The emergency management of biosafety for laboratory animals in Hunan Province is an essential component of the province's implementation of the national biosafety strategy.To strengthen the prevention and control of biosafety risks in laboratory animals and to ensure a quick and effective response to laboratory animal biosafety emergencies,Hunan Province has formulated the"Emergency Response Plan for Laboratory Animal Biosafety Emergencies in Hunan Province".This plan aims to minimize damages caused to practitioners,public health,and laboratory animal industry,protect lives and property,and safeguard public safety and social stability.This paper analyzes the necessity,guiding ideology,principles,and basis for formulating the plan.It details the main contents of the plan,which includes scope of application,incident classification,organizational structure and responsibilities,monitoring and early warning mechanisms,emergency reporting and response,post-incident assessment,and safeguard measures.Moreover,this paper provides a summary and outlook on the emergency management of biosafety laboratory animals in Hunan Province in recent years.

Objective:To explore the application value of patient data-based real-time quality control (PBRTQC) in enhancing the effectiveness of internal quality control (IQC) management.Methods:From the PBRTQC real-time quality control intelligent monitoring platform integrated with the laboratory information system (LIS), a total of 35,631 test results of red blood cell (RBC) count, white blood cell (WBC) count, and dehydroepiandrosterone sulfate (DHEA-S) were collected from patients of the Department of General Xi'an Area Medical Laboratory Center from August 1, 2023, to April 1, 2024. The platform was used in patient data distribution characteristics test, EWMA real-time quality control chart procedure establishment, performance validation, effect evaluation, best procedure selection, and real-time operation. The performance evaluation indexes of the best PBRTQC procedure establishment, the cut-off limit range, weighting coefficient, cumulative mean, standard deviation (SD), coefficient of variation ( CV) of the EWMA real-time quality control chart, and the cumulative mean, SD, and CV of its internal quality control data in the same period were counted, and at the same time compared with the quality target (1/3TEa). Coefficient of variation analyses were performed to compare the quality control status of PBRTQC and conventional internal quality control in the presence of warning or alarm prompts based on quality control process records, and alarm messages. Results:The evaluation indexes of the optimal procedures for RBC count, WBC count, and DHEA-S were the probability of error detection (Ped) between 93%-97% and greater than 90%, the false positive rate (FPR) between 0.0%-0.5%, the false negative rate (FNR) between 3.0%-7.0%, and the average number of the patient sample until error detection (ANPed) between 5-11, which is in line with the optimal quality control efficacy quality requirements for the PBRTQC procedure. The patient outcome cut-off concentrations for the optimal procedure EWMA quality control charts ranged from RBC count (3.92-5.16)×10 12/L, WBC count (4.28-7.50)×10 9/L, and DHEA-S (830-2 160) μg/L; (2 160-4 210) μg/L. The weighting coefficients were 0.05, 0.03, and 0.03, respectively. The real-world application of the EWMA real-time quality control charts showed stable and excellent analytical performance of the measurement system, such as out-of-control alarm: RBC count, 1 true alarm, Ped of 95.85%, and FPR of 0%. The cumulative CV of EWMA was less than the quality target; the cumulative CV of DHEA-S was 7.66% and 9.47%, respectively, and the cumulative CV of low level was greater than the quality target (8.33%), and the cumulative CV of high and low levels were 4.12% and 6.25%. Conclusion:The PBRTQC EWMA method can monitor the patient data - in real-time and continuous way. It can also dynamically identify and provide early indication of small changes in analytical performance during the analysis process, and can be used as a supplement to quality control products to improve the efficacy of laboratory quality management.

Objective:To understand and compare the clinical characteristics of children and adults infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant BA.5 and BA.2 subtypes in Shanghai City.Methods:The clinical data of 524 children hospitalized with coronavirus disease 2019(COVID-19) at the Children′s Hospital of Fudan University during the period of BA.5 predominance from December 1, 2022 to January 20, 2023 were collected, which included age, gender, clinical symptoms and laboratory examination results. And the clinical data of household close contacts were also collected. The clinical data of children and their household contacts infected with Omicron BA.2 subtypes during the period of BA.2 predominance from April 4 to April 30, 2022 were collected and compared.The clinical characteristic of critical and non-critical cases, child and adult cases during the period of BA.5 predominance were compared.Statistical analyses were conducted using independent samples t-test, Mann-Whitney U test, chi-square test or Fisher′s exact test. Results:The age of 524 hospitalized children was five days to 16 years old. Among them, 301(57.4%) were male and 223(42.6%) were female. Additionally, there were 29 critical cases (5.5%) and 495 non-critical cases (94.5%). Critical cases had significantly higher fever peak, more shortness of breath occurrence, more pneumonia and underlying diseases compared to non-critical cases, with statistically significant differences ( t=12.06, χ2=34.90, 10.04 and 31.10, respectively, all P<0.05). Regarding laboratory examinations, critical cases exhibited significantly higher frequencies of decreased lymphocyte count, elevated levels of C-reactive protein, procalcitonin and interleukin-6, abnormal liver function and kidney function, and abnormal creatine kinase isoenzyme compared to non-critical cases, with statistically significant differences ( χ2=8.18, Z=-4.61, Z=-4.28, Z=-5.13, χ2 =195.90, Fisher′s exact test and χ2=136.13, respectively, all P<0.05). Non-critical children cases infected with Omicron variant BA.5 subtype exhibited a higher proportion of symptomatic infections compared to adults. Among children, the occurrence rates of fever and gastrointestinal symptoms (nausea, vomiting, diarrhea) were higher, whereas among adults, the occurrence rate of cough was higher. The differences were statistically significant ( χ2=11.16, 11.83, 8.50 and 28.14, respectively, all P<0.05).From December 1, 2022 to January 20, 2023, a total of 588 children cases and 791 adult cases were collected, while from April 4 to April 30, 2022, a total of 355 children cases and 755 adult cases were collected.In the children group, the occurrence rates of cough, convulsions and critical cases were higher in BA.5 subtype-infected children compared to those infected with the BA.2 subtype, with statistically significant differences ( χ2=37.95, 40.78 and 15.54, respectively, all P<0.001).In the adult group, BA.5 subtype-infected individuals had higher fever peak, longer duration of fever, and higher occurrence of fever, cough and gastrointestinal symptoms, compared to those infected with the BA.2 subtype.The differences were statistically significant ( t=-4.40, Z=-9.64, χ2=47.29, 124.09 and 29.90, respectively, all P<0.001). Conclusions:During the peak periods of BA.5 subtype of the Omicron variant in Shanghai City, critical cases have severe systemic symptoms and a higher prevalence of underlying diseases compared to non-critical cases. Among non-critical cases infected with BA.5 subtype, the proportion of symptomatic infections in children is higher than adults, with fever and gastrointestinal symptoms more common than adults, while cough symptoms are more common seen in adults.The occurrence rate of convulsions and critical cases is higher in children infected with variant BA.5 subtype compared to those infected with BA.2 subtype.The systemic symptoms are more severe in adults infected with BA.5 subtype compared to those infected with BA.2 subtype.

Objective:To evaluate the clinical efficacy of allogeneic hematopoietic stem cell transplantation（allo-HSCT）in children with severe aplastic anemia（SAA）.Methods:Twenty-seven cases with SAA who had been treated with allo-HSCT from January 2020 to December 2022 were retrospectively analyzed and reviewed.Results:（1）A total of 27 SAA patients were enrolled，including 18 males and 9 females，with a median age of 8 (2-15) years.There were 20 cases of SAA-Ⅰ type,7 cases of SAA-Ⅱ type.Based upon donor sources，three cases of matched sibling donors hematopoietic stem cell transplantation,and 24 cases of haploidentical hematopoietic stem cell transplantation were adopted.（2）Hematopoietic reconstruction was achieved in all 27 cases.The median implantation time of neutrophils and platelets was 10（9-20）days and 12（7-26）days respectively.The cumulative incidence of acute graft-versus-host disease（GVHD）was 66.67%（18/27）.The incidence of grade Ⅰ-Ⅱ was 55.56%（15/27）and that of grade Ⅲ-Ⅳ was 11.11%（3/27）.The incidence of chronic GVHD was 7.41%（2/27）.Transplant-associated thrombotic microangiopathy (TA-TMA) occurred in 7.41%（2/27）patients,cytomegalovirus viremia in 62.96%（17/27）patients,epstein-barr virus infection in 33.33%（9/27）patients,and 14.81%（4/27）patients progressed to post-transplant lymphoproliferative disorder (PTLD).（3）The median follow-up time was 12 (2-28) months.The overall survival rate was 96.29%.Twenty-six patients survived,and one patient died due to multiple complications of severe acute GVHD,TA-TMA,cytomegalovirus infection,PTLD and secondary epilepsy.Conclusion:Allo-HSCT is an effective therapy for SAA in children.The effective rate of this research is 96.29%.Acute GVHD is still the key to therapy.The incidence rate of acute GVHD is 66.67% in this study.The blood incompatibility of donor and recipient may affect the incidence of GVHD.The intensity of GVHD prevention should be reduced after HLA-matched sibling donor-hematopoietic stem cell transplantation so as to avoid the complications of virus recurrence and PTLD.

Objective:To investigate diagnostic and prognostic value of actin-binding protein ANLN in clear cell renal cell carcinoma(ccRCC)and its relationship with tumor microenvironment.Methods:Gene expression data and clinical data for ccRCC were downloaded from The Cancer Genome Atlas(TCGA).Relationship between ANLN expression and clinicopathological features was assessed by Wilcoxon rank sum test and Logistic regression.Receiver operating characteristic(ROC)curve was used to assess diagnostic value of ANLN expression in ccRCC.Kaplan-Meier and Cox regression analysis were used to investigate effect of ANLN expression on overall survival.Gene set enrichment analysis(GSEA)was used to identify signaling pathways associated with ANLN in ccRCC.Relationship between ANLN expression and immune infiltration was analyzed by ESTIMATE algorithm,tumor immune estima-tion resource(TIMER)and CIBERSORT algorithms.Relationship between ANLN and drug sensitivity was calculated using CellMiner database.Results:ANLN expression was significantly upregulated in ccRCC tissues.ANLN expression in ccRCC was correlated with clinicopathological features.ROC analysis showed that ANLN had a high diagnostic value in ccRCC.High ANLN expression was signifi-cantly associated with poor prognosis.Multivariate Cox regression analysis showed that high ANLN expression was an independent risk factor for overall survival in ccRCC patients.GSEA showed that ANLN was associated with multiple signaling pathways.In terms of immunity,ANLN was closely associated with tumor microenvironment,immune infiltration and immune checkpoint molecules in ccRCC.ANLN expression was negatively correlated with sensitivity of most antitumor drugs.Conclusion:ANLN is a potential diagnos-tic and prognostic biomarker and immunotherapeutic target for ccRCC.

Myocardial infarction is one of the major diseases that seriously threaten human health. In the clinical treatment of myocardial infarction, there are unpredictable complications, and most patients will suffer a severe cardiac function decline due to excessive loss of myocardia and formation of scar tissue, eventually progressing to heart failure or even death. With rapid development of biological materials, they as an important part of tissue repair and regeneration research, have become a hot spot in the research and development of cardiovascular repair materials. Among them, decellularized extracellular matrix (dECM) materials, a class of natural materials with good histocompatibility, low immunogenicity, and suitable cell growth and metabolism characteristics, have been applied in clinical or preclinical cardiovascular tissue engineering or regenerative medicine. In this review, the application progress of dECM materials in tissue engineering, including the dECM preparation of 3D printed bioink, electrospinning, matrix hydrogel, and myocardial patch, in myocardial infarction treatment was summarized, and prospects and current challenges in the treatment of myocardial infarction were discussed.

Objective:To explore the correlation between right atrial function parameters and prognosis in patients with chronic obstructive pulmonary disease(COPD) complicated with pulmonary hypertension.Methods:Eighty-four patients with COPD combined with pulmonary arterial hypertension treated with bosentan combined with milrinone admitted to the First Affiliated Hospital of Xinjiang Medical University during the period of February 2020 to June 2022 were selected as the study subjects, and they were divided into the effective group (63 cases) and the ineffective group (21 cases) according to the treatment effect. Right cardiac function parameters were measured by Philips iE33 color ultrasonography before treatment and 72 h after treatment. Logistic regression was used to analyze the risk factors affecting the treatment outcome of patients, and receiver operating characteristics (ROC) curve was used to analyze the predictive value of right atrial function parameters in the poor prognosis of patients with COPD complicated with pulmonary hypertension.Results:The main pulmonary artery diameter (MPA), right ventricular base transverse diameter (RVd1), right ventricular middle transverse diameter (RVd2), right atrial diameter (RAd) and right ventricular free wall thickness (RVWT) in the effective group were lower than those in the ineffective group: (2.65 ± 0.23) cm vs. (2.90 ± 0.44) cm, (3.46 ± 0.43) cm vs. (3.76 ± 0.72) cm, (3.48 ± 0.42) cm vs. (3.88 ± 0.69) cm, (3.53 ± 0.81) cm vs. (4.03 ± 1.20) cm, (0.63 ± 0.12) cm vs. (0.72 ± 0.21) cm; end-diastolic to end-systolic tricuspid ring displacement (TAPSE) was higher than that in the ineffective group: (2.08 ± 0.32) cm vs. (1.82 ± 0.46) cm, there were statistical differences( P<0.05). Logistic regression analysis showed that RVd1 increased ( OR = 3.717, P<0.05), RVd2 increased ( OR = 2.162, P<0.05), RAd increased ( OR = 2.838, P<0.05) and TAPSE reduction ( OR = 1.704, P<0.05) were risk factors for treatment failure in patients. The results of ROC curve showed that the area under the curve of RVd1, RVd2, RAd, TAPSE in predicting the therapeutic effect of COPD patients with pulmonary hypertension were 0.820, 0.831, 0.872, 0.909, respectively. Conclusions:The independent influencing factors of ineffective patients with COPD combined with pulmonary arterial hypertension treated with bosentan combined with milrinone are the increase of structural parameters of the right heart and the decrease of systolic function parameters. The therapeutic effect of patients can be evaluated clinically according to the level of each parameter.

ObjectiveThis study aimed to investigate the current status of biosafety management in laboratory animal institutions in Hunan Province, identify management shortcomings, and provide targeted recommendations for improvement. MethodsA questionnaire survey was conducted in July 2023 among 40 laboratory animal institutions in Hunan Province, covering topics such as the establishment of laboratory management system and its overall operation status, emergency management for incidents, medical waste disposal, animal transportation, personnel practitioner management, environmental disinfection, and equipment maintenance. The awareness of biosafety, animal bite incidents, and vaccination history was surveyed from at least one animal feeder or experimental operation practitioner from each institution, totaling 50 practitioners. Through literature review and comparative analysis, this paper analyzed the current status of biosafety management in production, transportation, and use of laboratory animals in Hunan Province from aspects such as biosafety management systems, personnel training, disinfection of environmental facilities and waste disposal, and provided recommendations. ResultsAmong the 40 laboratory animal institutions in Hunan Province,39 institutions (97.5%) had established laboratory management systems, 37 (92.5%) had emergency response plans for incidents of to transport laboratory animals, 15 (37.5%) had complete records of emergency drills for laboratory animal biosafety, and 39 (97.5%) had established protocols for carcass and waste management. Moreover, 26 institutions (65.0%) had laboratory biosafety risk assessment reports. 4 out of 8 (50.0%) production units had emergency plans for animal transportation, with 7 (87.5%) using special vehicles to transport laboratory animals. 2 (4.0%) of the 50 practitioners were unaware of emergency response plans, 6 participants (12.0%) did not consistently wear personal protective equipment, and 38 participants (76.0%) had been bitten or scratched by laboratory animals. The results of the survey showed that emergency management, transportation management and personnel management of laboratory animal incidents still need improvement in Hunan Province. Relevant functional departments should strengthen supervision and management efforts, establish local regulations for the transportation management of laboratory animals, ensure strict compliance with relevant documents, conduct emergency drills in all units, and strengthen training for practitioners. ConclusionWhile daily management practices in the 40 laboratory animal institutions in Hunan Province are generally satisfactory, there remains a need for further improvement in emergency management, transportation management, personnel management, etc. Gradually enhancing the level of laboratory animal safety management is essential to collectively safeguard public health safety.

Primary central nervous system lymphoma (PCNSL) is a rare and aggressive non-Hodgkin’s lymphoma that affects the brain, eyes, cerebrospinal fluid, or spinal cord without systemic involvement. The outcome of patients with PCNSL is worse compared to patients with systemic diffuse large B-cell lymphoma. Given potential mortality associated with severe immune effector cell-associated neurotoxicity syndrome (ICANS), patients with PCNSL have been excluded from most clinical trials involving chimeric antigen receptor T-cell (CAR-T) therapy initially. Here, we report for the first time to apply decitabine-primed tandem CD19/CD22 dual-targeted CAR-T therapy with programmed cell death-1 (PD-1) and Bruton’s tyrosine kinase (BTK) inhibitors maintenance in one patient with multiline-resistant refractory PCNSL and the patient has maintained complete remission (CR) for a 35-month follow-up period. This case represents the first successful treatment of multiline resistant refractory PCNSL with long-term CR and without inducing ICANS under tandem CD19/CD22 bispecific CAR-T therapy followed by maintenance therapy with PD-1 and BTK inhibitors. This study shows tremendous potential in the treatment of PCNSL and offers a look toward ongoing clinical studies.