[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.

[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.

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.

[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.

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.

Effects of neural stem cells on synaptic proteins and memory in a mouse model of Alzheimer's disease.

Transplanting neural stem cells (NSC) to the damaged brain has been regarded as a potential treatment for neurodegenerative diseases such as Alzheimer's disease (AD), a condition characterized by memory loss. We hypothesized that transplantation of NSC into the hippocampal regions of APP + PS1 transgenic (Tg) mice, a well-established model of AD, would enhance the expression of synaptic proteins, which may be helpful for improving cognitive function. Our results showed that NSC transplantation significantly improved spatial learning and memory function in Tg mice. The results obtained by real-time RT-PCR, immunofluorescence, and Western blot analyses demonstrated that the expression of synaptophysin (SYN) and that of growth-associated protein-43 (GAP-43) in Tg-NSC mice, 8 weeks after transplantation, were significantly improved compared with what was observed in Tg-Veh (control) mice. This finding was confirmed by the increase in the number of synapses in Tg-NSC mice as observed via electron microscopy. Our results suggest that NSC-induced changes can recover memory loss in APP + PS1 transgenic mice, possibly by establishing new neural circuits resulting from the engrafted NSC.

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.

Non-equilibrium umbrella sampling applied to force spectroscopy of soft matter.

Physical systems often respond on a timescale which is longer than that of the measurement. This is particularly true in soft matter where direct experimental measurement, for example in force spectroscopy, drives the soft system out of equilibrium and provides a non-equilibrium measure. Here we demonstrate experimentally for the first time that equilibrium physical quantities (such as the mean square displacement) can be obtained from non-equilibrium measurements via umbrella sampling. Our model experimental system is a bead fluctuating in a time-varying optical trap. We also show this for simulated force spectroscopy on a complex soft molecule--a piston-rotaxane.

Genetic consequences of group living in Mongolian gerbils.

Social behavior can shape the local population genetic structure of mammals. Group living can increase pairwise genetic relatedness of mammals at a local level but differentiate the genetic structure at a population level through offspring philopatry and nonrandom mating. Our study aimed to test the hypothesis that social groups of Mongolian gerbils (Meriones unguiculatus) would consist of genetically related individuals due to offspring philopatry and would have distinct genetic structures because of restricted gene flow among social groups and nonrandom mating. We genotyped 327 wild gerbils, live captured from 28 social groups in Inner Mongolia, China, using nine microsatellite loci. The within-group pairwise genetic relatedness coefficient averaged 0.28 ± 0.14 (standard deviation), whereas the average pairwise genetic relatedness coefficient of the whole gerbil population was 0.0 ± 0.2. Additionally, the value of the global F statistic (F(st)) was 0.21, suggesting a substantial genetic differentiation among social groups of Mongolian gerbils. The Bayesian clustering divided the 327 gerbils into 23 distinct genetic clusters. Therefore, our results show that high within-group genetic relatedness and among-group genetic differentiation are the genetic consequences of group living in social mammals because of restricted gene flow, female philopatry, and nonrandom mating within social groups.

Hydrodynamic mobility of an optically trapped colloidal particle near fluid-fluid interfaces.

Using optical tweezers, we measure the anisotropic hydrodynamic mobility of a colloidal particle by tracking its thermal motion in an optical trap located near fluid-fluid interfaces, namely, liquid-vapor and liquid-liquid interfaces. The method requires no controlled fluid flow, is independent of conservative interactions between particle and interface, and resolves distance dependent friction to within a fraction of the particle radius. Near the liquid-vapor interface, the friction decreases below that in the bulk, corresponding to predictions of a "perfect-slip" surface.

Lens epithelial cell apoptosis appears to be a common cellular basis for non-congenital cataract development in humans and animals.

Cataract is a major ocular disease that causes blindness in many developing countries of the world. It is well established that various factors such as oxidative stress, UV, and other toxic agents can induce both in vivo and in vitro cataract formation. However, a common cellular basis for this induction has not been previously recognized. The present study of lens epithelial cell viability suggests such a general mechanism. When lens epithelial cells from a group of 20 cataract patients 12 to 94 years old were analyzed by terminal deoxynucleotidyl transferase (TdT) labeling and DNA fragmentation assays, it was found that all of these patients had apoptotic epithelial cells ranging from 4.4 to 41.8%. By contrast, in eight normal human lenses of comparable age, very few apoptotic epithelial cells were observed. We suggest that cataract patients may have deficient defense systems against factors such as oxidative stress and UV at the onset of the disease. Such stress can trigger lens epithelial cell apoptosis that then may initiate cataract development. To test this hypothesis, it is also demonstrated here that hydrogen peroxide at concentrations previously found in some cataract patients induces both lens epithelial cell apoptosis and cortical opacity. Moreover, the temporal and spatial distribution of induced apoptotic lens epithelial cells precedes development of lens opacification. These results suggest that lens epithelial cell apoptosis may be a common cellular basis for initiation of noncongenital cataract formation.

[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.

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.