The incidence of invasive candida infection in critically ill patients is rising year by year. It's clinical manifestation lacks specificity which is easy to result in missed diagnosis or misdiagnosis.Tradi-tional diagnosis methods need very long time and have low positive rate,which are easy to delay treatment,so early diagnosis is particularly important.1 ,3-β-D-glucan,mannan and antibodies,anti-enolase antibodies,can-dida score and colonization index may be helpful to make early diagnosis.

Along with the continuous publication of a series of large-scale clinical trials results,endovascular thrombolytic therapy (or combined with intravenous thrombolysis) has been recommended as the treatment of first choice for acute ischemic stroke caused by large intracranial artery occlusion.Nevertheless,there are a variety of factors that may affect the clinical outcome of endovascular recanalization procedure.This article aims to make a comprehensive review about the factors that may affect the prognosis of patients with acute ischemic stroke who are receiving endovascular treatment.

Objective To investigate the effects of leptin on Th17 cells and the possible mechanism. Methods The leptin-deficient ( ob/ob) mice and their homologous wild-type mice were used in the study.The percentages of Th17 cells in peripheral blood samples, spleen tissues and lymph nodes were measured by flow cytometry ( FCM) analysis.The splenic CD4+T cells, separated from the ob/ob mice and the wild-type mice by using magnetic beads,were respectively cultured with leptin at various concentrations and with anti-leptin neu-tralization antibody to evaluate the effects of leptin on Th17 cells.The quantitative real-time PCR was performed to analyze Th17 cell-related cytokines at transcriptional levels.The levels of IL-6 and IL-17A in the supernatants of CD4+T cell culture were measured with Luminex technology.Results Compared with the wild-type mice, the ob/ob mice showed lower percentages of Th17 cells in both peripheral blood samples and spleen tissues (0.49%±0.03%vs 1.29%±0.1%, 1.56%±0.22%vs 2.47%±0.11%).There was a decrease in the percentages of Th17 cells upon the in vitro treatment of CD4+T cells from wild-type mice with anti-leptin antibody.The per-centages of Th17 cells were increased in a dose-dependent manner upon the in vitro treatment of CD4+T cells from ob/ob mice with leptin.Moreover, the levels of IL-17A and IL-6 and the transcriptional levels of RORγt, IL-17A and IL-6 in leptin deficiency group were lower than those of wild-type group, but were increased upon the treatment with leptin.No significant difference with the transcriptional levels of TGF-βand IL-23 was ob-served between the two groups with and without intervention.Conclusion Leptin deficiency seriously hampered the generation of Th17 cells in mice and resulted in a decreased expression of RORγt, IL-17A and IL-6 at mRNA level.The treatment of CD4 T cells with leptin might promote the generation of Th17 cells through up-regulating the transcription of RORγt and IL-6.

Dysfunction in tyrosine kinase activity disrupts the nor-mal control of cellular phosphorylation signaling pathways,which plays a vital role in genesis and development of various tumors, and makes tyrosine kinases a class of targets of many anti-tumor drugs. Currently most approved tyrosine kinase inhibitors ( TKIs) are based on irreversible binding mechanisms, making them poorly selective, not potent or sustained enough regarding pharmacological effects and prone to triggering resistance. In the past decade, much progress has been made in the development of
a new class of TKIs which irreversibly inhibit their target proteins via the formation of covalent bonds, overcoming the drawbacks of irreversible TKIs. Several irreversible TKIs have entered markets or clinical research phases. This review is to summarize the structural, pharmacological and medicinal chemical properties of investigational and marketed irreversible TKIs as well as their re-cent developments.

Objective:To explore a new method of the cultivation of adoptive immunotherapy cells.Methods: Mononuclear cells was isoplated by density gradient centrifugation and then proliferated by using CD 40-agonist monoclonal antibody 5C11、cytokine of IFN-αand IL-7(CD40 group)in vitro.During the culturing procedure ,the cell morphology was obersved by optical microscope.The percentage of T-lymphocytes, NK-T cells, Treg cells and the cell proliferation, which were compared with CIK group CD3mAb activated,was detected on the 9th day.Results:There was no significant difference of CD 4+/CD8+T cells percentage between the two groups.But the Treg cells percentage of CIK group was far higher than that of CD 40 group,while the percentage of CD3+CD56+NK-T cells was lower than that of CD 40 group.And a group of Mo-NK-DC cells were observed in the CD 40 group.Conclusion: The new method of adoptive immunity therapy has been established in this study could increase the percentage of NK -T cells which had the ability to kill tumor cells.Simultaneously ,it is reduced the amount of Treg cells significantly.

Antibody-drug conjugate (ADC) is a new class of therapeutics composed of a monoclonal antibody and small cytotoxin moieties conjugated through a chemical linker. ADC molecules bind to the target antigens expressed on the tumor cell surfaces guided by the monoclonal antibody component. The binding ADC molecules can be internalized and subsequently the toxin moieties can be released within the tumor cells via chemical and/or enzymatic reactions to kill the target cells. The conjugation combines the merits of both components, i.e., the high target specificity of the monoclonal antibody and the highly potent cell killing activity of the cytotoxin moieties. However, such complexities make the pharmacokinetic and metabolic studies of ADCs highly challenging. The major challenges should include characterization of absorption, distribution, metabolism and excretion, investigation of underlying mechanisms, assessment of pharmacokinetic- pharmacodynamic relationship, and analytical method development of ADC drugs. This review will discuss common pharmacokinetic issues and considerations, as well as tools and strategies that can be utilized to characterize the pharmacokinetic and metabolic properties of ADCs.

Objective:To investigate the effect of thrombus burden on the clinical outcome of endovascular recanalization in large vessel occlusive stroke.Methods:Patients with acute anterior circulation occlusion who underwent endovascular treatment within 24 hours after onset in Zhengzhou University People′s Hospital from January 2018 to December 2019 were retrospectively collected. According to the clot burden score (CBS) of DSA, total objectives were divided into CBS≥6 group (24 cases) and CBS<6 group (38 cases). Clinical data of the two groups were collected and the modified Rankin scale (mRS) was used to evaluate the clinical outcome at 90 days after surgery. Independent sample t-test, Wilcoxon rank sum test and χ 2 test were used to compare the clinical data between the two groups. Independent risk factors affecting the clinical outcome were analyzed by binary logistic regression. Results:There were no statistically significant differences in basic demographic data, stroke risk factors and other factors between the CBS≥6 group and CBS<6 group ( P>0.05).The proportion of using tirofiban after surgery in the CBS≥6 group (63.2%, 24/38) was lower than that in the CBS<6 group (87.5%, 21/24) (χ2=4.380, P=0.044). The discharge NIHSS score of the CBS≥6 group was [5.0 (3.3, 7.8) points] lower than CBS<6 group [8.5 (1.8, 14.5) points] ( Z=5.221, P=0.022). The proportion of postoperative mRS 0-2 was (91.7%, 22/24) in the CBS≥6 group higher than CBS<6 group(39.5%, 15/38) (χ2=20.486, P=0.001), there were no statistically significant differences between the two groups ( P<0.05). The results of binary logistics regression analysis showed the CBS groups (OR=0.042, 95%CI 0.007-0.244 , P=0.001) was an independent risk factor affecting good outcome. Subgroup analysis of whether tirofiban was used or not showed there was no statistically significant difference in clinical prognosis between the two groups ( P>0.05). Conclusions:The clinical outcome of CBS≥6 group is significantly better than that of CBS<6 group, and patients with small thrombus burden are more likely to get a good clinical outcome of 90 days.

OBJECTIVETo explore new toxicity-reducing methods of Pinellia Rhizoma prepared by ethanol and the latest technical parameters.

METHODPinellia Rhizoma is prepared with ethanol. The orthogonal experimental design was adopted for investigating amount of ethanol, preparing time, ethanol concentration and preparing temperature. The optimal technology was determined by the comprehensive score of toxicological indicators of PGE2 content of rat celiac percolate, with the rabbit conjunctival irritation test as the intuitive validation on toxicology reduction. The pharmacodynamics validation was used to determine the reasonability of the preparation process.

RESULTThe optimal technology was that Pinellia Rhizoma was prepared by 75% ethanol at the temperature of 60 degrees C by 4 days, and then dried. The effect of relieving cough, reducing sputum and anti-inflammatory of Pinellia Rhizoma is not reduced after prepared by ethanol.

CONCLUSIONThe optimal technology of Pinellia Rhizoma prepared by ethanol is simple and reasonable that it can be used as the new method to reduce toxicity and keep efficacy of Pinellia Rhizoma.

Animals ; Anti-Inflammatory Agents ; chemistry ; isolation & purification ; pharmacology ; Cough ; drug therapy ; Desiccation ; Drugs, Chinese Herbal ; chemistry ; isolation & purification ; pharmacology ; Ethanol ; chemistry ; Female ; Hot Temperature ; Male ; Mice ; Mice, Inbred ICR ; Pinellia ; chemistry ; toxicity ; Plants, Medicinal ; chemistry ; toxicity ; Rabbits ; Rats ; Rats, Sprague-Dawley ; Rhizome ; chemistry ; toxicity ; Sputum ; drug effects ; Technology, Pharmaceutical ; methods ; Time Factors ; Toxicity Tests

Objective To analyze the clinical characteristics of patients with metastatic carcinoma of bone. Methods The clinical data of 217 patients with metastatic carcinoma of bone was retrospectively analyzed. The clinical features were summarized,including primary tumor,age distribution,first symptom,time of onset and bone metastatic site. Visual analogue scale(VAS)was used to evaluate the difference of pain in patients with bone metastases before and after zoledronic acid treatment. Results The bone metastasis occurred more frequently in men(male:female = 1.28:1). The majority of primary tumors were lung cancer(51.61％)and breast cancer (15.67％),respectively. The peak ages of the patients with metastatic carcinoma of bone were between 50 and 70 years old. Most of the patients with metastatic carcinoma of bone initially showed varying degrees of pain ,some of the patients with dysfunction,pathological fracture,or local lumps as the initial symptoms,only a tiny minority of patients were inadvertently found. Onset time was often within 3 months ,which accountings for 54.84％. Bone metastases were mostly in the spine,pelvis,femur and ribs,and most of the bone metastases were multiple. The VAS score of 108 patients who with bone metastases pain treated by zoledronic acid was 0～4(1.31 ± 1.07),with statistically significant differences compared with pretherapy(P<0.01). Conclusion In order to reduce the pain of patients,and to improve the quality of life and prolong the survival time,bone metastases should be diagnosed early and given comprehensive treatment.

Objective:To explore the application value of artificial intelligence-assisted diagnosis model based on convolutional neural network (CNN) in the differential diagnosis of benign and malignant breast masses.Methods:A total of 10 490 images of 2 098 patients with breast lumps (including 1 132 cases of benign tumor, 779 cases of malignant tumor, 32 cases of inflammation, 155 cases of adenosis) were collected from January 2016 to January 2018 in Beijing Tiantan Hospital Affiliated to the Capital University of Medical Sciences. They were divided into training set and test set and the auxiliary artificial intelligence diagnosis model was used for training and testing. Two sets of data training models were compared by two-dimensional imaging (2D) and two-dimensional and color Doppler flow imaging (2D-CDFI). The ROC curves of benign breast tumors, malignant tumors, inflammation and adenopathy were analyzed, and the area under the ROC curve (AUC) were calculated.Results:The accuracies of 2D-CDFI ultrasonic model for training group and testing group were significantly improved. ①For benign tumors, the result from training set with 2D image was: sensitivity 92%, specificity 95%, AUC 0.93; the result from training set with 2D-CDFI images was: sensitivity 93%, specificity 95%, AUC 0.93; the result for test set with 2D images was: sensitivity 91%, specificity 96%, AUC 0.94; the result for test set with 2D-CDFI images was: sensitivity 93%, specificity: 94%, AUC 0.94. ② For malignancies, the result for training set with 2D images was: sensitivity 93%, specificity 97%, AUC 0.94; the result for training set with 2D-CDFI images was: sensitivity 93%, specificity 96%, AUC 0.94; the result for test set with 2D images was: sensitivity 93%, specificity 96%, AUC 0.94; the result for test set with 2D-CDFI images was: sensitivity 93%, specificity 96%, AUC 0.94. ③For inflammation, the result for training set with 2D images was: sensitivity 81%, specificity 99%, AUC 0.91; the result for training set with 2D-CDFI images was: sensitivity 86%, specificity 99%, AUC 0.89; the result for test set with 2D images was: sensitivity 100%, specificity 98%, AUC 0.98; the result for test set with 2D-CDFI images was: sensitivity 100%, specificity 99%, AUC 0.96. ④For adenopathy, the result for training set with 2D images was: sensitivity 88%, specificity 97%, AUC 0.94; the result for training set with 2D-CDFI images was: sensitivity 93%, specificity 98%, AUC 0.94; the result for test set with 2D images was: sensitivity 94%, specificity 98%, AUC 0.93; the result for test set with 2D-CDFI images was: sensitivity 88%, specificity 99%, AUC 0.90. Its diastolic accuracy was not affected even if the maximum diameter of the tumor was less than 1 cm.Conclusions:Through the deep learning of artificial intelligence based on CNN for breast masses, it can be more finely classified and the diagnosis rate can be improved. It has potential guiding value for the treatment of breast cancer patients.