiran treatment over 12 months was comparable to that of the placebo,with no occurrence of treatment-related serious adverse events.Conclusions:In ASCVD patients or ASCVD high-risk subjects in Chinese mainland who have received diet control and maximum tolerable dose statins treatment(with or without other lipid-lowering treatments)and still have elevated LDL-C,inclisiran has a definite efficacy and good safety in reducing LDL-C.The efficacy and safety results of inclisiran assessed in Chinese mainland population are consistent with those of the general Asia population.

Objective:To explore the factors that can predict the outcome of non-invasive ventilation (NIV) in elderly patients with moderate acute respiratory distress syndrome (ARDS) and analyze their clinical application value.Methods:A total of 87 elderly patients with moderate ARDS caused by community-acquired pneumonia admitted to the Emergency Department of Beijing Friendship Hospital from January 2023 to December 2023 were retrospectively selected. Taking the need for conversion to invasive ventilation during treatment as the study endpoint, the patients were divided into NIV success group and failure group. Clinical data of patients were collected every 2 hours starting from 2 hours after the initiation of NIV, and differences between the two groups were compared. The predictive efficacy of potential risk factors was evaluated by receiver operating characteristic (ROC) curve and area under the curve (AUC).Results:Among the 87 patients, 38 cases failed NIV within 48 hours (overall failure rate 43.7%), including 18 cases failing within the first 12 hours and 20 new failures from 12 to 48 hours, while the remaining 49 cases succeeded. There were no statistically significant differences between the two groups in gender, age, prevalence of hypertension and diabetes, left ventricular ejection fraction, serum creatinine, total bilirubin, heart rate, N-terminal pro-brain natriuretic peptide (NT-proBNP), inspiratory positive airway pressure (IPAP), arterial blood pH, partial pressure of arterial carbon dioxide (PaCO 2), oxygenation index (PaO 2/FiO 2), mean arterial pressure, Sequential Organ Failure Assessment (SOFA) score, respiratory rate and other indicators (all P>0.05). The failure group had a significantly lower baseline VOX index [(SpO 2/FiO 2)/VT] than the success group. From 2 to 12 hours after the initiation of NIV (a total of 6 recording time points), the VOX index in the failure group was significantly lower than that in the success group (all P<0.001). ROC curve analysis showed that the VOX index had the best predictive efficacy at 4-6 hours after NIV initiation: at 4 hours, the AUC was 0.929, and the optimal cut-off value of 24.72 had the highest sensitivity (91.84%) for predicting failure; at 6 hours, the AUC was 0.870, and the optimal cut-off value of 24.58 had the highest specificity (90.91%) for predicting failure. Conclusions:The VOX index can effectively predict the failure outcome of NIV in elderly patients with moderate ARDS, and its predictive ability is the strongest at 4-6 hours after the initiation of NIV. Clinically, the 4-hour or 6-hour time window can be selected to evaluate the prognosis according to the patient′s specific conditions (such as respiratory drive intensity, weaning risk), providing a reference for timely adjustment of respiratory support plans.

Objectives:The ORION-18 study has demonstrated that inclisiran can significantly reduce low-density lipoprotein cholesterol(LDL-C)and has good safety in Asian atherosclerotic cardiovascular disease(ASCVD)patients or ASCVD high-risk population.This subgroup analysis aims to further evaluate the efficacy and safety of inclisiran in Chinese mainland population.Methods:ORION-18 study is a multi-center,randomized,double-blind,placebo-controlled,phase Ⅲ clinical trial among Asian subjects,Chinese mainland subgroup included 232 ASCVD patients or ASCVD high-risk subjects who had already been treated with diet control and maximum tolerated doses of statins treatment(with or without other lipid-lowering treatments)but still had elevated LDL-C levels.Subjects were randomized in a 1:1 ratio to the inclisiran group and the placebo group(n=116 each),and received 300 mg of inclisiran or placebo respectively on day 0,90 and 270.The primary endpoint was the percentage change in LDL-C from baseline to day 330.The secondary endpoints included the time-adjusted percentage change and absolute change in LDL-C from baseline after day 90 and up to day 360,the absolute change in LDL-C from baseline to day 330,and the percentage changes from baseline to day 330 in proprotein convertase subtilisin/kexin type 9(PCSK9),total cholesterol,apolipoprotein B(ApoB),non-high-density lipoprotein cholesterol(non-HDL-C).Other secondary endpoints included the proportion of participants reaching LDL-C levels of<1.8 mmol/L at day 330,the proportion of participants with≥50%LDL-C reduction from baseline to day 330 and the proportion of participants who attained global lipid targets(the LDL-C target was<1.4 mmol/L for ASCVD patients and<1.8 mmol/L for ASCVD high-risk subjects)at day 330.Safety endpoints included adverse events during treatment,aboratory test abnormalities during treatment,serious adverse events,and assessed their severity and relation to treatment.Results:The inclisiran group showed a placebo-corrected percentage change in LDL-C from baseline to day 330 of-61.16%,and an absolute change of-1.73 mmol/L(both P<0.0001).Compared to the placebo group,the inclisiran group's time-adjusted percentage change in LDL-C from baseline between day 90 and day 360 was-58.51%,and an absolute change of was-1.64 mmol/L(both P<0.0001).At day 330,reductions from baseline were observed in the inclisiran group for PCSK9,total cholesterol,ApoB,non-HDL-C,with placebo-corrected percentage changes of-77.44%,-35.65%,-43.43%,-50.90%(all P<0.0001),respectively.At day 330,79.6%(74/93)of patients in the inclisiran group and 7.8%(6/77)in the placebo group achieved LDL-C levels<1.8 mmol/L,69.9%(65/93)of patients in the inclisiran group and 0%(0/77)in the placebo group achieved≥50%LDL-C reduction from baseline,66.7%(62/93)of patients in the inclisiran group and 2.6%(2/77)in the placebo group achieved their global LDL-C targets.The safety profile of inclisiran treatment over 12 months was comparable to that of the placebo,with no occurrence of treatment-related serious adverse events.Conclusions:In ASCVD patients or ASCVD high-risk subjects in Chinese mainland who have received diet control and maximum tolerable dose statins treatment(with or without other lipid-lowering treatments)and still have elevated LDL-C,inclisiran has a definite efficacy and good safety in reducing LDL-C.The efficacy and safety results of inclisiran assessed in Chinese mainland population are consistent with those of the general Asia population.

Objective:To explore the factors that can predict the outcome of non-invasive ventilation (NIV) in elderly patients with moderate acute respiratory distress syndrome (ARDS) and analyze their clinical application value.Methods:A total of 87 elderly patients with moderate ARDS caused by community-acquired pneumonia admitted to the Emergency Department of Beijing Friendship Hospital from January 2023 to December 2023 were retrospectively selected. Taking the need for conversion to invasive ventilation during treatment as the study endpoint, the patients were divided into NIV success group and failure group. Clinical data of patients were collected every 2 hours starting from 2 hours after the initiation of NIV, and differences between the two groups were compared. The predictive efficacy of potential risk factors was evaluated by receiver operating characteristic (ROC) curve and area under the curve (AUC).Results:Among the 87 patients, 38 cases failed NIV within 48 hours (overall failure rate 43.7%), including 18 cases failing within the first 12 hours and 20 new failures from 12 to 48 hours, while the remaining 49 cases succeeded. There were no statistically significant differences between the two groups in gender, age, prevalence of hypertension and diabetes, left ventricular ejection fraction, serum creatinine, total bilirubin, heart rate, N-terminal pro-brain natriuretic peptide (NT-proBNP), inspiratory positive airway pressure (IPAP), arterial blood pH, partial pressure of arterial carbon dioxide (PaCO 2), oxygenation index (PaO 2/FiO 2), mean arterial pressure, Sequential Organ Failure Assessment (SOFA) score, respiratory rate and other indicators (all P>0.05). The failure group had a significantly lower baseline VOX index [(SpO 2/FiO 2)/VT] than the success group. From 2 to 12 hours after the initiation of NIV (a total of 6 recording time points), the VOX index in the failure group was significantly lower than that in the success group (all P<0.001). ROC curve analysis showed that the VOX index had the best predictive efficacy at 4-6 hours after NIV initiation: at 4 hours, the AUC was 0.929, and the optimal cut-off value of 24.72 had the highest sensitivity (91.84%) for predicting failure; at 6 hours, the AUC was 0.870, and the optimal cut-off value of 24.58 had the highest specificity (90.91%) for predicting failure. Conclusions:The VOX index can effectively predict the failure outcome of NIV in elderly patients with moderate ARDS, and its predictive ability is the strongest at 4-6 hours after the initiation of NIV. Clinically, the 4-hour or 6-hour time window can be selected to evaluate the prognosis according to the patient′s specific conditions (such as respiratory drive intensity, weaning risk), providing a reference for timely adjustment of respiratory support plans.

The major histocompatibility complex(MHC)is closely related to immune regulation.MHC shows distinct genetic polymorphism,and there are also species differences in MHC restriction.The human MHC is called human leukocyte antigen(HLA),and the mouse MHC is called H-2.The construction of humanized MHC transgenic mouse models is an important strategy to overcome the differences in MHC among species and simulate the characteristics of a human immune response.MHC transgenic mice are mainly divided into MHC Ⅰ or MHC Ⅱ single-transgenic mouse models and MHC Ⅰ and MHC Ⅱ double-transgenic mouse models.The development of HLA Ⅰ transgenic mouse model went through three stages,at present,the strategy of knocking out H-2Kb and H-2Db or murine β2m is adopted to eliminate the competitive inhibition of HLA Ⅰ molecules by endogenous H-2 class Ⅰ molecules.In the construction of an HLA Ⅱtransgenic mouse model,the β strand of murine origin is knocked out and HLA Ⅱ class genes are inserted.With the optimization of construction strategies,MHC transgenic mouse models have been applied to epitope vaccine development,tumor treatment,and genetic disease-association studies,becoming a powerful tool for preclinical trials.In this paper,we summarize the relevant data on MHC transgenic mouse models,as well as the construction strategies used for MHC transgenic mouse models and their application in vaccine development and disease treatment.

Nanobodies derived from camelids and sharks offer unique advantages in therapeutic applications due to their ability to bind to epitopes that were previously inaccessible. Traditional methods of nanobody development face challenges such as ethical concerns and antigen toxicity. Our study presents a synthetic, phagedisplayed nanobody library using trinucleotide-directed mutagenesis technology, which allows precise amino acid composition in complementarity-determining regions (CDRs), with a focus on CDR3 diversity. This approach avoids common problems such as frameshift mutations and stop codon insertions associated with other synthetic antibody library construction methods. By analyzing FDA-approved nanobodies and Protein Data Bank sequences, we designed sub-libraries with different CDR3 lengths and introduced amino acid substitutions to improve solubility. The validation of our library through the successful isolation of nanobodies against targets such as PD-1, ATXN1 and STAT3 demonstrates a versatile and ethical platform for the development of high specificity and affinity nanobodies and represents a significant advance in biotechnology.

Nanobodies derived from camelids and sharks offer unique advantages in therapeutic applications due to their ability to bind to epitopes that were previously inaccessible. Traditional methods of nanobody development face challenges such as ethical concerns and antigen toxicity. Our study presents a synthetic, phagedisplayed nanobody library using trinucleotide-directed mutagenesis technology, which allows precise amino acid composition in complementarity-determining regions (CDRs), with a focus on CDR3 diversity. This approach avoids common problems such as frameshift mutations and stop codon insertions associated with other synthetic antibody library construction methods. By analyzing FDA-approved nanobodies and Protein Data Bank sequences, we designed sub-libraries with different CDR3 lengths and introduced amino acid substitutions to improve solubility. The validation of our library through the successful isolation of nanobodies against targets such as PD-1, ATXN1 and STAT3 demonstrates a versatile and ethical platform for the development of high specificity and affinity nanobodies and represents a significant advance in biotechnology.

Nanobodies derived from camelids and sharks offer unique advantages in therapeutic applications due to their ability to bind to epitopes that were previously inaccessible. Traditional methods of nanobody development face challenges such as ethical concerns and antigen toxicity. Our study presents a synthetic, phagedisplayed nanobody library using trinucleotide-directed mutagenesis technology, which allows precise amino acid composition in complementarity-determining regions (CDRs), with a focus on CDR3 diversity. This approach avoids common problems such as frameshift mutations and stop codon insertions associated with other synthetic antibody library construction methods. By analyzing FDA-approved nanobodies and Protein Data Bank sequences, we designed sub-libraries with different CDR3 lengths and introduced amino acid substitutions to improve solubility. The validation of our library through the successful isolation of nanobodies against targets such as PD-1, ATXN1 and STAT3 demonstrates a versatile and ethical platform for the development of high specificity and affinity nanobodies and represents a significant advance in biotechnology.