Objective By organizing and implementing a laboratory proficiency validation plan for air change rate testing, this study aims to explore proficiency testing approaches in laboratory animal facilities, assess the current status of relevant laboratories regarding standard application and test capabilities, standardize air change rate testing methods, and ensure the accuracy and reliability of test results. Methods From September to November 2023, the National Institutes for Food and Drug Control (NIFDC) organized a laboratory proficiency validation plan for air change rate testing in laboratory animal facilities (Plan Number: NIFDC-PT-417). The proficiency testing was conducted on-site and consisted of two parts: a written test and practical operation. The written test was open-book. True/false questions focused on participants' understanding of specific clauses in relevant standards, while application-based questions assessed their ability to handle data processing in simulated testing scenarios. The practical operation was conducted according to the relevant criteria of the China National Accreditation Service for Conformity Assessment (CNAS). Two laboratory animal rooms were prepared as proficiency testing samples using a sample splitting approach. These rooms underwent uniformity and stability testing according to CNAS requirements and were approved. Participating laboratories were required to conduct three tests on each of the two laboratory animal rooms, complete the testing and calculation of air change rate within the specified timeframe, and submit their test result reports and original records. Results A total of 27 laboratories registered and participated in the proficiency testing. All participating laboratories submitted their results within the designated timeframe, and the outcomes of all tested laboratories were rated as satisfactory. Conclusion This proficiency validation program objectively and scientifically evaluates the air change rate testing capabilities of selected domestic laboratories, effectively promoting the overall improvement of testing capabilities in the industry. It provides technical support for regulatory authorities to standardize testing institutions and offers reliable references for the purchase of testing services. Through this activity, it was identified that some laboratories need to further enhance their calibration of instruments and the utilization of calibration results. Future efforts should focus on refining related standards to improve the accuracy and reliability of testing.

The animal laboratory of pharmaceutical and biological product inspection and testing institutions undertakes important basic support tasks for testing and scientific research work.This article summarizes the management experience accumulated in the operation of our institution's CNAS-CL06 quality management system,providing reference for similar institutions in operation to ensure the scientific nature of animal experimental data.In order to ensure the scientific nature of animal experimental data,the experimental animal institution has successfully passed the CNAS accreditation of the experimental animal institution,and has completed rectification on time during on-site supervision and evaluation.At the same time,regular self inspections of the system have been carried out in accordance with the"Quality and Capability Accreditation Guidelines for Experimental Animal Breeding and Use Institutions"(CNAS-CL06).During the self inspection process,we examined issues while improving the content of the system.Starting from animal procurement,occupational health and safety,animal disease treatment and care,and facility operation emergency drills,we enriched the content of the quality management system,ensured the continuous and effective operation of the system,and ensured the effectiveness and standardization of animal experiment data.At the same time,we contributed to the management ideas of our institution in sharing animal experiment platforms,provide hardware and software support for the construction of cloud platforms for animal experiments.This article aims to explore and form a quality management model for the experimental animal industry based on practical work,being focused in the standardization strategy,continue to deepen the reform of standardization work,and give full play to the basic and strategic role of standardization in the modernization of the animal experiments system.

Objective To investigate the relationship of changes in serum chromogranin A(CgA)and heat shock transcription factor 1(HSF1)levels with cardiac remodeling and myocardial injury in elderly patients with chronic heart failure(CHF).Methods A total of 165 elderly CHF patients admitted to our hospital from January 2019 to May 2022 were selected as the disease group,and according to NYHA classification,they were divided into Class Ⅰ(28 patients),Ⅱ(29 patients),Ⅲ(65 patients)and Ⅳ(43 patients)subgroups.Another 80 healthy individuals taking physical examination in our hospital during the same period were enrolled as the control group.The serum CgA and HSF1 levels were detected,and the indicators of cardiac remodeling and myo-cardial injury were collected at admission in the two groups.The correlation of serum CgA and HSF1 levels with cardiac remodeling and myocardial injury was determined with Pearson correla-tion analysis.During 1 year's follow-up,6 cases were lost,and the left 159 patients were divided into MACE group(51 cases)and non-MACE group(108 cases)according to whether MACE occurred.Univariate and multivariate logistic regression analyses were used to analyze the influen-cing factors of MACE,and ROC curve was plotted to analyze the predictive value of serum CgA and HSF1 levels for MACE.Results The disease group had significantly higher left ventricular mass index(LVMI),left ventricular end-systolic volume(LVESV),left ventricular posterior wall thickness(LVPWT),serum levels of CgA,cardiac troponin Ⅰ(cTnⅠ),creatine kinase isoenzyme(CK-MB)and N-terminal B-type natriuretic peptide precursor(NT-proBNP),and obviously lower HSF1 level and left ventricular ejection fraction(LVEF)when compared with the control group(P＜0.01).Pearson correlation analysis showed that serum CgA level was negatively correlated with LVEF and positively with LVMI,LVESV,LVPWT,and serum levels of cTnⅠ,CK-MB and NT-proBNP(P＜0.01);serum HSF1 level was positively correlated with LVEF and negatively with LVMI,LVESV,LVPWT,and serum cTnⅠ,CK-MB and NT-proBNP levels(P＜0.01).Multi-variate logistic regression analysis showed that CgA,HSF1,LVEF,LVMI,LVESV,LVPWT and cTnⅠ were influencing factors for MACE in elderly CHF patients(P＜0.05,P＜0.01).ROC curve analysis indicated that the cut-off value of CgA was 387.55 μg/L,the sensitivity was 74.51％,the specificity was 71.30％,and the AUC value was 0.802(95％CI:0.751-0.855);the cut-off value of HSF1 was 2.34 ng/L,the sensitivity was 74.51％,the specificity was 69.44％,and the AUC value was 0.760(95％CI:0.707-0.812).Conclusion In elderly CHF patients,serum levels of CgA and HSF1 are closely associated with cardiac remodeling and myocardial injury,and the two indicators can be used as prognostic indicators for MACE.

Chronic kidney disease(CKD)is a common chronic disease.There is homology between retina and kidneys.Diabetic retinopathy and retinal neurovascular injury both reveal common pathophysiological features of ocular retina and kidney.Optical coherence tomography angiography(OCTA)detects chorioretinal microcirculation with near-histological resolution.Changes in microvascular structure and function can promote the development of hypertension,diabetes,CKD and related cardiovascular disease(CVD).The examination of fundus nerve microvessels by OCTA in patients with CKD is helpful to the identification of high-risk groups,and provides a new perspective for the assessment of disease progression and CVD risk prediction of patients with CKD.The combination of the deep learning will further expand this aspect of research and become the forefront of future development.

ObjectiveTo investigate the influence of triglyceride （TG）/high-density lipoprotein cholesterol （HDL-C） ratio on the onset of primary liver cancer. MethodsA prospective cohort study was conducted. Physical examination data were collected from 99 750 cases of on-the-job and retired employees of Kailuan Group who participated health examination from July 2006 to December 2007， and they were followed up till December 31， 2021 to observe the onset of primary liver cancer. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups， and the Kruskal-Wallis H test was used for comparison of continuous data with skewed distribution between multiple groups； the chi-square test was used for comparison of categorical data between groups. According to the tertiles of TG/HDL-C ratio， the subjects were divided into Q1， Q2， and Q3 groups， and the incidence density of primary liver cancer was calculated for each group. The Kaplan-Meier method was used to calculate the cumulative incidence rate of primary liver cancer in each group， and the log-rank test was used to compare the difference in cumulative incidence rate between groups. The Cox proportional hazards model was used to analyze the influence of TG/HDL-C ratio on the onset of primary liver cancer. ResultsThere were significant differences between the three groups in age， proportion of male subjects， waist circumference， body mass index， fasting blood glucose， systolic pressure， diastolic pressure， triglyceride， total cholesterol， HDL-C， low-density lipoprotein cholesterol， alanine aminotransferase， high-sensitivity C-reactive protein， chronic liver diseases， hypertension， diabetes， the family history of malignant tumor， drinking， smoking， physical exercise， and educational level （P<0.05）. During the mean follow-up time of 14.06±2.71 years， there were 484 cases of new-onset liver cancer， among whom there were 446 male subjects and 38 female subjects. The incidence density of primary liver cancer was 0.39/1 000 person-years in the Q1 group， 0.35/1 000 person-years in the Q2 group， and 0.30/1 000 person-years in the Q3 group， and the cumulative incidence rates of primary liver cancer in the three groups were 6.03‰， 5.28‰， and 4.49‰， respectively， with a significant difference between the three groups based on the long-rank test （χ²=6.06， P=0.048）. After adjustment for the confounding factors considered， the Cox proportional hazards model showed that compared with the Q3 group， the Q1 group had a hazard ratio of 2.04 （95% confidence interval ［CI］： 1.61‍ ‍—‍ ‍2.58， P_{for trend}<0.05）， and the Q2 group had a hazard ratio of 1.53 （95%CI： 1.21‍ ‍—‍ ‍1.92， P_{for trend}<0.05）. ConclusionThe reduction in TG/HDL-C ratio is associated with an increase in the rask of primary liver cancer， especially in people with chronic liver diseases.

Objective To overcome the limitations of existing human respiratory syncytial virus(hRSV)animal models,such as semi-permissiveness and short duration of infection,this study established an IL2rg gene knockout(IL2rg-/-)rat model using TALEN gene editing technology.Methods The animal model was infected with hRSV intranasally.Clinical characteristics,body weight,and temperature changes were observed over the infection period(0～35 days).The total viral loads in respiratory organs,such as the nasal tissue,trachea,and lungs,were measured at various time points(4,11,20,and 35 days post-infection).Pathological analysis was conducted on target organs at the endpoint of observation(35 days post-infection).Changes in peripheral blood T,B,NK,and NKT cells and various cytokines were assessed at various time points(4,20,and 35 days post-infection).Results(1)IL2rg/-knockout rats sustained high viral loads in the nasal cavity upon intranasal inoculation with hRSV.The average peak titer rapidly reached 1 × 1010 copies/g in nasal tissue and 1 × 107 copies/g up to 5 weeks post-infection.(2)However,no significant pathological changes were noted in nasal,tracheal,or lung tissues.(3)An increase was observed in the content of peripheral blood B cells in hRSV-infected IL2rg--rats.(4)IL-6 and MCP-1 were increased in the early stage of infection and then decreased at the end of the observation period.Conclusions This study established a new IL2rg-/-rat model using TALEN technology and found that this model effectively supported high-level replication and long-term infection of hRSV,providing a good basis for antiviral drug screening and in vivo efficacy evaluation of anti-hRSV antibodies.

Science and technological advancements drive human progress, with laboratory animals serving as essential resources for developments in life sciences and medicine. However, the waste generated by these animals presents new challenges for urban management. Issues such as classification, recycling, effective utilization, and biohazard elimination must be addressed, necessitating the development of regulations, standards, and norms to keep pace with advancements. The construction of quality management system is the foundation and framework for the management of inspection and testing organizations. It should have strong operability and inspectability, enabling continuous improvement of the management level and enhancing the stability of basic management. However, current quality management systems often lack clarity in managing laboratory animal waste, including undefined disposal processes for non-medical institutions, inaccurate waste classification, and inadequate disposal methods for different waste categories. This paper addresses these challenges by identifying necessary processes to be added or removed in the quality management system of National Institutes for Food and Drug Control, developing effective SOPs, proposing practical measures to strengthen supervision and management, and integrating 6S management principles into our quality management system. In conclusion, effective management of laboratory animal waste should be centered on improving the quality management system, emphasizing waste classification and management at the source, controlling biological hazards, minimizing environmental pollution and promoting conditions for sustainable development.

Postoperative pain seriously affects the recovery process of patients, resulting in prolonged hospital stay and increased care costs. Appropriate application of patient-controlled analgesia devices can effectively relieve perioperative acute pain. In 1994 patient-controlled analgesia began to be used in Peking Union Medical College Hospital, and the Acute Pain Service Working Group was established in 2004. With the cooperation of anesthesiologists and specialist nurses, the group jointly has implemented the whole process and standardized management based on patient-controlled analgesia, and constantly improved and innovated working methods, laying a solid foundation for the development of postoperative pain management. This paper systematically reviews and summarizes the work from the aspects of clinical focus, nursing management experience, promotion and dissemination of pain treatment concepts, and development of acute pain service model under the new situation, with the hope of providing valuable reference for comprehensively strengthening pain management in the process of diagnosis and treatment, and enhancing patients' satisfaction with perioperative analgesia services.

Objective:To establishment an assay for HIV-1 intact proviral DNA assay through droplet digital PCR (ddPCR).Methods:DNA was extracted by culturing 8E5 cells, a Tlymphocyte cell line containing a single copy of integrated HIV-1 provirus. Serial diluting DNA were prepared by amplified 1-fold, 5-fold, 25-fold, 625-fold, 3 125-fold, and 15 625-fold across the HIV-1 Ψ region, env region, and eukaryotic chromosome 10 RPP30 regions, and the linear relationship was calculated and the minimum detection concentration. DNA solution of 5 μl, 3.1 μl, 2.5 μl was added to the ddPCR mixture respectively, with each dilution undergoing two batches of detection, and each was repeated four times. The intra-batch variation coefficient was detected, while the inter-batch variation coefficient was detected by the same DNA amount and different DNA amounts to determine the stability; 8E5 cell was used to detect the intact proviral content in cells.Results:The linear fitting goodness of Ψ region, env region and RPP30 region are R2≥0.999, R2≥0.993, R2≥0.996 in 6 dilutions of DNA, respectively. At a 3 125-fold dilution, the lowest positive droplets were detected in the Ψ region, env region and RPP30 region were 3, 2 and 2, respectively, the detected concentrations were 2.37 copies/μl, 1.21 copies/μl and 1.58 copies/μl. The ddPCR repeatability experimental detecting DNA showed that the Ψ region of the intra-batch variation coefficients ranged from 0.66% to 3.43%, with the inter-batch variation coefficients of the same DNA at 3.19%, 4.3% and 3.45% respectively, and the inter-batch variation coefficients of the different DNA at only 4.35%. The env region of the intra-batch variation coefficients ranged from 0.7% to 3.20%, with the inter-batch variation coefficients of the same DNA at 3.18%, 4.52% and 3.4% respectively, and the inter-batch variation coefficients of the different DNA at only 4.02%. The RPP30 region of the intra-batch variation coefficients ranged from 0.91% to 2.91%, with the inter-batch variation coefficients of the same DNA at 3%, 4.55% and 3.37% respectively, and the inter-batch variation coefficients of the different DNA at only 3.98%. The proportion of 8E5 cells containing defective provirus and the proportion of intact provirus were calculated to be approximately 90% and 45%, respectively. Conclusions:Droplet digital PCR used to detect HIV-1 intact proviral DNA, showed strong stability and provided a technical means for HIV-1 infection reservoir detection.

To explore the general clinical features and treatment outcomes of patients with AIDS-related diffuse large B-cell lymphoma (AIDS-DLBCL) and provide a theoretical basis for diagnosis and treatment, survival prognosis, prevention and management of AIDS-DLBCL patients. AIDS-DLBCL patients who received combined antiretroviral therapy (cART) at Changsha First Hospital from January 2017 to January 2020 were selected in this study. The survival curves were plotted using the Kaplan-Meier method, and the Cox proportional hazards regression model was used to analyze the association between AIDS-DLBCL specific variables and progression-free survival and overall survival. Correlation analysis was conducted based on the clinical features of the patients. A total of 50 AIDS-DLBCL patients were included. Their median age ( Q 1, Q 3) was 52 (44, 59) years, of whom 46 (92%) were male. About 20 (40%) patients received treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), while 23 patients (46%) received treatment with rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP). Survival curve analysis showed that the 2-year progression-free survival rate and overall survival rate of AIDS-DLBCL patients were 56.9% and 61.6%, respectively. Patients with RCHOP protocol combined with EBV-DNA≥1 000 copies/ml had higher progression-free survival rate (χ 2=3.844, P=0.043) and overall survival rate (χ 2=4.662, P=0.031) than those with CHOP protocol combined with EBV-DNA≥1 000 copies/ml. A multivariate analysis showed that male ( HR=2.70, 95% CI:1.10-6.80), EB viral load≥1 000 copies/ml ( HR=1.75, 95% CI:1.12-2.84), HIV-RNA≥200 copies/ml ( HR=4.64, 95% CI: 1.73-12.15), ECOG PS score of 2 to 4 points ( HR=3.54, 95% CI:1.62-7.33), and international prognostic index (IPI) score of 3 to 5 points ( HR=5.21, 95% CI:1.39-20.14) were at a higher risk of disease progression. Patients with EB viral load≥1 000 copies/ml ( HR=0.07, 95% CI:0.05-0.93) on the RCHOP regimen had a small risk of disease progression. Males ( HR=2.87, 95% CI:1.65-9.17), EB viral load≥1 000 copies/ml ( HR=1.61, 95% CI:4.02-9.36), HIV-RNA≥200 copies/ml ( HR=1.19, 95% CI:1.58-2.74), ECOG PS score of 2 to 4 ( HR=6.42, 95% CI:2.55-14.33), IPI score of 3 to 5 points ( HR=2.78, 95% CI:1.41-12.96) had a high risk of mortality. Patients with EB viral load≥1 000 copies/ml ( HR=0.24, 95% CI:0.64-0.90) on the RCHOP regimen had a low risk of mortality. In summary, males, ECOG physical status score of 2 to 4 points, IPI score of 3 to 5 points, EB viral load≥1 000 copies/ml and HIV viral load≥200 copies/ml are risk factors affecting progression-free survival and overall survival of AIDS-DLBCL patients. RCHOP regimen combined with EB viral load≥1 000 copies/ml is a protective factor affecting progression-free survival and overall survival in AIDS-DLBCL patients.