METTL14 is a chromatin regulator independent of its RNA N6-methyladenosine methyltransferase activity

METTL3 and METTL14 are two components that form the core heterodimer of the main RNA m6A methyltransferase complex (MTC) that installs m6A. Surprisingly, depletion of METTL3 or METTL14 displayed distinct effects on stemness maintenance of mouse embryonic stem cell (mESC). While comparable global hypo-methylation in RNA m6A was observed in Mettl3 or Mettl14 knockout mESCs, respectively. Mettl14 knockout led to a globally decreased nascent RNA synthesis, whereas Mettl3 depletion resulted in transcription upregulation, suggesting that METTL14 might possess an m6A-independent role in gene regulation. We found that METTL14 colocalizes with the repressive H3K27me3 modification. Mechanistically, METTL14, but not METTL3, binds H3K27me3 and recruits KDM6B to induce H3K27me3 demethylation independent of METTL3. Depletion of METTL14 thus led to a global increase in H3K27me3 level along with a global gene suppression. The effects of METTL14 on regulation of H3K27me3 is essential for the transition from self-renewal to differentiation of mESCs. This work reveals a regulatory mechanism on heterochromatin by METTL14 in a manner distinct from METTL3 and independently of m6A, and critically impacts transcriptional regulation, stemness maintenance, and differentiation of mESCs.

Short-term efficacy comparison of totally laparoscopy and open pancreatoduodenectomy in the treatment of periampullary carcinoma / 肿瘤研究与临床

Objective:To explore the short-term efficacy of totally laparoscopy pancreatoduodenectomy (TLPD) and open pancreatoduodenectomy (OPD) in the treatment of periampullary carcinoma.Methods:The clinical data of 50 patients with periampullary carcinoma in the First Hospital of Shanxi Medical University from June 2016 to March 2019 were retrospectively analyzed. According to the different surgical methods, the patients were divided into TLPD group (22 cases) and OPD group (28 cases). The perioperative and postoperative related indicators between the two groups were compared.Results:Both groups had successfully received the operation. The operating time in TLPD group was longer than that in OPD group, and the difference between the two groups was statistically significant [(665±213) min vs. (447±215) min, t = -0.356, P = 0.001]. The amount of intraoperative bleeding in TLPD group was less than that in OPD group, and the difference between the two groups was statistically significant [100 ml (50-325 ml) vs. 300 ml (100-500 ml), Z = -2.230, P = 0.026]. There were no significant differences in the proportion of intraoperative blood transfusion, lymph node dissection number, resected tumor diameter, postoperative diet restriction time, postoperative extubation time, postoperative hospital stay and the incidence of postoperative complication between TLPD group and OPD group (all P > 0.05). Conclusions:TLPD and OPD has a similar short-term efficacy in the treatment of periampullary carcinoma. The operating time of TLPD is longer than that of OPD, but TLPD can effectively control the intraoperative bleeding.

PIM Kinase as an Executional Target in Cancer

PIM (proviral integration site for moloney murine leukemia virus) kinase plays a key role as an oncogene in various cancers including myeloma, leukemia, prostate and breast cancers. The aberrant expression and/or activation of PIM kinases in various cancers follow an isoform-specific pattern. While PIM1 is predominantly expressed in hematological and solid tumors, PIM2 and PIM3 are largely expressed in leukemia and solid tumors, respectively. All of PIM kinases cause transcriptional activation of genes involved in cell survival and cell cycle progression in cancer. A variety of pro-tumorigenic signaling molecules, such as MYC, p21(Cip1/Waf1)/p27(kip1), CDC25, Notch1 and BAD have been identified as the downstream targets of PIM kinases. So far, three kinds of adenosine triphosphate-competitive PIM inhibitors, SGI-1776, AZD1208, and LGH447 have been in clinical trials for the treatment of acute myelogenous leukemia, prostate cancer, lymphoma, or multiple myeloma. This review sheds light on the signaling pathways involved in the PIM kinase regulation and current status of developing PIM kinase inhibitors as clinical success in combating human cancer.

Expression Level and Clinical Significance of Mybl2 in Cervical Tissues / 现代检验医学杂志

Objective To study the expression and clinical significance of Mybl2 in Cervical tissues.Methods 74 cases of cervical tissues were obtained from the department of obstetrics and gynecology.The expression level of Mybl2 was detected by Elisa method,and the relationship with clinical pathology was analyzed.Results Elisa results showed that the expression of Mybl2 was significant among inflammation,CINⅠ,CINⅡ,CINⅢ and ICC groups (F=27.39,P＜0.05).The expression level of Mybl2 was higher in the older group that the younger one which were in the same clinical pathology degree,but it was not was significant(P＞0.05).Conclusion The expression levels of Mybl2 were related with the pathological changes of cervix.Disturb expression level of Mybl2 maybe induce the development of cervical cancer.

Effect of Squamous Cell Antigen and Cyclin E on Cervical Intraepithelial Neoplasia and Cervical Cancer / 沈阳医学院学报

Objective: To study the level of squamous cell antigen (SCC?Ag) and cyclin E in cervical intraepithelial neoplasia ( CIN) and cervical cancer, and to explore the clinical significance. Methods: From Nov 2012 to Nov 2015, 308 patients with CIN or cervical cancer were chosen as research objects, and 170 patients with uterine leiomyoma or uterine gland muscle disease for hyster?ectomy and after pathological examination of the normalcases were chosen as control group. The SCC?Ag level, positive expression rate in blood, and positive expression of Cyclin E in cervical tissue for patients with different cervical lesions were compared. Results: The SCC?Aglevel , positive expression rate in blood, and positive expression of Cyclin E in cervical tissue for patients with cervical canc?er, CIN were higher that those in the control group ( P<0?05) . The SCC?Aglevel, positive expression rate in blood, and positive ex?pression of Cyclin E in different CIN grades and different stages of cervical cancer patient had significant difference ( P<0?05) . Con?clusion: Blood SCC?Ag level and positive expression, Cyclin E positive expression in the cervical tissue have a close relationship with occurrence and development of CIN and cervical cancer .

Study on protective effect of alcohol extract of Potentilla Anserinea against acute myocardial ischemia/reperfusion-induced myocardial apoptosis in rats / 中国中药杂志

<p><b>OBJECTIVE</b>To observe the protective effect of alcohol extract of Potentilla anserina against myocardial apoptosis induced by acute myocardial ischemia/reperfusion by arteria coronaria ligation and the effect on the expressions of Caspase-3 and Caspase-9 in myocardial apoptosis signal pathway.</p><p><b>METHOD</b>Male SD rats were randomly divided into the sham-operated group, the model group, the diltiazem group (30 mg x kg(-1)) and P. anserine alcohol extract intervention groups (0.9, 1.8, 3.6 g x kg(-1)). Rat acute myocardial ischemia/reperfusion model was established by ligating left anterior descending. Apoptosis of myocardial cells were detected by TUNEL (Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay). The expressions of Caspase-3 and Caspase-9 mRNA were assayed by reverse transcription-polymerase chain reaction (RT-PCR). Semi-quantitative analysis was made for the expressions of Caspase-3 and Caspase-9 by immunohistochemistry.</p><p><b>RESULT</b>According to TUNEL results, after I/R injury-induced myocardial apoptosis, the apoptotic index (AI) of model group was (31.5 +/- 3.6)%. All P. anserine alcohol extract intervention groups showed obvious inhibition of ischemia/reperfusion-induced myocardial apoptosis. In the model group, myocardial apoptosis caused increased expression of Caspase-3, Caspase-9 mRNA and proteins. After the administration of P. anserine alcohol extract, 1.8, 3.6 g x kg(-1) dose groups showed notable decrease in Caspase-9 mRNA (P < 0.05), while the 0.9 g x kg(-1) dose group showed no significant difference with the model group. Alcohol extract of P. anserina in all dosages showed inhibitory effect on the expression of Caspase-3 mRNA in myocardial cells compared with model group (P < 0.05). Immunohistochemistry showed that administration of all dosages of alcohol extract of P. anserina could significantly reduce Caspase-3 and Caspase-9 protein expressions after I/R injury (P < 0.05).</p><p><b>CONCLUSION</b>The administration with alcohol extract of P. anserina can protect the myocardial tissue from apoptosis after acute myocardial ischemia and reperfusion injury in rats and inhibit the expressions of Caspase-9 and Caspase-3 mRNA and proteins.</p>

Intramedullary compression interlocking nail in treatment of non-union and delayed union of femoral and tibial fractures / 中华创伤杂志

Objective To investigate the cause of non-union and delayed union of femoral and tibia] fractures and assess the clinical outcome after treatment with intramedullary compression interlocking nail (ICIN). Methods From February 1998 to December 2006, 21 patients with non-union and delayed union of femoral and tibial fractures (13 patients with femoral fractures and 8 with tibial fractures) were treated by ICIN. Bone grafting was performed in 18 patients, and the other three patients only rocoived reamed compression nailing. Five patients received bone grafting combined with knee adhesion release operation. Results All patients were followed up for 11.4-36 months (mean 13.6 months). Solid bone union was observed in all patients, with mean bone union time of 8.7 months and without malunion, infection or refracture. According to the Klemm grading, the clinical outcome was graded excellent in 19 patients and good in 2. Conclusions The main causes for non-union and delayed union of femoral and tibial fractures are improper indication selection and incorrect use of implants, which may result in bieenvironment disruption. ICIN shortens the time of functional recovery of knee and ankle joint. ICIN has advantages of stable fixation, early exercise of the knee and ankle as well as early weight loading and hence is one of effective alternatives in treatment of non-union and delayed union of femoral and tibial fractures. ICIN can accelerate the healing of bone and improves the function of knee joint when combined with bone grafting, reamed compression nailing and knee adhesion release.