Different doses of tenecteplase vs. alteplase for acute ischemic stroke within 4.5 hours of symptom onset: a network meta-analysis of randomized controlled trials.

Background: The optimal dose of tenecteplase vs. alteplase for acute ischemic stroke (AIS) has yet to be established. Therefore, we included the latest randomized controlled trials (RCT) to assess the efficacy and safety of different doses of tenecteplase vs. alteplase for AIS within 4.5 hours of symptom onset. Methods: Literature was searched in PubMed, Cochrane Library, Embase, Web of Science, and clinical trial registries until February 12, 2023. Odds ratios (OR) with 95% credible intervals (CrI) were estimated using Bayesian network meta-analysis (NMA). Treatments were ranked based on efficacy and safety using the surface under the cumulative ranking curve (SUCRA). Results: Eleven RCTs with 5,475 patients were included. Tenecteplase 0.25 mg/kg and alteplase 0.9 mg/kg had significantly higher rates of excellent functional outcome (tenecteplase: OR, 1.85; 95% CrI, 1.44-2.37; alteplase: OR, 1.60; 95% CrI, 1.29-1.97) and good functional outcome (tenecteplase: OR, 1.54; 95% CrI, 1.19-1.98; alteplase: OR, 1.40; 95% CrI, 1.14-1.74) than placebo, despite an increased risk of symptomatic intracranial hemorrhage. Furthermore, the NMA (OR, 1.16; 95% CrI, 1.01-1.33) and the pairwise meta-analysis (OR, 1.16; 95% CI, 1.02-1.33; P = 0.03) indicated that tenecteplase 0.25 mg/kg was superior to alteplase 0.9 mg/kg in excellent functional outcome. Alteplase 0.9 mg/kg (OR, 2.54; 95% CrI, 1.45-8.08) significantly increased the risk of any intracranial hemorrhage compared with placebo. SUCRA results demonstrated that tenecteplase 0.25 mg/kg ranked first and tenecteplase 0.4 mg/kg ranked last in efficacy outcomes. Conclusions: The NMA indicated that tenecteplase 0.25 mg/kg and alteplase 0.9 mg/kg are safe and significantly improve clinical outcomes in patients with AIS within 4.5 h of symptom onset. Furthermore, tenecteplase 0.25 mg/kg provides more benefit and has the potential to replace alteplase 0.9 mg/kg in AIS treatment. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/index.php, identifier: CRD42022343948.

Safety and efficacy of intravenous thrombolysis in patients with acute ischemic stroke taking direct oral anticoagulants prior to stroke: a meta-analysis.

BACKGROUND: To assess the safety and efficacy of intravenous thrombolysis (IVT) in patients with acute ischemic stroke (AIS) taking direct oral anticoagulants (DOACs) prior to stroke. METHODS: Literature was searched in PubMed, Cochrane Library, and Embase until March 13, 2023. The primary outcome was symptomatic intracranial hemorrhage (sICH). Secondary outcomes included excellent outcome (modified Rankin Scale [mRS] 0-1), functional independence (mRS 0-2), and mortality. Odds ratios (OR) with 95% confidence intervals (CI) were estimated using a random-effects model. RESULTS: Five non-randomized studies included 239,879 patients with AIS treated with IVT, with 3400 (1.42%) taking DOACs prior to stroke. The rates of sICH did not differ statistically between patients taking DOACs and those not taking anticoagulants (unadjusted OR 0.98; 95% CI 0.67-1.44; P = 0.92; adjusted OR 0.81; 95% CI 0.64-1.03; P = 0.09). Patients taking DOACs had significantly higher adjusted rates of excellent outcome (adjusted OR 1.22; 95% CI 1.06-1.40; P < 0.01) and functional independence (adjusted OR 1.25; 95% CI 1.10-1.42; P < 0.01) at discharge than those not taking anticoagulants. No significant difference was observed in mortality and other efficacy outcomes between groups after adjustment. CONCLUSION: The meta-analysis indicated that taking DOACs prior to stroke does not significantly increase the risk of sICH in selected patients with AIS treated with IVT. Furthermore, the benefits of IVT in selected patients taking DOACs appear to be comparable to those not taking anticoagulants. Further research is warranted to confirm the findings.

Altered Spontaneous Brain Activity in Cirrhotic Patients with Minimal Hepatic Encephalopathy: A Meta-Analysis of Resting-State Functional Imaging.

(1) Background: Minimal hepatic encephalopathy (MHE) is an important complication of decompensated cirrhosis. Previous studies have demonstrated spontaneous brain activity alterations in cirrhotic patients with MHE. However, the reported results are inconsistent, which has limited our understanding of the potential neural mechanisms. Thus, we conducted a quantitative meta-analysis of resting-state functional imaging studies to identify the regional activity alterations consistently involved in MHE. (2) Methods: We searched six databases to include resting-state functional imaging studies and compared spontaneous brain activity patterns between MHE patients and healthy controls (HCs), and between cirrhotic patients without minimal hepatic encephalopathy (NMHE) and HCs. Then, a separate whole-brain voxel-wise meta-analysis between MHE or NMHE patients and HCs was conducted using seed-based d mapping with permutation of subject images. We further conducted the conjunction analysis to assess the distinct regional activity alterations between MHE and NMHE patients as compared to HCs. (3) Results: Thirteen studies with twenty datasets were included in this meta-analysis. Compared with HCs, MHE patients showed decreased spontaneous brain activity in the left superior frontal gyrus, left median cingulate/paracingulate gyri, and right precuneus. Compared with NMHE patients, MHE patients indicated decreased spontaneous brain activity in the left superior frontal gyrus, left median cingulate/paracingulate gyri, and right precuneus. (4) Conclusions: MHE is associated with spontaneous brain activity alterations involving the left superior frontal gyrus and median cingulate/paracingulate gyri, which may implicate primarily in spatial working memory and emotional disorders. These findings may contribute to a better understanding of the potential neural mechanisms, and guide further research.

Endovascular treatment versus medical management for mild stroke with acute anterior circulation large vessel occlusion: a meta-analysis.

BACKGROUND: The effectiveness of endovascular treatment (EVT) in patients with mild stroke (National Institutes of Health Stroke Scale score ≤5) and acute anterior circulation large vessel occlusion (AACLVO) remains unknown. OBJECTIVE: To conduct a meta-analysis to compare the efficacy and safety of EVT in patients with mild stroke and AACLVO. METHODS: EMBASE, Cochrane Library, PubMed, and Clinicaltrials.gov databases were searched until October 2022. Both retrospective and prospective studies which compared the clinical outcomes between EVT and medical treatment were included. ORs and 95% confidence intervals (CIs) for excellent and favorable functional outcomes, symptomatic intracranial hemorrhage (ICH), and mortality were pooled using a random-effects model. A propensity score (PS)-based methods adjusted analysis was also performed. RESULTS: 4335 patients from 14 studies were included. In patients with mild stroke and AACLVO, EVT presented no marked differences in excellent and favorable functional outcomes and mortality compared with medical treatment. A higher risk of symptomatic ICH (OR=2.79; 95% CI 1.49 to 5.24; P=0.001) was observed with EVT. Subgroup analysis revealed that EVT had potential benefit for proximal occlusions with excellent functional outcomes (OR=1.68; 95% CI 1.01 to 2.82; P=0.05). Similar results were observed when PS-based methods adjusted analysis was used. CONCLUSION: EVT did not significantly benefit clinical functional outcomes in comparison with medical treatment in patients with mild stroke and AACLVO. However, it may improve functional outcomes when treating patients with proximal occlusion, despite being associated with an increased risk of symptomatic ICH. Stronger evidence from ongoing randomized controlled trials is required.

Frequency-Specific Changes of Amplitude of Low-Frequency Fluctuations in Patients with Acute Basal Ganglia Ischemic Stroke.

Objective: The purpose of this study was to investigate the characteristics of different frequency bands in the spontaneous brain activity among patients with acute basal ganglia ischemic stroke (BGIS). Methods: In the present study, thirty-four patients with acute BGIS and forty-four healthy controls were examined by resting-state functional magnetic resonance imaging (rs-fMRI) from May 2019 to December 2020. Two amplitude methods including amplitude of low-frequency fluctuations (ALFF) and fractional ALFF (fALFF) calculated in three frequency bands (conventional frequency band: 0.01-0.08 Hz; slow-5 frequency band: 0.01-0.027 Hz; and slow-4 frequency band: 0.027-0.073 Hz) were conducted to evaluate the spontaneous brain activity in patients with acute BGIS and healthy controls (HCs). Gaussian Random Field Theory (GRF, voxel p < 0.01 and cluster p < 0.05) correction was applied. The correlation analyses were performed between clinical scores and altered metrics values. Results: Compared to HCs, patients with acute BGIS showed decreased ALFF in the right supramarginal gyrus (SMG) in the conventional and slow-4 bands, increased fALFF in the right middle frontal gyrus (MFG) in the conventional and slow-4 bands, and increased fALFF in the bilateral caudate in the slow-5 frequency band. The fALFF value of the right caudate in the slow-5 frequency band was negatively correlated with the clinical scores. Conclusion: In conclusion, this study showed the alterations in ALFF and fALFF in three frequency bands between patients with acute BGIS and HCs. The results reflected that the abnormal LFO amplitude might be related with different frequency bands and promoted our understanding of pathophysiological mechanism in acute BGIS.

Progress on the role of TRIM8 protein in nervous system / 国际儿科学杂志

TRIM family proteins are considered to be E3 ubiquitin ligase, which involve in multiple biological processes.They participate in the genesis, development, proliferation and differentiation in the nervous system.TRIM8 is a member of TRIM family.TRIM8 plays divergent roles in many biological processes such as inflammation, tumor, cell proliferation.TRIM8 is involved in the pathological process of epilepsy, glioma, and stroke.This arttde reviews the role and mechanism of TRIM8 in nervous system diseases in order to provide new treatment ideas for the nervous system diseases.

Efficacy and safety of low-dose corticosteroids for acute respiratory distress syndrome: A systematic review and meta-analysis.

BACKGROUND: There are conflicting results regarding whether corticosteroids have better efficacy than placebo in acute respiratory distress syndrome (ARDS) patients. Therefore, we aim to further evaluate the efficacy and safety of corticosteroids in adult ARDS patients. METHODS: The databases, including Medline, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, were searched from their inception to May 2, 2020. Randomized controlled trials (RCTs) and observational cohort studies were selected to assess the use of corticosteroids in adult ARDS patients. The quality of the results was judged by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. The inverse-variance method with random or fixed effects modeling was used to compute pooled odds ratio (OR), standardized mean difference (SMD), and their 95% confidence interval (CI). RESULTS: Eight eligible RCTs and six cohort studies were included. The use of corticosteroids was associated with reduced mortality (OR 0.57, 95% CI 0.43-0.76, I2=35.1%, P=0.148) in ARDS patients, and the result was confirmed in the included cohort studies (OR 0.51, 95% CI 0.27-0.95, I2=66.7%, P=0.010). The subgroup analysis stratified by the initiation time and duration of corticosteroid use showed that early ARDS and prolonged corticosteroid use had significant survival benefits in the RCTs. The low-dose corticosteroid use was also associated with significantly more ventilator-free days and a reduced rate of new infections in ARDS patients. CONCLUSIONS: The low-dose corticosteroid therapy may be safe and reduce mortality, especially in patients with prolonged treatment and early ARDS.

Efficacy of mesenchymal stem cell therapy for sepsis: a meta-analysis of preclinical studies.

BACKGROUND: Multiple studies have reported that mesenchymal stem cell (MSC) therapy has beneficial effects in experimental models of sepsis. However, this finding remains inconclusive. This study was performed to systematically determine the connection between MSC therapy and mortality in sepsis animal models by pooling and analyzing data from newly published studies. METHODS: A detailed search of related studies from 2009 to 2019 was conducted in four databases, including MEDLINE, EMBASE, Cochrane Library, and Web of Science. After browsing and filtering out articles that met the inclusion criteria for statistical analysis, the inverse variance method of the fixed effects model was used to calculate the pooled odds ratios (ORs) and their 95% confidence intervals (CIs). RESULTS: Twenty-nine animal studies, including 1266 animals, were identified. None of the studies was judged to have a low risk of bias. The meta-analysis demonstrated that MSC therapy was related to a significantly lower mortality rate (OR 0.29, 95% CI 0.22-0.38, P < 0.001). Subgroup analyses performed based on the MSC injection dose (< 1.0 × 106 cells, OR = 0.33, 95% CI 0.20-0.56, P < 0.001; 1.0 × 106 cells, OR = 0.24, 95% CI 0.16-0.35, P < 0.001) and injection time (< 1 h, OR = 0.24, 95% CI 0.13-0.45, P < 0.001; 1 h, OR = 0.28, 95% CI 0.17-0.46, P < 0.001) demonstrated that treatment with MSCs significantly reduced the mortality rate of animals with sepsis. CONCLUSION: This up-to-date meta-analysis showed a connection between MSC therapy and lower mortality in sepsis animal models, supporting the potential therapeutic effect of MSC treatment in future clinical trials. The results in this study contradict a previous meta-analysis with regards to the ideal dose of MSC therapy. Thus, further research is required to support these findings.

Effect of low high-density lipoprotein levels on mortality of septic patients: A systematic review and meta-analysis of cohort studies.

BACKGROUND: An increase in high-density lipoprotein (HDL) is well associated with a decreased cardiovascular risk, especially atherosclerosis. Recent studies suggest that lower levels of HDL may also be associated with an increased risk of sepsis and an increased rate of mortality in septic patients. However, this conclusion remains controversial. METHODS: MEDLINE, EMBASE, and CENTRAL databases were searched from inception to September 30, 2019. All studies were conducted to evaluate the correlation of lipoprotein levels and the risk and outcomes of sepsis in adult patients. The primary outcomes were the risk and mortality of sepsis. RESULTS: Seven studies comprising 791 patients were included. Lower levels of HDL had no marked relevance with the risk of sepsis (odds radio [OR] for each 1 mg/dL increase, 0.94; 95% CI 0.86-1.02; P=0.078), whereas lower HDL levels were related to an increased mortality rate in septic patients (OR for below about median HDL levels, 2.00; 95% CI 1.23-3.24; P=0.005). CONCLUSION: This meta-analysis did not reveal a significant association between lower HDL levels and an increase in the risk of sepsis, whereas it showed that lower HDL levels are associated with a higher mortality rate in septic adult patients. These findings suggest that HDL may be considered as a promising factor for the prevention and treatment of sepsis in the future.

Related Network and Differential Expression Analyses Identify Nuclear Genes and Pathways in the Hippocampus of Alzheimer Disease.

BACKGROUND Alzheimer disease (AD) is a typical progressive and destructive neurodegenerative disease that has been studied extensively. However, genetic features and molecular mechanisms underlying AD remain unclear. Here we used bioinformatics to investigate the candidate nuclear genes involved in the molecular mechanisms of AD. MATERIAL AND METHODS First, we used Gene Expression Omnibus (GEO) database to obtain the expression profiles of the mRNAs from hippocampus microarray and identify differentially expressed genes (DEGs) the plier algorithm. Second, functional annotation and visualization of the DEGs were conducted by the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Finally, BioGRID, IntAct, STRING, and Cytoscape were utilized to construct a protein-protein interaction (PPI) network. Hub genes were analytically obtained from the PPI network and the microRNA (miRNA)-target network. RESULTS Two hippocampus microarrays (GSE5281 and GSE48350) were obtained from the GEO database, comprising 161 and 253 cases separately. Among these, 118 upregulated genes and 694 downregulated genes were identified. The upregulated DEGs were mainly involved in positive regulation of transcription from RNA polymerase II promoter, positive regulation of cartilage development, and response to wounding. The downregulated DEGs were enriched in chemical synaptic transmission, neurotransmitter secretion, and learning. By combining the results of PPI and miRNA-target network, 8 genes and 2 hub miRNAs were identified, including YWHAZ, DLG4, AGAP2, EGFR, TGFBR3, PSD3, RDX, BRWD1, and hsa-miR-106b-5p and hsa-miR-93-5p. These target genes are highly enriched in various key pathways, such as amyloid-beta formation, regulation of cardiocyte differentiation, and actin cytoskeleton reorganization. CONCLUSIONS In this study, YWHAZ, DLG4, AGAP2, EGFR, TGFBR3, PSD3, RDX, and BRWD1 were identified as candidate genes for future molecular studies in AD, which is expected to improve our understanding of its cause and potential molecular mechanisms. Nuclear genes, DEGs, and related networks identified by integrated bioinformatics analysis may serve as diagnostic and therapeutic targets for AD.

Predictive model for acute respiratory distress syndrome events in ICU patients in China using machine learning algorithms: a secondary analysis of a cohort study.

BACKGROUND: To develop a machine learning model for predicting acute respiratory distress syndrome (ARDS) events through commonly available parameters, including baseline characteristics and clinical and laboratory parameters. METHODS: A secondary analysis of a multi-centre prospective observational cohort study from five hospitals in Beijing, China, was conducted from January 1, 2011, to August 31, 2014. A total of 296 patients at risk for developing ARDS admitted to medical intensive care units (ICUs) were included. We applied a random forest approach to identify the best set of predictors out of 42 variables measured on day 1 of admission. RESULTS: All patients were randomly divided into training (80%) and testing (20%) sets. Additionally, these patients were followed daily and assessed according to the Berlin definition. The model obtained an average area under the receiver operating characteristic (ROC) curve (AUC) of 0.82 and yielded a predictive accuracy of 83%. For the first time, four new biomarkers were included in the model: decreased minimum haematocrit, glucose, and sodium and increased minimum white blood cell (WBC) count. CONCLUSIONS: This newly established machine learning-based model shows good predictive ability in Chinese patients with ARDS. External validation studies are necessary to confirm the generalisability of our approach across populations and treatment practices.

Features of Childhood Arterial Ischemic Stroke in China.

Objective: The aim of this study was to identify the features and risk factors for arterial ischemic stroke (AIS) in children. Methods: We retrospectively analyzed the initial symptoms, clinical manifestations, risk factors, neuroradiological findings, and treatment data of 75 Chinese children aged between 1 month and 14 years (median 5.7 years) who were diagnosed with AIS in our hospital between 2013 and 2018. Results: Among these 75 cases of childhood AIS, 53 patients (70.67%) were male, and the male-to-female ratio was 2.41:1. A total of 55 cases (73.33%) had respiratory tract infection with fever. Seventy cases had lesions in the basal ganglia (46 left, 24 right). All patients were treated conservatively without thrombolytic therapy. Intravenous immunoglobulin treatment was given to children with fever and drowsiness. Conclusion: Infection was an important risk factor for children with AIS in China. Infection and thrombophilia risk factors were more likely to occur in isolation. The stroke lesions commonly occurred in the basal ganglia region.

Adipose-derived mesenchymal stem cells ameliorate the inflammatory reaction in CLP-induced septic acute lung injury rats via sTNFR1.

We hypothesized that the adipose-derived mesenchymal stem cells (ADMSCs), which secrete high amounts of soluble molecules, such as soluble tumor necrosis factor receptor 1 (sTNFR1), may ameliorate sepsis-induced acute lung injury (ALI). A total of 120 male adult Sprague-Dawley rats were separated into four groups: the sham control (SC), sepsis induced by cecal ligation and puncture (CLP), CLP-ADMSCs, and CLP-sTNFR1 small interfering RNA (siRNA) groups; CLP groups underwent CLP and then received 1 × 106 ADMSCs with or without knockdown of sTNFR1 intravenously at 1 hr after surgery. Rats were killed at 3, 6, 24, and 48 hr after the SC or CLP procedures. 5-Ethynyl-2'-deoxyuridine-labeled ADMSCs extensively colonized the lungs at 6, 24, and 72 hr after injection. The lung wet/dry (W/D) weight ratios in the CLP group were higher than those in SC group; however, ADMSCs ameliorated the W/D weight ratios following CLP, and this effect was abolished by sTNFR1 siRNA treatment. The levels of serum sTNFR1 and interleukin-10 (IL-10) were higher in the CLP-ADMSCs group and lower in the SC group than in other groups; interestingly, these levels were higher in CLP and CLP-sTNFR1 siRNA groups than in SC group. Tumor necrosis factor-α and IL-6 levels increased significantly after CLP, and ADMSCs could alleviate these changes, but the effect was weakened by sTNFR1 siRNA treatment. The lung cell apoptosis and edema levels were consistent with IL-6 levels among all groups. Therapeutically administered ADMSCs secrete sTNFR1, which most likely protects against ALI in septic rats by ameliorating inflammation and lung edema.

Efficacy of stem cell therapy for pulmonary arterial hypertension: a systematic review and meta-analysis of preclinical studies.

BACKGROUND: Despite significant progress in drug treatment, the prognosis of patients with advanced pulmonary arterial hypertension (PAH) remains extremely poor. Many preclinical studies have reported the efficacy of stem cell (SC) therapy for PAH; however, this approach remains controversial. The aim of this systematic review and meta-analysis is to assess the potential efficacy of SC therapy for PAH. METHODS: The Medline, EMBASE, Cochrane Library, and Web of Science databases were searched from inception to August 12, 2018. Preclinical studies that evaluated the use of SC therapy for PAH were included. The primary outcome was pulmonary haemodynamics, as assessed by measurement of the right ventricular systolic pressure (RVSP), mean pulmonary arterial pressure (mPAP), and/or mean right ventricle pressure (mRVP). The secondary outcomes included the weight ratio of the right ventricle to the left ventricle plus septum (RV/LV+S), the right ventricle to body weight ratio (RV/BW), the percentage of pulmonary arteriole area index (WA), and/or the percentage of medial wall thickness of the pulmonary arteriole (WT). The quality of outcomes was evaluated using the SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE) bias risk tool. The inverse-variance method with random-effects modelling was used to calculate pooled weighted mean differences (WMDs) and 95% CIs. Statistical analysis was performed with STATA 14.0. RESULTS: Twenty-eight eligible articles (722 animals) were included. SC therapy reduced the pooled WMDs (95% CIs) of RVSP, mPAP, mRVP, RV/LV+S, RV/BW, WA, and WT for animals with PAH, with values of - 14.12 (- 14.63, - 13.61), - 11.86 (- 12.35, - 11.36), - 17.33 (- 18.10, - 16.56), - 0.10 (- 0.10, - 0.09), 0.23 (0.21, 0.24), - 13.66 (- 15.71, - 11.62), and - 7.96 (- 7.99, - 7.93), respectively. CONCLUSIONS: SC therapy is effective for PAH in preclinical studies. These results may help to standardise preclinical animal studies and provide a theoretical basis for clinical trial design in the future. SYSTEMATIC REVIEW REGISTRATION: PROSPERO ( http://www.crd.york.ac.uk/PROSPERO ).

Epidemiological characteristics of malaria before and after the elimination in Hangzhou / 预防医学

Objective To compare the epidemiological characteristics of malaria before and after the elimination in Hangzhou, and to provide scientific basis for formulating malaria control strategies. Methods We collected the data of confirmed malaria cases in Hangzhou from 2005 to 2016. We compared the differences in epidemiological characteristics (demographic features of malaria cases, source of infection, plasmodium species, etc.) and vectors of malaria before (2005-2010) and after (2011-2016) the elimination of malaria. Results Totally 340 malaria cases were reported before the elimination in Hangzhou with the annual incidence rate of 0.16/10 million, while 227 cases were reported after the elimination with the annual incidence rate of 0.25/10 million. Local cases accounted for 11.47% before the elimination, while no local cases but all imported cases were reported after the elimination. Compared the sex, occupation and age of malaria cases, epidemic season, report area, source of infection and species before and after the elimination, the proportion of men increased from 67.65% to 89.87%; the proportion of 18-60 years old group increased from 75.88% to 96.04%; the proportion of children / students decreased from 17.35% to 7.49%;the epidemic season changed from July to October to no obvious season; the main report area changed from suburb (55.88%) to urban area (81.06%); the source of infection changed from the domestic provinces (77.94%) to foreign countries (99.12%) ;the main species of malaria parasites changed from vivax malaria (88.24%) to ciparum malaria (71.81%) . The Anopheles mosquitoes caught by vector monitoring were Anopheles sinensis. The average density of Anopheles sinensis before and after the elimination was 10.0 and 5.0 /(person·night) . Conclusion After the elimination of malaria in Hangzhou, imported malaria cases from abroad were dominant. and the men and women who returned to and from abroad and 18-60 years old were the key prevention and control groups in the future.The epidemiological characteristics of malaria after the elimination in Hangzhou have changed greatly. The men who are 18-60 years old and return from abroad are the focus of malaria prevention and control.

Amyloid Arthropathy of the Hip Joint Associated with Multiple Myeloma: A Case Report.

Amyloidosis is a disease characterized by the deposition of non-soluble fibrous protein in multiple tissues with a number of possible causes. This protein deposition can occur in any tissue, yet is most commonly seen in kidneys, heart, and gastrointestinal tracts. However, invasion to bone tissues is not often reported. The deposition of amyloid proteins in bone tissues may result in joint pain and pathological fractures; it is important to elucidate the causes and detect early to determine prognosis and treat optimally. In the present case report, with relevant literature review, the authors report a case of total hip arthroplasty in an amyloidosis patient.

The effect of parathyroid hormone on osteogenic activities of human osteosarcoma cell line SaOS-2 / 中国地方病学杂志

Objective To observe the effects of recombinant human parathyroid hormone 1 to 34(referred to as hPTH) on the expression level of alkaline phosphatase(ALP) and bone gla protein(BCP) in human osteosarcoma cell line SaOS-2(referred to as SaOS-2 cells). Methods SaOS-2 cells were subcultured and treated with 1, 10 and 100 nmol/L hPTH for 12, 24 and 48 h. Total cellular RNA was extracted, cDNA was synthesized by reverse doses of hPTH, different duration of action, and their interaction on the expression level of ALP mRNA of SaOS-2 cells was significantly different(F = 29.32, 2.92, 7.64, all P < 0.05). The expression level of ALP mRNA(0.78 ± 0.43, 0.71 ± 0.05, 0.75 ± 0.19, 0.76 ± 0.14) of SaOS-2 cells after treatment with 0, 1, 10 and 100 nmol/L hPTH for 48 h was lower than those of treated for 12 h(1.01 ± 0.16, 1.37 ± 0.38, 1.49 ± 0.16, 2.52 ± 0.70, all P< 0.05) and 24 h (1.80 ± 0.47, 1.30 ± 0.36, 1.27 ± 0.17, 1.17 ± 0.11, all P< 0.05). The expression level of ALP mRNA of SaOS-2 cells after treatment with 100 nmol/L hPTH for 12 hours was higher than that of the control(P < 0.05); the expression level of ALP mRNA of SaOS-2 cells after treatment with 1, 10 and 100 nmol/L hPTH for 24 h interaction on the expression level of BGP mRNA of SaOS-2 were significantly different (F = 8.26, 10.33, 5.51, all P< 0.05). The expression level of BGP mRNA(1.17 ± 0.28, 0.98 ± 0.08, 0.92 ± 0.17 and 0.84 ± 0.59) of SaOS2 cells after treatment with 0, 1, 10 and 100 nmol/L hPTH for 48 h was lower than those of treated for 12 h( 1.01 ± 0.14, 1.21 ± 0.18, 1.34 ± 0.30, 1.68 ± 0.62, all P< 0.05), and 24 h(1.71 ± 0.35, 1.41 ± 0.47, 1.28 ± 0.31 and 1.01 ± 0.18, all P < 0.05). The expression level of BGP mRNA of SaOS-2 cells after treatment with 100 nmol/L hPTH for 12 h was higher than that of those groups treated with 0 and 1 nmol/L hPTH(all P< 0.05). The expression level of BGP mRNA of SaOS-2 cells after treatment with 10 and 100 nmol/L hPTH for 24 h and 48 h was lower than those of the control(all P < 0.05). The expression level of BGP mRNA of SaOS-2 cells after treatment with 100 nmol/L hPTH for 24 hours was lower than that the group treated with 1 nmol/L hPTH(P < 0.05). Conclusions In vitro, hPTH significantly enhances osteogenic activities of human osteoblast in a short time, however, with prolonged stimulation time, osteogenic activity can show a downward trend.

Effect of different doses of recombinant human bone morphogenetic protein 2 on osteogenic activities of human osteosarcoma cell line SaOS-2 / 中国地方病学杂志

Objective To investigate the effect of recombinant human bone morphogenetic protein 2 (rhBMP-2) on the osteogenic activities of human osteosarcoma cell line SaOS-2. Methods SaOS-2 cells were exposed to rhBMP-2 for 12,24,48 h at 0(control) ,2,20,200 μg/L, respectively. The mRNA expression of alkaline phosphatase(ALP) and bone gla(BCP) were detected by real time polymerase chain reaction. Results The mRNA expression of ALP and BGP of SaOS-2 cells increased gradually with rhBMP-2. The mRNA expression of ALP of the 20 μg/L group exposed for 48 h(1.60 ± 0.64), and the 200 μg/L group exposed for 12,48 h(1.70 ± 0.41, 1.80±0.19) were significantly higher than those of control (12 h: 0.80±0.25, 48 h: 0.74±0.21, allP<0.05). The mRNA expression of BGP of the 2 μg/L group exposed for 24 h(1.67 ± 0.33), the 20 μg/L group exposed for 12,24 h(2.42 ± 0.13,1.82 ± 0.14) and the 200 μg/L group exposed for 12,24 h(1.46 ± 0.11,1.24 ± 0.07) were significantly higher than those of control( 12 h: 1.01 ± 0.14, 24 h: 0.84 ± 0.12, all P< 0.05). Conclusions rhBMP-2 can promote the mRNA expression of ALP and BGP of SaOS-2 cells. They have a dose-response relationship, but represent a different dose-response effect.

Effect of fluoride on bone metabolism in rats / 中国地方病学杂志

Objective To study the effect of fluoride on bone metabolism in rats, and to understand the mechanism of pathogenesis of skeletal fluorosis. Methods A total of 80 Wistar rats were randomly divided into 4 groups that included control group (distilled water), low-dose group(NaF, 50 mg/L), medium-dose group (NaF,100 mg/L) and high-dose group(NaF, 150 mg/L), respectively. After being bred for 12 weeks, the rats were put to death (etherization). Incidence of dental fluorosis was estimated, and serum was collected. Radioimmunoassay was employed to detect the levels of osteocalcin (BGP), parathyroid hormone (PTH) and calcitonin (CT), respectively.Colorimetry method was employed to determine the levels of alkaline phosphatase (ALP) and acid phosphatase (ACP). Results Incidence of dental fluorosis between the four groups was significantly different statistically(x2 =82.81 ,P ＜ 0.01 ). The incidence was significantly different(x2 = 22.67, 40.00, 40.00, all P＜ 0.01 ) between low-dose ( 80%, 16/20), medium-dose ( 100%, 20/20), high-dose groups ( 100%, 20/20) and control group (0,0/20),respectively. Serum levels of BGP, PTH, CT were significantly different between the groups(F = 38.614, 20.778,3.023, P ＜ 0.01 or ＜ 0.05). There was no significant difference between the four.groups of ALP and ACP in serum (F = 0.609,2.895, all P ＞ 0.05 ). Serum BGP in low-dose, medium-dose and high-dose groups[ ( 19.60 ± 12.79),(33.41 ± 10.81 ), (39.46 ± 9.51 )mg/L, respectively] was significantly higher than that of the control group[ (7.35 ± 3.22)mg/L, all P ＜ 0.01 ]. Serum PTH in low-dose, medium-dose and high-dose groups[ (72.27 ± 25.38), (67.80 ± 12.01), (106.52 ± 36.37)pmol/L] was significantly higher than that of the control group[(47.08 ± 9.22)pmol/L,all P ＜ 0.01 ]. Serum PTH of the high-dose group was significantly higher than that of the low-dose and the mediumdose groups(all P ＜ 0.01 ). Serum CT in medium-dose and high-dose groups[ ( 13.39 ± 2.07), ( 15.05 ± 4.77)pmol/L ] was significantly lower than that of the control group[ (26.06 ± 28.31 ) pmol/L, all P ＜ 0.05 ] and also significantly lower than that of the low-dose group [ (24.49 ± 14. 10) pmol/L, all P ＜ 0.05 ]. Conclusions Fluoride affects bone metabolism in rats, BGP, PTH and CT play a key role in the pathogenesis of skeletal fluorosis.

In situ simultaneous organics and nitrogen removal from recycled landfill leachate using an anaerobic-aerobic process.

An anaerobic-aerobic process including a fresh refuse landfill reactor as denitrifying reactor, a well-decomposed refuse reactor as methanogenesis reactor and an aerobic activated sludge reactor as nitrifying reactor was operated by leachate recirculation to remove organic and nitrogen simultaneously. The results indicated that denitrification and methanogenesis were carried out successfully in the fresh refuse and well-decomposed landfill reactors, respectively, while the nitrification of NH(4)(+)-N was performed in the aerobic reactor. The maximum organic removal rate was 1.78 kg COD/m(3)d in the well-decomposed refuse landfill reactor while the NH(4)(+)-N removal rate was 0.18 kg NH(4)(+)-N/m(3)d in the aerobic reactor. The biogas from fresh refuse reactors and well-decomposed refuse landfill reactors were consisted of mainly carbon dioxide and methane, respectively. The volume fraction of N(2) increased with the increase of NO(3)(-)-N concentration and decreased with the drop of NO(3)(-)-N concentration. The denitrifying bacteria mustered mainly in middle layer and the denitrifying bacteria population had a good correlation with NO(3)(-)-N concentration.