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.

CRISPR/Cas9 technology has driven the development of various fields in life science.With continuous deepening of its understanding,researchers have made multiple improvements and optimizations to adapt to various application scenarios.The optimization of CRISPR/Cas9 technology has also provided breakthroughs in the establishment of genetically modified mouse models.This article briefly reviews the development process of CRISPR/Cas9 technology and summarizes optimization strategies of CRISPR/Cas9,establishment of conditional knockout/knockin gene-modified mouse models,and delivery systems for CRISPR/Cas9 elements and HDR templates.

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 effect of radon on the expressions of miR-16, miR-106b, miR-449a, let-7g, miR-21, miR-221 and miR-34a in peripheral blood plasma of miners.Methods:A total of 46 randomly selected miners worked underground(the underground group)and 38 miners worked aboveground (the control group). MiRNA levels in the underground and control groups were detected by qRT-PCR and their relationship with cumulative effective dose was further analyzed.Results:The levels of miR-106b, miR-21, miR-221 in plasma of the study group were significantly higher than those in the control group( Z=-2.32, -2.47, -2.79, P<0.05), the corresponding Fc values were 1.61, 1.75, 1.30, respectively. The levels of miR-16, miR-449a, let-7g and miR-34a were slightly higher than those in the control group ( P>0.05). After controlling of confounding factors such as age, BMI and smoking, the alteration of miR-16, miR-106b, let-7g, miR-21 and miR-221 in plasma of the underground group were positively correlated with the cumulative effective dose( t=2.50, 3.31, 2.60, 2.95, 3.25, P<0.05). No significant difference was observed in the plasma levels of miR-449a and miR-34a between the two groups ( P>0.05). Conclusions:miR-106b, miR-21 and miR-221 could be used as potential biomarkers of radon exposure.

Objective:To investigate the efficacy of CT virtual colonoscopy with carbon dioxide (CO 2) versus room air and the effects of bowel cleanliness on polyp detection rate. Methods:A total of 186 patients who underwent CT virtual colonoscopy in the Affiliated Hospital of Hangzhou Normal University (Hangzhou Second People's Hospital), China between October 2015 and November 2020 were included in this study. They were randomly divided into CO 2 and control groups ( n = 93/group). In the CO 2 and control groups, CO 2 and room air were respectively injected through the anus to fill the intestinal cavity. The Boston Bowel Preparation Scale (BBPS) score, abdominal distension score, Visual Analogue Scale (VAS) score, Bruggrmann comfort scale (BCS) score and polyp detection rate were compared between the two groups. Results:According to BBPS score, there were 62 and 60 patients with good bowel cleanliness (BBPS score ≥ 7 points), and 31 and 33 patients with poor bowel cleanliness (BBPS score < 7 points) in the CO 2 and control groups, respectively. There were no significant differences in abdominal distension score, VAS score and BCS score measured during the examination between the two groups (all P > 0.05). At 30 minutes after examination, abdominal distension score and VAS score in the CO 2 group were (2.21 ± 0.40) points and (1.43 ± 0.34) points, respectively, which were significantly lower than those in the control group [(3.50 ± 0.49) points, (3.03 ± 0.55) points, t = 2.59, 2.38, both P < 0.05)]. At 60 minutes after examination, abdominal distension score, VAS score and BCS score in the CO 2 group were (1.15 ± 0.39) points, (1.22 ± 0.28) points, (1.27 ± 0.35) points, which were significantly lower than those in the control group [(2.16 ± 0.43) points, (1.91 ± 0.32) points, (1.85 ± 0.37) points, t = 2.45, 2.27, 2.40, all P < 0.05). The detection rate of small (< 6 mm) - and large (≥ 6 mm) -sized polyps in the CO 2 group was 32.7% (34/104) and 88.1% (37/42), respectively and they were 29.0% (29/100) and 85.1% (40/47) respectively in the control group. There were no significant differences in the detection rate of small- and large-sized polyps between CO 2 and control groups (both P > 0.05). The detection rate of large-sized polyps in patients with good bowel cleanliness in the CO 2 group was 92.3% (24/26) and 89.7% (26/29), respectively, which were significantly higher than those in patients with poor bowel cleanliness in the control group [81.3% (13/16), 77.8% (14/18), χ2 = 6.03, 6.44, both P < 0.05]. The detection rate of small-sized polyps in patients with poor bowel cleanliness in the CO 2 group was 41.9% (26/62) and 42.9% (21/49), respectively, which were significantly higher than those in patients with poor bowel cleanliness in the control group [19.0% (8/42), 15.7% (8/51), χ2 = 15.32, 13.78, both P < 0.01]. Conclusion:CT virtual colonoscopy with CO 2 injection is less uncomfortable than CT virtual colonoscopy with room air and it does not affect polyp detection rate. Bowel cleanliness has a remarkable effect on polyp detection rate in virtual colonoscopy.

Objective To investigate and analysis the epidemiological characteristics of a cluster epidemic of COIVD-19 in a collective workplace in Tianjin, evduate the prevention and control measures based on limited evidence and experience in early period of COVID-19 epidemic. Methods Descriptive research method was used to describe the distribution and other epidemiological characteristics of the cluster cases of COVID-19. Results Since the onset of the first index case on January 15, ten confirmed COVID-19 cases had occurred in the workplace, and the epidemic had spread from the workplace to 4 families, infecting 7 family members. The median age of 17 cases was 55 (19-79) years. All the 10 employee cases were males, and in 7 family cases, 3 were males and 4 were females. Of the employee cases, 8 worked in CW workshop and 2 worked in administrative office building. The median exposure-onset interval of all the cases was 4 (0-12) days, and the median exposure-onset interval was 4.5 days in the employee cases and 4 days in the family cases. The median onset-medical care seeking interval was 4 days in the non-isolated cases, 2.5 days in the cases with home isolation after onset, and 0.5 day in the cases with home isolation before onset. Conclusion The clustering of COVID-19 cases was observed in this workplace in Tianjin, which affected 4 families. In the early stage of the epidemic, accurate and rapid blocking and control measures can completely prevent the large-scale spread of COVID-19.

OBJECTIVETo observe the effects of rehabilitation training (RT) combined with intradermal needling, RT combined with acupuncture and RT alone on core muscle stability in children with cerebral palsy, and to explore the superior therapy to improve core muscle stability in children with cerebral palsy.

METHODSA total of 120 children with cerebral palsy aged from 2 to 4 years old were randomly divided into a RT and intradermal needling group (group A), a RT and acupuncture group (group B) and a RT group (group C), 40 cases in each one. The patients in the group C were treated with kinesitherapy and core muscle stability training, once a day. Along with identical RT of group C, the patients in the group B were treated with acupuncture (once a day), while the patients in the group A were treated with intradermal needling at Yaoyangguan (GV 3), Mingmen (GV 4), Jiaji (EX-B 2, L-L), and 4-week treatment was taken as one course. The integrated electromyography (iEMG) of surface electromyography, root mean square (RMS) and mean power frequency (MPF) of erector spinae muscles, Berg balance scale as well as B area (siting), C area (climbing and kneeling), D area (standing) and E area (walking, running and jumping) of gross motor function measure (GMFM) were compared before and after 3-course treatment.

RESULTS① Compared before treatment, the iEMG and RMS of erector spinae muscles in the group A and group B as well as MPF in the group A were all increased after treatment (all <0.05); after treatment, all the electromyography indexes in the group A were higher than those in the group B and group C (all <0.05); the RMS in the group B was higher than that in the group C (<0.05). ② Compared before treatment, the Berg balance scale was all increased after treatment in the three groups (all <0.05), and the scale in the group A was higher those that in the group B and group C (both <0.05). ③ Compared before treatment, the B area and C area of GMFM in the three groups as well as D area in the group A and group B were all improved after treatment (all <0.05); the B area, C area and D area in the group A and group B were higher than those in the group C (all <0.05); the B area and C area in the group A were higher than those in the group B (both <0.05).

CONCLUSIONBased on RT, the intradermal needling could better improve core muscle stability and balance-motor ability in children with cerebral palsy, which is superior to regular acupuncture and RT alone.

Objective To study the relationships between differences in tumorigenicity and immu-nogenetic backgrounds of nude mice. Methods According to the Chinese Pharmacopoeia, positive and neg-ative groups were set up in both Laboratory A and B with ten nude mice in each group. Organ tissues were collected for clinicopathological analysis. Blood samples were collected and detected using flow cytometry. DNA was extracted and analyzed with 23 STR markers. Results The positive group of Laboratory B was in-valid (7/10 tumor formation). The two laboratories showed no significant difference in the results of patho-logical analysis, but had significant differences in CD25, CD8, CD4, Th1 and Th2. There were 13 and 18 polymorphic sites respectively found in nude mice of Laboratory A and B. Further analysis of the non-tumor-bearing nude mice in Laboratory B positive group revealed that CD25, Th2, D3Mit29 and D5Mit48 were the specific indexes. Conclusion Differences in tumorigenicity might be related to the diversity of immunoge-netic backgrounds of nude mice.

OBJECTIVETo investigate the effect of MTHFR gene on schizophrenia and its cognitive function.

METHODSWe recruited 254 schizophrenia patients with stable condition, 339 healthy controls for genetic analysis and 72 healthy controls for cognitive evaluation. The repeatable battery for the assessment of neuropsychological status (RBANS) was used for cognitive measurement. PCR-RFLP technique was carried out to genotype 677C/T polymorphism.

RESULTSThere were no significant differences in genotypic or allelic frequencies of the 677C/T polymorphism between the case and control groups (P> 0.05). In the RBANS, patients had higher scores of immediate memory, visuospatial skill, language, attention, delayed memory and total scores than healthy controls (P< 0.01); Patients with different genotypes of 677C/T polymorphism had significant differences in the scores of immediate memory, attention and total scores (P< 0.05).

CONCLUSIONOur results did not provide evidence for MTHFR gene conferring susceptibility to schizophrenia. However, there was a significant association between the MTHFR gene and cognitive impairment in patients with schizophrenia, especially in immediate memory and attention.

Adolescent ; Adult ; Cognition ; Genotype ; Humans ; Methylenetetrahydrofolate Reductase (NADPH2) ; genetics ; Middle Aged ; Polymorphism, Genetic ; Schizophrenia ; genetics ; Schizophrenic Psychology ; Young Adult