Identification of SULF1 as a Shared Gene in Idiopathic Pulmonary Fibrosis and Lung Adenocarcinoma / 中国肺癌杂志

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.

Construction of an evaluation index system for the response capacity of universities to public health emergencies / 中国学校卫生

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.

Zeaxanthin attenuates OVA-induced allergic asthma in mice by regulating the p38 MAPK/B-catenin signaling pathway

Background: Asthma is a heterogeneous and complex chronic airway disease with a high inci-dence rate, characterized by chronic airway inflammation. Although the anti-inflammatory effect of zeaxanthin has been demonstrated in various disease models, its explicit role in allergic asthma remains elusive.Methods: An allergic asthma model was established by ovalbumin (OVA) stimulation in BALB/c nude mice. The pathological examination, collagen deposition and expression of α-smooth mus-cle actin (α-SMA) in lung tissues were determined by hematoxylin and eosin (H&E), MASSON and immunofluorescence staining, respectively. Besides, the effect of zeaxanthin on inflam-mation and oxidative stress was assessed by the enzyme-linked immunosorbent assay (ELISA) and spectrophotometry measure. Moreover, the underlying mechanism was analyzed by detect-ing the expression of phosphorylated p38 (p-p38), p38, β-catenin, p-c-Jun N-terminal kinase (p-JNK) and JNK with western blot assays.Results: The distinct infiltration of inflammatory cells was observed in the OVA-induced asthma mice model with significantly increased concentra-tions of immunoglobulin E (IgE), interleukin-4 (IL-4), IL-5, IL-13 and eotaxin (p˂0.0 01), which were prominently reversed by zeaxanthin treatment (p˂0.001). In addition, zeaxanthin treat-ment decreased the OVA-induced collagen deposition and α-SMA expression. A similar inhibi-tory effect of zeaxanthin on the oxidative stress was also observed in the OVA-induced asthma mice model, as evidenced by the prominent decrease of malondialdehyde (MDA) concentration and the remarkable increase of superoxide dismutase (SOD), glutathione S transferase (GST) and Glutathione (GSH) concentrations (p˂0.001). Moreover, zeaxanthin introduction markedly reduced the relative expressions of p-p38/p38, β-catenin and p-JNK/JNK in the OVA-induced asthma mice model (p˂0.001) (AU)

Clinical expert consensus on platelet-rich plasma treatment for lateral epicondylitis (2022 version) / 中华创伤杂志

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.

Role of 11β-hydroxysteroid dehydrogenase 1 in metabolic diseases: the latest progress / 中华老年医学杂志

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.

Integrative Bioinformatics Analysis Provides Insight into the Molecular Mechanisms of 2019-nCoV

The 2019-nCoV is reported to share the same entry (ACE2) as SARS-CoV according to the updated findings. Analyzing the distribution and expression level of the route of coronavirus may help reveal underlying mechanisms of viral susceptibility and post-infection modulation. In this study, we found that the expression of ACE2 in healthy populations and patients with underlying diseases was not significantly different, suggesting relatively similar susceptibility. Besides, based on the expression of ACE2 in smoking individuals, we inferred that long-term smoking might be a risk factor for 2019-nCoV. Analyzing the ACE2 in SARS-CoV infected cells suggested that ACE2 was more than just a receptor but also participated in post-infection regulation, including immune response, cytokine secretion, and viral genome replication. Moreover, we also constructed Protein-protein interaction (PPI) networks and identified hub genes in viral activity and cytokine secretion. Our findings may explain the clinical symptoms so far and help clinicians and researchers understand the pathogenesis and design therapeutic strategies for 2019-nCoV.

Differential expression of miRNAs during white adipose tissue browning induced by different methods and its potential regulatory mechanisms / 中华老年医学杂志

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.

Non-coding RNA promoting the browning of white adipose tissue: Research progression and a current perspective / 中华老年医学杂志

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.

Prognostic Threshold of Neuroendocrine Differentiation in Gastric Carcinoma: a Clinicopathological Study of 945 Cases

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.

Effect of Lyn on expression of MUC5AC in human bronchial epithelial cells induced by house dust mite and its mechanism / 吉林大学学报(医学版)

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.

The Timing of Return to Sports after Anterior Cruciate Ligament Reconstruction in Elite Athletes: A Study Based on Isokinetic Knee Muscle Strength and Multiple Hop Tests / 中国运动医学杂志

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.

The clinical features and treatment of liver abscess formation after TACE for metastatic liver tumors / 介入放射学杂志

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.

Alterations of Glutamate and γ-Aminobutyric Acid Expressions in Normal and Myopic Eye Development in Guinea Pigs.

Purpose: The retina has an important role in the signal transmission related to eye development and myopia. Glutamate (Glu) and γ-aminobutyric acid (GABA) are the major excitatory and inhibitory neurotransmitters in the retina, which can affect the development of both the eye and myopia. Nevertheless, change in the balance between the excitatory and inhibitory neurotransmitters still is unclear during development of eyes and myopia. The purpose of this study was to explore the alterations of the ratio of Glu to GABA (RGG), which mediates the balance between the excitatory and inhibitory neurotransmitters in retina in the development of the eyes and lens-induced myopia (LIM) in a guinea pig model. Method: An LIM guinea pig model was established using a -10 diopter (D) negative lens. The levels of Glu, GABA, and the dynamic change of RGG were measured in the retina in normal and myopia guinea pigs at four time points (i.e., 0, 2, 4, and 6 weeks after onset of LIM). Considering that Glu and GABA are related closely to the occurrence of myopia, we further studied the changes of RGG in the retina in LIM guinea pigs. Result: Our results showed that the RGG was upregulated and was well correlated with diopter and axial length than either Glu or GABA during the development of normal eyes. Besides, we observed that the content of the RGG in the retina in myopia eyes was higher than that of Glu and GABA in normal subjects and was an obviously positive correlation. Conclusions: Taken together, our findings suggest that the RGG has a pivotal role in eye development and myopia. The abnormal retina signal induced by the unbalanced ratio between Glu and GABA is related closely to the occurrence of myopia.

Research progress in late-onset hypogonadism / 中华老年医学杂志

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.

Resveratrol down-regulates acute pulmonarythromboembolism-induced pulmonary artery hypertensionand monocyte chemoattractant protein-1 in rats / 中国药理学通报

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.

The effect evaluation of fast track surgery nursingon percutaneous lumbar diskectomy / 中国实用护理杂志

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.

The effect and mechanism of autophagy on acquired secondary resistance to epidermal growth factor receptor-tyrosine kinase inhibitors in patients of non-small cell lung cancers / 中国医师进修杂志

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.

The effect and mechanism of autophagy on acquired secondary resistance to epidermal growth factor receptor-tyrosine kinase inhibitors in patients of non-small cell lung cancers / 中国医师进修杂志

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.

Solitary fibrous tumor/hemangiopericytoma of central nervous system: a clinicopathologic analysis of 71 cases / 中华病理学杂志

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.

The Role of FUS/TLS in the Regulation of Gene Expression and the Correlation with Neurodegenerative Diseases / 昆明医科大学学报

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.