Roxadustat protects rat renal tubular epithelial cells from hypoxia-induced injury through the TGF-ß1/Smad3 signaling pathway.

OBJECTIVE: Roxadustat is used to treat renal anemia. The renoprotective effect of roxadustat needs to be further confirmed, and the mechanism of action is unknown. This study aims to evaluate the effect and mechanism of roxadustat in hypoxia-related nephropathy with the renal tubular epithelial cell line NRK-52E. MATERIALS AND METHODS: The cell Counting Kit-8 (CCK-8) assay was employed to assess cellular proliferation in the current investigation. Flow cytometry was used to conduct cell apoptosis analysis. The utilization of electron microscopy facilitated the identification of changes in cellular ultrastructure. Immunofluorescence was used to detect the expression trend of hypoxia-inducible factor-1α (HIF-1α). The connective tissue growth factor (CTGF), transforming growth factor-ß1 (TGF-ß1), Smad family member 3 (Smad3), p-Smad3, α-smooth muscle actin (α-SMA), collagen I, and HIF-1α were assessed by western blotting. Real-time fluorescent quantitative PCR (RT-qPCR) was used to measure TGF-ß1 and Smad3 mRNA. RESULTS: Significant growth inhibition and increased apoptosis were observed in NRK-52E cells cultured under hypoxic conditions (1% and 5% O2), which can be rescued by roxadustat. From a morphological perspective, it has been observed that roxadustat can counteract cellular damage features produced by hypoxia. These features include the contraction of the nuclear envelope and an increase in the formation of apoptotic bodies. Roxadustat increases HIF-1α expression acutely at 24 h, followed by a gradual reduction of HIF-1α expression to levels significantly below that of the hypoxia group by 72 h. Roxadustat can also inhibit hypoxia-induced increased expression of CTGF, TGF-ß1, p-Smad3, α-SMA, collagen I, and HIF-1α. Combined treatment with roxadustat and siRNA against TGF-ß1 synergistically reduced the expression of CTGF and HIF-1α, while the effect on TGF-ß1 and p-Smad3 were comparable to that of the individual treatment alone. Comparably, the combined administration of roxadustat and siRNA targeting Smad3 had a synergistic impact on diminishing the expression of CTGF. CONCLUSIONS: These findings indicate that roxadustat attenuates experimental renal fibrosis likely by inhibiting the TGF-ß1/Smad3 pathways, while its effect on CTGF and HIF-1α may involve other signaling pathways.

Use of Radiomics Models in Preoperative Grading of Cerebral Gliomas and Comparison with Three-dimensional Arterial Spin Labelling.

AIMS: To build machine learning-based radiomics models to discriminate between high- (HGGs) and low-grade gliomas (LGGs) and to compare the effectiveness of three-dimensional arterial spin labelling (3D-ASL) to evaluate which is a better method. MATERIALS AND METHODS: We retrospectively analysed the magnetic resonance imaging T1WI-enhanced images of 105 patients with gliomas that were pathologically confirmed in our hospital. We divided the patients into a training group and a verification group at a ratio of 8:2; 200 patients from the Brain Tumour Segmentation Challenge 2020 were selected as the test group for image segmentation, feature extraction and screening. We constructed models using multilayer perceptron (MLP), support vector machine, random forest and logistic regression and evaluated their predictive performance. We obtained the mean maximum relative cerebral blood flow (rCBFmax) value from 3D-ASL of 105 patients from the hospital to evaluate its efficacy in discriminating between HGGs and LGGs. RESULTS: In machine learning, the MLP classifier model exhibited the best performance in discriminating between HGGs and LGGs; the areas under the curve obtained by MLP and rCBFmax were 0.968 versus 0.815 (verification group) and 0.981 versus 0.815 (test group), respectively. The machine learning-based MLP classifier model performed better in discriminating between HGGs and LGGs than 3D-ASL. CONCLUSION: In our study, we found that machine learning-based radiomics models and 3D-ASL were valuable in discriminating between HGGs and LGGs and between them, the machine learning-based MLP model had better diagnostic performance.

[Role of pyroptosis pathway related molecules in acute lung injury induced by gas explosion in rats].

Objective: To explore the role and significance of pyroptosis in gas explosion-induced acute lung injury (ALI) in rats. Methods: In February 2018, 126 SPF male SD rats were selected and randomly divided into blank control group (18 rats) and experimental group (40 m, 80 m, 120 m, 160 m, 200 m and 240 m, 18 per group) . The experimental group carried out gas explosion in the roadway to build the ALI model, the control group did not carry out gas explosion, and other conditions were consistent with the experimental group. Respiratory function indexes such as respiratory frequency (f) , tidal volume (TV) , minute ventilation (MV) and airway stenosis index (Penh) were measured 24 hours after the explosion. 5 rats in each group were sacrificed after anesthesia, Hematoxylin-Eosin (HE) staining was used to observe the pathological morphology of lung tissue. Immunohistochemistry was used to detect the content of Caspase-1. Western blotting was used to detect the content of cell pyroptosis including nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) , Caspase-1, interleukin-1ß (IL-1ß) and interleukin-18 (IL-18) in lung tissue related protein expression. Results: The f and MV of rats in the experimental group were higher than those in the control group (P<0.05) . Except for the 40 m and 80 m groups, the TV of rats in the other experimental groups were higher than those in the control group (P<0.05) . Except for the 40 m group, the Penh of rats in the experimental groups were lower than those in the control group (P<0.05) . HE staining showed that the lung tissue of the experimental groups at different distance points showed obvious edema of the pulmonary interstitium and alveoli, a large number of red blood cells and inflammatory cells exuded in the alveolar space, thickening of the pulmonary interstitium, and increased lung injury score (P<0.05) . The results of immunohistochemistry showed that the positive expression of Caspase-1 in each experimental group was higher than that in the control group (P<0.05) . Western blotting results showed that the expression of pyroptosis-related proteins in each experimental group was higher than that in the control group (P<0.05) . Conclusion: Pyroptosis is involved in the pathophysiological process of gas explosion-induced ALI in rats.

Exosome-mediated delivery of SCD-1 siRNA promoted the death of anaplastic thyroid carcinoma cells via regulating ROS level.

PURPOSE: Anaplastic thyroid carcinoma (ATC) is one of the most aggressive cancers in the world. Stearoyl-CoA desaturase-1 (SCD-1) is one of major enzymes in the de novo synthesis of fatty acids and is related to cancer aggressiveness and poor patient prognosis. The study aimed to construct exosomes loaded SCD-1 interference, investigate its effects and mechanisms on the cell proliferation and apoptosis of ATC cells. METHODS: The expressions of SCD-1 in normal thyroid cell line and ATC cell lines were determined by qRT-PCR and western blotting, respectively. Exosomes were prepared and purification then loaded with SCD-1 siRNA by electroporation and observed by transmission electron microscopy. Higher SCD-1 mRNA and protein levels were found in ATC cell lines compared than normal thyroid cell line (P < 0.05), and both Hth-7 and FRO cells could uptake PKH67-labeled exosomes. The effects of exosomes loaded SCD-1 siRNA on ATC cells were measured by CCK8 assay and apoptosis detection kit. RESULTS: When compared with control group, the cell viability significantly decreased in both two ATC cell lines taken up exosomes loaded SCD-1 siRNA (P < 0.001), and apoptotic and necrotic cells obviously increased (P < 0.05). In order to explore the mechanism of exosomes loaded SCD-1 on ATC, the ROS level was detected by fluorescence reagent. It was found that exosomes loaded SCD-1 siRNA significantly increased intracellular ROS level of ATC cells (P < 0.05). CONCLUSIONS: Exosomes loaded SCD-1 siRNA inhibited ATC cellular proliferation and promoted cellular apoptosis, and the mechanisms involved maybe the regulation of fatty acids metabolism and ROS level. Our study provides a promising therapeutic strategy for ATC.

[Changes and significance of autophagy in rat lung injury induced by gas explosion].

Objective: To explore the changes and significance of autophagy in acute lung injury (ALI) induced by gas explosion in rats. Methods: In February 2018, the gas explosion in underground coal mine was simulated by large tunnel explosion experiment system, SD rats were randomly divided into control group and 6 distance groups (40 m, 80 m, 120 m, 160 m, 200 m, 240 m) with 18 rats in each group. The respiratory function of rats 24 h before and after explosion was detected. Post-explosion rats were anesthetized and sacrificed, histopathological changes of lung were observed by HE staining. Immunohistochemistry was performed to detect the in situ expression of autophagy marker protein microtubule-associated protein 1 light chain 3 (LC3B) . The expression levels of autophagy related gene 12 (Atg12) , LC3B, P62, lysosomal associated membrane protein 2 (Lamp2) , B-cell lymphoma/leukemia-2 (Bcl-2) and Bcl2 interaction protein (Beclin-1) were detected by Western blot. Results: After gas explosion, the rats in 80 m distance point group had the hightest mortality (n=13, 72.22%) and the most severe lung injury degree, and the histopathological scores was (4.00±0.00) point. After gas explosion, the minute ventilation volume (MVb) , maximum inspiratory flow rate (PIFb) and maximum expiratory flow rate (PEFb) of rats were lower than before the gas explosion (P<0.05) . The respiratory frequency of rats in 80 m, 200 m, and 240 m distance point groups were significantly higher than that in the control group (P<0.05) . The expression levels of LC3B in 40 m, 80 m, 120 m, 160 m, and 200 m distance point groups were higher than that in the control group (P<0.05) . The relative expression levels of Atg12 and LC3BⅡ/Ⅰ in lung tissues of rats in different distance point groups were higher than those in the control group (P<0.05) . The relative expression levels of Beclin1 in 40 m, 80 m, 120 m, and 160 m distance point groups were significantly higher than that in the control group (P<0.05) . The relative expression levels of P62 in 80 m, 160 m and 200 m distance point groups were lower than that in the control group (P<0.05) . The relative expression levels of Lamp2 and Bcl-2 in lung tissues of rats in all distance groups except 240 m distance group were lower than those in the control group (P<0.05) . Conclusion: Gas explosion could induce increased autophagy in lung tissues of ALI rats. Autophagy-related signaling pathway could be involved in the pathophysiological process of ALI in rats caused by gas explosion, then the autophagy and the severity of the lesion showed a significant positive correlation.

Elevated Serum FGG Levels Prognosticate and Promote the Disease Progression in Prostate Cancer.

Castration-resistant prostate cancer (CRPC) threatens the health of men in general and no effective therapeutics currently exists for the treatment of CRPC. It is therefore of great importance to find a novel molecule that can be a biomarker and a therapeutic target for CRPC. First, we found that the serum fibrinogen gamma (FGG) levels in patients with CRPC were significantly higher than those with localized prostate cancer (PCa) through iTRAQ proteomics and ELISA experiments. Immunohistochemistry, quantitative real-time polymerase chain reaction and western blot also showed an increase of FGG expression in CRPC tissues and cells. Then we proved the proliferation, invasion and migration ability of CRPC cells were significantly reduced after FGG knockdown. The number of apoptotic cells increased at least sixfold after FGG silencing, and was observed in conjunction with an upregulation of p53, caspase 3, clea-caspase 3, and Bax, and a downregulation of Bcl2 and survivin. FGG knockdown in DU145 cells resulted in smaller xenografts than control cells in a mouse model. and we established that FGG is modulated by IL-6 which was increased in CRPC patients via phosphorylation of STAT3. The data suggests that FGG may be a potential therapeutic target and prognostic marker for CRPC.

FBXW7 inhibited cell proliferation and invasion regulated by miR-27a through PI3K/AKT signaling pathway and epithelial-to-mesenchymal transition in oral squamous cell carcinoma.

OBJECTIVE: Our purpose was to detect the molecular mechanism of F-box and WD repeat domain containing 7 (FBXW7) in regulating cell growth and metastasis of oral squamous cell carcinoma (OSCC). PATIENTS AND METHODS: Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) and Western blot were applied to calculate the messenger ribonucleic acid (mRNA) and protein levels of genes and miR-27a. The proliferation and invasive abilities were measured by methyl thiazolyl tetrazolium (MTT) and transwell assays. The. Kaplan-Meier method was conducted to evaluate the 5-year overall survival of oral squamous cell carcinoma patients. RESULTS: FBXW7 was downregulated while miR-27a was upregulated in OSCC tissues and cells compared with the corresponding adjacent tissues. Downregulation of FBXW7 or upregulation of miR-27a in OSCC tissues predicted poor outcome of OSCC patients. FBXW7 suppressed the growth through the phosphatidylinositol 3-hydroxy kinase/protein kinase B (PI3K/AKT) signaling pathway in OSCC cell line HSC3. FBXW7 inhibited the invasion-mediated epithelial-mesenchymal transition (EMT) in HSC3 cells. The expression of FBXW7 was mediated by miR-27a by directly binding to the 3'-untranslated region (3'-UTR) of FBXW7 in HSC3 cells. MiR-27a reversed partial roles of FBXW7 on the proliferation and invasion in OSCC cells. CONCLUSIONS: FBXW7 was mediated by miR-27a and could inhibit the proliferation through the PI3K/AKT pathway and invasion-mediated EMT in OSCC cell line. The newly identified miR-27a/FBXW7/PI3K/AKT axis provides novel insights into the pathogenesis of osCC.

[Health management of breast cancer patients outside the hospital during the outbreak of 2019 novel coronavirus disease].

The outbreak of 2019 novel coronavirus disease (COVID-19) is spreading rapidly. In order to prevent cluster outbreaks, the government strengthened the management and control of personnel mobility, which had a great impact on the examination and treatment of breast cancer patients. This paper discusses how to realize scientific health management of breast cancer patients outside the hospital based on the existing epidemic situation, characteristics of breast cancer patients and public health safety factors. The breast cancer patients should synthetically consider the epidemic prevention situation of inhabitance, the disease stage and previous therapeutic schedule to decide the next therapeutic schedule. If necessary, after professional discussion and communication between doctors and patients online or offline, the hospital visiting time should be delayed through seeking alternative treatment schemes, and psychological counseling for patients should be paid attention to at the same time.

[Current status of body mass index and related influencing factors in the elderly aged 65 years and older in 8 longevity areas in China].

Objective: To understand the current status of BMI of the elderly and related factors in longevity areas in China, and provide scientific evidence for the control of BMI level in elderly population. Methods: Data used in this study were obtained from Healthy Aging and Biomarkers Cohort Study, a sub-cohort of the Chinese Longitudinal Healthy Longevity Survey. A total of 2 825 elderly in 8 longevity areas in China were surveyed and measured in 2017. The BMI levels of 2 217 elderly aged 65 years and older were calculated and in follow up. The ordered classification logistic regression model was used to analyze the influencd factors for the BMI in the elderly. Results: The BMI of the elderly in 8 longevity areas in China was (22.36±3.87) kg/m(2), and it was (22.76±3.58) kg/m(2) for males and (21.75±3.98) kg/m(2) for females. The BMI levels were normal in 1 165 elderly persons. The prevalence of underweight, overweight and obesity were 15.8%, 24.0% and 7.7%, respectively. Multivariate analysis showed that the main factors affecting the BMI of people under 100- years old were age (65-: OR=2.78, 95%CI: 1.87-4.15; 80-: OR=1.47, 95%CI: 1.00-2.17), smoking status (OR=0.46, 95%CI: 0.32-0.66), annual household income (<30 000 Yuan: OR=1.26, 95%CI: 1.07-1.47; 30 000-70 000 Yuan: OR=1.52, 95%CI: 1.12-1.86), and frequency of tea intake(OR=1.36, 95%CI: 1.01-1.71), while the factor in people aged ≥100 years was gender (OR=3.68, 95%CI: 1.32-10.36). Conclusions: The prevalence of underweight, overweight and obesity were high in the elderly from longevity areas in China. It is necessary to pay attention to the trend of overweight and obesity due to smoking, higher annual household income and regular tea drinking in the elderly men.

[Feasibility and toxicity of EC-T dose-dense adjuvant chemotherapy: A real world study in Chinese early-stage breast cancer patients with high recurrence risk].

Objective: We aimed to examine the feasibility and toxicity of EC-T dose-dense regimen and to demonstrate the suitable dose of epirubicin in a Chinese early-stage breast cancer population with high recurrence risk. Methods: 370 patients with early-stage breast cancer at high risk of recurrence were treated with EC-T dose-dense adjuvant chemotherapy and prophylactic administration of recombinant human granulocyte stimulating factor (G-CSF). The incidence of delayed chemotherapy, drug reduction and adverse reactions were retrospectively analyzed. Results: 370 patients completed the planned eight cycles of chemotherapy, 50 patients experienced chemotherapy delay, and 90 had chemotherapy dose reductions. Overall, 61.1% of the patients experienced grade 3 or 4 hematology toxicities, 4.1% of the patients experienced grade 3 gastrointestinal toxicity, 16.3% experienced grade 3 or 4 liver malfunction, and 1.9% experienced grade 3 alopecia. In the multivariate analysis, pretreatment epirubicin levels were associated with comprehensive and hematology toxicity risk (OR=1.268, P=0.046; OR=1.244, P=0.036). With G-CSF support, the probability of grade 3-4 dose limiting toxicity, i. e. neutropenia, abnormal liver function, and gastrointestinal adverse effects did not increase as the epirubicin dose level increased(P>0.05). However, there were no statistically significant associations between epirubicin grade and treatment delay (P=0.814) or dose reduction (P=0.282). Conclusions: EC-T dose-dense chemotherapy shows tolerable toxicity. High dose level is not a limiting factor for this regimen. With G-CSF support, epirubicin 85-90 mg/m(2) is appropriate tolerance dose for Chinese early breast cancer patients with high recurrence risk.

[Influence of low dose perfluorooctanoate acid exposure to the cell proliferation, migration and invasion of the human muscle rhabdomyosarcoma cell line].

Objective: This study aimed to explore the effect of perfluorooctanoate acid (PFOA) on the proliferation, migration and invasion of the human muscle rhabdomyosarcoma RD cell line and its related mechanisms. Methods: RD cells were cultured and exposed to PFOA of different concentrations with 6-72 hours. The cell viability was assessed by cell counting kit-8 (CCK-8) assay. Wound healing and transwell filter assay were used to evaluated the migration and invasion ability of the RD cells respectively. The cell cycles were detected by Flow cytometry. Quantitative real-time PCR and Western blot were used to quantify the mRNA and protein expression difference of related genes, respectively. Results: CCK-8 assay showed that, after treated the RD cell with different dose of PFOA for 72 h, low dose PFOA (1,10,50, 100 µmol/L) promotes the proliferation of RD cells while high dose PFOA (250, 500 mol/L) inhibits the proliferation (P<0.001). Flow cytometry showed that compared with the control group, there was no significant difference in G0/G1 phase, while cells in S phase deceased and G2/M phase cells increased after treated with PFOA (50 µmol/L) for 72 h. The relative proportions of S and G2/M were significantly different between the two groups (P<0.01). The results of qPCR showed that the mRNA relative expression of CDK2 of the control group and the PFOA (50 µmol/L) group were 0.97±0.07 and 2.64±0.11 respectively, and there was a significant difference (t=12.60, P<0.001); The mRNA relative expression of cyclin E2 of the control group and the PFOA (50 µmol/L) group were 1.33±0.17 and 3.35±0.22 respectively, and there was a significant difference (t=7.42, P<0.001); The results of Western blot showed that the protein relative expression of CDK2 of the control group and the PFOA (50 µmol/L) group were 0.35±0.01 and 0.84±0.03 respectively, and there was a significant difference (t=14.60, P<0.001); The protein relative expression of cyclin E2 of the control group and the PFOA (50 µmol/L) group were 0.67±0.04 and 0.86±0.01 respectively, and there was a significant difference (t=4.88, P<0.01); There was no significant difference in the mRNA and protein expression of p21 and p53 between the PFOA and control group (P>0.05). The wound healing rate of the PFOA (50 µmol/L) group was faster than that of the control group, and the relative migration area of the PFOA group was larger accordingly (P<0.001). After PFOA (50 µmol/L) treated, the number of the cell through the membranes was much more than the control group (t=54.40, P<0.001), which means PFOA significantly stimulated the invasion ability of the RD cells. The results of qPCR showed that the mRNA relative expression of vimentin of the control group and the PFOA (50 µmol/L) group were 0.71±0.03 and 2.53±0.16 respectively, and there was a significant difference (t=11.00, P<0.001); The mRNA relative expression of MMP2 of the control group and the PFOA (50 µmol/L) group were 1.09±0.04 and 10.73±1.20 respectively, and there was a significant difference (t=8.04, P<0.001). The results of Western blot showed that the protein relative expression of vimentin of the control group and the PFOA (50 µmol/L) group were 0.55±0.06 and 0.81±0.01 respectively, and there was a significant difference (t=4.50, P<0.05). The protein relative expression of cyclin E2 of the control group and the PFOA (50 µmol/L) group were 0.64±0.04 and 1.03±0.13 respectively, and there was a significant difference (t=2.94, P<0.05). Conclusions: Low dose PFOA (50 µmol/L) exposure promotes cell proliferation, migration and invasion in the human muscle rhabdomyosarcoma cell line through inducing the expressions of MMP2, vimentin and cell cycle related genes.

[Association of ambient fine particulate matters with anxiety in middle-aged and elderly people].

Objective: To investigate the association of ambient fine particulate matters (PM(2.5)) exposure with anxiety in middle-aged and elderly people in China. Methods: Using a stratified random sampling method, 5 997 middle-aged and elderly people (aged 40-89) who resided in the region for more than 2 years and had no hearing or language impairment were selected from 32 districts/counties in the key areas for air pollution prevention and control in China from October 10(th), 2017 to February 7(th), 2018. Information about demographic characteristics, socioeconomic factors and health status were collected by questionnaire survey and physical examination. The anxiety symptoms were assessed by 7-item Generalized Anxiety Disorder Scales. Three-year moving average concentrations of PM(2.5) were calculated to estimate exposure level. The multivariate logistic regression model was conducted to assess the association between PM(2.5) exposure and anxiety. The interaction of age, gender, overweight, education, smoking, drinking and chronic diseases was also analyzed by likelihood ratio test. Results: There were 2 995 (49.94%) males subjects, 4 092 (68.23%) subjects with education of secondary school or above and 2 576 (42.95%) subjects with self-reported chronic diseases among the 5 997 middle-aged and elder participants. The prevalence of anxiety was 6.64% (n=398). The mean±SD of 3-year moving average concentrations of PM(2.5), O(3) and SO(2) were (53.50±13.38), (90.58±13.26) and (40.29±12.56) µg/m(3), respectively. PM(2.5) had significantly association with anxiety, and the corresponding OR value was 1.17 (95%CI: 1.05,1.31) with a 10 µg/m(3) increment of 3-year moving average concentrations of PM(2.5). Compared with female (OR (95%CI)=1.07 (0.93,1.23)), those with no chronic diseases (OR (95%CI)=1.06 (0.93,1.20)) and those with primary school degree or below (OR (95% CI)=0.90 (0.75,1.09)), the association between PM(2.5) and anxiety was stronger among male (OR (95%CI)=1.35 (1.12,1.63)) and those with chronic diseases (OR (95%CI)=1.77 (1.31,2.38)), middle school education (OR (95%CI)=1.43 (1.22,1.67)), college education and above (OR (95%CI)=1.68 (1.05, 2.67)), all the P interaction values were <0.05. Conclusion: PM(2.5) exposure has significantly positive association with anxiety. The associations are stronger in male, people with higher educational qualifications and patients with chronic diseases.

[Expression of anaplastic lymphoma kinase fusion gene in patients with lung sarcomatoid carcinoma and treatment analysis].

Objective: To investigate the expression status of anaplastic lymphoma kinase (ALK) fusion gene in lung sarcomatoid carcinoma (LSC) and the role of ALK inhibitors for treatment. Methods: Total of 84 cases of LSC confirmed by histopathology were detected for ALK fusion gene from January 2011 to December 2014 in the Cancer Hospital of Chinese Academy of Medical Science&Peking Union Medical College and Shandong Zibo Wanjie Cancer Hospital. All patients were primarily treated by the multi-disciplinary mode in combination with chemotherapy or targeted therapy based on surgery. Postoperative adjuvant chemotherapy was given on platinum based two-drug combination regimen. In ALK fusion gene (+ ) patients with recurrence or metastasis, crizotinib target therapy was prefered. Chi-square test was applied for the comparison of 1, 3, 5-year survival rates between the two groups. Results: Eighty-two cases completed the follow-up. ALK fusion gene was found in 9(10.7%) patients. After application of crizotinib, 1 case was evaluated as complete remission, 6 cases as partial response, 2 cases as stable disease; the 1, 3, 5-year survival rate was 100% (9/9), 100% (9/9) and 88.9% (8/9) for the patients with ALK fusion gene, and it was 65.8% (48/73), 15.1% (11/73) and 6.8% (5/73) respectively for patients without ALK fusion gene. There was significant difference in the survival rate between the two groups (χ(2)=1.56, 1.56, 0.83, all P<0.05). Conclusion: ALK fusion gene maybe expressed in LSC patients. Compared with conventional chemotherapy, crizotinib can significantly prolong the survival time of patients with ALK fusion gene.

TSG-6 Induces Apoptosis of Human Hypertrophic Scar Fibroblasts via Activation of the Fas/FasL Signalling Pathway.

Tumour necrosis factor-stimulated gene 6 (TSG6) is a protective inflammatory reaction gene which is upregulated by inflammatory processes. Recent studies suggest that TSG-6 exhibits anti-scarring effects. However, the mechanism of TSG-6 action in the scar formation remains poorly understood. We investigated whether TSG-6 affects growth of the human hypertrophic scar fibroblasts (HSFs) via Fas/FasL signalling pathway. Cultured HSFs were transfected with a vector carrying the TSG6 gene (pLVX-Puro-TSG-6) or with a vector not containing the TSG6 gene (pLVX-Puro). Untransfected HSFs served as a control group to both transfected HSFs. The expressions level of TSG-6 was up-regulated in the pLVX-Puro-TSG-6 group at the protein and mRNA level. MTT and flow cytometry were used to assess the effect of TSG-6 on the growth and apoptotic status of HSFs. Finally, qRT-PCR and western blot were used to measure the expression levels of Fas, FasL, FADD, caspase-3 and caspase-8 in each group. The apoptosis rate was significantly enhanced and the growth rate reduced in the HSFs transfected with the TSG6 gene vector. The expression levels of Fas, FasL, FADD, caspase-3 and caspase- 8 were significantly raised in the TSG-6 overexpressing HSFs. It is concluded that increased expression of TSG-6 may induce apoptosis of human hypertrophic scar fibroblasts via activation of the Fas/FasL signalling pathway.

[Clinical significance of S100A6 and Notch1 in multiple myeloma patients].

Objective: To investigate the expression levels of S100A6, Notch1 in multiple myeloma (MM) patients and its clinical significance. Mathods: The expression levels of S100A6, Notch1 in 28 MM cases and 20 healthy controls were determined by real time quantitative PCR (RQ-PCR) , and their relationships with clinical features and outcomes were analyzed. Immunohistochemical was used to analysis the levels of S100A6 and Notch1 in bone marrow biopsy samples and intramedullary metastases soft tissues. RQ-PCR and Western blot were used to test the changes of Notch1 mRNA and Notch1 protein in U266 MM cells after S100A6 silenced by siRNA. Results: ①The expression levels of S100A6, Notch1 in primary MM patients was 2.19±1.25, 2.98±0.64, significantly higher than those in controls (0.71±0.20, 0.58±0.39, P<0.05) and patients in platform status (0.85±0.26, 0.72±0.40, P<0.05) . 8 cases with intramedullary metastasis had significantly higher levels of S100A6 (3.36±1.23) and Notch1 (5.71±3.96) , as compared to those without extra medullary metastases. ②S100A6 expression was positive correlation with Notch1 (r=0.505, P=0.007) . ③S100A6 and Notch1 proteins were positive in plasma cells of bone marrow biopsy samples and intramedullary metastases soft tissues. ④The Notch1 mRNA and Notch1 expression decreased significantly after 48 hours treatment by S100A6 siRNA in U266 cells. Conclusion: S100A6 and Notch1 were closely associated with MM progress and intramedullary metastasis. They have significant correlation and might be as two prognostic molecular markers in MM.

[Diagnosis and treatment of strabismus caused by nasal endoscopic surgery].

Objective: Strabismus with diplopia is the main orbital complication of functional endoscopic sinus surgery (FESS). This study was to analyze clinical findings, treatment and outcomes of such cases. Methods: Retrospective case series. Twenty-three cases were divided into 3 groups based on the disease severity: group A, partial transection of the medial rectus muscle, group B, complete transection of the medical rectus, group C, transection of the medial rectus combined with the other orbital injuries. Complete ophthalmology examinations, including eye alignment, eye motility, force duction test, force generation test, general eye exam, and medical imaging (orbital CT or MRI), were performed for each case. The treatment included botulinum toxin (Botox) injection to the lateral rectus muscle, transposition of the vertical rectus muscle, and orbital surgery if needed. Results: In group A with Botox injection, all the cases achieved single vision in primary position, but still remained some adduction weakness. In group B treated by vertical transposition surgery combined with Botox, 22% of the cases got single vision in primary gaze. In group C, even with more efforts of treatment, the cases with orbital injury can only get cosmetic improvement, and diplopia and adduction dysfunction were found in most cases. Conclusions: Due to the variety of the complications of FESS, force duction test is a crucial exam to detect the direction and severity of synechia in the orbit, which will give solid information to surgery approach as well as prognosis. Botox injection at early stage will minimize the contraction of antagonist lateral rectus, helping to postpone the transposition surgery which may cause anterior segment ischemia when performed right after the medial rectus transection injury. Botox may even reduce the synechia by minimizing the scarring process. Partial vertical rectus transposition combined with muscle resection may effectively correct the eye misalignment in primary gaze and improve eye motility. The prognosis of FESS induced orbital complications is quite related with the severity of the injury. Botox combined with surgery may help medial rectus transection cases to achieve single vision in primary gaze, but when there is any other orbital injury, treatment may only improve cosmetic appearance. (Chin J Ophthalmol, 2017, 53: 917-923).

[Surgical treatment of pituitary adenomas in childhood and adolescence].

Objective: To investigate the clinical characteristics and treatment of pituitary adenomas of childhood and adolescence. Methods: Thisarticle was a retrospective study of 140 pituitary adenomas of childhood and adolescence that was admitted into Peking Union Medical College Hospital from December 1987 to December 2014, whose clinical manifestations, hormone secretions, images, pathological types, surgical complications and follow-ups were studied. Results: A total of 58 (41.4%) males and 82 females (58.6%) were included, whose mean age was 12.5 years old (age range from 7 to 18). As for the type of tumors, ACTH adenoma, PRL adenoma, GH adenoma, non-functional adenoma and multiple-secreting adenoma accounted for 35.7%, 25.7%, 12.2%, 25.7% and 0.7%, respectively. Microadenoma accounted for 33.6% of total patients, while macroadenoma and giant adenoma accounted for 60.0% and 6.4% respectively. 19.3% of adenomas in our study wereinvasive. Transsphenoidal approach surgery was commonly used and accounted for 97.9% of cases in our study, 2 of which used intraoperative navigation assistance. Total resection was achieved in 93.6% of patients, and the rest achieved subtotal resection. 108 (77.1%) patients got full term follow-up until 1 year after surgery, and tumor recurred in 14 patients (13.0%). Conclusions: ACTH-secreting adenoma is the most common pituitary adenoma in childhood and adolescence which need surgical treatment. Transsphenoidal approach surgery is the most commonly used surgical procedure. The recurrence rate is about 13%, and the patients need regular examination of pituitary hormones and image study to confirm the recurrence.