Biomarkers for chimeric antigen receptor T cell therapy in B cell malignancies can assess therapeutic efficacy and toxicity / 中华检验医学杂志

Chimeric antigen receptor (CAR)-T cell immunotherapy have developed for nearly two decades and achieved great clinical success in the treatment of hematological malignancies. Efficacy monitoring and toxicity management of CAR-T cell immunotherapy are essential steps to ensure safety and improve overall survival in multicenter clinical trials and commercialized treatments. CAR-T cell immunotherapy related biomarkers can be used as an indicator of patient baseline characteristics, tumor biology, and CAR-T cell function. Besides, side effects during treatment can also be assessed by the biomarkers.

Effective and persistent antitumor activity of HER2-directed CAR-T cells against gastric cancer cells in vitro and xenotransplanted tumors in vivo

Human epidermal growth factor receptor 2 (HER2) proteins are overexpressed in a high proportion of gastric cancer (GC) cases and affect the maintenance of cancer stem cell (CSC) subpopulations, which are used as targets for the clinical treatment of patients with HER2-positive GC. Despite improvements in survival, numerous HER2-positive patients fail treatment with trastuzumab, highlighting the need for more effective therapies. In this study, we generated a novel type of genetically modified human T cells, expressing a chimeric antigen receptor (CAR), and targeting the GC cell antigen HER2, which harbors the CD137 and CD3ζ moieties. Our findings show that the expanded CAR-T cells, expressing an increased central memory phenotype, were activated by the specific recognition of HER2 antigens in an MHC-independent manner, and effectively killed patient-derived HER2-positive GC cells. In HER2-positive xenograft tumors, CAR-T cells exhibited considerably enhanced tumor inhibition ability, long-term survival, and homing to targets, compared with those of non-transduced T cells. The sphere-forming ability and in vivo tumorigenicity of patient-derived gastric cancer stem-like cells, expressing HER2 and the CD44 protein, were also inhibited. Our results support the future development and clinical application of this adoptive immunotherapy in patients with HER2-positive advanced GC.

Analysis on the status and influencing factors of aged people's aging attitude in old university / 中国实用护理杂志

Objective To investigate the status quo of aging attitude of aged elderly and analyze its influencing factors. Methods Totally 382 elderly people were surveyed by questionnaire, aging attitude scale and the mental capital scale of the elderly. Results The aging attitude of the elderly was 87.10 ± 12.41, which was in the middle level. Linear regression analysis results showed that the variables into the regression equation with health, exercise and interests at ordinary times, cultural degree, psychological capital dwelling place, family, children, spouses still alive (R2 = 0.340, F = 29.029, P <0.01). Conclusion Elderly college seniors' attitude toward aging is in the medium level, factors affecting the health of the old, exercise at ordinary times and hobbies, culture degree, psychological capital dwelling place, family, children, spouse still alive. Increasing age and social support of the aged education, encourage guide for old people to better adapt to the new era of social change, positive in the face of their own aging, promote the quality of life and subjective well-being among senior citizens steadily on the increase, and promote the formation of healthy aging.

Hypoxic pretreatment of human umbilical cord mesenchymal stem cells regulating macrophage polarization / 解放军医学杂志

Objective To investigate the effect of human umbilical cord mesenchymal stem cells (hUC-MSCs) on macrophage polarization under hypoxia. Methods hUC-MSCs were obtained by explants adherent culture and cultured under normoxia (21% O2) and hypoxia (5% O2). The multi-directional differentiation of hUC-MSCs was observed by osteogenic and adipogenic differentiation induction. Live/death staining was performed to detect the cell viability, and ELISA was executed to detect the protein content in supernatant of hUC-MSCs. Transwell chamber was employed to co-culture the hUC-MSCs cultured under normoxia and hypoxia and macrophage (THP-1) stimulated by lipopolysaccharide (IPS), then the polarization of THP-1 was detected by immunofluorescence, and the secretions of inflammatory factor and anti-inflammatory factor of THP-1 were detected by ELISA. Results hUC-MSCs cultured under hypoxia showed the ability of osteogenic and adipogenic multi-directional differentiation. Live/death staining showed the high cell viability of hUC-MSCs cultured under normoxia and hypoxia. The expression levels of prostaglandin E2 (PGE2) and indoleamine 2,3-dioxygenase (IDO) were significantly higher in the hUC-MSCs cultured under hypoxia than in those cultured under normoxia. hUCMSCs cultured under hypoxia promoted the polarization of THP-1 to M2, obviously reduced the expression of TNF-α and IL-1β, and increased the expression of IL-10 significantly. Conclusion hUC-MSCs cultured under hypoxia may promote the polarization of THP-1 to M2 and improve the viability of anti-inflammatory.

Application of gold nanoparticles in cancer therapy / 中国医学科学院学报

With their unique physicochemical properties including excellent stability and biocompatibility, large specific surface area, and easy surface modification, gold nanoparticles (AuNPs) can be used as delivery vectors for drugs, genes, proteins, etc. In addition, AuNPs have excellent photothermal effects and radiosensitization characteristics, and therefore can be widely applied in the photothermal therapy and radiotherapy of cancers. This article reviews the construction, cellular uptake, and drug release of AuNPs drug-delivery systems and their applications in the treatment of tumors.

Efficacy comparison of combined intracoronary administration of high-dose adenosine and tirofiban versus intracoronary tirofiban during primary percutaneous coronary intervention in patients with acute myocardial infarction / 中华心血管病杂志

<p><b>OBJECTIVE</b>To compare the efficacy of intracoronary administration of combined high-dose adenosine and tirofiban versus intracoronary tirofiban during primary percutaneous coronary intervention (PCI) in patients with acute myocardial infarction.</p><p><b>METHODS</b>Consecutive 258 patients with acute ST-segment elevation myocardial infarction (STEMI) underwent primary PCI, treated with thrombus aspiration and then intracoronary tirofiban, were randomly divided into adenosine group (n = 130) and control group (n = 128). Adenosine group received 2 times intracoronary adenosine (2 mg) after thrombus aspiration and after stenting of the infarct-related artery through the aspiration catheter. Control group received placebo. The primary end point was myocardial blush grade (MBG) after PCI. Secondary end points were thrombolysis in myocardial infarction (TIMI) flow grade and corrected TIMI frame count (CTFC) after PCI, ST-segment elevation resolution (STR), and major adverse cardiac events (MACE) at 30 days and 12 months.</p><p><b>RESULTS</b>TIMI flow grade post PCI did not differ between the 2 groups, while CTFC favored the adenosine-treated patients [(21.6 ± 6.5) frames] compared with the placebo-treated patients [(25.1 ± 7.8) frames, P = 0.001]. MBG 3 was more frequently observed in the adenosine compared to the control group [45.1% (55/122) vs.32.0% (39/122), P = 0.035]. Patients in the adenosine group had a trend of higher rate of compete STR after the procedure compared patients in the control group [53.6% (67/125) vs. 41.9% (52/124), P = 0.065]. The incidence of MACE was comparable between patients randomized to adenosine and placebo at 30 days [12.3% (16/130) vs. 17.2% (22/128), P = 0.295] and at 12 months [12.3% (16/130) vs. 18.0% (23/128), P = 0.227].</p><p><b>CONCLUSION</b>Intracoronary administration of high-dose adenosine combined with tirofiban provides further improvement on myocardial perfusion after primary PCI but does not affect the clinical outcomes in patients with STEMI.</p>

HBV genotype and liver histology effect of peginterferon alpha treatment of HBeAg-position chronic hepatitis B / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To investigate the efficacy of PEG-interferon alpha (PEG-IFN alpha) treatment of HBeAg-positive chronic hepatitis B and HBV genotypes and liver tissues effect of HBeAg seroconversion.</p><p><b>METHODS</b>54 cases confirmed by liver biopsy, genotype clear HBeAg positive chronic hepatitis B (CHB) patients according to body weight, respectively, subcutaneous injection of PEG-IFN-alpha2a 135 microg or 180 microg, or PEG-IFN-alpha2b 50 microg, 80 microg or 100 microg once weekly treatment for 48 weeks and followed for 24 weeks after discontinuation. Statistics of HBeAg seroconvertion, HBV genoty pes and liver histology e antigen seroconversion after the end of treatment.</p><p><b>RESULTS</b>54 patients were followed up at the end of HBeAg seroconversion rate was 29.63% (16/54). Genotype B patients with HBeAg seroconversion rate was 35.29%, 27.03% higher than the C-type patients, but the difference was not statistically significant (chi2 = 0.382, P = 0.537). Inflammation of the liver activity highter ( > G2) , the degree of fibrosis heavier ( > S1) HBeAg seroconversion rate (50.00% vs. 25.00%, 40.90% vs. 21.88%), but were not statistically significant (chi2 = 1.391, 1.444, P = 0.238, 0.229). Activity of HBV genotype, liver inflammation, liver fibrosis and other factors by multivariate Logistic regression analysis, only liver inflammation activity of the important factors of HBeAg seroconversion.</p><p><b>CONCLUSION</b>Important factors, liver inflammation activity of PEG-interferon alpha treatment of HBeAg-position chronic hepatitis B patients and HBV genotypes and liver fibrosis may be of little significance.</p>

Association of liver histopathology and clinical features among patients with chronic hepatitis B virus infection / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To explore the histopathological features of chronic hepatitis B virus (HBV) carriers and chronic hepatitis B (CHB) patients with mildly elevated serum alanine aminotransferase (ALT).</p><p><b>METHODS</b>105 patients were divided into three groups according to serum ALT levels: Group A [ALT level < or = 0.5 x upper limits of normal (ULN)], Group B (0.5 x ULN < ALT level < or = 1 x ULN) and Group C(1 x ULN < ALT level < 2 x ULN). Grade of liver inflammation and stage of liver fibrosis in the three groups were compared. The changes in clinical parameters were then observed in patients who had liver histopathological changes.</p><p><b>RESULTS</b>Among 40.95% of the patients, hepatitis degree went to G2 or even worse; and among 30.43% of the patients whose ALT level were normal, the hepatitis degree reached G2 or even worse. In 26.67% of the patients, degree of fibrosis went to S2 or even worse, and for the 17.39% patients whose ALT level were normal, degree of fibrosis went to S2 or even worse. The aggravation of liver inflammation and fibrosis was correlated with ALT and hyaluronic acid increasing (all P < 0.05).</p><p><b>CONCLUSIONS</b>Frequent monitoring of serum ALT and hyaluronic acid may help to understand histopathological changes in the liver. Liver biopsy applied to CHB should be regarded as a main basis if antiviral therapy should be conducted.</p>

Study on the relationship between HBV viral loads and the changes of liver pathological features in patients with HBeAg-negative chronic hepatitis B / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To investigate the relationship between serum HBV DNA loads and liver histology damage in the patients with HBeAg-negative chronic hepatitis B.</p><p><b>METHODS</b>The retrospective study was performed. The 514 patients were divided into two groups according to the HBeAg status and the HBeAg positive group was as control. The relationship among HBV DNA loads, live histological inflammation grades and fibrosis stages was analyzed.</p><p><b>RESULTS</b>The HBV DNA loads in HBeAg-negative group and HBeAg-positive group were (5.38 +/- 1.27) log10 copies/ml and (6.80 +/- 1.18) log10 copies/ml respectively (P < 0.001). The inflammation grades and fibrosis stages of liver tissues in HBeAg-negative group were all significantly higher than those in HBeAg-positive group (P < 0.001). In HBeAg-negative group, HBV DNA loads displayed a positive correlation with the inflammation grades and fibrosis stages of liver tissues (P < 0.001).</p><p><b>CONCLUSION</b>In the patients with HBeAg-negative chronic hepatitis B, HBV viral loads are lower than those with HBeAg-positive chronic hepatitis B, and HBV viral loads display a positive correlation with liver the inflammation grades and fibrosis stages of liver tissues.</p>

Influence of MgO and TiO2 on mechanical properties of zirconia toughened alumina ceramics formed by gel-casting technique / 华西口腔医学杂志

<p><b>OBJECTIVE</b>The objective of this study is to investigate the influence of mechanical properties and sintering performance by adding 5% weight percentage aids to nano-compound zirconia toughened alumina (ZTA) ceramics.</p><p><b>METHODS</b>Micrometer Al2O3 and nanometer ZrO2 (quality ratio 4:1) were used to get 55% volume percentage slurry. Magnesium oxide and titanium oxide were taken as aids which were 5% weight percentage of the Al2O3 and ZrO2 powder. Five groups (number 0, 1, 2, 3, 4 group) were divided according to different proportion of aids. After gel-casting, the porcelain pieces were sintered at 1150, 1200, 1300, 1400, 1450, 1500, 1600 degrees C for 2 hours. Static three-point flexure strength, line shrinkage, relative density were measured and scanning electron microscopy (SEM) was used to observe section.</p><p><b>RESULTS</b>Number 1 (MgO 1%, TiO2 4%) group had the highest bending strength. It was (401.78+/-19.50) MPa after sintering at 1600 degrees C for 2 hours and was higher than 0 group (380.64+/-44.50) MPa. Bending strength became lower than 0 group when MgO was more than 2% or more than that weight percentage of ZTA powder. When MgO content was higher than 2% or more than that weight percentage, there was no difference in relative density raising rate between each sintering assistants groups. When the sintering temperature was higher than 1200 degrees C, all groups showed obvious line-shrinkage and the groups which contained sintering assistants were all was higher than 0 group.</p><p><b>CONCLUSION</b>Adding MgO and TiO2 aids from 1% to 4% weight percentage of ZTA will promote fritting and increase ZTA nano-compound ceramics mechanical properties. Adding 2% MgO aids or more than that weight percent will has no obvious help to increase the relative density raising rate of ZTA nano-compound ceramics and will degrade the mechanical properties of ZTA nano-compound ceramics.</p>

Observation on therapeutic effect of auricular point sticking combined with Tongshiji treatment on child ametropic amblyopia / 中国针灸

<p><b>OBJECTIVE</b>To compare therapeutic effects of auricular point sticking combined with Tongshiji treatment and simple Tongshiji treatment on child ametropic amblyopia.</p><p><b>METHODS</b>Three hundred children of ametropic amblyopia were classified as mild, moderate and severe groups, 100 cases in each group. The each group was again randomly divided into a simple Tongshiji treatment (control group) and a auricular point sticking combined with Tongshiji treatment group (observation group). Their therapeutic effects were compared.</p><p><b>RESULTS</b>The total effective rate in the observation group were 100.0%, 79.8% and 71.0%, and in the control group were 100.0%, 54.3% and 48.2% respectivety for mild, moderate and severe groups. For the mild amblyopia children, there was no significant difference between the two groups in the therapeutic effect; for the moderate and severe ametropic amblyopia children, the therapeutic effect in the observation group was better than that in the control group (P<0.05).</p><p><b>CONCLUSION</b>Auricular point sticking combined with Tongshiji treatment for child ametropic amblyopia is of characteristics of convenient manipulation, obvious and rapid therapeutic effect.</p>

Primary percutaneous coronary intervention in patients with acute myocardial infarction induced by left main artery occlusion or severe stenosis / 中华心血管病杂志

<p><b>OBJECTIVE</b>The effects of primary percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI) induced by left main (LM) artery occlusion were analyzed retrospectively in this study.</p><p><b>METHODS</b>A total of 1343 consecutive AMI patients who underwent primary PCI between January 1995 and December 2004 were retrospectively studied.</p><p><b>RESULTS</b>LM occlusion or severe stenosis were found in 11 patients [all male, mean age (56.4 +/- 9.2) years (range 43-70 years)], cardiogenic shock was overt in 6 patients. Primary PCI were performed under the assistance of intra-aortic balloon pump (IABP) in these patients [8 stent implantation, 3 balloon dilation and 2 necessitating emergency CABG after balloon dilation]. In-hospital mortality was 45.5% (5/11). Three-month follow-up were made in all survivals (6/11). Analysis showed good collateral circulation flow from right coronary artery to left coronary artery was existed in all survival cases before PCI.</p><p><b>CONCLUSION</b>Prognosis of AMI patients with LM artery obstruction or severe stenosis was poor. Patients with pre-existed collateral circulation before primary PCI and IABP had a better clinical outcomes.</p>

Clinical analysis of patients with acute myocardial infarction induced by left main artery occlusion / 中华急诊医学杂志

Objective To study clinical data of patients with acute myocardial infarction (AMI) induced by left main (LM) artery occlusion,and to find out the clinical characteristics.Method From Janurany 1995 to May 2006,there were 15 patients with AMI related with LM obstruction from 1793 AMI patients,in whom primary PCls were performed.All patients were male with a mean age of (60.6?10.4) years old (ranging from 43 to 85 years old).The clinical and interventional data were retrospectively analyzed.Results Cardiogenic shock occurred in 10 patients at admission.Primary PCls were performed with intraaortic balloon pump (IABP) in all patients.Nine patients died during short follow-up,and the mortality was 60%.Three-month follow-up was made in the all survival patients,and one patient died after 4 years.Analysis showed good collateral circulation flow from right coronary artery to left coronary artery before operation affected the short-term prognosis.Conclusions AMI related with left main artery obstruction was critically fatal with high occurrence of cardiogenic shock and high mortality.Prognosis differs at,cording to different degree of collateral circulation.Primary PCI with IABP provides a promising strategy to improve clinical outcomes.

Recent applications of Hidden Markov Models in computational biology / 基因组蛋白质组与生物信息学报·英文版

This paper examines recent developments and applications of Hidden Markov Models (HMMs) to various problems in computational biology, including multiple sequence alignment, homology detection, protein sequences classification, and genomic annotation.