Intraventricular Hemorrhage Growth: Definition, Prevalence and Association with Hematoma Expansion and Prognosis.

BACKGROUND/OBJECTIVES: The objective of this study is to propose a definition of intraventricular hemorrhage (IVH) growth and to investigate whether IVH growth is associated with ICH expansion and functional outcome. METHODS: We performed a prospective observational study of ICH patients between July 2011 and March 2017 in a tertiary hospital. Patients were included if they had a baseline CT scan within 6 h after onset of symptoms and a follow-up CT within 36 h. IVH growth was defined as either any newly occurring intraventricular bleeding on follow-up CT scan in patients without baseline IVH or an increase in IVH volume ≥ 1 mL on follow-up CT scan in patients with initial IVH. Poor outcome was defined as modified Rankin Scale score of 3-6 at 90 days. The association between IVH growth and functional outcome was assessed by using multivariable logistic regression analysis. RESULTS: IVH growth was observed in 59 (19.5%) of 303 patients. Patients with IVH growth had larger baseline hematoma volume, higher NIHSS score and lower GCS score than those without. Of 44 patients who had concurrent IVH growth and hematoma growth, 41 (93.2%) had poor functional outcome at 3-month follow-up. IVH growth (adjusted OR 4.15, 95% CI 1.31-13.20; P = 0.016) was an independent predictor of poor functional outcome (mRS 3-6) at 3 months in multivariable analysis. CONCLUSION: IVH growth is not uncommon and independently predicts poor outcome in ICH patients. It may serve as a promising therapeutic target for intervention.

[Effect of Ginkgo biloba extract on the function of alveolar polymorphonuclear neutrophils in severe acute pancreatitis rats complicated with lung injury].

OBJECTIVE: To explore the effect of Ginkgo biloba extract (GBE) on the function of alveolar polymorphonuclear neutrophils (PMN) in severe acute pancreatitis (SAP) rats complicated with lung injury (LI). METHODS: Forty-eight adult SD rats were randomly divided into three groups, i.e., the sham-operation group, the SAP group, and the GBE treatment group, 16 in each group. The SAP model was successfully induced by retrograde injection of 5% sodium taurocholate solution into the biliopancreatic duct. Rats in the sham-operation group only received flipping of the duodenum. Those in the GBE treatment group received GBE intervention based on SAP model. Equal volume of normal saline was given to rats in the sham-operation group and the SAP group. Rats were sacrificed at 6 and 12 h after operation respectively. The lung tissue was sampled to evaluate the LI score. The wet/dry ratio (W/D) of lung tissues was detected. The activity of myeloperoxidase (MPO) was measured. Alveolar PMN was harvested by bronchoalveolar lavage. The content of neutrophil elastase (NE) in bronchoalveolar lavage fluid (BALF) was measured by enzyme-linked immunoabsorbent assay (ELISA). The percentage of CD11b/CD18 double positive PMN was detected using flow cytometry. The expression of intercellular adhesion molecule-1 (ICAM-1) and NE protein in the lung tissue was detected by Western blot. RESULTS: Compared with the sham-operation group, significant pathologic lesion occurred in the lung tissue of rats in the SAP group; the pathologic LI score, lung tissue W/D ratio, MPO, and NE content in BALF significantly increased, the expression of ICAM-1 and NE in the lung tissue was obviously up-regulated, and the percentage of CD11b/CD18 double positive PMN significantly increased (P < 0.01). Compared with the SAP group, pathological lesion of the lung tissue was obviously attenuated, and the above indices were all significantly declined in the GBE treatment group (P < 0.01). CONCLUSIONS: Expression of ICAM-1 in the lung tissue and the percentage of D11b/ CD18 double positive PMN were up-regulated in SAP rats complicated with LI, resulting in the adherence of PMN to pulmonary vascular endothelial cells, and then activating PMN to release NE and aggravate LI. GBE could alleviate LI through down-regulating the expression ICAM-1 and CD11b/CD18, and hindering the adherence and activation of PMN to pulmonary vascular endothelial cells.

Clypeasterol, a novel aromatic ergosterol skeleton from the mushroom Entoloma clypeatum.

Chemical investigation of the wild mushroom Entoloma clypeatum led to the isolation of one new A-nor B-aromatic C28 steroid (1), along with eight known compounds (2-9) from this mushroom. As far as we know, compound 1 represents an unprecedented type of natural product. The structure of the new compound was elucidated based on extensive spectroscopic data analysis of HR-ESI-MS, 1D, and 2D NMR, while the relative configuration was confirmed by NOESY correlations. In addition, the anti-inflammatory activity of compound 1 was evaluated against LPS induced NO production in RAW 264.7 macrophages. Compound 1 exhibited a moderate anti-inflammatory activity with an IC50 value of 24.56 ± 1.72 µM.

[Analysis of epidermal growth factor receptor expression and gene expression status in tissue microarray of cervical squamous cell carcinoma].

OBJECTIVE: To elucidate the protein expression and gene expression status and the relationship between epidermal growth factor receptor (EGFR) protein expression and EGFR gene status. METHODS: Tissue microarray containing 72 cervical squamous cell carcinoma tissues was constructed, and EGFR protein expression and gene status were evaluated by immunohistochemical and fluorescence in situ hybridization (FISH) techniques. RESULTS: Protein expression of EGFR: 69 of 72 cervical squamous cell carcinomas were observed. The results demonstrated it was significant association with invasion depth, lymph node metastasis and lymph-vessel invasion (χ(2) = 4.998, P < 0.05; χ(2) = 4.299, P < 0.05; χ(2) = 4.686, P < 0.05) in cervical squamous cell carcinomas. For FISH assessing EGFR gene, 64 of 72 carcinomas were observed; 7 of 64 cases showed EGFR gene amplification, and 25 disomy, 23 trisomy and 9 polysomy were detected. There were high levels of protein expression in all the EGFR gene amplification cases, and there were significant association between EGFR protein expression and the gene copy number (χ(2) = 13.564, P < 0.05). CONCLUSIONS: EGFR may participate in the occurrence, progression and metastasis of cervical squamous cell carcinoma. Overexpression of EGFR protein may result from gene amplification and gene copy number increases, which showed that EGFR gene expression status may be a more effective biological indicator of cervical squamous cell carcinoma targeted therapy.

[Expression of high mobility group box-1 in the lung tissue and serum of patients with pulmonary tuberculosis].

OBJECTIVE: To explore the expression of high mobility group box-1 (HMGB1) in the lung tissue and serum of patients with pulmonary tuberculosis and to explore its relationship with tumor necrosis factor (TNF)-α and interleukin(IL)-1ß. METHODS: Sixty samples of lung tissues were obtained from patients with pulmonary tuberculosis who had underwent pneumonectomy in Department of Chest Surgery, First Affiliated Hospital of Zunyi Medical College from June 2010 to December 2011. At the same period, 40 normal lung samples were also obtained from patients with pulmonary contusion and lung cancer by surgical resections as the control group. The mRNA expressions of HMGB1 was detected by reverse transcription-polymerase chain reaction (RT-PCR), and the protein level of HMGB1 was measured by immunohistochemical staining of tissue microarrays in lung tissue. Blood samples were taken from 89 patients with active pulmonary tuberculosis (pulmonary tuberculosis group), including hematogenous disseminated pulmonary tuberculosis (type II) in 35 cases and secondary pulmonary tuberculosis (type III) in 54 cases, and 50 healthy volunteers (control group). Furthermore, the 54 patients with secondary pulmonary tuberculosis were divided into different subgroups according to cavity formation and the lung fields involved: patients without lung cavity (35 cases) vs those with lung cavity (19 cases), patients with involvement of <2 lung fields (31 cases) vs ≥ 2 lung fields (23 cases). Serum concentration of HMGB1, TNF-α and IL-1ß were detected by ELISA. Two sample t-test was used to compare date among groups, liner correlation analysis was established for correlation analysis. RESULTS: The average optical density of HMGB1 in pulmonary tuberculosis (69 ± 29) was significantly higher than that in normal lung tissue (22 ± 12) (t = 2.389, P < 0.05). The mRNA relative transcript levels of HMGB1 in pulmonary tuberculosis (786 ± 86) was significantly higher than that in normal lung tissue (202 ± 60) (t = 3.872, P < 0.01). The serum concentration of HMGB1, TNF-α and IL-1ß in the pulmonary tuberculosis group were (5.0 ± 3.2) µg/L, (118 ± 77) ng/L and (33 ± 20) ng/L, respectively, which were significantly higher than those in the control group [(1.7 ± 1.0) µg/L, (40 ± 11) ng/L and (18 ± 12) ng/L, respectively], the respective t values being -0.928, 4.268 and 11.064, all P < 0.01. In the subgroup of patients with hematogenous disseminated pulmonary tuberculosis, the serum concentration of HMGB1 and TNF-α[ (6.4 ± 3.3) µg/L, (147 ± 89) ng/L] were significantly higher than those in patients with secondary pulmonary tuberculosis [(4.1 ± 2.7) µg/L, (85 ± 37) ng/L] (t = 3.643 and t = 3.111, both P < 0.01). HMGB1 were correlated positively with TNF-α and IL-1ß (r = 0.722 and r = 0.620, P < 0.01, respectively, n = 89) in the pulmonary tuberculosis group. CONCLUSIONS: Overexpression of HMGB1 in the lung tissue and serum of patients with pulmonary tuberculosis may play an important role in the inflammatory response of pulmonary tuberculosis. The measurement of serum HMGB1 is useful to evaluate the severity of disease.

Multimodality imaging in diagnosing lipomatous atrial septal hypertrophy with atrial septal defect: a case report.

Background: Lipomatous atrial septal hypertrophy (LASH) with atrial septal defect (ASD) is a rare congenital anomaly. Although LASH is a histologically benign cardiac lesion characterized by excessive fat deposition in the interatrial septum that spares the fossa ovale, it has been associated with supraventricular arrhythmias or sick sinus syndrome. Application of multimodal imaging is crucial for accurate diagnosis, appropriate treatment of LASH with ASD, and follow-up. Case summary: A 68-year-old female patient presented with recurrent chest tightness and palpitation. Multimodal imaging revealed the characterizations of LASH and ASD. Two-dimensional transesophageal echocardiography showed a "dumbbell"-shaped involvement of the cephalad and caudal regions with sparing of a single secundum ASD. The septum with a brightness feature is an uncommon condition characterized by the deposition of unencapsulated fat cells in the atrial septum. Real-time four-dimensional transesophageal echocardiography reflected the lipomatous hypertrophy of the atrial septum and an oval-shaped ASD. Cardiac computer tomography angiography later confirmed this finding. The patient achieved a good clinical response with an ASD percutaneous occlusion guided by intracardiac echocardiography (ICE). Conclusion: This case demonstrates a LASH combined with ASD. Multimodality imaging can provide an accurate diagnosis and may guide the procedure for precise occlusion.

Design and synthesis of oridonin derivatives as cytotoxic agents.

Oridonin is one of the ent-kaurane diterpenes that have been studied extensively for various bioactivities. In an effort to expand natural scaffold-based library as anticancer agents, we have designed and synthesised a number of novel oridonin derivatives and evaluated their bioactivities on a panel of human cancer cell lines (HCT116, A375, MCF-7, HepG2, and A549). Compound 4b bearing a 4-fluorophenyl moiety was found to be the most active compound with an IC50 value of 0.3 µM against MCF-7 cells, which was 7.4-fold more active than oridonin. This study could provide some insightful information for further synthesis of oridonin derivatives as anticancer agents.

Association of a Modified Blumgart Anastomosis With the Incidence of Pancreatic Fistula and Operation Time After Laparoscopic Pancreatoduodenectomy: A Cohort Study.

Objective: To explore the association between a modified Blumgart anastomosis technique and the operative time and surgical complications. Methods: This is a retrospective cohort study that analyzed the data of patients who underwent laparoscopic pancreaticoduodenectomy from January 2015 to March 2021. The primary outcome was to explore the association between the modified Blumgart anastomosis technique and operative time. Results: A total of 282 patients were enrolled. There were 177 cases of pancreatic duct-to-mucosa anastomosis in the traditional surgery group, and 105 cases of the modified three-step Blumgart anastomosis in the modified group. There were no statistically significant differences in the general and intraoperative characteristics found between the two groups (P > 0.05). The surgical method was an independent predictor of operative time. Overall complications postsurgery were less common in the modified group than in the traditional group. The incidence of postoperative pancreatic fistula was higher in the traditional group than in the modified group (45 cases (25.4%) and 11 cases (10.5%), respectively). Fourteen cases (7.9%) in the traditional group and four case (3.8%) in the modified group had postoperative pancreatic fistula of grades B + C. The two groups had statistically significant differences (P < 0.05). The results of the linear regression showed that the type of surgical method was associated with operation time (95% CI, -73.074 to -23.941, ß: -0.438, P < 0.001). Conclusion: This modified three-step Blumgart pancreaticojejunostomy was associated with the operation time.

Downregulation of miR-491-5p promotes neovascularization after traumatic brain injury.

MicroRNA-491-5p (miR-491-5p) plays an important role in regulating cell proliferation and migration; however, the effect of miR-491-5p on neovascularization after traumatic brain injury remains poorly understood. In this study, a controlled cortical injury model in C57BL/6 mice and an oxygen-glucose deprivation model in microvascular endothelial cells derived from mouse brain were established to simulate traumatic brain injury in vivo and in vitro, respectively. In the in vivo model, quantitative real-time-polymerase chain reaction results showed that the expression of miR-491-5p increased or decreased following the intracerebroventricular injection of an miR-491-5p agomir or antagomir, respectively, and the expression of miR-491-5p decreased slightly after traumatic brain injury. To detect the neuroprotective effects of miR-491-p, neurological severity scores, Morris water maze test, laser speckle techniques, and immunofluorescence staining were assessed, and the results revealed that miR-491-5p downregulation alleviated neurological dysfunction, promoted the recovery of regional cerebral blood flow, increased the number of lectin-stained microvessels, and increased the survival of neurons after traumatic brain injury. During the in vitro experiments, the potential mechanism of miR-491-5p on neovascularization was explored through quantitative real-time-polymerase chain reaction, which showed that miR-491-5p expression increased or decreased in brain microvascular endothelial cells after transfection with an miR-491-5p mimic or inhibitor, respectively. Dual-luciferase reporter and western blot assays verified that metallothionein-2 was a target gene for miR-491-5p. Cell counting kit 8 (CCK-8) assay, flow cytometry, and 2?,7?-dichlorofluorescein diacetate (DCFH-DA) assay results confirmed that the downregulation of miR-491-5p increased brain microvascular endothelial cell viability, reduced cell apoptosis, and alleviated oxidative stress under oxygen-glucose deprivation conditions. Cell scratch assay, Transwell assay, tube formation assay, and western blot assay results demonstrated that miR-491-5p downregulation promoted the migration, proliferation, and tube formation of brain microvascular endothelial cells through a metallothionein-2-dependent hypoxia-inducible factor-1α/vascular endothelial growth factor pathway. These findings confirmed that miR-491-5p downregulation promotes neovascularization, restores cerebral blood flow, and improves the recovery of neurological function after traumatic brain injury. The mechanism may be mediated through a metallothionein-2-dependent hypoxia-inducible factor-1α/vascular endothelial growth factor signaling pathway and the alleviation of oxidative stress. All procedures were approved by Ethics Committee of the First Affiliated Hospital of Chongqing Medical University, China (approval No. 2020-304) on June 22, 2020.

[Effect of Astragalus and Salvia's effective components and their compatibility on JAK/STAT pathway].

OBJECTIVE: To study the effect of Astragalus and Salvia's effective components and their compatibility on JAK/STAT pathway of rats' renal fibrosis. METHODS: 66 SD rats were randomly divided into 7 groups: normal group,model group,fosinopril group, salvianolic acids group, astragalus saponins group, granules compatibility of Astragalus and Salvia group, components combination of Astragalus and Salvia group. The variation of beta2-microglobulin(beta2-MG), the changes of renal pathology and JAK/STAT pathway were observed. RESULTS: The changes in renal pathology of treatment groups had different degrees of improvement; Astragalus and Salvia could reduce the urinary beta2-MG of unilateral ureteral obstruction (UUO) rat (P < 0.05), which was equal with fosinopril group. The rest of the treatment groups decreased especially fosinopril group while the difference was not significant when compared with the model group. Astragalus and its effective components could reduce the expression of renal tissue JAK, STAT1, STAT3 protein, among which fosinopril group and granules compatibility of Astragalus decreased significantly. Astragalus saponins group was not obvious, and the rest of the treatment group had significantly minor effect. CONCLUSION: Astragalus and Salvia's effective components and their compatibility may protect renal tubular function in unilateral ureteral obstruction, which may interfere with UUO rat kidney with JAK/STAT signaling pathway.

Hypoperfusion assessed by pressure reactivity index is associated with delayed cerebral ischemia after subarachnoid hemorrhage: an observational study.

BACKGROUND: Dysfunction of cerebral autoregulation is one of the pathophysiological mechanisms that causes delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH). Pressure reactivity index (PRx) have been confirmed to reflect the level of cerebral autoregulation and used to derive optimal cerebral perfusion pressure (CPPopt). The goal of this study is to explore the associations between autoregulation, CPPopt, PRx, and DCI. METHODS: Continuous intracranial pressure (ICP), arterial blood pressure (ABP), and cerebral perfusion pressure (CPP) signals acquired from 61 aSAH patients were retrospectively analyzed. PRx was calculated and collected by Pneumatic computer system. The CPP at the lowest PRx was determined as the CPPopt. The duration of a hypoperfusion event (dHP) was defined as the cumulative time that the PRx was > 0.3 and the CPP was

[Temporal Evolution and Main Influencing Factors of Black Carbon Aerosol in Nanjing].

Temporal evolution of black carbon (BC) in Nanjing was studied along with its main influencing factors. The multi-wavelength aethalometer (AE-33) was used to select the typical month of each season to observe BC mass concentration, combined with atmospheric pollutant data, meteorological elements, and boundary layer detection data. Seasonal, daily, weekly trends, and source characteristics of BC were analyzed. The results showed that the BC concentration in Nanjing had obvious seasonal changes, which were higher in spring and winter, in the decreasing order:spring[(3351±919) ng·m-3] > winter[(3234±2102) ng·m-3] > in autumn[(3064±967) ng·m-3] > summer[(2632±1705) ng·m-3]. The diurnal changes in BC during the four seasons are bimodal, with peaks at 06:00-08:00 and 21:00-23:00. The morning and evening peak distribution characteristics of BC in different seasons are different. The peak concentration of BC was highest in the early morning peak spring and the highest in the late peak winter. The morning peak timing of winter is 2 h behind other seasons, while the summer peak timing is 2 h ahead of other seasons. The effect of the wind speed on the seasonal distribution of BC diurnal variation is significantly larger than that on RH. The mechanism of the influence of the inversion layer on the concentration of atmospheric pollutants is complicated. The effects of height, thickness, and temperature of the inversion layer on the pollutants are different in different seasons. Weekly BC effects vary seasonally. The effect of RH and wind speed on the weekly BC effect is small, and the difference in the inversion layer is the main reason behind it. Liquid fuel combustion in Nanjing has a greater contribution to BC, whereas solid combustion contributes by a lesser extent.

[Advances in the clinical research on acupuncture in treatment of respiratory diseases].

This article reviews the clinical studies on acupuncture in the treatment of asthma, chronic bronchitis, and acute exacerbation and stable phase of chronic obstructive pulmonary disease in China over the past 10 years, and the results suggest that acupuncture has a good clinical effect. At present, there are still several problems in related clinical studies, including lacking of standard operation procedure for acupuncture, unreasonable design of control group, and low quality of clinical research. Therefore, in the future, top-level design should be standardized and large-sample multicenter clinical studies should be conducted to provide stronger evidence of evidence-based medicine for acupuncture in the treatment of respiratory diseases.

[Change in Characteristics of Pollution Gas and Water-soluble Ions at Different Development Stages of Haze].

To explore the variation in characteristics of atmospheric pollutants at different stages of haze, the monitor for aerosols and gases in ambient air (MARGA) was used to observe the concentrations of precursor pollutants (NH3, HNO3, and SO2) and eight water-soluble ions in a regional haze in the Yangtze River Delta region from November 18 to December 07, 2018. Combined with environmental data (PM2.5, NO2, CO, and O3) and meteorological data, the causes of regional haze formation, diurnal variation characteristics of air pollutants, and distribution characteristics of air pollutants in different stages of haze were analyzed. The results showed that the Yangtze River Delta region was mainly controlled by a ridge of high pressure during the haze process and the weather situation was stable, which was conducive to the accumulation of air pollutants. On hazy days, the concentrations of PM2.5, NO2, NO3-, SO42-, NH4+, Cl-, and Na+ were (118.91±39.23), (61.62±26.34), (45.64±16.01), (18.80±8.02), (20.82±7.16), (3.02±2.25), and (0.23±0.22) µg·m-3, respectively, and these were 2.73, 1.63, 2.64, 1.94, 2.50, 2.05, and 2.56 times the levels found on clean days, respectively. The concentration of CO was (1.34±0.39) mg·m-3 on hazy days, which was 1.86 times that found on clean days. Diurnal variation characteristics of different air pollutants were different, as were the distribution characteristics of air pollutants at different haze stages. The concentrations of SO2 was the highest in the haze occurrence stage. The concentrations of PM2.5, NO2, NH3, CO, and SNA were highest in the haze development stage, and the concentrations of O3, Cl-, Na+, and K+ were highest in the haze dissipation stage. The relative contributions of SNA to PM2.5 in different stages of haze could reach 94%-96%, and their growth rate was largest in the development stage. The order of growth rate was NO3- > NH4+ > SO42-. SNA mainly existed in the form of NH4NO3 on clean days and in the occurrence and development stages, and (NH4)2SO4 in the dissipation stage. This haze process was mainly caused by the growth of NO3-, which was mainly generated by gas-phase homogeneous phase reaction, and NO3-contributes 51.06%, 51.85%, and 48.22%, respectively, to PM2.5 in the occurrence, development, and dissipation stages of haze.

DNM1L, a key prognostic predictor for gastric adenocarcinoma, is involved in cell proliferation, invasion, and apoptosis.

Dynamin-1-like protein (DNM1L) encodes a member of the dynamin superfamily of GTPases. It mediates mitochondrial and peroxisomal division and is involved in the regulation of apoptosis. However, its role in gastric cancer remains unclear. MKN-45 gastric cancer cells were transfected with short hairpin RNA (shRNA) to suppress DNM1L expression. MTT, flow cytometry, and Transwell assays were used to detect the changes in cell proliferation, apoptosis, and invasion, respectively. Immunohistochemistry was used to detect DNM1L expression in gastric adenocarcinoma specimens, and the association of DNM1L expression with clinicopathological features and prognosis was analyzed. After the suppression of endogenous DNM1L expression in MKN-45 cells with shRNA, cell proliferation and invasion rates were significantly reduced, whereas apoptosis was significantly increased (all P<0.01). The expression of DNM1L was significantly higher in gastric adenocarcinoma specimens compared with that in pericarcinoma tissues (P<0.001). The expression of DNM1L increased with increasing infiltration depth, lymphatic metastasis, and higher tumor node metastasis stage (P<0.05). The expression of DNM1L associated negatively with prognosis (P<0.01). DNM1L plays a critical role in the proliferation, invasion and apoptosis of human gastric adenocarcinoma. DNM1L expression has prognostic significance for the survival of patients with gastric adenocarcinoma.

Effects of Omega-3 in the treatment of violent schizophrenia patients.

OBJECTIVE: This study was designed to explore the relationship in between the daily consumption of fish oil (360mg DHA+540mg EPA), and reduction of symptoms and violent behavior among patients with schizophrenia. METHOD: Fifty inpatients meeting ICD-10 criteria for schizophrenia and scoring more than four of Modified Overt Aggression Scale (MOAS) with antipsychotics treatment were randomly assigned to receive either fish oil (N=28) or a placebo (N=22) in a twelve week, double-blind supplementation trial. Assessments were performed at baseline and at weeks 4, 8 and 12. RESULTS: The PANSS and CGI scores decreased at the week of 4, 8 and 12, but no differences were found between the two groups. MOAS scores declined significantly at weeks 4, 8 and 12. At week 12, MOAS scores of the fish oil group declined significantly than the placebo group (t=-2.40, P<0.05). CONCLUSIONS: violent schizophrenia patients treated with fish oil (360mg DHA+540mg EPA) demonstrated a decrease in violence, but improvement in positive and negative symptoms was no greater than patients treated with the placebo after twelve weeks.

SP1 reduces autophagic flux through activating p62 in gastric cancer cells.

Gastric cancer is the most common type of gastrointestinal cancer, causing mortality worldwide. However, the underlying molecular mechanism in gastric cancer progression remains unclear. The autophagic flux was determined in gastric cancer cells overexpressing or inhibiting Sp1 transcription factor (SP1) using western blotting, reverse transcription­polymerase chain reaction and immunofluorescence staining. Luciferase and ChIP assays were performed to detect the potential underlying mechanism of SP1 in gastric cancer cells. Lastly, immunohistochemistry was also performed on SP1 and p62 expression levels in human gastric cancer specimens. It was demonstrated that SP1 diminished autophagic flux via activating p62 in gastric cancer. Moreover, SP1 deficiency increased the rate of autophagy of gastric cancer cells. Notably, it was observed that SP1 enhanced the expression levels of p62 by directly binding to the promoter of p62. Analysis of gastric cancer specimen staining established that p62 expression levels were increased in SP1­positve gastric tissues. The present study provided evidence for a novel mechanism regulating autophagy in gastric cancer cells.

Polymorphism of SG13S114T/A in the ALOX5AP gene and the risk for stroke in a large Chinese cohort.

The 5-lipoxygenase activating protein, an important regulator in the biosynthesis of proinflammatory leukotrienes, has been reported to confer risks for cardiovascular diseases and stroke. The purpose of this study is to assess whether genetic variants in the ALOX5AP encoding the 5-lipoxygenase activating protein will influence the risk for stroke in the Chinese population. A total of 1,773 patients with stroke and 1,713 controls were recruited from seven clinical centers. Polymorphisms of SG13S114T/A and SG13S89G/A in the ALOX5AP were genotyped by the polymerase chain reaction and the restriction enzyme analysis. The multivariate logistic regression model was used to exclude the influence of the conventional vascular risk factors on stroke. The frequency of SG13S114A allele in the ALOX5AP was significantly higher in male patients with thrombotic stroke (33.6%) than in controls (29.2%; P=0.014). The SG13S114AA genotype was significantly associated with a 1.62-fold risk for thrombotic stroke in men (95% confidence interval, 1.11 to 2.35; P=0.012). The SG13S89G/A variant was not associated with stroke or its subtypes. Haplotype analysis showed no significant differences between stroke patients and controls. The present study suggested that a common genetic variant SG13S114T/A in the ALOX5AP gene is associated with an increased risk for atherothrombotic stroke in Chinese males, and racial differences in allele and genotype frequencies may account partially for the different association findings between populations.

[The effect of interleukin-7 and interleukin-15 on the production of Th1 and Th2 cytokines by peripheral blood mononuclear cells from patients with tuberculosis].

OBJECTIVE: To investigate the effect of interleukin-7 and interleukin-15 on the production of Th1 cytokines interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha) and Th2 cytokines interleukin-4 (IL-4), IL-10 by peripheral blood mononuclear cells (PBMC) from patients with tuberculosis. METHODS: Peripheral blood was obtained from 60 tuberculosis patients and 25 healthy controls with a positive tuberculin test. PBMCs were isolated by centrifugation on a Ficoll-hypaque density gradient. According to the different stimulators, each sample was divided into six groups: RPMI-1640 group, PPD group, PPD + IL-7 group, PPD + anti-IL-7 group, PPD + IL-15 group, and PPD + anti-IL-15 group. The samples were cultured for 72 h and the supernatants were collected. The levels of IFN-gamma, TNF-alpha, IL-4 and IL-10 in the supernatants were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Compared with the PPD group, IL-7 increased the production of IFN-gamma and TNF-alpha in the patients [(107 +/- 42) ng/L to (157 +/- 74) ng/L, (460 +/- 128) ng/L to (887 +/- 242) ng/L, respectively], but decreased the production of IL-4 and IL-10 [(58 +/- 15) ng/L to (31 +/- 9) ng/L, (153 +/- 40) ng/L to (112 +/- 32) ng/L, respectively]; IL-7 also increased the production of IFN-gamma and TNF-alpha in the healthy controls [(211 +/- 57) ng/L to (292 +/- 92) ng/L, (1,203 +/- 390) ng/L to (1,722 +/- 503) ng/L, respectively], and decreased the production of IL-4 and IL-10 [(43 +/- 13) ng/L to (36 +/- 11) ng/L, (135 +/- 37) ng/L to (96 +/- 36) ng/L, respectively]. IL-15 increased the production of IFN-gamma and TNF-alpha in the patients [(107 +/- 42) ng/L to (231 +/- 62) ng/L, (460 +/- 128) ng/L to (843 +/- 208) ng/L, respectively], but decreased the production of IL-4 and IL-10 [(58 +/- 15) ng/L to (37 +/- 9) ng/L, (153 +/- 40) ng/L to (116 +/- 41) ng/L, respectively]; IL-15 also increased the production of IFN-gamma and TNF-alpha in the healthy controls [(211 +/- 57) ng/L to (343 +/- 108) ng/L, (1,203 +/- 390) ng/L to (1,468 +/- 235) ng/L, respectively], and decreased the production of IL-4 and IL-10 [(43 +/- 13) ng/L to (36 +/- 8) ng/L, (135 +/- 37) ng/L to (90 +/- 35) ng/L , respectively]. Anti-IL-7 and anti-IL-15 decreased the production of IFN-gamma and TNF-alpha, but increased the production of IL-4 and IL-10. The levels of IFN-gamma and TNF-alpha were lower in tuberculosis patients than those in the healthy controls (P < 0.05). The levels of IL-4 and IL-10 were not different between the two groups (P > 0.05). CONCLUSION: IL-7 and IL-15 could affect the balance between Th1 and Th2 cytokines by inducing IFN-gamma and TNF-alpha production and inhibiting IL-4 and IL-10 expression. It is suggested that IL-7 and IL-15 may enhance the defense against infection of tuberculosis, and therefore may be useful for the treatment of the disease.

Enhanced expression of polysialic acid correlates with malignant phenotype in breast cancer cell lines and clinical tissue samples.

Polysialic acid (PSA) is highly expressed during embryonic development, but barely expressed during postnatal development, and may be 're-expressed' in cancer tissues. In this study, motility and migration assays were performed to compare the changes in cell behavior between non-malignant and maligant cells. Next, the expression levels of PSA were evaluated in 4 human and mouse normal breast or breast cancer (BC) cell lines using 1,2-diamino-4,5-methylenedioxybenzene-labeling HPLC technology, as well as in human clinical BC tissue samples. PSA expression was significantly higher in malignant cells (where it appeared to facilitate cell migration and motility) than in non-malignant cells. Enhanced PSA expression levels were also observed during epithelial-mesenchymal transition (EMT), a leading cause of cancer cell metastasis, which was induced in the NMuMG and MCF10A cells by treatment with transforming growth factor-ß1 (TGF-ß1). An increased PSA expression also correlated with the disease stage in the patients with BC (P<0.0001). Using RT-qPCR, we found that polysialyltransferase ST8SiaIV (PST) and polysialyltransferase ST8SiaII (STX), which are responsible for PSA synthesis, were differently expressed in the tested BC samples. However, PST, but not STX, was re-expressed in 14 out of 20 clinical BC samples. The findings of the present study indicate that the pathophysiology of BC involves the aberrant regulation of PSA expression and PST gene expression.