M2-Macrophage-Derived Exosomes Promote Meningioma Progression through TGF-ß Signaling Pathway.

Tumor-associated macrophages (TAMs) have been shown to be an essential component of the tumor microenvironment and facilitate the proliferation and invasion of a variety of malignancies. However, the contribution of TAMs to meningioma progression has not been characterized in detail. In this study, we aimed to discover a novel regulatory pathway by which exosome-mediated M2-polarized macrophages participate in meningioma tumorigenesis and progression. Methods. First, the distribution and functional phenotype of macrophages in meningioma tissues were assessed by immunohistochemistry. Macrophage-derived exosomes (MDEs) were characterized, and further cell coculture experiments were performed to explore the effects of M2-MDEs on the proliferation, migration, and invasion of meningioma cells. RNA sequencing was used to analyze the transcriptomic signatures in meningioma cells treated with M2-MDEs. Three-dimensional tumorspheres and xenograft tumor models were used to evaluate the effects of M2-MDEs on meningioma tumorigenesis and development. Results. We found that M2 macrophages were enriched in meningioma tissue. Coculture with meningioma cells induced the M2 polarization of macrophages. We also found that M2-MDEs were able to significantly promote cell proliferation, cell migration, cell invasion, and tumorigenesis in meningiomas. Bioinformatic analysis suggested that the TGF-ß pathway was activated in meningioma cells treated with M2-MDEs. Functional experiments demonstrated that blocking the TGF-ß signaling pathway could effectively reverse the tumor-promotive effects mediated by M2-MDEs. Conclusions. Overall, our study showed that M2-MDEs promoted meningioma development and invasion by activating the TGF-ß signaling pathway. Targeting exosome-mediated intercellular communication in the tumor microenvironment may be a novel therapeutic strategy for meningioma patients.

Combination of crizotinib and chemotherapy in patients with relapsed or refractory anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL).

Our aim was to explore the role of crizotinib, targeted anaplastic lymphoma kinase (ALK), on r/r systemic anaplastic large cell lymphoma (sALCL). The treated group prospectively screened 20 patients. After taking crizotinib in the first week, 16 patients who were tolerant and sensitive received the combination of crizotinib with chemotherapy. The control group included 27 patients receiving chemotherapy in the same hospital during the same period. The objective remission rates of the treated and control group were 81.3% and 74.1% (p = .869), respectively. The progression-free survival rates at two years in treated and control group were 68.7% and 45.0% (HR = 0.42, 95% CI 0.17-0.99, p < .05), respectively. The overall survival rates at two years in the treated and control group were 86.1% and 78.9% (p = .385, HR = 0.51, 95% CI 0.11-2.30), respectively. The main adverse events included elevated transaminase, diarrhea, and vision abnormalities. Thus, the combination of crizotinib with chemotherapy might be effective in ALK-positive and crizotinib sensitive r/r sALCL patients.

Concentration of target genes of SARS-CoV-2 and influencing factors in the confirmed cases with COVID-19 in Ningbo / 预防医学

Objective@#To learn the concentration of target genes of severe acute respiratory syndrome coronavirus 2 ( SARS-CoV-2 ) and the influencing factors in the confirmed cases with coronavirus disease 2019 ( COVID-19 ) in Ningbo.@*Methods@#Demographic information and clinical diagnosis of COVID-19 cases reported in Ningbo from January 21 to February 20, 2020 were collected through China Disease Control and Prevention Information System. The Ct values of ORF1ab and N of the cases were collected through Ningbo Center for Disease Control and Prevention and designated hospitals, and analyzed in terms of gender, age, severity, clinical classification, source of case, sampling time and specimen type. @*Results@#There were 157 confirmed COVID-19 cases, including 56 males ( 35.67% ) and 101 females ( 64.33% ). Sixty-seven cases ( 42.68% ) aged between 40 and 60 years old. The Ct values of ORF1ab and N in females were 29.96±5.28 and 30.38±4.90, which were higher than 27.56±4.94 and 28.03±4.88 in males ( P<0.05 ). The Ct values of ORF1ab and N were the lowest when sampled at 1-7 days after onset ( P<0.05 ), which were 27.84±4.80 and 28.35±4.65. The Ct values of ORF1ab ( rs=0.288, P=0.001 ) and N ( rs=0.296, P=0.001 ) were positively correlated with sampling time. The Ct values of ORF1ab in pharyngeal swab and sputum were 29.19±4.85 and 28.74±6.40, the Ct values of N in pharyngeal swab and sputum were 29.61±4.60 and 29.22±6.10, both without significant differences between different samples ( P>0.05 ). @*Conclusions@#Sampling time has a great influence on the Ct values of ORF1ab and N of SARS-CoV-2.

Value of elastography point quantification in improving the diagnostic accuracy of early diabetic kidney disease.

BACKGROUND: Diabetic kidney disease (DKD) is a common complication of diabetes. The patient's prognosis is poor once DKD progresses to advanced stage. Accurate diagnosis and timely treatment of early DKD are important for improving patient's prognosis and reducing mortality. AIM: To explore the value of elastography point quantification (ElastPQ) in improving the accuracy of early DKD diagnosis. METHODS: A total of 69 patients with type 2 diabetes were recruited from Naval Military Medical University Affiliated Gongli Hospital. Patients were divided into early DKD group and medium DKD group according to pathological results and urinary albumin excretion rate (UAER). Another 40 patients with simple diabetes were included as the diabetes group. The baseline data, laboratory diagnostic indicators, and ultrasound indicators for each patient were recorded. The differences of the indicators in the three groups were compared. Multivariate logistic regression was used to analyze the influencing factors of the development from simple diabetes into early DKD and from early DKD into medium DKD. Receiver operating characteristic analyses of potential indicators in identifying early DKD and medium DKD, and early DKD and simple diabetes were established. RESULTS: Multivariate logistic regression analysis showed that UAER (P < 0.001), renocortical Young's Modulus (YM) (P < 0.001), and renal parenchymal thickness (P = 0.013) were the independent influencing factors of the development from early DKD into medium DKD. Diabetes duration (P = 0.041), UAER (P = 0.034), and renocortical YM (P = 0.017) were the independent influencing factors of the development from simple diabetes into early DKD. Receiver operating characteristic analysis indicated that UAER, renocortical YM, and renal parenchymal thickness were accurate in identifying early DKD and medium DKD [all area under curve (AUC) > 0.9]. The accuracy of UAER (AUC = 0.744), diabetes duration (AUC = 0.757), and renocortical YM (AUC = 0.782) for the diagnosis of early DKD and simple diabetes were limited. However, the combined diagnosis of UAER, diabetes duration, and renocortical YM was accurate in identifying early DKD and simple diabetes (AUC = 0.906), which was significantly higher than any of the three indicators (all P < 0.05). CONCLUSION: ElastPQ is of great value in the diagnosis of early DKD. When combined with the diabetes duration and UAER, it is expected to diagnose accurately early DKD.

Wall shear stress can improve prediction accuracy for transient ischemic attack.

BACKGROUND: Early prediction of transient ischemic attack (TIA) has important clinical value. To date, systematic studies on clinical, biochemical, and imaging indicators related to carotid atherosclerosis have been carried out to predict the occurrence of TIA. However, their prediction accuracy is limited. AIM: To explore the role of combining wall shear stress (WSS) with conventional predictive indicators in improving the accuracy of TIA prediction. METHODS: A total of 250 patients with atherosclerosis who underwent carotid ultrasonography at Naval Military Medical University Affiliated Gongli Hospital were recruited. Plaque location, plaque properties, stenosis rate, peak systolic velocity, and end diastolic velocity were measured and recorded. The WSS distribution map of the proximal and distal ends of the plaque shoulder was drawn using the shear stress quantitative analysis software, and the average values of WSS were recorded. The laboratory indicators of the subjects were recorded. The patients were followed for 4 years. Patients with TIA were included in a TIA group and the remaining patients were included in a control group. The clinical data, laboratory indicators, and ultrasound characteristics of the two groups were analyzed. Survival curves were plotted by the Kaplan-Meier method. Receiver operating characteristic curves were established to evaluate the accuracy of potential indicators in predicting TIA. Logistic regression model was used to establish combined prediction, and the accuracy of combined predictive indicators for TIA was explored. RESULTS: The intraclass correlation coefficients of the WSS between the proximal and distal ends of the plaque shoulder were 0.976 and 0.993, respectively, which indicated an excellent agreement. At the end of the follow-up, 30 patients suffered TIA (TIA group) and 204 patients did not (control group). Hypertension (P = 0.037), diabetes (P = 0.026), homocysteine (Hcy) (P = 0.022), fasting blood glucose (P = 0.034), plaque properties (P = 0.000), luminal stenosis rate (P = 0.000), and proximal end WSS (P = 0.000) were independent influencing factors for TIA during follow-up. The accuracy of each indicator for predicting TIA individually was not high (area under the curve [AUC] < 0.9). The accuracy of the combined indicator including WSS (AUC = 0.944) was significantly higher than that of the combined indicator without WSS (AUC = 0.856) in predicting TIA (z = 2.177, P = 0.030). The sensitivity and specificity of the combined indicator including WSS were 86.67% and 92.16%, respectively. CONCLUSION: WSS at plaque surface combined with hypertension, diabetes, Hcy, blood glucose, plaque properties, and stenosis rate can significantly improve the accuracy of predicting TIA.

Differences in treatment outcomes between ultrasound-guided percutaneous microwave ablation and endoscopic thyroidectomy for patients with papillary thyroid microcarcinoma: Protocol for a systematic review and meta-analysis.

BACKGROUND: The differences in treatment outcomes between ultrasound (US)-guided percutaneous microwave ablation (PMWA) and endoscopic thyroidectomy for patients with papillary thyroid microcarcinoma (PTMC) remains unknown. METHODS: An electronic search will be performed for randomized controlled trials or observational studies that reported recurrence and mortality rates in PTMC patients with US-guided PMWA or endoscopic thyroidectomy. Hazard ratios with their 95% confidence intervals will be calculated using fixed- or random-effects models according to heterogeneity. RESULTS: This study will present the differences in treatment outcomes between US-guided PMWA and endoscopic thyroidectomy for patients with PTMC by pooling the results of individual studies. CONCLUSION: The results of this study would provide vigorous evidence in this issue and offer the guidance to both clinical decision-making and future research. ETHICS AND DISSEMINATION: Ethical approval is not applicable for this study. PROSPERO REGISTRATION NUMBER: CRD42018112320.

[Protective effect and mechanism of total lignans from Tibetan medicinal Herpetospermum seeds on carbon tetrachloride-induced liver fibrosis in rats].

This experiment was aimed to discuss the protective effect and mechanism of total lignans from Tibetan medicinal Herpetospermum seeds on carbon tetrachloride (CCl4)-induced liver fibrosis in rats. Forty-eight male Sprague-Dawley rats were randomly divided into the blank control group (G1), model group (G2), total lignans high, middle and low dose groups (400,200, and 100 mg•kg⁻¹â€¢d⁻¹)(G3/4/5) and the glycyrrhizin positive control group (25 mg•kg⁻¹â€¢d⁻¹)(G6), n=8 in each group. The rats in blank group received normal feeding; the rats in model group, total lignans low, middle and high dose groups and glycyrrhizic group were subcutaneously in jected with 3 mL•kg⁻¹ olive oilsolution containing 40%CCl4 every two or three days for Eight weeks. During the course, the rats inblank group and model group were orally administered with 2 mL normal saline, and the rats in total lignans groups and the glycyrrhizin positive control group received corresponding doses of drugs by intragastric administration. Eight weeks later, after the the last time modeling, the rats were sacrificed. Then the biochemical analysis was used to determine alanine aminotransferase(ALT), aspartate aminotransferase(AST), and alkaline phosphatase (ALP) levels in serum while enzyme-linked immuno sorbent assay(ELISA) was applied for detecting transforming growth factor ß1(TGF-ß1), hyaluronic acid(HA), hydroxy-proline(HYP) and superoxide dismutase(SOD) levels in serum. HE and Masson's trichrome stainings were conducted in liver tissues to observe the pathological variations and grades of hepatic fibrosis. The results showed that as compared with the model group, the levels of ALT, AST, ALP, TGF-ß1, HA, HYP and SOD in serum of total lignans groups were significantly decreased (P<0.05, P<0.01); levels of SOD in the liver tissue homogenate were increased(P<0.05, P<0.01); the pathological damage of the liver tissues were relieved (P<0.05, P<0.01), and liver fibrosis scores were decreased(P<0.05, P<0.01). The above experimentsindicated that total lignans from Tibetan medicinal Herpetospermum seeds can effectively reduce carbon tetrachloride-induced hepatic injury of rat liver fibrosis, reduce the degree of liver fibrosis, and its mechanism maybe associated with down-regulating TGF-ß1 expression.

The prevalence of EGFR mutation in patients with non-small cell lung cancer: a systematic review and meta-analysis.

OBJECTIVES: Estimate the epidermal growth factor receptor (EGFR) mutation prevalence in all non-small cell lung cancer (NSCLC) patients and patient subgroups. RESULTS: A total of 456 studies were included, reporting 30,466 patients with EGFR mutation among 115,815 NSCLC patients. The overall pooled prevalence for EGFR mutations was 32.3% (95% CI 30.9% to 33.7%), ranging from 38.4% (95% CI: 36.5% to 40.3%) in China to 14.1% (95% CI: 12.7% to 15.5%) in Europe. The pooled prevalence of EGFR mutation was higher in females (females vs. males: 43.7% vs. 24.0%; OR: 2.7, 95% CI: 2.5 to 2.9), non-smokers (non-smokers vs. past or current smokers: 49.3% vs. 21.5%; OR: 3.7, 95% CI: 3.4 to 4.0), and patients with adenocarcinoma (adenocarcinoma vs. non-adenocarcinoma: 38.0% vs. 11.7%; OR: 4.1, 95% CI: 3.6 to 4.8). MATERIALS AND METHODS: PubMed, EMBASE, and the Cochrane Library were searched to June 2013. Eligible studies reported EGFR mutation prevalence and the association with at least one of the following factors: gender, smoking status and histology. Random-effects models were used to pool EGFR mutation prevalence data. CONCLUSION: This study provides the exact prevalence of EGFR mutations in different countries and NSCLC patient subgroups.

A meta-regression evaluating the effectiveness and prognostic factors of oral phosphodiesterase type 5 inhibitors for the treatment of erectile dysfunction.

The effectiveness of phosphodiesterase type 5 inhibitors (PDE5-Is) for erectile dysfunction (ED) varies considerably among trials, but available studies investigating the factors that affect the effectiveness are few and findings are not consistent. A systematic search was performed in PubMed, Cochrane Library, and EMBASE to identify randomized controlled trials comparing PDE5-Is with placebo for the treatment of ED. The methodological quality of included studies was assessed by the Cochrane Collaboration's tool for assessing risk of bias. The associations between prespecified study-level factors and effectiveness were tested by a random effects meta-regression model. This study included 93 trials with 26 139 patients. When all PDE5-Is were grouped together, Caucasian ethnicity was associated with 15.636% (95% confidence interval [CI]: 0.858% to 32.579%) increase in risk ratio (RR) for Global Assessment Questionnaire question-1 (GAQ-1), and 1.473 (95% CI: 0.406 to 2.338) score increase in mean difference (MD) for posttreatment International Index of Erectile Function-Erectile Function domain score (IIEF-EF), compared to Asian ethnicity. A one-score increase in baseline IIEF-EF was associated with -5.635% (95% CI: -9.120% to -2.017%) reduction in RR for GAQ-1, and -0.229 (95% CI: -0.425 to -0.042) score decrease in MD for posttreatment IIEF-EF. In conclusion, PDE5-Is are more effective in Caucasians than Asians, and in patients with more severe ED.

Interleukin-2 as maintenance therapy for children and adults with acute myeloid leukaemia in first complete remission.

BACKGROUND: Acute myeloid leukaemia (AML) is a malignant cancer of hematopoietic stem cells. The treatment of AML consists of two treatment phases: the remission induction phase to achieve a rapid, complete remission (CR) and the consolidation phase to achieve a durable molecular remission. People in CR are at risk of AML relapse, and people with relapsed AML have poor survival prospects. Thus, there is a continuous need for treatments to further improve prognosis. Interleukin-2 (IL-2), an immune-stimulatory cytokine, is an alternative to standard treatment for people with AML to maintain the efficacy after consolidation therapy. Maintenance therapy is not an integral part of the standard treatment for AML. Studies have been conducted to evaluate the efficacy of IL-2 as maintenance therapy for people with AML in first CR, but the effect of IL-2 is not yet fully established. OBJECTIVES: To evaluate the efficacy and safety of IL-2 as maintenance therapy for children and adults with AML who have achieved first CR and have not relapsed. SEARCH METHODS: We systematically searched the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library 2015, Issue 8), MEDLINE (1950 to August 2015), EMBASE (1950 to August 2015), LILACS (1982 to August 2015), CBM (1978 to August 2015), relevant conference proceedings (2000 to 2015), and metaRegister of Controlled Trials (since inception to August 2015) of ongoing and unpublished trials. In addition, we screened the reference lists of relevant trials and reviews. SELECTION CRITERIA: Eligible studies were randomised controlled trials (RCTs) comparing IL-2 with no treatment in people with AML who had achieved first CR and had not relapsed. We did not identify studies comparing IL-2 versus best supportive care or maintenance chemotherapy or studies comparing IL-2 plus maintenance chemotherapy versus maintenance chemotherapy alone. DATA COLLECTION AND ANALYSIS: Two review authors independently screened studies, extracted data with a predefined extraction form, and assessed risk of bias of included studies. We extracted data on the following outcomes: disease-free survival, overall survival, event-free survival, treatment-related mortality, adverse events, and quality of life. We measured the treatment effect on time-to-event outcomes and dichotomous outcomes with hazard ratio (HR) and risk ratio, respectively. We used inverse-variance method to combine HRs with fixed-effect model unless there was significant between-study heterogeneity. MAIN RESULTS: We included nine RCTs with a total of 1665 participants, comparing IL-2 with no treatment. Six studies included adult participants, and three studies included both adults and children. However, the latter three studies did not report data for children, thus we were unable to conduct subgroup analysis of children. One Chinese study did not report any outcomes of interest for this review. We included six trials involving 1426 participants in the meta-analysis on disease-free survival, and included five trials involving 1355 participants in the meta-analysis on overall survival. There is no evidence for difference between IL-2 group and no-treatment group regarding disease-free survival (HR 0.95; 95% CI 0.86 to 1.06, P = 0.37; quality of evidence: low) or overall survival (HR 1.05; 95% CI 0.95 to 1.16, P = 0.35; quality of evidence: moderate). Based on one trial of 161 participants, IL-2 exerted no effect on event-free survival (HR 1.02; 95% CI 0.79 to 1.32, P = 0.88; quality of evidence: low). Adverse events (including thrombocytopenia, neutropenia, malaise/fatigue, and infection/fever) were more frequent in participants receiving IL-2, according to one trial of 308 participants. No mortality due to adverse events was reported. None of the included studies reported treatment-related mortality or quality of life. AUTHORS' CONCLUSIONS: There is no evidence for a difference between IL-2 maintenance therapy and no treatment with respect to disease-free survival or overall survival of people with AML in first CR; however, the quality of the evidence is moderate or low, and further research is likely or very likely to have an important impact on the estimate or our confidence in the estimate. Adverse events seem to be more frequent in participants treated with IL-2, but the quality of the evidence is very low and our confidence in the estimates is very uncertain. Thus, further prospective randomised trials are needed before definitive conclusions can be drawn on these issues.

Activation of the Notch signaling pathway promotes neurovascular repair after traumatic brain injury.

The Notch signaling pathway plays a key role in angiogenesis and endothelial cell formation, but it remains unclear whether it is involved in vascular repair by endothelial progenitor cells after traumatic brain injury. Therefore, in the present study, we controlled the Notch signaling pathway using overexpression and knockdown constructs. Activation of the Notch signaling pathway by Notch1 or Jagged1 overexpression enhanced the migration, invasiveness and angiogenic ability of endothelial progenitor cells. Suppression of the Notch signaling pathway with Notch1 or Jagged1 siRNAs reduced the migratory capacity, invasiveness and angiogenic ability of endothelial progenitor cells. Activation of the Notch signaling pathway in vivo in a rat model of mild traumatic brain injury promoted neurovascular repair. These findings suggest that the activation of the Notch signaling pathway promotes blood vessel formation and tissue repair after brain trauma.

Comparative Effectiveness and Safety of Monodrug Therapies for Lower Urinary Tract Symptoms Associated With Benign Prostatic Hyperplasia: A Network Meta-analysis.

A wide array of drugs are available for the treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia (BPH), but the evidence for the comparative effectiveness is controversial.The objective of this study is to evaluate the comparative effectiveness and safety of monodrug therapies for BPH.Data sources are MEDLINE, EMBASE, and the Cochrane Library.We included randomized controlled trials that compared α-blockers, 5-alpha reductase inhibitors (5ARIs), muscarinic receptor antagonists (MRAs), phosphodiesterase-5 inhibitor (PDE5-Is), or placebo for the treatment of BPH.Comparative effectiveness and safety were pooled by both traditional meta-analysis and network meta-analysis. Summary effect size was calculated as mean difference (MD) and relative risk (RR), together with the 95% confidence intervals (CIs).This study included 58,548 participants from 124 trials in total. When compared with placebo, α-blockers, 5ARIs, and PDE5-Is reduced International Prostate Symptom Score (IPSS) by -1.35 to -3.67 points and increased peak urinary flow rate (PUF) by -0.02 to 1.95 mL/s, with doxazosin (IPSS: MD, -3.67[-4.33 to -3.02]; PUF: MD, 1.95[1.61 to 2.30]) and terazosin (IPSS: MD, -3.37 [-4.24 to -2.50]; PUF: MD, 1.21[0.74 to 1.66]) showing the greatest improvement. The improvement in the IPSS was comparable among tamsulosin, alfuzosin, naftopidil, silodosin, dutasteride, sildenafil, vardenafil, and tadalafil. The incidence of total adverse events and withdraws due to adverse events were generally comparable among various agents.In conclusion, α-blockers, 5ARIs, and PDE5-Is are effective for BPH, with doxazosin and terazosin appearing to be the most effective agents. Drug therapies for BPH are generally safe and well-tolerated, with no major difference regarding the overall safety profile.

Colorectal cancer: using blood samples and tumor tissue to detect K-ras mutations.

We performed a meta-analysis to assess whether blood can be substituted for tumor tissue in K-ras mutation testing. PubMed, EMBASE, MEDLINE, and BIOSIS databases were searched. Twenty-three studies including 1261 patients were included. The pooled overall sensitivity, specificity, and concordance rate were 0.69 (95% CI: 0.59-0.78), 0.96 (95% CI: 0.93-0.97), and 0.86 (95% CI: 0.82-0.89), respectively. Subgroup analysis indicated that plasma (sensitivity: 0.74; mutation rate: 0.34) exhibited superior sensitivity compared with serum (sensitivity: 0.45; mutation rate: 0.24). We conclude that blood is a suitable substitute for tumor tissue in K-ras mutation testing. K-ras mutation positivity in blood can be used to identify patients who should not receive EGFR monoclonal antibody therapy, but the absence of blood positivity does not necessarily imply negativity.

Blood as a Substitute for Tumor Tissue in Detecting EGFR Mutations for Guiding EGFR TKIs Treatment of Nonsmall Cell Lung Cancer: A Systematic Review and Meta-Analysis.

Tumor tissues are often absent or insufficient for testing epidermal growth factor receptor (EGFR) mutations to guide EGFR tyrosine kinase inhibitors (TKIs) treatment of patients with nonsmall cell lung cancer (NSCLC). We conducted this systematic review and meta-analysis to assess whether blood can be used as a substitute for tumor tissue in detecting EGFR mutations. MEDLINE, EMBASE, and the Cochrane Library were searched for studies that provided data to estimate the accuracy of blood testing against tissue testing in NSCLC patients and/or those directly compared the efficacy of EGFR TKIs in EGFR mutant and wild-type patients according to sources of specimens. Sensitivity, specificity, and concordance rate were used as measures of the accuracy. Risk ratio (RR) for objective response and hazard ratio (HR) for progression-free survival (PFS) and overall survival (OS) were used as measures for treatment efficacy. We combined the effects by using the fixed-effects model unless there was evidence of heterogeneity, in which case a random-effects mode was used. This systematic review included 25 studies with 2605 patients. The pooled overall sensitivity, specificity, and concordance rate were 0.61, 0.90, and 0.79, respectively. Serum showed lower sensitivity (0.56 vs 0.65) but higher specificity (0.95 vs 0.85) and higher concordance (0.86 vs 0.74) than plasma. EGFR mutations (exon 19 or 21) in blood were significantly associated with objective response (RR: 4.08; 95% confidence interval [CI] 2.48-6.70), PFS (HR: 0.72; 95% CI 0.64-0.80), and OS (HR: 0.71; 95% CI 0.50-0.99). Importantly, the association of the mutations with the 3 clinical outcomes for serum was similar to that for tumor tissue and higher than that for plasma. Blood, in particular serum, is a good substitute when tumor tissue is absent or insufficient for testing EGFR mutations to guide EGFR TKIs treatment in patients with NSCLC. EGFR mutation positivity in blood could be used to recommend EGFR TKIs treatment, but the absence of blood positivity should not necessarily be construed with confirmed negativity.

Tong-xin-luo capsule for patients with coronary heart disease after percutaneous coronary intervention.

BACKGROUND: Percutaneous coronary intervention (PCI) is a standard treatment for coronary heart disease (CHD). Restenosis, defined as a 50% reduction in luminal diameter at six months after PCI, indicates a need for revascularisation. Restenosis has proven to be a major drawback to PCI. Tong-xin-luo is one of the prophylactic strategies for cardiovascular events in patients after PCI that is widely used in China, but its efficacy and safety have not been systematically evaluated. OBJECTIVES: To systematically assess the efficacy and safety of Tong-xin-luo capsules in preventing cardiovascular events after PCI in patients with CHD. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials in The Cochrane Library, MEDLINE (OVID), EMBASE (OVID), WanFang, Chinese Biomedical Database, Chinese Medical Current Contents, and China National Knowledge Infrastructure from their inception to June 2014. We also searched other resources, including ongoing trials and research registries. We applied no language restrictions. SELECTION CRITERIA: Randomised controlled trials of participants with CHD after PCI were included. Participants in the intervention group received Tong-xin-luo capsules for at least three months. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed the risk of bias. Any disagreements were resolved by discussion with a third review author. The primary outcomes included occurrence of angiographic restenosis and adverse events; the secondary outcomes included myocardial infarction, heart failure, angina, all cause mortality, mortality due to any cardiovascular event, use of revascularisation, patient acceptability, quality of life and cost-effectiveness. Dichotomous data were measured with risk ratios (RRs) with 95% confidence intervals (CIs). MAIN RESULTS: Sixteen studies involving 1063 participants were identified. The risk of bias for fifteen studies was high and along with imprecision and possible publication bias, this lowered our confidence in the results. There was low quality evidence that Tong-xi-luo reduced the rates of angiographic restenosis (RR 0.16, 95% CI 0.07 to 0.34), myocardial infarction (RR 0.32, 95% CI 0.16 to 0.66), heart failure (RR 0.26, 95% CI 0.11 to 0.62), and use of revascularisation (RR 0.26, 95% CI 0.15 to 0.45). There was very low quality evidence for the effect of Tong-xin-luo on all-cause mortality (RR 0.38, 95% CI 0.06 to 2.56), angina (RR 0.24, 95% CI 0.17 to 0.34) and death due to any cardiovascular event (RR 0.31, 95% CI 0.08 to 1.12). Adverse events were seldom reported, and included gastrointestinal reactions and nausea. AUTHORS' CONCLUSIONS: The addition of Tong-xin-luo to conventional Western medicine may possibly prevent restenosis and recurrence of cardiovascular events in patients with CHD after PCI. However, the data are limited by publication bias and high risk of bias for included studies. Further high-quality trials are required to evaluate the potential effects of this intervention.

Treatment with CA-074Me, a Cathepsin B inhibitor, reduces lung interstitial inflammation and fibrosis in a rat model of polymyositis.

Cathepsin B (CB) is involved in the turnover of proteins and has various roles in maintaining the normal metabolism of cells. In our recent study, CB is increased in the muscles of polymyositis/dermatomyositis (PM/DM). However, the role of CB in interstitial lung disease (ILD) has not been reported. ILD is a frequent complication of PM/DM, which is the leading cause of death in PM/DM. It carries high morbidity and mortality in connective tissue diseases, characterized by an overproduction of inflammatory cytokines and induced fibrosis, resulting in respiratory failure. The etiology and pathogenesis of ILD remain incompletely understood. This study investigated whether treatment with CA-074Me, a specific inhibitor of CB, attenuates ILD in PM. CB expression, inflammation, and fibrosis were analyzed in the lung tissues from patients with PM/DM. The animal model of PM was induced in guinea pigs with Coxsackie virus B1 (CVB1). CA-074Me was given 24 h after CVB1 injection for 7 consecutive days. At the end of the experiment, the animals were killed and lung tissues were collected for the following analysis. Inflammation, fibrosis and apoptosis cells, and cytokines were assessed by histological examinations and immunohistochemical analyses, western blot analysis and transferase-mediated dUTP nick-end labeling assay. In patients with PM/DM, the protein levels of CB were significantly elevated in lung tissues compared with healthy controls, which correlated with increases in inflammation and fibrosis. Similarly, the expression of CB, inflammation and fibrosis, CD8(+) T cell, CD68(+) cell, tumor necrosis factor-alpha, transforming growth factor-beta1 infiltrations, and apoptotic cell death were significantly increased in lung tissues of the guinea-pig model of CVB1-induced PM. These changes were attenuated by the administration of CA-074Me. In conclusion, this study demonstrates that PM/DM increases CB expression in lung tissues and inhibition of CB reduces ILD in a guinea-pig model of CVB1-induced PM. This finding suggests that CB may be a potential therapeutic target for ILD.

An internet-based epidemiological investigation of the outbreak of H7N9 Avian influenza A in China since early 2013.

BACKGROUND: In early 2013, a new type of avian influenza, H7N9, emerged in China. It quickly became an issue of great public concern and a widely discussed topic on the Internet. A considerable volume of relevant information was made publicly available on the Internet through various sources. OBJECTIVE: This study aimed to describe the outbreak of H7N9 in China based on data openly available on the Internet and to validate our investigation by comparing our findings with a well-conducted conventional field epidemiologic study. METHODS: We searched publicly accessible Internet data on the H7N9 outbreak primarily from government and major mass media websites in China up to February 10, 2014. Two researchers independently extracted, compared, and confirmed the information of each confirmed H7N9 case using a self-designed data extraction form. We summarized the epidemiological and clinical characteristics of confirmed H7N9 cases and compared them with those from the field study. RESULTS: According to our data updated until February 10, 2014, 334 confirmed H7N9 cases were identified. The median age was 58 years and 67.0% (219/327) were males. Cases were reported in 15 regions in China. Five family clusters were found. Of the 16.8% (56/334) of the cases with relevant data, 69.6% (39/56) reported a history of exposure to animals. Of the 1751 persons with a close contact with a confirmed case, 0.6% (11/1751) of them developed respiratory symptoms during the 7-day surveillance period. In the 97.9% (327/334) of the cases with relevant data, 21.7% (71/327) died, 20.8% (68/327) were discharged from a hospital, and 57.5% (188/327) were of uncertain status. We compared our findings before February 10, 2014 and those before December 1, 2013 with those from the conventional field study, which had the latter cutoff date of ours in data collection. Our study showed most epidemiological and clinical characteristics were similar to those in the field study, except for case fatality (71/327, 21.7% for our data before February 10; 45/138, 32.6% for our data before December 1; 47/139, 33.8% for the field study), time from illness onset to first medical care (4 days, 3 days, and 1 day), and time from illness onset to death (16.5 days, 17 days, and 21 days). CONCLUSIONS: Findings from our Internet-based investigation were similar to those from the conventional field study in most epidemiological and clinical aspects of the outbreak. Importantly, publicly available Internet data are open to any interested researchers and can thus greatly facilitate the investigation and control of such outbreaks. With improved efforts for Internet data provision, Internet-based investigation has a great potential to become a quick, economical, novel approach to investigating sudden issues of great public concern that involve a relatively small number of cases like this H7N9 outbreak.

Telomere recombination preferentially occurs at short telomeres in telomerase-null type II survivors.

In telomerase negative yeast cells, Rad52-dependent recombination is activated to maintain telomeres. This recombination-mediated telomere elongation usually involves two independent pathways, type I and type II, and leads to generation of type I and type II survivors. It remains elusive whether the recombination-mediated telomere elongation prefers to take place on shorter or longer telomeres. In this study, we exploited the de novo telomere addition system to examine the telomere recombination event in telomerase negative cells. We show that recombination preferentially occurs on shorter rather than longer telomeres in both pre-survivors and established type II survivors. In type II survivors, the short VII-L telomeres could invade either terminal TG1-3 sequence or short tracts of TG1-3 sequence in subtelomeric Y'-X and Y'-Y' junction to initiate recombination. Unexpectedly, short VII-L telomere recombination still takes place in type II survivors lacking either Rad50 or Rad59, which are required for type II survivor generation in senescing telomerase-null cells. Our results support the notion that Rad50 and Rad59 are not essential for the maintenance of type II survivors once established.

[Clinical analysis of 22 cases community-acquired Pseudomonas aeruginosa urinary tract infection].

OBJECTIVE: To study the characteristics of community-acquired urinary tract infections (CAUTIs) in children, analyze the risk factors and the susceptibility of antibiotics, thus to provide references to the diagnosis and medication of Pseudomonas aeruginosa (PA)-CAUTIs. Mothod Totally 22 cases of PA-CAUTIs were selected in one hospital from Jan, 2006 to Jan, 2012, their clinical information, laboratory results and radiological images were collected, and were compared with the CAUTIs cased by E. coli of those randomly selected over the same period. RESULT: In those 22 cases with PA-CAUTIs, the mean value of protein level was (32.25 ± 13.81) mg/ml, 19 of them were hospitalized, 6 had urinary operation history, 7 of them had long-term usage of glucocorticoids or immunosuppressive agents, and 20 had underlying diseases. A total of 22 children with 26 PA-CAUTIs episodes were compared to E. coli-CAUTIs. Compared with E. coli-CAUTIs patients, children with PA-CAUTIs more often presented with a lower albumin (P = 0.017), a history of urinary operation(P = 0.03), more cases had a history of urinary operation (P = 0.03), a long-term usage of glucocorticoids or immunosuppressive medication (P = 0.044). Through multivariate logistic regression of variables that were significant in univariate analysis (with hospitalizations, long-term usage of glucocorticoids or immunosuppressive, albumin, underlying disease and urinary operation histories), and it turned out that underlying diseases (odds ratio 8.500, 95% CI 1.513 - 47.761, P = 0.037) and with urinary operation histories (odds ratio 6.196, 95% CI 1.120 - 34.273, P = 0.037) were proved as the independent risk factors for PA-CAUTIs. Those PA bacterial strains had a 36.36% resistance rate to piperacillin, aztreonam and gentamicin, a 31.82% resistance rate to cefepime and ceftazidime, while the resistance rate (4.55%) to carbapenem antibiotics was relatively low, only to bacillosporin all the strains were sensitive. CONCLUSION: Underlying diseases and the urinary operation histories are the independent risk factors of the occurrence of PA-CAUTIs, carbapenem antibiotics and bacillosporin can be considered as the drugs of choice for its treatment.

[Pituitary functional recovery and hormone replacement therapy of patients with pituitary adenoma surgery].

OBJECTIVE: To study the pituitary functional recovery of patients with pituitary adenoma surgery and to identify appropriate dosages of hormone replacement for those patients. METHODS: Serum hormone levels of 187 patients with pituitary adenoma were detected before and after surgery. RESULTS: The lowest serum hormone levels were detected on the 3rd day after surgery (P < 0.05). The hormone levels were partly recovered on the 30th day (P < 0.05) and continued to rise to a relatively high level on the 90th day and one year after surgery (P < 0.05). Patients with older ages were more likely to suffer from hypopituitarism and had less satisfying recovery (P < 0.05) than their younger counterparts. The dosages of Euthyrox and Prednisone that were needed for hormone replacement therapy reached a relatively stable level on the 90th day after surgery (P < 0.05). CONCLUSION: Most patients with pituitary adenoma experienced hypopituitarism shortly after surgery, especially for the elderly who recovered more slowly. Low dosage of hormone replacement therapy based on their symptoms can help the patients reach a stable level of hormone within three months. As a result, the 90th day after surgery can be regarded as a cut-off time for measuring functional recovery of glandula pituitaria.