Myocarditis has diverse clinical manifestations,which might develop into acute heart failure,cardiogenic shock and chronic dilated cardiomyopathy.Early diagnosis of myocarditis is crucial for improving prognosis.Cardiac MRI(CMRI)can display myocardial necrosis,fibrosis and edema,having become the best imaging method for evaluating myocarditis.The progresses in multi-parameter CMRI researches of acute myocarditis were reviewed in this article.

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.

Cortical interneurons can be categorized into distinct populations based on multiple modalities, including molecular signatures and morpho-electrical (M/E) properties. Recently, many transcriptomic signatures based on single-cell RNA-seq have been identified in cortical interneurons. However, whether different interneuron populations defined by transcriptomic signature expressions correspond to distinct M/E subtypes is still unknown. Here, we applied the Patch-PCR approach to simultaneously obtain the M/E properties and messenger RNA (mRNA) expression of >600 interneurons in layer V of the mouse somatosensory cortex (S1). Subsequently, we identified 11 M/E subtypes, 9 neurochemical cell populations (NCs), and 20 transcriptomic cell populations (TCs) in this cortical lamina. Further analysis revealed that cells in many NCs and TCs comprised several M/E types and were difficult to clearly distinguish morpho-electrically. A similar analysis of layer V interneurons of mouse primary visual cortex (V1) and motor cortex (M1) gave results largely comparable to S1. Comparison between S1, V1, and M1 suggested that, compared to V1, S1 interneurons were morpho-electrically more similar to M1. Our study reveals the presence of substantial M/E variations in cortical interneuron populations defined by molecular expression.
Mice ; Animals ; Neocortex/physiology* ; Mice, Transgenic ; Interneurons/physiology*

Approximately 140 million people worldwide are homozygous carriers of APOE4 (ε4), a strong genetic risk factor for late onset familial and sporadic Alzheimer's disease (AD), 91% of whom will develop AD at earlier age than heterozygous carriers and noncarriers. Susceptibility to AD could be reduced by targeted editing of APOE4, but a technical basis for controlling the off-target effects of base editors is necessary to develop low-risk personalized gene therapies. Here, we first screened eight cytosine base editor variants at four injection stages (from 1- to 8-cell stage), and found that FNLS-YE1 variant in 8-cell embryos achieved the comparable base conversion rate (up to 100%) with the lowest bystander effects. In particular, 80% of AD-susceptible ε4 allele copies were converted to the AD-neutral ε3 allele in human ε4-carrying embryos. Stringent control measures combined with targeted deep sequencing, whole genome sequencing, and RNA sequencing showed no DNA or RNA off-target events in FNLS-YE1-treated human embryos or their derived stem cells. Furthermore, base editing with FNLS-YE1 showed no effects on embryo development to the blastocyst stage. Finally, we also demonstrated FNLS-YE1 could introduce known protective variants in human embryos to potentially reduce human susceptivity to systemic lupus erythematosus and familial hypercholesterolemia. Our study therefore suggests that base editing with FNLS-YE1 can efficiently and safely introduce known preventive variants in 8-cell human embryos, a potential approach for reducing human susceptibility to AD or other genetic diseases.
Humans ; Apolipoprotein E4/genetics* ; Cytosine ; Mutation ; Blastocyst ; Heterozygote ; Gene Editing ; CRISPR-Cas Systems

CRISPR-Associated Protein 9 ; Gene Editing ; CRISPR-Cas Systems/genetics*

Objective:To investigate the death risk prediction factors of acute pancreatitis (AP) patients in intensive care unit (ICU), and to establish a death prediction model and evaluate its efficacy.Methods:A retrospective cohort study was conducted using the data in the Medical Information Mart for Intensive Care-Ⅲ (MIMIC-Ⅲ). The clinical data of 285 AP patients admitted to the ICU in the database were collected, including age, gender, blood routine and blood biochemical indicators, comorbidities, simplified acute physiology score Ⅲ (SAPS Ⅲ) and hospital prognosis. By using univariate analysis, the differences in the clinical data of the patients were compared between the two groups. Binary multivariate Logistic regression analysis was used to screen out independent predictors of in-hospital death in AP patients. A death prediction model was established, and the nomogram was drawn. The receiver operator characteristic curve (ROC curve) was plotted, and the area under the ROC curve (AUC) was used to test the discrimination of the prediction model. In addition, the prediction model was compared with the SAPSⅢ score in predicting in-hospital death. The calibration ability of the prediction model was evaluated by the Hosmer-Lemeshow goodness of fit test, and a calibration map was drawn to show the calibration degree of the prediction model.Results:Among 285 patients with AP, 29 patients died in the hospital and 256 patients survived. Univariate analysis showed that the patients in the death group were older than those in the survival group (years old: 70±17 vs. 58±16), and had higher white blood cell count (WBC), total bilirubin (TBil), serum creatinine (SCr), blood urea nitrogen (BUN), red blood cell volume distribution width (RDW), proportion of congestive heart failure and SAPSⅢ score [WBC (×10 9/L): 18.5 (13.9, 24.3) vs. 13.2 (9.3, 17.9), TBil (μmol/L): 29.1 (15.4, 66.7) vs. 16.2 (10.3, 29.1), SCr (μmol/L): 114.9 (88.4, 300.6) vs. 79.6 (53.0, 114.9), BUN (mmol/L): 13.9 (9.3, 17.8) vs. 6.1 (3.7, 9.6), RDW: 0.152 (0.141, 0.165) vs. 0.141 (0.134, 0.150), congestive heart failure: 34.5% vs. 14.8%, SAPSⅢ score: 66 (52, 90) vs. 39 (30, 48), all P < 0.05]. Multivariate Logistic regression analysis showed that age [odds ratio ( OR) = 1.038, 95% confidence interval (95% CI) was 1.005-1.073], WBC ( OR = 1.103, 95% CI was 1.038-1.172), TBil ( OR = 1.247, 95% CI was 1.066-1.459), BUN ( OR = 1.034, 95% CI was 1.014-1.055) and RDW ( OR = 1.344, 95% CI was 1.024-1.764) were independent risk predictors of in-hospital death in patients with AP. Logistic regression model was established: Logit ( P) = 0.037×age+0.098×WBC+0.221×TBil+0.033×BUN+0.296×RDW-12.133. ROC curve analysis showed that the AUC of the Logistic regression model for predicting the in-hospital death of patients with AP was 0.870 (95% CI was 0.794-0.946), the sensitivity was 86.2%, and the specificity was 78.5%, indicating that the model had good predictive performance, and it was superior to the SAPSⅢ score [AUC was 0.831 (95% CI was 0.754-0.907), the sensitivity was 82.8%, and the specificity was 75.4%]. A nomogram model was established based on the result of multivariate Logistic regression analysis. The calibration map showed that the calibration curve of the nomogram model was very close to the standard curve, with the goodness of fit test: χ 2 = 6.986, P = 0.538, indicating that the consistency between the predicted death risk of the nomogram model and the actual occurrence risk was relatively high. Conclusions:The older the AP patient is, the higher the WBC, TBil, BUN, and RDW, and the greater the risk of hospital death. The death prediction Logistic regression model and nomogram model constructed based on the above indicators have good discrimination ability and high accuracy for high-risk patients with hospital death, which can accurately predict the probability of death in AP patients and provide a basis for prognosis judgment and clinical treatment of AP patients.

Image 1.

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

The status of lymph node metastasis is an important prognostic factor for many malignant tumors, including lung cancer. In the 8th edition of the TNM staging system for lung cancer, the T staging had obvious changes and refinements, but the N staging had little changes. Recently, several studies have found that the prognosis of patients with the same N stage can vary greatly, suggesting that a more detailed subgroup of patients with the same N stage should be subdivided, including the inclusion of extra-capsular lymph node metastases (ENE). In this review, we reviewed the definition, classification/grading, imaging diagnosis, pathological diagnosis, related molecular markers and their relationship with the prognosis of lung cancer patients.

Objective To construct a three-dimensional finite element model to investigate the biomechanical mechanism of carotid blast injuries.Methods Based on the head and neck CT angiography data of a healthy male volunteer,the 3D geometric model was extracted by Mimics software.The 3D solid model was obtained by fitting the geometric model to the non-uniform rational B-splines (NURBS) by Geomagic Studio software.The mesh of blood vessels,blood and soft tissue was divided by HyperMesh software to obtain the three-dimensional finite element model of the carotid artery.The material parameters and boundary conditions were set,and the vessel wall rupture damage threshold was 1 MPa.The dynamic process of carotid injury caused by MK3A2 grenade explosion shock wave at the distance of 60,70 and 80 cm to the neck was simulated using the LS-DYNA,generating the shock waveform and peak overpressure.The stress cloud map was used to analyze the stress distribution and damage morphology,and the stress curve was used to analyze the mechanical changes.Results The peak values of shock wave overpressure were 0.45,0.63 and 0.96 MPa at the distance of 80,70 and 60 cm away from the explosion center,respectively.At 80 cm,the peak stress of vessel wall was 0.43 MPa,and the vessel wall was not ruptured;at 70 cm,the peak stress of anonyma was greater than 1 MPa,which resulted in small rupture;at 60 cm,the peak stress of both anonyma the ascending aorta were greater than 1 MPa,leading to obvious rupture.The root part of the common carotid artery,anonyma and the arch of the aorta were high stress concentration areas,manifested as high-prevalence areas of damage and rupture.Conclusions The finite element model of explosive carotid artery injury is successfully constructed,which can be used to analyze the mechanical response and damage mechanism of carotid blast injuries.The main cause of injury and rupture is that the sudden change of stress in the process of explosion shock reaches or exceeds the threshold of vascular wall injury.Carotid artery rupture will occur when the vessel wall stress peak is greater than 1 MPa at 60 and 70 cm away from the explosion center,providing references for the clinical treatment and injury prevention.