Adenoid cystic carcinoma of the lung (ACCL) is a rare salivary gland-type malignant neoplasm that occurs infrequently as a primary tumor of the airway. Owing to its low incidence, the clinicopathological features, immunohistochemical expression spectrum, treatment and long-term survival have not been fully elucidated. The present study retrospectively assessed the clinical features, immunohistochemical characters, treatment strategy and long-term survival of 34 patients diagnosed with ACCL at the Beijing Chest Hospital, Capital Medical University (Beijing, China) between January 1993 and June 2014. ACCL tended to occur in younger patients, with an approximate male/female ratio of 1:1. The majority of ACCL arose from the central airway. Positive immunochemical staining was found in wide-spectrum keratin (n=17), cytokeratin (CK)7 (n=11), p63 (11/12), S-100 (7/8), vimentin (10/12) and smooth muscle actin (6/9). No staining of thyroid transcription factor-1 (0/14), synaptophysin (0/7), cluster of differentiation 56 (0/7), CK20 (0/4) or chromogranin A (0/4) was observed. In the operable group (n=26), the addition of adjuvant radiotherapy to a positive margin resection (R1 resection) obtained long-term survival times equivalent to that found in patients with a negative margin resection (R0 resection). No significant survival benefit from post-operative radiotherapy was observed in the R0 resection group. For advanced cases, palliative radiotherapy and chemotherapy did not work efficiently. In addition, epidermal growth factor receptor mutation was a rare event in the ACCL patients. The results indicated that surgical resection is the optimal management for ACCL whenever feasible. Adjuvant radiotherapy with R1 resection is able to obtain long-term survival times comparable with those found using an R0 resection. The recommendation of post-operative radiotherapy for all patients with ACCL undergoing resection appears controversial. Owing to a poor response to radiotherapy and chemotherapy, more focus should be placed on the study of advanced ACCL in order to improve overall survival.
adenoid cystic carcinoma; lung; clinicopathology; immunohistochemistry; treatment; survival
Objective: This study aimed to estimate the prevalence of diabetes mellitus (DM) and impaired fasting glucose (IFG) in a Kazakh population aged ≥18 years living in the YiLi District of Xinjiang, China and to evaluate the associated risk factors of diabetes. Methods: Randomly selected adults, living for at least 6 months in the YiLi District in Xinjiang had their clinical characteristics and standard blood chemistries measured. DM and IFG were defined according to WHO 1999 criteria. The adjusted odds ratio (ORs) and 95% confidence intervals were calculated for the association of diabetes risk factors in multivariate logistic regression models. Results: A total of 3919 subjects were randomly selected. The age-and gender-standardized prevalence of DM and IFG were 5.9% and 10.0%, respectively. The prevalence of DM and IFG increased with age and BMI. Prevalence of 7.4%, 12.2% in males and 4.9%, 8.6% in females for DM and IFG. Compared by sex, prevalence of DM and IFG was higher in males. Prevalence of 3.4%, 8.1% in normal, 6.7%, 11.9% in overweight and 12.0%, 13.0% in obesity for diabetes and IFG. In the multivariable logistic models, male sex, older age, unmarried, overweight, obesity, hypertension, triglycerides and smoking were all significantly associated with an increased risk of diabetes. Conclusions: The prevalence of DM and IFG among minorities was lower than the overall national level both in men and women (9.7% in total, 10.6% in males, 8.8% in females), and also lower than among the Han ethnicity (9.26%) which predominates in China today.
diabetes mellitus; impaired fasting glucose; rural; associated factors
Objectives: To evaluate the clinical significance of cyclin-dependent kinase 1 (CDK1) in 77 oral squamous cell carcinomas (OSCC) using immunohistochemical methods.
Study Design: Immunohistochemical expression of CDK1 was compared with various clinicopathological features in 77 OSCC and 60 controlled epithelia adjacent to the tumours. In addition, correlation of CDK1 expression and prognostic and the 5-year accumulative survival rate of OSCC were investigated.
Results: The CDK1 protein was expressed in 52 cases of 77 tumor tissues (67.5%), compared with 21 cases of 60 controlled (35.0%). The expression of CDK1 was significantly correlated with the histological grade of OSCC (P<0.05). The CDK1 protein was over-expressed in recurrent tumors or in those with lymph node metastasis. Statistical analysis showed a significant reduction in the 5-year accumulative survival rate in CDK1 positive cases compared with CDK1 negative cases (P<0.05). Namely, the CDK1 positive patients had poor prognosis.
Conclusions: The expression of CDK1 might serve as malignant degree and prognostic markers for the survival of OSCC.
Key words:Cyclin-dependent kinase 1 (CDK1), oral squamous cell carcinoma (OSCC), immunohistochemistry, cell proliferation.
Marching towards the elimination of schistosomiasis in China, both the incidence and prevalence have witnessed profound decline over the past decades, with the strategy shifting from morbidity control to transmission control. The current challenge is to find out hotspots of transmission risk for precise targeted control in low-prevalence areas. This study assessed the risk at the village level, using the spatial and temporal characteristics of Schistosomiasis japonica in Anhui province from 2006 to 2012.
The comprehensive database was generated from annual surveillance data at village level in Anhui province between 2006 and 2012, comprising schistosomiasis prevalence among humans and cattle, occurrence rate of infected environments and incidence rate of acute schistosomiasis. The database parameters were matched with geographic data of the study area and fine scale spatial-temporal cluster analysis based on retrospective space-time scan statistics was used to assess the clustering pattern of schistosomiasis. The analysis was conducted by using SaTScan 9.1.1 and ArcGIS 10.0. A spatial statistical modelling was carried out to determine the spatial dependency of prevalence of human infection by using Geoda 1.4.3.
A pronounced decline was found in the prevalence of human infection, cattle infection, occurrence rate of environment with infected vector snails and incidence rate of acute schistosomiasis from 2006 to 2012 by 48.6%, 71.5%, 91.9% and 96.4%, respectively. Meanwhile, all 4 indicators showed a statistically significant clustering pattern both in time and space, with a total of 16, 6, 8 and 4 corresponding clustering foci found respectively. However, the number of clustering foci declined with time, and none was found after year 2010. All clustering foci were mainly distributed along the Yangtze River and its connecting branches. The result shows that there is a direct spatial relationship between prevalence of human infection and the other indicators.
A decreasing trend in space-time clustering of schistosomiasis endemic status was observed between 2006 and 2012 in Anhui province. Nevertheless, giving the complexity in schistosomiasis control, areas within the upper-stream of Yangtze River in Anhui section and its connecting branches should be targeted for effective implementation of control strategies in the future.
Fine scale spatial-temporal scan statistics; Schistosomiasis japonica; Infection risk analysis; Anhui province
To discuss the feasibility and experience of treating valvular heart diseases with thoracoscopy-assisted mitral valve replacement concomitant with tricuspid valvuloplasty, with domestically manufactured pipeline products for cardiopulmonary bypass.
A total of 135 patients with valvular heart disease were admitted to our hospital between January 2011 and January 2013. They received thoracoscopy-assisted mitral valve replacement concomitant with tricuspid valvuloplasty, with domestically manufactured pipeline products. A cardiopulmonary bypass with domestically-manufactured pipeline products was established during the surgery. The procedure was accomplished with the assistance of thoracoscopy through a small incision in the right chest wall.
All 135 patients underwent a successful surgery, and were followed up for the duration of half a year to two years. None of them displayed any evidence of complications. Our procedure had the advantage of fewer complications and a significantly shortened time period for the patient care and hospitalization. As opposed to imported pipeline products for cardiopulmonary bypass, our procedure had the advantage of similar clinical results at a lower cost.
Thoracoscopy-assisted mitral valve replacement concomitant with tricuspid valvuloplasty was proved to be a safe and effective method for cardiopulmonary bypass, with the use of domestically manufactured pipeline products.
Thoracoscopy assistance; Minimally invasive; Mitral valve surgery
Laribacter hongkongensis is a gram-negative emerging bacterium associated with invasive bacteremic infections in patients with liver disease and fish-borne community-acquired gastroenteritis and traveler's diarrhea. Although the complete genome of L. hongkongensis has been sequenced, no animal model is available for further study of its pathogenicity mechanisms. In this study, we showed that adult zebrafish infected with L. hongkongensis by immersion following dermal abrasion or intraperitoneal injection suffered mortality in a dose-dependent manner, with lethal dose 50 (LD50) of 2.1×104 and 1.9×104 colony-forming units (CFU)/mL, respectively. All mortalities occurred in the first four days post-infection. Zebrafish that died showed characteristic clinicopathological features: swimming near water surface, marked lethargy and sidestroke; abdominal hemorrhage, ulcers and marked swelling with ascites; and hydropic degeneration and necrosis of hepatocytes around central vein and inflammatory cells infiltration. L. hongkongensis was recovered from the ascitic fluid and tissues of zebrafish that died. Of the 30 zebrafish infected with 2.1×104 CFU/mL (LD50) L. hongkongensis isolated from dead zebrafish using the immersion following dermal abrasion method, 18 (60%) died. All zebrafish that died also showed the characteristic clinical and pathological features. Histopathological studies also showed dilation of hepatic central vein and hydropic degeneration. L. hongkongensis was isolated from the zebrafish that died. The Koch's postulates for L. hongkongensis as an infectious agent have been fulfilled. This highly reproducible and effective zebrafish model is of crucial importance for future studies on virulence factors for L. hongkongensis infection.
animal model; infection; Laribacter hongkongensis
Galectin-3, a member of the beta-galactoside-binding lectin family, is a multifunctional protein with various biological functions, including the proliferation and differentiation of tumor cells, angiogenesis, cancer progression, and metastasis. We aimed to clarify if expression of galectin-3 is related to the clinicopathological characteristics and prognosis of hepatocellular carcinoma (HCC) patients, and to explore the possible mechanisms of galectin-3 in hepatocellular carcinoma.
First, we investigated galectin-3 mRNA and protein expression by using RT-PCR and Western blotting. Second, tissues from 165 HCC patients were used to evaluate clinicopathological characteristics and prognosis through immunohistochemical analyses. Furthermore, the functions of galectin-3 were analyzed with respect to the proliferation, cell cycle,apoptosis, migration, and invasion of HCC cell lines. Finally, we analyzed galectin-3 expression and micro-vessel density (MVD) by immunohistochemistry (IHC) to find its correlation with angiogenesis in Hepatocellular Carcinoma. Flow cytometer was used to explore apoptosis and Western-blot was used to detect the pathway proteins of apoptosis.
Galectin-3 showed high expression at the mRNA and protein levels in HCC cancer tissues and cell lines. Clinicopathological analyses revealed that increased expression of galectin-3 in tumors was closely associated with a poor prognosis. Galectin-3 knockdown by siRNA significantly inhibited cell growth, migration, and invasion, and induced apoptosis in HCC cells in vitro, whereas galectin-3 overexpression promoted cell growth, migration, and invasion. Correlation analysis of galectin-3 expression and micro-vessel density (MVD) showed that galectin-3 expression in tumor cells stimulates angiogenesis. The observed regulation of cell apoptosis was accompanied by the galectin-3-mediated modulation of caspase3 signaling pathways in HCC cells.
These data suggest that galectin-3 plays an important part in HCC progression and may serve as a prognostic factor for HCC.
Galectin-3; Hepatocellular carcinoma; Angiogenesis; Apoptosis; Prognostic factor
The global pandemic of obesity has become a disastrous public health issue that needs urgent attention. Previous studies have concentrated in high-income urban settings and few cover low-income rural settings especially nomadic residents in mountain areas. This study focused on low-income rural and nomadic minority people residing in China’s far west and investigated their prevalence and ethnic differences of obesity.
A questionnaire-based survey and physical examination of 8,036 individuals were conducted during 2009–2010, using stratified cluster random sampling method in nomadic Kazakhs and rural Uyghur residents (≥18 years old) in 18 villages, Xinjiang, China, about 4,407 km away from capital Beijing. Obesity was defined by BMI and WC.
The overall prevalence of general and abdominal obesity in Kazakh adults were 18.3% and 60.0%, respectively and in Uyghur, 7.6% and 54.5%, respectively. Female’s prevalence of obesity was higher than male’s for general obesity (45–54 age group in Uyghur, P = 0.041) and abdominal obesity (≥55 years in Kazakhs, P55∼ = 0.010, P65∼ = 0.001; and ≥18 years in Uyghurs, P<0.001). Kazakh’s prevalence of obesity was higher than Uyghur’s (general obesity: ≥35 years, P<0.001; abdominal obesity: ≥25 years in males and ≥65 years in females, P<0.01). The prevalence of obesity increased after 18 years old and subsequently decreased after 55 years old. Meat consumption, older age, and female gender had a higher risk of obesity in these two minorities.
Both general and abdominal obesity were common in rural ethnic Kazakhs and Uyghurs. The prevalence rates were different in these two minorities depending on ethnicity, gender, and age. Kazakhs, females and elderly people may be prioritized in prevention of obesity in western China. Because of cost-effectiveness in measuring BMI and WC, we recommend that BMI and WC be integrated into local preventive policies in public health toward screening obesity and related diseases in low-income rural minorities.
Dual anti-human epidermal growth factor receptor 2 (HER2) therapies have been shown to improve outcomes of HER2-positive breast cancer patients. We undertook a systematic review to compare treatment outcomes for patients who received single or combined anti-HER2 therapies.
We identified randomized control trials that compared dual anti-HER2 therapy and anti-HER2 monotherapy in patients with HER2-positive breast cancer. Outcomes included pathologic complete response (pCR), overall survival (OS), progression-free survival (PFS), and adverse events. Included in the analysis were seven trials that recruited 2,609 patients.
In the neoadjuvant setting, the pooled pCR rate in the dual anti-HER2 therapy and monotherapy groups in combination with chemotherapy was 54.8% and 36%, respectively. This difference was statistically significant (relative risk, 1.56; 95% confidence interval (CI), 1.23–1.97; p < 0.001). In the metastatic setting, dual anti-HER2 therapy demonstrated significant benefits in both PFS (hazard ratio (HR), 0.71; 95% CI, 0.62–0.81; p < 0.001) and OS (HR, 0.68; 95% CI, 0.57–0.82; p < 0.001). Subgroup analyses indicated that the addition of chemotherapy to dual anti-HER2 therapy could greatly improve pCR in the neoadjuvant settings. However, in the metastatic setting, similar PFS and OS were found in patients receiving dual anti-HER2 therapy with or without chemotherapy. Dual anti-HER2 therapy was associated with more frequent adverse events than monotherapy, but no statistical differences were observed in cardiac toxicity.
This systematic review provides a summary of all the data currently available, and confirms the benefits and risks of dual anti-HER2 therapy for HER2-positive breast cancer.
anti-HER2 therapy; HER2-positive breast cancer; Systematic review
The anti-oxidative and anti-inflammatory activities of electro-acupuncture (EA), a traditional clinical method, are widely accepted, but its mechanisms are not yet well defined. In this study, we investigated the role of extracellular signal-regulated kinases1/2 (ERK1/2) pathways on electro-acupuncture – mediated up-regulation of heme oxygenase-1 (HO-1) in rabbit lungs injured by LPS-induced endotoxic shock.
Seventy rabbits were randomly divided into 7 groups: group C, group M, group D, group SEAM, group EAM, group EAMPD, and group PD98059. Male New England white rabbits were given EA treatment on both sides once a day on days 1–5, and then received LPS to replicate the experimental model of injured lung induced by endotoxic shock. Then, they were killed by exsanguination at 6 h after LPS administration. The blood samples were collected for serum examination, and the lungs were removed for pathology examination, determination of wet-to-dry weight ratio, MDA content, SOD activity, serum tumor necrosis factor-α, determination of HO-1 protein and mRNA expression, and determination of ERK1/2 protein.
The results revealed that after EA treatment, expression of HO-1and ERK1/2 was slightly increased compared to those in other groups, accompanied with less severe lung injury as indicated by lower index of lung injury score, lower wet-to-dry weight ratio, MDA content, and serum tumor necrosis factor-α levels, and greater SOD activity (p<0.05 for all). After pretreatment with ERK1/2 inhibitor PD98059, the effect of EA treatment and expression of HO-1 were suppressed (p<0.05 for all).
After electro-acupuncture stimulation at ST36 and BL13, severe lung injury during endotoxic shock was attenuated. The mechanism may be through up-regulation of HO-1, mediated by the signal transductions of ERK1/2 pathways. Thus, the regulation of ERK1/2 pathways via electro-acupuncture may be a therapeutic strategy for endotoxic shock.
Acupuncture; Acute Lung Injury; Mitogen-Activated Protein Kinase 1
Carbohydrate antigen 19-9 (CA19-9) is the most frequently applied serum tumor marker for diagnosis of cancers in the digestive organs. However, some patients with benign diseases can have elevated serum levels of CA19-9 as well. The current study presents a 55-year-old female who was admitted to our hospital for further evaluation of a nodular cavity shadow in the right lower lobe and clarification of the cause of the marked elevation of serum CA19-9 levels. Abdominal MRI and gastrointestinal endoscopy did not find any malignancy. As lung cancer cannot be excluded in this patient, a video-assisted thoracoscopic surgery was carried, intraoperative and postoperative biopsy analysis both suggested chronic bronchitis with fungal infection (due to Histoplasma capsulatum or Penicillium marneffei) and organization. Immunohistochemistry showed marked positive staining for CA19-9 in the damaged lung tissue. The CA19-9 levels quickly returned to the normal range following lobe resection. Therefore, the marked elevation of serum CA19-9 levels, in this case, may have resulted from the chronic bronchitis with fungal infection.
Carbohydrate antigen 19-9; chronic bronchitis; fungal infection; immunohistochemistry
The epidemiology of Functional abdominal bloating (FAB) and its impact on health-related quality of life (HRQoL) in Chinese people remains unclear.
Randomised, stratified, multi-stage sampling methodology was used to select a representative sample of the general population from five cities in China (n = 16,078). All respondents completed the modified Rome II questionnaire; 20% were asked to complete the 36-item Short Form (SF-36). The associated factors of FAB were analyzed. The effects of FAB on HRQoL were estimated with gender stratification using propensity score techniques in 20% subsample.
Overall, 643 individuals (4.00%) had FAB and it was more prevalent in males than in females (4.87% vs. 3.04%, P<0.001). For males, self-reported history of dyspepsia was most strongly associated with FAB (OR = 2.78; 95% CI: 1.59, 4.72). However, the most strongly associated factor was self-reported health status for females (moderate health vs. good health: OR = 2.06, 95% CI: 1.07, 3.96. P = 0.030; poor health vs. good health: OR = 5.71, 95% CI: 2.06, 15.09). Concerning HRQoL, FAB was found to be related to two domains: role limitation due to physical problems (P = 0.030) and bodily pain (P<0.001) in females. While, in males, there were significant differences in multiple domains between those with and without FAB.
The prevalence of FAB in China was lower than previous reports. Males who had ever been diagnosed with dyspepsia and females who were in a poor self-reported health status were correlated with a higher prevalence of FAB. FAB affected only physical health in females, but impaired both physical and mental health in males.
Glutamine (GLN) has been reported to improve clinical and experimental sepsis outcomes. However, the mechanisms underlying the actions of GLN remain unclear, and may depend upon the route of GLN administration and the model of acute lung injury (ALI) used. The aim of this study was to investigate whether short-term GLN supplementation had an ameliorative effect on the inflammation induced by direct acid and lipopolysaccharide (LPS) challenge in mice.
Female BALB/c mice were divided into two groups, a control group and a GLN group (4.17% GLN supplementation). After a 10-day feeding period, ALI was induced by intratracheal administration of hydrochloric acid (pH 1.0; 2 mL/kg of body weight [BW]) and LPS (5 mg/kg BW). Mice were sacrificed 3 h after ALI challenge. In this early phase of ALI, serum, lungs, and bronchoalveolar lavage fluid (BALF) from the mice were collected for further analysis.
The results of this study showed that ALI-challenged mice had a significant increase in myeloperoxidase activity and expression of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α in the lung compared with unchallenged mice. Compared with the control group, GLN pretreatment in ALI-challenged mice reduced the levels of receptor for advanced glycation end-products (RAGE) and IL-1β production in BALF, with a corresponding decrease in their mRNA expression. The GLN group also had markedly lower in mRNA expression of cyclooxygenase-2 and NADPH oxidase-1.
These results suggest that the benefit of dietary GLN may be partly contributed to an inhibitory effect on RAGE expression and pro-inflammatory cytokines production at an early stage in direct acid and LPS-induced ALI in mice.
Glutamine (GLN); Acute lung injury (ALI); Receptor for advanced glycation end-products (RAGE); Inflammation
Decreased P300 amplitude is one of the most consistent findings in patients with schizophrenia. However, whether prolonged P300 latency occurs in patients with schizophrenia, especially first-episode schizophrenia (FES) patients, remains controversial.
A meta-analyses of P300 aberration in FES patients and healthy control(HC) group was conducted. The meta-regression analysis was performed using a random effects model. The pooled standardized effect size (PSES) was calculated as the division of the difference between the means of the two groups by the common standard deviation.
A total of 569 FES patients and 747 HCs were included in this meta- analysis. P300 amplitude was significantly reduced (PSES = −0.83, 95% CI: −1.02–0.65, P = 0.00001) and P300 latency was delayed significantly in FES patients (PSES = −0.48, 95% CI: 0.14–0.81, P = 0.005). The meta-regression analysis showed that task difficulty was a source of heterogeneity.
The meta-analysis confirms that disrupted information processing is found in FES patients, which is manifested by smaller P300 amplitude and delayed P300 latency.
The expression of hypoxia-induced factor (HIF)-1α is up-regulated in tumor microenvironments under hypoxia condition. However, the prognostic significance of HIF-1α in esophageal squamous cell carcinoma (ESCC) is still elusive. We measured the HIF-1α expression by immunochemistry in tumor specimens from 136 resected ESCC; in the current study, the HIF-1α expression in tumor cells was significantly associated with tumor stage (P = 0.003) and lymph node metastasis (P = 0.006); whereas the HIF-1α expression in tumor-infiltrating lymphocytes (TILs) had no relationship with patients’ clinicopathological parameters. Patients with high HIF-1α expression in tumor cells or in TILs showed worse survival related to those with low HIF-1α expression. Multivariate analysis demonstrated that expression of HIF-1α in TILs was an independent factor for DFS (P = 0.007) and OS (P = 0.013). Additionally, the expression of HIF-1α in tumor cells was an independent factor for DFS (P = 0.037) and OS (P = 0.033) in locoregional ESCC patients, whereas the expression of HIF-1α in TILs was an independent factor for DFS (P = 0.048) and OS (P = 0.039) in metastatic ESCC patients. Correlation analysis revealed that expressions of HIF-1α in tumor cells and in TILs were positively correlated, and patients with combined high HIF-1α in both tumor cells and TILs had the worst survivals (P < 0.05). These findings suggest that the HIF-1α expressions in different cell populations of ESCC microenvironments have different clinical relevance and prognostic impact on patients.
Esophageal squamous cell carcinoma; HIF-1α; tumor microenvironments; clinical prognosis; tumor-infiltrating lymphocytes
This study aimed to investigate the prevalence of abdominal obesity and its association with the health-related quality of life (HRQOL) in a randomly selected Chinese sample.
A population-based sample of 3,600 residents aged 18–80 years was selected randomly from 5 Chinese cities. Demographic information, and waist and hip circumference measurements were obtained. The Mandarin version of the Short Form 36 Health Survey questionnaire (SF-36) was used to assess the HRQOL. Waist circumference (WC) and waist-to-hip ratio (WHR) were used as measures of abdominal obesity, and the prevalence of abdominal obesity and its association with HRQOL were analysed.
Among the 3,184 participants included in the analysis, the prevalence of abdominal obesity was about 45% in both women and men as evaluated by WC, and about 40% in women and 33% in men as evaluated by WHR. The prevalence varied by city, region, age, marital status, education level, family income, smoking, and the presence of chronic diseases. Both WC and WHR increased with age, and men had larger WC and WHR than women in most age groups. In women, abdominal obesity, as determined by both WC and WHR, was associated with meaningful impairments in 4 physical health scales and 2 mental health scales. In men, abdominal obesity, as determined by WC, was associated with 1 physical health scale and 1 mental health scale, and it was associated with 2 physical health scales based on WHR.
Physical health, but not mental health, was more vulnerable to impairment with abdominal obesity, and the impairments varied between genders. Public health agencies should emphasize that abdominal obesity impairs physical health.
Abdominal obesity; Waist circumference; Waist-to-hip ratio; Health-related quality of life
A constitutive model for the stress-strain relationship of single forest root system was developed in order to provide theoretical foundations for the mechanisms of soil-reinforcement by root system and offer a reliable basis for the analysis of root tensile strength character. This study started a general form of linear and non-linear stress-strain relation that was mathematically defined by four boundary conditions observed in typical tensile tests of single roots. The parameters of the model were determined by experiment data and had definite physical meaning. The model was verified by experiment data, which showed that the calculated values were in good agreement with the experimental single root tensile test results. The constitutive model was validated and found to be feasible for modeling single root tensile stress.
The incidence and burden of stroke in China is increasing rapidly. However, little is known about trends in mortality during stroke hospitalization. The objectives of this study were to assess trends of in-hospital mortality among patients with stroke and explore influence factors of in-hospital death after stroke in China.
109 grade III class A hospitals were sampled by multistage stratified cluster sampling. All patients admitted to hospitals between 2007 and 2010 with a discharge diagnosis of stroke were included. Trends in in-hospital mortality among patients with stroke were assessed. Influence factors of in-hospital death after stroke were explored using multivariable logistic regression.
Overall stroke hospitalizations increased from 79,894 in 2007 to 85,475 in 2010, and in-hospital mortality of stroke decreased from 3.16% to 2.30% (P<0.0001). The percentage of severe patients increased while odds of mortality (2010 versus 2007) decreased regardless of stroke type: subarachnoid hemorrhage (OR 0.792, 95% CI = 0.636 to 0.987), intracerebral hemorrhage (OR 0.647, 95% CI = 0.591 to 0.708), and ischemic stroke (OR 0.588, 95% CI = 0.532 to 0.649). In multivariable analyses, older age, male, basic health insurance, multiple comorbidities and severity of disease were linked to higher odds of in-hospital mortality.
The mortality of stroke hospitalizations decreased likely reflecting advancements in stroke care and prevention. Decreasing of mortality with increasing of severe stroke patients indicated that we should pay more attention to rehabilitation and life quality of stroke patients. Specific individual and hospital-level characteristics may be targets for facilitating further declines.
We conducted a dose–response meta-analysis of prospective studies to summarize evidence of the association between tea consumption and the risk of breast, colorectal, liver, prostate, and stomach cancer.
We searched PubMed and two other databases. Prospective studies that reported risk ratios (RRs) with 95% confidence intervals (CIs) of cancer risk for ≥3 categories of tea consumption were included. We estimated an overall RR with 95% CI for an increase of three cups/day of tea consumption, and, usingrestricted cubic splines, we examined a nonlinear association between tea consumption and cancer risk.
Forty-one prospective studies, with a total of 3,027,702 participants and 49,103 cancer cases, were included. From the pooled overall RRs, no inverse association between tea consumption and risk of five major cancers was observed. However, subgroup analysis showed that increase in consumption of three cups of black tea per day was a significant risk factor for breast cancer (RR, 1.18; 95% CI, 1.05-1.32).
Ourresults did not show a protective role of tea in five major cancers. Additional large prospective cohort studies are needed to make a convincing case for associations.
Tea consumption; Dose–response; Meta-analysis; Cancer
Knowledge of drug safety in the pediatric population of China is limited. This study was designed to evaluate ADRs in children reported to the spontaneous reporting system (SRS) of Shanghai in 2009.
Methodology and Principal Findings
Crude ADR reports submitted to Shanghai SRS in 2009 for individuals aged from birth to 17 years (including 17 years) were included. Data were analyzed with respect to age, gender, category of ADR (System Organ Class [SOC]), the severity of reports and type of reporter.
A male overrepresentation was observed regarding the total number of reports. The most frequently reported group of drugs were vaccines (42.15%). Skin rash and fever were the commonest symptoms reported in the total pediatric dataset. The proportion of children that suffered from a serious ADR was 2.16% and that for drug related deaths was 0.34%. And we found that the multiple drug exposure experienced a high proportion of serious ADRs compared with the single drug use (χ2 = 15.99, P<0.0001). Sixty-five percent of ADRs were for children less than 6 years of age. And more than half of reports were from doctors.
In our study, consumers were more likely to report new ADRs though they appear to contribute a relatively small percentage of total reports. We propose that patients would take an active role in reporting ADRs. More researches are needed in order to achieve better understanding the characteristics of ADRs in pediatric population of China.
Statins are commonly used to lower total cholesterol levels in the general population to prevent cardiovascular events. However, the effects of statins in patients with chronic kidney disease remain unclear. We therefore performed a meta-analysis to assess the effects of statin therapy on cardiovascular outcomes in patients with mild to moderate chronic kidney disease.
We systematically searched PubMed, EmBase, the Cochrane Central Register of Controlled Trials, proceedings of major meetings, and reference lists of articles for relevant literature. Only randomized clinical trials were included. Outcomes analysed included cardiovascular disease, total mortality, myocardial infarction, stroke, cardiovascular death, and possible drug-related adverse events. Subgroup analyses were also performed based on the population characteristics and clinical indexes.
Twelve trials met our inclusion criteria. Overall, statin therapy resulted in a 24% reduction in the risk of cardiovascular disease (RR = 0.76,95% confidence interval [CI], 0.72– 0.80), a 21% reduction in the risk of total mortality (RR = 0.79,95% CI, 0.72–0.86), a 34% reduction in the risk of myocardial infarction (RR = 0.66,95% CI, 0.52–0.83), a 30% reduction in the risk of stroke (RR = 0.70,95% CI, 0.57–0.85), and a 17% reduction in the risk of cardiovascular mortality (RR = 0.83,95% CI, 0.73– 0.93). No statistically significant drug-related adverse events were noted. Subgroup analysis indicated that some important factors such as baseline creatinine level ≥1.5 mg/dL, baseline glomerular filtration rate (GFR), and cardiovascular disease history could affect cardiovascular outcomes.
Statin therapy had a clear effect on cardiovascular disease, total mortality, stroke, and myocardial infarction in patients with mild to moderate renal disease. Subgroup analysis indicated that baseline GFR, baseline creatinine level, and a history of cardiovascular disease might play an important role in the cardiovascular outcomes.
Statin; Cardiovascular events; Chronic kidney disease; Meta-analysis
In vitro amplified human leukocyte antigen (HLA)-haploidentical donor immune cell infusion (HDICI) is not commonly used in children. Therefore, our study sought to evaluate its safety for treating childhood malignancies. Between September 2011 and September 2012, 12 patients with childhood malignancies underwent HDICI in Sun Yat-sen University Cancer Center. The median patient age was 5.1 years (range, 1.7-8.4 years). Of the 12 patients, 9 had high-risk neuroblastoma (NB) [7 showed complete response (CR), 1 showed partial response (PR), and 1 had progressive disease (PD) after multi-modal therapies], and 3 had Epstein-Barr virus (EBV)-positive lymphoproliferative disease (EBV-LPD). The 12 patients underwent a total of 92 HDICIs at a mean dose of 1.6×108 immune cells/kg body weight: 71 infusions with natural killer (NK) cells, 8 with cytokine-induced killer (CIK) cells, and 13 with cascade primed immune cells (CAPRIs); 83 infusions with immune cells from the mothers, whereas 9 with cells from the fathers. Twenty cases (21.7%) of fever, including 6 cases (6.5%) accompanied with chills and 1 (1.1%) with febrile convulsion, occurred during infusions and were alleviated after symptomatic treatments. Five cases (5.4%) of mild emotion changes were reported. No other adverse events occurred during and after the completion of HDIDIs. Neither acute nor chronic graft versus host disease (GVHD) was observed following HDICIs. After a median of 5.0 months (range, 1.0-11.5 months) of follow-up, the 2 NB patients with PR and PD developed PD during HDICIs. Of the other 7 NB patients in CR, 2 relapsed in the sixth month of HDICIs, and 5 maintained CR with disease-free survival (DFS) ranging from 4.5 to 11.5 months (median, 7.2 months). One EBV-LPD patient achieved PR, whereas 2 had stable disease (SD). Our results show that HDICI is a safe immunotherapy for childhood malignancies, thus warranting further studies.
Childhood malignancies; HLA-haploidentical donor cells; immunotherapy; safety
ErbB2 tyrosine kinase inhibitors (TKI) block tyrosine autophosphorylation and activation of the full-length transmembrane ErbB2 receptor (p185ErbB2). In addition to p185ErbB2 truncated forms of ErbB2 exist in breast cancer cell lines and clinical tumors. The contribution of these truncated forms, specifically those expressed in tumor cell nuclei, to the development of therapeutic resistance to ErbB2 TKIs has not been previously demonstrated. Here we show that expression of a 95 kDa tyrosine phosphorylated form of ErbB2, herein referred to as p95L (lapatinib-induced p95) was increased in ErbB2+ breast cancer cells treated with potent ErbB2 TKIs (lapatinib, GW2974). Expressed in tumor cell nuclei, tyrosine phosphorylation of p95L was resistant to inhibition by ErbB2 TKIs. Furthermore, the expression of p95L was increased in ErbB2+ breast cancer models of acquired therapeutic resistance to lapatinib that mimic the clinical setting. Pretreatment with proteasome inhibitors blocked p95L induction in response to ErbB2 TKIs, implicating the role of the proteasome in the regulation of p95L expression. In addition, tyrosine phosphorylated c-terminal fragments of ErbB2, generated by alternate initiation of translation and similar in molecular weight to p95L, were expressed in tumor cell nuclei, where they too were resistant to inhibition by ErbB2 TKIs. When expressed in the nuclei of lapatinib sensitive ErbB2+ breast cancer cells, truncated ErbB2 rendered cells resistant to lapatinib-induced apoptosis. Elucidating the function of nuclear truncated forms of ErbB2, and developing therapeutic strategies to block their expression and/or activation, may enhance the clinical efficacy of ErbB2 TKIs.
Truncated; nuclear; ErbB2; resistance; tyrosine kinase inhibitors
Objective: To investigate the inhibitory effect of plasmid-based survivin-specific short hairpin RNA and GRIM-19 on the growth of Hep-2 laryngeal cancer cells. Methods: The plasmid expressing survivin-specific short hairpin RNA (shRNA) and GRIM-19 (p-siRNA survivin/GRIM-19) was prepared and transfected into Hep-2 cells with Lipofectamine 2000. The mRNA and protein expression of surviving and GRIM-19 were measured with RT-PCR and western blot assay, respectively. MTT assay was employed to detect the proliferation of Hep-2 cells, and flow cytometry and AO/EB assay were done to determine the apoptosis of Hep-2 cells. Results: In the p-siRNA survivin/GRIM-19, the mRNA and protein expression of survivin was markedly reduced by 54.4% and 42.2%, and the reduction in protein expression of surviving was more obvious than that in the p-siRNA survivin group (37%) (P<0.05). The protein expression of GRIM-19 was markedly enhanced when compared with the control group (P<0.01). MTT assay revealed the proliferation of Hep-2 cells undergoing transfection with p-siRNA survivin/GRIM-19 was markedly inhibited, and the inhibition rate was as high as 79%, which was higher than that in the psi-survivin group (45%) and p-GRIM-19 group (35%). AO/EB assay and flow cytometry indicated that the apoptotic cells in the p-siRNA survivin/GRIM-19 group were dramatically increased as compared to the psi-survivin group and p-GRIM-19 group. Conclusion: The p-siRNA survivin/GRIM-19 has marked decrease in survivin expression and dramatic increase in GRIM-19 expression. Moreover, silencing of survivin and over-expression of GRIM-19 can significantly inhibit the growth and induce the apoptosis of Hep-2 in vitro and in vivo.
Co-expression plasmid; gene silencing; survivin; laryngeal cancer