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Objective@#To construct an evaluation index system to assess the response capacity of universities to public health emergencies, so as to provide a basis for improvements the response capacity.@*Methods@#In November 2019, in order to develop an evaluation system based on literature review and expert discussions, 15 experts were invited to conduct a subjective evaluation used hierarchical analysis. The objective evaluation was conducted in 120 universities in Jiangsu Province used the inverse entropy weighting method, and the final evaluation employed the joint subjective and objective weighting method.@*Results@#The indicator system consisted of four primary indicators, nine secondary indicators, 32 tertiary indicators and 67 quaternary indicators. The analysis of the combined weighting method showed that the primary indicators, in descending order, included incident handling capability ( 0.666 ), incident detection capability (0.203), prior preparation capability (0.101) and post event recovery capability ( 0.031 ). The top three secondary indicator weights were emergency response (0.480), monitoring and reporting (0.203) and command and coordination (0.151). The results of the evaluation of the consistency indicators showed that the expert authority coefficient was 0.909 and the Kendall s W coordination coefficient was 0.836 ( P <0.01), with all consistency scale values < 0.1.@*Conclusion@#The evaluation system is highly scientific and credible, and provides basis for evaluating the response capability of universities to public health emergencies.
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BACKGROUND@#Idiopathic pulmonary fibrosis (IPF) is an idiopathic chronic, progressive interstitial lung disease with a diagnosed median survival of 3-5 years. IPF is associated with an increased risk of lung cancer. Therefore, exploring the shared pathogenic genes and molecular pathways between IPF and lung adenocarcinoma (LUAD) holds significant importance for the development of novel therapeutic approaches and personalized precision treatment strategies for IPF combined with lung cancer.@*METHODS@#Bioinformatics analysis was conducted using publicly available gene expression datasets of IPF and LUAD from the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis was employed to identify common genes involved in the progression of both diseases, followed by functional enrichment analysis. Subsequently, additional datasets were used to pinpoint the core shared genes between the two diseases. The relationship between core shared genes and prognosis, as well as their expression patterns, clinical relevance, genetic characteristics, and immune-related functions in LUAD, were analyzed using The Cancer Genome Atlas (TCGA) database and single-cell RNA sequencing datasets. Finally, potential therapeutic drugs related to the identified genes were screened through drug databases.@*RESULTS@#A total of 529 shared genes between IPF and LUAD were identified. Among them, SULF1 emerged as a core shared gene associated with poor prognosis. It exhibited significantly elevated expression levels in LUAD tissues, concomitant with high mutation rates, genomic heterogeneity, and an immunosuppressive microenvironment. Subsequent single-cell RNA-seq analysis revealed that the high expression of SULF1 primarily originated from tumor-associated fibroblasts. This study further demonstrated an association between SULF1 expression and tumor drug sensitivity, and it identified potential small-molecule drugs targeting SULF1 highly expressed fibroblasts.@*CONCLUSIONS@#This study identified a set of shared molecular pathways and core genes between IPF and LUAD. Notably, SULF1 may serve as a potential immune-related biomarker and therapeutic target for both diseases.
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Humans , Lung Neoplasms/genetics , Adenocarcinoma of Lung/genetics , Idiopathic Pulmonary Fibrosis/genetics , Adenocarcinoma , Cancer-Associated Fibroblasts , Prognosis , Tumor Microenvironment , SulfotransferasesABSTRACT
Objective:To investigate the molecular features of hand, foot and mouth disease (HFMD) caused by coxsackievirus A10 (CVA10) in Qingdao and analyze the clinical features of mild and severe cases.Methods:A total of 6 677 cases of HFMD routinely monitored by Qingdao Women and Children Hospital from 2014 to 2021 were enrolled. Throat swab samples were collected. Clinical data of these cases were retrospectively analyzed. Virus nucleic acid was extracted from the samples and the serotypes of enteroviruses were identified. The VP1 genes of CVA10 strains were amplified and sequenced. A phylogenetic tree based on the VP1 gene sequences was constructed using MEGA7. 0 software. SPSS23.0 software was used for statistical analysis.Results:There were 285 cases positive for CVA10, including 183 males and 102 females, and children under five years old accounted for 89.8%. Most of CVA10 infection occurred between the months of April to September. The count of white blood cells, the percentage of neutrophils, the concentration of hemoglobin, and the levels of aspartate aminotransferase and alanine transaminase were significantly higher in severe patients than in mild patients. Besides, chest radiography and brain CT revealed more abnormalities in severe patients, and the duration of ECG monitoring was longer in them. Compared with mild cases, severe cases developed rash early than fever with rash mostly on buttocks ( P<0.05). Phylogenetic analysis showed that most of the CVA10 strains circulating in Qingdao between 2014 and 2021 belonged to clade Ⅰ, and there were two variations A23V and I283V in the amino acid sequence of clade Ⅰ. Conclusions:This study showed that children of all ages were susceptible to CVA10, especially those under five years old. CVA10 showed complex and diverse epidemic trends in different regions and years.
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Lateral epicondylitis is a common clinical disease with characteristics of lateral elbow pain, insidious onset and easy recurrence, which can cause forearm pain and decreased wrist strength, seriously affecting patients′ daily life and work. Although there are various treatment methods for lateral epicondylitis with different effects, standard treatments are still lacking nowadays. Platelet-rich plasma (PRP) has good effects on bone and tendon repair, and is now widely used in the treatment of lateral epicondylitis. However, there is a lack of a unified understanding of the technology and specifications of PRP in the treatment of lateral epicondylitis. Therefore, the Sports Medicine Branch of the Chinese Medical Association and Physical Medicine and Rehabilitation Branch of the Chinese Medical Association organized experts in the fields of sports medicine and rehabilitation medicine in China to formulate the "clinical expert consensus on platelet-rich plasma treatment for lateral epicondylitis (2022 version)", and proposed suggestions based on evidence-based medicine mainly from the concept, epidemiology and pathophysiology of lateral epicondylitis, symptoms, signs and imaging manifestations of lateral epicondylitis, PRP concept and application component requirements, quality control of PRP preparation technology, indications and contraindications of PRP in the treatment of lateral epicondylitis, PRP injection in the treatment of lateral epicondylitis, application of PRP in the operation of lateral epicondylitis, related problems after PRP treatment of lateral epicondylitis, evaluation of the results after PRP treatment of lateral epicondylitis, and health and economic evaluation of PRP treatment of lateral epicondylitis, so as to provide guidance for clinical diagnosis and treatment.
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The 11β-hydroxysteroid dehydrogenase type 1(11β-HSD1)is the only enzyme in the body, which can convert inactive cortisone(11-dehydrocorticosterone in rodents)to active cortisol(corticosterone in rodents)in vivo.And it is vital for regulating the level of active glucocorticoids in local tissues.It has been implicated that glucocorticoid dysregulations are closely related to various metabolic diseases, such as obesity and type 2 diabetes mellitus(T2DM), etc.Therefore 11β-HSD1 may be a potential target for the treatment of metabolic diseases.In this review, we summarize the biological function and tissue distribution of 11β-HSD1, discuss how 11β-HSD1 participates in physiological and pathological mechanisms of obesity, T2DM, non-alcoholic fatty liver disease, hypertension and sarcopenia, and sum up the advanced developments of 11β-HSD1 inhibitors.
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Objective:To investigate the differential expression of miRNAs during white adipose tissue(WAT)browning in mice under different stimulation conditions, and to analyze the potential regulatory mechanisms.Methods:Mouse models of subcutaneous WAT(sWAT)browning were established by different methods: cold-induced browning and intraperitoneal injection of CL316-243.HE staining and analysis of thermogenesis-related gene expression were used to validate the browning models.miRNAs expression profiles in different conditions were described by RNA-sequencing(RNA-seq)and miRNAs with similar expression patterns in the two groups were detected via screening.Target genes of miRNAs were predicted by bioinformatics, and their expression levels were verified by quantitative real-time PCR(qRT-PCR).Results:Both cold-induced browning and intraperitoneal injection of CL316-243 were able to activate the browning of sWAT, and the miRNA expression profile of sWAT showed significant differences before and after induction.After screening differentially expressed miRNAs, the expression of Mir-30E-3p was increased and the expression of Mir-181A-5p was decreased under different browning-inducing conditions in WAT.The prediction and validation of target genes revealed that cyclin-dependent kinase 6(Cdk6)and sirtuin 1(Sirt1)were potential targets regulated by miR-30e-3p and miR-181a-5p in the browning of sWAT, respectively.Conclusions:There are significant differences in miRNA expression during the browning of sWAT in mice induced by cold stimulation and CL316-243 injection.MiR-30e-3p and miR-181a-5p may be involved in the regulation of the sWAT browning process through target genes Cdk6 and Sirt1, respectively.
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PURPOSE: The significance of neuroendocrine differentiation (NED) in gastric carcinoma (GC) is controversial, leading to ambiguous concepts in traditional classifications. This study aimed to determine the prognostic threshold of meaningful NED in GC and clarify its unclear features in existing classifications. MATERIALS AND METHODS: Immunohistochemical staining for synaptophysin, chromogranin A, and neural cell adhesion molecule was performed for 945 GC specimens. Survival analysis was performed using the log-rank test and univariate/multivariate models with percentages of NED (PNED) and demographic and clinicopathological parameters. RESULTS: In total, 275 (29.1%) cases were immunoreactive to at least 1 neuroendocrine (NE) marker. GC-NED was more common in the upper third of the stomach. PNED, and Borrmann's classification and tumor, lymph node, metastasis stages were independent prognostic factors. The cutoff PNED was 10%, beyond which patients had significantly worse outcomes, although the risk did not increase with higher PNED. Tumors with ≥10% NED tended to manifest as Borrmann type III lesion with mixed/diffuse morphology and poorer histological differentiation; the NE components in this population mainly grew in insulae/nests, which differed from the predominant growth pattern (glandular/acinar) in GC with <10% NED. CONCLUSIONS: GC with ≥10% NED should be classified as a distinct subtype because of its worse prognosis, and more attention should be paid to the necessity of additional therapeutics for NE components.
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Humans , Adenocarcinoma , Chromogranin A , Classification , Immunohistochemistry , Lymph Nodes , Neoplasm Metastasis , Neural Cell Adhesion Molecules , Prognosis , Stomach , Stomach Neoplasms , SynaptophysinABSTRACT
White fat with lipids storage in the body can be stimulated by physiological or medical conditions to have the brown fat-like functions of an increased heat production and a high-energy consumption,becoming a beige fat.The browning of white fat can be used as a potential target for the treatment of diseases such as obesity and metabolic syndrome.There are many factors,such as non-coding RNA (ncRNA),can promote the browning of white fat,with the resulting energy metabolism homeostasis of brown fat function.This paper reviews recent advances on the study of ncRNAs promoting the browning of white fat.
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Objective:To investigate the effect of Lyn on the expression of MUC5AC in human bronchial epithelial cells induced by house dust mite(HDM),and to explore its possible mechanism.Methods:The human bronchial epithelial cells(16 HBE)were divided into PBS group and HDM group(1 μg·L-1HDM).The cells were transfected by liposome.The luciferase report gene of MUC5AC promoter was constructed.The relative luciferase unit(RLU)was detected by double luciferase report gene assay.The expression of MUC5AC in the cells was detected by immunofluorescence technique and observed by confocal microscope.The expression level of STAT6 in the 16HBE cells was detected by Western blotting method.Results:The results of double luciferase report gene assay showed that the RLU in HDM group was higher than that in PBS group(P<0.05).The RLU of cells in HDM group treated with LynsiRNA intervention was higher than that of the cells without LynsiRNA intervention(P<0.05).The immunofluorescence results demonstrated that the expression level of MUC5AC in HDM group was higher than that in PBS group(P<0.05),and the expression level of MUC5AC in HDM group was increased after LynsiRNA intervention(P<0.05).The Western blotting results indicated that the expression level of STAT6 was up-regulated in HDM group when the cells were intervened with LynsiRNA(P<0.05). Conclusion:Deficiencyof Lyn can increase the expression of MUC5AC in the human bronchial epithelial cells,and its mechanism may be related to regulating the STAT6 signal pathway by Lyn.
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Objective To investigate the clinical features,related risk factors,the efficacy and safety of clinical management about liver abscess formation occurring after transcatheter arterial chemoembolization (TACE) for metastatic liver cancer.Methods Among 1812 patients with metastatic liver tumors who were receiving TACE,23 patients developed liver abscess.The clinical features and risk factors for abscess formation were retrospectively analyzed.The curative effects and safety of percutaneous puncture cavity drainage (PCD),or combined with percutaneous transhepatic cholangiography and drainage (PTCD) were analyzed.Results The incidence of liver abscess after TACE for metastatic liver tumors was 1.3% (23/1812).Postoperative high fever,chill,elevated white blood cell count and increased neutrophil proportion were the main clinical features of liver abscess.The mean time before the diagnosis of liver abscess was confirmed was (11.3±3.7) days after TACE.The hepatic metastatic malignancy originated from the malignant tumor of digestive tract was seen in 73.9% of patients,18 patients (78.3%) had a history of gastroenteric surgery,and 12 patients (52.2%) had a history of diabetes mellitus.The number of hepatic metastatic lesions was more than 3 in 19 patients (82.6%).After the formation of liver abscess,the liver functions became worse in all patients (P=0.024).In 19 patients (82.6%),angiography showed that the metastases were hypovascular lesions.Blood and pus cultures revealed that E.coli was the main infectious bacteria of liver abscess.The mean time of using anti-infective drugs before hepatic abscess developed liquefaction was (10.4±3.3) days,and the mean time of abscess liquefaction was (15.9±3.7) days.The mean value of the maximum diameters of abscesses was (9.2±2.0) cm.PCD was employed in all patients,the average times of PCD procedure was (3.7±1.7) times.PCD followed by PTCD was performed in 7 patients as they had biloma associated with obstructive jaundice.The average drainage time for liver abscess was (3.1 ±1.7) months.No infectious peritonitis,tumor rupture,or tumor implantation at puncture point was observed.The median survival time of 23 patients with liver abscess was (8.0±0.7) months.The median survival time in patients who received PCD procedure only was (9.0±1.0) months,while it was (5.0±0.7) months in patients who received PCD together with PTCD,and statistically significant difference in the median survival time existed between the above two groups (P=0.041).Conclusion The risk factors of liver abscess formation after TACE in patients with metastatic liver tumors include the site of primary tumor and gastrointestinal surgery.Diabetes may be one of the risk factors.Clinically,the lesions of liver abscess are usually multiple and they often occur in hypovascular lesions with central necrosis,The nain infectious bacteria are from digestive tract,and biloma is easy to develop.Active and effective antibiotic treatment plus puncture drainage of abscess cavity,or combined with PTCD,are effective treatment measures for this kind of liver abscess.
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Objective To compare the knee function recovery at different times of returning to sport after anterior cruciate ligament reconstruction(ACLR) among elite athletes using knee isokinetic muscle strength test and various hop test.Methods Forty-one elite athletes(14 males,27 females,mean age 22.6 ± 4.1 years) undergoing ACLR between January 2013 and September 2014 were chosen from the database of the National Institute of Sports Medicine and Shanghai Huashan Hospital.Rehabilitation was performed using the same protocol by professional physiotherapists and trainers,who recorded the time of returning to sport of each athlete.One week prior to the scheduled return,bilateral knee isokinetic muscle strength test(test value:peak torque;angle velocity:60°/s,180°/s;motion:flexion,extension) and four hop tests(single hop for distance,side-to-side hop,up-down hop and 8 hop) were applied with the limb symmetry index(LSI) calculated.The athletes were then grouped by their returntime referring to surgery into the premature group(6~8 months),timely return group(9~12 months) and delayed group(over 12 months).The tests results were recorded and compared among the three groups.Results Fourteen athletes were selected into the premature group,with 19 in the timely group and 8 in the delayed group.The average LSI of 60°/s flexion peak torque of the premature group (87.4% ± 7.5%) was significantly lower than the timely group(95.8% ± 6.6%) and the delayed group(96.0% ± 2.4%) (P<0.01).Significant differences were observed between the premature group and delayed group regarding the 60° extension peak torque(85.8% ± 9.4% and 94.8% ± 4.8%,P<0.05),180°/s flexion peak torque(90.7% ± 8.7% and 101.4% ± 6.8%,P<0.05),and 180°/s extension peak torque (90.6% ± 5.2% and 97.8% ± 5.6%,P<0.05).The average LSL of the premature group at single hop for distance,side-to-side hop and up-down hop(93.A% ± 8.5%,84.7% ± 7.3% and 112.5% ± 5.7%) was significantly lower than that of the timely group(95.7% ± 6.0%,104.2% ± 4.3% and 105.3% ± 7.9%) and the delayed group regarding(98.1% ± 1.9%,104.7% ± 4.0% and 106.3% ± 7.4%) (P<0.01 for all).The relative peak torque of 60°/s extension of the premature group(2.48 ± 0.58 Nm/kg) was significantly lower than the delayed group(3.21 ± 0.51 Nm/kg) (P<0.01).Conclusions For elite athletes,returning to sport within 9 months after ACLR results in insufficient restoration of the knee function.Delayed return to sport doesn't improve the outcomes of hop tests,but can enhance the maximum extension torque peak,which needs further study.
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Aim To investigate the relationship between monocyte chemoattractant protein-1(MCP-1) and pulmonary artery hypertension after acute pulmonary thromboembolism(PTE), and to explore the effects and mechanisms of resveratrol with MCP-1 in the acute PTE as well.Methods The acute PTE model of Sprague-Dawley rats was replicated using self-thrombosis.The rats were randomly divided into five groups(Normal, Solvent, acute PTE, antibody Cl142, and resveratrol), and 1h, 4h, 8h and 3 points were observed in each group.A model of acute PTE was established by infusion of an autologous blood clot into the pulmonary artery through a polyethylene catheter.Resveratrol or Cl142, dissolved in 1% dimethyl sulfoxide(DMSO), was administered to the animals through caudalvein 1 h prior to the beginning of acute PTE modeling.Rats in normal control group and solvent control group were injected with normal saline and 1% DMSO respectively.The mean pulmonary artery pressure(MPAP) and the mRNA and protein expression of MCP-1 were measured at each time point.Results ① The acute PTE group MPAP, MCP-1 mRNA and protein expression were significantly higher than those of the control group(P<0.05) at the same time;② The resveratrol group′s MPAP and MCP-1 mRNA, protein expression were significantly lower than those of the acute PTE group(P<0.05) at the same time;③ The Cl142 group MPAP and MCP-1 mRNA, protein expression were markedly reduced in the acute PTE group(P<0.05) at the same time.Conclusions The large expression of MCP-1 after acute PTE is involved in the formation of pulmonary hypertension after acute PTE.Resveratrol can reduce the pressure of pulmonary artery after acute PTE by down-regulating the MCP-1 expression.
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Objective To evaluate the effect of fast track surgery nursing on percutaneous lumbar diskectomy. Methods A total of 126 patients were randomly divided into the control group and the experimental group,the control group received traditional nursing plan, the experimental group was given fast track surgery nursing plan. The nursing effect was observed. Results Postoperative anal exhaust time, feeding time, walking time, length of hospital stay ofthe experimental group were (1.61±0.71) days, (2.01±0.71) days, (4.70±2.12) days, (12.72±2.07) days, whichwere significantly shorter than those of the control group, which were (3.37±0.93) days, (2.27±0.63) days, (8.40±3.21) days, (15.81±2.14) days, the difference between two groups were statistically significant (t=4.012-6.068, P0.05). The Rdand Morris Questionnaire score of the experimental group was 21.67±3.48, which was higher than that of the control group(14.43 ± 2.01), the difference between two groups was statistically significant(χ2=6.077, P <0.05). Conclusion Fast track surgery nursing can promote the patient's postoperative rehabilitation ,reduce the postoperative complications, shorten the length of hospital stay and improve the quality of life.
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Objective@#As solitary fibrous tumor (SFT) and hemangiopericytoma (HPC) share the same molecular genetics features, the 2016 WHO classification of central nervous system (CNS) tumors had created the combined term SFT/HPC and assigns three grades. This study aims to investigate the clinicopathologic characteristics, diagnosis, differential diagnosis and prognosis of CNS SFT/HPC.@*Methods@#Seventy-one cases of CNS SFT and HPC were retrospectively reclassified and studied. Histopathological, immunohistochemical and imaging features were analyzed. The follow-up data were analyzed.@*Results@#There were 37 male and 34 female patients. The median age was 48 years (range, 3-77 years). Twelve cases (17%) were WHO grade Ⅰ, 26 (37%) were WHO grade Ⅱ and 33 (46%) were WHO grade Ⅲ. Microscopically the tumor could show traditional SFT phenotype, HPC phenotype or mixed phenotype. Immunochemically, 97%(69/71) were positive for STAT6, with 96%(66/69)showing diffuse strong staining. Approximately 90% were diffusely positive for bcl-2, CD99 and vimentin. The expression rate of CD34 decreased with increasing tumor grade, and the mean expression rate was 78%. SSTR2a was variably expressed in 10% (7/71) of cases including one case showing strong cytoplasmic staining. A few cases expressed EMA, CD57 and S-100 focally. The Ki-67 index ranged from 1% to 50%. Thirty four patients were followed up for 8-130 months; 12 patients(35%)had recurrences, and two (6%) had liver metastases.@*Conclusions@#CNS SFT/HPC is relatively uncommon. There was significant morphological overlap or transition between different grades. STAT6 is a specific marker for the diagnosis of this tumor. Surgical resection is the preferred treatment. WHO grade Ⅱ and Ⅲ SFT/HPC show rates of local recurrence and systemic metastasis, with liver being the most common site of extracranial metastasis.
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Objective To investigate the effect of autophagy on acquired secondary resistance to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) in patients of non-small cell lung cancers (NSCLC). Methods Ninety-eight patients with pathological confirmation of lung adenocarcinoma were selected, and they were treated with EGFR-TKI. Among them, 49 patients were sensitive to EGFR-TKI, (EGFR-TKI sensitive group), and the others were resistant (EGFR-TKI resistant group). The expressions of mTOR, Beclin-1 and LC3 were detected by immunohistochemistry, reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot method. Results The immunohistochemistry results showed that the Beclin-1 and LC3 positive expression rates of tumor tissue in EGFR-TKI resistant group were significantly lower than those in EGFR-TKI sensitive group:24.49%(12/49) vs. 83.67%(41/49) and 22.45% (11/49) vs. 85.71% (42/49), and the mTOR positive expression rate was significantly higher than that in EGFR-TKI sensitive group: 77.55% (38/49) vs. 20.41% (10/49), and there were statistical differences (P<0.05). The RT-PCR results showed that the Beclin-1 and LC3 positive expressions of tumor tissue in EGFR-TKI resistant group were significantly lower than those in EGFR-TKI sensitive group: 0.723 ± 0.029 vs. 2.542 ± 0.104 and 0.886 ± 0.034 vs. 2.234 ± 0.164, and the mTOR positive expression was significantly higher than that in EGFR-TKI sensitive group:2.142 ± 0.132 vs. 0.638 ± 0.031, and there were statistical differences (P<0.05). The Western blot results showed that the Beclin-1 and LC3 positive expressions of tumor tissue in EGFR-TKI resistant group were significantly lower than those in EGFR-TKI sensitive group:0.315 ± 0.037 vs. 1.226 ± 0.017 and 0.420 ± 0.016 vs. 1.023 ± 0.014, and the mTOR positive expression was significantly higher than that in EGFR-TKI sensitive group: 0.986 ± 0.032 vs. 0.282 ± 0.021, and there were statistical differences (P<0.05). In EGFR-TKI sensitive group and EGFR-TKI resistant group, the Beclin-1 and LC3 showed positive correlation, and the Beclin1 and LC3 showed negative correlation with mTOR. Conclusions The signaling molecules of autophagy play an important role in secondary resistance to EGFR-TKI in patients of NSCLC. As a regulation mechanism of autophagy, mTOR takes part in the procedure of resistance to EGFR-TKI, and give a new biological marker of the predication of drug resistance. Meanwhile, it gives a new target of drug resistance reversal and individualized treatment.
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Objective To investigate the effect of autophagy on acquired secondary resistance to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) in patients of non-small cell lung cancers (NSCLC). Methods Ninety-eight patients with pathological confirmation of lung adenocarcinoma were selected, and they were treated with EGFR-TKI. Among them, 49 patients were sensitive to EGFR-TKI, (EGFR-TKI sensitive group), and the others were resistant (EGFR-TKI resistant group). The expressions of mTOR, Beclin-1 and LC3 were detected by immunohistochemistry, reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot method. Results The immunohistochemistry results showed that the Beclin-1 and LC3 positive expression rates of tumor tissue in EGFR-TKI resistant group were significantly lower than those in EGFR-TKI sensitive group:24.49%(12/49) vs. 83.67%(41/49) and 22.45% (11/49) vs. 85.71% (42/49), and the mTOR positive expression rate was significantly higher than that in EGFR-TKI sensitive group: 77.55% (38/49) vs. 20.41% (10/49), and there were statistical differences (P<0.05). The RT-PCR results showed that the Beclin-1 and LC3 positive expressions of tumor tissue in EGFR-TKI resistant group were significantly lower than those in EGFR-TKI sensitive group: 0.723 ± 0.029 vs. 2.542 ± 0.104 and 0.886 ± 0.034 vs. 2.234 ± 0.164, and the mTOR positive expression was significantly higher than that in EGFR-TKI sensitive group:2.142 ± 0.132 vs. 0.638 ± 0.031, and there were statistical differences (P<0.05). The Western blot results showed that the Beclin-1 and LC3 positive expressions of tumor tissue in EGFR-TKI resistant group were significantly lower than those in EGFR-TKI sensitive group:0.315 ± 0.037 vs. 1.226 ± 0.017 and 0.420 ± 0.016 vs. 1.023 ± 0.014, and the mTOR positive expression was significantly higher than that in EGFR-TKI sensitive group: 0.986 ± 0.032 vs. 0.282 ± 0.021, and there were statistical differences (P<0.05). In EGFR-TKI sensitive group and EGFR-TKI resistant group, the Beclin-1 and LC3 showed positive correlation, and the Beclin1 and LC3 showed negative correlation with mTOR. Conclusions The signaling molecules of autophagy play an important role in secondary resistance to EGFR-TKI in patients of NSCLC. As a regulation mechanism of autophagy, mTOR takes part in the procedure of resistance to EGFR-TKI, and give a new biological marker of the predication of drug resistance. Meanwhile, it gives a new target of drug resistance reversal and individualized treatment.
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Late-onset hypogonadism(LOH)is an aging related syndrome with representative clinical manifestations.It has a serious impact on men's reproductive health and quality of life and is characterized by a deficiency in serum testosterone levels.Decline in Leydig cell number and function is the chief etiological factor.Changes in the biological activity of male hormones,androgen receptor abnormalities and hypothalamic-pituitary testicular axis feedback regulation dysfunction underliethe pathogenesis of LOH.Research directed at identifying safe and effective treatment methods for LOH will bring highly valuable development.
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Neurodegenerative diseases are chronic lesions caused by neuronal degeneration and secondary demyelination.Recent studies have shown that a DNA/RNA binding protein named fused in sarcoma/translocated in liposarcoma protein (FUS/TLS) is associated with neurodegenerative diseases,such as amyotrophic lateral sclerosis (ALS),frontotemporal dementia (FTD) and polyglutamine diseases.Mutations or dysfunction in FUS/TLS are responsible for the abnormal processes in the related gene transcription,RNA processing,transportation and translation and are highly correlated with the development of neurodegenerative disease.Discovery and the research of FUS/TLS not only contribute to the understanding of neurodegenerative disease at RNA level,but also provide a new way for the prevention and treatment of neurodegenerative diseases.
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Objective To study the growth difference and possible mechanism between nasopharyngeal carcinoma (NPC) cell line CNE-2 and its subclone S-18.Methods CNE-2 and S-18 cells were cultured in vitro.6 x 105 cells/mouse were xenografted subcutaneously in the back of nude mice.The volumes of rumors were measured on the 3 rd,7 th,10 th,14 th day after grafting.Mice were sacrificed on the 14 th day and tumors were isolated and weighed.RNA from tumor tissues were extracted and transcriptional levels of HSP27 and NF-K B were detected.Results (1) S-18,instead of CNE-2,grew to form tumor mass 7 days after xenografting subcutaneously;both cell lines formed tumor mass 10 days after xenografting,however,the volumes of S-18 tumors [(223.13 ± 21.32) mm3,10 th day;(420.25 ± 24.52) mm3,14 th day] were significant bigger than CNE-2tumors [(113.70±11.70) mm3,10thday;(279.86±25.78) mm3,14thday];The weights of S-18 umors were significantly higher than CNE-2 tumors on the 14 th day after xenografting;(2) The transcriptional levels of HSP27 and NF-KB in S-18 tumor were significantly higher than in CNE-2 tumor.Conclusion Xenografted S-18 NPC grows faster than Xenografted CNE-2 NPC.HSP27 and NF-κ B are probably involved in the regulation of growth in NPC.
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Objective To evaluate the molecular mechanism of 11 beta-hydroxysteroid dehydrogenase type 1 (11 β-HSD1)in tumor necrosis factor-α (TNF-α) induced insulin resistance.Methods The optimal concentration and incubation time of TNF-α for treating HepG2 cells were selected.Real-time polymerase chain reaction(PCR)and Western blot analysis were used to explore the effect of TNFα on the mRNA and protein expression levels of 11β-HSD1,glucocorticoid receptor (GR),phosphoenolpyruvate carboxylase(PEPCK)and glucose 6-phosphatase(G6Pase).Glucose(GO) Assay Kit was used to determine the level of gluconeogenesis.Liver/Muscle glycogen assay kit,PAS/Glycogen Stain kit were used to detect glycogen synthesis.The expression of AKT/GSK pathway was analyzed by Western blot analysis.In addition,HepG2 cells were pre-treated with BVT2733,a specific inhibitor of 11β-HSD1,before exposure to TNFα The expression of AKT/GSK pathway,the level of gluconeogenesis and glycogen synthesis were analyzed.Results The expression of 11β-HSD1 was increased along with the increasing concentration of TNF-α,showing a dose-dependent effect.When HepG2 cells treated with the optimal dose of TNF-α 10 μg/L for 24 hours,the levels of GR,gluconeogenesis and gluconeogenesis-related genes PEPCK and G6Pase were increased,while conversely,the levels of phosphorylation of AKT and GSK,and glycogen synthesis were decreased.However,all the above effects induced by TNF-α in HepG2 cells were greatly reversed by BVT2733 pre treatment.Conclusions 11 β-HSD1 participates in TNF-α-induced insulin resistance in HepG2 cells,and BVT2733 could significantly improve insulin sensitivity.