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.

Objective:To explore the evaluation value of sequential organ failure assessment (SOFA) score at different time points in the prognosis of patients with severe pneumonia combined with acute respiratory distress syndrome (ARDS).Methods:A retrospective cohort study method was conducted, including patients with severe pneumonia and ARDS admitted to the emergency intensive care unit (ICU) of General Hospital of Ningxia Medical University from January 2015 to December 2019. General clinical data such as gender, age, and the SOFA scores at 1, 2, 3, and 7 days after admission were recorded. According to the diagnostic test, the prognostic evaluation value of SOFA score in patients with severe pneumonia combined with ARDS at different time points and different ages was analyzed.Results:A total of 88 cases were included in this study, eventually, 42 cases were survived and 46 cases died, the mortality was 52.27%. The age of the death group was significantly older than the survival group (years old: 60.67±14.66 vs. 51.91±15.97), the SOFA score at each time point were significantly higher than those in the survival group (9.83±3.50 vs. 7.54±2.67, 9.98±3.75 vs. 7.48±2.92, 10.84±4.14 vs. 7.23±2.94, 11.71±4.03 vs. 6.51±3.22, respectively at 1, 2, 3, 7 days after admission, all P < 0.01). The receiver operator characteristic curve (ROC curve) showed that the SOFA score at 1, 2, 3, and 7 days after admission had a certain predictive value for the prognosis of patients with severe pneumonia combined with ARDS (all P < 0.01), and with the prolong of ICU stay, the area under ROC curve (AUC) of SOFA score had gradually increased. On the 7th day after admission, the SOFA score had the highest sensitivity in predicting severe pneumonia combined with ARDS patients, which was 92.86%, and the specificity was the highest on the 3rd day after admission, which was 88.10%. The AUC in day 7 was significantly higher than day 2 (0.85 vs. 0.72) , there was no statistically significant difference of AUC at other time points. After stratifying by age, the diagnostic of sensitivity, specificity, accuracy, and AUC of SOFA score for the prognosis had gradually increased, and the predictive value was better. However, only on day 3 after admission, the AUC of SOFA score was significantly higher than day 1 (0.80 vs. 0.77, P < 0.05), and there was no significant difference in AUC at other time points. In patients older than 60 years old, the AUC of the SOFA score predicting the prognosis of patients was relatively small on day 1 and day 2 (0.67, 0.68, respectively), the ability was poor. There was no statistically significant difference in the AUC of SOFA scores at each time point in evaluating the prognosis of patients. The trends over time of patients at different ages and time points showed that regardless of age, the SOFA scores of the patients in the death group showed an upward trend, while showed a downward trend in the survival group, the difference reached the largest on the 7th day after admission, and the death group was significantly higher than the survival group (age < 60 years old: 12.50 vs. 6.69; age≥60 years old: 11.58 vs. 6.21). Conclusion:The initial SOFA score has a certain value in the evaluation of prognosis of severe pneumonia patients combined with ARDS, but the effect is poor for elderly patients.

Objective:To investigate the effects of osimertinib on proliferation, migration and invasion of procollagen-lysine 2-oxoglutarate 5-dioxygenase 2 (PLOD2) overexpressing HCC827 cells and explore the potential mechanism of PLOD2 induced osimertinib resistance.Methods:We transfected HCC827 cells with LV-vector and LV-over/PLOD2. The expression of PLOD2 was detected by quantitative real time polymerase chain reaction (qRT-PCR) and western blotting. The effects of osimertinib on the proliferation of HCC827-vector and HCC827-PLOD2 cells were evaluated by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide (MTT) assay. The effects of osimertinib on the migration and invasion of HCC827-vector and HCC827-PLOD2 cells were determined by Transwell assays. The expressions of E-cadherin and vimentin in cells were detected by immunofluorescence (IF). The expressions of epithelial-mesenchymal transition (EMT), FAK-PI3K/AKT and MAPK signal pathway related proteins were detected by western blotting.Results:The MTT assay showed that HCC827-PLOD2 cells were hyposensitive to osimertinib. The 50% inhibitory concentration (IC 50) and resistance index of osimertinib for HCC827-PLOD2 cells was over 1 000 nmol/L and over 100, respectively. The result of wound healing assay showed that the migration distance of HCC827-PLOD2 was about (2.13±0.21) fold changes as that of HCC827-vector cells. The result of Transwell assay showed that the numbers of HCC827-PLOD2 passing through the matrix membrane were (212.78±10.43), significantly higher than (101.32±12.52) of HCC827-vector cells ( P<0.01). The result of IF showed that compared with HCC827-vector cells, the expression of E-cadherin was down-regulated while vimentin was up-regulated in HCC827-PLOD2 cells. Osimertinb downregulated E-cadherin and upregulated vimentin expression in HCC827-vector cells but had limited effect in HCC827-PLOD2 cells. The result of western blotting showed that PLOD2 significantly increased vimentin expression level while decreased E-cadherin expression level. Osimertinib inhibited the expression of p-EGFR, but did not affect the expressions of PLOD2, p-FAK, p-AKT, p-ERK, vimentin and E-cadherin in HCC827-PLOD2 cells. Conclusion:PLOD2 confers resistance to osimertinib in HCC827 cells by regulating EMT, FAK-PI3K/AKT and MAPK signal pathways.

Objective:To investigate the effects of osimertinib on proliferation, migration and invasion of procollagen-lysine 2-oxoglutarate 5-dioxygenase 2 (PLOD2) overexpressing HCC827 cells and explore the potential mechanism of PLOD2 induced osimertinib resistance.Methods:We transfected HCC827 cells with LV-vector and LV-over/PLOD2. The expression of PLOD2 was detected by quantitative real time polymerase chain reaction (qRT-PCR) and western blotting. The effects of osimertinib on the proliferation of HCC827-vector and HCC827-PLOD2 cells were evaluated by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide (MTT) assay. The effects of osimertinib on the migration and invasion of HCC827-vector and HCC827-PLOD2 cells were determined by Transwell assays. The expressions of E-cadherin and vimentin in cells were detected by immunofluorescence (IF). The expressions of epithelial-mesenchymal transition (EMT), FAK-PI3K/AKT and MAPK signal pathway related proteins were detected by western blotting.Results:The MTT assay showed that HCC827-PLOD2 cells were hyposensitive to osimertinib. The 50% inhibitory concentration (IC 50) and resistance index of osimertinib for HCC827-PLOD2 cells was over 1 000 nmol/L and over 100, respectively. The result of wound healing assay showed that the migration distance of HCC827-PLOD2 was about (2.13±0.21) fold changes as that of HCC827-vector cells. The result of Transwell assay showed that the numbers of HCC827-PLOD2 passing through the matrix membrane were (212.78±10.43), significantly higher than (101.32±12.52) of HCC827-vector cells ( P<0.01). The result of IF showed that compared with HCC827-vector cells, the expression of E-cadherin was down-regulated while vimentin was up-regulated in HCC827-PLOD2 cells. Osimertinb downregulated E-cadherin and upregulated vimentin expression in HCC827-vector cells but had limited effect in HCC827-PLOD2 cells. The result of western blotting showed that PLOD2 significantly increased vimentin expression level while decreased E-cadherin expression level. Osimertinib inhibited the expression of p-EGFR, but did not affect the expressions of PLOD2, p-FAK, p-AKT, p-ERK, vimentin and E-cadherin in HCC827-PLOD2 cells. Conclusion:PLOD2 confers resistance to osimertinib in HCC827 cells by regulating EMT, FAK-PI3K/AKT and MAPK signal pathways.

[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 whether hypertonic saline would partake in regulating Notch signaling in microglia in experimentally induced cerebral ischemic rats.Methods Male SD rats were randomly divided into sham group, cerebral ischemia group, normal saline group ( NS group ) , 10%hypertonic saline group (10%HS group) , the model of cerebral ischemia were established in all rats except the sham group by using middle cerebral artery occlusion ( MCAO) .After 2 hours of MCAO, the rats were through reperfusion for 24 h.In addition, rats in the normal saline group and 10% HS group were respectively treated with a continuous intravenous injection of normal saline (0.3 mL/h) and 10%HS (0.3 mL/h) by tail vein for 24 h.Immunofluorescence methods, RT-PCR and Western blot were used to detect the expression of Notch1 and intracellular Notch receptor domain ( NICD) .All data was analyzed by one-way analysis of variance ( ANOVA) , The intergroup comparisons were analyzed by the least-significant-difference (LSD) tests.Differences were considered statistically significant if P<0.05.Results Immunofluorescence showed that the expression of Notch1 and NICD were significantly increased in the microglia around peri-ischemia area in cerebral ischemia group and normal saline group compared to sham group;the expression of Notch1 and NICD in the microglia around peri-ischemia area were significantly reduced in 10% HS group compared to ischemia group and NS group.RT-PCR showed that the mRNA expression of Notch1 was significantly increased in ischemia group and NS group compared to sham group ( sham group: 1.000 ± 0.076; ischemia group: 2.203 ±0.283; NS group: 1.616 ±0.185; P <0.01 ); however, it was significantly reduced in 10% HS group compared to ischemia group and NS group ( ischemia group:2.203 ±0.283; NS group: 1.616 ±0.185; 10%HS group: 1.202 ±0.177; P <0.05 ) .Western blot showed that the protein expression of Notch1 was significantly increased in ischemia group and NS group compared to sham group ( sham group: 0.290 ±0.079; ischemia group: 0.750 ±0.029; NS group:0.765 ±0.182;P<0.01);but was significantly reduced in 10%HS group compared to ischemia group and NS group ( ischemia group:0.750 ±0.029; NS group:0.765 ±0.182;10%HS group:0.390 ±0.195;P<0.05 ) .The protein expression of NICD was significantly increased in ischemia group and NS group compared to sham group ( sham group: 0.401 ±0.196; ischemia group: 0.906 ±0.359; NS group:0.847 ±0.153;P<0.01);but was significantly reduced in 10%HS group compared to ischemia group and NS group ( ischemia group:0.906 ±0.359; NS group:0.847 ±0.153;10%HS group:0.561 ±0.165;P<0.05 ) .Conclusion Our results suggest that HS markedly suppresses Notch signaling in microglia around the ischemia tissue area in experimental induced cerebral ischemic rats.

A new anastomat for digestive tract operations, based on the magnetic compressive technique and mechanical transmission mechanism, is composed of a removable head and a reusable body. The head includes two parts: the proximal end can be fixed to the body, and the distal end could be used for performing a purse string suture. The procedure of anastomosis is similar to that of the stapler, and the anastomoses is established using a pair of magnetic rings. The instrument makes magnamosis more simple and feasible, and it would facilitate the clinical application. The body of the anastomat is reusable and the head could be replaced according to the clinical scenarios, these could reduce the medical cost. The magnetic rings would be excreted with the feces, and there is no foreign body response at last.
Anastomosis, Surgical ; instrumentation ; methods ; Gastrointestinal Tract ; surgery ; Humans ; Magnetics

A new anastomat for digestive tract operations, based on the magnetic compressive technique and mechanical transmission mechanism, is composed of a removable head and a reusable body. The head includes two parts: the proximal end can be fixed to the body, and the distal end could be used for performing a purse string suture. The procedure of anastomosis is similar to that of the stapler, and the anastomoses is established using a pair of magnetic rings. The instrument makes magnamosis more simple and feasible, and it would facilitate the clinical applicaion. The body of the anastomat is reusable and the head could be replaced according to the clinical scenarios, these could reduce the medical cost. The magnetic rings would be excreted with the feces, and there is no foreign body response at last.

Objective In order to examine the value of the combination of carotid artery ultrasound and Transcrani-al Doppler (TCD) in the evaluation of carotid artery stenosis stenting. Methods Seventy-one carotid stenosis cases con-firmed by digital subtraction angiography (DSA) who had cerebral ischemia symptoms and received stent implantation were reviewed. Carotid artery ultrasound and TCD were adopted to measure the vessel diameter, peak systolic velocity (PSV) of the narrow segment, PSV and pulsatility index (PI) of ipsilateral middle cerebral artery (MCA) before and after the treatment of intravascular stents, and a comparison analysis was made. Results Carotid stent implantation significant-ly improved the inner diameter, PSV of the narrow part, PSV and PI of the MCA on the stenotic side. Inner diameter of the narrow part was 3.13±0.83, 4.77±0.51 and 4.64±0.52 mm at before, one week and one year after the implantation, re-spectively (P<0.05). The PSV of the narrow part was 190.69±113.65, 86.15±30.52 and 90.28±29.79 cm/s at before, one week and one year after the implantation, respectively(P<0.05).PSV of the MCA on the stenotic side was 77.68±14.66, 115.62±22.32 and 108.89±20.29 cm/s at before, one week and one year after the implantation, respectively(P<0.05). PI of the MCA on the stenotic side was 0.81±0.01, 1.07±0.01 and 1.06±0.02 at before, one week and one year after the implantation, respectively (P<0.05). Conclusions The present study demonstrates that the combination of carotid artery ultrasound and TCD can quantitatively detect the vascular structural and hemodynamic improvements following the endo-vascular stenting, indicating that the combination of carotid artery ultrasound and TCD can be used for the accurate as-sessment and follow up of carotid artery stenting treatment.

Objective To investigate the characteristic changes in cerebral infarction and brain edema. Method A total of 122 Healthy adult male Spraque-Dawley rats were randomly (random number) divided into three groups: normal group ( n = 12), sham operated group (n=12) and cerebral ischemia group ( n = 98). Cerebral infarction and brain edema were induced by a permanent occlusion of right middle cerebral artery (POM-CA) with ligature. According to the duration of POMCA, the rats of cerebral ischemia group were further divided into seven sub-groups, 2 h, 4 h, 6 h, 12 h, 18 h, 24 h and 30 hours. The hemispheric ratio was detected by staining with 2% 2,3,5-triphenyltetrazolium chloride solution, and brain water content was assayed by dry/wet ratio 2 h, 4 h, 6 h, 12 h, 18 h, 24 h and hours after POMCA. Results There was a focal cerebral infarction in the rats of cerebral ischemia group 4 hours after POMCA. There was no significant difference in hemispheric ratio between 4 hours and 6 hours after POMCA by One-way ANOVA (P = 0.091). Compared with 6 h sub-group, the hemispheric ratio increased significantly in 12 h, 18 h, 24 h and 30 h sub-groups (P < 0.01), and the peak was in the 24 h sub-group. The brain water content began to increase 4 hours after POMCA and aggravated 6 hours later, and reached the peak 24 hours after POMCA. The brain water content of the non-ischemic hemisphere increased 18 h,24 h and 30 hours after POMCA. Furthermore, there was a significant correlation between the hemispheric ratio and brain water content ( r = 0.834, P < 0.01). Conclusions The critical point of cerebral infarction and brain edema aggravated is 6 hours after POMCA. Both brain edema and cerebral infarction reach the most serious degree 24 hours after POMCA. It is an important experimental evidence for evaluating the milieu conducive to the pathogenesis, and choosing the suitable time window for the treatment of cerebral infarction and brain edema.