Objective:We aimed to observe the effects of loganin(Log)on serum glycolipid levels and probe the mechanisms focusing on intestinal flora and AMP-activated protein kinase(AMPK)signaling in obese mice.Methods:A high-fat diet was given for 12 consecutive weeks to generate the obesity model in institute of cancer research(ICR)mice.Body weight was measured weekly and fasting blood glucose(FBG)was determined every 2 weeks.Both the oral glucose tolerance test and the intraperitoneal insulin tolerance test were performed.The serum levels of total cholesterol(TC),triglyceride,high-density lipoprotein-cholesterol,low-density lipoprotein-cholesterol(LDL-C),and free fatty acids(FFA)were measured.The expression of key proteins in the AMPK signaling pathway in skeletal muscle tissue was detected by immunoblotting,and gut microbiota were characterized using 16S rDNA sequencing.Results:Log significantly decreased the body weight and the FBG in obese mice(P＜.05),and it could restore FBG to normal levels.The total cholesterol,LDL-C,and FFA levels were significantly reduced by Log compared with the obese controls(TC:P=.0020;LDL-C:P=.0233;FFA:P=.0127),and the glucose tolerance of animals was significantly improved(P=.0477).The western blot results showed that Log could upregulate the protein expression of Adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPKα),Sirtuin 1(SIRT1),and peroxisome proliferator-activated receptor-gamma coactivator-1 alpha(PGC1α)in skeletal muscle tissue of obese mice.16S rDNA sequencing indicated that Log reduced the diversity of the gut flora in feces and altered the floral composition of obese mice.Conclusions:Log was effective in reducing body weight and improving glucolipid metabolism in obese mice,probably through activating AMPK signaling and regulating intestinal microbial diversity.

[摘 要] 目的：观察miR-26b-3p在食管鳞状细胞癌（ESCC）组织中的表达水平及其对ESCC细胞增殖、侵袭和迁移能力的影响，并探讨其分子调控机制。方法: 选取河北医科大学第四医院2018年4月1日至2018年12月25日手术切除的ESCC组织及相应癌旁组织各60例，利用qPCR法检测ESCC组织、癌旁组织和ESCC细胞中miR-26b-3p的表达。选取miR-26b-3p表达水平较低的ESCC细胞TE1和KYSE150，转染miR-26b-3p mimic，并设立阴性对照。利用细胞增殖实验、划痕愈合实验和Transwell实验检测过表达miR-26b-3p对TE1和KYSE150细胞增殖、迁移和侵袭能力的影响。荧光素酶报告基因实验检测miR-26b-3p与STAT3的3'UTR靶点部位的结合情况。随后同时转染miR-26b-3p mimic和pcDNA3.0-STAT3，利用细胞增殖实验、划痕愈合实验和Transwell实验检测STAT3是否可逆转过表达miR-26b-3p对细胞增殖、迁移和侵袭能力的影响。qPCR和WB法检测甲基化酶抑制剂5-Aza-DC对ESCC细胞甲基化的影响和miR-26b-3p与STAT3表达的影响。结果: miR-26b-3p在ESCC组织中的表达低于癌旁组织（P<0.01），其在ESCC细胞TE1、KYSE150和LYSE170中表达水平显著低于人正常食管上皮细胞HEEC（均P<0.01）。与miR-26b-3p NC组相比，miR-26b-3p mimic转染可明显上调TE1和KYSE150细胞中miR-26b-3p的表达（均P<0.01），但可明显抑制两种细胞的增殖、迁移和侵袭能力（P<0.05或P<0.01）。荧光素酶报告基因实验结果表明，在TE1和KYSE150细胞中，miR-26b-3p明显抑制了野生型STAT3载体的荧光素酶活性（P<0.05或P<0.01），而突变型的荧光素酶活性不受影响。同时转染miR-26b-3p mimic和pcDNA3.0-STAT3可部分逆转miR-26b-3p mimic对TE1和KYSE150细胞增殖、迁移和侵袭能力的抑制作用（P<0.05或P<0.01）。5-Aza-DC处理后，TE1和KYSE150细胞中miR-26b-3p表达上调（均P<0.01）、STAT3 mRNA和蛋白水平降低（P<0.05），miR-26b-3p呈现去甲基化状态。结论: miR-26b-3p的启动子高甲基化导致其在ESCC组织和细胞中的表达下调，其作为抑癌因子可通过靶向STAT3而抑制ESCC细胞的增殖、侵袭和迁移能力。

Since December 2019, a novel coronavirus (2019-nCoV, SARS-CoV-2) pneumonia (COVID-19) outbreak has occurred in Wuhan, Hubei Province, and the epidemic situation has continued to spread. Such cases have also been found in other parts of the country. The spread of the novel coronavirus pneumonia epidemic has brought great challenges to the clinical practice of thoracic surgery. Outpatient clinics need to strengthen the differential diagnosis of ground glass opacity and pulmonary plaque shadows. During the epidemic, surgical indications are strictly controlled, and selective surgery is postponed. Patients planning to undergo a limited period of surgery should be quarantined for 2 weeks and have a nucleic acid test when necessary before surgery. For patients who are planning to undergo emergency surgery, nucleic acid testing should be carried out before surgery, and three-level protection should be performed during surgery. Patients who are planning to undergo emergency surgery in the epidemic area should be confirmed with or without novel coronavirus pneumonia before operation, and perform nucleic acid test if necessary. Surgical disinfection and isolation measures should be strictly carried out. Among postoperative patients, cases with new coronavirus infection were actively investigated. For the rescue of patients with novel coronavirus infection, attention needs to be paid to prevention and treatment and related complications, including mechanical ventilation-related pneumothorax or mediastinal emphysema, and injury after tracheal intubation.

Objective: To investigate the inhibitory effect of bortezomib (PS-341) on enterovirus replication. Methods: The methyl thiazolyl tetrazolium (MTT) assay was used to value cell viability in response to PS-341 treatment. The protein and viral gene mRNAs were measured by real-time quantitative PCR (qRT-PCR). Results: Our result show that after enterovirus (EV)-D68 or coxsackievirus B3 (CV-B3) infected cells were treated with PS-341, compared with the control group, the inhibition rate of the intracellular viral RNA reached 50%~70% or 60%~90%. PS-341 was added after RD cells were infectd with EV-D68, the intracellular virus titer was down-regulated by 90.23% and 83.40% in the supernatant, the intracellular virus titer was down-regulated by 93% and 90% in the supernatant and in RD cells. PS-341 had no effect on virus adsorption and importing. The cells were treated with PS-341 and apoptosis-inhibiting agent Ac-YVAD-CHO, the viral RNA replication inhibition rate reached 10%-30%, and the expression of viral protein was increased, which indicated that the inhibitory effect of PS-341 on viral replication was attenuated. Conclusions According to the result of the study, PS-341 could reduce apoptosis by regulating the proteasome pathway, inhibiting the gene replication and assemble, without effect on virus adsorption, entry and release. In addition, PS-341 also inhibited the replication of CV-B3 in cells, which suggest that PS-341 has a broad spectrum anti-EVs effects.

Mucor infection is rarely reported in non-immunocompromised population, especially in isolated gastrointestinal tracts. IgG₄-related diseases (IgG₄-RD) have been recognized in recent years, but secondary causes of IgG₄ elevation should be differentiated. We reported a young man with duodenal mass and ulcer and high serum IgG₄ level. Histological biopsy of the mass revealed positive mucor mycelium and infiltration of IgG₄ positive plasma cells. Serum IgG₄ decreased to normal range after surgical resection and systemic antifungal treatment. This case suggests that isolated mucor mycosis infection can develop in the digestive tract and mimics as IgG₄-related disease.

Objective To investigate clinical significance and the correlation between oxygen uptake efficiency slope(OUES) measured by the cardiopulmonary exercise test(CPET) and echocardiographic left ventricular function in elderly patients with coronary heart diseases after the percutaneous coronary intervention.Methods Patients aged 65 years and over after PCI and CPET were enrolled to collect relevant parameters including the peak oxygen consumption(VO2peak),oxygen pulse(VO2/HR),OUES and cardiorespiratory fitness(CRF) index,also mitral annulus systolic peak speed(Sm),early diastolic mitral flow velocity Em and mitral annular early diastolic peak velocity Em ratio(E/Em) using the echocardiography.Patients with systolic velocity of mitral annulus(Sm)≥8 cm/s were assigned to the normal Sm group,while the rest were selected into the lower Sm group.The correlation between the cardiopulmonary fitness and cardiac function was analyzed.Results Four hundred and two patients were enrolled,with an average age of 71 ± 5 years,283 males(70.40％),and 119 females(29.60％).Among them,111 (27.61％) were 75 years of age or older,202(50.25％) ranging from 65 to 69 and 89 (22.14％) between 70 and 74.Totally 227 patients were diagnosed as angina pectoris(56.47％),62 as acute myocardial infarction (15.42％),and 113 patients with old myocardial infarction (28.11％).It was found that the heart systolic function was associated with CRF:Sm and OUES were positively correlated independently(r=29.220,P=0.001);Em was positively related to VO2peak(r=0.176,P＜0.001) andOUES (r=0.151,P=0.003).However,E/Em was negatively correlated with VO2peak (r=-0.199,P＜0.001),VO2/HR (r=-0.118,P=0.018) and OUES (r=-0.201,P＜0.001).The left atrial pressure was negatively correlated with VO2peak (r=-0.187,P＜0.001),VO2/HR (r=-0.108,P=0.030) and OUES (r=-0.185,P＜ 0.001).Left ventricular ejection fraction and left ventricular end diastolic diameter were not found to be related to cardiorespiratory fitness parameters (P＞0.05).Conclusion The cardiopulmonary exercise test can be used as a practical method to evaluate and guide the rehabilitation exercises.The CRF parameters can evaluate the heart function exercise and is significantly correlated to the resting cardiac systolic and diastolic function parameters.

Objective To observe the anti-relapse and anti-graft versus host disease (GVHD) effects and side effects of ruxolitinib on patients who have relapsed leukemia after allo-hematopoietic stem cell transplantation (HSCT).Methods The clinical data of four patients sufferring from relapsed leukemia were collected and analyzed retrospectively.Three cases had a positive gene and 1 case had a extramedullary recurrence.All of them had serious GVHD involving multiparts,as the result of attenuating immunosuppressant aggressively.One case had central nervous system leukemia before allo-HSCT.Those patients were treated with ruxolitinib,according to the degree of GVHD,the treatment strategy and curative effect of GVHD,and the residual condition of original leukemia.Then,the degree of GVHD,the residual condition of original leukemia and the side effects of ruxolitinib were revaluated once a month after taking ruxolitinib.Results One case achieved completer remission (CR) and there partial remission (PR) in consideration of GVHD.Up to date,2 cases had no relapse in any level and 2 cases replased according to any of the results related to bone marrow aspiration.Conclusion Ruxolitinib is effective in patients with GVHD after allo-HSCT and doesn't influence GVL effect or increase the risk of relapse at the same time.Ruxolitinib doesn't have obvious side effects when treating GVHD.

Objective: To investigate the expression of ciRS-7 in esophageal squamous cell carcinoma (ESCC) and its effect on the cellular proliferation, migration and invasion. Methods: The cancer tissues and paired adjacent normal tissues from 60 ESCC patients treated in the Fourth Hospital of Hebei Medical University between May, 2016 andApril, 2017 were selected for this study. The expressions of ciRS-7 were detected by qRT-PCR. After over-expressing or silencing of ciRS-7, the proliferation of ESCC cell line TE1 was measured by CCK-8 assay; and the migration and invasion were tested by wound healing assay and Transwell invasion assay，respectively. Finally, the effect was validated via animal experiment. Results: CiRS-7 was highly expressed in ESCC tissues (P<0.05), and its expression level was closely related to pathological grade and lymph node metastasis (P<0.05). Over-expression of ciRS-7 significantly increased the proliferation, migration and invasion (all P<0.05) of TE1 cells; while silencing of ciRS-7 remarkably suppressed the proliferation, migration and invasion (all P<0.05). Conclusion: CiRS-7 was up-regulated in ESCC and could enhance ESCC cell proliferation, migration and invasion, suggesting that ciRS-7 could be used as a potential target for the diagnosis and treatment of ESCC.

Objective: To investigate the effect of miR-124 on the invasion and migration of esophageal cancer KYSE170 cells by regulating autophagy. Methods: miR-124 mimic was transfected into esophageal cancer KYSE170 cells. Transwell assay was used to detect the change of invasion and migration ability of cells. Dual luciferase reporter gene assay was used to verify the targeted regulation of BECN1 (Beclin1) by miR-124, and Western blotting was used to analyze the expressions of BECN1, P62 and LC3 protein. siRNA targeting BECN1 was transfeted into KYSE170 cells, and then the cell invasion and migration ability was calculated by Transwell assay. The expressions of BECN1, P62 and LC3 protein were detected by Western blotting. miR-124 mimic and BECN1 over-expression plasmid were co-transfected into KYSE170 cells, and then Transwell assay was used to detect the changes of cell invasion and migration ability, and Western blotting to examine the expression levels of autophagy-related gene. Results: The invasion and migration ability of KYSE170 cells were significantly inhibited after transfection with miR-124 mimic (All P<0.05). The expression of autophagyrelated protein P62 was increased, and the expression of BECN1 and LC3 was significantly decreased (All P<0.01); in addition, the activity of luciferase reporter gene was also significantly reduced (P<0.01). Silencing BECN1 expression inhibited the invasion and migration of esophageal cancer KYSE170 cells (P<0.01). However, after co-transfection with BECN1 over-expression plasmids, the effects of miR-124 mimic on the autophagy, invasion and migration of esophageal carcinoma KYSE170 cells were significantly weakened (P<0.01), it was also accompanied with lower P62 expression, and higher LC3 expression (P<0.01). Conclusion: miR-124 mimic can inhibit the invasion and migration of esophageal carcinoma cells. The mechanism may be related to the autophagy-related gene BECN1 expression.

BACKGROUND:JNKs and p38 MAPK, as important members of mitogen-activated protein kinase (MAPK), play critical roles in the cell proliferation, differentiation, transformation and apoptosis. OBJECTIVE:To observe the effects of Liuwei Dihuang Pill on the MAPK signaling cascade of nucleus pulposus cells in a rabbit model of intervertebral disc degeneration. METHODS:100 discs samples with endplate cartilages were equivalently randomized into five groups and cultured in the medium containing 10 mg/L tumor necrosis factor-α(TNF-α, 2μL), p38-JNK/SAPK blockers (10μL of 20μmol/L SB203580 and SP600125, 2μL of 10μmol/L TNF-α), 10%Liuwei Dihuang Pill serum, 10 mg/L TNF-α(2μL) plus 10%Liuwei Dihuang Pill serum, respectively. Those cells received no intervention as controls. Samples were collected and detected at 2, 4, 8 and 14 days of culture. RESULTS AND CONCLUSION:Real time-PCR and western blot assay showed that mRNA and protein expressions of JNK and P38 pathways by the nucleus pulposus cells were upregulated with time, while all above indicators were significantly decreased by the Liuwei Dihuang Pill serum. These findings reveal that Liuwei Dihuang Pill can delay the process of disc degeneration by blocking JNK and P38 signaling pathways, thus exerting protective effect on the intervertebral discs.