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

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 BRCAl.These results illustrate chemosensitivity can partly be measured by detecting γH2AX and drug resistance can be reversed by inhibiting γH2AX.

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 investigate the role of infiltrating inflammatory cells in photoaging process by comparing the type and number of these cells in sun-exposed and-unexposed skin.Methods The expression of CD3,CD45RO and CD68 were detected by immunohistochemieal staining in 46 paraffin-embeded skin samples from the extensor forearms(sun-exposed)and upper-inner arms(sun-unexposed) of 23 healthy female volunteers.The number of positive cells in sun-exposed and -unexposed sites was counted and statistically tested by paired samples t test,and Pearson correlation analysis was performed to assess the relationship between the number of positive cells and age of these volunteers.Results The number of cells positive for CD3,CD45RO and CD68 per square millimetre in sun-exposed skin was significantly higher than that in sun-unexposed skin(48.91±13.173 vs.40.61±11.571,46.83±12.915 vs.38.00±10.109,85.43±22.346 vs.73.48±16.208,respectively,P<0.01 or 0.05).The number of cells positive for CD3 and CD45RO increased significantly with age (r=0.557,0.555,respectively,both P<0.01) in the sun-exposed skin but not in sun-unexposed skin,and the number of CD68-positive cells was uncorrelated with age in either sunexposed or -unexposed skin.Conclusion T lymphocytes and macrophages may play a role in the process of photoaging.

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 describe epidemiological characteristics of scalp psoriasis in China,and to determine its influencing factors through a hospital-based,multicenter and large-scale survey.Methods An epidemiological survey was conducted on patients with scalp psoriasis in 42 hospitals in 11 provinces and 4 municipalities.A questionnaire was designed to collect general and clinical information of patients,including clinical type,lesion distribution,psoriasis scalp severity index (PSSI),aggravating factors,influence on quality of life,treatment course,degree of satisfaction with treatment,etc.Participants were asked to fill out the questionnaire with the help of well-trained dermatologists.Data were processed with the EpiData software.The WPS system and Epi Info 5.0 statistics software were used for descriptive analysis of the data.Results Totally,3 901 patients participated this study,and 3 586 valid questionaires were obtained.The mean age at onset of scalp lesions was (27.40 ± 13.34) years,and the male to female ratio was 1.6∶1 with a mean PSSI score of 13.61 ± 12.31.The hairline of the forehead was the most frequently affected area with the constituent ratio of forehead psoriasis being 74.3％ (2 663/3 586).The duration of scalp psoriasis reached 3 to 6 months every year in 1 136 (31.7％) patients,and the area affected by scalp psoriasis was less than 25％ of the total surface area of the scalp in 1 649 (46％) patients.The most frequent clinical presentation was scaling (92.1％),followed by erythema (80.6％),itching(76.7％),bunchy hairs (39.9％) and hair loss(18.0％).Disease aggravation was most frequently associated with seasons (76.7％),emotions (47.4％),stress (47.1％) and fatigue (46.6％).The quality of life (especially social,outdoor and entertainment activities) was reported to be negatively influenced by this entity to different degrees in 2 529 (70.5％) patients.Of these patients,583 (17.8％) received combination therapy (topical and systemic),with glucocorticoid ointment (27.5％),calcipotriol scalp solution (22.7％) and glucocorticoid-containing solution (11.9％) being the most commonly used topical drugs; only 38.6％ complied with medication requirements and doctors' advice for 3 to 5 weeks,and 35.2％ believed that the primary reason for poor compliance was unsatisfactory response to drugs.It was considered that an ideal drug for the treatment of scalp psoriasis should be highly effective (50.3％),safe (17.8％) and easy to apply (11％) with a rapid onset of action(11.9％).Conclusions Scalp psoriasis has a predilection for the hairline of the forehead with scaling as the main clinical presentation.Winter and spring seasons appear to be the most common aggravating factor of scalp psoriasis.The quality of life is negatively influenced to different degrees in many patients with scalp psoriasis.Topical corticosteroids plus non-hormonal drugs should be the first choice for the treatment of scalp psoriasis.Patients consider that the ideal drugs for the treatment of scalp psoriasis should be effective,safe,and easy to apply.

Objective To study the effects of different stimulators on the production of matrix metalloproteinases (MMPs) by peripheral blood mononuclear cells (PBMCs),and to evaluate the effects of the culture supernatant of activated PBMCs,named conditioned media (CM),on the proliferation of and production of MMPs by cultured human fibroblasts.Methods PBMCs were isolated from the venous blood samples of healthy volunteers and divided into three groups to be stimulated by phytohemagglutinin (PHA group),the combination of antibodies against CD3 and CD28 (double-antibody group),or the RPMI 1640 medium containing 10％ fetal calf serum (control group).After 72-hour stimulation,CM was collected from all the three groups,diluted to several different degrees.Cultured human fibroblasts were classified into several groups to be treated with different dilutions of CM from the three groups for 48 or 24 hours,with the fibroblasts untreated with CM serving as the control group.Methyl thiazolyl tetrazolium (MTT) assay was performed to evaluate cellular proliferative activity,semi-quantitative reverse transcription (RT)-PCR to detect the expressions of MMP-1,MMP-3 and MMP-9 mRNAs in cells,and enzyme-linked immunosorbent assay (ELISA) to measure the levels of interleukin (IL)-6,MMP-1,MMP-3 and MMP-9 proteins in the culture supernatant of cells.Statistical analysis was carried out mainly by using one-way analysis of variance (ANOVA),Tukey HSD test,and GamesHowell test.Results Compared with the control group,the PHA group showed increased cellular proliferative activity,IL-6 and MMP-3 protein levels in the culture supernatant of activated PBMCs (all P ＜ 0.05).Significant differences were observed among the PHA group,double-antibody group and control group in the relative mRNA expression level (expressed as the ratio of target mRNA to β-actin mRNA) of MMP-1 in activated PBMCs (0.083 ± 0.016 vs.0.188 ± 0.030 vs.0.714 ± 0.104,F =85.905,P ＜ 0.05),but neither MMP-3 nor MMP-9 mRNA was expressed by activated PBMCs.MMP-3 protein was detectable in the culture supernatant of fibroblasts after the treatment with CM,and the level of MMP-3 protein was highest in that of fibroblasts treated with undiluted CM,and lowest with 1/10 diluted CM;at the same dilutions,the level of MMP-3 protein was highest in the culture supernatant of fibroblasts treated with CM from the PHA group,but lowest with that from the control group.Neither MMP-1 nor MMP-9 protein was detected in the culture supernatant of activated PBMCs or treated fibroblasts.There were no significant differences in cellular proliferative activity of and mRNA expressions of MMP-1 or MMP-3 in fibroblasts among these groups (all P ＞ 0.05),and MMP-9 mRNA expression was undetected in the treated fibroblasts.Conclusions PBMCs can be induced to express MMP-1 mRNA and secret MMP-3 protein after activation.However,the culture supernatant of activated PBMCs has no capacity to stimulate the expressions of MMP-1,MMP-3 and MMP-9 mRNAs or proteins by fibroblasts,suggesting that inflammatory cells may function through self-production of MMPs.