McAN: an ultrafast haplotype network construction algorithm

SummaryHaplotype network is becoming popular due to its increasing use in analyzing genealogical relationships of closely related genomes. We newly proposed McAN, a minimum-cost arborescence based haplotype network construction algorithm, by considering mutation spectrum history (mutations in ancestry haplotype should be contained in descendant haplotype), node size (corresponding to sample count for a given node) and sampling time. McAN is two orders of magnitude faster than the state-of-the-art algorithms, making it suitable for analyzation of massive sequences. AvailabilitySource code is written in C/C++ and available at https://github.com/Theory-Lun/McAN and https://ngdc.cncb.ac.cn/biocode/tools/BT007301 under the MIT license. The online web service of McAN is available at https://ngdc.cncb.ac.cn/ncov/online/tool/haplotype. SARS-CoV-2 dataset are available at https://ngdc.cncb.ac.cn/ncov/.

Genomic epidemiology of SARS-CoV-2 in Pakistan

Pakistan has been severely affected by the COVID-19 pandemic. To investigate the initial introductions and transmissions of the SARS-CoV-2 in the country, we performed the largest genomic epidemiology study of COVID-19 in Pakistan and generated 150 complete SARS-CoV-2 genome sequences from samples collected before June 1, 2020. We identified a total of 347 variants, 29 of which were over-represented in Pakistan. Meanwhile, we found over one thousand intra-host single-nucleotide variants. Several of them occurred concurrently, indicating possible interactions among them. Some of the hypermutable positions were not observed in the polymorphism data, suggesting strong purifying selections. The genomic epidemiology revealed five distinctive spreading clusters. The largest cluster consisted of 74 viruses which were derived from different geographic locations and formed a deep hierarchical structure, indicating an extensive and persistent nation-wide transmission of the virus that was probably contributed by a signature mutation of this cluster. Twenty-eight putative international introductions were identified, several of which were consistent with the epidemiological investigations. No progenies of any of these 150 viruses have been found outside of Pakistan, most likely due to the nonphmarcological intervention to control the virus. This study has inferred the introductions and transmissions of SARS-CoV-2 in Pakistan, which could provide a guidance for an effective strategy for disease control.

Mechanism of human umbilical cord mesenchymal stem cells alleviating ischemia-reperfusion injury of hepatocytes through mitochondrial transfer / 器官移植

Objective To explore the mechanism of human umbilical cord mesenchymal stem cell (HUC-MSC) alleviating ischemia-reperfusion injury (IRI) of liver cells through mitochondrial transfer. Methods Normal human liver cell line L02 was divided into the blank control group, oxygen-glucose deprivation (OGD) group, experimental control group, and L02 and HUC-MSC co-culture group (L02+HUC-MSC group). L02+HUC-MSC group was further divided into 10:1 co-culture subgroup (group A), 4:1 co-culture subgroup (group B), 2:1 co-culture subgroup (group C), 1:1co-culture subgroup (group D) and 1:2 co-culture subgroup (group E) according to different co-culture ratio of L02 and HUC-MSC. The apoptosis rate and relative reactive oxygen species (ROS) level of L02 cells were detected by flow cytometry. The MitoTracker positive rate of L02 cells was detected by flow cytometry. The mitochondrial transfer from HUC-MSC to L02 cells was observed by laser confocal microscope. Results The apoptosis rate and relative ROS level of L02 cells in the OGD group were significantly higher than those in the blank control group (both P < 0.05). Compared with the OGD group, the apoptosis rates of L02 cells in group B, C, D and E were significantly decreased (all P < 0.05), and the relative ROS level of L02 cells in group E was significantly declined (P < 0.05). The MitoTracker positive rate of L02 cells did not significantly differ between group A and experimental control group (P>0.05), whereas the MitoTracker positive rates of L02 cells in group B, C, D and E were significantly higher than that in the experimental control group in a concentration-dependent manner (all P < 0.05). Under the laser confocal microscope, mitochondrial transfer fromHUC-MSC to L02 cells could be observed through tunneling nanotube (TNT). Conclusions HUC-MSC may alleviate cell apoptosis and reduce ROS level of liver cells after IRI via direct mitochondrial transfer between cells.

Construction strategy of medical resource integration in regional medical alliance based on grounded theory / 中华医院管理杂志

Objective:To explore the integration path of medical resources in regional medical consortium, find out the problems affecting the process of integration, and put forward relevant suggestions.Methods:Methods According to the purposive sampling and combined with grounded theoretical research methods, semi-structured interviews were conducted with 73 government officials, heads and backbones of medical institutions in different regions of a city from August to November 2019. The data obtained from semi-structured interviews were analyzed by using grounded theory, and the path framework of medical resource integration in regional medical consortium was constructed through open coding, spindle coding and selective coding.Results:Four key links of medical resource integration in the regional medical alliance were sorted out, namely, integration prerequisites, integration strategies, support conditions, and integration methods, which together constituted the main axis of the theoretical framework. In addition, integration methods were affected by integration prerequisites, integration strategies and support conditions. The four factors and integration willingness served as influencing factors to exert impact on the integration tendency.Conclusions:The integration of medical resources in the medical alliance is a systematic project, which emphasizes the organic and overall governance of each key link, and the interaction between various elements will affect the final effect of medical resource integration.

Radiomics based on machine learning in predicting the long-term prognosis for triple-negative breast cancer after neoadjuvant chemotherapy / 中华放射学杂志

Objective:To explore the value of different radiomics models based on machine learning in predicting the risk of distant recurrence and metastasis of triple-negative breast cancer after neoadjuvant therapy.Methods:The clinical and imaging data of 150 patients with triple-negative breast cancer (TNBC) confirmed by histopathology were retrospectively analyzed. All patients underwent neoadjuvant chemotherapy and surgical resection from August 2011 to May 2017 in Fudan University Shanghai Cancer Center and Ruijin Hospital, Shanghai Jiao Tong University School of Medicine. One hundred and nine patients from Shanghai Fudan University Shanghai Cancer Center were used as the training group, and 41 patients from Ruijin Hospital, Shanghai Jiao Tong University School of Medicine were used as the validation group. The features were extracted from dynamic contrast-enhanced MRI (DCE-MRI) before treatment and were added with time domain features innovatively. Least absolute shrinkage and selection operator cross validation and recursive feature elimination were applied to select features. Six different supervised machine learning algorithms (logistic regression, linear discriminant analysis, k-nearest neighbor, naive bayesian, decision tree, support vector machine) were used to predict the prognosis. ROC curve, accuracy and F1 measure were used to evaluate the performance of the six algorithms, and also verified by the validation group.Results:The support vector machine algorithm had the best predictive effect in the recurrence and metastasis model based on 15 features, with the highest area under curve (training group was 0.917, validation group was 0.859), and the highest accuracy rate (training group was 87.5%, validation group was 82.9%) and the highest F1 measure (training group was 0.800, validation group was 0.741). In addition, of the 15 imaging features, 12 were the time domain features and 3 were spatial features.Conclusion:With the help of the time domain features and machine learning algorithms, radiomics signatures based on preoperative DCE-MRI can help predict the distant prognosis for TNBC after neoadjuvant chemotherapy and provide support for clinical decision making and follow-up management.

Coronavirus GenBrowser for monitoring adaptive evolution and transmission of SARS-CoV-2

Genomic epidemiology is important to study the COVID-19 pandemic and more than two million SARS-CoV-2 genomic sequences were deposited into public databases. However, the exponential increase of sequences invokes unprecedented bioinformatic challenges. Here, we present the Coronavirus GenBrowser (CGB) based on a highly efficient analysis framework and a movie maker strategy. In total, 1,002,739 high quality genomic sequences with the transmission-related metadata were analyzed and visualized. The size of the core data file is only 12.20 MB, efficient for clean data sharing. Quick visualization modules and rich interactive operations are provided to explore the annotated SARS-CoV-2 evolutionary tree. CGB binary nomenclature is proposed to name each internal lineage. The pre-analyzed data can be filtered out according to the user-defined criteria to explore the transmission of SARS-CoV-2. Different evolutionary analyses can also be easily performed, such as the detection of accelerated evolution and on-going positive selection. Moreover, the 75 genomic spots conserved in SARS-CoV-2 but non-conserved in other coronaviruses were identified, which may indicate the functional elements specifically important for SARS-CoV-2. The CGB not only enables users who have no programming skills to analyze millions of genomic sequences, but also offers a panoramic vision of the transmission and evolution of SARS-CoV-2.

The global landscape of SARS-CoV-2 genomes, variants, and haplotypes in 2019nCoVR

On 22 January 2020, the National Genomics Data Center (NGDC), part of the China National Center for Bioinformation (CNCB), created the 2019 Novel Coronavirus Resource (2019nCoVR), an open-access SARS-CoV-2 information resource. 2019nCoVR features a comprehensive integration of sequence and clinical information for all publicly available SARS-CoV-2 isolates, which are manually curated with value-added annotations and quality evaluated by our in-house automated pipeline. Of particular note, 2019nCoVR performs systematic analyses to generate a dynamic landscape of SARS-CoV-2 genomic variations at a global scale. It provides all identified variants and detailed statistics for each virus isolate, and congregates the quality score, functional annotation, and population frequency for each variant. It also generates visualization of the spatiotemporal change for each variant and yields historical viral haplotype network maps for the course of the outbreak from all complete and high-quality genomes. Moreover, 2019nCoVR provides a full collection of SARS-CoV-2 relevant literature on COVID-19 (Coronavirus Disease 2019), including published papers from PubMed as well as preprints from services such as bioRxiv and medRxiv through Europe PMC. Furthermore, by linking with relevant databases in CNCB-NGDC, 2019nCoVR offers data submission services for raw sequence reads and assembled genomes, and data sharing with National Center for Biotechnology Information. Collectively, all SARS-CoV-2 genome sequences, variants, haplotypes and literature are updated daily to provide timely information, making 2019nCoVR a valuable resource for the global research community. 2019nCoVR is accessible at https://bigd.big.ac.cn/ncov/.

Predictive value of IVIM-DWI and DCE-MRI quantitative parameters on the early efficacy of concurrent chemoradiotherapy for cervical squamous cell carcinoma / 中华放射肿瘤学杂志

Objective:To evaluate the application value of intravoxel incoherent motion diffusion weighted imaging (IVIM-DWI) and dynamic contrast enhancement MRI (DCE-MRI) in the prediction of the early efficacy of concurrent chemoradiotherapy (CCRT) for cervical squamous cell carcinoma.Methods:Fifty patients with cervical squamous cell carcinoma confirmed by pathology were included. Before CCRT, IVIM-DWI and DCE-MRI were scanned, and the values of quantitative parameters including ADC, D, D * and f of IVIM-DWI and K trans, K ep, V e and V p of DCE-MRI before treatment were measured for all patients. MRI reexamination was performed 1 month after the end of CCRT, and all patients were divided into the cure group and the residual group according to the tumor remission. The parameters of IVIM-DWI and DCE-MRI before treatment were statistically compared between two groups. The optimal predictive parameters and predictive thresholds were determined by drawing the receiver operating characteristic (ROC) curve. Results:Twenty-four patients were assigned into the cure group and twenty-six patients in the residual group. The ADC, D and V e values before treatment in the cure group were significantly lower than those in the residual group (all P<0.05), whereas the f and K trans values were significantly higher than those in the residual group (both P<0.05). The other parameters did not significantly differ between two groups (all P>0.05). The area under ROC curve (AUC=0.823) of D value was the largest, followed by K transvalue (AUC=0.754). The combined prediction efficacy of D and K trans (AUC=0.867) was higher than that of either D or K trans alone. The sensitivity was 88.5%, 85.8% and 88.8%, and the specificity was 70.8%, 66.7% and 79.2%, respectively. Conclusions:Quantitative parameters of IVIM-DWI and DCE-MRI before treatment have certain predictive value for the early efficacy of CCRT in cervical squamous cell carcinoma, among which the predictive efficacy of D value is the highest, and the combined application of D and K trans can improve the predictive efficacy.

Increasing transgenic expression in recombinant Chinese hamster ovary cells using introns in different directions / 生物工程学报

The aim of this study is to investigate the effect of the chimeric intron in different directions on the expression of the nerve growth factor (NGF) in recombinant Chinese hamster ovary (CHO) cells. The chimeric intron that contained the splice sequence of the first intron of the human β-globin and the human immunoglobulin heavy chain variable region intron was used. NGF gene was cloned into the expression vectors containing the chimeric intron in the forward or reverse direction, followed by transfecting into CHO cells, and screened under G418 to produce the stable transfected CHO cells. Fluorescence quantitative PCR, ELISA, and Western blotting were performed to detect the recombinant NGF gene expression in CHO cells. The results showed that the chimeric introns could significantly enhance the expression of NGF in recombinant CHO cells. Moreover, the enhancing effect on NGF expression level by the intron in the forward direction showed stronger than that of the reverse direction both at mRNA and protein level. In conclusion, the chimeric intron could increase NGF expression in stably transfected CHO cells and the effect is associated with the direction of the intron insertion.

Intravitreal injection of conbercept during vitrectomy surgery to treat severe proliferative diabetic retinopathy / 中华实验眼科杂志

Objective To observe and analysis the clinical effects and postoperative complications of intravitreal injection of conbercept during vitrectomy surgery (VRS) in severe proliferative diabetic retinopathy (PDR) treatment.Methods This is a prospective non-randomized controlled clinical study.A total of fifty-seven patients (sixty eyes) with severe PDR were enrolled in Tianjin Eye Hospital from June 2015 to March 2016,and the patients were divided into conbercept injection group and control group according to the patients' surgical method intention selection.The patients in conbercept injection group received an intravitreal injection of 0.05 ml conbercept solution during the surgery.The patients in control group only received VRS.The operations of the two groups were completed by the same doctor,and the follow-up time was 6 to 10 months after the surgery.The incidence of postoperative complications including a transient high intraocular pressure,early and late incidence of vitreous hemorrhage(VH),epiretinal membrane and traction retinal detachment (TRD),neovascular glaucoma (NVG),the central retinal thickness (CRT) and the best corrected visual acuity (BCVA) (LogMAR visual acuity) were comparatively analyzed.Results The incidence of early VH was 6.7％ (2/30) in conbercept injection group,which was significantly lower than 26.7％ (8/30) in control group (x2 =4.32,P =0.04).The incidences of late VH were 3.3％ (1/30) and 10.0％ (3/30) in conbercept injection group and control group,and the differences had no statistically significant difference (x2 =1.07,P＞0.05).The incidences of a transient high intraocular pressure,TRD and NVG between the two groups had no statistically significant difference (x2=0.69,0.22,2.07;all at P＞0.05).The change of CRT from one week to one month after the operation in conbercept injection group was more remarkable than that in the control group,and the difference was statistically significant (t=-3.23,P＜0.05).The mean LogMAR BCVA in two groups at 1 month and 6 months after operation were both improved in different degrees compared with the preoperative vision.The difference of mean LogMAR BCVA at 6 months was statistically significant (P＜0.05).Conclusions The intravitreal injection of conbercept during VRS in severe PDR patients can effectively prevent postoperative early VH,decrease CRT and improve visual acuity.

Intravitreal injection of conbercept during vitrectomy surgery to treat severe proliferative diabetic retinopathy / 中华实验眼科杂志

Objective To observe and analysis the clinical effects and postoperative complications of intravitreal injection of conbercept during vitrectomy surgery ( VRS ) in severe proliferative diabetic retinopathy ( PDR) treatment. Methods This is a prospective non.randomized controlled clinical study. A total of fifty.seven patients (sixty eyes) with severe PDR were enrolled in Tianjin Eye Hospital from June 2015 to March 2016,and the patients were divided into conbercept injection group and control group according to the patients ' surgical method intention selection. The patients in conbercept injection group received an intravitreal injection of 0. 05 ml conbercept solution during the surgery. The patients in control group only received VRS. The operations of the two groups were completed by the same doctor, and the follow.up time was 6 to 10 months after the surgery. The incidence of postoperative complications including a transient high intraocular pressure, early and late incidence of vitreous hemorrhage(VH),epiretinal membrane and traction retinal detachment(TRD),neovascular glaucoma(NVG),the central retinal thickness ( CRT ) and the best corrected visual acuity ( BCVA ) ( LogMAR visual acuity ) were comparatively analyzed. Results The incidence of early VH was 6. 7％( 2/30 ) in conbercept injection group, which was significantly lower than 26. 7％(8/30) in control group (χ2=4. 32,P=0. 04). The incidences of late VH were 3. 3％(1/30) and 10. 0％(3/30) in conbercept injection group and control group,and the differences had no statistically significant difference (χ2=1. 07,P>0. 05). The incidences of a transient high intraocular pressure,TRD and NVG between the two groups had no statistically significant difference (χ2=0. 69,0. 22,2. 07;all at P>0. 05). The change of CRT from one week to one month after the operation in conbercept injection group was more remarkablethan that in the control group,and the difference was statistically significant (t=-3. 23,P<0. 05). The mean LogMAR BCVA in two groups at 1 month and 6 months after operation were both improved in different degrees compared with the preoperative vision. The difference of mean LogMAR BCVA at 6 months was statistically significant (P<0. 05). Conclusions The intravitreal injection of conbercept during VRS in severe PDR patients can effectively prevent postoperative early VH,decrease CRT and improve visual acuity.

Abnormal bone mineral density in health checkup population with subclinical thyroid dysfunction / 中华健康管理学杂志

Objective To investigate the relationship between abnormal bone mineral density (BMD) and subclinical thyroid dysfunction. Methods Thyroid function, biochemical indicators of bone metabolism and BMD were reviewed retrospectively in the subjects who received health checkups from July 1, 2009 to January 31, 2017 in the Health Check-up Department of Peking Union Medical College Hospital. People who had thyroid dysfunction, recognized risk factors for osteoporosis, and medication history were excluded. A cross-sectional analysis of thyroid status and biochemical indicators of bone metabolism was performed by the standard methods. BMD at the lumbar spine and femoral neck was measured using dual energy X-ray absorptiometry. Results A total of 6884 subjects (3726 women and 3158 men) were enrolled in the study, with an average age of (50.74 ± 10.41) years. They were divided into three groups:subclinical hyperthyroid, subclinical hypothyroid, and euthyroidism. The alkaline phosphatase in subclinical hyperthyroid group was higher than that in the euthyroidism group[ (67.95±20.64)U/L vs. (63.88±18.99)U/L]. Calcium and phosphorus in blood were higher in both subclinical hyperthyroid and subclinical hypothyroid groups. The rate of abnormal BMD in male euthyroidism, subclinical hyperthyroid and subclinical hypothyroid groups were 36.10％(1049/2906), 29.27％(12/41) and 27.01％(57/211), respectively. The rate of abnormal BMD showed no difference between subclinical hyperthyroid group and euthyroidism group (P>0.05). The rate of abnormal BMD was lower in subclinical hypothyroid group than in euthyroidism group (χ2=7.0901, P0.05). Conclusion There is no significant difference in the rate of abnormal BMD between subclinical thyroid dysfunction group and euthyroidism group, possibly because abnormal serum biochemical indicators preceded the presence of low BMD. More sensitive methods used to determine the status of bone metabolism await to be developed.

The Status research of ICU Nurses career situations of tertiary general hospital in Shangdong Province / 中国实用护理杂志

Objective To understand the status quo of ICU nurses career situations and its influencing factors in Shandong province. Methods A total of 247 ICU nurses were investigated by questionnaires on career condition. Results The career condition score was 79.19 ± 11.63. In addition, statistical significances were revealed by occupational career questionnaire of ICU nurses in different aspect of the scores with age, gender, working years in the ICU, access years to ICU nurses specialist, whether to participate in career training. The scores of career condition and career identity ICU nurses were different, the 40-years-older group was higher than 31-40 years group (P=0.007, P=0.005). The dimension scores of male nurses organizational commitment was higher than that of female nurses(P=0.002). The scores of career condition whose ICU working life more than 16 years were higher than those of within 5 years(P=0.013). The career condition scores of the ICU nurses with access years of specialist qualifications 7-9 years was higher than those of within 3 years(P=0.011). Conclusions The career condition score of ICU clinical nurse specialists was at a medium level, it still needs to be further improved, managers should pay attention to the different levels of nurses to provide career training, in order to promote the professional development of critical care nurses.

Construction of transgenic tobacco expressing tomato GGPS2 gene and analysis of its low light tolerance / 生物工程学报

To explore the influence of low light on the synthesis of carotenoids, chlorophyll and the adaptability of transgenic plants with tomato Solanum lycopersicon L. GGPS2 gene, we constructed a vector containing a GGPS2 gene with green fluorescent protein (GFP) as report gene under the control of a cauliflower mosaic virus 35S promoter and introduced it into tobacco Nicotiana tabacum L. cv. Wisconsin 38 by Agrobacterium tumefaciens-mediated transformation. PCR analysis of the DNA from kanamycin resistant tobacco indicated that the transgenic tobacco containing the nptII gene, SlaGGPS2 gene and without contamination of Agrobacterium. We also detected the root tip of kanamycin resistant tobacco showing characteristic fluorescence. The contents of carotenoid, chlorophyll and photosynthesis of transgenic tobacco increased in comparison with wild tobacco after low light treatment. In addition, leaf mass per unit area, total dry weight, ratio of root to shoot in transgenic tobacco were all higher than that of the wild tobacco, which proved that the transgenic tobacco could increase the accumulation of biomass and promote it transport to root. The transgenic tobacco with SlaGGPS2 gene can increase the contents of carotenoid, chlorophyll, enhance the photosynthetic rate, promote the biomass accumulation and its distribution to root. Hence, the transgenic tobacco with SlaGGPS2 gene had increased low light tolerance and the SlaGGPS2 gene maybe can be used in other crops.

Analysis of ND4 gene mutations in acute myelogenous leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the relationship of the mutational status of the ND4 gene and the clinical features of acute myelogenous leukemia (AML) patients with ND4 mutations.</p><p><b>METHODS</b>Using PCR combined with directly sequencing, we identified somatic mutations of ND4 in 121 primary AML patients to couple with their clinical features.</p><p><b>RESULTS</b>There were 58 male patients and 63 female patients (median age 49 years, 10-86 years). Eight of 121 patients (6.6%) with de novo AML were found harboring missense mutation of ND4 gene, including 3 patients with A131V (3/8, 37.5%), 2 patients with A404T (2/8, 25%), 1 patient with F149L (1/8, 12.5%), 1 patient with G242D (1/8, 12.5%) and 1 patient with Y409H (1/8, 12.5%), respectively. Patients with ND4 mutations were associated with good karyotype (P=0.049), regardless of gender, age, white blood cell, hemoglobin, platelet, blast cells of bone marrow or immunophenotype (P>0.05). There were no statistical significance in mutations of FLT3-ITD, NPM1, CEBPA, c-KIT and DNMT3A between patients with ND4 mutation and wild-type (wt) ND4 (P>0.05). The median overall survival of patients with ND4 mutations and wt ND4 were all not reached. The median relapse-free survival were not reached and 29(2-53) months, respectively (P>0.05). There was no significance in the ratio of CR and RR patients between wt ND4 and ND4 mutated groups (P>0.05).</p><p><b>CONCLUSION</b>It was concluded that novel ND4 mutations could be found in de novo AML patients, especially in patients with good karyotype. Thus, ND4 mutations might play an important role in AML prognosis. However, whether the mitochondria dysfunction contribute to leukemogenesis needs to be further investigated.</p>

Serum Caspase-3 Activity in Tuberculosis Patients / 现代检验医学杂志

Objective To explore serum caspase-3 activity in pulmonary tuberculosis patients.Methods 38 tuberculosis pa-tients in Infectious Disease Department in the First Affiliated Hospital of Guangxi Medical University were recruited and the peripheral venous blood was collected in December,2010.Among them,sputum smear-positive patients which were first treated were 13,sputum smear-negative patients which were first treated were 15,10 cases were drug resistance.In addition, 22 unrelated healthy individuals from a routine health survey were enrolled as controls.Spectrophotometry was used to de-tect serum caspase-3 activity in tuberculosis patients,which was absorbancy-A of 4-nitroaniline generated by caspase-3.Re-sults The activity of caspase-3 in sputum smear-positive patients,sputum smear-negative patients,drug resistance patients, and healthy controls were 37.15±5.06,50.38±6.29,45.32±3.32 and 23.89±2.29,respectively.The caspase-3 activity was significantly different from each other (F=10.68,P0.05).In the same way,there was no significant difference in male/female ratio[χ2=0.38 (DL=3),P=0.94]and mean age (F=0.82,P=0.49)among the four group.Conclusion Caspase-3 closely associated with the development of tuberculosis occurrence, which might promote apoptosis of cells through the activation of caspase-3 and produce the body immune process of tubercu-losis.

Expression and significance of heparin binding-epidermal growth factor-like growth factor in paclitaxel-resistant ovarian cancer / 中华妇产科杂志

Objective To examine the expression of heparin binding-epidermal growth factor-like growth factor (HB-EGF) in paclitaxel-resistant ovarian cancer and elucidate the relationship between HB-EGF and the resistance of ovarian cancer to paclitaxel. Methods The human ovarian carcinoma cell line A2780 and the paclitaxel-resistant human ovarian carcinoma cell line A2780/Taxol were cultured in vitro. Western blot was used to dectect the expression of HB-EGF protein in A2780 and A2780/Taxol groups. The A2780 cells were treated with cross-reacting material 197 (CRM197 and A2780 + CRM197 group) or dimethyl sulphoxide (DMSO;A2780 group), while the A2780/Taxol cells were treated with CRM197 (A2780/Taxol+CRM197 group) or DMSO (A2780/Taxol group). The effects of CRM197 on growth and proliferation was tested by methyl thiazolyl tetrazolium( MTT) and the results were showed as absorbance (A).The effects of CRM197 on cell cycles was tested by flow cytometry, while the effects of CRM197 on apoptosis was examined by caspase-3 activity assay and the results were showed as p-nitroaniline(pNa). In animal experiment, four groups of cells were inoculated to BALB/c nude mouse subcutaneously to observe tumor formation ability following CRM197 treatment. Immunohistochemistry was used to determine the expression of HB-EGF protein in A2780 and A2780/Taxol group. Results The expression level of HB-EGF protein in A2780/Taxol group (2.11±0.41) was significantly higher than that of A2780 group (0.75±0.20;P<0.01). The inhibition effect of CRM197 on the cell growth of A2780+CRM197 and A2780/Taxol+CRM197 group was accompanied by the acceleration of CRM197 concentration(P<0.01). When CRM197≥1 μg/ml, the inhibition effect of CRM197 on the cell growth of A2780/Taxol+CRM197 group was significantly higher than that in A2780/Taxol group(P<0.05). In cell cycle experiment, CRM197 induced the cell-cycle arrest at the G0/G1 phase in A2780+CRM197 cells[(67 ± 4)%] compared with A2780 cells[(54 ± 6)%;P<0.01], while CRM197 significantly induced the cell-cycle arrest at the G0/G1 phase in A2780/Taxol+CRM197 cells [(72± 4)%] compared with A2780/Taxol cells [(24±8)%;P<0.01]. CRM197 treatment in A2780+CRM197 group [(40 ± 6)μmol/L] led to the acceleration of the caspase-3 activity when compared to A2780 group [(6 ± 6)μmol/L;P<0.01], while CRM197 treatment in A2780/Taxol+CRM197 group [(66 ± 12)μmol/L] led to significant acceleration of the caspase-3 activity when compared to A2780 group [(9 ± 6)μmol/L;P<0.01]. In experiments in vivo, the expression scores of HB-EGF protein in A2780/Taxol tumors(10.8 ± 3.3) were higher than that in A2780 tumors (5.0±2.2;P<0.01). The tumor size and tumor weight of the A2780/Taxol+CRM197 group were both higher than those of the A2780+CRM197 group [(546 ± 85) mm3 vs (1 355 ± 119) mm3,(0.56 ± 0.09) g vs (1.31 ± 0.27) g; all P<0.01]. The CRM197 inhibition rate of the A2780+CRM197 and A2780/Taxol + CRM197 group were 43% and 68% respectively, showed that CRM197 significantly suppressed the growth of A2780/Taxol xenografts in vivo(P<0.01). Conclusions HB-EGF is over-expressed in paclitaxel-resistant ovarian cancer and may be contributes to drug resistance. Inhibition of HB-EGF expression potently enhances apoptosis and inhibit the growth of paclitaxel-resistant ovarian cancer, shedding light on the HB-EGF-targeted therapy options for chemoresistant ovarian cancer patients.

Endotoxin contamination and control in surface water sources and a drinking water treatment plant in Beijing, China.

In this paper, endotoxin contamination was determined in treated water following each unit of a drinking water treatment plant (WTP) in Beijing, China and its source water (SW) from a long water diversion channel (Shijiazhuang-Beijing) originating from four reservoirs in Hebei province, China. The total-endotoxin activities in SW ranged from 21 to 41 EU/ml at five selected cross sections of the diversion channel. The total-endotoxin in raw water of the WTP ranged from 11 to 16 EU/ml due to dilution and pretreatment during water transportation from Tuancheng Lake to the WTP, and finished water of the WTP ranged from 4 to 10 EU/ml, showing a 49% decrease following the full-scale treatment process at the WTP. Compared with the 31% removal of free-endotoxin, the WTP removed up to 71% of bound-endotoxin in raw water. The traditional treatment processes (coagulation, sedimentation and filtration) in the WTP removed substantial amounts of total-endotoxin (up to 63%), while endotoxin activities increased after granular activated carbon (GAC) adsorption and chlorination. The total-endotoxin in the actual water was composed of free-endotoxin and bound-endotoxin (endotoxin aggregates, bacteria-bound endotoxins and particle-attached endotoxins). The endotoxin aggregates, bacteria-bound endotoxins and particle-attached endotoxins co-exist as suspended particles in water, and only the bacteria-bound endotoxins were correlated with bacterial cells suspended in water. The particle distribution of endotoxin aggregates in ultrapure water was also tested and the results showed that the majority (64-89%) of endotoxin aggregates had diameters <2 µm. The endotoxin contamination and control in treated water following each unit of the WTP processes and its SW from reservoirs are discussed and compared with regard to bacterial cell counts and particle characteristics, which were dependent, to a certain extent, on different flow rates and turbulence of the water environments.

Expression of integrin-linked kinase and E-cadherin in primary gallbladder cancer and its significance / 中国肿瘤临床

Objective: To detect the protein expression and relationship between integrin-linked kinase (ILK) and E-cadherin (E-cad) in primary gallbladder cancer (PGC), as well as to evaluate their clinical significance. Methods:ILK and E-cad were examined in 48 cases with PGC, 25 with gallbladder adenoma and 25 with chronic cholecystitis tissues by immunohistochemistry. Then, the corre-lation between clinical and pathological features, as well as their relationship, was investigated. Results:The positive rate of ILK was significantly higher in the gallbladder cancer group (66.7%;32/48) than in the gallbladder adenoma (36.0%;9/25) and chronic cholecys-titis groups (24.0%;6/25) (P<0.05). However, the positive rate of E-cad, namely, 45.8%(22/48), was significantly lower than those of the benign groups (P<0.05). When the depth of invasion was aggravated and lymph node metastasis had occurred, the ILK expression level became significantly higher. Nevertheless, negative E-cad results were produced (P<0.05). A negative correlation between the ex-pression of ILK and E-cad in gallbladder cancer existed (r=-0.411, P<0.05). Conclusion:The expression of ILK and E-cad is signifi-cantly correlated with tumor invasion and metastasis. A negative correlation exists between these expressions. Detection of these two in-dexes is useful in predicting tumor progression and prognosis.

Effect analysis of implementing proactive monitoring on elderly stroke women with Escherichia coli infection caused by indwelling urinary catheter / 中国实用护理杂志

Objective To explore the control effect of proactive monitoring on senile stroke women with Escherichia coli infection caused by indwelling catheter.Methods From October 2011 to September 2012 elderly female stroke patients with indwelling urinary catheter were chosen in the department of neurology and were given proactive monitoring,which included the following:management of antibiotics has been humanized,urinary catheter care used first-cleaning and then disinfection method,pathogen monitoring professionals directly went to the bacteria room for obtaining information.The monitoring results were compared with those last year.Results The urinary Escherichia coli infection in monitoring popu-lations declined sharply,Escherichia coli infection rate reduced from 20.5％ to 3.6％.The urinary infection rate in hospitalized patients reduced from 10.8％ to 5.7％ respectively.The preventive application of an-tibacterial drugs greatly reduced from 70.0％ to 24.7％.The nursing staff all mastered the nursing method of the catheter.Conclusions To give proactive monitoring to senile stroke women with indwelling urinary catheter can control Escherichia coli and other bacteria induced urinary infection due to indwelling catheter significantly,demonstrate a deterrent effect on unreasonable application of antibiotics,which can be recommended to control other indwelling catheter induced urinary hospital infection.