ABSTRACT
@#Acute myeloid leukemia (AML) is a disease caused by abnormal cloning of hematopoietic stem cells in the bone marrow, which leads to accumulation of a large number of abnormally differentiated myeloid cells. It is difficult to cure by traditional treatment. The successful application of chimeric antigen receptor T cell (CAR-T) immunotherapy indicates that the treatment of hematological tumors has entered a new stage of precision immunotherapy. However, CAR-T immunotherapy has been found to have many problems in clinical applications, including long treatment cycle, expensive prices, off-target effects, cytokine release syndrome, etc. Therefore, it is necessary to expand the application of CAR or adopt improved measures to enhance the therapeutic effect. This article reviews the new strategies for genetic engineering modification of CAR immune cells and the research progress and application of in situ programming to generate CAR-T, and besides, briefly introduces the new methods about the delivery of gene drugs in vivo, aiming to provide new ideas and theoretical basis for expanding and improving the application of precision immunotherapy in AML.
ABSTRACT
Renal hematuria is caused by glomerular damage and basement membrane rupture due to coagulation dysfunction, ischemia and hypoxia, and immune function damage, resulting in red blood cells exuding through glomerular filtration membrane and excreting with urine. It is mainly manifested as microscopic and macroscopic hematuria. Among them, microscopic hematuria is characterized by microscopic urine sediment examination, there are three or more red blood cells per high-power microscopic field. Traditional Chinese medicine (TCM) believes that the pathogenesis of renal hematuria always belongs to ''asthenia in origin and sthenia in superficiality'', and ''asthenia in origin'' is caused by the deficiency of the three viscera of the lung, spleen, and kidney, while ''sthenia in superficiality'' is caused by the combination of dampness and blood stasis and the external disturbance of wind pathogens. The key pathogenesis features are ''deficiency, dampness, heat, blood stasis, and wind''. After consulting the TCM literature related to renal hematuria, the author found that the common syndrome types of renal hematuria in clinical practice were the deficiency of both Qi and Yin, the deficiency of both Yin and fire, the unsteadiness of kidney Qi, the deficiency of spleen and kidney Yang, the wind heat hurting the collateral, the dampness-heat blocking, and the blood stasis and internal resistance. The commonly used classical or temporal prescriptions included Shenqi Dihuangtang(参芪地黄汤), Zhibai Dihuangtang(知柏地黄汤), Wubi Shanyaowan(无比山药丸), Jisheng Shenqiwan(济生肾气丸), Sishenwan(四神丸), Yinqiaosan(银翘散), Bazhengsan(八正散), Sanrentang(三仁汤), Xuefu Zhuyutang(血府逐瘀汤), Danggui Shaoyaosan(当归芍药散), Xiaoji Yinzi(小蓟饮子), Buzhong Yiqitang(补中益气汤), et al. Self prepared prescriptions mainly include Tongluo Ningxue prescription (通络宁血方), Qingre Zhixue prescription( 清热止血方) and Wuteng Tongluo drink (五藤通络饮). The traditional Chinese medicine is commonly used for the treatment of Xueniaoling granules(血尿灵冲剂), Xueniaoan capsules(血尿安胶囊), Ningmitai capsules(宁泌泰胶囊), Huangkui capsules(黄葵胶囊) and Yishen nixuexiao granules(益肾溺血消颗粒), which constantly enriched the treatment of renal hematuria. The combination of TCM and western medicine has obvious advantages. The treatment of renal hematuria in clinical practice often combines with modern medical methods, which has a good therapeutic effect on the improvement of symptoms and indicators of renal hematuria. At present, many doctors have made in-depth exploration on the etiology, pathogenesis, and clinical treatment of renal hematuria, but few scholars have made detailed induction and collation in recent years. Therefore, the author has collated the clinical data on the treatment of renal hematuria with TCM in the past ten years, and reviewed it from the aspects of etiology, pathogenesis, and clinical research, to provide useful references for clinical intervention and delay the progress of renal disease.
ABSTRACT
Objective:To evaluate the effect of inhibition of interleukin-6 (IL-6) trans-signaling on sepsis-associated encephalopathy (SAE) in mice.Methods:Eighty healthy male C57BL/6J mice, aged 8-10 weeks, weighing 22-24 g, were divided into 4 groups using a random number table method: sham operation group (Sham group, n=10), SAE group ( n=35), SAE plus sgp130Fc group ( n=25) and sgp130Fc group ( n=10). Sepsis was induced by cecal ligation and puncture (CLP) in anesthetized animals.Sham and sgp130Fc groups received no CLP.In group sgp130Fc and group SAE+ sgp130Fc, sgp130Fc 0.5 mg/kg was intraperitoneally injected at 1 h after sham operation or CLP.The survival rates, body weight and neurological function scores were recorded within 1-10 days after sham operation or CLP.Four mice in each group were selected at 24 h after sham operation or CLP to detect the expression of occlusin in hippocampus by Western blot.Five mice in each group were selected to measure cognitive function using Morris water maze test at day 4 after sham operation or CLP. Results:Compared with group Sham, the survival mice, body weight and neurological function scores on days 2-10 after CLP were significantly decreased, the expression of occludin was down-regulated, the frequency of crossing the original platform was decreased, and the time spent in target quadrant was shortened in group SAE ( P<0.05), and no significant change was found in the indexes mentioned above in group sgp130Fc ( P>0.05). Compared with group SAE, the survival rate and neurological function scores on days 3-10 after CLP were significantly increased, the expression of occludin was up-regulated, the frequency of crossing the original platform was increased, and the time spent in target quadrant was prolonged ( P<0.05), and no significant change was found in body weight in group SAE+ sgp130Fc ( P>0.05). Conclusions:Inhibition of IL-6 trans-signaling can reduce the damage to the blood brain barrier and SAE in mice.
ABSTRACT
Objective To study the feasibility and value of magnetic resonance diffusion tensor imaging (DTI) to monitor non?arteritic anterior ischemic optic neuropathy (NAION). Methods Thirty eight NAION patients (56 eyes) were divided into acute period in 17 eyes, progressive period in 16 eyes and chronic period in 23 eyes at the base of onset time. According to matching principle, 56 eyes in 38 normal controls (NCs) were enrolled. All the patients and NCs underwent MR and DTI scan. The raw data were processed by two experienced radiologists, mean diffusivity (MD), axial diffusivities (λ//), radial diffusivities (λ┴), fractional anisotropy (FA) and Length value were got. The independent sample t test was used for the parameter values between the NAION group and the NCs group. A single factor variance analysis was used to compare the parameters among different stages of NAION group. Results Compared to the NCs group, the values of FA and Length in NAION group were reduced [0.20±0.11 vs 0.31±0.12, (5.85±0.92) vs (65.11± 6.89) mm], and the differences were statistically significant (t=-4.28,-5.25;P<0.05). The values of MD andλ┴were increased [(0.16±0.04)×10-3 vs (0.10±0.04)×10-3 mm2/s, (0.16±0.05)×10-3 vs (0.09±0.03)×10-3 mm2/s] in NAION group and the differences were statistically significant (t=6.83, 7.10;P<0.05). The value of FA and Length in acute period, progressive period and chronic period of the NAION group decreased differently compared to the NCs group. At the same time, the value of MD value and λ┴in the three periods of the NAION group increased compared to the NCs groupand the differences were statistically significant (P<0.05). The value of FA between the acute period, the progressive period, and the chronic period of NAION group were statistically signficant (F=10.88, P<0.05). However, no significant differences were found in the values of MD, λ┴and Length of the NAION group (F=0.23, 0.64, 0.33, 1.38;P=0.79, 0.54, 0.72, 0.27). Conclusion The parameters of DTI can be used to monitor the damage of optic nerve and development in NAION.
ABSTRACT
We investigated the correlation between toxin gene exoS,exoU and fluoroquinolone resistance in lower respiratory tract infection with P.aeruginosa so as to provide guidance for reasonable treatment of clinical infections.We collected P.aeruginosa of sputum samples in hospitalized patients from October 2015 to March 2016.The antimicrobial susceptibility was tested by liquid dilution method.The exoS and exoU genes were detected by PCR technique.Results showed that forty-six P.aeruginosa strains were identified from sputum.The exoS and exoU gene positive rate were 86.96 % (40/46) and 69.57 % (32/ 46) respectively,and the highest proportion of genotype was exoS+/exoU+ (60.87%,28/46).Among them,36.96% (17/ 46) were multiple drug-resistant bacteria(MDR).Fluoroquinolone non-sensitive (FQ-NS) strain were 78.95% (15/19) for MDR and 89.47 % (17/19) exoU gene were positive,which was significantly higher than the fluoroquinolone sensitive strains (FQ-S).Compared with the FQ-S strain,FQ-NS strains were serious drug resistance.The drug resistant rate of eefepime and aztreonam were more than 70%,and then meropenem and imipenem were more than 50%.The drugs of lower resistance rate in FQ-NS strain had polymyxin B(10.53%,2/19),amikacin(10.53%,2/19),ceftazidime (15.79%,3/19) and gentamicin (21.05%,4/19).P.aeruginosa of lower respiratory infection carried toxin genes exoS and exoU were higher,the main genetpy was exoS+/exoU+.FQ-NS strains were higher drug resistance rate and a higher proportion of exoU+ strains than FQ-S strains.We should strengthen virulence genes test and drug resistance monitoring in clinical practice.