Combination immunotherapy of glioblastoma with dendritic cell cancer vaccines,anti-PD-1 and poly I:C / 药物分析学报

Glioblastoma(GBM)is a lethal cancer with limited therapeutic options.Dendritic cell(DC)-based cancer vaccines provide a promising approach for GBM treatment.Clinical studies suggest that other immu-notherapeutic agents may be combined with DC vaccines to further enhance antitumor activity.Here,we report a GBM case with combination immunotherapy consisting of DC vaccines,anti-programmed death-1(anti-PD-1)and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy,and the patient remained disease-free for 69 months.The patient received DC vaccines loaded with multiple forms of tumor antigens,including mRNA-tumor associated antigens(TAA),mRNA-neoantigens,and hypochlorous acid(HOCl)-oxidized tumor lysates.Furthermore,mRNA-TAAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histo-compatibility complex(MHC)class Ⅰ and Ⅱ antigen presentation.The treatment consisted of 42 DC cancer vaccine infusions,26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions.The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells.No immunotherapy-related adverse events were observed during the treatment.Robust antitumor CD4+and CD8+T-cell responses were detected.The patient remains free of disease progression.This is the first case report on the combination of the above three agents to treat glioblastoma patients.Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient.A large-scale trial to validate these findings is warranted.

Research progress of FAPI PET/CT in the diagnosis of malignant liver tumors / 中华肝脏病杂志

Malignant liver tumors have a high incidence and mortality rate. Therefore, it is of great significance to promptly learn about tumor advancement status through relevant examinations for patients' follow-up, diagnosis, and therapy as well as the improvement of the five-year survival rate. The primary lesions and intrahepatic metastases of malignant liver tumors have been better demonstrated in the clinical study with the use of various isotope-labeled fibroblast activating protein inhibitors because of their low uptake in liver tissues and high tumor/background ratio, which provides a new method for early diagnosis, precise staging, and radionuclide therapy. In light of this context, a review of the research progress of fibroblast-activating protein inhibitors for the diagnosis of liver malignant tumors is presented.

Associations of sex hormone levels with body mass index (BMI) in men: a cross-sectional study using quantile regression analysis / 亚洲男科学杂志(英文版)

Body mass index (BMI) has been increasing globally in recent decades. Previous studies reported that BMI was associated with sex hormone levels, but the results were generated via linear regression or logistic regression, which would lose part of information. Quantile regression analysis can maximize the use of variable information. Our study compared the associations among different regression models. The participants were recruited from the Center of Reproductive Medicine, The First Hospital of Jilin University (Changchun, China) between June 2018 and June 2019. We used linear, logistic, and quantile regression models to calculate the associations between sex hormone levels and BMI. In total, 448 men were included in this study. The average BMI was 25.7 (standard deviation [s.d.]: 3.7) kg m-2; 29.7% (n = 133) of the participants were normal weight, 45.3% (n = 203) of the participants were overweight, and 23.4% (n = 105) of the participants were obese. The levels of testosterone and estradiol significantly differed among BMI groups (all P < 0.05). In linear regression and logistic regression, BMI was associated with testosterone and estradiol levels (both P < 0.05). In quantile regression, BMI was negatively associated with testosterone levels in all quantiles after adjustment for age (all P < 0.05). BMI was positively associated with estradiol levels in most quantiles (≤80th) after adjustment for age (all P < 0.05). Our study suggested that BMI was one of the influencing factors of testosterone and estradiol. Of note, the quantile regression showed that BMI was associated with estradiol only up to the 80th percentile of estradiol.

Methamphetamine: Mechanism of Action and Chinese Herbal Medicine Treatment for Its Addiction / 中国结合医学杂志

With the proliferation of synthetic drugs, research on the mechanism of action of addictive drugs and treatment methods is of great significance. Among them, methamphetamine (METH) is the most representative amphetamine synthetic drug, and the treatment of METH addiction has become an urgent medical and social problem. In recent years, the therapeutic effects of Chinese herbal medicines on METH addiction have gained widespread attention because of their non-addictiveness, multiple targets, low side effects, low cost, and other characteristics. Previous studies have identified a variety of Chinese herbal medicines with effects on METH addiction. Based on the research on METH in recent years, this article summarizes the mechanism of action of METH as the starting point and briefly reviews the Chinese herbal medicine-based treatment of METH.

Effect of Combined Therapy of Lung and Intestine on VIP and p38 MAPK Signaling Pathways in Bronchial Asthma Mice / 中国实验方剂学杂志

ObjectiveTo observe the therapeutic effects of the combined therapy of lung and intestine， a common treatment for pulmonary diseases in traditional Chinese medicine （TCM）， on bronchial asthma mice， and further detect the changes of vasoactive intestinal peptide （VIP） and p38 mitogen-activated protein kinase （p38 MAPK） signaling pathway-related proteins which are closely related to the pathogenesis of asthma， in order to elucidate the mechanism of the combined therapy of lung and intestine in the treatment of bronchial asthma. MethodA total of 60 Kunming mice were randomly divided into normal group， model group， dexamethasone group （0.5 mg·kg-1·d-1）， TCM group （2.73 g·kg-1·d-1）， and lung-intestine treatment group （6.825 g·kg-1·d-1）， 12 mice in each group. All mice except the normal group were sensitized by ovalbumin to induce bronchial asthma. After 30 days of intragastric administration， serum and lung tissue samples were obtained. The content of VIP， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） in the serum of mice in each group was detected by enzyme-linked immunosorbent assay （ELISA）. The mRNA levels of TNF-α， IL-6， and p38 MAPK in lung tissues of mice were detected by real-time quantitative polymerase chain reaction （Real-time PCR）， and the protein levels of TNF-α， IL-6， p38 MAPK， and phosphorylated p38 MAPK （p-p38 MAPK） in lung tissues of mice were assayed by Western blot （WB）. ResultCompared with the normal group， the model group showed decreased content of serum VIP （P<0.05）， increased content of TNF-α and IL-6 （P<0.05）， up-regulated mRNA levels of TNF-α， IL-6， and p38 MAPK， and elevated protein levels of TNF-α， IL-6， and p-p38 MAPK/p38 MAPK in lung tissues （P<0.05）. Compared with the model group， the treatment groups exhibited increased content of serum VIP， TNF-α， and IL-6 （P<0.05）， down-regulated mRNA levels of TNF-α， IL-6， and p38 MAPK， and lower protein levels of TNF-α， IL-6， and p-p38 MAPK/p38 MAPK in lung tissues （P<0.05）. As compared with the lung-intestine treatment group， the serum TNF-α and IL-6 levels in the dexamethasone group were increased （P<0.05）， and the mRNA and protein levels of TNF-α and IL-6 in lung tissues were down-regulated （P<0.05）， while the levels of p38 MAPK， VIP mRNA， and p-p38 MAPK/p38 MAPK protein in lung tissues were up-regulated （P<0.05）. The serum VIP， TNF-α， and IL-6 levels in the TCM group were decreased （P<0.05）， and the mRNA levels of TNF-α， IL-6， p38 MAPK and protein levels of TNF-α， IL-6， p-p38 MAPK/p38 MAPK in lung tissues were up-regulated （P<0.05）， while the level of VIP mRNA in lung tissues was down-regulated （P<0.05）. ConclusionThrough increasing endogenous VIP and inhibiting the excessive activation of p38 MAPK signaling pathway， the combined therapy of lung and intestine can reduce the release of inflammatory factors， inhibit pulmonary inflammation response， and treat bronchial asthma.

Research Progress of Targeted Ultrasound Contrast Agent BR55 / 中国医学科学院学报

BR55 is an ultrasound contrast agent targeting vascular endothelial growth factor receptor 2,which can be used to detect tumor neovascularization and improve the diagnostic accuracy.Overseas researchers have used BR55 for human ultrasound molecular imaging,which showed good safety and tolerance.We reviewed the research progress on BR55 applied in the evaluation of tumor neovascularization from the composition,characteristics,animal experiments,and clinical studies of BR55.

Research progress on bidirectional effect of microRNA on Alzheimer's disease and intervention with traditional Chinese medicine / 中国中药杂志

Alzheimer's disease(AD) is a chronic progressive neurodegenerative disease with recent memory impairment as the main clinical manifestation and senile plaques and neurofibrillary tangles as the main pathological changes. In recent years, the effect of microRNAs on AD has attracted widespread attention. Patients with AD have abnormal expression of miRNA, which is closed related to regulation of AD pathophysiology-related genes. Therefore, this paper first elaborated neuroprotective and toxic effects of microRNA in AD, and then explored relevant traditional Chinese medicines that can regulate miRNA in the treatment of AD, so as to provide basis for revealing the pathogenesis relationship between miRNA and AD and provide ideas for further development of anti-AD traditional Chinese medicine.

Expression and regulation of XBP1 in mouse uterus during early pregnancy / 生理学报

The transcription factor X-box binding protein-1 (XBP1) plays a key role in unfolded protein reaction. This study was aimed to investigate the expression pattern and regulation of XBP1 in the mouse uterus during early pregnancy. The methods of immunohistochemistry (IHC) and real time quantitative RT-PCR were used to test XBP1 expression in early pregnancy, artificial decidualization, oestrous cycle and hormone-regulated mouse models. The results showed that XBP1 was spatiotemporally expressed in mouse uterus during early pregnancy. The XBP1 protein was mainly detected in the luminal and glandular epithelia on days 1-4 of pregnancy, and was strongly detected in the decidual area on days 5-8 of pregnancy. Similarly, XBP1 expression was also mainly expressed in decidual cells following artificial decidualization. During the oestrous cycle, Xbp1, Xbp1u, and Xbp1s mRNA was predominantly present in proestrus. In the ovariectomized uterus, the expression of XBP1 in luminal and glandular epithelia was up-regulated after estrogen treatment. These results suggest that XBP1 is associated with embryo implantation and decidualization during early pregnancy in mice, and the expression of XBP1 in luminal and glandular epithelia may be regulated by estrogen.

Effect of different melatonin treatment regimens on white matter damage in neonatal rats with hypoxic-ischemic brain damage / 中国当代儿科杂志

OBJECTIVE@#To study the effect of different melatonin treatment regimens on long-term behavior and white matter damage in neonatal rats with hypoxic-ischemic brain damage (HIBD), and to seek an optimal melatonin treatment regimen.@*METHODS@#Healthy Sprague-Dawley rats, aged 7 days, were randomly divided into four groups: sham-operation, HIBD, single-dose immediate treatment (SDIT), and 7-day continuous treatment (7DCT), with 8 rats in each group. A neonatal rat model of HIBD was prepared according to the classical Rice-Vannucci method. On day 21 after HIBD, the Morris water maze test was used to evaluate spatial learning and memory abilities. On day 70 after HIBD, immunofluorescence assay was used to measure the expression of neuronal nuclear antigen (NeuN) in the cerebral cortex and the hippocampal CA1 region of neonatal rats, and double-label immunofluorescence was used to measure the expression of myelin basic protein (MBP) and neurofilament 200 (NF200) in the corpus striatum and the corpus callosum.@*RESULTS@#The results of the Morris water maze test showed that the SDIT and 7DCT groups had a significantly shorter mean escape latency than the HIBD group, and the 7DCT group had a significantly shorter mean escape latency than the SDIT group (@*CONCLUSIONS@#Both SDIT and 7DCT can improve long-term behavior and reduce white matter damage in neonatal rats with HIBD, and 7DCT is more effective than SDIT.

A fluorescence polarization immunoassay for the detection of aflatoxins in herbal teas / 药学学报

A rapid fluorescence polarization immunoassay (FPIA) has been developed for the determi-nation of aflatoxins in samples of naturally-contaminated herbal teas. The tracers were synthesized by chemical method and determined by thin layer chromatography (TLC) and mass spectroscopy (MS). Fluorescence polarization was evaluated by the detection of polarized light. The results showed that the limit of detection (LOD) of FPIA for aflatoxins was 20 ng·mL-1, the IC50 was 371.80 ng·mL-1, and the linear range of the developed FPIA was 92.76-252.32 ng·mL-1. Compared with conventional HPLC methods, the FPIA developed in this study has the advantages of short analysis time and low cost. This method may be suitable for high- throughput screening of aflatoxins in herbal teas.

Expression of PD-1 and PD-L1 in patients infected with Brucella / 中国免疫学杂志

Objective:To investigate the roles of PD-1 and PD-L1,as well as related cytokines TGF-βand IL-10 in patients infected with Brucella.Methods:The expression of PD-1/PD-L1 in peripheral blood mononuclear cell CD 3+T cells,CD4+T cells,CD8+T cells,and dendrites cells was detected by flow cytometry in 60 patients infected with Brucella and 34 patients receiving follow-up cured and 60 healthy controls,the serum levels of TGF-βand IL-10 were detected by CBA.The correlations of PD-1 with TGF-βand IL-10 levels in patients infected with Brucella were analyzed by pearson correlation test .Results: Compared with control,brucellosis patients had the higher PD-1/PD-L1,TGF-βand IL-10 expression (P<0.05),while in the patients receiving follow-up cured,the PD-1/PD-L1,TGF-βand IL-10 were remarkably lower than those in pretherapy (P<0.01),the change of PD-1 was positively correlated with the levels of TGF-β(r=0.817,P<0.01) and IL-10 (r=0.835,P<0.01).Conclusion: High expression of PD-1/PD-L1 and TGF-βand IL-10 in patients with Brucella may be involved in the negative regulation of Brucella on host immune response .

Protective effect of wenfei huayin recipe on lung of rats with chronic obstructive pulmonary diseases / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the mechanism of Wenfei Huayin Recipe (WHR) in treating chronic obstructive pulmonary diseases (COPD).</p><p><b>METHODS</b>The COPD model was induced by modified fumigating method and intra-tracheal instillation of lipopolysaccharide. Then reformed COPD model of cold-phlegm retention in Fei syndrome type. All the model rats were randomly divided into two groups, the model group and the treated group, treated respectively with WHR and saline for 14 successive days. Besides, a blank group without any intervention was set up for control. The general condition, weight growth rate, pathological changes of lung tissue under light microscope, ultrastructure under electron microscope, arterial blood gas analysis and levels of interleukin 4 (IL-4), interleukin 8 (IL-8), tumor necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) in lung homogenate by radio-immunity assay were observed.</p><p><b>RESULTS</b>In the treated group, as compared with the control group, the symptoms of aversion to cold, swarming, wheezing, the degree of epithelial cell degeneration and necrosis, the inflammatory cell infiltration and the volume of cilia lodging, sloughing, and bullae of lung were lessened and weight growth rate was higher (P<0.01). Moreover, the treated group was superior to the control group in decreasing levels of PaCO2, IL-4, IL-8, TNF-alpha and increasing PaO2, IFN-gamma and IFN-gamma/IL-4 ratio (P<0.01 or P<0.05).</p><p><b>CONCLUSION</b>WHR can correct the Th1/Th2 imbalance and inhibit the inflammatory reaction, displaying an important role in improving the airway function and structure in COPD rats.</p>

Professor He Pu-ren: the founder of Santong method of acupuncture and moxibustion / 中国针灸

Professor He Pu-ren, the founder of Santong method of acupuncture and moxibustion, is a well known acupuncturist at home and abroad. His main contributions include combined martial arts and Chinese medicine, showing obvious therapeutic effect; taking part in establishment of The Department of Acupuncture, Beijing Chinese Medicine Hospital; creating Santong method of acupuncture and moxibustion; advocating fire needle therapy; writing medical books and teaching students; advocating the culture of acupuncture; making the metal model of acupuncture and moxibustion, and others. His achievements have become an important part of acupuncture and moxibustion science.

Effects of TCM treatment according to syndrome differentiation on expressions of nuclear factor-kappaB and gamma-glutamylcysteine synthetase in rats with chronic obstructive pulmonary disease of various syndrome types / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the mechanism of traditional Chinese medicine (TCM) treatment according to syndrome differentiation in treating chronic obstructive pulmonary disease (COPD) by observing the changes of nuclear factor-kappaB (NF-kappaB) and gamma-glutamylcysteine synthetase (gamma-GCS) expression levels in rats.</p><p><b>METHODS</b>COPD model was established by modified method of combining fumigation and lipopolysaccharide (LPS) intra-tracheal dripping. Model rats were treated respectively for succesive 14 days according to their syndrome, that is, Xiaoqinglong Decoction to the rats of cold-phlegm accumulation in Fei, Maxing Shigan Decoction to those of heat-phlegm accumulation in Fei, Yupingfeng Decoction to those of Fei-qi deficiency, Liujunzi Decoction to those of Pi-qi deficiency, Renshen Gejie Decoction to those of Shen qi-deficiency. Besides, model rats in the model control group received 2mL normal saline daily, and no intervention was applied in the normal control group. The expression of gamma-GCS and NF-kappaB was detected by immunochemistry before and after treatment.</p><p><b>RESULTS</b>Compared with that in the normal rats, the expressions of gamma-GCS and NF-kappaB in bronchial and alveolar epithelium of COPD rats before treatment were significantly higher, but the positive expression rates were lowered after treatment significantly (P<0.05).</p><p><b>CONCLUSION</b>TCM treatment according to syndrome differentiation could rectify imbalance of oxidation/anti-oxidation and alleviate inflammatory reaction in COPD rats, thus to treat COPD effectively.</p>

Changes of element contents and their interrelationship in tibia of osteoporotic rats / 浙江大学学报·医学版

OBJECTIVE: To observe the changes of bone element contents in osteoporosis and their interrelationship. METHODS: Twelve female SD rats,10-month-old, were bilaterally ovariectomized (OVX group) and another ten rats were received sham-operation under anesthesia (SHAM group).The element contents in tibia, including Ca, P, Mg, Zn, Mn, Fe, Cu, Mo and Cr, were determined by atomic absorption spectrophotometer 7 month later. The data of contents of all elements were analyzed by simple regression. RESULTS: Compared with the SHAM group rats, the contents of Ca, P and Mg were decreased by 6.6 %(P<0.05), 6.3 %(P<0.05) and 14.9 %(P<0.01) respectively. The contents of Zn and Fe were reduced by 15.2 %(P<0.01) and 35.1 %(P<0.01) separately, Mo and Cr were decreased by 12.2 %(P>0.05) and 14.0 %(P>0.05), while the contents of Mn, Cu and Co were shown no change. There was a significant correlation among the contents of Mg, Mn, Zn, Ca and P. CONCLUSION: The contents of Ca, P, Mg, Zn and Fe were matkedly reduced in bone of osteoporotic rats induced by ovariectomy.