ObjectiveToinvestigatethecorrelationbetween-2578C>Apolymorphismofvascular endothelium grow th factor (VEGF) gene and carotid atherosclerosis in Chinese Han population in Shandong, China. Methods A total of 384 subjects aged 45-85 in Chinese Han population in Shandong, China w ere enroled. They were divided into either an increased intima-media thickness (IMT) group ( n=248) or a control group (n=136) according to the vascular ultrasound results. The baseline clinical data, such as the demographic data, vascular risk factors, and blood biochemical indicators in both groups were colected. Polymerase chain reaction w as used to detect the VEGF gene -2578C>A polymorphism genotype and alele. Multivariate logistic regression analysis was used to identify the independent risk factors for increased carotid IMT. Results The proportions of hypertension ( 70.6%vs.59.6%;χ2 =4.793, P=0.032), diabetes (18.4%vs.29.0%; χ2 =5.281, P=0.027), hyperlipidemia ( 45.2%vs.33.1%; χ2 =7.883, P=0.006), previous previous stroke or transient ischemic attack (29.0%vs.16.9%;χ2 =6.294, P=0.009), smoking (35.9%vs.19.9%;χ2 =10.708, P=0.001), as w el as total cholesterol ( 4.82 ±1.25 mmol/L vs.4.57 ± 0.94 mmol/L; t= -2.072, P= 0.039 ), triglyceride ( median, interquartile range; 1.71[0.84-2.22] mmol/L vs.1.53[1.08-2.59] mmol/L;Z= -2.560 P=0.010), low-density lipoprotein cholesterol (2.86 ±1.01 mmol/L vs.2.64 ±0.85 mmol/L; t= -2.407, P= 0.033 ), and high-density lipoprotein cholesterol (1.58 ±0.72 mmol/L vs.1.43 ±0.46 mmol/L;t= -2.183, P=0.030) in the increased IMT group, and there w ere significant differences compared w ith the control group. There w as significant difference in genotype frequency betw een the 2 groups (χ2 =10.131; P=0.006). There w as significant difference in C alele frequency between the increased IMT group and the control group (78.2% vs. 70.2%;χ2 =6.068, P=0.014). Multivariate logistic regression analysis showed that CC genotype (odds ratio 1.132, 95%confidence interval 1.021-2.141;P=0.029) w as an independent risk factor for increased carotid IMT. In 248 patients w ith increased IMT, 213 had at least 1 plaque, 76 (39.6%) of them w ere 1-2, 107 (43.15%) w ere 3-4, and 30 (12.1%) w ere 5-8 in plaque index. There w ere no significant differences in frequencies of genotypes (χ2 =6.766, P=0.149) and alele (χ2 =0.185, P=0.667) in the different plaque index groups. Conclusions -2578 single nucleotide polymorphism in the VEGF gene promoter is associated w ith carotid atherosclerosis, and C al ele may be its genetic susceptibility factor in Chinese Han population in Shandong, China.

Objective To provide a device and an effective method for tail vein injection in mice. Methods Doing the tail vein injection in mice with the self-designed device which is consisted of constant temperature part, lighting part and holding part.The difficulty and time of injection with and without the device were compared.Results It was faster and more accurate to perform the tail vein injection in mice with this self-designed device.Conclusion Using this self-designed device can significantly improve the efficiency and save the injection time.

Objective To prepare the coating of dexamethasone-eluting intravascular stent and observe the features of its delayed release in vitro.Methods Spray painting and dipping coating were used respectively to prepare stent coating,and then high performance liquid chromatography(HPLC)was used to detect the drug loading.The stents prepared by dipping coating were set in a flow of 50 ml PBS buffer at a velocity of 20 ml/min,and 0.5 ml buffer was collected at 6 h and 1,2,4,6,8,10,12,15 d respectively with another 0.5 ml fresh PBS being added immediately.The drug content of the 0.5 ml buffer was detected by HPLC for drug sustained release in vitro.Results The drug loading of stents prepared by spray painting was(24.26?5.23)?g,while that stents prepared by dipping coating for 4 d was(93.15?7.83)?g.Drugs were released slowly and the release rate reached 84% at 15 d.Conclusion The dipping coating-prepared stents have evident effect of sustained release.

Objective:To explore the mediating effects of mindfulness and perceived stress between childhood trauma and psychotic-like experiences.Methods:In October 2021, 602 freshmen from a university in Guangdong Province were tested by childhood trauma questionnaire(CTQ), mindful attention awareness scale(MAAS), perceived stress scale(PSS), and community assessment of psychic experiences(CAPE). SPSS 21.0 and Mplus 8.3 were used for data analysis. Mann-Whitney U test was used to compare the differences between groups, and Spearman correlation analysis was used to investigate the correlation among childhood trauma, mindfulness, perceived stress and psychotic-like experiences. Bias-corrected nonparametric percentile Bootstrap method was used to examine the mediating roles of mindfulness and perceived stress between childhood trauma and psychotic-like experiences. Results:(1) In the past one month, 59.5% of the freshmen had psychotic-like experiences, and 8.5% of them experienced the distress. (2)Childhood trauma was positively correlated with perceived stress( r=0.29, P<0.01), frequency ( r=0.14, P<0.01)and distress( r=0.17, P<0.01) of psychotic-like experiences, and was negatively correlated with mindfulness( r=-0.28, P<0.01). (2)Mindfulness and perceived stress played individual mediating effects and chain mediating effect between childhood trauma and frequency of psychotic-like experiences, with effect size of 0.08, 0.04, 0.03, accounting for 53.33%, 26.67%, 20.00% of the total indirect effect(effect size=0.15), respectively. Mindfulness and perceived stress played individual mediating effects and chain mediating effect between childhood trauma and distress of psychotic-like experiences, with effect size of 0.07, 0.04, 0.03, accounting for 50.00%, 28.57%, 21.43% of the total indirect effect(effect size=0.14), respectively. Conclusion:Childhood trauma can affect psychotic-like experiences and distress through the indirect effects of mindfulness and perceived stress, or through the chain mediating effect of mindfulness-perceived stress.

Objective:To understand the electrocardiogram and echocardiography examination results of population in key areas of unexplained sudden death in Yunnan Province (referred to as Yunnan sudden death).Methods:From 2014 to 2022, electrocardiogram examination was performed on population (including same incident cases, relatives of the cases, villagers of the affected villages, and control individuals) in key areas of Yunnan sudden death from May to October each year. Echocardiography examination was performed on relatives of the cases and villagers of the affected villages, and the types of electrocardiogram and echocardiography changes were sorted out and analyzed.Results:Electrocardiogram examination was conducted on 1 same incident case, 241 relatives of the cases, 464 villagers of the affected villages, and 99 control individuals, respectively. The types of electrocardiogram changes in the same incident case were Q-T interval prolongation and sinus tachycardia. A total of 17 types of electrocardiogram changes were detected in the relatives of the cases, mainly including sinus arrhythmia (12.45%, 30/241), sinus bradycardia (11.20%, 27/241), and left axis deviation (8.30%, 20/241). A total of 21 types of electrocardiogram changes were detected in the villagers of the affected villages, mainly including left axis deviation (9.48%, 44/464), sinus bradycardia (8.19%, 38/464), and T-wave abnormalities (7.76%, 36/464). A total of 10 types of electrocardiogram changes were detected in the control individuals, mainly including sinus arrhythmia (12.12%, 12/99), T-wave abnormalities (9.09%, 9/99), and sinus bradycardia (7.07%, 7/99). Echocardiography examination was conducted on 49 relatives of the cases and 365 villagers of the affected villages, respectively. A total of 12 types of echocardiography changes were detected in the relatives of the cases, mainly including tricuspid regurgitation (18.37%, 9/49), decreased right ventricular diastolic function (8.16%, 4/49), aortic regurgitation (6.12%, 3/49), and atrial septal defect (6.12%, 3/49). A total of 15 types of echocardiography changes were detected in the villagers of the affected villages, mainly including tricuspid regurgitation (8.77%, 32/365), aortic regurgitation (6.85%, 25/365), and decreased left ventricular diastolic function (6.58%, 24/365).Conclusion:There are many types of changes in electrocardiogram and echocardiography in the population of key areas of Yunnan sudden death.

BACKGROUND:It has been shown that neural stem cells can differentiate into neurons,astrocytes,and oligodendrocytes.Mesenchymal stem cells-derived extracellular vesicles have also been shown to cross the blood-brain barrier to reach sites of central nervous injury and promote neural repair.However,it is not clear whether neuron-derived extracellular vesicles promote the differentiation of neural stem cells in a direction that is beneficial for neurogenesis. OBJECTIVE:To investigate whether neuron-derived extracellular vesicles facilitate neural stem cell differentiation towards neurogenesis. METHODS:Neurons and neural stem cells were extracted from neonatal SD rat cerebral cortex by trypsin digestion.Cell supernatants of neurons were collected.Neuron-derived extracellular vesicles were extracted.Neural stem cells cultured for 10 days were co-cultured with neuron-derived extracellular vesicles or PBS for 7 days.Immunoblotting,immunofluorescence,and RT-qPCR were used to detect proteins specifically expressed by neurons,neural stem cells,oligodendrocytes,and astrocytes. RESULTS AND CONCLUSION:The neural stem cells co-cultured with neuron-derived extracellular vesicles showed high expression of neuron-specific proteins and oligodendrocyte-specific proteins including β3-tubulin,neurofilament 200 and myelin basic protein,and low expression of astrocyte-specific protein glial fibrillary acidic protein.These results suggest that neuron-derived extracellular vesicles can promote the differentiation of neural stem cells into neurons and oligodendrocytes and prevent the differentiation of neural stem cells into astrocytes.

Objective:To analyze common pathogenic gene mutations of arrhythmogenic right ventricular cardiomyopathy (ARVC) in Yunnan unexplained sudden death (hereinafter referred to as Yunnan sudden death) cases, and explore the etiological relationship between Yunnan sudden death and ARVC.Methods:Four typical Yunnan sudden death affected counties (cities) were selected as investigation sites. Cryopreserved autopsy cardiac cavity blood samples were collected from Yunnan sudden death cases ( n = 3), and peripheral venous blood samples were harvested from their relatives (first, second, third and immediate degree of kinship, n = 67) and control population ( n = 49). The DNA of blood samples was extracted for amplification and sequencing of 97 exons of 5 common ARVC desmosomal protein [desmoplakin (DSP), desmocollin-2 (DSC2), desmoglein-2 (DSG2), plakophilin-2 (PKP2) and junction plakoglobin (JUP)] genes, and genetic lineage of Yunnan sudden death cases was investigated. Results:A total of 17 gene mutation sites were discovered in Yunnan sudden death cases and their relatives, with 6, 5, 4, 1 and 1 in the DSP, DSC2, DSG2, PKP2 and JUP genes, which were not found in the control population. Among them, 9 were newly discovered mutation sites and 8 were reported mutation sites. The DSP gene exon 24 c.8472 G>C, a pure contractual sense mutation, was common in the relatives of 4 cases in the same family surveyed; and one immediate relative carried a deletion mutation at c.2368 - 2370 of exon 15 of DSC2 gene.Conclusion:Yunnan sudden death cases and their relatives carry mutations in the ARVC desmosomal protein DSP, DSC2, DSG2, PKP2, and JUP genes, and the onset of some Yunnan sudden death may be associated with mutations in the ARVC desmosomal protein genes.

Objective:To evaluate the effect of comprehensive intervention measures on Yunnan unexplained sudden death (YUSD) in Dali Prefecture, Yunnan Province, and to provide scientific basis for improving the prevention and control measures.Methods:Since 2010, Yunnan Province had implemented comprehensive intervention measures in ward areas according to the etiological pattern of YUSD. In July 2019, 47 families with YUSD were selected as case families and 23 families without YUSD were selected as control families in 31 natural villages of Heqing, Xiangyun, Yunlong, Eryuan, Jianchuan, Binchuan and Nanjian counties of Dali Prefecture. A unified questionnaire was used to investigate the basic information, economic status, dietary structure, and health literacy of the families during the two periods of "the first sudden death case" and "the present".Results:The annual household income of the case families at present (median, 20 492.6 yuan) was significantly higher than that of the first sudden death case (3 883.4 yuan), and the difference was statistically significant ( Z = - 5.27, P < 0.001). At present, rice (76.6%, 36/47) was the main diet of the case families; at the time of the first sudden death case, 23.4% (11/47) of the case families could not eat enough, and there was no such situation in the case families at present. Compared with the time of the first sudden death case, the dietary habits of the case families at present were as follows: the proportion of eating Trogia venenata decreased from 19.0% (39/205) to 0 (0/190), the proportion of eating wild fruit decreased from 17.1% (35/205) to 9.5% (18/190), and the proportion of drinking raw water decreased from 55.1% (113/205) to 42.1% (80/190), and the differences were statistically significant (χ 2 = 22.37, 4.90, 6.86, P < 0.05). Lifestyle and health awareness: the proportion of those who washed their hands before meals and after using the toilet increased from 9.8% (20/205) to 41.6% (79/190), those who did not overwork increased from 16.6% (34/205) to 34.2% (65/190), and those who took good protection when spraying pesticides increased from 7.3% (15/205) to 21.6% (41/190), and the differences were statistically significant (χ 2 = 53.17, 33.94, 16.48, P < 0.001). Toilet habits: the proportion of using outdoor toilet decreased from 75.6% (155/205) to 9.5% (18/190), the difference was statistically significant (χ 2 = 175.21, P < 0.001). When the first sudden death case occurred, the proportions of eating Trogia venenata and using outdoor toilet in the case families were higher than those in the control families (χ 2 = 22.37, 23.70, P < 0.001), the proportions of those who washed their hands before meals and after using the toilet and those who did not overwork in the case families were lower than those in the control families (χ 2 = 7.38, 4.93, P < 0.05). Conclusions:The economic conditions, production and living conditions of YUSD areas in Dali Prefecture have been significantly improved, and the health literacy and health prevention awareness of the population have been greatly improved. Economic conditions and living standard, dietary structure and health literacy may be related factors of YUSD.

Background: Tigecycline, eravacycline, and omadacycline are recently developed tetracyclines. Susceptibility of microbes to these tetracyclines and their molecular mechanisms have not been well elucidated. We investigated the susceptibility of Moraxella catarrhalis to tigecycline, eravacycline, and omadacycline and its resistance mechanisms against these tetracyclines. Methods: A total of 207 non-duplicate M. catarrhalis isolates were collected from different inpatients. The minimum inhibitory concentrations (MICs) of the tetracyclines were determined by broth microdilution. Tigecycline-, eravacycline-, or omadacycline-resistant isolates were induced under In Vitro pressure. The tet genes and mutations in the 16S rRNA was detected by PCR and sequencing. Results: Eravacycline had a lower MIC50 (0.06 mg/L) than tigecycline (0.125 mg/L) or omadacycline (0.125 mg/L) against M. catarrhalis isolates. We found that 136 isolates (65.7%) had the tetB gene, and 15 (7.2%) isolates were positive for tetL; however, their presence was not correlated with high tigecycline, eravacycline, or omadacycline ( ≥ 1 mg/L) MICs.Compared with the initial MIC after 160 days of induction, the MICs of tigecycline or eravacycline against three M. catarrhalis isolates increased ≥ eight-fold, while those of omadacycline against two M. catarrhalis isolates increased 64-fold. Mutations in the 16S rRNA genes (C1036T and/or G460A) were observed in omadacycline-induced resistant isolates, and increased RR (the genes encoding 16SrRNA (four copies, RR1-RR4) copy number of 16S rRNA genes with mutations was associated with increased resistance to omadacycline. Conclusions Tigecycline, eravacycline, and omadacycline exhibited robust antimicrobial effects against M. catarrhalis. Mutations in the 16S rRNA genes contributed to omadacycline resistance in M. catarrhalis.

Objective:To explore the cause of death of 2 suspected Yunnan sudden unexplained death (YNSUD) cases in Dayao County, Yunnan Province.Methods:The field epidemiological investigation and autopsy of 2 cases of YNSUD in Dayao County from June 15 to 20, 2020 were conducted; and blood and tissue samples were collected for qualitative analysis of common poisons and drugs.Results:The areas where the two cases were located were all seriously ill villages with a history of YNSUD, and the time of death occurred in the onset season of YNSUD. There was no blood relationship between the 2 cases, no obvious abnormal symptoms before death, no special diet, no history of exposure to pesticides and other toxic chemicals, and the test results of common poisons were all negative. Autopsy pathological examination results showed that case 1 died of acute cardiac dysfunction caused by sudden acute myocardial infarction of coronary heart disease, and case 2 died of central respiratory and circulatory failure caused by spontaneous subarachnoid hemorrhage.Conclusions:The two cases are excluded from YNSUD through autopsy, and the cause of death is determined. It is suggested that emergency response should be taken as soon as possible for YNSUD cases, and autopsy should be actively carried out to clarify the cause of death from a pathological point of view.