In January 2021, an acute chemical poisoning incident occurred at a fluorine polymerization plant. Through the analysis of the occupational health situation of the enterprise, combined with the clinical manifestations of the poisoned patients and the laboratory examination results, it was determined that the incident was an acute poisoning incident caused by the inhalation of organic fluorine mixed gas in the fluorine polymerization plant. Subsequently, it was clarified that the accident was caused by the illegal operation of the employees of the fluorine polymerization plant, which caused the discharge of the organic fluorine mixed gas containing high concentration of octafluoroisobutene, resulting in the poisoning of the on-site construction personnel. In order to avoid the occurrence of similar incidents, enterprises should implement the main responsibility of safety production, regularly organize supervision and inspection, eliminate illegal operations, conduct safety education and training for the staff of the unit and outsourced staff, and improve the emergency rescue ability of sudden poisoning incidents.

In January 2021, an acute chemical poisoning incident occurred at a fluorine polymerization plant. Through the analysis of the occupational health situation of the enterprise, combined with the clinical manifestations of the poisoned patients and the laboratory examination results, it was determined that the incident was an acute poisoning incident caused by the inhalation of organic fluorine mixed gas in the fluorine polymerization plant. Subsequently, it was clarified that the accident was caused by the illegal operation of the employees of the fluorine polymerization plant, which caused the discharge of the organic fluorine mixed gas containing high concentration of octafluoroisobutene, resulting in the poisoning of the on-site construction personnel. In order to avoid the occurrence of similar incidents, enterprises should implement the main responsibility of safety production, regularly organize supervision and inspection, eliminate illegal operations, conduct safety education and training for the staff of the unit and outsourced staff, and improve the emergency rescue ability of sudden poisoning incidents.

Chronic cerebral hypoperfusion leads to white matter injury (WMI), which subsequently causes neurodegeneration and even cognitive impairment. However, due to the lack of treatment specifically for WMI, novel recognized and effective therapeutic strategies are urgently needed. In this study, we found that honokiol and magnolol, two compounds derived from Magnolia officinalis, significantly facilitated the differentiation of primary oligodendrocyte precursor cells (OPCs) into mature oligodendrocytes, with a more prominent effect of the former compound. Moreover, our results demonstrated that honokiol treatment improved myelin injury, induced mature oligodendrocyte protein expression, attenuated cognitive decline, promoted oligodendrocyte regeneration, and inhibited astrocytic activation in the bilateral carotid artery stenosis model. Mechanistically, honokiol increased the phosphorylation of serine/threonine kinase (Akt) and mammalian target of rapamycin (mTOR) by activating cannabinoid receptor 1 during OPC differentiation. Collectively, our study indicates that honokiol might serve as a potential treatment for WMI in chronic cerebral ischemia.
Magnolia ; White Matter ; Brain Ischemia/metabolism* ; Oligodendroglia/metabolism*

Objective:To observe the changes of serum histone H4 level and its predictive value in patients with septic cardiomyopathy.Methods:A prospective study was conducted. A total of 147 patients with sepsis and septic shock were collected in emergency department. The general data were recorded. Transthoracic echocardiography and plasma histone H4 were conducted within 24 hours and 7 days after admission.The scores of sequential organ failure assessment(SOFA), acute physiology and chronic health evaluationⅡ(APACHEⅡ), and nutritional risk screening 2002 (NRS2002) were evaluated within 24 hours. According to whether septic cardiomyopathy occurred, the patients were divided into two groups, and dynamic changes of histone H4 on the first and seventh day of the two groups were observed. The factors influencing the occurrence of septic cardiomyopathy were analyzed by multivariate logistic regression. The prediction ability of serum histone H4 on septic cardiomyopathy was evaluated by receiver operating curve (ROC).Results:The incidence of septic cardiomyopathy was 28.6% (42 / 147). The level of histone H4 in septic cardiomyopathy group was higher than that in non septic cardiomyopathy group ( Z = 4.449, P < 0.001), and dynamic detection showed that the level of histone H4 on the seventh day was lower than that on admission ( Z=3.057, P=0.002). Multivariate logistic regression showed that the high serum histone H4 level [Odd Ratio( OR)=1.337, 95% confidence interval (95% CI) was 1.173-1.522, P < 0.001], SOFA ( OR= 1.474, 95% CI 1.227-1.769, P < 0.001), older age ( OR = 1.074, 95% CI 1.019-1.132, P = 0.008) were independent risk factors for septic cardiomyopathy. The area of ROC curve for serum histone H4 to predict septic cardiomyopathy was 0.729 ( P < 0.001), the predictive cut-off value was 10.81 ng/ml, which yielded a sensitivity 0.524 and a specificity of 0.914. Conclusions:The level of histone H4 showed dynamic change in septic cardiomyopathy, and high serum histone H4 level has a good predictive value for the occurrence of septic cardiomyopathy.

Objective:To explore the application value of chromosome karyotype analysis, chromosomal microarray analysis (CMA) and whole exome sequencing (WES) in prenatal diagnosis of isolated corpus callosum abnormality (CCA) fetus.Methods:Fetuses diagnosed with isolated CCA by ultrasound and MRI and receiving invasive prenatal diagnosis in Guangzhou Women and Children′s Medical Center and Qingyuan People′s Hospital from January 2010 to April 2021 were selected. Karyotype analysis and/or CMA [or copy number variation sequencing (CNV-seq)] were performed on all fetal samples, and WES was performed on fetal samples and their parents whose karyotype analysis and/or CMA (or CNV-seq) results were not abnormal.Results:Among 65 fetuses with isolated CCA, 38 cases underwent karyotype analysis, and 3 cases were detected with abnormal karyotypes, with a detection rate of 8% (3/38). A total of 49 fetuses with isolated CCA underwent CMA (or CNV-seq) detection, and 6 cases of pathogenic CNV were detected, the detection rate was 12% (6/49). Among them, the karyotype analysis results were abnormal, and the detection rate of further CMA detection was 1/1. The karyotype results were normal, and the detection rate of further CMA (or CNV-seq) detection was 14% (3/21). The detection rate of CMA as the first-line detection technique was 7% (2/27). A total of 25 fetuses with isolated CCA with negative results of karyotyping and/or CMA were tested by WES, and 9 cases (36%, 9/25) were detected with pathogenic genes. The gradient genetic diagnosis of chromosomal karyotyping, CMA and WES resulted in a definite genetic diagnosis of 26% (17/65) of isolated CCA fetuses.Conclusions:Prenatal genetic diagnosis of isolated CCA fetuses is of great clinical significance. The detection rate of CMA is higher than that of traditional karyotyping. CMA detection could be used as a first-line detection technique for fetuses with isolated CCA. WES could increase the pathogenicity detection rate of fetuses with isolated CCA when karyotype analysis and/or CMA test results are negative.

Objective:To establish a clinical diagnostic scoring system for septic cardiomyopathy (SCM) and evaluate its diagnostic efficacy.Methods:A prospective cohort study was performed. Patients with sepsis and septic shock admitted to the department of emergency of China Rehabilitation Research Center were enrolled from January 2019 to December 2020. The baseline information, medical history, heart rate (HR), mean arterial pressure (MAP), body temperature and respiratory rate (RR) on admission were recorded. Laboratory indexes such as white blood cell count (WBC), hypersensitivity C-reactive protein (hs-CRP), N-terminal pro-brain natriuretic peptide (NT-proBNP), and blood lactic acid (Lac) were measured. Transthoracic echocardiography was conducted within 24 hours and on the 7th after admission. Sequential organ failure assessment (SOFA) score, acute physiology and chronic health evaluationⅡ(APACHEⅡ), and nutritional risk screening 2002 scale (NRS2002) were also assessed. The patients were divided into two groups according to whether SCM occurred or not. The risk factors of SCM were screened by univariate and multivariate Logistic regression. The cut-off value of continuous index was determined by receiver operator characteristic curve (ROC curve) and discretized concerning clinical data. The regression coefficient β was used to establish the corresponding score, and the clinical diagnostic score system of SCM was established. The diagnostic value of the model was evaluated by ROC curve.Results:In total, 147 patients were enrolled in the study and the incidence of SCM was 28.6% (42/147). Univariate Logistic regression analysis showed the risk factors of SCM included: ① continuous indicators: age, NT-proBNP, RR, MAP, Lac, NRS2002, SOFA, APACHEⅡ; ② discrete indicators: shock, use of vasoactive drugs, history of coronary heart disease, acute kidney injury (AKI). Multivariate Logistic regression analysis after discretization of above continuous index showed that age≥87 years old, NT-proBNP≥3 000 ng/L, RR≥30 times/min, Lac≥3 mmol/L and SOFA≥10 points were independent risk factors for SCM [age ≥87 years: odds ratio ( OR) = 3.491, 95% confidence interval (95% CI) was 1.371-8.893, P = 0.009; NT-proBNP≥3 000 ng/L: OR = 2.708, 95% CI was 1.093-6.711, P = 0.031; RR≥30 times/min: OR = 3.404, 95% CI was 1.356-8.541, P = 0.009; Lac≥3 mmol/L: OR = 3.572, 95% CI was 1.460-8.739, P = 0.005; SOFA≥10 points: OR = 8.693, 95% CI was 2.541-29.742, P = 0.001]. The clinical diagnostic score system of SCM was established successfully, which was composed of age≥87 years old (1 point), NT-proBNP ≥ 3 000 ng/L(1 point), RR≥30 times/min (1 point), Lac≥3.0 mmol/L (1 point), SOFA≥10 points (2 points), and the total score was 6 points. ROC curve analysis showed the cut-off value of the scoring system for diagnosing SCM was 3 points, the area under ROC curve (AUC) was 0.833, 95% CI was 0.755-0.910, P < 0.001, with the sensitivity of 71.4%, and specificity of 86.7%. Conclusion:The clinical diagnostic scoring system has good diagnostic efficacy for SCM and contributes to early identification of SCM for clinicians.

Objective:To evaluate the value of whole exome sequencing (WES) in prenatal clinical application.Methods:A total of 1 152 cases of congenital abnormal [including structural malformation, nuchal translucency (NT) thickening and intrauterine growth restriction] with traditional prenatal diagnosis [including G-band karyotype analysis and chromosome microarray analysis (CMA)] negative were analyzed. The congenital abnormal fetuses were divided into retrospective group and prospective group according to the time of WES detection, that is whether the pregnancy termination or not. According to the specific location of fetal malformation and their family history, the cohort was divided into subgroups. The clinical prognosis of all fetuses were followed up, and the effect of WES test results on pregnancy decision-making and clinical intervention were analyzed. According to the follow-up results, the data of fetuses with new phenotypes in the third trimester or after birth were re-analyzed.Results:Among 1 152 families who received WES, 5 families were excluded because of nonbiological parents. Among the remaining 1 147 families, 152 fetuses obtained positive diagnosis (13.3%,152/1 147), including 74 fetuses in the retrospective group (16.1%,74/460) and 78 fetuses in the prospective group (11.4%,78/687). In fetuses with negative CMA and G-band karyotype analysis results but new phenotypes in the third trimester or after birth, the positive rate by WES data re-analysis was 4.9% (8/163). A total of 34 (21.3%, 34/160) fetuses were directly affected by the corresponding positive molecular diagnosis. Among 68 cases of live births with diagnostic variation grade 4, 29 cases (42.7%, 29/68) received appropriate medical intervention through rapid review of WES results.Conclusions:WES could increase the detection rate of abnormal fetuses with negative G-banding karyotype analysis and CMA by 13.3%. Prenatal WES could guide pregnancy decision-making and early clinical intervention. It might be an effective strategy to pay attention to the special follow-up of the third trimester and postnatal fetus and to re-analyze the WES data.

OBJECTIVE: To investigate the application value of whole exome sequencing technology in fetuses with congenital structural abnormalities. METHODS: The chromosomal abnormalities of 1147 families were analyzed. According to the follow-up results, the data of fetuses with new phenotypes in late pregnancy or after birth were reanalyzed. Subgroups were divided according to the organs involved and whether single malformation or not. The gene regulatory network map was drawn by using string database and Cytoscape software. Fisher exact probability method was used to compare the difference of the diagnostic rate of pathogenic genes among the groups. RESULTS: A total of 160 fetal cases received positive molecular diagnosed, involving 178 variant sites of 125 pathogenic genes, including 8 cases (4.9%, 8/163) by data reanalysis, and the overall positive diagnosis rate was 13.9%. Diagnostic rate was highest in the group of skeletal malformation (31.5%, 39/124) and lowest in that with thoracic malformation (0, 0/32). The gene clusters of fetal edema and intrauterine growth restriction were independent, and were not associated with the major structural malformations. The probability of each parent carrying the same recessive gene variant was 0.03 (39/1146) and 0.08 (4/53) with positive family history. CONCLUSION For fetuses with congenital structural abnormalities that are negative for conventional genetic tests, 13.9% of phenotypic associated pathogenic/likely pathogenic genetic variants can be detected by whole exome sequencing technology. Its application value for prenatal diagnosis varies in fetus with different organs involved. Reanalysis of sequencing data for cases with new phenotypes in late pregnancy or after birth can further improve the molecular diagnosis rate. Further investigations are needed to explore the related genetic mechanisms.
Female ; Fetal Diseases ; Fetus/diagnostic imaging* ; Humans ; Pregnancy ; Prenatal Diagnosis ; Technology ; Ultrasonography, Prenatal ; Whole Exome Sequencing

Renal cell carcinoma (RCC) is one of the most common malignant tumors affecting the urogenital system, accounting for 90% of renal malignancies. Traditional chemotherapy options are often the front-line choice of regimen in the treatment of patients with RCC, but responses may be modest or limited due to resistance of the tumor to anticarcinogen. Downregulated expression of organic cation transporter OCT2 is a possible mechanism underlying oxaliplatin resistance in RCC treatment. In this study, we observed that miR-489-3p and miR-630 suppress OCT2 expression by directly binding to the OCT2 3'-UTR. Meanwhile, 786-O-OCT2-miRNAs stable expression cell models, we found that miRNAs could repress the classic substrate 1-methyl-4-phenylpyridinium (MPP), fluorogenic substrate ,-dimethyl-4-(2-pyridin-4-ylethenyl) aniline (ASP), and oxaliplatin uptake by OCT2 both and in xenografts. In 33 clinical samples, miR-489-3p and miR-630 were significantly upregulated in RCC, negatively correlating with the OCT2 expression level compared to that in adjacent normal tissues, using tissue microarray analysis and qPCR validation. The increased binding of c-Myc to the promoter of pri-miR-630, responsible for the upregulation of miR-630 in RCC, was further evidenced by chromatin immunoprecipitation and dual-luciferase reporter assay. Overall, this study indicated that miR-489-3p and miR-630 function as oncotherapy-obstructing microRNAs by directly targeting OCT2 in RCC.

Objective: The gene engineering technique was used to express the P[6] genotype rotavirus (rotaviruses, RVs) GST-VP8^*-Z84 protein from pigs, and the binding characteristics of the protein to oligosaccharide and salivary receptor were studied. Methods: The GST-VP8^*-Z84 protein was purified by GST Escherichia coli expression system and affinity chromatography using porcine P[6]. Enzyme-linked immunosorbent assay (ELISA) saliva binding test and oligosaccharide binding test were used to analyze the binding characteristics of the genotype to receptors. Results: Porcine P[6] GST-VP8^*-Z84 protein bound well to mucin core 2. Conclusions The potential receptor of P[6] RV may be the core of mucin, which may provide the experimental basis and theoretical basis for the mechanism of rotavirus and receptor interaction and the development of RV vaccine and highly effective therapeutic drugs.