Objective:To investigate the clinical value of prospective ECG-gated high-pitch protocol scanning of third generation DSCT in the diagnosis of pediatric congenital heart disease (CHD).Methods:A total of 243 children with confirmed CHD who were expected to undergo surgical treatment were prospectively collected and randomly divided evenly into 3 groups, with first group for prospective ECG-gated high-pitch scanning in third generation DSCT (Flash 3rd), second group for prospective ECG-gated high-pitch scanning in second generation DSCT (Flash 2nd) and third group for prospective sequential scanning in third generation DSCT (Sequence 3rd). The SD value and SNR of aortic root and pulmonary artery of each child were recorded. The 5-point system is adopted with subjective scoring. Based on the result of operation, the diagnosis accuracy in 3 groups was analyzed. Results:The E values in Flash 3rd, Flash 2nd and Sequence 3rd group were 0.24 (0.19, 0.27), 0.11 (0.10, 0.14) and 0.44 (0.39, 0.48) mSv ( H=207.04, P<0.05), respectively. Subjective scores of group Flash 3rd and Sequence 3rd were significantly higher than that of group Flash 2nd [4 (4, 4) vs. 4(3, 4) vs. 3(3, 3), H=124.05, P<0.05] and no difference between these two groups. SD value of aortic root and pulmonary artery of group Flash 3rd and Sequence 3rd were significantly lower than that of group Flash 2nd( H= -40.27-33.38, P<0.05). SNR of aortic root and pulmonary artery of group Flash 3rd was significantly higher than that of group Flash 2nd and Sequence 3rd ( H=-0.90-51.42, P<0.05). Diagnosis accuracy of intracardiac malformation for group Flash 2nd was significantly lower than that of Flash 3rd and Sequence 3rd (77.7%, 90.9%, 88.9%, K=9.36, P<0.05), and there was no significant difference between the latter two groups. There was no difference in diagnosis accuracy of extracardiac malformation among 3 groups (88.6%, 94.8%, 92.2%, K=3.11, P=0.21). Conclusions:The prospective ECG-gated high-pitch scanning in third generation DSCT can take into account radiation dose and image quality, which has important clinical value in the diagnosis of CHD.

Objective To construct and evaluate the rat model of thyroid nodule liver-qi depression syndrome with the combination of disease and syndrome,so as to lay a foundation for the exploration of the mechanism and clinical research of traditional Chinese medicine in the treatment of thyroid nodule.Methods 36 rats were randomly divided into three groups.The model was induced by chronic unpredictable mild stress(CUMS)stimulation combined with propylthiouracil(PTU).The rats in the blank group were fed with saline at the dose of 1 mL·100 g-1·d-1,and the rats in the PTU group were fed with 0.1%PTU solution at the dose of 1 mL·100 g-1·d-1.The rats in the CUMS+PTU group were fed with CUMS stimulation in a single cage and intragastric administration of 0.1%PTU solution according to the dose of 1 mL·100 g-1·d-1,and the modeling time lasted for 6 weeks.After the establishment of the model,the model of combination of disease and syndrome was evaluated comprehensively by means of animal behavior detection,ultrasonic image,apparent morphology observation,pathological staining and serum hormone index detection.Results Compared with control group and PTU group,the total distance in the open field was significantly shortened,the sucrose preference rate was significantly decreased,and the swimming suspension time was significantly prolonged in the CUMS+PTU group,showing obvious symptoms of liver qi stagnation.In addition,compared with the other two groups,the thyroid gland of CUMS+PTU group showed obvious enlargement and nodule formation,thyroid index significantly increased,and thyroid follicular epithelial cells showed a high phase of proliferation.In terms of hormone levels,compared with control group,the serum levels of free triiodothyronine(FT3)and free thyroxine(FT4)in CUMS+PTU group were significantly lower,while the level of thyroid stimulating hormone(TSH)was significantly higher,which was in line with the current evaluation criteria of thyroid nodule model.Conclusion The method of CUMS stimulation combined with PTU drug induction can successfully prepare the rat model of thyroid nodule liver-qi depression syndrome,and the comprehensive evaluation method is stable and reliable,which is helpful to improve the scientific nature of the disease-syndrome combination model.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Objective:To investigate the optimal delay time in the quantitative assessment of myocardial fibrosis based on dual-energy CT extracellular volume fraction (DECT-ECV), using MRI as a reference.Methods:Thirty patients with confirmed or suspected of cardiomyopathy were prospectively enrolled in this study. All the patients underwent both cardiac DECT and MRI examination within one week. According to the imaging features of late gadolinium enhancement (LGE) on MRI, myocardial segments were classified into 3 types: ischemic LGE segments, non-ischemic LGE segments and negative LGE segments. According to the DECT delay time, the whole and segmental myocardium were divided into 3 groups: delay of 3 min (Group A), delay of 5 min (Group B) and delay of 7 min (Group C). Correlation and agreement between CT-ECV and MRI-ECV were performed on a basis of overall myocardium and segmental myocardium. Pearson or Spearman test was used for correlation analysis and Bland-Altman test was used for consistency analysis.Results:Thirty patients with 480 segments were finally included in our study. In the analysis based on overall myocardium, MRI-ECV was 33.12%±4.29%, and CT-ECV were 35.81%±4.48%, 36.02%±4.56%, and 36.58%±4.69% in Group A, B, and C, respectively. The agreement between DECT-ECV and MRI-ECV results was good, with the correlation coefficients of 0.878 (group A), 0.955 (Group B) and 0.947 (Group C) (all P<0.001). In the analysis based on segmental myocardium, as for the ischemic LGE myocardial segments, MRI-ECV was 34.60%(31.70%,39.40%), and CT-ECV were 37.50 (34.20, 41.90), 38.20%(36.20%, 40.60%)and 39.40%(35.50%,42.40%)in Group A, B, and C, respectively. The agreement between DECT-ECV and MRI-ECV results was good, with the correlation coefficients of 0.559, 0.695 and 0.682 (all P<0.001) for groups A, B and C, and as for non-ischemic LGE myocardial segments, MRI-ECV was 35.10% (32.68%, 38.70%), and CT-ECV were 38.15% (35.13%, 41.75%), 39.25% (35.78%, 42.20%) and 39.60% (35.88%,42.90%) in Group A, B, and C. The correlation coefficients of CMR-ECV and DECT-ECV of groups A, B and C were 0.531, 0.772 and 0.744 (all P<0.001), showing good agreement; as for negative LGE myocardial segments, MRI-ECV and CT-ECV of Group A, Group B, Group C were 28.50%(27.00%, 30.10%), 31.10%(28.70%, 34.60%), 31.30%(28.40%, 33.80%), 31.30%(29.20%, 34.80%). The correlation coefficients between MRI-ECV and DECT-ECV of group A, B and C were 0.273, 0.508 and 0.425 (all P<0.001), which also showed good agreement. Conclusions:DECT-ECV can be used for quantitative evaluation of myocardial histological features. DECT-ECV with a 5 min and 7 min delay shows good correlation and agreement with MRI-ECV. In order to make this technology more well-known and improve its application capability, our recommendation for clinical practice is a 5 min delay after contrast administration in clinical practice.

BACKGROUND: This study aimed to develop a comprehensive instrument for evaluating and ranking clinical practice guidelines, named Scientific, Transparent and Applicable Rankings tool (STAR), and test its reliability, validity, and usability. METHODS: This study set up a multidisciplinary working group including guideline methodologists, statisticians, journal editors, clinicians, and other experts. Scoping review, Delphi methods, and hierarchical analysis were used to develop the STAR tool. We evaluated the instrument's intrinsic and interrater reliability, content and criterion validity, and usability. RESULTS: STAR contained 39 items grouped into 11 domains. The mean intrinsic reliability of the domains, indicated by Cronbach's α coefficient, was 0.588 (95% confidence interval [CI]: 0.414, 0.762). Interrater reliability as assessed with Cohen's kappa coefficient was 0.774 (95% CI: 0.740, 0.807) for methodological evaluators and 0.618 (95% CI: 0.587, 0.648) for clinical evaluators. The overall content validity index was 0.905. Pearson's r correlation for criterion validity was 0.885 (95% CI: 0.804, 0.932). The mean usability score of the items was 4.6 and the median time spent to evaluate each guideline was 20 min. CONCLUSION The instrument performed well in terms of reliability, validity, and efficiency, and can be used for comprehensively evaluating and ranking guidelines.
Reproducibility of Results ; Surveys and Questionnaires ; Practice Guidelines as Topic ; Humans

Background: Inactivated vaccines are limited in preventing foot-and-mouth disease (FMD) due to safety problems. Recombinant virus-like particles (VLPs) are an excellent candidate for a novel vaccine for preventing FMD, given that VLPs have similar immunogenicity as natural viruses and are replication- and infection-incompetent. Objectives: The 3C protease and P1 polyprotein of type O FMD virus (FDMV) was expressed in yeast Hansenula polymorpha to generate self-resembling VLPs, and the potential of recombinant VLPs as an FMD vaccine was evaluated. Methods: BALB/c mice were immunized with recombinant purified VLPs using CpG oligodeoxynucleotide and aluminum hydroxide gel as an adjuvant. Cytokines and lymphocytes from serum and spleen were analyzed by enzyme-linked immunosorbent assay, enzyme-linked immunospot assay, and flow cytometry. Results: The VLPs of FMD were purified successfully from yeast protein with a diameter of approximately 25 nm. The immunization of mice showed that animals produced high levels of FMDV antibodies and a higher level of antibodies for a longer time. In addition, higher levels of interferon-γ and CD4 + T cells were observed in mice immunized with VLPs. Conclusions The expression of VLPs of FMD in H. polymorpha provides a novel strategy for the generation of the FMDV vaccine.

ObjectiveTo observe the effects of Aurantii Fructus Immaturus， Atractylodis Macrocephalae Rhizoma， and their combination on slow transit constipation via PTEN-induced putative kinase 1 （PINK1）/Parkin pathway-mediated mitophagy. MethodFifty-six male SD rats were randomly assigned into normal group， model group， natural recovery group， Aurantii Fructus Immaturus group， Atractylodis Macrocephalae Rhizoma group， Aurantii Fructus Immaturus combined with Atractylodis Macrocephalae Rhizoma group， and mosapride group， with 8 rats in each group. Slow transit constipation model was established by gavage with loperamide （3 mg·kg^-1·d^-1） for 14 days in other groups except the normal group. After successful modeling， except that the model group was continuously induced by loperamide， the normal group and the natural recovery group were administrated with 0.9% normal saline by gavage， and the rats in the Aurantii Fructus Immaturus （1.35 g·kg^-1·d^-1） group， the Atractylodis Macrocephalae Rhizoma （2.7 g·kg^-1·d^-1） group， the Aurantii Fructus Immaturus combined with Atractylodis Macrocephalae Rhizoma （4.05 g·kg^-1·d^-1） group， and the mosapride （1.56 mg·kg^-1·d^-1） group were administrated with corresponding drugs by gavage for 7 days. The amount of feces， fecal water content， and intestinal propulsion rate of rats were determined. The pathological changes of the colon were evaluated by hematoxylin-eosin （HE） staining and Alcian blue-periodic acid-Schiff （AB-PAS） staining. The activity of respiratory chain complex and the ultrastructure of the colon tissue were determined by ultraviolet spectrophotometry and observed by transmission electron microscopy， respectively. Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） was employed to determine the mRNA levels of PINK1， Parkin， and p62， and Western blot to determine the protein levels of microtubule-associated protein 1 light chain 3 （LC3）， PINK1， and Parkin. ResultCompared with the normal group， the model group and the natural recovery group showed decreases in the amount of feces， fecal water content， intestinal propulsion rate （P<0.05，P<0.01）， and activities of mitochondrial respiratory chain complexes Ⅱ， Ⅲ， and Ⅳ in the colon tissue （P<0.05，P<0.01）. Further， the mRNA levels of PINK1 and Parkin and the protein levels of PINK1， Parkin， and LC3 were up-regulated （P<0.01） and the mRNA level of p62 was down-regulated in the model group （P<0.05） and the natural recovery group. Compared with the model group and the natural recovery group， the Aurantii Fructus Immaturus combined with Atractylodis Macrocephalae Rhizoma group showed increased amount of feces， fecal water content， intestinal propulsion rate， and activities of mitochondrial respiratory chain complexes Ⅱ， Ⅲ， and Ⅳ （P<0.05，P<0.01）. Moreover， the combination meliorated the degree of mitochondrial swelling in the colon tissue， down-regulated the mRNA levels of PINK1 and Parkin and the protein levels of PINK1， Parkin， and LC3 （P<0.05，P<0.01）， and up-regulated the mRNA level of p62 （P<0.05）. ConclusionAurantii Fructus Immaturus and Atractylodis Macrocephalae Rhizoma， and their combination may remedy the colonic motility disorders in rats with slow transit constipation by blocking PINK1/Parkin signaling pathway to inhibit the excessive mitophagy in interstitial cells of Cajal in the colon tissue.

Episodic ataxia (EA) is a group of disorders characterized by recurrent spells of vertigo, truncal ataxia, and dysarthria. Episodic ataxia type 2 (EA2), the most common subtype of EA, is an autosomal dominant disease caused by mutation of the CACNA1A gene. EA2 has been rarely reported in the Chinese population. Here we present an EA2 family admitted to Xiangya Hospital in October 2018. The proband was a 22-year-old male who complained of recurrent spells of vertigo, slurred speech, and incoordination for 4 years. Brain magnetic resonance imaging (MRI) showed cerebellar atrophy. He had neuropsychological development disorder in childhood, and cognitive assessment in adulthood showed cognitive impairment. The proband's mother and grandmother had a similar history. Peripheral blood samples from the proband and family members were collected, and genomic DNA was isolated. Whole exome sequencing of the proband detected a heterozygous frameshift mutation c.2042_2043del (p.Q681Rfs*100) of CACNA1A gene. This mutation was verified in the proband and 2 family members using Sanger sequencing. One family member carrying this mutation was free of symptoms and signs, suggesting an incomplete penetrance of the mutation. We reported a variant c.2042_2043del of CACNA1A gene as the pathogenic mutation in a Chinese EA2 family for the first time. This case enriched the clinical spectrum of CACNA1A related EA2, and contributed to the understanding of clinical and genetic characteristics of EA2 to reduce misdiagnosis.
Adult ; Ataxia ; Calcium Channels/genetics* ; Humans ; Male ; Mutation ; Nystagmus, Pathologic ; Pedigree ; Vertigo ; Young Adult

Objective:To determinate the active ingredients and predicte action targets in Sanhua Decoction for treating cerebral ischemia based on HPLC and network pharmacology methods. Methods:The HPLC analysis was performed on HC-C18 (250 mm × 4.6 mm, 5 μm) with the mobile phase of methanolacetonitrile-0.05% phosphoric acid with gradient elution at the flow rate of 1.0 ml/min and 0.8 ml/min. The detection wavelength was set at 254 nm, the column temperature was at 30 ℃, and the injection volume was 10 μl. TCMIP v2.0 platform was used to search the action targets of rhein, emodin, chrysophanol, hesperidin, magnolol and notopterygiol. We used Cerebral ischemia as a keyword searching the databases such as Genecards, OMIM, TTD, and Disgenet to screen six potential targets for the treatment of cerebral ischemia by active ingredients, construct a protein interaction (PPI) network and a disease-component-target-pathway integration network.Results:The literature search determined that rhein, emodin, chrysophanol, hesperidin, magnolol and qianhuol were the index components for the determination of Sanhua Decoction. Their linear ranges were 0.080 4-0.804 0 μg, 0.015 3-0.382 0 μg, 0.041 8-0.626 4 μg, 0.312 6-3.908 0 μg, 0.037 9-0.568 8 μg, 0.045 3-1.359 6 μg, respectively. The correlation coefficient R 2 is greater than 0.999 0. The content ranges of the above six components in seven samples were 0.887-0.971 mg/g, 0.094-0.101 mg/g, 0.110-0.119 mg/g, 1.494-1.669 mg/g, 0.126-0.145 mg/g and 0.153-0.167 mg/g, respectively. Network pharmacology analysis found that the targets of the six components for the treatment of cerebral ischemia may be TNF, TP53, MAPK14, JUN, IL1B, MYC, ESR1, ICAM1, PTGS2, PPARG and so on. Conclusions:A quality control method forthe six active ingredients in Sanhua Decoction treating cerebral ischemia was established. This method is simple and repeatable. The ten potential targets of the six active ingredients in Sanhua Decoction for the treatment of cerebral ischemia have been clarified, laying a foundation for further research on the action mechanism.

OBJECTIVE: To carry out G-banded chromosomal karyotyping and chromosomal microarray analysis (CMA) for a fetus featuring multiple malformations. METHODS: The fetus was found to have increased nuchal thickness, generalized edema, asymmetric lower limbs, tetralogy of Fallot, nasal bone anomaly and cleft palate. Following amniocentesis, G-band karyotyping and CMA were carried out. RESULTS: The fetus had a karyotype of 47,XX,+i(12)(p10) [14]/46,XX[6]. CMA has identified a 33.9 Mb duplication at 12p13.33-p11.1, which was suggestive of tetrasomy 12p. CONCLUSION Combined chromosomal karyotyping and CMA can delineate the origin of abnormal chromosomal fragments during prenatal diagnosis. The fetus was diagnosed with Pallister-Killian syndrome.