Escherichia coli-Induced cGLIS3-Mediated Stress Granules Activate the NF-κB Pathway to Promote Intrahepatic Cholangiocarcinoma Progression.

Patients with concurrent intrahepatic cholangiocarcinoma (ICC) and hepatolithiasis generally have poor prognoses. Hepatolithiasis is once considered the primary cause of ICC, although recent insights indicate that bacteria in the occurrence of hepatolithiasis can promote the progression of ICC. By constructing in vitro and in vivo ICC models and patient-derived organoids (PDOs), it is shown that Escherichia coli induces the production of a novel RNA, circGLIS3 (cGLIS3), which promotes tumor growth. cGLIS3 binds to hnRNPA1 and G3BP1, resulting in the assembly of stress granules (SGs) and suppression of hnRNPA1 and G3BP1 ubiquitination. Consequently, the IKKα mRNA is blocked in SGs, decreasing the production of IKKα and activating the NF-κB pathway, which finally results in chemoresistance and produces metastatic phenotypes of ICC. This study shows that a combination of Icaritin (ICA) and gemcitabine plus cisplatin (GP) chemotherapy can be a promising treatment strategy for ICC.

A Novel Trojan Horse Nanotherapy Strategy Targeting the cPKM-STMN1/TGFB1 Axis for Effective Treatment of Intrahepatic Cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (ICC) is characterized by its dense fibrotic microenvironment and highly malignant nature, which are associated with chemotherapy resistance and very poor prognosis. Although circRNAs have emerged as important regulators in cancer biology, their role in ICC remains largely unclear. Herein, a circular RNA, cPKM is identified, which is upregulated in ICC and associated with poor prognosis. Silencing cPKM in ICC cells reduces TGFB1 release and stromal fibrosis, inhibits STMN1 expression, and suppresses ICC growth and metastasis, moreover, it also leads to overcoming paclitaxel resistance. This is regulated by the interactions of cPKM with miR-199a-5p or IGF2BP2 and by the ability of cPKM to stabilize STMN1/TGFB1 mRNA. Based on these findings, a Trojan horse nanotherapy strategy with co-loading of siRNA against cPKM (si-cPKM) and paclitaxel (PTX) is developed. The siRNA/PTX co-loaded nanosystem (Trojan horse) efficiently penetrates tumor tissues, releases si-cPKM and paclitaxel (soldiers), promotes paclitaxel sensitization, and suppresses ICC proliferation and metastasis in vivo. Furthermore, it alleviates the fibrosis of ICC tumor stroma and reopens collapsed tumor vessels (opening the gates), thus enhancing the efficacy of the standard chemotherapy regimen (main force). This novel nanotherapy provides a promising new strategy for ICC treatment.

The role of apolipoprotein C3 in the regulation of nonalcoholic fatty liver disease, glucose and lipid metabolism, and islet β cell function / 生理学报

As a member of the apolipoprotein C (ApoC) family with a relatively high content, ApoC3 plays a major role in the regulation of triglyceride metabolism, and plays an important role in the occurrence and development of cardiovascular diseases, glucose and lipid metabolism disorders. Nonalcoholic fatty liver disease (NAFLD) refers to the accumulation of a large amount of fat in the liver in the absence of a history of chronic alcohol consumption or other damage to the liver. A large number of previous studies have shown that there is a correlation between the gene polymorphism and high expression of ApoC3 and NAFLD. In the context of hypertriglyceridemia (HTG), this article reviews the relationship between ApoC3 and NAFLD, glucose and lipid metabolism, and islet β cell function, showing that ApoC3 can not only inhibit lipoprotein lipase (LPL) and hepatic lipase (HL) activity, delay the decomposition of triglyceride in plasma to maintain the body's energy metabolism during fasting, but also be significantly increased under insulin resistance, prompting the liver to secrete a large amount of very low-density lipoprotein (VLDL) to induce HTG. Therefore, targeting and inhibiting ApoC3 might become a new approach to treat HTG. Increasing evidence suggests that ApoC3 does not appear to be an independent "contributor" to NAFLD. Similarly, our previous studies have shown that ApoC3 is not an independent factor triggering islet β cell dysfunction in ApoC3 transgenic mice, but in a state of excess nutrition, HTG triggered by ApoC3 high expression may exacerbate the effects of hyperglycemia and insulin resistance on islet β cell function, and the underlying mechanism remains to be further discussed.

Analysis of the causes of soft tissue complications after volar locking plate for the treatment of dorsal displaced distal radius fractures / 中国骨伤

OBJECTIVE@#To investigate the causes of soft tissue complications in patients with dorsal displacement distal radius fractures (DRF) after volar locking plate surgery.@*METHODS@#From July 2016 to May 2021, 112 patients with dorsal displacement DRF were treated with volar locking plate surgery, including 45 males and 67 females. The average age was (46.24±10.08) years old, ranging from 18 to 85 years old. According to whether there were soft tissue complications after operation, they were divided into complication group (40 cases) and non complication group (72 cases). Compared with preoperation, the radial metacarpal inclination and ulnar deflection angle, wrist flexion activity and dorsal extension activity, and grip strength of patients after operation were significantly improved (P<0.05). Compared with the non complication group, the proportion of patients in the complication group whose age was>60 years, body mass index (BMI) more than 30 kg·m-2, smoking, diabetes, fracture type C, open fracture and operation time more than 90 min was higher (P<0.05). The age, BMI, smoking, diabetes, fracture AO classification, fracture type and operation time were analyzed by multifactor Logistic regression to determine the independent risk factors affecting the occurrence of postoperative soft tissue complications of patients, establish a nomogram prediction model, and evaluate the model.@*RESULTS@#At the latest follow-up, the excellent and good rate of wrist joint function recovery was 83.93% (94/112), and the excellent and good rate of fracture reduction was 84.82% (95/112). Multivariate Logistic regression analysis showed that age more than 60 years old, diabetes, fracture type C, open fracture and operation time more than 90 min were independent risk factors for postoperative soft tissue complications (P<0.05). The receiver operating characteristic (ROC), calibration curve and clinical decision curve of the nomogram prediction model showed discrimination, accuracy and validity were good.@*CONCLUSION@#Age more than 60 years, diabetes mellitus, fracture type C, open fracture, and operation time more than 90 min are all independent risk factors for soft tissue complications after DRF volar plate fixation. In clinical treatment, perioperative soft tissue management should be done in such patients to prevent complications.

2.5 in Xi'an / 公共卫生与预防医学

Objective To analyze the pollution characteristics of 12 kinds of metals and metalloid elements in PM2.5 in Xi'an city, and to assess the health risks. Methods In 2018, PM2.5 samples were collected regularly every month at two monitoring points in Lianhu District and Yanta District of Xi'an City. The content of twelve metal and metalloid elements (Sb, Al, As, Be, Cd, Cr, Hg, Pb, Mn, Ni, Se, and Ti) in the samples were determined. The test results were statistically analyzed and evaluated according to different regions and seasons. The health risk assessment model recommended by the US Environmental Protection Agency (EPA) was used to assess the health risks of the metal and metalloid elements. Results A total of 165 PM2.5 samples were collected and analyzed. The qualified rates of As and Cd were 51.52% and 83.03%, respectively, and there was no significant difference between regions (P＞0.05). The qualified rate of As in each season from high to low was summer> autumn> winter> spring. The average concentration of As was 8.21 ng/m3, being 1.37 times higher than the standard. The average concentration of As in each season exceeded the standard, and the order from high to low was winter> spring> autumn> summer. The average concentrations of other elements did not exceed the standard. HQ value and HI value of As, Cd, Cr, Pb, Mn, Ni, Hg, Ti and Se were all less than 1. The ILCR value of carcinogenic elements As, Cd, Cr and Ni was between 3.63×10-07 ~2.58×10-05. The ILCR value was highest for As, followed by Cr. The ILCR value was highest in winter, followed by spring and autumn, and lowest in summer. The order of ILCR value was adult males> adult females> children and adolescents. Conclusion The pollution of metal and metalloid elements in the atmospheric PM2.5 in Xi'an in the winter is most serious. Arsenic and chromium in PM2.5 pose a higher potential health risk to the population through the respiratory route.

Curative effects of bipolar electrocoagulation for gastric antral vascular ectasia (with video) / 中华消化内镜杂志

To evaluate the efficacy and feasibility of bipolar electrocoagulation in the treatment of gastric antral vascular ectasia(GAVE). Six patients with GAVE who underwent gastroscopy and bipolar electrocoagulation between January 2018 and December 2019 in the Affiliated Hospital of Medical School of Ningbo University were included in the study.The operation and clinical response were observed. All the 6 patients underwent bipolar electrocoagulation successfully. The mean operation time was 32 min (range 25-45 min). Mean number of sessions required for eradication of GAVE was 1.17. No severe complications related to endoscopic treatment occurred. There was no recurrence of GAVE at a mean time of 10.8 months (range 2-25 months) of follow-up. Stabilization of hemoglobin levels and decrease in blood transfusion requirements along with endoscopically complete or near-complete eradication of GAVE were observed in all patients during the follow-up.Bipolar electrocoagulation in the treatment of GAVE is effective, safe, and simple.

Clinical value of radiomics based on CT examination in preoperative differential diagnosis of pancreatic serous cystadenoma and mucinous cystadenoma / 中华消化外科杂志

Objective:To investigate the clinical value of radiomics based on computed tomography (CT) examination in preoperative differential diagnosis of pancreatic serous cystadenoma (SCA) and mucinous cystadenoma (MCA).Methods:The retrospective case-control study was conducted. The clinicopathological and imaging data of 154 patients with pancreatic cystic neoplasms who were admitted to the First Affiliated Hospital, Zhejiang University School of Medicine from January 2012 to December 2019 were collected. There were 24 males and 130 females, aged (50±13)years. Of the 154 patients, 99 cases were diagnosed as SCA and 55 cases were diagnosed as MCA. All the 154 patients underwent plain and enhanced CT scan of pancreas before operation. The clinical characteristics, radiology features and radiomics features of all patients were collected to construct the clinical characteristics model, radiology model, radiomics model and fused model. The receiver operating characteristic (ROC) curve of each model was drawn, and those constructed models were evaluated by area under the curve (AUC), accuracy, sensitivity, specificity, positive predictive value and negative predictive value. Based on the optimal model, the nomogram was constructed. Observation indicators: (1) establishment and validation of clinical characteristics model; (2) establishment and validation of radiology model; (3) establishment and validation of radiomics model; (4) establishment and validation of fused model; (5) nomogram of fused model. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test or Fisher exact probability. Results:(1) Establishment and validation of clinical characteristics model: 3 clinical characteristics, including age, symptoms and preoperative serum CA19-9, were selected using multinomial logistic linear regression analysis to construct the clinical characteristics model. Result of the multinomial logistic linear regression analysis was expressed by formula ①: clinical characteristics model score=0.635-0.007×age+0.054×clinical symptoms+0.108×preoperative serum CA19-9. The ROC curve for the test dataset of clinical characteristics model was drawn. The AUC, accuracy, sensitivity, specificity, positive predictive value and negative predictive value of clinical characteristics model were 0.611(95% confidence interval as 0.488?0.734, P<0.05), 56.6%, 66.7%, 56.3%, 41.5%, 78.4% for the training dataset and 0.771(95% confidence interval as 0.624?0.919, P<0.05), 77.8%, 63.1%, 88.5%, 80.1%, 76.7% for the test dataset, respectively. (2) Establishment and validation of radiology model: 5 radiology characteristics, including tumor location, the number of tumors, tumor diameter of cross section, lobulated tumor and polycystic tumor (more than 6), were selected using multinomial logistic linear regression analysis to construct the radiology model. Result of the multinomial logistic linear regression analysis was expressed by formula ②: radiology model score=?0.034+0.300×tumor location+0.202×the number of tumors+0.014×tumor diameter of cross section?0.251×lobulated tumor?0.170×polycystic tumor (more than 6). The ROC curve for the test dataset of radiology model was drawn. The AUC, accuracy, sensitivity, specificity, positive predictive value and negative predictive value of radiology model were 0.862(95% confidence interval as 0.791?0.932, P<0.05), 78.8%, 81.8%, 77.5%, 62.8%, 90.2% for the training dataset and 0.853(95% confidence interval as 0.713?0.994), P<0.05), 88.9%, 89.4%, 88.5%, 85.0%, 92.0% for the test dataset, respectively. (3) Establishment and validation of radiomics model: 4 categories of a total 1 067 radiomics features were extracted from 154 patients with pancreatic cystic neoplasms, including 7 first-order histogram features, 53 texture features, 848 wavelet features and 159 local binary pattern features. A total of 896 stable radiomics features were retained to construct the model, based on the condition of intraclass correlation coefficient >0.9. After selected by variance threshold and correlation coefficient threshold, 350 radiomics features were retained. Fifty synthetic radiomics features were constructed based on the original features in order to obtain potential radiomics features, and the total number of radiomics features was 400. After analyzed by the five-fold recursive feature elimination, 22 radiomics features were screened out, including 13 wavelet features, 7 synthetic radiomics features and 2 local binary pattern features. The support vector machine algorithm was used to construct the radiomics model. The penalty coefficient 'C' and parameter 'γ' of the radiomics model were 35.938 and 0.077, respectively. The kernel function of the radiomics model was 'radial basis function kernel'. The ROC curve of radiomics model using 5-fold cross validation was drawn. The average AUC, accuracy, sensitivity, specificity, positive predictive value and negative predictive value of the radiomics model were 0.870 ( P<0.05), 83.1%, 81.8%, 83.8%, 73.8% and 89.2%, respectively. (4) Establishment and validation of fused model: the fused model was constructed after selecting the tumor location and lobulated tumor of radiology characteristics and radiomics score. Result of the multinomial logistic linear regression analysis was expressed by formula ③: fused model socre=?0.154+0.218×tumor location?0.223×lobulated tumor+0.621×radiomics score. The ROC curve for the test dataset of fused model was drawn. The AUC, accuracy, sensitivity, specificity, positive predictive value and negative predictive value of fused model were 0.893(95% confidence interval as 0.828?0.958, P<0.05), 83.7%, 81.8%, 84.5%, 71.1%, 90.9% for the training dataset and 0.966(95% confidence interval as 0.921?0.999, P<0.05), 91.1%, 84.2%, 96.2%, 94.1%, 89.3% for the test dataset, respectively. (5) Nomogram of fused model: the nomogram of fused model was illustrated with the Youden index of 0.416. Conclusion:The prediction model based on the radiomics signature and radiological features extracted from preoperative CT examination can make the differential diagnosis of pancreatic SCA from MCA.

Transboundary Frontiers: An Emerging Priority for Biodiversity Conservation.

The world's biomes and their associated ecosystems are artificially fractured by geopolitical boundaries that define countries. Yet 'transboundary' landscapes often overlap with biodiversity hotspots, contain surprisingly important ecosystems, and provide critical habitats for threatened species. Notwithstanding, biodiversity in these landscapes is increasingly imperiled by infrastructure, including walls and fences along borders and cross-border roads that drive landscape fragmentation and the loss of ecological connectivity. Associated problems due to reduced governance (e.g., illegal wildlife trade) also undermine conservation efforts in these important regions. In this review, we distinguish positive and negative effects of transboundary frontiers on biodiversity conservation, discuss lessons from existing frameworks, and identify scenarios that can maximize opportunities for biodiversity conservation in transboundary frontiers.

Disentangling the evolutionary history and biogeography of hill partridges (Phasianidae, Arborophila) from low coverage shotgun sequences.

The advent of the phylogenomic era has significantly improved our understanding of the evolutionary history and biogeography of Southeast Asia's diverse avian fauna. However, the taxonomy and phylogenetic relationships of many Southeast Asian birds remain poorly resolved, especially for those with large geographic ranges, which might have experienced both ancient and recent geological and environmental changes. In this study, we examined the evolutionary history and biogeography of the hill partridges (Galliformes: Phasianidae: Arborophila spp.), currently the second most speciose galliform genus, and thought to have colonized Southeast Asia from Africa. We present a well-resolved phylogeny of 14 Arborophila species inferred from ultra-conserved elements, exons, and mitochondrial genomes from both fresh and museum samples, which representing almost complete coverage of the genus. Our fossil-calibrated divergence time estimates and biogeographic modeling showed the ancestor of Arborophila arrived in Indochina during the early Miocene, but the initial divergence within Arborophila did not occur until ~10 Ma when global cooling intensified. Subsequent dispersal and diversification within Arborophila were driven by several tectonic and climatic events. In particular, we found evidence of rapid radiation in Indochinese Arborophila during the Pliocene global cooling and extensive dispersal and speciation of Sundaic Arborophila during the Pleistocene sea-level fluctuations. Taken together, these results suggest that the evolutionary history and biogeography of Arborophila were influenced by complex interactions among historical, geological and climatic events in Southeast Asia.

The study of multiple diagnosis models of human prostate cancer based on Taylor database by artificial neural networks.

BACKGROUND: Prostate cancer (PCa) is the most common malignancy seen in men and the second leading cause of cancer-related death in males. The incidence and mortality associated with PCa has been rapidly increasing in China recently. METHODS: Multiple diagnostic models of human PCa were developed based on Taylor database by combining the artificial neural networks (ANNs) to enhance the ability of PCa diagnosis. Genetic algorithm (GA) is used to select feature genes as numerical encoded parameters that reflect cancer, metastatic, or normal samples. Back propagation (BP) neural network and learning vector quantization (LVQ) neural network were used to build different Cancer/Normal, Primary/Metastatic, and Gleason Grade diagnostic models. RESULTS: The performance of these modeling approaches was evaluated by predictive accuracy (ACC) and area under the receiver operating characteristic curve (AUC). By observing the statistically significant parameters of the three training sets, our Cancer/Normal, Primary/Metastatic, and Gleason Grade models' with ACC and AUC can be drawn (97.33%, 0.9832), (99.17%, 0.9952), and (90.48%, 0.8742), respectively. CONCLUSION: These results indicated that our diagnostic models of human PCa based on Taylor database combining the feature gene expression profiling data and artificial intelligence algorithms might act as a powerful tool for diagnosing PCa. Gleason Grade diagnostic models were used as novel prognostic diagnosis models for biochemical recurrence-free survival and overall survival, which might be helpful in the prognostic diagnosis of PCa in patients.

Increasing of FKBP9 can predict poor prognosis in patients with prostate cancer.

BACKGROUND: FK506 binding protein 9 (FKBP9) has been reported and identified for a long time, but its relationship with cancer is rarely studied. For example, the role of FK506 binding protein 9 in prostate cancer (PCa) is still unclear. Therefore, we decided to detect the expression level of FKBP9 in PCa and explore its clinical significance. METHODS: The expression level of FKBP9 protein was detected by immunohistochemistry. In addition, it was demonstrated by high-throughput sequencing of mRNA levels in the TCGA (cancer genome atlas) dataset of 499 patients. Kaplan-meier analysis and Cox proportional hazard regression model were used to evaluate the relationship between FKBP9 expression and survival in prostate cancer patients. RESULTS: The expression of FKBP9 was localized in the cytoplasm, which in normal prostate tissues was obviously lower than that in PCa tissues (P = 0.001). High expression of FKBP9 was related with lymph node metastasis (P = 0.022) and distant metastasis (P = 0.028). Kaplan-Meier survival analysis revealed that the BCR-free survival of PCa patients with high FKBP9 level was significantly shortened (P=0.041). CONCLUSIONS: FKBP9 may be a cancer promoter that enhances PCa progression, and the level of FKBP9 may be used as an independent precursor of PCa patients.

Analysis of the status of rural garbage and sewage treatment in Shanxi Province, 2016-2018 / 公共卫生与预防医学

Objective To understand the status and dynamic changes in the treatment of rural garbage and sewage in Shaanxi Province and provide the basis for relevant departments to formulate policies and measures. Methods Every year from 2016 to 2018, 600 administrative villages in 30 agricultural counties were randomly selected as monitoring points, and 3 000 households were selected as monitoring households. Monitoring data was obtained through data reading, interviews, and on-site observations. Results The three-year rural population coverage rate of the garbage treatment plant was 28.31%, 36.10%, 39.36%, respectively, and the sewage treatment plant coverage rate was 12.27%, 20.39%, 15.02%, respectively. The annual differences were statistically significant（χ2=23.24、22.42，P=0.00）. The proportion of monitoring points for the three-year unified collection of domestic garbage was 30.50%, 43.67%, 51.00%, respectively, and the percentage of monitoring points for incineration garbage was 16.67%, 15.00%, 8.33%, respectively, and the annual differences were statistically significant（χ2=53.25、20.19，P=0.00）. The proportion of domestic sewage discharge monitoring points through pipelines was 12.67%, 11.17%, 31.17%, respectively, and the proportion of monitoring points discharged into treatment plants was 4.33%, 6.00%, 15.17%, respectively, and the annual differences were both statistically significant（χ2=99.45、52.50，P=0.00）. Conclusion In recent years, the rural garbage and sewage treatment situation in Shaanxi Province had improved, but there was still much room for improvement. It is recommended to increase environmental protection publicity and government investment, strengthen daily supervision, pay equal attention to construction and management, control the random stacking and discharging of garbage and sewage, and enhance the disposal rate of garbage and sewage.

Comparison of intravascular ultrasound and venography in the intraoperative evaluation of iliac vein compression syndrome / 中华普通外科杂志

Objective To compare intravascular ultrasound (IVUS) with venography in the intraoperative evaluation of iliac vein compression syndrome (IVCS).Methods From Sep 2017 to Mar 2018,consecutive patients with suspicious iliac vein compression,underwent both venography and IVUS.The results were compared between IVUS and venography.Results 40 patients with 48 limbs were enrolled.Venography underestimated both the diameter and area stenosis compared with IVUS (39.63％ ± 15.48％ vs.64.97％ ±16.42％,P＜0.001;51.83％ ±18.23％ vs.59.19％ ±14.17％,P=0.021,respectively).The eccentricity detected by venography was lower than IVUS (0.69 ±0.17 vs.0.93 ±0.17,P ＜0.001).Taking IVUS as gold standard,the sensitivity and the specificity of venography for detecting a ≥50％ stenosis was 18.92％ and 81.82％,and the intertechnique agreement was extremely low between venography and IVUS (κ =0.004).Conclusion Compared with IVUS,venography underestimated the degree of stenosis in IVCS.The sensitivity of venography in detecting a significant stenosis was very low.

Comparison of intravascular ultrasound and venography in the intraoperative evaluation of iliac vein compression syndrome / 中华普通外科杂志

Objective@#To compare intravascular ultrasound (IVUS) with venography in the intraoperative evaluation of iliac vein compression syndrome (IVCS).@*Methods@#From Sep 2017 to Mar 2018, consecutive patients with suspicious iliac vein compression, underwent both venography and IVUS. The results were compared between IVUS and venography.@*Results@#40 patients with 48 limbs were enrolled. Venography underestimated both the diameter and area stenosis compared with IVUS (39.63%±15.48% vs. 64.97%±16.42%, P<0.001; 51.83%±18.23% vs. 59.19%±14.17%, P=0.021, respectively). The eccentricity detected by venography was lower than IVUS (0.69±0.17 vs. 0.93±0.17, P<0.001). Taking IVUS as gold standard, the sensitivity and the specificity of venography for detecting a ≥50% stenosis was 18.92% and 81.82%, and the intertechnique agreement was extremely low between venography and IVUS (κ=0.004).@*Conclusion@#Compared with IVUS, venography underestimated the degree of stenosis in IVCS. The sensitivity of venography in detecting a significant stenosis was very low.

Analysis on HIV/AIDS surveillance among pregnant women in Taizhou City from 2014 to 2018 / 中华疾病控制杂志

Objective To analyze the time trend of HIV epidemic and to provide basis for comprehensive HIV infection prevention among pregnant women. Methods From 2014 to 2018, continuous cross-sectional surveys were conducted among pregnant women in two maternity and child health care hospitals. 800 blood samples were collected each year to test HIV infection, syphilis and hepatitis C virus (HCV). Results A total of 4 000 eligible pregnant women completed the interview and blood testing. The awareness rate of knowledge about HIV/AIDS was 91.2%, and the rate was increasing year by year. Multivariate Logistic regression analysis showed that the awareness rate was associated with at age of more than 35, with lower education than college and the husband used to work in other places. Conclusions The rate of HIV infection among PRGs was at a low level in Taizhou.

A cross-talk between integrin ß4 and epidermal growth factor receptor induces gefitinib chemoresistance to gastric cancer.

BACKGROUND: Gastric cancer presents a major health burden worldwide. Therefore, many molecular targeting agents have been evaluated for treatment of gastric cancer. Gefitinib has shown anticancer activity against gastric cancer which work through inhibiting epidermal growth factor receptor (EGFR). However, the effect of gefitinib is limited due to its resistance. Therefore, understanding the mechanisms of gefitinib resistance is desperately needed to formulate novel strategies against gastric cancer. Here, we analyzed resistance mechanism from the crosstalk between EGFR and integrin ß4. METHODS: Integrin ß4-expression vector or siRNA were used to analyze the functional effects of integrin ß4 on chemoresistance of gastric cancer cells to gefitinib. EGFR and integrin ß4 expression, proliferation and apoptosis of gastric cancer cells were assayed by indirect immunofluorescence, western blot, MTT and flow cytometry respectively. EGFR and integrin ß4 expression were also assayed on patient samples. RESULTS: It was found that the integrin ß4 expression was increased in gefitinib-resistant gastric cell line. The upregulated integrin ß4 expression was identified to promote gefitinib resistance and proliferation, and inhibit apoptosis, while downregulation of integrin ß4 was to inhibit gefitinib resistance and proliferation, and induce apoptosis. Moreover, the overexpression of integrin ß4 in SGC7901 cells resulted in the down-regulation of p-EGFR protein levels while down-regulation of integrin ß4, significantly resulted in overexpression of p-EGFR. The results of western blot from patients also showed there was obvious negative correlation between p-EGFR and integrin ß4 in gastric cancer patients. CONCLUSION: Considering the above results, it is concluded that the interaction of EGFR and integrin ß4 may change the sensitivity of gefitinib treatment.

Efficacy and safety of simulated artificial pancreas in modulating stress hyperglycemia in critically ill patients:a prospective randomized controlled study / 中华危重病急救医学

Objective To explore efficacy and safety of simulated artificial pancreas in modulating stress hyperglycemia in critically ill patients. Methods A prospective randomized controlled study was performed. Seventy-two critically ill patients with stress hyperglycemia, aged 18-85 years, acute physiology and chronic health evaluationⅡ(APACHEⅡ) score over 15, two consecutive random blood glucose 11.1 mmol/L or higher, glycated hemoglobin (HbA1C) below 0.065, unable to eat food for 3 days after inclusion, or only accepting parenteral nutrition, admitted to intensive care unit (ICU) in Shanghai Punan Hospital of Pudong New District from January 1st, 2015 to June 30th, 2017 were enrolled. The patients were divided into three groups according to the random number table method, high-intensity group and low-intensity group were injected Novolin R (high-intensity group 2/3 dosage, low-intensity group 1/3 dosage) to modulate stress hyperglycemia by simulated artificial pancreas. Simulated artificial pancreas consisted of Guardian real time glucose monitoring system (GRT system), close-circle control algorithm and micro-pump;subcutaneous injection of Humulin 70/30 was applied to modulate stress hyperglycemia in humulin group. Real-time glucose levels of interstitial fluid in abdominal wall, equivalent to blood glucose levels, 10 minutes each time, were monitored by using of GRT system for all patients in three groups. Fasting serum levels of stress hormones including epinephrine and cortisol and insulin resistance index (IRI) were recorded within 24 hours after inclusion. Mean blood glucose, blood glucose variation coefficient, blood glucose target-reaching rate, blood glucose target-reaching time, hypoglycemia rate and 6-month mortality were measured. Twenty healthy adults from health administration department of the hospital were recruited as healthy control group. Results A total of 60 eligible critically ill patients were included in this study, each group with 20 patients. There was no significant difference in gender, age, APACHE Ⅱ scores among three groups. The levels of serum epinephrine, cortisol and IRI within 24 hours after inclusion in the three groups were significantly higher than those in healthy control group. The mean blood glucose levels of humulin group, low-intensity group, high-intensity group were decreased (mmol/L: 10.2±3.2, 8.4±2.6, 8.1±2.2), the blood glucose target-reaching rate were increased [40.2% (3 295/8 196), 71.1% (5 393/7 585), 80.4% (6 286/7 818)], the blood glucose target-reaching time were shortened (hours: 49.1±5.8, 24.6±4.6, 17.5±4.2), the hypoglycemia rates were increased respectively [1.3% (108/8 196), 2.8% (211/7 585), 4.0% (313/7 818)], with statistically significant differences (all 1 = 0.000). There was no significant difference in blood glucose variation coefficient and 6-month mortality among three groups [blood glucose variation coefficient: (29.4±3.7)%, (28.5±5.3)%, (26.1±4.6)%, 6-month mortality: 55.0%, 45.0%, 40.0%, all 1 > 0.05]. Conclusions Simulated artificial pancreas could effectively and safely modulate stress hyperglycemia in critically ill patients, high-intensity modulation could bring about better efficacy in the regulation of hyperglycemia. High-frequency blood glucose monitoring by using GRT system could promptly identify hypoglycemia and help it to be corrected.

Predictive value of intracerebral hemorrhage score for stroke-associated pneumonia in patients with primary intracerebral hemorrhage / 中国脑血管病杂志

Objective To investigate the predictive value of intracerebral hemorrhage (ICH) score for stroke-associated pneumonia (SAP) in patients with primary intracerebral hemorrhage. Methods From January 2014 to July 2015,209 consecutive patients with ICH at the Emergency Department,Shanghai Jiading District Central Hospital were enrolled retrospectively.The general information of the patients were analyzed. They were divided into either a SAP group (n=73) or a non-SAP group (n=136) according to whether they had SAP or not.Based on the ICH score,the incidence and mortality of SAP were analyzed;the occurrence of SAP was prejudged by ICH score.The ROC curve was plotted,and the sensitivity,specificity and the best cut-off value were calculated. Results (1) The incidence of SAP was 34.9% (73/209) and the mortality was 21.1% (44/209) in patients with ICH.(2) There were significant differences in age (73 ± 12 and 63 ± 14),hematoma volume (23.4 [9.6,51.1] and 6.2 [3.1,16.0],and ICH score (2[1,3] and 1 [0,2]) between the SAP group and the non-SAP group (all P<0.01).Compared with non-SAP group,Glasgow coma scale(GCS) score of the SAP group was significantly decreased(8 [4,11] and 15 [13,15],P<0.01).The area under the ROC curve of the ICH score predicting the occurrence of SAP was 0.775 (95% CI 0.709-0.842,P<0.01).When the maximum Youden index was 0.453,the best cut-off value of the corresponding ICH score was 2,its sensitivity was 74%,specificity was 71%,the positive predictive value was 0.58,and the negative predictive value was 0.84. Conclusions The incidence of SAP in patients with ICH is higher.The ICH score may predict the clinical value of the occurrence of SAP. Clinical attention should be paid to the risk of occurring SAP in patients with ICH whose ICH score≥2.

Correlation of serum C-telopeptide cross-linked collagen type Ⅰ with bone mineraI density in a rat modeI of disuse osteoporosis / 中国组织工程研究

BACKGROUND: C-telopeptide and N-telopeptide cross-linked collagen type Ⅰ (CTx and NTx, respectively) are specific biochemical bone markers that can reflect bone formation and resorption. OBJECTIVE: To analyze the association of CTx with disuse osteoporosis. METHODS: Male Sprague-Dawley rats, weighing 180-220 g, were randomly divided into control and disuse osteoporosis groups. Right hind limbs of the rats in the disuse osteoporosis group were immobilitzed for 4 weeks by ankle-tail fixation to establish the rat model of disuse osteoporosis. Peritoneal venous blood was collected before and after modeling, and the femur was then removed to measure the serum CTx level and bone mineral density of the bilateral femurs. RESULTS AND CONCLUSION: The serum CTx level did not differ significantly between groups before modeling (P > 0.05). At 4 weeks after modeling, the serum CTx level in the disuse osteoporosis group was significantly higher than that in the control group and at baseline (P <0.01). The serum CTx level showed no significant change in the control group before and after modeling (P > 0.05). The increment of serum CTx in the disuse osteoporosis group exhibited a negative correlation with the bone mineral density of the bilateral femurs (r=0.426, P < 0.01). The bone mineral density of the right femur in the disuse osteoporosis group was significantly lower than that of the left one in the disuse osteoporosis group and the right one in the control group (P < 0.01), and there was no significant difference in the bone mineral density between left and right femurs in the control group (P > 0.05). These results imply that the model of disuse osteoporosis by ankle-tail fixation is established successfully. Disuse osteoporosis can promote the production of CTx further reducing bone mineral density; CTx is positively correlated with the degree of bone loss, so it can be used for therapeutic assessment and diagnosis of osteoporosis.