Construction of molecular subgroups of ulcerative colitis.

OBJECTIVE: Ulcerative colitis (UC), a chronic inflammatory disease of the colon with unknown etiology, is characterized by remission and recurrence. At present, a considerable number of UC cases are misdiagnosed or delayed in diagnosis and treatment. We aimed to identify UC-related genes to aid the development of drugs for this condition. PATIENTS AND METHODS: Transcriptome data of 362 patients with UC and 126 control subjects were obtained from the Gene Expression Omnibus. The 362 patients with UC were subgrouped using unsupervised machine learning. R software was used to analyze the clinical characteristics of the subgroups, screen subgroup-specific genes, assess the relationships between gene modules and clinical characteristics using weighted gene co-expression network analysis, and perform Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the subgroups. RESULTS: Patients with UC were classified into two subgroups. Genes specific to subgroup I included IL21R, ATP8B2, and PLEKHO1. Severe disease tended to be associated with immune cell infiltration; anti-tumor necrosis factor (TNF)-α antibodies and ustekinumab may have been effective in this subgroup. Subgroup II-specific genes included SLC4A4, EPB41L4B, and PLCE1. Patients in this subgroup had mild clinical conditions; however, their disease was more likely to progress to colorectal cancer. Thus, 5-aminosalicylic acid-based drugs may be effective for the treatment of UC in these patients. CONCLUSIONS: We divided UC into two molecular subgroups based on transcriptome data, providing molecular evidence for the development of diagnostic methods and individualized treatment strategies for UC.

[Genetic analysis of a family with hereditary hemorrhagic telangiectasia caused by endoglin gene mutation].

Objective: To explore the genetic characteristics of a family with hereditary hemorrhagic telangiectasia (HHT) caused by endoglin (ENG) gene mutations. Methods: A total of 17 individuals from a 3-generation HHT family attending the First Affiliated Hospital of Dali University were selected as the research subjects. Clinical data and familial disease status of the HHT family proband were collected. Whole exome sequencing technology was used to screen for suspected pathogenic genes in the proband, and Sanger sequencing was used for family validation. Results: The proband and her mother had recurrent epistaxis and skin mucosal telangiectasia, and enhanced CT scans of the chest of the proband and her mother, daughter, and cousin indicated the presence of varying degrees of pulmonary arteriovenous malformations. The results of the full exon sequencing results showed that the proband carried the ENG gene c.579_599del non-shift deletion mutation, and Sanger sequencing showed that the mother, daughter, and cousin carried the same mutation. Conclusion: ENG gene c.579_ 599del mutation may be the genetic basis of HHT in this family.

[Advances in indocyanine green fluorescence imaging during hepatectomy].

While surgical operation is the preferred treatment for liver malignancies,the postoperative recurrence rate remains high. In the early 21st century,Japanese scientists first reported the use of indocyanine green(ICG) in liver resection. Follow-up studies also found its potential applications such as identifying tumors,determining surgical margins,delineating segmental boundaries,and preventing bile leakage. At present,ICG fluorescence imaging is applied to some types of hepatectomy with excellent effect and is expected to assist in generating surgical strategies for liver malignancies. However,its safety and efficacy still need further studies to evaluate.

[Clinical analysis of 16 children with traumatic basal ganglia stroke].

Objective: To investigate the clinical characteristics and risk-factors of traumatic basal ganglia stroke (TBGS) in children. Methods: A retrospective case study was conducted to analyze the clinical and imaging data of 16 children with TBGS in the First Hospital of Jilin University from January 2014 to June 2017. A total of 16 TBGS cases (11 males, 5 females) were diagnosed and the age ranged from 0.5 to 13.0 years. The prognosis of children with TBGS at different ages (≥5 years and<5 years) and with different traumatic stroke (infarction and hemorrhage) were compared. Fisher 's test was used to compare the prognosis of different groups. Results: All cases had clear history of head trauma and varying degrees of limb paralysis after injury, including 4 cases of facial paralysis, 3 cases of consciousness disturbance and 1 case of seizures. Head CT scan of the 16 cases showed 11 cases of ischemic stroke and 5 cases of hemorrhagic stroke. Moreover, scattered calcification was observed in the bilateral basal ganglia point of 8 cases. Neurotrophic treatment, microcirculation improvement and nerve rehabilitations were given according to the clinical and imaging data. One patient was treated with craniotomy and hematoma clearance. Of the 16 cases, 11 cases were restored to normal, while 3 cases developed limb paralysis and 2 cases died. The prognosis of 11 cases of traumatic basal ganglia infarction (10 cases recovered and 1 case remained hemiplegic) was relatively better than that of 5 cases of hemorrhage (1 case recovered, 2 cases remained hemiplegic and 2 cases died) (χ(2)=8.045, P=0.013). In addition, the children younger than 5-year-old (all 8 cases recovered) had a better prognosis than the children older than 5-year-old (8 cases, 3 of whom recovered, 3 cases remained hemiplegia, 2 cases died)(χ(2)=12.121, P<0.01). Conclusions: The anatomical characteristics of basal ganglia and calcification of the lenticulostriate artery are risk-factors for TBGS in children. The prognosis of infarcted children and younger children is relatively better.

A stress-induced cellular aging model with postnatal neural stem cells.

This corrects the article DOI: 10.1038/cddis.2014.82.

[A prospective multi-center trial of non-interventional and observational study of lenalidomide in Chinese patients with multiple myeloma].

Objective: To evaluate the efficacy and safety of lenalidomide in a real-world clinical practice in Chinese patients with multiple myeloma (MM). Methods: It was a prospective, multi-center, observational study. A total of 165 consecutive patients with MM treated with lenalidomide-based regimens were enrolled in 12 hospitals from June 2013 to November 2015. Relevant information was recorded, such as baseline clinical data, cytogenetic abnormalities, treatment regimens, and duration of treatment, safety, and survival. Results: (1)There were 126 relapsed and refractory MM (RRMM) patients, 25 newly diagnosed patients and 19 maintenance patients. The evaluable RRMM patients accounted for 120 cases, among which 74 cases(61.7%) reached the partial response (PR) or above, and a very good partial response (VGPR) in 16 patients (13.3%), a complete response (CR) in 14 cases (11.7%), a strictly complete response (sCR) in 4 cases (3.3%). Thus, a VGPR or above in 34 patients accounted for 28.3%. (2)The median follow-up was 13 months, the median time to progression 12 months. The median survival after receiving lenalidomide was 19 months, and the median overall survival (OS) was 62 months. (3) The univariate analysis in 120 RRMM patients suggested that prognostic factors for significant improvement in PFS included normal karyotype, international staging system (ISS) Ⅰ-Ⅱ, t(4; 14) negative (detected by fluorescence in situ hybridization), non-bortezomib resistance and response to previous regimens. As to OS, non-bortezomib resistance, response to previous regimens and non-primary refractoriness were positive factors. Multivariate analysis showed that the response to previous regimens (PR or better) was an independent good prognostic factor for progress-free survival(PFS), non-bortezomib resistance and non-primary refractoriness for OS. (4) Grade 3 or 4 adverse events that occurred in more than 10% of all enrolled patients were neutropenia (12.7%), leukocytosis(11.5%) and thrombocytopenia (12.7%). Owing to intolerance of toxic side effects, 7 cases withdrew lenalidomide. Conclusions: No matter what combination, regimens containing lenalidomide are effective to RRMM patients with overall response rate 61.7%, a time to progression 12 months and an overall survival 62 months.The toxicity is quite tolerable and manageable. In addition, the response to previous treatment (reached PR or above) is the independent good prognostic factor for PFS, non-bortezomib resistance and non-primary refractoriness for OS. Clinical trail registration: Clinicaltrials.gov, NCT01947309.

Analysis of circulating long non-coding RNA UCA1 as potential biomarkers for diagnosis and prognosis of osteosarcoma.

OBJECTIVE: The aim of this investigation was to examine the potential usefulness of long non-coding RNA UCA1 (UCA1) as a biomarker for diagnosis and prognosis in osteosarcoma. PATIENTS AND METHODS: The expression level of UCA1 was determined using TaqMan real-time PCR in human osteosarcoma tissues and patients' sera. Next, we investigated to clarify the relationship of UCA1 with clinicopathological features. The receiver operating characteristic (ROC) curve was performed to estimate the diagnostic value of UCA1. Finally, the prognosis of patients with osteosarcoma was assessed by Kaplan-Meier method and Cox proportional hazards model. RESULTS: We observed that UCA1 was significantly increased in osteosarcoma tissue compared with normal bone tissue (p<0.001) and the serum expression of UCA1 was significantly higher in patients with osteosarcoma than that in healthy controls (p<0.01). Up-regulation of UCA1 was correlated with clinical stage (p=0.001) and metastasis (p=0.007). Furthermore, serum UCA1 levels were observed to be robust in differentiating osteosarcoma patients from control subjects [area under the curve (AUC) = 0.831; 95% confidence interval (CI)= 0.746 to 0.916]. Kaplan-Meier analysis showed that that high UCA1 expression level was associated with poorer overall survival (p<0.001) and disease-free survival (p<0.001). Finally, Cox regression analyses showed that UCA1 expression might be an independent prognostic parameter to predict poor prognosis. CONCLUSIONS: Our study firstly showed that UCA1 could be a specific and noninvasive candidate biomarker for the diagnosis and prognosis of UCA1.

miR-542-3p targets sphingosine-1-phosphate receptor 1 and regulates cell proliferation and invasion of breast cancer cells.

OBJECTIVE: MicroRNAs (miRs) regulate the proliferation and metastasis of numerous cancer cell types. This study aimed to reveal the role of microRNA-542-3p (miR-542-3p) in breast cancer (BC) cell proliferation and its potential mechanisms. MATERIALS AND METHODS: MiR-542-3p expression was detected by reverse transcription-polymerase chain reaction (RT-PCR) and sphingosine-1-phosphate receptor 1(S1PR1) protein expression was measured by Western blotting. TargetScan was used to predict the downstream target genes of miR-542-3p, which were confirmed by luciferase and RNA immunoprecipitation assays. Biological functions of miR-542-3p and S1PR1 were analyzed using CKK-8, colony formation, migration, and invasion. RESULTS: It was demonstrated that the expression of miR-542-3p was downregulated in BC tissues and cell lines. We also showed that the expression of S1PR1 was upregulated in BC tissues and cell lines. Furthermore, we found that the expression level of miR-542-3p was negatively correlated with the expression level of S1PR1 in BC tissues. Over-expression of miR-542-3p inhibited BC cell proliferation, colony formation, migration and invasion. The dual luciferase reporter experiments showed that miR-542-3p regulated the expression of S1PR1 by combining with its 3'UTR. Finally, we showed that down-expression of miR-542-3p inhibited BC cell proliferation, colony formation, migration and invasion. CONCLUSIONS: Our study provides the new insight that miR-542-3p inhibited colon cancer cells via targeting S1PR1, suggesting that miR-542-3p/S1PR1 can serve as a potential therapeutic target for BC.

[Outcomes of mini-flank incision for open partial nephrectomy for stage T1b renal tumor].

Objective: To evaluate the safety and efficacy of mini-flank incision for open partial nephrectomy for stage T1b renal tumor. Methods: The data of patients with stage T1b renal tumor who underwent mini-flank incision for open partial nephrectomy between January 2010 to September 2015 were retrospectively reviewed. The Nephron-sparing surgery (NSS) was performed through mini-flank supra-12th rib incision under general anesthesia. Results: A total of 47 patients(31 male and 16 female) were enrolled in our study. The median age was 40 years (range 22-67 years). The Zhongshan Score(ZS score) of renal tumors was 6 in 5 cases, 7 in 13 cases, 8 in 12 cases, 9 in 5 cases, 10 in 6 cases, 11 in 2 cases, 12 in 2 cases, 13 in 2 cases. The length of incision was from 7 cm to 9 cm, with an average of 8.1 cm. The operative time was from 70 min to 150 min, with an average of 96 min. The blood loss was from 50 ml to 600 ml, with an average of 135 ml. The warm ischemia time was from 20 min to 35 min, with an average of 28 min. All of the surgery margin were negative. One patient had fluid in surgical region and relieved after the drainage, and one patient had acute myocardial infarction. The hospital stay time was from 5 d to 14 d, with an average of 8 d. The pathological diagnosis included clear cell carcinoma in 37 cases, multilocular cystic renal carcinoma in 1 case, chromophobe cell tumor in 4 cases, and papillary carcinoma in 5 cases. The mean preoperative serum creatinine level was 87 µmol/L(48-150 µmol/L) and with a mean of 91 µmol/L(52-148 µmol/L) at 3 month follow-up after surgery, and there was no difference between the preoperative and postoperative period(P>0.05). A total of 45 out of 47 patients were followed up for 36 to 78 months, with an average of 60 months, and no one had recurrence or metastasis during follow-up. Conclusion: Mini-flank incision for open partial nephrectomy for renal tumor with stage T1b is safe and effective, which is worthy of promotion and application for small incision and quick recovery.

Comparative analysis of platelet 5-HT concentrations in Han and Li patients with post-traumatic stress disorder.

We investigated the role of serotonin (5-HT) in the pathogenesis of post-traumatic stress disorder (PTSD) by determining the platelet 5-HT concentrations in Li and Han patients with PTSD in Hainan Province, China. Li and Han control groups of the same sample size have no statistical differences in gender and age distribution compared to those in the PTSD groups who were also examined. The platelet 5-HT concentrations were determined by high-performance liquid chromatography. In addition, the patients and controls were evaluated by the impact of event scale-revised (IES-R). IES-R showed that the total and sub-scale scores of three factors (avoidance, intrusion, and hyperarousal) of Li patients with PTSD were significantly higher than those of Han patients with PTSD. Scores of both PTSD groups were higher than those of their respective control groups. The platelet 5-HT concentration of the Li patients with PTSD (120.56 ± 118.05 ng/10(9) platelets) was lower than that of the Han patients with PTSD (271.43 ± 181.66 ng/10(9) platelets) and that of both Li and Han control groups (338.54 ± 156.46, 350.58 ± 169.19 ng/10(9) platelets, respectively). Differences existed in symptoms of PTSD in terms of avoidance, intrusion, and hyperarousal in the Li and Han patients with PTSD. The diminished 5-HT activity in patients with PTSD may be relevant to biochemical changes in the brain and body. The differences in these factors between ethnic groups could be due to their customs, social status, and culture.

PET/CT imaging in diagnosing lymph node metastasis of esophageal carcinoma and its comparison with pathological findings.

OBJECTIVE: To investigate the usefulness of 18F-FDG PET/CT imaging in the diagnosis of lymph node metastasis of esophageal carcinoma and to compare its results with pathological findings. PATIENTS AND METHODS: This study examined 43 cases of patients (32 males and 11 females, aged 54 ± 13 years old) being diagnosed with lymph node metastasis of esophageal carcinoma in our hospital between 2005 and 2014. All of these patients accepted 18F-FDG PET/CT imaging 10 days before the operation. Before reconstruction, each patient went through the body scan. PET/CT images were subject to comprehensive diagnostic analyses, by three experienced radiologists and/or professional nuclear physicians, on the number of metastatic lymph nodes and the maximum standardized uptake value (SUVmax). A control study was also performed on the pathological findings according to the latest esophageal cancer lymph node partition. RESULTS: A total of 846 lymph nodes were taken out from the patients, among which 154 were confirmed with metastasis. When the SUVmax cutoff values were set at 2.5 and 5, 201 and 173 metastatic lymph nodes were found by 18F-FDG PET/CT imaging, respectively. Additionally, under such condition, 18F-FDG PET/CT imaging had the esophageal sensitivity of 69.48% vs 87.66%, specificity of 92.71% vs 94.51%, accuracy of 83.33% vs 93.26%, positive predictive value of 53.23% vs 78.03%, and negative predictive value of 92.71% vs 97.18%. CONCLUSIONS: 18F-FDG PET/CT had high accuracy in imaging lymph node metastasis of esophageal cancer. SUVmax cutoff value of 5 had a higher diagnostic accuracy and should be recommended in clinical practice.

Emittance and lifetime measurement with damping wigglers.

National Synchrotron Light Source II (NSLS-II) is a new third-generation storage ring light source at Brookhaven National Laboratory. The storage ring design calls for small horizontal emittance (<1 nm-rad) and diffraction-limited vertical emittance at 12 keV (8 pm-rad). Achieving low value of the beam size will enable novel user experiments with nm-range spatial and meV-energy resolution. The high-brightness NSLS-II lattice has been realized by implementing 30-cell double bend achromatic cells producing the horizontal emittance of 2 nm rad and then halving it further by using several Damping Wigglers (DWs). This paper is focused on characterization of the DW effects in the storage ring performance, namely, on reduction of the beam emittance, and corresponding changes in the energy spread and beam lifetime. The relevant beam parameters have been measured by the X-ray pinhole camera, beam position monitors, beam filling pattern monitor, and current transformers. In this paper, we compare the measured results of the beam performance with analytic estimates for the complement of the 3 DWs installed at the NSLS-II.

Identification of key genes involved in HER2-positive breast cancer.

OBJECTIVE: As an invasive cancer, breast cancer is the most common tumour in women and is with high mortality. To study the mechanisms of HER2-positive breast cancer, we analyzed microarray of GSE52194. MATERIALS AND METHODS: GSE52194 was downloaded from Gene Expression Omnibus including 5 HER2-positive breast cancer samples and 3 normal breast samples. Using cuffdiff software, differentially expressed genes (DEGs) and differentially expressed long non-coding RNAs (DE-lncRNAs) were screened. Functions of the DEGs were analyzed by Gene Ontology (GO) and pathway enrichment analyses. Then, protein-protein interaction (PPI) network of the DEGs was constructed using Cytoscape and modules of the PPI network were screened by CFinder. Moreover, lncRNA-DEG pairs were screened. RESULTS: Total 209 lncRNA transcriptions were predicted, and 996 differentially expressed transcriptions were screened. Besides, FOS had interaction relationships with EGR1 and SOD2 separately in module E and F of the PPI network for the DEGs. Moreover, there were many lncRNA-DEG pairs (e.g. TCONS_00003876-EGR1, TCONS_00003876-FOS, lnc-HOXC4-3:1-FOS, lnc-HOXC4-3:1-BCL6B, lnc-TEAD4-1:1-FOS and lnc-TEAD4-1:1-BCL6B), meanwhile, co-expressed DEGs of TCONS_00003876, lnc-HOXC4-3:1 and lnc-TEAD4-1:1 were enriched in p53 signaling pathway, MAPK signaling pathway and cancer-related pathways, respectively. CONCLUSIONS: ANXA1, EGR1, BCL6, SOD2, FOS, TCONS_00003876, lnc-HOXC4-3:1 and lnc-TEAD4-1:1 might play a role in HER2-positive breast cancer.

Clinical research of persimmon leaf extract and ginkgo biloba extract in the treatment of vertebrobasilar insufficiency.

This paper aims to compare the curative effects of persimmon leaf extract and ginkgo biloba extract in the treatment of headache and dizziness caused by vertebrobasilar insufficiency. Sixty patients were observed, who underwent therapy with persimmon leaf extract and ginkgo biloba extract based on the treatment of nimodipine and aspirin. After 30 days, 30 patients treated with persimmon leaf extract and 30 patients with ginkgo biloba extract were examined for changes in hemodynamic indexes and symptoms, such as headache and dizziness. The results showed statistically significant differences of 88.3% for the persimmon leaf extract and 73.1% for the ginkgo biloba extract, P < 0.05. Compared to the group of ginkgo biloba extract, the group of persimmon leaf extract had more apparent improvement in the whole blood viscosity, plasma viscosity, fibrinogen, hematokrit, and platelet adhesion rate, and the difference was statistically significant (P < 0.05 or P < 0.01). Based on these analyses, it can be concluded that persimmon leaf extract is better than ginkgo biloba extract in many aspects, such as cerebral circulation improvement, cerebral vascular expansion, hypercoagulable state lowering and vertebrobasilar insufficiency-induced headache and dizziness relief.