Endurance Training Inhibits the JAK2/STAT3 Pathway to Alleviate Sarcopenia.

Aging leads to a decrease in muscle function, mass, and strength in skeletal muscle of animals and humans. The transcriptome identified activation of the JAK/STAT pathway, a pathway that is associated with skeletal muscle atrophy, and endurance training has a significant effect on improving sarcopenia; however, the exact mechanism still requires further study. We investigated the effect of endurance training on sarcopenia. Six-month-old male SAMR1 mice were used as a young control group (group C), and the same month-old male SAMP8 mice were divided into an exercise group (group E) and a model group (group M). A 3-month running exercise intervention was performed on group E, and the other two groups were kept normally. Aging caused significant signs of sarcopenia in the SAMP8 mice, and endurance training effectively improved muscle function, muscle mass, and muscle strength in the SAMP8 mice. The expression of JAK2/STAT3 pathway factor was decreased in group E compared with group M, and the expression of SOCS3, the target gene of STAT3, and NR1D1, an atrophy-related factor, was significantly increased. Endurance training significantly improved the phenotypes associated with sarcopenia, and the JAK2/STAT3 pathway is a possible mechanism for the improvement of sarcopenia by endurance training, while NR1D1 may be its potential target. Keywords: Sarcopenia, Endurance training, Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3), Nuclear receptor subfamily 1, group D member 1 (Nr1d1).

[MiR-125b-5 suppresses ovarian cancer cell migration and invasion by targeted downregulation of CD147].

OBJECTIVE: To investigate whether miR-125b-5p regulates biological behaviors of ovarian cancer cells by targeted regulation of CD147 expression. METHODS: RT-qPCR was used to detect the expression of miR-125b-5p and CD147 mRNA in ovarian cancer tissues and cancer cell lines. SKOV3 cells transfected with miR-125b-5p mimic and HO8910 cells transfected with miR-125b-5p inhibitor were examined for changes in proliferation, migration and invasion using CCK-8 assay, colonyforming assay and Transwell assay. Starbase was used to predict the potential binding sites between miR-125b-5p and CD147, and double luciferase reporter gene assay was used to verify the targeting relationship. In SKOV3 cells, the effects of cotransfection with miR-125b-5p mimic and pcDNA3.1-CD147 (or pcDNA3.1) plasmid on cell proliferation, migration and invasion were assessed with CCK-8 assay and Transwell assay. RESULTS: The expression of miR-125b-5p was significantly lowered and that of CD147 was increased in both ovarian cancer tissues and ovarian cancer cell lines (P < 0.05). Overexpression of miR-125b-5p in SKOV3 cells resulted in significantly suppressed cell proliferation, migration and invasion, while downregulation of miR-125b-5p in HO8910 cells promoted cell proliferation, migration and invasion. Bioinformatic analysis predicted that miR-125b-5p binds to CD147, which was confirmed by luciferase reporter gene assay. RT-qPCR and Western blotting showed that miR-125b-5p negatively regulated CD147 expression (P < 0.05). In SKOV3 cells, the inhibitory effects of miR-125b-5p mimic on cell proliferation, invasion and migration were significantly attenuated by co-transfection of the cells with pcDNA3.1-CD147 plasmid. CONCLUSION: miR-125b-5p inhibits the migration and invasion of ovarian cancer cells by negatively regulating the expression of CD147.

Sodium MRI at 7T for Early Response Evaluation of Intracranial Tumors following Stereotactic Radiotherapy Using the CyberKnife.

BACKGROUND AND PURPOSE: Conventionally, early treatment response to stereotactic radiotherapy in intracranial tumors is often determined by structural MR imaging. Tissue sodium concentration is altered by cellular integrity and energy status in cells. In this study, we aimed to investigate the feasibility of sodium MR imaging at 7T for the preliminary evaluation of radiotherapeutic efficacy for intracranial tumors. MATERIALS AND METHODS: Data were collected from 16 patients (12 men and 4 women, 24-75 years of age) with 22 intracranial tumors who were treated with stereotactic radiation therapy using CyberKnife at our institution between December 1, 2016, and August 15, 2019. Sodium MR imaging was performed at 7T before and 48 hours, 1 week, and 1 month after CyberKnife radiation therapy. Tissue sodium concentration (TSC) was calculated and analyzed based on manually labeled regions of tumors. RESULTS: Ultra-high-field sodium MR imaging clearly showed the intratumoral signal, which is significantly higher than that of normal tissue (t = 5.250, P <.001)., but the edema zone has some influence. The average TSC ratios of tumor to CSF in the 22 tumors, contralateral normal tissues, edema zones, frontal cortex, and frontal white matter were 0.66 (range, 0.23-1.5), 0.30 (range, 0.15-0.43), 0.58 (range, 0.25-1.21), 0.25 (range, 0.17-0.42), and 0.30 (range, 0.19-0.49), respectively. A total of 12 tumors in 8 patients were scanned at 48 hours, 1 week, and 1 month after treatment. The average TSC at 48 hours after treatment was 0.06 higher than that before treatment and began to decrease at 1 week. The TSC ratios of 10 continued to decline and 2 tumors increased at 1 month, respectively. Tumor volume decreased by 2.4%-99% after 3 months. CONCLUSIONS: Changes in the TSC can be quantified by sodium MR imaging at 7T and used to detect radiobiologic alterations in intracranial tumors at early time points after CyberKnife radiation therapy.

[The effects of sequence of radiotherapy and chemotherapy on prognosis of patients with early-stage extranodal NK/T cell lymphoma (nasal type) and its individualized application].

Objective: To analyze the effects of the sequence of radiotherapy and chemotherapy on the efficacy of early-stage extranodal NK/T-cell lymphoma (nasal type, ENKTCL) patients, and to provide a quantitative evaluation method for individualized radiotherapy and chemotherapy. Methods: The Chinese Lymphoma Collaborative Group (CLCG) collected the clinical data of 2 008 patients with early-stage Ⅰ/Ⅱ ENKTCL who received radiotherapy and chemotherapy from January 2000 to early September 2019 from 21 hospitals across the country, including 1 417 males and 591 females, aged 2 to 83 (42±14) years. According to the sequence of radiotherapy and chemotherapy, patients were divided into radiotherapy-first group (388 cases) and chemotherapy-first group (1 620 cases). Survival rate was estimated using Kaplan-Meier method, and multivariate Cox proportional risk model was used to screen and identify independent prognostic factors. The prognostic prediction models of the two therapies were constructed separately, and the models were used to predict the individualized mortality risk of all patients to determine the appropriate radiotherapy and chemotherapy regimen for each patient. Results: The 5-year overall survival rate was 74.2% (95%CI: 69.6%-79.2%) in the radiotherapy-first group and 69.7% (95%CI: 67.1%-72.4%) in the chemotherapy-first group. Although the 5-year overall survival rate of patients in the radiotherapy-first group was numerically higher than that of the chemotherapy-first group, the difference was not statistically significant (χ2= 2.26, HR=0.84 (95%CI: 0.68-1.05), P=0.133). Six variables including age, gender, ECOG score, LDH, Ann Arbor staging, and PTI (primary tumor invasion) were screened out as independent prognostic factors (the chemotherapy-first group: HR were 1.01, 1.25, 2.07, 0.77, 1.34, 1.49, respectively, all P<0.05; radiotherapy-first group: HR were 1.02, 1.31, 1.66, 0.78, 1.37, 1.29, all P>0.05). The mean 5-year predicted mortality risk for all patients receiving radiotherapy-first regimen was lower than those receiving chemotherapy-first regimen (26.8% vs 30.2%, P<0.001). There were individualized differences in the predicted mortality risk of patients with different clinical characteristics who received radiotherapy-first regimen or chemotherapy-first regimen. Conclusion: Patients with stage Ⅰ/Ⅱ ENKTCL treated with radiotherapy-first regimen had a better expected prognosis than patients treated with chemotherapy-first regimen. The quantitative assessment of the differential effects of the sequence of radiotherapy and chemotherapy on the mortality risk of individual patients based on their clinical characteristics was helpful for the clinical development of the optimal radiotherapy and chemotherapy plan for each patient.

[Outcome of radiotherapy for low-risk early-stage patients with extranodal NK/T-cell lymphoma, nasal-type].

Objective: To evaluate the prognosis and determine the failure patterns after radiotherapy for low-risk early-stage patients with extranodal NK/T-cell lymphoma, nasal-type (ENKTCL). Methods: A total of 557 patients from 2000-2015 with low-risk early-stage ENKTCL who received radiotherapy (RT) with or without chemotherapy (CT) from China Lymphoma Collaborative Group were retrospectively reviewed. Among them, 427 patients received combined modality therapy, whereas 130 patients received RT alone. Survivals were calculated by Kaplan-Meier method and compared with Log-rank test. Overall survival (OS) was compared with age and sex-matched general Chinese population using expected survival and standardized mortality ratio (SMR). Cox stepwise regression model was used for multivariate analysis. Results: The 5-year OS and progression-free survival (PFS) were 87.2% and 77.2%. The SMR was 3.59 (P<0.001) at 1 year after treatment, whereas it was 1.50 at 4 years after treatment, without significant difference between ENKTCL group and country-matched general population (P=0.146). Compared with RT alone, CMT did not result in significantly superior 5-year OS (87.0% vs 87.4%, P=0.961) or PFS (76.1% vs 80.7%, P=0.129). Local failure (11.5%, 64/557) and distant failure (10.8%, 60/557) were the main failure modes, while regional failure was rare (2.9%, 16/557). The 5-year locoregional control rate (LRC) was 87.2% for the whole group, with 89.5% for ≥50 Gy versus 73.7% for <50 Gy (P<0.001). Radiotherapy dose was an independent factor affecting LRC(P<0.05). Conclusions: Radiotherapy achieves a favorable prognosis in patients with low-risk early-stage ENKTCL. The incidence of either locoregional or distant failure is low. Radiation dose still is an important prognostic factor for LRC.

[Clinical features and treatment outcome of extranodal nasal-type NK/T-cell lymphoma of the extra-upper aerodigestive tract].

Objective: To investigate the clinical features and prognosis of extranodal nasal-type NK/T-cell lymphoma of the extra-upper aerodigestive tract (extra-UADT NKTCL). Methods: The clinical data of 159 patients with extra-UADT NKTCL from the China Lymphoma Collaborative Group (CLCG) database between November 2001 and December 2015 were retrospectively analyzed. Kaplan-Meier survival analysis and Log-rank test were used to evaluate the prognosis. The Cox regression model is used for multi-factor analysis. Results: Extra-UADT NKTCL commonly occurs in skin and soft tissues (106/159, 66.7%) and gastrointestinal tract (31/159, 19.5%). The incidences of elevated lactate dehydrogenase (LDH) and Ann Arbor Ⅲ~Ⅳ stage were 47.8% (76/159) and 64.2% (102/159), respectively. The 3-year overall survival (OS) and progression-free survival (PFS) rates were 43.6% and 27.9%, respectively. The corresponding OS rates of primary skin/soft tissue site and gastrointestinal tract site were 41.0% and 59.4% (P=0.281), while the PFS rates were 24.8% and 48.3%, respectively (P=0.109). Combined modality treatment improved the 3-year OS of all the patients (58.4% vs 33.9%, P=0.001) and 3-year PFS (40.7% vs 20.7%, P=0.008) when compared with chemotherapy alone. LDH elevation, Ann Arbor synthesising and ≥2 junction external bits were intrusive as independent risk factors for total survival (P<0.05), LDH elevation and ≥2 junction outer bits were intrusive as independent risk factors for progressionless survival(P<0.05). The distant extranodal dissemination was the primary failure patterns. Conclusions: Extra-UADT NKTCL appears to have distinct clinical characteristics and poor outcome. Compared with chemotherapy alone, combined modality treatment may improve the prognosis of patients with extra-UADT NKTCL.

Association of improved overall survival with decreased distant metastasis following asparaginase-based chemotherapy and radiotherapy for intermediate- and high-risk early-stage extranodal nasal-type NK/T-cell lymphoma: a CLCG study.

BACKGROUND: This study evaluated the survival benefit of asparaginase (ASP)-based versus non-ASP-based chemotherapy combined with radiotherapy in a real-world cohort of patients with early-stage extranodal nasal-type natural killer/T-cell lymphoma (ENKTCL). PATIENTS AND METHODS: We identified 376 patients who received combined radiotherapy with either ASP-based (ASP, platinum, and gemcitabine; n = 286) or non-ASP-based (platinum and gemcitabine; n = 90) regimens. The patients were stratified into low-, intermediate-, and high-risk groups using the early stage-adjusted nomogram-revised risk index. Overall survival (OS) and distant metastasis (DM)-free survival (DMFS) between the chemotherapy regimens were compared using inverse probability of treatment weighting (IPTW) and multivariable analyses. RESULTS: ASP-based (versus non-ASP-based) regimens significantly improved 5-year OS (84.5% versus 73.2%, P = 0.021) and DMFS (84.4% versus 74.5%, P = 0.014) for intermediate- and high-risk patients, but not for low-risk patients in the setting of radiotherapy. Moreover, ASP-based regimens decreased DM, with a 5-year cumulative DM rate of 14.9% for ASP-based regimens compared with 25.1% (P = 0.014) for non-ASP-based regimens. The survival benefit of ASP-based chemotherapy and radiotherapy remained consistent after adjusting the confounding variables using IPTW and multivariate analyses; additional sensitivity analyses confirmed these results. CONCLUSIONS: The findings provided support for ASP-based chemotherapy and radiotherapy as a first-line treatment strategy for intermediate- and high-risk early-stage ENKTCL.

Long-term survival case of a non-small cell lung cancer bone metastasis patient treated with bone cement, radiation and gefitinib.

OBJECTIVE: We explore the treatment of bone metastases in advanced non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: We reported a 76-year-old female patient, who was diagnosed with NSCLC with bone metastasis eight years ago (stage IVA). Due to unbearable diarrhea, she refused chemotherapy, and we adopted local treatment, including local radiotherapy 50 Gy and bone cement to lumbar spinal metastases, 62 Gy local radiotherapy of primary lung tumor, TKI inhibitor gefitinib and zoledronic acid. RESULTS: She survived more than eight years and is still in follow-up. CONCLUSIONS: The median survival time for NSCLC patients with bone metastases is often less than 1 year. We reported the patient with more than eight years of survival, showed that some special cases can adopt the methods of local treatment including bone cement, treatment benefit patients, radiation therapy and targeted therapy in clinic to expand the survival.

Progress in the study of markers related to glioma prognosis.

OBJECTIVE: In the era of precision medicine, molecular and genetic biomarkers act as the key indicators for glioma patients' recurrence and prognosis. MATERIALS AND METHODS: We summarize the biomarkers of glioma prognosis from molecular level, gene level and microRNA level. RESULTS: In molecular biomarkers, cyclinD1 high expression/P16 low expression, MIF high expression and VEGF high expression were all related to glioma patients' poor prognosis; in genetic biomarkers, MGMT promoter methylation absence, IDH1 wild type, HIF-α high expression, Chromosome 1p/19q non-deletion and TERT promoter mutation were associated with poor prognosis for glioma; in microRNA biomarkers, miR-524-5p, miR-586, miR-433, miR-619, miR-548d-5p, miR-525-5p, miR-301a, miR-210, miR-10b-5p, miR-15b-5p and miRNA-182 high expression, miR-124, miR-128, miR-146b and miR-218 low expression were commonly seen in glioma poor prognosis patients. CONCLUSIONS: With the continuous development of science and technology, the diagnosis of glioma will tend to the gene and molecular level. Finding specific markers is helpful for the early diagnosis and accurate prognosis of glioma, which provides the possibility for individualized treatment.

[The cytotoxity of DOP on PC12 cells and it's effect on processing of APP-enzymolysis].

Objective: To study the toxicity of dioctyl phthalate (DOP) on adrenal pheochromocytoma (PC12) cells and its effect on processing of amyloid precursor protein (APP) -enzymolysis. Methods: In vitro experiments, PC12 cells were divided into blank control (CT) , low DOP (DOP1) , medium DOP (DOP2) , high DOP (DOP3) , low DOP+Aß(25-35) (DOP1+Aß) , medium DOP+Aß(25-35) (DOP2+Aß) , high DOP+Aß(25-35) (DOP3+Aß) , Aß(25-35) (Aß) , a total of 8 groups, each with 4 samples. The cell viability was measured by MTT assay, the contents of lactate dehydrogenase (LDH) , malondialdehyde (MDA) and nitric oxide (NO) were measured, and cysteine protease 3 (Caspase-3) was determined by Western blot. In the transfection experiment, the hamster ovary (CHO) cells were transfected with APP695 and treated with different concentrations of DOP. They were divided into V-Flag control (V-Flag) , APP695-Flag (APP695) , low DOP (DOP1+APP695) , medium DOP (DOP2+APP695) , high DOP (DOP3+APP695) , a total of 5 groups, each with 4 samples. Enzyme-linked immunosorbent assay (ELISA) was used to determine the content of Aß(1-40) and the activity of γ-secretase. In vivo experiment, 50 male Kunming mice of SPF grade, weighing (20±2) g, were selected and randomly divided into control, lead (Pb) , low DOP (DOP1＇) , medium DOP (DOP2＇) , high DOP (DOP3＇) consisted of 5 groups, each with 10 mice, continuously gavage for 6 weeks. Morris water maze method was used to detect the effect of different concentrations of DOP on learning and memory in mice, and ELISA method was used to detect ß-secretase, γ-secretase activity and Aß(1-40) content in brain tissue. Results: Compared with the CT group, the cell viabilities of the DOP2 and DOP3 groups were decreased, and the contents of LDH, MDA, and NO were increased, and the differences were statistically significant (P<0.05) . Compared with the CT group, the cell viabilities of DOP1+Aß, DOP2+Aß and DOP3+Aß groups were decreased, the contents of LDH, MDA, NO were increased, the differences were statistically significant (P<0.05) . Compared with the Aß group, the cell viability of DOP3+Aß group was decreased, the contents of LDH, MDA, NO were increased, the differences were statistically significant (P<0.05) . Compared with the Aß group, the contents of LDH and NO in the DOP2+Aß group were increased, and the differences were statistically significant (P<0.05) . Compared with the CT group, the expression levels of Caspase-3 in the DOP2 and DOP3 groups were increased, and the differences were statistically significant (P<0.05) . Compared with the Aß group, the expression levels of Caspase-3 in the DOP2+Aß and DOP3+Aß groups were increased, and the differences were statistically significant (P<0.05) . Compared with the APP695 group, the contents of Aß(1-40) and the activities of γ-secretase of the DOP2+APP695 and DOP3+APP695 groups were increased (P<0.05) . Compared with the control group, the activities of ß-secretase, γ-secretase and the content of Aß(1-40) in the brain tissue of DOP3＇group were increased, and the differences were statistically significant (P<0.05) . Compared with the Pb group, the activities of ß-secretase, γ-secretase and the content of Aß(1-40) of the DOP3＇group were increased, and the differences were statistically significant (P<0.05) . Compared with the control group, the target quadrant stay time and the number of crossings in the DOP2＇and DOP3＇groups were reduced, and the differences were statistically significant (P<0.05) . Conclusion: DOP has a certain toxic effect on PC12 cells, causing learning and memory impairment in mice, and may promote the pathological progression of Alzheimer＇s disease.

Comparison of IMRT and VMAT radiotherapy planning for Graves' ophthalmopathy based on dosimetric parameters analysis.

OBJECTIVE: To compare volumetric modulated arc therapy (VMAT) and intensity-modulated radiation therapy (IMRT) for the treatment of Graves' ophthalmopathy (GO) based on the dosimetric data. PATIENTS AND METHODS: 19 patients diagnosed with GO were recruited in this study. For each patient, a dual-partial-arc VMAT plans and a 7-fixed-field IMRT plans were replanned. Dosimetric parameters of the targets and organs at risk (OARs) originated from the two kinds of plans were compared and analyzed. RESULTS: Homogeneity index (HI) was superior in IMRT plans compared with VMAT (p=0.0014) but there was no significant statistical difference in conformity index (CI) between them (p=0.0673). IMRT plans revealed advantage in the OARs protection especially for the left and right lenses, optic nerves and eyeballs (p<0.05). CONCLUSIONS: VMAT and IMRT are both feasible techniques in radiotherapy in GO from the perspective of dosimetric parameters. Homogeneity and OAR protection were slightly superior in IMRT plans compared with VMAT plans.

H3K27M mutant diffuse midline glioma: a case report.

OBJECTIVE: Diffuse midline glioma with H3K27M mutation is a new tumor type of WHO central nervous system tumor classification. It often occurs in the midline structure and usually has a poor prognosis. CASE REPORT: A 38-year-old male patient presented with 2 years history of right limb with facial numbness, tumors in the left thalamic region and lateral ventricle was detected by imaging. The patient underwent the first surgery. RESULTS: The pathological examination results: Glioblastoma. He recovered well after surgery and received a total of 30 times of radiotherapy and temozolomide for one year. Fourteen months later, tumours were observed in the left thalamic region and left parieto-occipital lobe, the patient underwent the second operation. Immunohistochemistry showed: H3K27M(+). He experienced limitation of right limb movement after surgery and started taking oral apatinib 250 mg qd. After one-year, multiple tumors were found in the left brainstem, bilateral ventricles, bilateral basal ganglia, etc. The patient was given radiotherapy 7 times and then took apatinib 250 mg qd. Now the patient is still alive. CONCLUSIONS: H3K27M mutant diffuse midline glioma is characterized by diffuse infiltrative growth. Its pathological classification is diverse, imaging features lack specificity, and prognostic factors are complex. Traditional radiochemotherapy has limited effects, molecular targeted therapy, especially intervention of epigenetic regulation is being explored.

RNA-seq reveals transcriptome changes of the embryonic lens cells in Prox1 tissue specific knockout mice.

OBJECTIVE: Prox1 is expressed in both lens epithelial cells and fiber cells and is essential for lens fiber cell elongation. This study aimed to explore the molecular mechanisms of how Prox1 mutations influence lens fiber cells development. MATERIALS AND METHODS: Comparative transcriptomes analysis of Prox1 conditional knockout (cKO) lens and wild-type (WT) lens were performed using the data GSE69940 downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were determined by the R package "edgeR" of Trinity software. GO (Gene Ontology) enrichment analysis and KEGG (Kyoto Encyclopedia of Genes and Genomes databases) enrichment analysis were performed using the cluster Profiler R package. Then, the protein-protein interaction (PPI) network was predicted using Cytoscape, and the Module analysis of the PPI network was analyzed through the Cytoscape MCODE plugin. Moreover, MotifDb package in R was used to predict the transcription factors binding to Prox1 promoter regions. RESULTS: In total, 2263 differentially expressed genes were identified between the two groups. GO and KEGG analysis showed that the down-regulated genes were enriched in camera-type eye term, nucleosome assembly, lens fiber cell differentiation, and cell modified and amino acid metabolism. The KEGG pathway of up-regulated genes was associated with lens development, including Hedgehog signaling pathway and MAPK signaling pathway. GO terms of up-regulated DEGs were mainly relevant to bone morphological development, muscle development, and sensory organ morphological development. Next, the PPI network of DEGs was constructed, and 4 modules were analyzed. Moreover, 30 transcription factors were predicted, which are likely to be downstream targets of Prox1 with potential roles in lens development in mice. CONCLUSIONS: This study provides insights into the unique transcriptome profile of lens cells in Prox1 conditional knockout mice, which is a valuable resource for further study of mouse lens genomics.

Up-regulation of long non-coding RNA MFI2 functions as an oncogenic role in cervical cancer progression.

OBJECTIVE: Cervical cancer is one of the gynecologic tumors in the world. The main aim of this study was to elucidate the functional role of MFI2 in cervical cancer and provide novel insight into biomarkers and therapeutic strategies for cervical cancer. PATIENTS AND METHODS: The relative expression level of MFI2 was examined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Cell counting kit-8 (CCK-8) assay was involved to determine the ability of cell proliferation. Flow cytometric analysis was performed to detect cell apoptosis. Transwell assay and Matrigel assay were involved to determine cell migration and invasion. Expressions of protein kinase B (AKT), phosphorylated-AKT (p-AKT), B-cell lymphoma-2 (BCL2), and BCL2-Associated X (Bax) protein levels were detected in Western blotting. Transfected cells were used to perform tumor xenograft formation assay. RESULTS: Our research validated that MFI2 was up-regulated in cervical cancer by qRT-PCR. Through CCK-8 assay, flow cytometric analysis, transwell assay, and Matrigel assay, we verified that MFI2 can promote cell proliferation, cell metastasis and inhibit cell apoptosis in cervical cancer. Subsequently, we used Western blotting assay to determine the alteration of protein expression of p-AKT, BCL2, and Bax. The results indicated that MFI2 may exert its function by regulating phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway. In tumor xenograft formation assay, up-regulated MFI2 accelerated tumor formation. CONCLUSIONS: Current research elucidated that MFI2 promoted cell proliferation, cell metastasis and inhibited cell apoptosis in cervical cancer by regulating the PI3K/AKT signaling pathway. Our results may provide a novel insight into finding new therapeutic targets and biomarkers for cervical cancer.

[Ultrastructural and clinical findings of mitochondrial encephalomyopathy:report of 27 cases].

Objective: To investigate the ultrastructural features of muscle in patients with mitochondrial encephalomyopathy for its diagnosis and differential diagnosis. Methods: The clinical data of 27 mitochondrial encephalomyopathy patients who underwent left or right biceps brachii muscle biopsy at Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University from July 2006 to August 2017 were analyzed retrospectively. The muscle biopsy specimens were examined underlight microscope and transmission electron microscope. Results: There were 27 patients (17 males, 10 females) with an age range of 12 to 62 years (mean 29 years). The age of onset ranged from 3 to 38 years. The course of disease ranged from 1 month to 24 years. Twenty-two cases presented with lactic acidosis and stroke-like episodes (MELAS) syndrome, four with myoclonic epilepsy with ragged red fibers (MERRF) syndrome, and one with chronic progressive paralysis of extraocular muscle (CPEO) syndrome. Skeletal muscle biopsy showed abundant ragged red fibers and strongly SDH-reactive vessel. Genetic studies showed 17 of 22 cases of MELAS syndrome had A3243G mutation, and the other 5 cases had no abnormality. A8344G mutation was found in 3 of 4 cases of MERRF syndrome. No single or multiple mtDNA mutations were found in the single case of CPEO. Transmission electron microscopy of all 27 cases showed diffuse proliferation of mitochondria between the myofibrils and beneath the sarcolemma, with increased spacing between muscle cells. Seven cases showed numerous glycogen and four showed subsarcolemmal lipid droplets, 13 cases showed unusual mitochondrial morphology, including mitochondrial electron-dense substances and paracrystal line inclusions ("parking lot" change)in eight cases. Conclusions: Transmission electron microscopy shows significant differences in ultrastructural pathological changes among different patients with mitochondrial encephalomyopathy. Some patients with mild clinical symptoms have increased mitochondrial number, increased metabolism of glycogen and lipid droplets, while others with severe clinical symptoms have abnormal mitochondrial morphology. Typical crystalloid inclusions are found in mitochondria, which are of great value in the diagnosis of this disease.

Effect of Hypotensive Brain Death on the Donor Liver and Its Mechanism in an Improved Bama Miniature Pig (Sus scrofa domestica) Model.

BACKGROUND: We aimed to observe the effect of hypotensive brain death on the donor liver and understand its pathophysiological mechanism in improved pig model. METHODS: The model was induced using the modified intracranial water sac inflation method in 16 Bama miniature pigs. Effects of hypotensive brain death on liver function and tissue morphology were evaluated via changes in liver function enzyme index, liver tissue alkaline phosphatase levels, hourly bile flow, and liver tissue pathology. Its pathophysiological mechanism was examined on the basis of changes in portal vein blood flow, hepatic artery blood flow, portal venous endotoxin level, and liver tissue cytokine levels. RESULTS: After model establishment, portal vein blood flow, hepatic arterial blood flow, hourly bile flow, and alkaline phosphatase content in hepatic tissue significantly decreased, and serum aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase levels significantly increased. Hematoxylin-eosin staining of liver tissue showed that after model establishment, hepatic tissue injury was gradually aggravated and hepatic cells were irreversibly damaged at 7 hours. Portal vein endotoxin levels significantly increased after brain death. Tumor necrosis factor α, interleukin 1, and endothelin 1 levels in liver tissues significantly increased at 3, 6, and 12 hours after brain death (P < .05), and hypoxia-inducible factor 1-α and nitric oxide levels significantly decreased (P < .05). CONCLUSIONS: Hepatic injury was progressively aggravated under hypotensive brain death. The mechanism of donor liver injury under hypotensive brain death may involve low liver perfusion, release of intestinal endotoxin and inflammatory factors (eg, tumor necrosis factor α and interleukin 1), decreased hypoxia-inducible factor 1-α, and endothelin 1 and nitric oxide imbalance.

[The associations between comorbidity and exacerbation risk in patients with chronic obstructive pulmonary disease].

Objective: To study the association between comorbidity and acute exacerbation risk in patients with chronic obstructive pulmonary disease (COPD). Methods: This was a prospective cohort study with 64 stable COPD patients included. There were 64 males and 18 females with an average age of (68±9) years. Clinical characteristics, the number and type of comorbidities were recorded, and Charlson comorbidity index (CCI) was calculated. The patients were interviewed by phone calls every 3 months since baseline in which the number of acute exacerbations was recorded until 12 months. The impact of CCI, the number of comorbidities and certain comorbidities in the prediction of COPD exacerbation risk were analyzed. Results: Compared to patients with a lower CCI score, patients with a higher CCI score were older (75±6 vs 62±8), and had more severe lung function impairment [FEV(1)%pred: (40±18)% vs (52±18)% ], higher number of comorbidities [4(3, 7) vs 1(1, 3)] and higher frequency of hospital admission due to acute exacerbation [1(0, 2) vs 0(0, 0.25)]. In comparison with patients with lower number of comorbidities, patients with higher number of comorbidities were older (72±7 vs 64±10), and had higher mMRC score [2(1, 3) vs 2(1, 2)] and more severe lung function impairment [FEV(1)%pred: (42±15)% vs (53±19)% ], higher age adjusted CCI score [5(3, 5) vs 3(2, 3) ] and more courses of systemic corticosteroids [2(0, 3) vs 0(0, 0.75)] and/or antibiotics use [3(2, 4) vs 1.5(1, 2.75)]. The number of hospitalizations and total number of exacerbations were higher in COPD patients with bronchiectasis than those without (P<0.005). Conclusion: The inclusion of clinically meaningful comorbidities into the combined assessment of COPD for the prediction of disease prognosis deserves further study.

[Prevalence and risk factors of diabetic retinopathy in hospital patients].

Objective: To analyze the prevalence and risk factors of diabetic retinopathy (DR) in ophthalmic patients. Methods: A cross-sectional study was performed. Diabetic patients who were admitted to Department of Ophthalmology, Traditional Chinese Medicine Hospital of Muping between October 2012 and June 2013 were included. General information and medical history were obtained from each subject by questionaires. Laboratory and detailed ophthalmic examinations were performed during the study. DR was diagnosed and graded by mydriatic fundus photography. Prevalence of DR was calculated and logistic regression was used to analyze the relationship between DR and various factors. Results: A total of 676 diabetic patients were included, and 455 of them presented with DR at a morbidity rate of 67.31%. Among DR patients, the number of mild, moderate, severe non-proliferative diabetic retinopathy (NPDR) patients and proliferative diabetic retinopathy (PDR) patients were 211 (46.37%), 167 (36.70%), 57 (12.53%) and 20 (4.40%), respectively. There was no significant difference in the prevalence of DR among different age groups (χ(2)=6.527, P=0.089). However, there was a significant difference between different disease duration groups (χ(2)=39.401, P<0.001), as well as between insulin therapy group and non-insulin therapy group (χ(2)=7.378, P=0.007). The multivariate logistic regression analysis demonstrated the independent risk factors for DR occurrence were hemoglobin A1c (HbA1c) (OR=1.131, 95%CI: 1.022-1.252, P=0.011) and duration of diabetes (OR=1.077, 95%CI: 1.046-1.108, P<0.001). Conclusions: The prevalence of DR in ophthalmic patients was associated with duration of diabetes, HbA1c, obesity, smoke, nephropaty and insulin therapy. Increased HbA1c level and longer duration of diabetes were independent risk factors for DR in diabetic patients.

Protective Effect of a Novel Technique for Liver Transplantation in the Rat.

The rat orthotopic liver transplantation model with extremely short anhepatic phase was established to study its protective effect on the recipients and graft. One hundred fifty adult male Wistar rats were randomly divided into three groups: group A (n = 30), using magnetic rings for the suprahepatic vena cava reconstruction; group B (n = 30), using 7/0 Prolene sutures for suprahepatic vena cava running anastomosis as control; and a sham-operated group (n = 30) as a blank control group. The changes in liver enzyme, serum creatinine, endotoxin, and cytokine levels and histopathology were recorded. The serum creatinine, potassium, alanine transaminase, and alkaline phosphatase levels at different points in time in group A were lower than those in group B (P < .05). The level of portal vein blood endotoxin in group A was significantly lower than that in group B at each point (P < .01). At the same time, all the cytokines in group B were higher than those in group A, and the two groups were higher than those in the sham operation group. The mean levels of tumor necrosis factor-α (TNF-α), interferon-γ, (IFN-γ), and interleukin-1ß (IL-1ß) at 3 hours were higher than at 6 hours in group A. IL-10 and tissue inhibitor of metalloproteinase-1 (TIMP-1) were all higher at 3 hours in groups A and B. Levels of monocyte chemotactic protein-1, L-selectin, and TIMP-1 in group A and IL-10, monocyte chemotactic protein-1, L-selectin, and TIMP-1 in group B were higher in blood than in the liver. Levels of TNF-α, IFN-γ, IL-1, IL-10, and intracellular adhesion molecule-1 in group A and TNF-α, IFN-γ IL-1ß, and intracellular adhesion molecule-1 in group B were higher in the liver than in blood. We conclude that the extremely short anhepatic phase has protective effects on recipients and grafts in rat liver transplantation because it is related to alleviating ischemia-reperfusion injury and reducing the endotoxin release.

Prognostic significance of downregulated BMAL1 and upregulated Ki-67 proteins in nasopharyngeal carcinoma.

This study assessed the prognostic value of BMAL1 and Ki-67 expression in patients with nasopharyngeal carcinoma. Level of BMAL1 mRNA was assessed in tissue specimens from 36 nasopharyngeal carcinomas and 20 nasopharyngeal chronic inflammations using quantitative reverse transcriptase-polymerase chain reaction. Expression of BMAL1 and Ki-67 proteins was analyzed immunohistochemically in 90 paired nasopharyngeal carcinoma and distant normal tissues. The Kaplan-Meier curves and the Log-rank test were used to calculate prognostic significance stratified by BMAL1 and Ki67 protein expression and the COX regression model was to analyze the multivariate prognosis. BMAL1 mRNA was significantly reduced in nasopharyngeal carcinoma (4.67 ± 0.27 versus 6.64 ± 0.51 in chronic inflammation tissues, p = 0.002). Level of BMAL1 mRNA was associated with tumor distant metastasis (3.37 ± 0.66 versus 5.04 ± 0.27 compared with non-metastasis, p = 0.011). Level of BMAL1 protein was also reduced in tumor tissues and BMAL1 expression was associated with better 1-, 3- and 5-year overall survival (OS) of cancer patients (92.6%, 69.2% and 62.3% versus 59.1%, 40.9% and 0% in patients with low BMAL1 expressed tumors; p = 0.000). BMAL1 expression and age were independent prognostic factors for OS (p = 0.032). Furthermore, Ki-67 expression was high in tumor versus normal tissues and associated with poor OS of cancer patients (p = 0.035). The Pearson correlation analysis showed that there was an inverse association between BMAL1 and Ki-67 protein expression (p = 0.021). This study demonstrated that lost BMAL1 and Ki-67 overexpression were associated with poor OS of nasopharyngeal carcinoma patients.