Advances in the application of nonselective β-receptor blockers in treatment of liver cirrhosis / 临床肝胆病杂志

Nonselective β-receptor blockers (NSBBs) are first-line drugs for the prevention and treatment of complications in cirrhotic patients with portal hypertension and are widely used in the primary and secondary prevention of esophagogastric variceal bleeding. In recent years, studies have shown that in patients with clinically significant portal hypertension (CSPH), NSBBs can used to prevent liver decompensation events besides variceal bleeding, such as ascites and hepatic encephalopathy. However, in patients without CSPH, current research evidence does not support the use of NSBBs. Although reliable data currently support the use of NSBBs in end-stage liver cirrhosis, there are still drug safety issues in patients with refractory ascites and spontaneous bacterial peritonitis, and further studies are needed to explore the dose and timing of administration. This article reviews the clinical research advances in the use of NSBBs (especially carvedilol) in patients with liver cirrhosis and summarizes the therapeutic window used reasonably in the whole-course management of liver cirrhosis, so as to provide a basis for clinical decision-making.

Effect of Lactobacillus coryniformis FZU63 on the flavor quality of black tea beverage / 生物工程学报

The tea beverages will be endowed with distinct aroma and taste, as well as various biologically active compounds including probiotic factors, when fermented with lactic acid bacteria (LAB). However, at present, few studies on the dynamics of flavors in tea soup at different fermentation stages were conducted. In this study, the composition of monosaccharides, aromatic components, free amino acids, and organic acids were measured, when the black tea beverages were fermented with Lactobacillus coryniformis FZU63 which was isolated from Chinese traditional kimchi. The results indicated that monosaccharides including glucose, fructose, mannose and xylose in black tea beverages are the main carbon sources for fermentation. In addition, the abundance of aromatic compounds in black tea soup are increased significantly at different fermentation stages, which endow the fermented black tea soup with fruit aroma on the basis of flowery and nutty aroma. Moreover, some bitter amino acids are reduced, whereas the content of sweet and tasty amino acids is elevated. Furthermore, the levels of lactic acid, malic acid, citric acid and other organic acids are accumulated during the fermentation. Additionally, sensory evaluation displays that black tea beverage is acquired with comprehensive high-quality after being fermented for 48 h. This study provides a theoretical basis to steer and control the flavor formation and quality of the fermented tea beverages during LAB fermentation.

Circular RNA HECTD1 participates in oxygen-glucose deprivation-induced neuronal cell damage by regulating miR-98-5p/ephrin A4 expressions / 中华神经医学杂志

Objective:To explore whether circular RNA HECTD1 (circ-HECTD1) is involved in oxygen-glucose deprivation (OGD)-induced neuronal cell damage by regulating the expressions of miR-98-5p/ephrin A4 (EPHA4).Methods:Mouse primary cortical neuronal cells were isolated and cultured in vitro. The targeting relations of circ-HECTD1 and miR-98-5p with EPHA4 were detected by dual luciferase reporter assay and RNA binding protein immunoprecipitation assay. These neurons were randomly divided into control group (cultured for 24 h under normal condition) and 6, 12 and 24 h OGD treatment groups (treated with OGD for 6, 12 and 24 h, respectively), OGD+Vector group and OGD+circ-HECTD1 group, OGD+small interfering RNA (siRNA) negative control (si-NC) group and OGD+siRNA circ-HECTD1 (si-circ-HECTD1) group, OGD+micro RNA (miR) negative control (miRNC) group and OGD+miR-98-5p mimic group, OGD+miRNA inhibitor negative control (anti-miRNC) group and OGD+miR-98-5p inhibitor (anti-miR-98-5p) group, OGD+miR-98-5p mimic+pcDNA group and OGD+miR-98-5p mimic+EPHA4 group, OGD+si-circ-HECTD1+anti-miR-NC group and OGD+si-circ-HECTD1+miR-98-5p inhibitor group; pCD5-ciR empty vector, pCD5-ciR-circ-HECTD1, si-NC, si-circ-HECTD1, miR-NC, miR-98-5p mimic, anti-miR-NC or anti-miR-98-5p were transfected into the neurons, and miR-98-5p mimi and pcDNA3.1 empty vector, miR-98-5p mimic and pcDNA3.1-EPHA4 overexpression vector, si-circ-HECTD1 and anti-miR-NC, or si-circ-HECTD1 and anti-miR-98-5p were co-transfected into the neurons. After 24 h of OGD treatment, the circ-HECTD1, miR-98-5p and EPHA4 mRNA expressions were detected by real-time fluorescent quantitative PCR (qRT-PCR), the EPHA4 protein expression was detected by Western blotting, the proliferation activity was detected by MTT assay, the apoptosis rate was detected by flow cytometry, the levels of interleukin (IL)-1β and tumor necrosis factor (TNF)-α in cell culture medium were detected by ELISA, and the activities of superoxide dismutase (SOD) and malondialdehyde (MDA) were detected by kit assay. Results:(1) Targeting relations between circ-HECTD1 and miR-98-5p, and EPHA4 and miR-98-5p were verified. (2) As compared with the control group, the neurons in 6, 12 and 24 h OGD treatment groups had significantly increased circ-HECTD1 and EPHA4 protein expressions and significantly decreased miR-98-5p expression ( P<0.05). (3) As compared with OGD+Vector group, OGD+circ-HECTD1 group had significantly increased circ-HECTD1 expression, and significantly decreased miR-98-5p expression ( P<0.05); as compared with OGD+si-NC group, OGD+si-circ-HECTD1 group had significantly increased miR-98-5p expression, and significantly decreased EPHA4 mRNA and protein expressions ( P<0.05); as compared with OGD+miR-NC group, OGD+miR-98-5p mimic group had significantly increased miR-98-5p expression, and significantly decreased EPHA4 protein expression ( P<0.05); as compared with OGD+anti-miR-NC group, OGD+anti-miR-98-5p group had significantly decreased miR-98-5p expression, and significantly increased EPHA4 protein expression ( P<0.05); as compared with the OGD+si-circ-HECTD1+anti-miR-NC group, OGD+si-circ-HECTD1+anti-miR-98-5p group had significantly increased EPHA4 mRNA and protein expressions ( P<0.05). (4) As compared with the control group, the OGD groups had significantly decreased cell viability and SOD activity, and significantly increased IL-1β and TNF-α levels, apoptosis rate and MDA activity ( P<0.05); as compared with the OGD+si-NC group, the OGD+si-circ-HECTD1 group had significantly decreased cell apoptosis rate, IL-1β and TNF-α levels, and MDA activity, and significantly increased cell viability and SOD activity ( P<0.05); as compared with the OGD+si-circ-HECTD1+anti-miR-NC group, the OGD+si-circ-HECTD1+anti-miR-98-5p group had significantly decreased cell viability and SOD activity, and significantly increased IL-1β and TNF-α levels, apoptosis rate and MDA activity ( P<0.05); as compared with the OGD+miR-NC group, OGD+miR-98-5p mimic group had significantly decreased cell apoptosis rate, IL-1β and TNF-α levels, and MDA activity, and significantly increased cell viability and SOD activity ( P<0.05); as compared with OGD+miR-98-5p mimic+pcDNA group, OGD+miR-98-5p mimic+EPHA4 group has significantly increased cell apoptosis rate, IL-1β and TNF-α levels, and MDA activity, and significantly increased cell viability and SOD activity ( P<0.05). Conclusion:Knockdown of circ-HECTD1 could ameliorate the OGD-induced neuronal cell damage in mice by targeting the expressions of miR-98-5p/EPHA4.

Preferred thrombectomy strategies for acute embolic occlusion of the vertebrobasilar artery: a comparative study / 中华神经医学杂志

Objective:To investigate the efficacy of different preferred thrombectomy strategies for embolic acute vertebrobasilar artery occlusion (AVBAO).Methods:Forty-four patients with embolic AVBAO who underwent endovascular treatment in Department of Neurology, Nanyang Central Hospital from January 2019 to June 2021 were included in the study. Patients were divided into stent-retriever thrombectomy group ( n=27) and aspiration thrombectomy group ( n=17) according to different preferred thrombectomy strategies. Modified Rankin scale (mRS) was used to evaluate the prognoses of these patients 90 d after surgery; the differences of clinical data, surgery-related characteristics, prognoses and complications between the two groups were compared. Results:There was no significant difference between the 2 groups in terms of time from onset to puncture, sites of target vessel occlusion, proportion of patients accepted intraoperative remedial measures, and successful recirculation rate of target vessels ( P>0.05). Compared with the aspiration thrombectomy group, the stent-retriever thrombectomy group had significantly decreased utilization rate of middle catheters, significantly increased retrieval attempts in thrombectomy, statistically lower re-recanalization rate of first-time thrombectomy on the target vessels, significantly longer time from puncture to re-recanalization, and significantly higher incidence of new embolism ( P<0.05). There was no significant difference between the 2 groups in incidences of vascular rupture and postoperative spontaneous intracerebral hemorrhage (sICH), and good prognosis rate 90 d after surgery ( P>0.05). Conclusion:For embolic AVBAO patients, similar recanalization and short-term good prognosis can be obtained by aspiration thrombectomy to those by stent-retriever thrombectomy; besides that, aspiration thrombectomy has advantages as shorter recanalization time, less new embolic complications and higher re-recanalization rate of first-time thrombectomy.

Research status and prospect of hypervirulent Clostridioides difficile strain BI/NAP1/027 / 中华检验医学杂志

Clostridioides difficile is a kind of opportunistic pathogen ubiquitous in human intestinal tracts. It can induce intestinal inflammation by releasing its unique toxins when the body has dysbacteriosis due to various triggers, causing patients to experience a variety of clinical symptoms ranging from simple diarrhea to fatal septic shock. In recent years, the BI/NAP1/027 strain of Clostridioidesdifficile has been detected in stool samples of patients from medical institutions all around China. This kind of strain can produce higher levels of toxins and spores that are more difficult to eradicate. More importantly, the strain will pose tremendous threats and challenges to global public health security once it spreads. In this paper, the epidemiological characteristics, virulence, pathogenic mechanisms, molecular diagnostic techniques and the treatment methods of hypervirulent Clostridioides difficile strain BI/NAP1/027 were summarized based on the existing research results and case reports at home and abroad. The possible future research hotspots and endeavors in the field have also been suggested. This article aimed to make a comprehensive understanding of hypervirulent Clostridioides difficile strain BI/NAP1/027, and to provide a theoretical basis for more in-depth analysis of its pathogenic mechanism and more scientific formulation of its prevention and treatment plans in the future.

TREVO stent thrombotomy combined with tirofiban in patients with acute large-artery occlusion of the anterior circulation / 中华神经医学杂志

Objective:To analyze the clinical effect of TREVO stent thrombectomy combined with tirofiban on patients with acute large-artery occlusion of the anterior circulation.Methods:Seventy-two patients with acute large-artery occlusion of the anterior circulation accepted thrombectomy in our hospital from November 2016 to May 2020 were divided into two groups according to different treatment methods: 35 patients in the control group were treated with TREVO stent thrombectomy, and 37 patients in the treatment group were treated with TREVO stent thrombectomy combined with tirofiban via intra-variceal injection. The success rate of recanalization, specific conditions of thrombolysis, improvement degrees of nerve defect, coagulation function, prognoses 90 d after thrombectomy, and complications were compared between the two groups.Results:The success rate of postoperative vascular recanalization in the treatment group and control group was 91.89% (34/37) and 88.57% (31/35), respectively, without statistically significant difference ( P>0.05). The time and times of thrombotomy in the treatment group were significantly shorter/smaller than those in the control group (P<0.05). The National Institute of Health stroke scale (NIHSS) scores of patients from the treatment group 14 d after thrombectomy were significantly lower than those of the control group ( P<0.05). The postoperative thrombin time, prothrombin time, and activated partial thrombin time of the treatment group were significantly longer than those of the control group ( P<0.05). The good prognosis rate of patients in the treatment group and control group 90 d after thrombectomy was 86.49% (32/37) and 60.0% (21/35), with significant differences ( P<0.05); and the incidence of complications was 8.11% (3/37) and 14.29% (5/35), without significant differences ( P>0.05). Conclusion:TREVO stent thrombectomy combined with tirofiban has a significant effect on treatment of acute large-artery occlusion of the anterior circulation, enjoying high safety.

Effect of ketogenic diet on seizures, electroencephalogram and neurobehavioral development in children with epilepsy / 中华实用儿科临床杂志

Objective:To investigate the effects of ketogenic diet on seizures, electroencephalogram(EEG) changes and neurobehavioral development in children diagnosed with epilepsy.Methods:A total of 122 children diagnosed with spastic epilepsy in Nanyang Central Hospital from March 2016 to March 2019 were enrolled.The patients were divided into the observation group and the control group, by the computerized random number table method with 61 cases in each group.The children in the control group were treated with conventional therapy, and the children in the observation group were combined with the ketogenic diet on the basis of conventional treatment.The Gesell developmental schedules scale scores were compared between the two groups to evaluate seizure control and EEG improvement.Results:The seizure control in the observation group was significantly better than that in the control group [78.69%(48/61 cases) vs.54.10%(33/61 cases)], and the difference was statistically significant ( χ2 = 12.114, P <0.05). The EEG improvement in the observation group was significantly better than that in the control group [81.97%(50/61 cases) vs.55.74%(34/61 cases)], and the difference was statistically significant ( χ2=13.623, P<0.05). After 12 months of treatment, the children in the observation group had significantly higher fitness, gross motor, fine motor, language, and personal social, and total development quotient scores than the control group [(56.64±13.29) scores vs.(46.04±12.86) scores, (54.84±12.18) scores vs.(47.62±11.91) scores, (54.44±10.70) scores vs.(44.31±11.56) scores, (51.48±12.99) scores vs.(42.04±11.18) scores, (57.88±11.04) scores vs.(47.42±13.16) scores, (275.28±54.71) scores vs.(227.42±55.79) scores], the differences were statistically significant ( t=5.997, 5.887, 6.003, 5.889, 6.007, 6.010, all P<0.05). Conclusion:The ketogenic diet can significantly reduce seizures, improve EEG and neurobehavioral development in children with epilepsy.

Initial clinical results of laparoscopic pancreaticoduodenectomy using the No-touch isolation technique for pancreatic head carcinoma / 中华肝胆外科杂志

Objective:To study the preliminary clinical results of the No-touch technique in laparoscopic pancreaticoduodenectomy for pancreatic head cancer.Methods:A retrospective analysis was consulted on 11 patients who underwent laparoscopic pancreaticoduodenectomy for pancreatic head cancer at the Pancreas Center of Guangdong Provincial Hospital of Traditional Chinese Medicine from April 2019 to April 2020. There were 5 males and 6 females, with a Mean±SD age of (63.6±12.2) years. Preoperative evaluation showed all patients were diagnosed to have resectable pancreatic head carcinoma with no local invasion into adjacent arteries and veins, and without metastasis. The surgical strategy consisted of no initial Kocher manoeuvre with no flipping or pulling of the pancreaticoduodenal area. Through unwinding of the pancreatic uncinate process, the pancreatic blood vessels, nerves and lymphatic vessels were completely detached to isolate the tumor. Finally, the pancreaticoduodenal area was totally resected and the digestive tract was reconstructed using the Child’s method. The operation time, intraoperative blood loss, postoperative complications, postoperative pathology and follow-up data of the patients were evaluated.Results:All patients completed the laparoscopic operation without any need for conversion to laparotomy. The operation time of the 11 patients was (422.2±102.2) min, and the bleeding volume was (102.7±65.4) ml. There were 2 patients who developed pancreatic fistula, with 1 patient having a biochemical fistula and 1 patient a grade B fistula. There was no grade C fistula. Other complications included 1 patient with delayed gastric emptying. There were no biliary fistula, no postoperative abdominal bleeding, and no perioperative death. Postoperative pathology showed 6 patients had lymph node metastases, with a positive lymph nodes rate of (4.8±4.4)%. All patients had R 0 resection. The follow-up survival data of the 11 patients showed one patient to develop intrahepatic metastasis 1 month after operation and he died 9 months after operation. Another patient developed liver metastases 2 months after operation. The remaining patients were tumor-free. Conclusion:Laparoscopic pancreaticoduodenectomy using the No-touch isolation and resection technique could achieve complete resection of tumors, and it can safely and effectively be applied to patients with pancreatic head cancer.

Association of plasma kallikrein and bradykinin receptor 1 with prognosis of cerebral infarction in elderly rats after ischemic stroke / 中华老年医学杂志

Objective:To explore the correlation of plasma kallikrein and bradykinin receptor 1 with prognosis of cerebral infarction in elderly rats after ischemic stroke.Methods:A total of 40 male Sprague-Dawley rats were randomly divided into 4 groups: the stroke model group(intraperitoneally injected with 150 μl 0.9% saline, n=10), the DX-88 group(intravenously injected with kallikrein inhibitor DX-88 30 μl/time, n=10), the R-954 group(intravenously injected with bradykinin B1 receptor antagonist R-954 30 μl/time, n=10)and the DX-88 combined with R-954 treatment group(intravenously injected with DX-88 and R-954, n=10). Protein expression levels of plasma kallikrein and bradykinin receptor 1 were determined by Western blotting.mRNA expression levels of interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α)and caspase-3 were analyzed by using qRT-PCR.A neurologic function scale was used to score cerebral nerve injury and calculate the middle cerebral infarction area and cerebral swelling in experimental rats.Cerebral blood-brain barrier permeability was assessed by the cerebral infarction area.Results:Neurological injury scores decreased in the DX-88, R-954 and DX-88 + R-954 groups compared with the stroke model group(5.35±1.35, 6.49±1.16, 4.92±0.92 vs.11.17±2.18, F=15.589, P=0.022). Compared with the stroke model group, the cerebral infarction area was reduced in the DX-88, R-954 and DX-88+ R-954 groups[(4.35±1.05) mm 2, (5.43±0.26) mm 2, (3.88±0.13) mm 2vs.(8.26±1.24) mm 2, F=13.476, P=0.034)]. The extent of brain swelling was smaller in the DX-88, R-954 and DX-88+ R-954 groups than in the stroke model group[(31.28±7.45) %, (35.19±8.57) %, (19.68±3.14) % vs.(74.26±15.66) %, F=16.587, P=0.026)]. Plasma kallikrein protein levels were lower in the DX-88 and DX-88+ R-954 groups than in the stroke model group( P<0.05). The expression of bradykinin-1 receptor mRNA was lower in the R-954 and DX-88+ R-954 groups than in the stroke model group( P<0.05). The above results indicated that antagonism of plasma kallikrein and bradykinin receptor 1 played an important role.mRNA transcription levels of IL-1β, TNF-α and caspase-3 were higher in the stroke model group than in the DX-88, R-954 and DX-88+ R-954 groups( F=12.665、14.574 and 13.665, P=0.021、0.015 and 0.003). Conclusions:Inhibiting plasma kallikrein and bradykinin receptor 1 may provide protection against cerebral nerve injury in cerebral ischemia, and improve the prognosis of cerebral infarction.

Application of 3D laparoscopy in pancreaticoduodenectomy / 临床肝胆病杂志

Pancreaticoduodenectomy is one of the most difficult abdominal operations, and the difficulty in resection and complicated digestive tract reconstruction have brought great challenges for surgeons. At present, laparoscopic pancreaticoduodenectomy has been widely used in clinical practice, and compared with traditional 2D laparoscopy, 3D laparoscopy has the features of high magnification, high definition, and three-dimensional vision, which enables surgeons to see more clearly and operate more accurately, and thus it has great potential to be widely used in pancreaticoduodenectomy.

Expression of microRNA506 in brain tissue of mice with cerebral ischemia reperfusion injury and its effect on proliferation and apoptosis of SH-SY5Y cells / 中华行为医学与脑科学杂志

Objective To explore the expression of microRNA506 in brain tissue of mice with cere-bral ischemia reperfusion injury and its effect on proliferation and apoptosis of SH-SY5Y cells. Method-s Middle cerebral artery occlusion(MCAO)was used to establish the model of cerebral ischemia reperfu-sion in mice,and RT-PCR(reverse transcription polymerase chain reaction)was used to detect the expres-sion level of microRNA506 in the brain tissue of mice. MicroRNA506 overexpression plasmids and interfer-ence plasmids were constructed and transfected into SH-SY5Y cells respectively.Cell apoptosis was detected by flow cytometry,and cell proliferation was detected by MTT assay. Results The level of microRNA506 in brain tissue of cerebral ischemia reperfusion model mice was significantly higher than that of sham operation group((51.16±1.64)vs(12.82±1.66),P=0.008). The siRNA targeting microRNA506 significantly re-duced the growth of SH-SY5Y cells(P=0.0072),and induced the apoptosis of SH-SY5Y cells(P=0.0073). Transfection of microRNA506 enhanced the proliferation rate(P=0.020)of SH-SY5Y cells,and reduced the apoptosis of SH-SY5Y cells(P=0.017).Conclusions The expression level of microRNA506 in brain tissue of mice with cerebral ischemia reperfusion is increased.Overexpression of microRNA506 promotes the cell proliferation and decreases the apoptosis rate of SH-SY5Y cell while the low expression of microRNA506 de-creases the growth rate and induce cell apoptosis of SH-SY5Y cell.

Leptin promotes proliferation and inhibits apoptosis of human breast cancer BT-474 and MDA-MB-231 cells by down-regulating the expression of FBP 1 gene / 肿瘤

Objective: To investigate the effects of leptin on the proliferation and apoptosis of human breast cancer BT-474 and MDA-MB-231 cells, and to explore its underlying molecular mechanism. Methods: After treatment with 200 ng/mL leptin, the proliferation and apoptosis of BT-474 and MDA-MB-231 cells were measured by CCK-8 assay and FCM, respectively; the expression levels of proliferation-and apoptosis-Associated proteins c-myc, cyclin D1, Bcl-2 and Bax were determined by Western blotting; while the levels of fructose-1, 6-bisphosphatase 1 (FBP1) mRNA and protein were detected by real-Time fluorescent quantitative PCR and Western blotting, respectively. After the recombinant plasmids carrying FBP 1 gene were transfected by liposome into BT-474 and MDA-MB-231 cells which were treated with 200 ng/mL leptin, the expression levels of FBP1 mRNA and protein were detected by real-Time fluorescent quantitative PCR and Western blotting to verify the over-expression of FBP 1 gene. Then, the proliferation abilities of BT-474 and MDA-MB-231 cells were measured by CCK-8 assay, the expression levels of proliferation-Associated proteins c-myc and cyclin D1 were determined by Western blotting, the apoptosis rates of the two cell lines were detected by FCM, and the expression levels of apoptosis-Associated proteins Bcl-2 and Bax were determined by Western blotting. Results: After treatment with 200 ng/mL leptin, the proliferation abilities of human breast cancer BT-474 and MDA-MB-231 cells were significantly increased (both P < 0.01); the expressions of proliferation-Associated proteins c-myc and cyclin D1 were significantly upregulated (both P < 0.01); while the apoptosis rates were apparently reduced (both P < 0.01); the expression of apoptosis-Associated protein Bcl-2 was apparently up-regulated (P < 0.01), but the expression of Bax was apparently down-regulated (P < 0.01); the mRNA and protein levels of FBP1 in BT-474 and MDA-MB-231 cells were obviously down-regulated (both P < 0.05). However, after transfection with FBP1 over-expression plasmids, the expressions of FBP1 mRNA and protein were significantly up-regulated in BT-474 and MDA-MB-231 cells (both P < 0.01), while the effects of leptin on proliferation and apoptosis of BT-474 and MDA-MB-231 cells were dramatically reversed (all P < 0.01). Conclusion: Leptin promotes the proliferation and inhibits the apoptosis of human breast cancer BT-474 and MDA-MB-231 cells, and the potential mechanism may be related to the down-regulation of FBP 1 gene expression.

Research of oxaliplatin inhibit growth in glioma U87 cells by regulating PI3K/Akt signal pathway / 中国免疫学杂志

Objective:To investigate the effect of oxaliplatin inhibit the growth in glioma U 87 cells by regulating PI3K/Akt sig-nal pathway.Methods:The glioma U87 cells were cultivated in vitro ,using 0,20,40,80 μg/ml oxaliplatin treated U87 cells 24,36, 48,72 h respectively,MTT was used to detect cell proliferation.Using 40 μg/ml oxaliplatin treated U87 cells 48 h,flow cytometry was used to detect cell cycle and apoptosis .Cells apoptosis protein and PI 3K/Akt pathway protein expression after 40 μg/ml oxaliplatin treated U87 cells 48 h was detected by Western blot .Results:MTT assay showed that compared with the 0μg/ml treatment ,oxaliplatin treatment could significantly inhibited U 87 cell survival ( P0.05).Conclusion:Oxaliplatin may suppress U87 cell proliferation,ar-rest cell cycle,and promote apoptosis by inhibit PI3K/Akt signaling pathway.

Quercetin inhibits proliferation and promotes apoptosis of glioma stem cells via the STAT pathway / 中国组织工程研究

BACKGROUND:Several studies have reported that quercetin can inhibit the proliferation and migration but promotes apoptosis of tumor cel s. OBJECTIVE:To explore the effect of quercetin on the proliferation and apoptosis of glioma stem cel s and the signal pathway involved. METHODS:Glioma stem cel s were isolated by immunomagnetic beads and treated in culture medium containingdifferent concentrations of quercetin (0, 25, 50, 100μmol/L). Cel proliferation was measured by MTT and apoptosis measured by flow cytometry at 48 hours after culture. The expression levels of Bcl-2, Bax and survivin, which are related to apoptosis, were detected by western blot. The expression of proliferating cel nuclear antigen (PCNA), which is related to proliferation, was also detected by western blot. The expression of STAT3 and p-STAT3 was also determined by western blot. RESULTS AND CONCLUSION:(1) Compared with the control (0μmol/L) group, quercetin inhibited the proliferation of glioma stem cel s in a dose-depended manner (P<0.05). With the increase of the concentration of quercetin, the expression of PCNA was increased (P<0.05). (2) Quercetin induced apoptosis of glioma stem cel s dose-dependently (P<0.05). With the increase of the concentration of quercetin, the expression of Bcl-2 and survivin was decreased, while the expression Bax was increased. (3) Quercetin could also inhibit phosphorylation of STAT3 dose-dependently, but the level of STAT3 was not changed. To conclude, these results show that quercetin could inhibit the proliferation of glioma stem cel s and promote apoptosis via the STAT pathway.

Over-expression of fructose-1, 6-bisphosphatase 1 gene inhibits the migration of breast cancer tamoxifen-resistant cells and induces apoptosis / 肿瘤

Objective: To investigate the effects of over-expressing fructose-1, 6-bisphosphatase 1 (FBP 1) gene on migration and apoptosis of tamoxifen-resistant MCF-7 human breast cancer cells. Methods: The levels of FBP1 mRNA and protein in human breast cancer tamoxifen-sensitive MCF-7 cells and tamoxifen-resistant MCF-7R cells were measured by real-time fluorescent quantitative PCR and Western blotting, respectively. Then, the FBP1 over-expression plasmids were transfected into MCF-7R cells by lipofectin, and the expression levels of FBP1 mRNA and protein were detected by real-time fluorescent quantitative PCR and Western blotting in order to verify the over-expression of FBP 1 gene. After that, the morphology of MCF-7R cells with FBP1 over-expression was observed under an inverted optical microscope, the abilities of cell migration and apoptosis were measured by cell wound healing experiment and FCM assay, respectively. Furthermore, the expressions of apoptosis-associated proteins Bcl-2 and Bax as well as the epithelial-mesenchymal transition (EMT) markers E-cadherin and vimentin were detected by Western blotting. Results: The mRNA and protein levels of FBP1 in human breast cancer tamoxifen-resistant MCF-7R cells were lower than those in tamoxifen-sensitive MCF-7 cells (both P< 0.01). After the transfection of FBP1 over-expression plasmids, the mRNA and protein expressions of FBP1 were significantly up-regulated in MCF-7R cells (both P< 0.01), MCF-7R cells had a change from mesenchymal-like morphology to epithelial-like morphology, the apoptotic index of MCF-7R cells was increased (P < 0.01), but the ability of cell migration was decreased (P < 0.01). Moreover, the protein expressions of Bcl-2 and vimentin were obviously down-regulated (both P<0.01), while the protein expressions of Bax and E-cadherin were significantly up-regulated (both P<0.01). Conclusion: The over-expression of FBP 1 gene can significantly inhibit cell migration and EMT in human breast cancer tamoxifen-resistant MCF-7R cells, and promote apoptosis through decreasing Bcl-2 expression and increasing Bax expression.

Effects of Fosinopril on Oxidative Stress and Vascular Function in Experimental Rats With Spontaneous Hypertension / 中国循环杂志

Objective: To explore the effects of fosinopril on oxidative stress and vascular function in experimental rats with spontaneous hypertension. Methods: The rats were divided into 3 groups: Control group, with normal healthy rats (n=15), Spontaneous hypertension (SH) group (n=15), SH rats received intragastric administration of normal saline and Treatment group (n=15), SH rats received intragastric administration of fosinopril 10mg/(kg?d). All animals were treated for 7 weeks. Caudal artery systolic blood pressure (SBP) was measured at each week. blood levels of superoxide dismutase (SOD), reactive oxygen species (ROS), malonaldehyde (MDA) and NO2-/NO3- were determined in different groups respectively after 7 weeks. Moreover, thoracic aorta was taken to examine its diastolic reactive rate by acetylcholine (Ach)/sodium nitroprusside (SNP) induction. Results: From the 1st week until the end of experiment, compared with SH group, Treatment group had decreased SBP,P<0.05. With 7 weeks treatment, compared with Control group, SH group had decreased SOD activity, while increased protein levels of MDA and ROS, allP<0.05; compared with SH group, Treatment group showed elevated SOD activity (P=0.010), while reduced protein levels of MDA (P=0.021) and ROS (P=0.009). Compared with Control group, SH group had the lower content of NO2-/NO3-(P<0.001); both SH group and Treatment group had decreased diastolic rates by Ach/SNP induction,P<0.05. Compared with SH group, Treatment group presented the higher content of NO2-/NO3- and higher diastolic rate by Ach induction, allP<0.001. Conclusion: Fosinopril could improve vascular diastolic function via anti-oxidative stress in experimental SH rats, which might be one of its anti-hypertensive mechanisms.

Study on Preparation of Immobilized Thrombin Treated with Silk Fibroin / 中国药师

Objective: To investigate the effects of silk fibroin on the immobilization of thrombin. Methods: The immobilized thrombin was prepared using silk fibroin as the carrier and glutaraldehyde as the crosslinking agent. With activity yield as the index, the process conditions of silk fibroin immobilized thrombin were determined by an orthogonal test. Results:The optimum process con-ditions of immobilized thrombin treated with silk fibroin were as follows:the immobilization time was 6 h, the enzyme dosage was 2 400 NIH·g-1 casein, the temperature was 25℃ and pH was 7. 6. The activity recovery of immobilized thrombin was 67. 22%. Conclu-sion:Silk fibroin has the positive immobilization effect on thrombin.

Construction of legitimate interest safeguard mechanism for mental health workers / 中国心理卫生杂志

The legitimate rights of mental health workers don't get expected protection,which has caused negative influence on the development of mental health work.By introducing the Gantt v.Arnie Sethcase,we an-alyzed the law applicable disputes of doctors who are hurt by the patients with mental disorders,and made legal e-valuation on the views of relevant responsibility identification at home and abroad,and attempted to come up with some suggestions on construction of legitimate interest safeguard mechanism for mental-health workers from the as-pects of legislation and administrative policy.

Effects of recombinant human granulocyte-macrophage colony-stimulating factor on wound healing and microRNA expression in diabetic rats / 中华烧伤杂志

<p><b>OBJECTIVE</b>To investigate the effects of recombinant human granulocyte macrophage colony-stimulating factor (rhGM-CSF) on wound healing and microRNA expression in diabetic rats.</p><p><b>METHODS</b>Eighteen male SD rats of clean grade were used to reproduce diabetes model. Four weeks later, a total of 64 full-thickness skin wounds were created on the back of 16 rats with established diabetes, with 4 wounds on each rat. Two symmetrical wounds on either side of the spine were created as a pair according to paired design. Then the wounds were divided into groups A and B according to the random number table and blind method (red and blue tags on the rhGM-CSF or the gel vehicle), with 32 wounds in each group. The ointment with red tag was applied on the wounds of group A and the blue one on group B. The application was conducted once a day, with a thickness of 3 mm, up to post injury day (PID) 14. Gross observation of wound healing was conducted on PID 3, 7, 14. The wound healing rate was determined on PID 3 and 7. On PID 3, 7, 14, tissues from 2, 4, and 8 wounds were harvested from each group respectively for the observation of the histopathological changes with HE staining, and also for analyzing the expression of proliferating cell nuclear antigen (PCNA) and CD31 with immunohistochemical staining (denoted as absorbance value). On PID 7, tissues from 6 wounds in each group were harvested for microarray gene chip to screen the differentially expressed microRNAs. Enrichment analysis of Kyoto encyclopedia of genes and genomes (KEGG) signaling pathway on the differentially expressed microRNAs were performed after the microRNA screening results were validated by real-time fluorescent quantitative RT-PCR. Data were processed with paired t test or two-sample t test.</p><p><b>RESULTS</b>(1) On PID 3, the wound area was significantly decreased, and the wound granulation was significantly proliferated in both groups. On PID 7, the wound area was further decreased, and the wound area was almost filled by granulation in both groups; the conditions in group A were better. On PID 14, all the wounds in group A were almost healed, while a small area of raw wound with incrustation still remained in some wounds of group B. On PID 3 and 7, the wound healing rates of group A were (41 ± 5)% and (75 ± 4)%, significantly higher than those of group B [(31 ± 9)% and (71 ± 4)%, with t values respectively 10.13 and 8.06, P values below 0.001]. (2) On PID 3, the epidermal cells, endothelial cells, and Fbs in the wounds of 2 groups were sparse, with heavy infiltration of inflammatory cells. The above condition in the wounds was better in group A than in group B. On PID 7, the epidermal cells, endothelial cells, and Fbs were gradually well arranged in group A; infiltration of inflammatory cells decreased, and the condition was better than that of group B. On PID 14, the wounds of group A were completely covered by epidermis, while infiltration of inflammatory cells still remained in some wounds of group B. (3) On PID 3, 7, 14, the positive expressions of CD31 and PCNA in group A were respectively 0.275 ± 0.018, 0.345 ± 0.034, 0.305 ± 0.023; 0.406 ± 0.063, 0.223 ± 0.011, 0.045 ± 0.022. They were significantly higher than those of group B (0.222 ± 0.020, 0.229 ± 0.018, 0.197 ± 0.015; 0.324 ± 0.039, 0.162 ± 0.012, 0.018 ± 0.020, with t values from 2.281 to 9.652, P < 0.05 or P < 0.01). (4) According to the microRNAs detection and screening, as compared with group B, 18 microRNAs were up-regulated while 13 were down-regulated in the wounds of group A. (5) The results of real-time fluorescent quantitative RT-PCR had good consistency with the results of microRNAs detection. (6) Enrichment analysis of KEGG signaling pathway showed that among the 31 differentially expressed microRNAs, 4 took part in the MAPK signaling pathway, 3 took part in the Wnt signaling pathway, 1 took part in the TGF-β signaling pathway, 3 took part in the epidermal growth factor receptor signaling pathway, 2 took part in the cell cycle pathway, 5 took part in the axon guidance signaling pathway, 6 took part in the focal adhesion pathway, 3 took part in the regulation of actin cytoskeleton pathway, 1 took part in the extracellular cell matrix receptor pathway, 3 took part in the adherens junction pathway, and 1 took part in the cell adhesion molecules pathway. After disclosing the blind, it showed that the ointment with red tag was the rhGM-CSF gel and the blue one was gel vehicle.</p><p><b>CONCLUSIONS</b>The rhGM-CSF gel can promote wound healing in diabetic rats, producing significant differential microRNA expression in wounds, and they may be the target at gene post-transcriptional level of rhGM-CSF gel in promoting wound healing.</p>

Study Progress in Methods and Mathematical Models for the Prediction of Drug Metabolism and Interac-tions on the Basis of in vitro Investigations / 中国药师

Objective: To provide the evidence for the development of new drugs, the modification in chemical structures of the registered drugs and the establishment of the therapeutic treatment involving several drugs. Method:Using cytochrome, drug interac-tion and in vitro investigations as the keywords, CHKD and PubMed were searched, and the corresponding references were summarized from 2003 to 2013. The biological characters of the cytochrome oxidase and the ways on the choice of the suitable enzyme system for the research of drug in vitro pharmacokinetic parameters were analyzed in order to predict the potential drug interactions in vivo. Result:The [I]/Ki value had close relation with the possibility of the potential interactions, however, the calculation of [I] was the difficult point, and the methods should be modified according to the specific situation. Conclusion:The prediction technology of drug metabo-lism and interactions on the basis of in vitro investigations can avoid the in vivo complicated process to the greatest extent, reduce the cycle time and the economic cost for the new drug development, and provide the logical evidence and the risky level for the reasonable application of clinical drugs.