ObjectiveTo monitor the real-time changes in ammonia concentration in the laboratory animal facility environment before, during, and after the air conditioning system stops supplying air, so as to provide a basis and reference for developing emergency plans for the shutdown of the air conditioning system. MethodsThe laboratory animal facilities of the Wuhan Institute of Biological Products were used as the research object. Ammonia concentration detectors were used to monitor ammonia concentration continuously in the environment of conventional rabbit production facility, SPF hamster production facility, and SPF guinea pig experimental facility before and after the passive shutdown due to repairs and active maintenance shutdown of the air conditioning system, as well as the time for the ammonia concentration to return to daily levels after resuming air supply. ResultsUnder both shutdown modes of the air conditioning system, the trend of ammonia concentration changes in different laboratory animal facilities was consistent, showing a rapid increase after shutdown and a rapid decrease after resuming air supply. Under active maintenance shutdown, the maximum ammonia concentrations in the conventional rabbit production facilities, SPF hamster production facilities, and SPF guinea pig experimental facilities were 9.81 mg/m³, 14.27 mg/m³, and 6.98 mg/m³, respectively. Within 12 minutes after resuming air supply, ammonia concentration could return to normal daily levels. Under passive long-term shutdown, ammonia concentration value was positively correlated with the duration of air supply suspension. As the shutdown duration increased, ammonia concentration continued to increase. The maximum ammonia concentration values in the three facilities occurred at 88 minutes (38.06 mg/m³), 40 minutes (18.43 mg/m³), and 34 minutes (15.61 mg/m³) after air supply suspension, respectively.Within 11 minutes after resuming air supply, ammonia concentration could return to normal daily levels. ConclusionShutdown of the air conditioning system causes a rapid increase in ammonia concentration in laboratory animal facilities, and the rise in ammonia concentration is positively correlated with the duration of air supply suspension. Therefore, when an emergency shutdown of the air-conditioning system is required due to maintenance or other reasons, backup fans should be provided in accordance with the requirements of GB 50447-2008 "Architectural and Technical Code for Laboratory Animal Facilities". Older facilities should make adequate preparations and develop a scientifically sound emergency plan.

Objective:The aim of this study is to analyze the clinical characteristics and genetic variants of a late-onset auditory neuropathy pedigree caused by maternally inherited- mitochondrial mutation.Methods:A male proband who presented with bilateral sensorineural hearing loss at Henan Children′s Hospital in September 2023 was chosen, along with his family members (4 generations, 20 individuals) as the study subjects. Data from this pedigree were collected, organized, and analyzed for clinical genetic characteristics. Medical histories were obtained from family members, pedigree charts were drawn, audiological, imaging, and physical examinations were conducted. Pathogenic genes and mutations were screened using high-throughput sequencing. Sanger sequencing was employed for variant confirmation and segregation validation in the family.Results:In this family, a total of 12 members (10 members collected) had sensorineural hearing loss, characterized by late-onset hearing impairment with an onset age ranging from 9 to 30 years. The patients exhibited poor speech recognition rates, and audiometric examinations are consistent with auditory neuropathy. There was no history of ototoxic drug use. High-throughput sequencing identified the variant NC_012920.1:m.7471dup in the mitochondrial MT-TS1 gene as the pathogenic variant. Sanger sequencing results confirmed that the pathogenic gene mutation site perfectly co-segregated with the auditory neuropathy phenotype in this family. According to the classification criteria and guidelines for genetic variations by the American College of Medical Genetics and Genomics, the variant was classified as a pathogenic mutation. Conclusion:The mitochondrial MT-TS1 gene mutation m.7471dup is considered to be the pathogenic cause in this late-onset auditory neuropathy pedigree.

Objective:The aim of this study is to analyze the clinical characteristics and genetic variants of a late-onset auditory neuropathy pedigree caused by maternally inherited- mitochondrial mutation.Methods:A male proband who presented with bilateral sensorineural hearing loss at Henan Children′s Hospital in September 2023 was chosen, along with his family members (4 generations, 20 individuals) as the study subjects. Data from this pedigree were collected, organized, and analyzed for clinical genetic characteristics. Medical histories were obtained from family members, pedigree charts were drawn, audiological, imaging, and physical examinations were conducted. Pathogenic genes and mutations were screened using high-throughput sequencing. Sanger sequencing was employed for variant confirmation and segregation validation in the family.Results:In this family, a total of 12 members (10 members collected) had sensorineural hearing loss, characterized by late-onset hearing impairment with an onset age ranging from 9 to 30 years. The patients exhibited poor speech recognition rates, and audiometric examinations are consistent with auditory neuropathy. There was no history of ototoxic drug use. High-throughput sequencing identified the variant NC_012920.1:m.7471dup in the mitochondrial MT-TS1 gene as the pathogenic variant. Sanger sequencing results confirmed that the pathogenic gene mutation site perfectly co-segregated with the auditory neuropathy phenotype in this family. According to the classification criteria and guidelines for genetic variations by the American College of Medical Genetics and Genomics, the variant was classified as a pathogenic mutation. Conclusion:The mitochondrial MT-TS1 gene mutation m.7471dup is considered to be the pathogenic cause in this late-onset auditory neuropathy pedigree.

Objective:To evaluate the relationship between intestinal mucosal mast cells and intestinal flora during intestinal ischemia-reperfusion(I/R) in mice.Methods:Forty-eight healthy male C57BL/6 mice, aged 9-12 weeks, weighing 20-25 g, were divided into 4 groups ( n=12 each) using a random number table method: sham operation group (group Sham), sham operation plus mast cell membrane stabilizer cromolyn sodium (CS) group (group Sham+ CS), I/R group and I/R+ CS group.The intestinal I/R injury was induced by clamping the superior mesenteric artery for 45 min followed by 4 h of reperfusion in I/R and I/R+ CS groups.The superior mesenteric artery was only exposed but not occluded in Sham and Sham+ CS groups.CS 50 mg/kg was intraperitoneally injected once a day for two weeks before surgery in Sham+ CS and I/R+ CS groups.The equal volume of normal saline was intraperitoneally injected once a day for two weeks before surgery in Sham and I/R groups.Mice were then sacrificed and intestinal tissues were harvested for examination of the pathological changes of intestinal mucosa with a light microscope after HE staining, and the damage to intestinal tissues was assessed and scored according to Chiu.The expression of mast cell tryptase was detected using the immunohistochemical SP staining method, and the mast cells were counted.The intestinal contents were collected, the total amount of bacteria in intestinal flora was detected by 1% agarose gel electrophoresis, and the diversity (Chao1 index and Shannon index) and relative abundance of intestinal microbial bacteria were detected by 16S rDNA sequencing method. Results:Compared with Sham group, the Chiu′s score and mast cell count were significantly increased, the expression of mast cell tryptase was up-regulated, the total amount of intestinal flora bacteria was increased, Chao1 index and Shannon index were decreased, the relative abundance of Bacteroidetes, Proteobacteria, Bacteroides and Enterobacteriaceae were increased, and the relative abundance of Firmicutes, Lactobacillus and Bifidobacteria was reduced in I/R group ( P<0.05 or 0.01), and no significant change was found in the parameters mentioned above in Sham+ CS group ( P>0.05). Compared with I/R group, the Chiu′s score and mast cell count were significantly decreased, the expression of mast cell tryptase was down-regulated, the total amount of intestinal flora bacteria was decreased, Chao1 index and Shannon index were increased, the relative abundance of Bacteroidetes, Proteobacteria, Bacteroides and Enterobacteriaceae were reduced, and the relative abundance of Firmicutes, Lactobacillus and Bifidobacteria was increased in I/R+ CS group ( P<0.05 or 0.01). Conclusion:The activation of intestinal mucosal mast cell can lead to imbalance of intestinal flora, decrease the number of probiotics and increase the number of potential pathogenic bacteria, and thus be involved in the pathophysiological mechanism of intestinal I/R injury in mice.

OBJECTIVE: To investigate the relationship between the polymorphism of TET2 gene SNP rs3733609 and JAK2V617F allele burden in patients with myeloproliferative neoplasms (MPN). METHODS: The exon 9 of TET2 gene was amplified by RT-PCR, and the nucleotide sequence of SNP rs3733609 site was analyzed by gene sequencing. The MGB Taqman probe PCR method was used to detect the JAK2V617F allele burden. The correlation of TET2 gene SNP rs3733609 C/T with the JAK2V617F allele burden and clinical parameters was analyzed. RESULTS: TET2 gene rs3733609 C/T heterozygosity (normal T/T) could be detected in 19 cases of 85 cases of JAK2V617F positive MPN (22.4%) patients, while the TET2 gene rs3733609 C/T heterozygosity could be detected only in 9 of the 106 healthy volunteers, and the incidence was only 8.5% (9/106). Compared with the negative group (TET2 rs3733609 T/T), there was no significant difference in the median age, hemoglobin level and platelet count in the patients with TET2 gene SNP rs3733609 (CT/TC) positive, but the WBC count of peripheral blood and JAK2V617F allele burden significantly increased. In JAK2V617F high allele burden group, TET2 gene SNP rs3733609 was positive in 7 cases (36.8%, 7/19), the ratio was higher than that in the low allele burden group(18.2%, 12/66). CONCLUSION TET2 SNP rs3733609 C/T may be a new susceptible allelee, which affects the clinical characteristics and clonal evolution of MPN patients.
Alleles ; DNA-Binding Proteins ; genetics ; Exons ; Humans ; Janus Kinase 2 ; genetics ; Mutation ; Myeloproliferative Disorders ; genetics ; Neoplasms ; Proto-Oncogene Proteins ; genetics

【Objective】To assess the efficacy and safety of Tongxinluo Capsules for cerebrovascular disorders by meta analysis.【Methods】Randomized controlled trials(RCT) of Tongxinluo Capsules for cerebrovascular disorders were got by searching China Journal Full-text Database(from 1996 to May,2006),China Best Doctoral and Master's Dissertations(from 1996 to May,2006),MEDLINE(from 1996 to May,2006),and Cochrane Library with computer,and were screened by manual search.RevMan 4.2 software and SAS were used in Meta-analysis.【Results】Thirty seven RCT were included,in which involved 2791 patients.Among them,1764 patients were treated with Tongxinluo Capsules,and other 1572 served as the controls. Meta-analysis results showed that the difference of the total efficacy in 31 RCT was significant(P