[Acute lymphoblastic leukemia complicated with cerebral venous thrombosis in 14 children].

Objective: To explore the clinical characteristics and management of childhood acute lymphoblastic leukemia (ALL) complicated with cerebral venous thrombosis (CVT). Methods: The clinical data of 14 ALL children complicated with CVT who were admitted to Department of Pediatrics of Sun Yat-sen Memorial Hospital and underwent chemotherapy from January 2011 to October 2019 were collected retrospectively. The clinical manifestations, coagulation function, imaging findings, treatment plan and prognosis of patients were analyzed. Results: CVT was diagnosed in 14 (2.8%, 14/505) cases, with a median age of 10 (3-14) years at onset, 11 cases occurred in the stage of induction remission, and the acute onsets were mainly characterized by convulsions (9 cases), consciousness disorders (6 cases) and headache (4 cases). Coagulation function test showed that, before the CVT, antithrombin Ⅲ activity was lower than 60% in 8 cases, D-dimer elevated on the day of onset in 8 cases. Arteriovenous angiography showed filling defects in single (9 cases) or multiple (5 cases) venous sinuses. The most common site of venous sinus enlargement was superior sagittal sinus (10 cases). Secondary cerebral hemorrhage was found in 5 cases. Anticoagulation therapy included combination of low-molecular-weight heparin (LMWH) and warfarin in 9 cases, sequential application of LMWH and warfarin in 2 cases, and LMWH alone in 3 cases. Patients accepted further asparaginase and no CVT recurrence or progression was found. Conclusions: The secondary coagulation dysfunction during induction remission chemotherapy is the major risk factor for CVT in ALL, which needs active monitoring and early prevention. Arteriovenous angiography can diagnose accurately, and the prognosis of anticoagulant therapy with LMWH and warfarin is optimistic.

[Statistical parametric mapping analysis of 18F-FDG PET in Parkinson's disease with mild cognitive impairment].

Objective: To investigate the characteristics of cerebral metabolism associated with mild cognitive impairment (MCI) Parkinson's disease (PD), cognitive normal PD and normal control to find a PET biomarker for the diagnose and estimate of PD-MCI. Methods: Forty-seven patients diagnosed with PD (included 15 with mild cognitive impairment) and 20 control subjects were enrolled. All the subjects were evaluated with FDG-PET and clinical scale. The statistical parametric mapping (SPM) were analyzed to determine metabolic patterns that may be useful in differentiating between the three groups. Results: SPM analysis showed that significant hypometabolism were observed in both side of front lobe, parietal lobe, left temporal lobe and left occipital lobe; in the contrast, the relative hypermetabolism had been observed in the cerebellum, vermis, hippocampus and supplement motor area (SMA) in patients with PD-MCI. PD without MCI showed hypometabolism in both side of front lob, caudate and putamen. PD-MCI showed that the significant hypermetabolism were in the insular and cerebellum while hypometabolism were in the both side of occipital compared to PD without MCI. Conclusion: A voxel-by-voxel based SPM method i. e. SPM8 analysis by PET scan is an effective way to analysis the FDG uptake pattern of PD patients. The hypermetabolism in the insula and cerebellum and hypometabolism in the both side of occipital may be a biomarker for make a diagnosis of PD-MCI.

[A comparison of dosimetric variance for external-beam partial breast irradiation using three-dimensional and four-dimensional computed tomography].

Objective: To investigate the potential dosimetric benefits of four-dimensional computed tomography (4DCT) compared to three-dimensional CT (3DCT) in the planning of radiotherapy for external-beam partial breast irradiation (EB-PBI). Methods: Three-DCT and 4DCT scan sets were acquired for 20 patients who underwent EB-PBI. For each patient a conventional 3D conformal plan (3D-CRT) was generated based on end-inhalation phase (EI). The treatment plan based on the 4DCT EI phase images was copied and applied to the end-exhalation phase (EE) and 3DCT images (defined as EB-PBI(EI), EB-PBI(EE), EB-PBI(3D), respectively). Results: The median volumes of the tumour bed based on 3DCT, EI and EE were 20.99 cm(3,) 19.28 cm(3,) and 18.78 cm(3,) respectively. The tumour bed volume based on 3DCT was significantly greater than that of EI and EE volumes (P<0.05). The planning target volumes (PTV) coverage of EB-PBI(3D), EB-PBI(EI) and EB-PBI(EE) were 96.85%, 97.51%, 97.03%, respectively. The planning target volume (PTV) coverage of EB-PBI(3D) was significantly less than that of EB-PBI(EI) and EB-PBI(EE) (P<0.05). The median homogeneity indexs (HI) based on 3DCT, EI and EE were 0.13, 0.13, 0.13, respectively. The median conformal indexs (CI) based on 3DCT, EI and EE were 0.68, 0.69, 0.68, respectively. The median mean doses (D(mean)) based on 3DCT, EI and EE were 36.20 Gy, 36.20 Gy, 36.22 Gy, respectively. However there were no significant differences in the homogeneity index, conformity index and the mean dose of PTV between the three treatment plans (P>0.05). The EB-PBI(3D) plan resulted in the largest organs at risk dose (P<0.05). Conclusion: There was a significant benefit when using 4DCT to plan 3D-CRT for EB-PBI with regard to reduced non-target organ exposure, and might result in poor dose coverage when the PTV is determined using 3DCT.

Expression of the fetal hematopoiesis regulator FEV indicates leukemias of prenatal origin.

The origin of cancers is associated with etiology as well as therapeutics. Several studies reveal that malignancies in children can originate in utero. However, a diagnostic approach to distinguish between cancers initiated pre- or postnatally is absent. Here we identified a transcriptional factor FEV (fifth Ewing variant) that was expressed in fetal hematopoietic cells and became silent after birth. We characterized that FEV was essential for the self-renewal of hematopoietic stem cells (HSCs). We next found that FEV was expressed in most infant leukemia samples, but seldom in adult samples, in accord with the known prenatal origins of the former. We further determined the majority of pediatric acute lymphoid leukemia (ALL) and acute myeloid leukemia (AML) were FEV positive. Moreover, FEV knockdown markedly impaired the leukemia-propagating ability of leukemic stem cells. We therefore identified FEV is unique to fetal HSCs and stably expressed in leukemic cells of prenatal origin. It may also provide a tractable therapeutic target.

Relative contributions of testosterone deficiency and metabolism syndrome at the risk of reduced quality of life: A cross-sectional study among Chinese mid-aged and elderly men.

Testosterone deficiency and metabolism syndrome (MetS) are universal among ageing males, and they have been suggested responsible for poorer quality of life (QoL). We aimed to evaluate the relative contributions of reproductive hormones and components of MetS at the risk of reduced QoL among Chinese mid-aged and elderly men. A cross-sectional study recruited 2,364 males aged 40-79 years, and 2,165 was included for analysis eventually. The Chinese version of ageing male symptoms scale, 36-item Short Form and Beck Depression Inventory were applied to assess QoL. Bivariate correlation analysis and multiple linear regression analysis were used to assess the relative contributions of reproductive hormones and components of MetS at the risk of reduced QoL. Testosterone deficiency and MetS contributed to poorer QoL, of which higher fasting blood glucose made the primary contribution, lower total testosterone mainly contributed to poorer physical functioning.

The rs5934505 single nucleotide polymorphism (SNP) is associated with low testosterone and late-onset hypogonadism, but the rs10822184 SNP is associated with overweight and obesity in a Chinese Han population: a case-control study.

Low testosterone is associated with late-onset hypogonadism (LOH) and obesity. Recently, studies have shown that four single nucleotide polymorphisms (SNPs), rs12150660, rs727428, rs5934505, and rs10822184, are associated with testosterone levels in populations of European descent. Therefore, we investigated whether the SNP loci are related to low testosterone, LOH, or obesity in a Chinese Han population. Ruling out co-morbidities, DNA was prepared from 409 men (aged 40-65 years) with low serum testosterone (defined as total testosterone <11.6 nmol/L) and 1 : 1 normal controls (matched age, body mass index (BMI), and the same living area) who were selected from 6898 males. According to the same standards, 310 men with LOH and 1 : 1 normal controls were selected from 6898 males. Excluding the cases with an unreliable sequencing result, genetic analyses were performed. The minor allele frequencies of the SNP loci rs12150660, rs727428, rs5934505, and rs10822184 were 0.1%, 44.6%, 18.7%, and 38.9%, respectively. rs5934505 was associated with the serum total testosterone and calculated free testosterone (CFT) levels (p = 0.045 and p = 0.021). rs5934505 (C>T) was associated with an increased risk of low total testosterone, low CFT, and LOH and adjusted for other factors, with an odds ratio (OR) of 2.01 (1.34-3.01), 2.14 (1.42-3.20), and 1.64 (1.04-2.58). rs10822184 was significantly correlated with weight and BMI (p = 0.035 and p = 0.027). rs10822184 (T>C) was associated with an increased risk of overweight and obesity. We adjusted for other factors, with odds ratios (ORs) of 1.94 (1.36-2.78) and 1.56 (1.00-2.43). In summary, our study provided convincing evidence that rs5934505 (C>T) was associated with the risk of low testosterone and LOH in Chinese populations. We were the first to find that rs10822184 (T>C) was significantly correlated with the risk of overweight and obesity in Chinese populations. However, further large and functional studies are warranted to confirm our findings.

The silkworm GSTe4 is sensitive to phoxim and protects HEK293 cells against UV-induced cell apoptosis.

Glutathione S-transferases (GSTs, EC 2.5.1.18) are a family of super enzymes with multiple functions that play a major role in the detoxification of endogenous and xenobiotic compounds. In our previous study, we have predicted 23 putative cytosolic GSTs in the silkworm genome using bioinformatic methods. In this study, we cloned and studied the insect-specific epsilon-class GST gene GSTe4 from the silkworm, Bombyx mori. The recombinant BmGSTe4 (Bac-BmGSTe4) was overexpressed in SF-9 cell lines, and it was found to have effective GST activity. We also found that the expression of BmGSTe4 was especially down-regulated after the silkworms were fumigated with or ingested phoxim. Moreover, BmGSTe4 protected HEK293 cells against UV-induced cell apoptosis. These results demonstrated that BmGSTe4 has GST activity, is sensitive to phoxim, and plays a role in inhibition of UV-induced cell apoptosis.

Transcatheter arterial embolization of acute gastrointestinal tumor hemorrhage with Onyx.

BACKGROUND: Endovascular embolization has been used to control gastrointestinal tumor bleeding. Lots of embolic agents have been applied in embolization, but liquid embolic materials such as Onyx have been rarely used because of concerns about severe ischemic complications. AIM: To evaluate the clinical efficacy and safety of transcatheter arterial embolization (TAE) with Onyx for acute gastrointestinal tumor hemorrhage. MATERIALS AND METHODS: Between September 2011 and July 2013, nine patients were diagnosed as acute gastrointestinal tumor hemorrhage by clinical feature and imaging examination. The angiographic findings were extravasation of contrast media in the five patients. The site of hemorrhage included upper gastrointestinal bleeding in seven cases and lower gastrointestinal bleeding in two cases. TAE was performed using Onyx in all the patients, and the blood pressure and heart rate were monitored, the angiographic and clinical success rate, recurrent bleeding rate, procedure related complications and clinical outcomes were evaluated after therapy. The clinical parameters and embolization data were studied retrospectively. RESULTS: All the patients (100%) who underwent TAE with Onyx achieved complete hemostasis without rebleeding and the patients were discharged after clinical improvement without a second surgery. No one of the patients expired during the hospital course. All the patients were discharged after clinical improvement without a second surgery. Postembolization bowel ischemia or necrosis was not observed in any of the patients who received TAE with Onyx. CONCLUSIONS: TAE with Onyx is a highly effective and safe treatment modality for acute gastrointestinal tumor hemorrhage, even with pre-existing coagulopathy.

Erosive pustular dermatosis of the leg mimicking lower limb cellulitis.

Erosive pustular dermatosis (EPD) of the leg is an unusual form of amicrobial pustulosis, which typically affects elderly patients with chronic venous insufficiency. We report a patient who presented with painful erythema, crusted erosions and pustules on her right lower leg. Histology showed a dermal infiltration made up predominantly of neutrophils. Bacteria were isolated from the lesions. The condition was initially diagnosed as cellulitis, but antibiotic treatment was unsuccessful. After the correct diagnosis was made, complete resolution was obtained with betamethasone 0.05%.

Development and clinical validation of an unobtrusive ambulatory knee function monitoring system with inertial 9DoF sensors.

Patients suffering from end-stage knee osteoarthritis are often treated with total knee arthroplasty, improving their functional mobility. A number of patients, however, report continued difficulty with stair ascent and descent or sportive activity after surgery and are not completely satisfied with the outcome. State-of-the-art analyses to evaluate the outcome and mobility after knee replacement are conducted under supervised settings in specialized gait labs and thus can only reflect a short period of time. A number of external factors may lead to artificial gait patterns in patients. Moreover, clinically relevant situations are difficult to simulate in a stationary gait lab. In contrast to this, inertial sensors may be used additionally for unobtrusive gait monitoring. However, recent notable approaches found in literature concerning knee function analysis have so far not been applied in a clinical context and have therefore not yet been validated in a clinical setting. The aim of this paper is to present a system for unsupervised long-term monitoring of human gait with a focus on knee joint function, which is applicable in patients' everyday lives and to report on the validation of this system gathered during walking with reference to state-of-the-art gait lab data using a vision system (VICON Motion System). The system KINEMATICWEAR - developed in close collaboration of computer scientists and physicians performing knee arthroplasty - consists of two sensor nodes with combined tri-axial accelerometer, gyroscope and magnetometer to be worn under normal trousers. Reliability of the system is shown in the results. An overall correlation of 0.99 (with an overall RMSE of 2.72) compared to the state-of-the-art reference system indicates a sound quality and a high degree of correspondence. KINEMATICWEAR enables ambulatory, unconstrained measurements of knee function outside a supervised lab inspection.

EZH2 supports nasopharyngeal carcinoma cell aggressiveness by forming a co-repressor complex with HDAC1/HDAC2 and Snail to inhibit E-cadherin.

The enhancer of zeste homolog 2 (EZH2) is upregulated and has an oncogenic role in several types of human cancer. However, the abnormalities of EZH2 and its underlying mechanisms in the pathogenesis of nasopharyngeal carcinoma (NPC) remain unknown. In this study, we found that high expression of EZH2 in NPC was associated closely with an aggressive and/or poor prognostic phenotype (P<0.05). In NPC cell lines, knockdown of EZH2 by short hairpin RNA was sufficient to inhibit cell invasiveness/metastasis both in vitro and in vivo, whereas ectopic overexpression of EZH2 supported NPC cell invasive capacity with a decreased expression of E-cadherin. In addition, ablation of endogenous Snail in NPC cells virtually totally prevented the repressive activity of EZH2 to E-cadherin, indicating that Snail might be a predominant mediator of EZH2 to suppress E-cadherin. Furthermore, co-immunoprecipitation (IP), chromatin IP and luciferase reporter assays demonstrated that in NPC cells, (1) EZH2 interacted with HDAC1/HDAC2 and Snail to form a repressive complex; (2) these components interact in a linear fashion, not in a triangular fashion, that is, HDAC1 or HDAC2 bridge the interaction between EZH2 and Snail; and (3) the EZH2/HDAC1/2/Snail complex could closely bind to the E-cadherin promoter by Snail, but not YY1, to repress E-cadherin. The data provided in this report suggest a critical role of EZH2 in the control of cell invasion and/or metastasis by forming a co-repressor complex with HDAC1/HDAC2/Snail to repress E-cadherin, an activity that might be responsible, at least in part, for the development and/or progression of human NPCs.

CIP2A mediates effects of bortezomib on phospho-Akt and apoptosis in hepatocellular carcinoma cells.

Previously, we reported that Akt inactivation determines the sensitivity of hepatocellular carcinoma (HCC) cells to bortezomib. In this study, we report that cancerous inhibitor of protein phosphatase 2A (CIP2A), a cellular inhibitor of protein phosphatase 2A (PP2A), mediates the apoptotic effect of bortezomib in HCC. Silencing PP2A by small interference RNA (siRNA) abolishes bortezomib-induced down-regulation of phospho-Akt and apoptosis. Bortezomib increases PP2A activity in sensitive HCC cells, including Sk-Hep1, Hep3B and Huh-7, but not in resistant PLC5 cells. Bortezomib down-regulates CIP2A in a dose- and time-dependent manner in all sensitive HCC cells, whereas no alterations in CIP2A were found in resistant PLC5 cells. Knockdown of CIP2A by siRNA restored bortezomib's effects on apoptosis and PP2A activity in PLC5 cells. Moreover, over-expression of CIP2A up-regulated phospho-Akt and protected Sk-Hep1 cells from bortezomib-induced apoptosis. It is significant that, ectopic expression of CIP2A decreased Akt-related PP2A activity, whereas silencing CIP2A increased this activity, indicating that CIP2A negatively regulates Akt-related PP2A activity in HCC cells, furthermore, our in vivo data showed that bortezomib down-regulates CIP2A and up-regulates PP2A activity in Huh-7 tumors, but not in PLC5 tumors. In conclusion, inhibition of CIP2A determines the effects of bortezomib on apoptosis and PP2A-dependent Akt inactivation in HCC.

Combined silencing of K-ras and Akt2 oncogenes achieves synergistic effects in inhibiting pancreatic cancer cell growth in vitro and in vivo.

Cancer is a complex disease involving multiple oncogenes with diverse actions. Inhibiting only one oncogene is unlikely to eliminate the malignancy of cancer cells. The goal of this study was to investigate whether synergistic effects can be achieved by combined silencing of two oncogenes, K-ras and Akt2, which are key players in the Ras/MAPK and PI3K/Akt signaling pathways. The pancreatic cancer cell line, Panc-1, was selected for these studies as it has elevated expression of K-ras and Akt2. Compared with inhibiting each oncogene alone, simultaneously silencing the two oncogenes with RNA interference (RNAi) more effectively inhibited Panc-1 cell proliferation and colony formation, induced a significantly higher percentage of apoptosis and resulted in greater inhibition of c-myc expression in vitro. Furthermore, when delivered by polyethyleneimine into Panc-1 tumors in nude mice, RNAi simultaneously targeting K-ras and Akt2 inhibited tumor growth more efficiently than RNAi targeting the individual oncogenes. Therefore, RNAi simultaneously silencing the oncogenes K-ras and Akt2 may offer potential opportunities for pancreatic cancer gene therapy.

Diagnosis and treatment of caecal volvulus.

Caecal volvulus is an infrequently encountered clinical condition and an uncommon cause of intestinal obstruction. Patients with this condition may present with highly variable clinical presentations ranging from intermittent, self limiting abdominal pain to acute abdominal pain associated with intestinal strangulation and sepsis. Lack of familiarity with this condition is a factor contributing to diagnostic and treatment delays. The objective of this review is to promote clinicians' awareness of this disease through patient case illustration, discussion of disease pathogenesis, clinical features, and management strategies.

Application of three-dimensional body scanner: observation of prevalence of metabolic syndrome.

BACKGROUND AND AIMS: This retrospective cross-sectional study correlates blood pressure, blood glucose, lipid and uric acid levels with anthropometric measurements. METHODS: A total of 3975 visitors to the Department of Health Management were randomly selected to participate in this cross-sectional study. Whole body three-dimensional (3-D) laser scans were used to obtain anthropometric measurements. A health index (HI) was also designed based on anthropometric parameters. Subjects were defined as having metabolic syndrome when three of the following criteria were met: obesity (BMI of at least 30 kg/m(2); or a WHR of over 0.9 for males and 0.85 for females); triglyceride of at least 150 mg/dl; high-density lipoprotein (HDL)-cholesterol below 35 mg/dl for males and 39 mg/dl for females; fasting sugar levels of at least 110 mg/dl and hypertension. RESULTS: Of 3975 subjects, 341 (8.6%) met the criteria for diabetes mellitus (DM); of these, 32.8% were diagnosed with hypertension. This proportion exceeded 18% of the subjects had normal glucose levels. Of the 3975 subjects, 658 (16.6%) met the criteria for metabolic syndrome. Proportionally, more male subjects than female subjects were diagnosed with metabolic syndrome (18.5% vs 14.7%). Of these, central obesity, elevated triglyceride and low HDL-cholesterol were the main factors in men, while fasting glucose, hypertension and central obesity were the main factors in women. This investigation found that larger proportions of subjects with impaired glucose tolerance (41.1%) and DM (64.2%) than of subjects with normal glucose subjects, suffered from metabolic syndrome (9.5%). CONCLUSIONS: 3-D body scanning is useful in correlating pertinent factors with metabolic syndrome, these factors include central obesity, hyperglycemia, dyslipidemia, hyperuricemia and hypertension.

Protective effects of Chinese herbs on D-galactose-induced oxidative damage.

A mixture of traditional Chinese herbs ('FTDA') was found to improve several oxidation-related biomarkers in D-galactose-induced mimetic aging mice. FTDA consists of seven herbal components: Cuscutae Semen, Schisandrae Fructus, Dioscoreae Rhizoma, Lonicerae Flos, Nelumbinis Semen, Angelica Radix and Poria, and is routinely used for treating mice with D-galactose-induced oxidative damage. Measurements of antioxidant status, including superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), total antioxidant status (TAS) and malondialdehyde (MDA) were made on blood, brain and liver tissue collected from animals after 60 days of treatment with D-galactose subcutaneous injections. High-dose, medium-dose and control groups exhibited higher levels of SOD, GSH-Px and TAS in their blood, as well as lower levels of serum MDA activity, compared with the D-galactose group. In the liver, all three experimental and PBS groups demonstrated significant increases in SOD activity and a decrease in MDA activity. The MDA activity decreased in medium-dose, high-dose and PBS groups, while medium-dose and PBS groups demonstrated increased SOD activity compared with that seen in the brain. These results support the efficacy of FTDA in improving the antioxidant status of D-galactose-induced mimetic aging mice.