[The impact of human umbilical cord-derived mesenchymal stem cells on the pancreatic function of type 2 diabetic mice and their regulatory role on NLRP3 inflammasomes].

Objective: To investigate the effect and regulation of umbilical cord-derived mesenchymal stem cells (UC-MSCs) on islets function and NOD-like receptor family, pyrin domain containing 3 (NLRP3) and autophagy in type 2 diabetic mellitus (T2DM) mice. Methods: Experimental study. Twenty, 8-week-old, male C57BL/6J mice were selected and divided into a normal control group (n=5) and a high-fat feeding modeling group (n=15). The model of T2DM was established by high-fat feeding combined with intraperitoneal injection of low-dose streptozotocin. After successful modeling, those mice were divided into a diabetes group (n=7) and a UC-MSCs treatment group (n=7). The UC-MSCs treatment group was given UC-MSCs (1×106/0.2 ml phosphate buffer solution) by tail vein infusion once a week for a total of 4 weeks; the diabetes group was injected with the same amount of normal saline, and the normal control group was not treated. One week after the treatment, mice underwent intraperitoneal glucose tolerance tests and intraperitoneal insulin tolerance tests, and then the mice were sacrificed to obtain pancreatic tissue to detect the expressions of interleukin-1ß (IL-1ß) and pancreatic and duodenal homeobox 1 (PDX-1) by immunofluorescence. The bone marrow-derived macrophages were stimulated with lipopolysaccharide and adenosine triphosphate (experimental group) in vitro, then co-cultured with UC-MSCs for 24 h (treatment group). After the culture, enzyme-linked immunosorbent assay was used to detect the secretion level of IL-1ß in the supernatant, and immunofluorescence staining was used to detect the expression of NLRP3 inflammasome, and related autophagy proteins. Statistical analysis was performed using unpaired one-way analysis of variance, repeated measure analysis of variance. Results: In vivo experiments showed that compared with the diabetes group, the UC-MSCs treatment group partially repaired islet structure, improved glucose tolerance and insulin sensitivity (all P<0.05), and the expression of PDX-1 increased and IL-1ß decreased in islets under confocal microscopy. In vitro experiments showed that compared with the experimental group, the level of IL-1ß secreted by macrophages in the treatment group was decreased [(85.9±74.6) pg/ml vs. (883.4±446.2) pg/ml, P=0.001], the expression of NLRP3 inflammasome and autophagy-related protein P62 was decreased, and the expressions of microtubule-associated protein 1 light chain 3ß (LC3) and autophagy effector Beclin-1 were increased under confocal microscopy. Conclusions: UC-MSCs can reduce the level of pancreatic inflammation in T2DM mice, preserving pancreatic function. This might be associated with the ability of UC-MSCs to inhibit the activity of NLRP3 inflammasomes in macrophages and enhance autophagy levels.

[Study on revision of standard limits for benzene in"Standards for indoor air quality（GB/T 18883-2022）"in China].

Benzene, as a major indoor pollutant, has received widespread attention. In order to better control indoor benzene pollution and protect people's health, the limit value of benzene in the"Standards for indoor air quality (GB/T 18883-2022)'' was reduced from 0.11 mg/m3 to 0.03 mg/m3. This study reviewed and discussed the relevant technical contents of the determination of benzene limit value, including the exposure status of benzene, health effects, and derivation of the limit value. It also proposed prospects for the future direction of formulating indoor air benzene standards.

[The efficacy and safety of nerve loop blocking in the treatment of blepharospasm in Meige syndrome].

Objective: To evaluate the efficacy and safety of nerve loop blocking in the treatment of blepharospasm caused by Meige syndrome. Methods: It was a retrospective case series study. Patients with Meige syndrome characterized by blepharospasm or blepharospasm-oromandibular dystonia who underwent nerve loop blocking in the Ophthalmology Department of Henan No. 3 Provincial People's Hospital from April 2018 to January 2020 were included. Before and after surgery, blepharospasm was graded, and the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) was used to score the symptoms of ocular and oral dystonia. The improvement rate of ocular spasm was calculated after surgery according to the scores. The postoperative complications were observed. The Wilcoxon rank test was used to compare the BFMDRS movement subscale scores before and after surgery. The independent sample Mann-Whitney U test was used to compare the improvement rates of eye spasm between male and female patients and between patients with and without combined oromandibular dystonia. Results: Among the 199 patients included, 64 (32.2%) were males, and 135 (67.8%) were females, aged 58 (51, 64) years (22-79 years). The postoperative follow-up period was 24 (21, 28) months. Preoperatively, blepharospasm was graded as grade 3 in 12 patients (6.0%) and grade 4 in 187 patients (94.0%), while the postoperative blepharospasm grades were grade 0 in 100 patients (50.3%), grade 1 in 64 patients (32.2%), grade 2 in 31 patients (15.6%), and grade 3 in 4 patients (2.0%). There was statistically significant difference in the BFMDRS scores of ocular dystonia before and after surgery [8.0 (8.0, 8.0) vs. 0.0 (0.0, 1.0); Z=-12.41, P<0.001]. The improvement rate of blepharospasm in all patients was 100% (87.5%, 100%), ranging from 43.8% to 100%, with no statistically significant difference between patients of different genders and between patients with and without combined oral dystonia (both P>0.05). Statistically significant difference existed in the scores of oral dystonia before and after surgery [2.0 (0.5, 4.5) vs. 1.0 (0.5, 2.0); Z=-4.38, P<0.001], with 25 of 65 patients (38.5%) having their oral symptoms improved. Postoperative complications included eyelid valgus (7.5%, 15/199), frontal numbness (100%, 199/199) and tearing (89.9%, 179/199). Conclusion: Nerve loop blocking is a relatively safe and effective method in the treatment of blepharospasm symptoms of Meige syndrome.

Association of oxidative stress and Kashin-Beck disease integrated Meta and Bioinformatics analysis.

OBJECTIVE: To explore the association between oxidative stress (OS) and Kashin-Beck disease (KBD). METHODS: Terms associated with "KBD" and "OS" were searched in the six different databases up to October 2021. Stata 14.0 was used to pool the means and standard deviations using random-effect or fixed-effect model. The differentially expressed genes in the articular chondrocytes of KBD were identified, the OS related genes were identified by blasting with the GeneCards. The KEGG pathway and gene ontology enrichment analysis was conducted using STRING. RESULTS: The pooled SMD and 95% CI showed hair selenium (-4.59; -6.99, -2.19), blood selenium (-1.65; -2.86, -0.44) and glutathione peroxidases (-4.15; -6.97, -1.33) levels were decreased in KBD, whereas the malondialdehyde (1.12; 0.60, 1.64), nitric oxide (2.29; 1.31, 3.27), nitric oxide synthase (1.07; 0.81, 1.33) and inducible nitric oxide synthase (1.69; 0.62, 2.77) were increased compared with external controls. Meanwhile, hair selenium (-2.71; -5.32, -0.10) and glutathione peroxidases (-1.00; -1.78, -0.22) in KBD were decreased, whereas the malondialdehyde (1.42; 1.04, 1.80), nitric oxide (3.08; 1.93, 4.22) and inducible nitric oxide synthase (0.81; 0.00, 1.61) were elevated compared with internal controls. Enrichment analysis revealed apoptosis was significantly correlated with KBD. The significant biological processes revealed OS induced the release of cytochrome c from mitochondria. The cellular component of OS located in the mitochondrial outer membrane. CONCLUSIONS: The OS levels in KBD were significantly increased because of selenium deficiency, OS mainly occurred in mitochondrial outer membrane, released of cytochrome c from mitochondria, and induced apoptotic signaling pathway.

Prospective associations of circulating thrombospondin-2 level with heart failure hospitalization, left ventricular remodeling and diastolic function in type 2 diabetes.

BACKGROUND: Circulating thrombospondin-2 (TSP2) levels were associated with the development of heart failure (HF) in recent studies. However, these studies included only a minority of patients with type 2 diabetes, which is associated with an increased HF risk. As hyperglycemia induces TSP2 expression and its tissue expression increases in type 2 diabetes, we investigated the prospective association of circulating TSP2 with incident HF hospitalization (HHF), and its associations with longitudinal changes of echocardiographic parameters in type 2 diabetes. METHODS: Baseline serum TSP2 levels were measured in 4949 patients with type 2 diabetes to determine its association with incident HHF using multivariable Cox regression analysis. In the echocardiographic study, baseline serum TSP2 levels were measured in another 146 patients with type 2 diabetes but without cardiovascular diseases who underwent detailed transthoracic echocardiography at baseline and after 1 year. RESULTS: Over a median follow-up of 7.8 years, 330 of 4949 patients (6.7%) developed incident HHF. Baseline serum TSP2 levels were independently associated with the development of HHF (HR 1.31, 95%CI 1.06-1.62, p = 0.014) after adjustments for baseline conventional cardiovascular risk factors, atrial fibrillation, estimated glomerular filtration rate, albuminuria and high-sensitivity C-reactive protein level, use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, loop-diuretics, aspirin, insulin, metformin and sodium-glucose co-transporter 2 inhibitors. Moreover, baseline serum TSP2 levels were independently associated with increase in average E/e' and left atrial volume index (p = 0.04 and < 0.01, respectively). CONCLUSION: Serum TSP2 levels were independently associated with both incident HHF and deterioration in diastolic function in type 2 diabetes. TRIAL REGISTRATION: Not Applicable.

The interplay between host cellular and gut microbial metabolism in NAFLD development and prevention.

Metabolism regulation centred on insulin resistance is increasingly important in nonalcoholic fatty liver disease (NAFLD). This review focuses on the interactions between the host cellular and gut microbial metabolism during the development of NAFLD. The cellular metabolism of essential nutrients, such as glucose, lipids and amino acids, is reconstructed with inflammation, immune mechanisms and oxidative stress, and these alterations modify the intestinal, hepatic and systemic environments, and regulate the composition and activity of gut microbes. Microbial metabolites, such as short-chain fatty acids, secondary bile acids, protein fermentation products, choline and ethanol and bacterial toxicants, such as lipopolysaccharides, peptidoglycans and bacterial DNA, play vital roles in NAFLD. The microbe-metabolite relationship is crucial for the modulation of intestinal microbial composition and metabolic activity. The intestinal microbiota and their metabolites participate in epithelial cell metabolism via a series of cell receptors and signalling pathways and remodel the metabolism of various cells in the liver via the gut-liver axis. Microbial metabolic manipulation is a promising strategy for NAFLD prevention, but larger-sampled clinical trials are required for future application.

[Risk factors of perivalvular leakage after transcatheter aortic valve replacement with Venus-A valve].

Objective: To investigate the risk factors of moderate or severe perivalvular leakage (PVL) after transcatheter aortic valve replacement (TAVR) with Veneus-A valve. Methods: This study was a single-center case-control study. The clinical data of patients with severe aortic stenosis, who underwent TAVR in the Department of Cardiology of Second Affiliated Hospital of Army Medical University from October 2017 to January 2021, were analyzed. According to the circumferential extent of prosthetic valve paravalvular regurgitation measured by transthoracic echocardiography before discharge (patients who died in hospital were referred to transesophageal echocardiography results after valve implanted), the patients were divided into moderate or severe PVL group and mild or non-PVL group. The clinical features, CT scan and analysis results of aortic root were compared between the two groups. Multivariate logistic regression analysis was used to identify the independent risk factors of postoperative moderate or severe PVL, and receiver operating characteristic (ROC) curve was used to explore the predictive value of related factors. Results: Eighty-two patients (mean age: (70.9±6.5) years, 46 males) were included in the analysis, there were 16 patients in the moderate or severe PVL group and 66 patients in the mild or non-PVL group. The proportion of male gender, depth of valve implantation, size of valve annulus and left ventricular outflow tract (LVOT), and coverage index of LVOT were significantly higher in moderate or severe PVL group than those in mild or non-PVL group (Pall<0.05). As there was a strong collinearity among the valve annular short diameter, LVOT short diameter and LVOT coverage index (partial correlation coefficient R 0.251-0.779, P<0.05), these parameters were not entered in regression model. Multivariate logistic regression analysis showed that valve implantation depth(OR=1.239,95%CI 1.036-1.442,P=0.023), aortic angulation(OR=1.128, 95%CI 1.044-1.312,P=0.038)and LVOT tract coverage index (OR=1.123, 95%CI1.003-1.315, P=0.032) were independent risk factors for moderate or severe PVL after TAVR. The ROC curve showed that the valve implantation depth could predict the occurrence of moderate or severe PVL after TAVR (area under ROC curve (AUC)=0.697, 95%CI 0.554-0.851, P=0.039). Conclusion: Among patients with severe aortic stenosis who undergo TAVR with Venus-A valve, the implantation depth, aortic angulation and LVOT coverage index are independent risk factors of moderate/severe PVL after TAVR, among which valve implantation depth could be used to predict the occurrence of moderate/severe PVL after TAVR.

[Experts consensus for the diagnosis, treatment, and prevention of coronavirus disease 2019 in the elderly].

Coronavirus disease 2019 (COVID-19) can cause great damage to the elderly patients and lead to high mortality. The clinical presentations and auxiliary examinations of the elderly patients with COVID-19 are atypical, due to the physiological ageing deterioration and basal pathological state. The treatment strategy for the elderly patients has its own characteristics and treatment protocol should be considered accordingly. To improve the diagnosis, treatment, and prevention of COVID-19 in the elderly, the Expert Committee of Geriatric Respiratory and Critical Care Medicine, China Society of Geriatrics established the "Expert consensus for the diagnosis, treatment, and prevention of coronavirus disease 2019 in the elderly" . We focused on the clinical characteristics and key points for better treatment and prevention of COVID-19 in the elderly. (1) For diagnosis, atypical clinical presentation of COVID-19 in the elderly should be emphasized, which may be complicated by underlying disease. (2) For treatment, strategy of multiple disciplinary team (mainly the respiratory and critical care medicine) should be adopted and multiple systemic functions should be considered. (3) For prevention, health care model about integrated management of acute and chronic diseases, in and out of hospital should be applied.

[Electrophysiological features of patients with subacute combined degeneration].

Objective: To investigate the electrophysiological features of patients with subacute combined degeneration (SCD). Methods: The electrophysiological data of 85 hospitalized patients in Department of Neurology, First Medical Centre, Chinese PLA General Hospital from January 2014 to September 2018 were retrospectively analyzed. Results: Abnormality rate of motor nerve conduction (27.4%(93/339)) was lower than that of sensory nerve conduction (45.9%(107/233)) (P<0.001). Abnormality of sensory nerve action potential amplitude was more frequent than conduction velocity abnormality (22.7%(53/233) vs 4.7%(11/233), P=0.001). Abnormality rate of needle electromyogram (EMG) was higher in lower limbs than upper limbs (31.9%(59/185) vs 5.7%(5/87), P<0.001). Spontaneous potentials were unrelated to disease duration or severity. Abnormal somatosensory evoked potential (SEP) results appeared more frequent in lower limbs (80.8%(118/146)) than upper limbs (61.1%(77/126)) (P<0.001). SEP abnormalities (71.7%(195/272)) were more common than nerve conduction abnormalities (35.0%(200/572)). Abnormal findings presented in 15/16 of visual evoked potential (VEP) studies. Neurological severity score were correlated with electrophysiological findings. Conclusions: Posterior funiculus is more likely to be affected than peripheral nerves in SCD patients. The sensory nerves rather than motor nerves, lower limbs rather than upper limbs, axons of sensory nerves rather than myelin, are more severely affected. Electrophysiological tests can provide evidence in early diagnosis, lesions location, and disease severity evaluation for SCD.

[Time-series analysis on the relationship between ambient PM2.5 and daily outpatient visits due to allergic conjunctivitis among children in Shenzhen].

Objective: To explore the short-term effects of ambient PM2.5 on the outpatient visits of allergic conjunctivitis among children in Shenzhen. Methods: It was a ecological study. Data on daily visits including date of visit, sex and age from children with allergic conjunctivitis were collected from Shenzhen Eye Hospital and Shenzhen Children's Hospital in 2018. Related data on air pollution (PM2.5, PM10, SO2, NO2, CO and O3) and meteorology (atmospheric pressure, temperature and relative humidity) were also collected. Pearson correlation analysis was used for normal distribution data and Spearman rank correlation analysis was used for non-normal distribution data. Generalized additive model was used to estimate the impact of PM2.5 pollution on allergic conjunctivitis outpatients and the lagging effects. Results: In 2018, there were 16 133 allergic conjunctivitis outpatients in the two hospitals. The maximum age was 18 years and the minimum age was 2 months. Males accounted for 49.3%. The daily average concentration of PM2.5 was 22 (15, 31) µg/m3. Changes of the concentration of PM2.5 had a positive correlation with the amount of allergic conjunctivitis visits, and the Spearman correlation coefficient was 0.150 (P=0.004). The single pollutant model showed that the strongest effect appeared at 3 days (RR=1.111， 95%CI:1.071-1.152). A 10 µg/m3 increase of PM2.5 would result in an excessive number of allergic conjunctivitis outpatients as much as 11.112% (95%CI：7.011%-15.212%). In the multiple air pollutants models, after the introduction of NO2, O3 and CO, the concentration of PM2.5 showed an enhanced effect on the number of hospital visits due to allergic conjunctivitis on the same day, and the difference was statistically significant (P<0.05). Conclusion: Changes of the concentration of PM2.5 had a positive correlation with daily outpatient visits of allergic conjunctivitis among children in Shenzhen. (Chin J Ophthalmol, 2020, 56: 608-614).

The headache under-response to treatment (HURT) questionnaire, an outcome measure to guide follow-up in primary care: development, psychometric evaluation and assessment of utility.

BACKGROUND: Headache disorders are both common and burdensome but, given the many people affected, provision of health care to all is challenging. Structured headache services based in primary care are the most efficient, equitable and cost-effective solution but place responsibility for managing most patients on health-care providers with limited training in headache care. The development of practical management aids for primary care is therefore a purpose of the Global Campaign against Headache. This manuscript presents an outcome measure, the Headache Under-Response to Treatment (HURT) questionnaire, describing its purpose, development, psychometric evaluation and assessment for clinical utility. The objective was a simple-to-use instrument that would both assess outcome and provide guidance to improving outcome, having utility across the range of headache disorders, across clinical settings and across countries and cultures. METHODS: After literature review, an expert consensus group drawn from all six world regions formulated HURT through item development and item reduction using item-response theory. Using the American Migraine Prevalence and Prevention Study's general-population respondent panel, two mailed surveys assessed the psychometric properties of HURT, comparing it with other instruments as external validators. Reliability was assessed in patients in two culturally-contrasting clinical settings: headache specialist centres in Europe (n = 159) and primary-care centres in Saudi Arabia (n = 40). Clinical utility was assessed in similar settings (Europe n = 201; Saudi Arabia n = 342). RESULTS: The final instrument, an 8-item self-administered questionnaire, addressed headache frequency, disability, medication use and effect, patients' perceptions of headache "control" and their understanding of their diagnoses. Psychometric evaluation revealed a two-factor model (headache frequency, disability and medication use; and medication efficacy and headache control), with scale properties apparently stable across disorders and correlating well and in the expected directions with external validators. The literature review found few instruments linking assessment to clinical advice or suggested actions: HURT appeared to fill this gap. In European specialist care, it showed utility as an outcome measure across headache disorders. In Saudi Arabian primary care, HURT (translated into Arabic) was reliable and responsive to clinical change. CONCLUSIONS: With demonstrated validity and clinical utility across disorders, cultures and settings, HURT is available for clinical and research purposes.

[Intervention effect assessment of response to heatwave in communities of four cities, China].

Objective: To evaluate the intervention effects of response to heatwave in communities of four cities, China. Methods: Baseline survey on heatwave and climate change related knowledge, attitude and practice (KAP) was conducted in the pilot communities in Harbin, Nanjing, Shenzhen and Chongqing, using face-to-face questionnaire interview in November, 2011 to November, 2013. Finally, 1 604 residents were interviewed. Intervention measures were implemented in summers of 2013 and 2014, including delivering early warning information of heatwave health risk and launching health education and promotion. The second survey was conducted in same communities using the same questionnaire and sampling method as baseline survey in November, 2014, and 1 640 residents were interviewed. The Chi-square test was used to compare the demographic characteristics and KAP of community residents between before and after intervention, and the factors that affected the intervention effect were selected by logistic multiple stepwise regression model. Results: The age of the residents interviewed before and after intervention was (46.4 ± 15.5) years and (45.0 ± 15.9) years, respectively. Overall, the residents' awareness rates of heatwave before and after intervention were 70.5% (1 131/1 604) and 82.9% (1 359/1 640) (χ2=69.40, P<0.001). The rate of residents who had wished to receive early warning information increased 6.3% (χ2=41.11, P<0.001), which reached 94.6% (1 551/1 604) after intervention from 88.3% (1 416/1 604) in baseline survey. Both heatwave health risk early warning and health education had big impacts to residents. There were 92.7% (1 105 residents) among the 1 192 residents who had received the early warning information arrange work and rest time according to the early warning information and 93.0% (1 231 residents) among the 1 323 residents who knew about health education activities being conducted in community thought that the community health education activities had made active role in protecting health from heatwaves. After a series of intervention, male had a effect on attitude about hot wave than female in Nanjing and Chongqing, OR (95%CI) were 1.48(1.02-2.16) and 1.45 (1.18-2.05) , respectively; compared with subjects below primary school education, people with college degree or above had higer KAP in all cities (ORs range from 1.18 to 2.05), P<0.05; regular physical exercise (ORs range from 1.39 to 2.70) also had profound impacts on KAP in all cities (P<0.05). Conclusion: s Early warning and health education were effective measures to enhance residents' response capacity to climate change.

[Efficacy and safety of catheter-directed interventional therapy in patients with acute pulmonary embolism].

Objective: To evaluate the efficacy and safety of catheter-directed interventional therapy in patients with acute pulmonary embolism(PE). Methods: PE was diagnosed by CT pulmonary angiography(CTPA). After risk stratification, a total of 79 PE patients (age (58.9±14.9) years old)were treated with catheter-directed interventional therapy via pulmonary vessels. The changes of pulmonary hemodynamics were compared before and after treatment. The risk of complications and side effects were observed. Results: The pulmonary artery pressure was changed followed by interventional therapy. The interventional therapy significantly decreased mean pulmonary arterial pressure (mPAP) from (35.3±11.2)mmHg (1 mmHg=0.133 kPa) to (30.0±10.6)mmHg (t=8.803,P<0.05) and the echocardiographic derived right ventricular dimension to left ventricular dimension (RV/LV) ratio from 0.93±0.16 to 0.83±0.15 (t=6.868,P<0.05). The arterial partial pressure of oxygen was increased from (69.0±8.6)mmHg to (75.1±9.9)mmHg (t=8.561,P<0.05) . The oxygen saturation was also increased from (93.9±2.9)% to (95.1±1.9)% at 24 h after the treatment (t=2.621,P<0.05) . Patients were further grouped as high-risk group (n=28) and intermediate risk group (n=51). mPAP and RV/LV ratio were significantly reduced in the two subgroups (all P<0.05) and the range of reduction was more significant in the high-risk group. Five patients experienced minor bleeding complication, 3 patients suffered worsened dispone post procedure and were treated with mechanical ventilation, 1 patient died, and 1 patient developed recurrent PE. Conclusion: The catheter-directed interventional therapy improves pulmonary hemodynamics and reduces load of right ventricle both in high-risk or intermediate risk PE patients, this therapy strategy is safe and effective for patients with PE.

[Impact of PM2.5 on daily outpatient numbers for respiratory diseases in Shenzhen, China].

Objective: To assess the association between the concentration of the air pollutant PM2.5 and daily outpatient visits for respiratory disease. Methods: All records of daily outpatient visits to three hospitals in Shenzhen from January 1 to December 31, 2013 were collected. Daily air pollution monitoring and meteorology data from the same period were also collected in Shenzhen. The data were analyzed using a semiparametric generalized additive model with Poisson distribution of time series analysis controlling for long-term and seasonal trends, flu, DOW, public holidays, and meteorological factors. The excess risk(ER)of respiratory disease and its 95% CI value were calculated, along with the incremental increase of 10 µg/m3 in PM2.5 concentration. Results: Number of outpatient visits for respiratory diseases totaled 1 428 672(daily range: 1 790-5 228). The annual average PM2.5 concentration was 40.2 µg/m3(daily range: 7.2-137.1 µg/m3). The lag1 factor had the most significant impact on the lag effect. We estimated that a 10 µ g/m3 increase in day-before PM2.5 concentration was associated with a 1.809%(95% CI: 1.709%-1.909%)ER of visits for respiratory disease. After controlling for other pollutants(NO2, CO, and O3), the effect remained stable. When NO2, CO, and O3 were introduced separately, for every 10 µg/m3 rise in PM2.5 concentration, the excess risk of daily outpatient visits for respiratory disease was 1.814%(95% CI: 1.706%-1.923%), 2.780%(95% CI: 2.668%-2.892%), and 1.513%(95% CI: 1.403%-1.624%), respectively. With simultaneous control of NO2 and O3, NO2 and CO, and CO and O3, for every 10 µg/m3 rise in PM2.5 concentration, the excess risk of respiratory disease was 1.369%(95% CI: 1.242%-1.497%), 2.709%(95% CI: 2.590%-2.828%), and 2.577%(95% CI: 2.452%-2.702%), respectively. With simultaneous control of NO2, CO, and O3, for every 10 µg/m3 rise in PM2.5 concentration, the excess risk of respiratory disease was 2.370%(95% CI: 2.231%-2.509%). Conclusions: PM2.5 can increase the risk of outpatient visits for respiratory disease in Shenzhen.

THE EFFECT OF DIHYDROARTEMISININ ON THE PROLIFERATION, METASTASIS AND APOPTOSIS OF HUMAN OSTEOSARCOMA CELLS AND ITS MECHANISM.

This study aims to research the effect of dihydroartemisinin on the proliferation, metastasis and apoptosis in human osteosarcoma cells 143B and the underlying mechanism. This study designed five groups for experiment and control, using dimethylsulfoxide (DMSO), and docosahexaenoic acid (DHA) at concentrations of 15, 25, 35 µmol.L-1 respectively. Experiments including methyl thiazolyl tetrazolium (MTT) assay, clone formation assay, Hoechst 33258 staining assay, luciferase reporter plasmid assay, Western blot and scratch test were carried out. In addition, SPSS 18.0 software from IBM was used for statistical analysis and all the data obtained from the experiments were expressed as mean ± SD, and variance was used to compare the difference between the groups. DHA is proved to be able to inhibit the proliferation and metastasis of osteosarcoma cells, as well as leaving a positive effect on apoptosis in the cytomorphosis. It achieves regulation over the human osteosarcoma cells by keeping the expression of related protein under control.

SNPs in the transforming growth factor-ß pathway as predictors of outcome in advanced lung adenocarcinoma with EGFR mutations treated with gefitinib.

BACKGROUND: The aim of this study was to evaluate whether genetic variations in the transforming growth factor-ß (TGF-ß) pathway influenced clinical outcome of advanced lung adenocarcinoma with epidermal growth factor receptor (EGFR) mutations treated with gefitinib. PATIENTS AND METHODS: Two hundred six patients with advanced lung adenocarcinomas were enrolled in this study. EGFR mutation in these tumors was detected. Among them, 106 patients with EGFR mutation and 37 of 100 patients with wild type were treated with gefitinib. Genotype of 33 single-nucleotide polymorphisms (SNPs) from 13 genes involved in the TGF-ß signaling pathway was determined, and their association with survival time was analyzed. Univariate and multivariate analyses were carried out to assess the role of biological/clinical parameters in progression-free survival (PFS) and overall survival (OS) using Pearson's χ(2) test, log-rank test, and Cox proportional hazards model. RESULTS: Among SNPs analyzed, multivariate analysis showed the cytidylate and thymidine (CT) genotype of SMAD3: rs11632964 was associated with a longer OS and PFS when the entire cohort of 143 patients were included; the association was significant in the patients with EGFR mutant tumors (30.8 versus 17.5 months; log-rank P = 0.020; and 20.8 versus 9.4 months; log-rank P = 0.001), when compared with patients with wild-type EGFR tumors. In patients with mutant EGFR, the CT genotype of SMAD3: rs11071938 and the cytidylate and cytidylate genotype of SMAD3: rs6494633 were also found to be associated with better PFS. Dual luciferase reporter assays showed gefitinib-resistant PC9/G cells transfected with SMAD3: rs11632964T allelic reporter construct showed significantly lower luciferase activities compared with cells expression C allelic reporter construct. There was significantly decreased expression of SMAD3 and pi-SMAD3 in the PC-9/G cells compared with PC-9. CONCLUSIONS: Among the candidate genes involved in the TGF-ß pathway, the polymorphisms of SMAD3 appear to be highly predictive of outcome of patients with lung adenocarcinoma after gefitinib treatment, especially in those with EGFR mutations.

Role of nephrin phosphorylation inducted by dexamethasone and angiotensin II in podocytes.

The phosphorylation of nephrin plays an important role in maintaining the normal structure and function in podocytes. Dexamethasone (Dex) is usually used to treat glomerular diseases with proteinuria. In this study, we observated the effect of Dex and angiotensin II (AngII) on the change of nephrin phosphorylation in cultured podocytes. In vitro, cultured podocytes were exposed to AngII (10(-6) mol/L) pretreated with or without Dex (100 nM) for different time periods. Nck or Fyn were silenced by small interfering RNA (siRNA), nephrin and its phosphorylation expression were analyzed by Western blotting. In vitro, the phosphorylation of nephrin was significantly reduced after AngII stimulation (P < 0.05). Dex significantly resisted podocyte injury inducted by AngII via increasing the phosphorylation of nephrin (P < 0.05), siRNA silencing Nck can partially inhibited nephrin phosphorylation, siRNA silencing Fyn can completely inhibited nephrin phosphorylation. Phosphorylation of nephrin is important for the survival status of podocytes. Glucocorticoid treatment for human glomerulonephritis may exert its function by regulating Nck and Fyn complex to promote phosphorylation of nephrin. These results elucidate a novel mechanism of glucocorticoid treatment for glomerulonephritis.

Impact of Annexin A3 expression in gastric cancer cells.

Annexin A3 participates in various biological processes, including tumorigenesis, drug resistance, and metastasis. The aim of this study was to investigate the expression of Annexin A3 in gastric cancer and its relationship with cell differentiation, migration, and invasion of gastric cancer cells. Annexin A3 expression in gastric cancer tissues was detected by quantitative real-time PCR and Western blotting. The proliferation of gastric cancer cells was measured by the MTT assay. Cell migration and invasion were determined via wound healing and transwell assays, respectively. Knock down of endogenous Annexin A3 in gastric cancer BGC823 cells was performed using siRNA technology. The expression of Annexin A3 was significantly upregulated in gastric cancer tissues, and negatively correlated with the differentiation degree. Silencing of endogenous Annexin A3 suppressed the proliferation, migration, and invasion of BGC823 cells. Additionally, the expression of p21, p27, TIMP-1, and TIMP-2 was upregulated, and the expression of PCNA, cyclin D1, MMP-1, and MMP-2 decreased in cells treated with Annexin A3-siRNA. Annexin A3 was upregulated in gastric cancer cells. Deletion of endogenous Annexin A3 significantly inhibited gastric cancer cell proliferation, migration, and invasion.

Phylogenetic, molecular and drug-sensitivity analysis of HA and NA genes of human H3N2 influenza A viruses in Guangdong, China, 2007-2011.

Annual H3N2 subtype influenza outbreaks in Guangdong, China are a severe public health issue and require ongoing monitoring of emerging viral variants. The variation and evolution of haemagglutinin (HA) and neuraminidase (NA) genes of influenza isolates from Guangdong during 2007-2011 and others from GenBank were analysed using Lasergene 7.1 and MEGA 5.05, and serological analysis of antigens was determined by haemagglutination inhibition (HI). Susceptibility to antiviral drugs was correlated with genetic mutations. Phylogenetic analysis and alignment of HA and NA genes were performed on 18 Guangdong isolates and 26 global reference strains. The non-synonymous (dN) evolutionary rate of HA1 was 3.13 times that of HA2. Compared with the A/Perth/16/2009 vaccine HA gene, homologies of Guangdong isolates were between 98.8-99.7% and 98.0-98·4% in 2009 and 2010, respectively. Amino-acid substitutions were found in five epitopes of HA1 from Guangdong isolates between 2007 and 2011, especially in epitopes B (N160K) and D (K174R/N). The K189E/N/Q and T228A mutations in the receptor-binding site (RBS) occurred in the 2010 strains, which affected the antigenicity of HA1. The antigenicity of the epidemic H3N2 isolates in 2010 was somewhat different from that of A/Perth/16/2009. The Guangdong H3N2 isolates were determined to be oseltamivir-resistant with IC50 of 0.396 ± 0.085 nmol/l (n=17) and zanamivir-resistant with IC50 of 0.477 ± 0.149 nmol/l (n=18). Variations were present in epitopes B and D, two sites in the RBS and two glycosylation sites in the Guangdong H3N2 HA1 gene. The majority of the Guangdong H3N2 isolates were sensitive to oseltamivir and zanamivir. Compared to the World Health Organization 2012 vaccine strains, Guangdong H3N2 strains varied genetically and antigenically to some degree.