Induction of cancer cell ferroptosis has been proposed as a potential treatment in several cancer types. Tumor-associated macrophages (TAMs) play a key role in promoting tumor malignant progression and therapy resistance. However, the roles and mechanisms of TAMs in regulating tumor ferroptosis is still unexplored and remains enigmatic. This study shows ferroptosis inducers has shown therapeutic outcomes in cervical cancer in vitro and in vivo. TAMs have been found to suppress cervical cancer cells ferroptosis. Mechanistically, macrophage-derived miRNA-660-5p packaged into exosomes are transported into cancer cells. In cancer cells, miRNA-660-5p attenuates ALOX15 expression to inhibit ferroptosis. Moreover, the upregulation of miRNA-660-5p in macrophages depends on autocrine IL4/IL13-activated STAT6 pathway. Importantly, in clinical cervical cancer cases, ALOX15 is negatively associated with macrophages infiltration, which also raises the possibility that macrophages reduce ALOX15 levels in cervical cancer. Moreover, both univariate and multivariate Cox analyses show ALOX15 expression is independent prognostic factor and positively associated with good prognosis in cervical cancer. Altogether, this study reveals the potential utility of targeting TAMs in ferroptosis-based treatment and ALOX15 as prognosis indicators for cervical cancer.

Next-generation sequencing has revolutionized family-based association tests for rare variants. As the lower power of genome wide association study for detecting casual rare variants, methods aggregating effects of multiple variants have been proposed, such as burden tests and variance component tests. This paper summarizes the methods of rare variants association test that can be applied for family data, introduces their principles, characteristics and applicable conditions and discusses the shortcomings and the improvement of the present methods.
Computer Simulation ; Family Relations ; Genetic Association Studies ; Genetic Variation ; Genome-Wide Association Study/methods* ; Humans

Objective: To evaluate the indication, safety and effectiveness of transoral robotic surgery (TORS) for oropharyngeal cancer based on our preliminary experience. Methods: Twelve patients, including six with tonsil cancer, five with tongue base cancer and one with posterior pharyngeal wall cancer, who underwent TORS with Da Vinci Si surgical system from March 2017 to October 2018 at Tongji Hospital of Huazhong University of Science Technology were respectively analyzed. And the surgical time, intraoperative blood loss, postoperative local bleeding, dyspnea, nerve function injury, oral intake time, whether or not to receive chemoradiotherapy were analyzed. Results: All tumors in the 12 patients were en bloc removed by TORS. Surgical time ranged from 25 to 80 min with an average of 34.2 min. The blood loss ranged from 10 ml to 50 ml with an average of 20.8 ml. The recovery time for oral intake ranged from 1 day to 30 days with an average of 8.4 days. No patient underwent tracheostomy after TORS. Also, no patient manifested with airway obstruction, bleeding or nerve injury symptoms after operation. All 12 patients reached pathologically negative surgical margins. The patients were followed up for 4 to 22 months, with a median of 12 months. All patients who combined with more advanced than T3 stage, or more advanced than N2 stage were recommended to oncologist, then, followed with radiotherapy or chemoradiotherapy if no relevant contradictions occurred. No local recurrence or distant metastasis case was found. Conclusion With proper indications, the application of TORS in oropharyngeal cancer is a relatively safe, effective and minimal invasive therapy, which merits more clinical applications.

Objective: To explore the relationship between glycemic control and visceral adiposity index (VAI) among type 2 diabetes mellitus (T2DM) patients.Methods: A community-based epidemiological field study for patients with T2DM aged ≥ 40 years was conducted in China.Every participant underwent physical examinations, biochemical tests of fasting glucose, glycosylated hemoglobin (HbA1c), total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and so on, and a questionnaire, including anthropometric characteristics, lifestyle, disease history, family history, and medication use.Those participants with HbA1c ≥7.0% were classified as the poorly controlled in our analysis of relationship between glycemic control and VAI.Anthropometric characteristics, lifestyle, and biochemical indexes of the participants were compared among the groups of different VAI levels.Logistic models were applied in multiple analysis adjusting for possible confounders.Results: A total of 1 607 patients with T2DM were recruited in our analysis with a mean age of (59.4±8.1) years and an average T2DM duration of (7.0±6.4) years.Among them, 78.3% were on hypoglycemic therapy.The cutoff points of quartiles of VAI were calculated for the males and females, respectively.According to the ascending order of the quartiles of VAI, the participants were divided into four groups, i.e.Q1, Q2, Q3, and Q4.The poor glycemic control rate for these groups were 60.6%, 65.7%, 70.1%, and 71.0%, respectively (Trend χ2=12.20, P<0.001).After adjustment for age, gender, systolic blood pressure (SBP), diastolic blood pressure (DBP), LDL-C, smoking, cardio-cerebral vascular disease (CVD) history, hypoglycemic therapy, T2DM duration, and family history of diabetes, the Logistic regression models showed that the glycemic control rate was significantly associated with VAI levels among the patients with T2DM.Compared with the participants in group Q1, the ORs of poor glycemic control for those in groups Q2, Q3, and Q4 were 1.239 (95%CI 0.918 to 1.672), 1.513 (95%CI 1.117 to 2.050), and 1.535 (95%CI 1.128to 2.088), respectively (trend P=0.003).With each quartile increase in VAI, the OR of poor glycemic control was 1.162 (95%CI 1.054 to 1.282).Conclusion: The glycemic control among the patients with T2DM is significantly associated with VAI.High level of VAI is an indicator of poor glycemic control.

Objective To explore the relationship between type 2 diabetes mellitus(T2DM)and serum stromal cell derived factor-1(SDF-1)levels. Methods A community-based epidemiological field study for T2DM patients and non-T2DM subjects was conducted in Beijing,China. Every subject underwent physical examinations, biochemical tests of stromal cell derived factor 1 and so on,and completed a standardized questionnaire. A total of 756 subjects were recruited in our analysis ,including 267 T2DM patients and 489 non-T2DM subjects ,T2DM patients were further divided into 81 simple T2DM patients and 186 macrovascular complication patients on the basis of the status of macrovascular complication. The correlation between serum SDF-1 levels and T2DM was analyzed. Results Compared with non-T2DM group,the level of SDF-1 in T2DM group was higher(P=0.019). The level of SDF-1 in simple T2DM group was also higher than macrovascular complication group(P=0.044). In the multi-ple linear regression analysis,after adjustment for age,gender,smoking,drinking,dyslipidemia,hypertension and BMI,SDF-1 level in simple T2DM group was higher than macrovascular complication group(P = 0.049), still. Conclusions Simple T2DM patients had a higher serum SDF-1 level than T2DM patients with macrovascular complications as well as those who did not suffer T2DM,suggesting that the stromal cell derived factor-1 may play a certain role in the development of T2DM and macrovascular complications.

Purpose To explore brain MRI features in newborn infants with incontinentia pigmenti,and to enhance the understanding and diagnosis level of this disease.Materials and Methods A retrospective analysis on MRI data of 13 neonates with incontinentia pigmenti admitted to Hunan Children's Hospital from January 2009 to December 2016 and further confirmed by clinical,pathology and gene diagnosis were conducted.Such conventional MRI sequences as T1WI and T2WI as well as DWI and SWI sequences wereincorporated.Results Five out of 13 newborn infants with incontinentia pigmenti were abnormal in the MRI features.In the conventional sequence,slightly short T1 signals in bilateral frontal lobe and right parietal occipital cortex were identified in 3 cases,right basal ganglia hemorrhage in 1 case.Slightly short TI and long T2 signals in bilateral basal ganglia were observed in 1 case;1 case of subarachnoid hemorrhage and 1 ease of bilateral lateral ventriculomegaly were noticed as well.The lesion sites of 4 cases were observed high density signal in DWI findings,three of which were widely distributed in abnormal signals.Lobes deep in bilateral cerebral hemispheres and subcortical white matter,bilateral basal ganglia,thalamus,internal capsule,corpus callosum,brain stem and cerebellum were the most affected areas.DWI could detect lesion area earlier and more accurate thanconventional sequences.Conclusion Incontinentia pigmenti among newborn infants demonstrates a high incidence.MRI examination should be adopted the moment neurological symptoms occur.Incontinentia pigmenti is relatively distinct in DWI findings,and hence is helpful for early detection of lesions and evaluation of clinical prognosis.

Purpose Brain complications severely threaten the treatment and survival of children with leukemia. This paper aims to investigate the MRI manifestations and differences of brain complications in leukemia before and after chemotherapy for a clinical guidance.Materials and Methods The clinical data and MRI findings of 37 children with leukemia and brain complications were retrospectively analyzed. Thirty-four of them underwent MRI scan twice or more, among whom 28 received contrast-enhanced MRI scan.Results Twenty-two patients were discovered with brain complications before chemotherapy, 2 of whom were with two kinds of complications. Meningopathy was found in 7 patients who showed widespread or localized meningeal thickening. Among them, 5 patients'' lesions reduced or disappeared after chemotherapy. Intracerebral multiple small and micro bleed was found in these 7 patients, 2 of them combined with hematoma. Three patients were found with intracranial tumor which all proved to be temporal bone tumor, 1 of whom combined with temporal lobe tumor and 1 had tumor disappeared after chemotherapy. The other complications before chemotherapy included leukoencephalopathy (n=2), subdural collection of fluid (n=2), meninges and parenchymal infiltration of leukemia (n=1), fungal infection (n=1) and cerebral infarction (n=1). On the contrary, 17 patients were discovered with brain complications after chemotherapy, 8 of whom were with two or more complications. Two patients had different kinds of complications before and after chemotherapy. Brain atrophy was observed in 13 patients. Leukoenphalopathy was found in 9 patients who presented high signal in white matter of double periventricular and/or semi-oval center on T2WI; the lesions of 4 patients were reduced or disappeared after withdrawal. Infectious diseases were diagnosed in 3 patients, including viral encephalitis in 2 cases, tuberculous meningitis combined with tuberculoma in 1 case. The other complications included intracranial tumor (n=2), sinus thrombosis (n=1), posterior reversible encephalopathy syndrome (n=1) after chemotherapy. Conclusion The MRI findings of brain complications in childhood leukemia are various and demonstrate significantly different features before and after chemotherapy. The major complications before treatment include meningopathy and intra-cerebral hemorrhage;while after chemotherapy the main complications are brain atrophy, leukoencephalopathy and infectious diseases. MRI proves to be a valuable method to detect, observe and follow up these complications.

Objective:To explore the correlation between glycemic control of type 2 diabetes mellitus (T2DM) patients and brachial-ankle pulse velocity (baPWV). Methods:A community-based cross-sec-tional study was conducted in Beijing, China. Every subject underwent physical examinations, glycated hemoglobin ( HbA1 c ) , blood lipid and baPWV measurements and completed a standardized question-naire. T2DM patients were divided into well controlled and poorly controlled groups according to HbA1c levels. The correlation between glycemic control of T2DM patients and baPWV was analyzed. Results:In this study, 1 341 subjects were recruited, including 733 T2DM patients and 608 non-diabetes sub-jects. Compared with non-diabetes subjects, abnormal baPWV ( baPWV≥1 700 cm/s) rate for T2DM patients was higher (40. 8% vs. 26. 8%, P<0. 001). With HbA1c<6. 5% or <7. 0% as the aim of glycemic control in T2DM patients, the abnormal baPWV rates for non-diabetes subjects, well controlled and poorly controlled T2DM patients were significantly different (non-diabetes vs. HbA1c<6. 5% T2DM vs. HbA1c≥6. 5% T2DM: 26. 8% vs. 32. 8% vs. 42. 6%, P <0. 001; non-diabetes vs. HbA1c <7. 0% T2DM vs. HbA1c≥7. 0% T2DM:26. 8% vs. 36. 1% vs. 43. 4%, P<0. 001). After being ad-justed for gender, age, smoking status, diabetes mellitus family history, T2DM duration, cardiovascular diseases ( CVD ) , waist hip ratio ( WHR ) , systolic blood pressure ( SBP ) , diastolic blood pressure ( DBP) , total triglycerides ( TG) , high density lipoprotein cholesterol ( HDL-C) , and low density lipo-protein cholesterol ( LDL-C ) , the Logistic regression models suggested that glycemic control status of T2DM patients was associated with abnormal baPWV. Compared with non-diabetes subjects, the ORs for abnormal baPWV in HbA1 c <6 . 5% T2 DM patients and HbA1 c≥6 . 5% T2 DM patients were 0 . 927 (95%CI 0. 560-1. 537) and 1. 826 (95%CI 1. 287-2. 591). Compared with non-diabetes subjects, the ORs for abnormal baPWV in HbA1c<7. 0% T2DM patients and HbA1c≥7. 0% T2DM patients were 1. 210 (95%CI 0. 808-1. 811) and 1. 898 (95%CI 1. 313-2. 745). Conclusion:The glycemic con-trol status of T2DM patients from communities is significantly associated with baPWV. Poor glycemic con-trol is a risk factor for abnormal baPWV. Keeping HbA1c under control might lower the risk of cardiovas-cular diseases in T2DM patients.

Experimental pathology is an important part of life science research associated with animal experiment. Acquisition and fixation of optimum specimen and subsequent section of paraffin embedded tissue and dyeing are key factors playing important role in reliability, authenticity of pathological diagnosis.This paper summarizes the problems encountered in pathological section making of animal experiment and it correspond solutions.

Objective To screen the splicing isoforms of estrogen receptor βin the Beagle hypothalamic -pituitary -gonadal axis.Methods For ERβmRNA CDS sequence of eight exons, primers were designed confined to the CDS sequences of two sequential exons.Beagle hypothalamus, pituitary, ovary and uterus tissue cDNA were used as template, and corresponding sequences were amplified by PCR.PCR products were sequenced and aligned in the NCBI web site.The correct gene was then analyzed with DNAMAN comparative analysis software and handwork checking up, thus got the ERβsplicing isoforms of Beagle. Results Four beagle ER beta splicing isomers were obtained:exon 4 complete skipping ER βisomer (300 bp missing), two kind of Beagle ERβisoforms with partial exon 4 and partial exon 5 complicated missing (isoformⅠ334 bp missing and isoformⅡ265 bp missing), and exon 7 complete missing ERβsplicing isoforms (181 bp missing).Exon 4 complete skipping and exon 7 complete missing isomers had been obtained full length coding sequence, and the other two splicing isomers were partial coding sequence.Conclusion This project gained four ERβsplicing isomers of Beagle, and that will lay an important foundation for further study of their roles in the Beagle reproductive regulation mechanism.