Objective To compare effectiveness between the modified and traditional pressure-overload myocardial hypertrophy(POMH) model by abdominal aorta coarctation (AAC) method. Methods Totally 45 rats were divided into three groups(n = 15 per group), sham group, traditional group, and modified group. In the traditional group, the diameter ol the abdominal aorta was narrowed to 0. 70 mm through a midline incision for 4 weeks; in the modified group, the diameter of the abdominal aorta was narrowed above the left kidney to 0. 45 mm for 1 week, and then the narrowing was lifted postoperatively. The cardiac index, heart weight (HW) /body weight (BW) and left ventricular index, left ventricular weight (LVW)/BW were measured from the heart specimens, and the cross-sectional area of cardiac myocytes, myocardial collagen area, and myocardial collagen area Iraction were measured in the pathological sections by HE staining and Masson staining. Results Compared with the sham group, the differences in end-systolic interventricular septum thickness (IVSs), left ventricular end-systolic posterior wall thickness (LVPWs), HW/BW, LVW/BW, cardiomyocyte cross-sectional area, myocardial collagen area, myocardial collagen area fraction, and brain natriuretic peptide (BNP) expression levels were statistically significant (P<0. 05) in the modilied and traditional groups of rats. The differences in these indices were not statistically significant between the modified and traditional groups (P>0. 05). Conclusion The modified abdominal aortic constriction method used in this experiment is time-saving, stable, homogeneous and easy to replicate, and is a more ideal approach to establish a rat model of POMH.

Objective To investigate the detection rate,epidemiology and resistance mechanism of methicil-lin-resistant Staphylococcus aureus(MRSA)in a hospital in recent 5 years.Methods A total of 762 strains of non repetitive Staphylococcus aureus detected from 2016 to 2020 in a hospital were collected retrospectively.Methicillin-sensitive Staphylococcus aureus(MSSA)was 392 strains(MSSA group)and 370 strains caused by MRSA(MRSA group),and 95 strains of MRSA isolated in 2020 were further used for resistance mechanism.Staphylococcus aureus was identified and tested for drug sensitivity by Vitek 2 automatic microbial system.Molecular epidemiological typing was determined by multilocus sequence typing.The biofilm formation was performed by crystal violet staining.PCR amplification was used to detect drug resistance genes,virulence genes and biofilm related genes,and logistic regression analysis was used to investigate the independent risk factors of its occurrence.Results The detection rate of MRSA in past five years was 48.56％,mainly was from pus samples and secretion samples(38.38％,33.51％respectively).MRSA was found in the general sur-gery(18.65％)and otorhinolaryngology(12.70％).ST88 was the most common multilocus sequence typing(37.89％),and followed by ST951(24.21％).Moderate biofilm formation was the most common,accounting for 74.73％.Multivariate regression analysis showed that compared with MSSA group,hypoproteinemia,en-docrine system diseases,wound infection and history of antibiotic use within six months were the independent risk factors for infection in MRSA group.Compared with the control group,hospital transfer,wound infection and tumor were independent risk factors for infection in MRSA group(P＜0.05).Conclusion The detection rate of MRSA in a hospital is high,and the carrying rate of various drug-resistant genes is high.The hospital should pay attention to the prevalence of MRSA and related risk factors,so as to prevent it early.

Acute ST-segment elevation myocardial infarction with multivessel disease is one of the high-risk types of coronary heart disease.Early opening of infarct-related artery and reperfusion of myocardium could significantly reduce the mortality in acute phase.However,the presence of non-culprit lesions in non-infarct-related arteries is still at risk and has an important impact on the long-term prognosis of patients.It remains controversial on how to precisely evaluate the clinical significance and revascularization value of non-culprit lesions.This article aims to review the research status and progress of guidance strategies of non-culprit lesion revascularization in patients with ST-segment elevation myocardial infarction and multivessel disease.

The Flash radiotherapy(Flash-RT),which is the key breakthrough in the basic field of radiotherapy technique,which is expected to cause a new major transformation in the field of radiotherapy.In this paper,we reviewed the latest research advances of the application and the mechanism exploration of Flash-RT in tumor treatment.Current studies have found that both the Flash-RT with electron beams and photon and the Flash-RT with proton can reduce injury of normal tissue than radiotherapy with conventional dose-rate,but the relevant mechanisms are not yet clearly understood,which includes but not limited to oxygen depletion,DNA damage,cellular senescence,apoptosis and immune response.The difference of Flash-RT injury between tumor tissue and normal tissue further reduces the limitations of radiotherapy,and reduces the adverse reaction and complication compared with conventional radiotherapy,which has wide application prospects.

Objective To establish a mouse model of type Ⅰ tricho-hepato-enteric syndrome(THES)induced by Ttc37 deficiency.Methods Ttc37 flox strain was established by site-specifically inserted loxP sites into Ttc37 gene via CRISPR/CAS9 technology.Ubiquitously expressed CAG-Cre was introduced for all-tissue removal of Ttc37 in Ttc37flox/flox;CAG-Cre mice.The knock-out effect was confirmed by fluorescence quantitative PCR and Western blot.Phenotypic evaluations were conducted in 8-week-old mice including hematoxylin-eosin staining of skin,spleen,liver,bladder,and gastrointestinal tract(GI),serum enzyme activity assay of aspartate aminotransferase(AST)and alanine aminotransferase(ALT),measurement of serum hemoglobin level,and ELISA for IgG and IgM level upon antigen immunization.Results Similar to type Ⅰ THES patients,Ttc37flox/flox;CAG-Cre mice exhibited impaired development of hair shaft,epidermis,B cell and eyes,while liver,GI,bladder and serum hemoglobin level seemed normal under unstressed condition.Conclusion A novel mouse model of typeⅠ THES was constructed successfully,which was applicable for pathological study.

Objective To investigate the genetic causes of auditory neuropathy with optic atrophy in a family.Methods The proband's medical history and family history were inquired in detail,and relevant clinical examina-tions were performed to confirm the diagnosis of auditory neuropathy with optic atrophy,and the genetic pedigree of the family was drawn.Peripheral blood of proband(Ⅲ-7)was collected for whole exome sequencing,and the patho-genicity of the detected mutations were interpreted.Blood samples of proband's wife(Ⅲ-8),eldest daughter(Ⅳ-7),second daughter(Ⅳ-9)and son(Ⅳ-10)were tested for mutation sites by Sanger sequencing.Combined with clinical manifestations and examination results,the family was studied.Results The genetic pattern of this family was autosomal dominant.The proband showed decreased visual acuity at the age of 19,bilateral sensorineural deaf-ness at the age of 30,and decreased speech recognition rate.Among 20 members of the family of 5 generations,10(2 deceased)showed similar symptoms of hearing and visual impairment.Proband(Ⅲ-7),eldest daughter(Ⅳ-7)and son(Ⅳ-10)underwent relevant examination.Pure tone audiometry showed bilateral sensorineural deafness.ABR showed no response bilaterally.The 40 Hz AERP showed no response in both ears.OAE showed responses in some or all of the frequencies.No stapedial reflex was detected.The eye movement of Ⅲ-7 and Ⅳ-10 were reasona-ble in all directions,and color vision was normal.Ocular papilla atrophy was observed in different degrees in fundus examination.OCT showed thinning of optic disc nerve fibers in both eyes,and visual evoked potential showed pro-longed P100 wave peak.They were diagnosed as hereditary auditory neuropathy with optic atrophy.A mutation of the OPA1 gene c.1334G＞A(p.Arg445His,NM_015560.2)at a pathogenic locus on chromosome 3 was detected by whole exon detection in Ⅲ-7.The results of generation sequencing analysis showed that the OPA1 gene c.1334G＞A(p.Arg445His,NM_015560.2)mutation of chromosome 3 was also found in Ⅳ-7 and Ⅳ-10.Meanwhile,the gen-otypes of Ⅲ-8 and Ⅳ-9 were wild homozygous,that is,no mutation occurred.Conclusion The OPA1 c.1334G＞A(p.Arg445His,NM_015560.2)mutation site might be the pathogenic mutation in this family.

Objective To investigate the disease spectrum and pathogenic genes of inherited metabolic disorder(IMD)among neonates in Gansu Province of China.Methods A retrospective analysis was conducted on the tandem mass spectrometry data of 286 682 neonates who received IMD screening in Gansu Provincial Maternal and Child Health Hospital from January 2018 to December 2021.A genetic analysis was conducted on the neonates with positive results in tandem mass spectrometry during primary screening and reexamination.Results A total of 23 types of IMD caused by 28 pathogenic genes were found in the 286 682 neonates,and the overall prevalence rate of IMD was 0.63‰(1/1 593),among which phenylketonuria showed the highest prevalence rate of 0.32‰(1/3 083),followed by methylmalonic acidemia(0.11‰,1/8 959)and tetrahydrobiopterin deficiency(0.06‰,1/15 927).In this study,166 variants were identified in the 28 pathogenic genes,with 13 novel variants found in 9 genes.According to American College of Medical Genetics and Genomics guidelines,5 novel variants were classified as pathogenic variants,7 were classified as likely pathogenic variants,and 1 was classified as the variant of uncertain significance.Conclusions This study enriches the database of pathogenic gene variants for IMD and provides basic data for establishing an accurate screening and diagnosis system for IMD in this region.

Inflammation-to-tumor transition is one of the important mechanisms by which the cervical high-risk human papillomavirus(HR-HPV)infection develops into cervical cancer.Persistent cervical HR-HPV infection is an important cause of cervical cancer,and the focal uncontrolled inflammatory microenvironment caused by persistent cervical HR-HPV infection is the underlying mechanism of cervical cancer.The macroscopic and microscopic pathological process of inflammation-to-tumor transition is consistent with the pathogenesis evolution of damp-heat accumulation resulting into toxin in traditional Chinese medicine(TCM):the accumulation of damp-heat is the driving factor of inflammation-to-tumor transition,long-term retention of damp-heat leading to spleen deficiency and liver depression contributes to the characteristics of pathogenesis evolution,and long-term retention of damp-heat toxin causes the disorder of liver and spleen and then blood stasis accumulates in the cervical orifice,which eventually becomes cancer toxin.The process of inflammation-to-tumor transition caused by persistent cervical HR-HPV infection is due to the pathological factors of damp,heat,deficiency and toxin in TCM.Therefore,the regulation of inflammatory microenvironment caused by persistent cervical HR-HPV infection is the key approach to the prevention and treatment of cervical cancer.For the treatment of cervical cancer,methods of clearing heat and drying dampness,strengthening the spleen and soothing the liver are the key therapies.By intervention with the proper pathogen-eliminating methods and with simultaneous regulation of the interior and exterior,the process of inflammation-to-tumor transition can be interrupted.The exploration of inflammation-to-tumor transition caused by persistent cervical HR-HPV infection from the perspective of damp-heat accumulation resulting into toxin will provide thoughts for the prevention and treatment of cervical cancer with TCM and for Chinese medicine in intervening inflammation-to-tumor transition.

Objective:To analyze the association between waist circumference (WC) and ischemic stroke (IS).Methods:The data for the present study were from the prospective cohort study of China Kadoorie Biobank in Qingdao. Using baseline information and IS events of the participants, the Cox proportional hazard regression model and restricted cubic spline (RCS) were used to analyze the association between WC and IS.Results:A total of 33 355 participants were included in the study, with 302 008.88 person-years of follow-up. A total of 1 093 new cases of IS were observed. Multivariate Cox proportional hazard regression model analysis showed that compared to the respondents with normal WC (male <85.0 cm, female <80.0 cm), respondents with excessive WC (male ≥85.0 cm, female ≥80.0 cm) had a 78% higher risk of IS incidence [hazard ratio( HR)=1.78, 95% CI: 1.51-2.10], and the risk increased by 72% ( HR=1.72, 95% CI: 1.40-2.12) and 83% ( HR=1.83, 95% CI: 1.40-2.39) in men and women. According to the RCS, the increase in WC and the risk of IS showed an "S" trend of nonlinear dose-response relationship. Conclusions:The risk of IS would increase with the WC. Keeping a normal WC is important for preventing IS.

This study was aimed at comparing performance differences among three metagenomic sequencing platforms,MGISEQ-2000,Illumina NextSeq 2000,and Ion GeneStudio S5 Plus,to optimize the sequencing process for trace samples.The three sequencing platforms were used to perform high-throughput sequencing on DNA standards and simulated samples.Through analysis of the quality of raw data and microbial detection capabilities,systematic differences among platforms were compared.The sequencing results were optimized for trace samples by incorporation of exogenous nucleic acids during the li-brary preparation process.In terms of data output per batch and base quality,MGISEQ-2000 surpassed the other two plat-forms.Illumina NextSeq 2000 had the lowest proportion of duplicate reads,whereas Ion GeneStudio S5 Plus had the highest proportion,and significant differences were observed across platforms(P＜0.001).In sequencing uniformity,MGISEQ-2000 and Illumina NextSeq 2000 were superior to Ion GeneStudio S5 Plus.MGISEQ-2000 provided a substantial advantage in microbial detection capability(P＜0.001),but the advantage diminished with decreasing bacterial fluid concentration.Ion GeneStudio S5 Plus had the shortest duration for single-batch sequencing.Moreo-ver,for trace samples with DNA content ≤0.05 ng,the experi-mental group(with added exogenous nucleic acids)achieved a higher number of reads than the control group(without exogenous nucleic acids),with a 11.09±8.03 fold increase.In conclu-sion,the different sequencing platforms each had advantages and disadvantages,thus allowing researchers to choose the appro-priate platform according to specific needs.Furthermore,the addition of exogenous nucleic acids improved the microorganism detection efficiency,and provided better support for subsequent diagnosis and evaluation of results.