[Objective] To describe a case of a rare,novel mutation causing recurrent chorioamniotic membrane separation in a Chinese family with combined next-generation sequencing (NGS) and Sanger sequencing.[Methods] For the affected fetus,potential mutation were detected by the conbinedcombined next-generation sequencing (NGS) and Sanger sequencing.And the prenatal diagnosis were identified by Sanger sequencing.[Results] A frameshifting mutation c.1389_1390delAG (inherited from mother),and a missense mutationc.1006 G ＞ C (inherited from mother) have been identified in the affected fetus (the second pregnancy).The prenatal diagnosis of the third fetus turns out to be a carrier,the mutation was inherited from father.[Conclusions] We describe a novel mutation in gene ZMPSTE24,which was considered with mandibuloacral dysplasia with type B,and that may be the cousecoursecausing of recurrent chorioamniotic membrane separation.This rare mutation constitutes an additional heterogeneous defect causing chorioamniotic membrane separation.And the conbinedcombined next-generation sequencing (NGS) and Sanger sequencing allows high resolution characterization of novel mutions that are not readily detected by present methods.

Objective:To explore the change of blood-brain barrier (BBB) permeability in septic rats.Methods:A rat model of sepsis was established by cecal ligation and puncture. Rats were randomly (random number) grouped according to the intervention time: sham-operated group, sepsis 1-day group, sepsis 4-day group, and sepsis 7-day group. Fluorescein sodium was used to test the permeability of the BBB. Western blot and immunofluorescence methods were applied to detect the expression of tight junction proteins including Claudin-5, Occludin and ZO-1.Results:Compared with the sham-operated group, rats in the sepsis group presented quick breath, slow response, decreased intake of food and water, obvious abdominal distension and loose stools. After abdominal anatomy of sepsis rats, we found mesenteric adhesions, dilatation of proximal intestinal, black cecum ligation site with purulent exudate, enlarged liver and diffused bloody exudate. Compared with the sham-operated group, body weight of sepsis rats was reduced remarkably ( P < 0.05). The body weight of rats of sepsis 7-day group was the lowest, which was significantly lower than that of rats of sepsis 4-day group ( P< 0.05) and 1-day group ( P< 0.05). Compared with the sham-operated group, the content of fluorescein sodium in sepsis 1-day rats was increased remarkably ( P< 0.05). The content of fluorescein sodium in rats of sepsis 7-day group was the highest, which was significantly higher than that in rats of sepsis 4-day group ( P< 0.05) and 1-day group ( P< 0.05). Compared with the sham-operated rats, the expression of Claudin-5, Occludin and ZO-1 in sepsis rats were decreased remarkably (all P < 0.05). The expression of Claudin-5, Occludin and ZO-1 were the lowest in rats of the sepsis 7-day group, which were significantly decreased than those of rats in the sepsis 4-day group (all P< 0.05) and rats in sepsis 1-day group (all P < 0.05). Conclusions:Sepsis rats showed increased permeability of the BBB, and the permeability of BBB increased continuously along with the duration of sepsis.

OBJECTIVETo identify the pathogenic mutation in a family affected with tuberous sclerosis.

METHODSFor the proband and its parents, mutational hotspots in the 11 exons of TSC1 and TSC2 gene were analyzed with DNA sequencing and bioinformatics tools.

RESULTSA heterozygous c.4493G>C missense mutation was identified in the proband. The same mutation was however not found in the parents.

CONCLUSIONThe missense mutation c.4493G>C probably underlie the tuberous sclerosis complex seen in the child.

Base Sequence ; Child ; DNA Mutational Analysis ; Exons ; Female ; Humans ; Molecular Sequence Data ; Point Mutation ; Tuberous Sclerosis ; genetics ; Tumor Suppressor Proteins ; genetics

Objective:To investigate the diagnostic and early-warning value of laboratory test indicators for sepsis-induced myocardial injury (SIMD).Methods:The clinical data of 183 patients with sepsis admitted to the Department of Emergency and Critical Care Medicine of Guangdong Provincial People's Hospital from August 2016 to October 2020 were collected. The patient's age, gender, past medical history, vital signs and pathogen culture results were extracted. Cardiac function, blood routine, liver function, renal function, inflammatory factors, coagulation function, APACHE Ⅱ and SOFA scores were recorded at enrollment and 72 h after admission. SIMD was defined as cTnT ≥300 pg/mL and NT-proBNP ≥1243 pg/mL twice in 72 h intervals between enrolled cases, and the early-warning factors of patients with SIMD were analyzed. The differences in various indicators between the two groups were compared, and Logistic regression analysis was used to explore the diagnostic efficacy of cTnT and NT-proBNP combined for SIMD, and the correlation between PCT/PLT ratio and the occurrence of SIMD.Results:Among 250 patients, 67 patients were excluded for lack of the main indicators, and 183 patients (including 62 patients with history of cardiac disease) were enrolled finally. Among 183 patients with sepsis, 105 patients (57.38%) with cTNT ≥300 pg/mL and NT-proBNP ≥1 243 pg/mL, were diagnosed as myocardial injury; after excluding 62 patients with history of cardiac disease, 59 patients (48.76%) with cTNT ≥300 pg/mL and NT-proBNP ≥1 243 pg/mL were diagnosed as myocardial injury. Logistic regression analysis showed that increased PCT/PLT ratio ( OR=1.585, 95% CI: 1.124-2.237, P=0.009) was an independent risk factor for early-warning of SIMD. The PCT/PLT ratio ( OR= 1.850, 95% CI: 1.103-3.102, P=0.020) could stably predict the occurrence of SIMD in patients without previous history of heart disease. ROC curve analysis showed that PCT/PLT ratio could effectively predict the occurrence of SIMD (AUC=0.693, 95% CI: 0.617-0.769, P<0.001), the optimal cut-off value was 0.177 (sensitivity: 65.7%, specificity: 66.7%). The PCT/PLT ratio was still effective in predicting the occurrence of SIMD after excluding patients with previous history of heart disease (AUC=0.733, 95% CI: 0.643-0.823, P<0.001), and the optimal cut-off value was 0.429 (sensitivity: 55.9%, specificity: 83.9%). Conclusions:The combination of cTnT and NT-proBNP has certain diagnostic value for SIMD, and the PCT/PLT ratio could warn the occurrence of SIMD.

Objective:To investigate whether stress hyperglycemia (SH) is an independent risk factor for the occurrence and mortality of sepsis-associated encephalopathy (SAE).Methods:From August 2016 to October 2021, sepsis patients admitted to the ICU of Guangdong Provincial People's Hospital were selected as the study subjects. According to whether they developed to SH (RBG>11.1 mmol/L) within 7 days of enrollment, the pat ients were divided into the SH group and the non-SH group for analysis. Logistic regression was used to analyze whether SH was an independent risk factor for SAE occurrence, and ROC curve was used to analyze the predictive value of SH to SAE. Kaplan-Meier curve was used to compare the 90-day survival of SAE patients with or without SH. Cox regression analysis was used to analyze the risk factors of 28-day and 90-day death in SAE patients.Results:A total of 183 sepsis patients were included, including 62 patients in the SH group and 121 in the non-SH group. Logistic regression analysis demonstrated that SH was an independent risk factor for SAE ( OR=4.452, 95% CI: 2.021-9.808, P <0.001). ROC curve demonstrated that SH could accurately predict SAE (AUC=0.831; Sensitivity=78.4%; Specificity=76.8%; and Yoden index=0.553). Kaplan-Meier curve demonstrated that the 90-day survival of SAE patients with SH significantly declined (log-rank test: P<0.01). Cox regression analysis suggested that SH was a risk factor for death at day 28 and day 90 in SAE patients (28 d, HR=2.272, 95% CI: 1.212-4.260, P=0.010; 90 d, HR=2.456, 95% CI: 1.400-4.306, P<0.01). Conclusions:SH is an independent risk factor for SAE and can predict SAE occurrence. SH significantly reduces 90-day survival and increase mortality at 28 and 90 days in SAE patients.

Purpose To explore the cardioprotective effect of cang-ai volatile oil(CAVO)on rats with cardiac function impairment model under low-pressure and low-oxygen environment in Tibet Plateau based on 7.0T cardiovascular magnetic resonance(CMR)imaging.Materials and Methods Forty SD rats were randomly divided into the normal group,the high altitude model group,the CAVO-treated group and the rhodiola rosea-treated group,with 10 rats in each group.Except for the normal group,the rats in other groups were transferred from the plain(500 m above sea level)to the Tibet Plateau(4 250 m above sea level)for two months,and then administered with the corresponding drugs by gavage for 14 d.The left ventricle function was measured by using a 7.0T high-field strength CMR and myocardial strain was analysed by using tissue tracing technique.HE staining was used to observe the morphology of cardiomyocytes,Masson staining to observe interstitial fibrosis,wheat germ agglutinin staining to observe cardiomyocyte hypertrophy,and transmission electron microscopy to observe the morphological changes of mitochondria in each group.Serum levels of creatine kinase,creatine kinase isoenzyme,lactate dehydrogenase,cardiac troponin T,superoxide dismutase,malondialdehyde and glutathione peroxidase were detected.Intracellular reactive oxygen species levels were detected using flow cytometry.Results The left ventricular ejection fraction of rats in the CAVO-treated group was higher than that of the high altitude model group[(66.61±1.38)％vs.(60.94±3.21)％;t=3.969,P=0.032];meanwhile,the global circumferential strain of the left ventricle in the CAVO-treated group was higher than that of the high altitude model group(-25.68±1.30 vs.-22.84±1.17;t=3.967,P=0.003).HE,Masson and wheat germ agglutinin staining showed hypertrophy and necrosis as well as interstitial fibrosis and ultrastructural disruption of cardiomyocytes in the high altitude model group,which improved after CAVO treatment.The level of cardiac troponin T in the serum of rats with CAVO treatment group was significantly decreased compared with that of the high altitude model group[(314.03±20.05)pg/ml vs.(518.30±18.13)pg/ml;1=13.090,P=0.001].Conclusion CAVO treatment can reduce cardiac injury caused by low-pressure hypoxia in high altitude,and its effect can be detected dynamically and non-invasively by 7.0T high-field strength CMR.