lncRNA MALAT1通过miR-124-3p/SOX7分子轴促进视网膜血管内皮细胞增殖及迁移和血管生成

目的:探讨lncRNA MALAT1对视网膜血管内皮细胞增殖、迁移及血管生成的影响及其分子机制。方法:qPCR检测正常对照组、糖尿病患者无视网膜病变组、糖尿病视网膜病变患者组血清中lncRNA MALAT1的表达水平以及葡萄糖培养对lncRNA MALAT1的表达水平的影响。qRT-PCR检测miR-124-3p表达水平;Western blotting检测SOX7表达水平;双荧光素酶报告系统检测lncRNA MALAT1与miR-124-3p、miR-124-3p与SOX7的靶向作用关系;CCK-8实验检测细胞的增殖活力;Transwell实验检测细胞的迁移能力;体外成管实验检测hRMECs血管形成能力。结果:lncRNA MALAT1在糖尿病视网膜病变患者血清中的表达水平显著高于糖尿病患者无视网膜病变组和正常对照组(P<0.001);体外葡萄糖培养显著促进lncRNA MALAT1在hRMECs细胞的表达,并显著促进hRMECs细胞的增殖、迁移和血管形成(均P<0.05)。敲低lncRNA MALAT1显著抑制hRMECs细胞的增殖、迁移和成管能力(均P<0.05)。双荧光素酶报告基因实验表明,lncRNA MALAT1与miR-124-3p、miR-124-3p与SOX7之间存在靶向结合作用。过表达miR-124-3p显著抑制hRMECs细胞的增殖、迁移和成管能力(均P <0.05);过表达lncRNA MALAT1+miR-124-3p,同时过表达miR-124-3p+SOX7,敲低lncRNA MALAT1+过表达SOX7均显著消除了过表达miR-124-3p对hRMECs细胞增殖、迁移和血管形成的抑制作用(均P<0.05)。结论:lncRNA MALAT1通过下调miR-124-3p对SOX7的负调控作用促进糖尿病视网膜病变中视网膜内皮细胞增殖、迁移和血管形成。lncRNA MALAT1在糖尿病视网膜病变患者的异常上调可能是微血管功能障碍的潜在生物标志。

Glycyrrhizic acid attenuates CCl_4-induced hepatocyte apoptosis in rats via a p53-mediated pathway

AIM: To investigate the effect of glycyrrhizic acid (GA) on carbon tetrachloride (CCl4)-induced hepatocyte apo-ptosis in rats via a p53-dependent mitochondrial path-way. METHODS: Forty-five male Sprague-Dawley rats were randomly and equally divided into three groups, the control group, the CCl4 group, and the GA treatment group. To induce liver fibrosis in this model, rats were given a subcutaneous injection of a 40% solution of CCl4 in olive oil at a dose of 0.3 mL/100 g body weight biweekly for 8 wk, while controls received the same isovolumetric dose of olive oil by hypodermic injection, with an initial double-dose injection. In the GA group,rats were also treated with a 40% solution of CCl4 plus 0.2% GA solution in double distilled water by the intraperitoneal injection of 3 mL per rat three times a week from the first week following previously published methods, with modifications. Controls were given the same isovolumetric dose of double distilled water. Liver function parameters, such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were de-termined. Pathologic changes in the liver were detected by hematoxylin and eosin staining. Collagen fibers were evaluated by Sirius red staining. Hepatocyte apoptosis was investigated using the terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-triphosphate nick end labeling (TUNEL) assay and the cleaved caspase-3 immunohistochemistry assay. The expression levels of p53 and apoptosis-related proteins were evaluated by immunohistochemistry or Western blotting analysis. RESULTS: After 8 wk of treatment, GA significantly re-duced serum activity of ALT (from 526.7 ± 57.2 to 342 ± 44.8, P<0.05) and AST (from 640 ± 33.7 to 462.8 ± 30.6, P<0.05), attenuated the changes in liver his-topathology and reduced the staging score (from 3.53 ± 0.74 to 3.00 ± 0.76, P<0.05) in CCl4 -treated rats. GA markedly reduced the positive area of Sirius red and the ratio of the hepatic fibrotic region (from 7.87% ± 0.66% to 3.68% ± 0.32%, P<0.05) compared with the CCl4 group. GA also decreased the expression level of cleaved caspase-3 compared to the CCl4 group. TU-NEL assay indicated that GA significantly diminished the number of TUNEL-positive cells compared with the CCl4 group (P<0.05). GA treatment clearly decreased the level of p53 (P<0.05) detected by immunohis-tochemistry and Western blotting analysis. Compared with the CCl4 group, we also found that GA reduced the Bax/Bcl-2 ratio (P<0.05), the expression of cleaved caspase-3 (P<0.05), cleaved caspase-9 (P<0.05), and inhibited cytochrome C and second mitochondria-derived activator of caspases (Smac) release from mito-chondria to cytoplasm, i.e. , GA reduced the expressionlevel of Smac, which inhibited c-IAP1 activity (P<0.05), ultimately inhibiting the activity of caspase-3, according to Western blotting analysis. As a result, GA suppressed activation of the caspase cascades and prevented he-patocyte apoptosis.

Application of indocyanine green-enhanced near-infrared fluorescence-guided imaging in laparoscopic lateral pelvic lymph node dissection for middle-low rectal cancer

BACKGROUND As one effective treatment for lateral pelvic lymph node(LPLN)metastasis(LPNM),laparoscopic LPLN dissection(LPND)is limited due to the complicated anatomy of the pelvic sidewall and various complications after surgery.With regard to improving the accuracy and completeness of LPND as well as safety,we tried an innovative method using indocyanine green(ICG)visualized with a near-infrared(NIR)camera system to guide the detection of LPLNs in patients with middle-low rectal cancer.AIM To investigate whether ICG-enhanced NIR fluorescence-guided imaging is a better technique for LPND in patients with rectal cancer.METHODS A total of 42 middle-low rectal cancer patients with clinical LPNM who underwent total mesorectal excision(TME)and LPND between October 2017 and March 2019 at our institution were assessed and divided into an ICG group and a non-ICG group.Clinical characteristics,operative outcomes,pathological outcomes,and postoperative complication information were compared and analysed between the two groups.RESULTS Compared to the non-ICG group,the ICG group had significantly lower intraoperative blood loss(55.8±37.5 mL vs 108.0±52.7 mL,P=0.003)and a significantly larger number of LPLNs harvested(11.5±5.9 vs 7.1±4.8,P=0.017).The LPLNs of two patients in the non-IVG group were residual during LPND.In addition,no significant difference was found in terms of LPND,LPNM,operative time,conversion to laparotomy,preoperative complication,or hospital stay(P>0.05).CONCLUSION ICG-enhanced NIR fluorescence-guided imaging could be a feasible and convenient technique to guide LPND because it could bring specific advantages regarding the accuracy and completeness of surgery as well as safety.

Acetyl-11-keto-β-boswellic acid extracted from Boswellia serrata promotes Schwann cell proliferation and sciatic nerve function recovery

Frankincense can promote blood circulation. Acetyl-11-keto-β-boswellic acid （AKBA） is a small molecule with anti-inflammatory properties that is derived from Boswellia serrata. Here, we hypothesized that it may promote regeneration of injured sciatic nerve. To address this hypothesis, we established a rat model of sciatic nerve injury using a nerve clamping method. Rats were administered AKBA once every 2 days at doses of 1.5, 3, and 6 mg/kg by intraperitoneal injection for 30 days from the 1st day after injury. Sciatic nerve function was evaluated using the sciatic functional index. Degree of muscle atrophy was measured using the triceps surae muscle Cuadros index.Neuropathological changes were observed by hematoxylin-eosin staining. Western blot analysis was used to detect expression of phospho-extracellular signal-regulated kinase 1 and 2 （p-ERK1/2） in injured nerve. S100 immunoreactivity in injured nerve was detected by immunohistochemistry. In vivo experiments showed that 3 and 6 mg/kg AKBA significantly increased sciatic nerve index, Cuadros index of triceps muscle, p-ERK1/2 expression, and S100 immunoreactivity in injured sciatic nerve of sciatic nerve injury model rats. Furthermore,for in vitro experiments, Schwann cells were treated with AKBA at 0–20 μg/mL. Proliferation of Schwann cells was detected by Cell Counting Kit-8 colorimetry assay. The results showed that 2 μg/mL AKBA is the optimal therapeutic concentration. In addition, ERK phosphorylation levels increased following 2 μg/mL AKBA treatment. In the presence of the ERK1/2 inhibitor, PD98059 （2.5 μL/mL）, the AKBA-induced increase in p-ERK1/2 protein expression was partially abrogated. In conclusion, our study shows that AKBA promotes peripheral nerve regeneration with ERK protein phosphorylation playing a key role in this process.

起振方案对模式竞争的影响（英文）

当回旋管工作在高次模式或者高次谐波时,模式竞争尤为剧烈。通常最佳工作状态下,回旋管工作在单模,起振方案对回旋管是否单模工作影响很大。文章研究了等离子体聚变托克马克系统中的应用于电子回旋共振加热的120GHz回旋管,该回旋管工作模式为TE_(22,6+),计算了不同起振方案中电子参数的时间演变并将其用于研究模式起振。根据计算结果可知,当设计合适的起振方案后回旋管可工作在单模下。文章基于的理论为线性理论,并且应用的模式为基模,但是该分析方法同样适用于高次谐波。仿真结果显示,三极管类型起振方案和其他两个起振方案下,工作模式TE_(22,6+)可以单独起振。

Intra-corporeal delta-shaped anastomosis in laparoscopic right hemicolectomy for right colon cancer:a safe and effective technique

Background and objective:Intra-corporeal delta-shaped anastomosis(IDA)is an important development in laparoscopic digestive-tract reconstruction.We applied it in laparoscopic right hemicolectomy for right colon cancer and compared the short-term outcomes between the patients treated with IDA and conventional extracorporeal anastomosis(EA).Methods:Between 1 January 2016 and 1 October 2017,36 and 50 patients who underwent IDA and EA,respectively,were included.Data on clinicopathological characteristics,surgical outcomes,post-operative recovery and complications were collected and compared between the two groups.Results:Surgical outcomes and clinicopathological characteristics were similar between the two groups except the length of incision,which was significantly shorter in the IDA group than in the EA group(4.660.6 vs 5.660.7 cm,P<0.001).The time to ground activities,fluid diet intake and post-operative hospitalization did not differ between the groups;however,the time to first flatus was significantly shorter in the IDA group than in the EA group(2.860.5 vs 3.260.8 days,P=0.004).The post-operative visual analogue scale for pain was lower in the IDA group than in the EA group on post-operative Day 1(4.060.7 vs 4.561.0,P=0.002)and post-operative Day 3(2.760.6 vs 3.460.6,P<0.001).The surgical complication rates were 8.3 and 16.0%in the IDA and EA groups(P=0.470),respectively.No complications such as anastomotic bleeding,stenosis and leakage occurred in any patient.Conclusions:IDA is safe and feasible and shows more satisfactory short-term outcomes than EA.

Chaetomium-like fungi causing opportunistic infections in humans:a possible role for extremotolerance

Members of the family Chaetomiaceae are ubiquitous ascosporulating fungi commonly,which reside in soil enriched with manure or cellulosic materials.Their role as human pathogens is largely ignored.However,the ability of some species to grow at high temperature enables them to play an important role as opportunistic pathogens.The family contains several genera and species that have never been reported to cause human infection.Hereby,three new species are described;two belong to the genus Subramaniula and one represents a Chaetomium species.Subramaniula asteroides was isolated from various sources including eye and skin infections as well as from the natural environment,and S.obscura was isolated from a toe infection.Chaetomium anamorphosum was isolated from a kidney transplant patient suffering from fungal peritonitis.All species described were previously misidentified as Papulaspora spp.due to the formation of cellular clumps or bulbil-like structures,which are characteristic of Papulaspora.The isolates failed to form sexual fruit bodies and ascospores remained absent,which is an unusual feature for the generally ascosporulating genera Chaetomium and Subramaniula;minute conidia from phialides were sometimes observed.

Oversleeve anastomosis in laparoscopic sphincter-preserving surgery for low rectal cancer:an overlapped end-to-end anastomosis technique without prophylactic stoma

Introduction With recent advances in laparoscopic-surgery techniques and neoadjuvant therapy options,there have been improvements in sphincter-preservation outcomes in patients with low rectal cancer[1-3].However,several issues remain controversial,such as the incidence of anastomotic leakage,the local recurrence rate,and anal-function outcome[4-5].Moreover,prophylactic stoma at the end of sphincter-preserving surgery is necessary to prevent anastomotic leakage,especially in patients undergoing neoadjuvant chemoradiotherapy[7].To avoid prophylactic colostomy and decrease excessive expense,we developed a new method of overlapped end-to-end anastomosis for treating low rectal cancer—a technique referred to as‘oversleeve anastomosis’.

Stereochemical determination of tetrahydropyran-substituted xanthones from fungus Chaetomium murorum

Chaetoxanthone D（1）, a new tetrahydropyran-substituted xanthone originated from polyketide pathway, together with the four known natural products chaetoxanthone C（2）, alternariol methyl ether（3）, alternariol（4） and 2,5-dimethyl-7-hydroxychromone（5） was isolated from a strain of Chaetomium murorum. The structures of these compounds were elucidated based on extensive spectroscopic analyses. The absolute configurations of 1 and 2 were determined by using quantum chemical electronic circular dichroism（ECD） calculations.