Chimeric antigen receptor T cells (CAR-T) therapy is progressing rapidly, and its safety has been widely concerned. At the 62nd American Society of Hematology Annual Meeting, a series of reports on the mechanism, predictive indicators and treatment strategies of major adverse reactions were carried out. These reports have certain guiding significance for comprehensively improving the safety of CAR-T therapy.

ObjectiveTo study the reliability to asses s interstitial fibrosis in myocardium of advanced age spontaneous hypertension rats(SHR) by acoustic densitometry. MethodsFifteen 20-month-old spontanous hypertension rats and fifteen age matched Wistar Kyoto(WKY) as control group were included. Ultrasonic backscatter parameters were acquired at interventricular septum, left ventricular posterior wall, left ventricular lateral wall. Normalized values of integrated backscatter of left ventricular lateral wall were compared with results by stereological approach under eletronic and light microscope. Results Compared with control group, SHR group showed different integrated backscatter at interventricular septum, left ventricular posterior wall and left ventricular lateral wall(P

Objective To investigate the changes and possible mechanisms of the expressions of metabolic pattern glutamic acid receptor 1(mGluR1) and mGluR3 in hippocampus of juvenile rats submitted to lithium chloride-pilocarpine induced model of epilepsy in 6 h,5 d,60 d after status epilepticus(SE) onset.Methods Seizures were induced in the juvenile rats with lithium and pilocarpine injected intraperito-neally,and behavioral changes and EEG were observed.Eighteen SD juvenile rats with SE were randomly divided into following groups: groupⅠ,in which the rats were killed at 6 h after SE onset(6 h SE),group Ⅱ,in which the animals were killed during the seizure-free period(5 days after SE onset),and group Ⅲ,in which the animals were killed in 60 days after SE induction(period of spontaneous recurrent seizures).And intraperitoneal injection of saline water control groups were divided into: groupⅠa,group Ⅱa and group Ⅲa.The hippocampus tissues after the rats were put to death were collected,the expressions of mGluR1 and mGluR3 mRNA were detected by reverse transcriptase polymerase chain reaction(RT-PCR) in the hippocampus of juvenile rats.Results EEG of rats in group Ⅰ were abnormal,but normal in groupⅡ,and 5(83%) cases of the juvenile rats in group Ⅲ manifested dissemination of sharp waves,spikes or spike wave.The saline control group did not spontaneously attack.There was more significant upregulation of mGluR1 mRNA expression(Pa0.05).The expressional levels of mGluR3 mRNA were upregulated in groupⅠ,group Ⅱ and group Ⅲ(Pa

Objective To study the expression of matrix metalloproteinase(MMP)-1,-3 and-9 in sun-exposed and-unexposed skin as weil as its significance in the mechanism of skin photoaging.Methods Skin samples were resected from the exmnsor side of forearm(sun-exposed area)and flexor side of upper arm(sun-unexposed area)of 23 healthy female volunteers.The expression of MMP-1,-3 and-9 was detected by immunohistochemical staining in 46 skin samples.Immunoreactive intensity distribution index (IRIDI)was calculated to assess the expression of MMP-1,-3 and-9.Wilcoxon signed ranks test,Mann-Whitney U-test and Spearman rank correlation analysis were performed.Results MMP-1,-3 and-9 were expressed in both sun-exposed and -unexposed skin.The average IRIDI value for MMP-1,-3 and-9 was 7.70(range,3 to 12).9.22(range,6 to 12),8.30(range,6 to 12)in sun-exposed skin,and 4.26 (range,2 to 6),5.39(range,2 to 9),4.04(range,1 to 6)in sun-unexposed skin,respectively;significant difierence existed between sun.exposed and-unexposed skin in the three parameters(all P＜0.01).A significant inerease was observed in the average IRIDI value for MMP-1,-3 and-9 in sun-exposed skin vs.sun-unexposed skin in women above 50 years of age (9.17 vs 4.75,10.58 vs 6.42,8.92 vs 4.33,respectively,all P＜0.05).In women younger than 50 years,the average IRIDI value for MMP-1,-3 and-9 was 6.09(range,3 to 8),7.73(range,6 to 9),7.64(range,6 to 12)in sun-exposed skin,significantly higher than that in sun-unexposed skin[3.73(range,2 to 6),4.27(range,2 to 8),3.73(range,1 to 6),all P＜0.05].Increased IRIDI scores of MMP-1,-3 and -9 were noticed in sun-exposed skin in women above 50 years of age vs.those younger than 50 years.but there was no statistical difrerence in MMP-I or MMP-9 between the two aged groups in sun-unexposed skin(all P＞0.05).The IRIDI scores of MMP-1,MMP-3 and MMP-9 were positively correlated with age(r=0.66,0.69,0.74,all P＜0.01)in sun-exposed skin,but the IRIDI scores of MMP-1 and MMP-9 uncorrelated with age in sun-unexposed skin.Conclusions There isan elevated expression of MMP-1,-3 and.9 in sun-exposed skin VS.SUn.unexposed skin.hinting that these three MMPs play a role in the occurrence and development of photoaging,but their biological mechanism may be different.

AIM: To analyze curative effect of four regulating-intestines prescriptions (Wumei Wan, Baitouweng Tang, Shenling Baizhu San and Tongxie Yao-fang) on the treatment of ulcerative colitis (UC) through summing up the previous animal experimental results.METHODS: We collected the conclusions in the papers related to four regulating-intestines prescriptions for the treatment of UC which were published recently, made comparisons from the aspectsof symptoms, physical sign, pathological change, cytokine and its protein expression, blood adhesion molecule, cell apoptosis and controlling gene and analyzed the pathogenesis of UC and action mechanism of four regulating-intestines prescriptions. Four regulating-intestines prescriptions included Wumei Wan,Baitouweng Tang, Shenling Baizhu San and Tongxie Yaofang. Wumei Wan is from Treatise on Exogenous Febrile Diseases and Synopsis of the Golden Chamber, which consists of dark plum, asarum herb, dried ginger, Chinese goldthread, Chinese angelica root, aconite root, pricklyash peel, cassia twig,ginseng (sun-dried ginseng) and bark of cork tree and has marked effect in treating colic caused by ascariasis and persistent dysentery. Baitouweng Tang, from Treatise on Exogenous Febrile Diseases, consists of medicinal herbs such as pulsatilla root, Chinese goldthread, bark of cork tree and ash bark, which has functions of clearing away the heat-evil, expelling superficial evils and relieving dysentery. In addition, it has marked effect in treating heat-type dysentery. Shenling Baizhu San, from Prescriptions of Peaceful benevolent Dispensary, consists of medicinal herbs such as pulp of lotus seed, coix seed, amomum fruit, balloon flower root, white hyacinth bean, poria, ginseng (sun-dried ginseng), glycyrrhiza, bighead atractylodes and rhizoma dioscoreae, which has the nature of replenishing qi to invigorate the spleen and eliminate wetness to arrest diarrhea and has marked effect on treating diarrhea due to the hypofunction of spleen. Tongxie Yao-fang which is from The Complete Works of Zhang Jingyue consists of four herbals of agehead atractylodes, root of herbaceous peony, dried tangerine peel and ledebouriella root and has the functions of soothing liver and invigorating spleen and stopping diarrhea, and has marked effect on treating liver sthenia and deficient spleen, borborygmus and abdominal pain and diarrhea.RFSULTS: ① Because UC is a chronic protracted dysentery with deficiency of vital energy and existing of evil energy, the vital energy will be harmed if its treatment is specialized in removing and dissolving the stagnation, evil energy will continue to exist and stagnation will continue to accumulate if its treatment is specialized in strengthening vital energy and inducing astringency. Only supporting healthy energy and expelling evil energy is the correct therapy method. This is in accordance with the main treatment of Wumei Wan ②Eliminating dampness and pathogenic heat from the blood to treat diarrhea is the main treatment method of Baitouweng Tang, and this is incompletely suitable for the treatment of UC.③Shenling Baizhu San had the effect on soothing liver and invigorating spleen and stopping diarrhea, and this is also incompletely suitable for the treatment of UC. ④ The prescription of Tongxie Yaofang is used for treating diarrhea caused by deficient spleen and liver sthenia, and spleen controlled by liver, and abnormal ascent and descent. It accords with main pathogenesis of UC, deficient spleen, excessive dampness of deficient spleen and it is weaker in invigorating the spleen in catabasis of UC than Shenling Baizhu San. Therefore, Wumei Wan has the best curative effect,Baitouweng Tang the second, Shengling Baizhu San the third and Tongxie Yaofang a little poor.CONCLUSION: UC belongs to recurrent dysentery, and its pathogenesis is in accordance with the main treatment of Wumei Wan, but not the other three prescriptions, so Wumei Wan is the most efficient prescription in treating ulcerative colitis. Diagnosis and treatment based on an overall analysis of signs and symptoms of TCM is the premise of obtaining the best curative effect. Modeling of animal tests must be consistent with the type of syndrome of the traditional Chinese medicine. Ating ulcerative colitis (UC) from aspects such as symptom, physical sign, pathological changes, adherence factor, cytokine and its protein expression, apoptosis and its controlling gene by means of modeling, which proves their functions and effects are different and their curative effect are also different due to their different ingredient though they all have the functions of treating. Results of this test show Wumei Wan has the best curative effect, Baitouweng Tang the second, Shenling Baizhu San the third and Tongxie Yaofang a little poor[1-11] Mechanism of four regulating-intestines prescription in the treatment of ulcerative colitis is discussed from the viewpoints of traditional Chinese medicine as follows.

Objective To observe the expression changes of CD34 and M30 in skin homogenate from a mouse model of scleroderma after irradiation with different doses of UVA1, and to investigate the effect of UVA1 phototherapy on vascular endothelial cell function in scleroderma. Methods The experimental mouse models of scleroderma were established by the injection with bleomycin and randomly divided into model control group (n = 10), UVA1 irradiation group (n = 30) and unirradiated group (n = 10). The UVA1 irradiation group was further equally divided into 3 groups, HD-UVA1 group irradiated with UVA1 at 100 J/cm2, MD-UVA1group with UVA1 at 60 J/cm2, and LD-UVA1 group with UVA1 at 20 J/cm2; phototherapy was performed thrice weekly for 10 weeks followed by the sacrifice of mice. The mice in model control group were killed immediately after the establishment of models, and the mice in unirradiated group received no irradiation after the establishment of models and were maintained till the killing of mice in UVA1 irradiation groups. Skin specimens were obtained from the bleomycin-induced scleroderma lesions of mice and separated into two parts, one was subjected to histopathological examination, and the other one was used to prepare skin homogenate for the detection of CD34 and M30 content with ELISA assay. Results After 30 sessions of treatment with UVA1,the softening and thinning of sclerotic skin were seen by the naked eye, with the most obvious changes in HDUVA1 group; pathological examination revealed a reduction in dermal thickness and the presence of hair follicular structures in subcutaneous fat tissue with no obvious proliferation of collagen in these mice. Compared with the mice in model control group and unirradiated group, there was an increase in CD34 and decrease in M30 content in skin homogenate from UVA 1-irradiated mice, with the most marked changes in mice irradiated with UVA1 at 100 J/cm2. The concentration of CD34 and M30 in skin homogenate from unirradiated group and model control group was significantly different from that in HD-UVA1 group (22.25 ± 8.91 μg/L and 31.97 ±17.97 μg/L vs. 72.39 ± 13.04 μg/L, 162.41 ± 58.00 U/L and 195.71 ± 71.09 U/L vs. 38.06 ± 19.89 U/L, all P ＜ 0.01 ). Additionally, significant differences were observed between the three UVA1 groups in the concentration of CD34 and M30 (F = 21.23, 15.32, respectively, both P ＜ 0.01 ). Conclusions UVA1 phototherapy could up-regulate the expression of CD34 but down-regulate that of M30 in skin homogenate from the mouse model of scleroderma, and the effect is correlated with the intensity and cumulative dose of irradiation.

DNA repair processes play a role in the development of drug resistance which represents a huge obstacle to leukemia chemotherapy. Histone H2AX phosphorylation (ser139) (γH2AX) occurs rapidly at the onset of DNA double strand break (DSB) and is critical to the regulation of DSB repair. If DNA repair is successful, cells exposed to anti-neoplastic drugs will keep entering the cycle and develop resistance to the drugs. In this study, we investigated whether γH2AX can be used as an indicator of tumor chemosensitivity and a potential target for enhancing chemotherapy. K562 and multi-drug resistant cell line K562/A02 were exposed to adriamycin (ADR) and γH2AX formed. Flow cytometry revealed that percentage of cells expressing γH2AX was increased in a dose-dependent manner and the percentage of K562/A02 cells was lower than that of K562 cells when treated with the same concentration of ADR. In order to test the potential of γH2AX to reverse drug resistance, K562/A02 cells were treated with PI3K inhibitor LY294002. It was found that LY249002 decreased ADR-induced γH2AX expression and increased the sensitivity of K562/A02 cells to ADR. Additionally, the single-cell gel electrophoresis assay and the Western blotting showed that LY249002 enhanced DSBs and decreased the expression of repair factor BRCA1. These results illustrate chemosensitivity can partly be measured by detecting γH2AX and drug resistance can be reversed by inhibiting γH2AX.

Objective To study the relationship of sunlight exposure and photoprotection with clinical activity in systemic lupus erythematosus. Methods A structured questionaire was administered to 107 SLE patients, to assess their attitudes and behavior regarding sunlight exposure and photoprotection. The clinical manifestations, laboratory findings and treatment were evaluated. Results All patients were classified into two groups based on the duration of exposure to sunlight per day. Fourty-eight (44.86%) patients were exposed to direct sunlight for an average of less than one hour per day in one group and 59 (55.14%) for one hour or more in the other group. Twenty-four (22.43%) patients reported use of photoprotective measures in spring and summer. The patients in the former group had significantly lower incidences of photosensitivity, arthritis, alopecia, exacerbations, presence of anti-dsDNA antibody, decrease of complement C3, C4 and CH50 than those in the latter group(P

Objective To evaluate the sunscreen application and the level of photoprotective knowledge in both dermatologists and photosensitive patients. Methods The style, sites and amount of the sunscreen applied were examined by 0. 05 % dipyridamole cream in 39 dermatologists and 41 photosensitive patients with Wood's light. The participants were asked to fill in a questionnaire about the photoprotective knowledge. Results Frequent mistakes made by participants in this study were as follow: (1) using an inadequate amount of sunscreen; (2) putting sunscreen in the palm of the hand and rubbing the hands together before application; (3) lacking a systematic approach to sunscreen application. The median quantity of individual sites ranged from 0. 5 mg/cm2 to 1 mg/cm2 except for the forehead of the female dermatologist that had a median thickness of 1. 5 mg/cm2. The questionnaire survey showed that dermatologists also had less knowledge on sun protection even though better than photosensitive patients. Conclusions Dermatologists and photosensitive patients always fail to apply sunscreen in some prominently exposed sites and to paint the average thickness of sunscreen used far less than that of experimentally measured dose (2 mg/cm2). Continuing education and training about pho-toprotection for dermatologists should be carried out to provide better education for the patients on sun protection.