Cellular therapies have revolutionized the treatment of hematological malignancies since their conception and rapid development. Chimeric antigen receptor (CAR)-T cell therapy is the most widely applied cellular therapy. Since the Food and Drug Administration approved two CD19-CAR-T products for clinical treatment of relapsed/refractory acute lymphoblastic leukemia and diffuse large B cell lymphoma in 2017, five more CAR-T cell products were subsequently approved for treating multiple myeloma or B cell malignancies. Moreover, clinical trials of CAR-T cell therapy for treating other hematological malignancies are ongoing. Both China and the United States have contributed significantly to the development of clinical trials. However, CAR-T cell therapy has many limitations such as a high relapse rate, adverse side effects, and restricted availability. Various methods are being implemented in clinical trials to address these issues, some of which have demonstrated promising breakthroughs. This review summarizes developments in CAR-T cell trials and advances in CAR-T cell therapy.
Humans ; Receptors, Chimeric Antigen ; Receptors, Antigen, T-Cell/genetics* ; Immunotherapy, Adoptive/adverse effects* ; Hematologic Neoplasms/therapy* ; Multiple Myeloma/etiology* ; Cell- and Tissue-Based Therapy

Acute lymphoblastic leukemia (ALL) is a malignancy originating from B-/T-lineage lymphoid progenitor cells. With the continuous development of new drugs as well as therapeutic regimens, adult ALL patients have improved complete remission rates and overall survival rates, but the survival rate of patients after relapse remains low. The positive minimal residual disease after complete remission is an important reason for relapse. Although minimal residual disease monitoring has been found to be important in predicting patients prognosis in recent years, the uniform stratified treatment protocols have not yet been developed in the clinical practice of adult ALL. This article reviews the prognostic significance of minimal residual disease monitoring at different time points, as well as the progress of removal methods of minimal residual disease.

Objective A serum metabolic profiling in acute myocardial infarction (AMI) rat was established to screen potential metabolic markers of AMI prognosis and complication. Methods Male Wistar rats(n=20)were divided randomly into AMI 1 week group and control group. Anterior descending coronary was ligated in rats in AMI 1 week group to establish AMI model. After one week, these rats were sacrificed and the blood was collected from heart. And metabolomics platform was used to analyze serum metabolic profile. After PCA (principal component analysis) and OPLS-DA (Orthogonal partial least squares-Discriminant Analysis) were established, SPSS 19.0 was used to analysis data to get the potential metabolic markers. Results The PCA and OPLS-DA were established successfully and 27 metabolites present differently in levels between AMI 1 week group and the control group. Among these metabolites, LysoPC (lysophosphatidylcholine) and LysoPE (lysophosphatidyl ethanolamine) demonstrate significant differeance between these two groups. Conclusion The metabolic disorder in AMI patients can be reflected from the serum metabolic profiling. And these significant metabolites provide sup?port and reference for the prevention of AMI complication and its treatment.

Due to the air-filled alveoli and delicate vascular structure,the lung is the most easily damaged organ when human or animal is subjected to a shock wave.Primary pulmonary blast injury resulting from shock wave is an important cause of trauma not only in military conflicts but also in terrorism or accidents involving civilians.The physiological,pathological and biochemical changes after blast injury may lead to inflammatory response,cell apoptosis in the lung,boost the activation of cytokines including TNF-α,IL-6,IL-8 and IL-1β,and finally result in acute respiratory distress syndrome (ARDS).This paper presents the evolution and characteristics of pulmonary blast injury,and demonstrates four relevant experimental setups including biological shock tube,segmented shock wave generator,mini blast wave generator and laser-induced stress wave generator.Besides,this paper reviews the scoring system of pulmonary blast injury,pathological and biochemical measurement aiming to provide helpful reference to establish pulmonary blast injury models.

Objective To analyze injury characteristics and treatment of hospitalized patients wounded in Wenehuan earthquake so as to provide references for medical rescue in disasters. Methods The study involved data of seismic patients from Trauma Database System Version 3.0 that collected clini-cal data of seismic patients admitted into West China Hospital of Sichuan University, Chengdu, and First and Second Hospitals of Deyang City. Trauma Database System Version 3.0 was developed by Research Institute for Traffic Medicine of PLA, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing. A comparative analysis was done on patient distribution, injury severity and medical treatment. Results There were 826 qualified patients including 410 males and 416 females ( at age range of 1-102 years, mean 45.8 years). Of all, the patients at age of 31-60 years accounted for 50. 2%. The patients were mainly peasants (43.8%, 208/477), workers (15.7%, 75/477) and students (14.1%, 67/477). Blunt injury (53.2%), crush/bury injury (22.5%) and slip/fall injury were three main causes for injury. The patients for 92.1% were admitted into two hospitals of the City of Deyang within four days after earthquake, while 81.7% of patients were admitted into West China Hospital in Chengdu at days 3-9 after earthquake. Patients with bone injuries accounted for 75.3%. The patients had abbreviated injury score (AIS) for mainly 1-3 points, with incidence rate of se-vere multiple trauma ( ISS > 16 points) of 8.2%. Internal fixation was done in 120 patients ( 34. 1% ), debridement and suturing in 103 (29.3%), external fixation in 55 ( 15.6% ), extremity amputation in 22 (6.3%) and intracerebral surgery in 2 (0.6%). Conclusions The injuries are mainly induced by collapse of buildings during earthquake. Bone injuries are predominant injury type, with AIS of mainly 1-3 points and few severe multiple trauma. The results show that the patients receive late special treat-ment and slow evacuation, indieating necessity of strengthening capacity of early medical treatment and ef-fective evacuation during destructive natural disasters.

Objective To observe the effect of intact vagus nerve stimulation(IVNS)on liver inflammation and mRNA expression of suppressors of cytokoine signaling(SOCS)in rats. Methods Eighty Sprague Dawley rats were randomly divided into control group(n=20),sham group(n=20),LPS group(n=20,with intravenous injection of LPS to induce system inflammatory response)and LPS +IVNS group(n=20,with intact vagus nerve stimulation after LPS administration).The level of TNFαand IL-10 in the liver was detected with enzyme linked immunosorbent assay at 0,2,4,6 hours post-injection time.mRNA expressions of SOCS1 and SOCS3 in the liver were also determined with reverse transcription and polymerase chain reaction(RT-PCR). Resuits The liver TNFαin LPS+INVS group was lower than that of LPS group after LPS injection at 2,4 and 6 hours(P＜0.05).Compared with LPS group,liver IL-10 level in LPS+IVNS group was higher(P＜0.05)at post-injection time points(4 and 6 hours).After four hours of LPS challenge,mRNA expressions of both SOCS1 and SOCS3 were significantly increased.Compared with LPS group,mRNA expression of SOCS3 in LPS+INVS group was upregulated more significantly(P＜0.01),while mRNA expression of SOCS1 showed insignificant difference. Conclusions IVNS can depress liver inflammation and the anti-inflammatory mechanism involves SOCS signal transduction pathway.

OBJECTIVETo investigate the possible effects of long-term exposure to dust containing thorium and thoron progeny on dust-exposed miners.

METHODSA negative, high voltage, exhaled thoron progeny measurement system was used to estimate the miners' thorium lung burden.

RESULTSThe highest thorium lung burden of 638 miners was 11.11 Bq. The incidence of stage 0(+) pneumoconiosis was higher among dust-exposed miners. Lung cancer mortality of the dust-exposed miners was significantly higher than that of controls (P < 0.005).

CONCLUSIONThere is a difference in cancer rates between those who have long-term exposure to dust containing thorium (in which carcinogenic ThO(2) and SiO(2) exist) and thoron progeny and those who have not.

Air Pollutants, Radioactive ; adverse effects ; Body Burden ; China ; epidemiology ; Dust ; Follow-Up Studies ; Humans ; Lung Neoplasms ; epidemiology ; Mining ; Occupational Diseases ; epidemiology ; Occupational Exposure ; adverse effects ; Thorium ; adverse effects

Objective To study the mechanism and characteristic of traffic injury of front crash. Methods Thirty rabbits were divided randomly into 3 groups according to crash velocity. The initial velocity of GroupⅠ was 30 km/h, group Ⅱ 40 km/h, and group Ⅲ 50 km/h. The rabbits were fixed on the seats in a sitting position and the injury process were started by driving power system with the velocity and acceleration set primarily. The crashing velocity and deceleration were recorded by laser velocity measuring system and high speed camera system. The injury characteristics of rabbits were observed and then the AIS-ISS score was compared. Results During 1 hour after injury, all rabbits survived except one in group Ⅱ and three in group Ⅲ. No organ injury was found in group Ⅰ, but organ injuries in thorax and abdomen were found in group Ⅱ and Ⅲ. The score of AIS (MAIS) and ISS were (2.30?0.65), (14.50?2.10) in group Ⅱand (4.20?0.70), (36.40?4.58) in group Ⅲ respectively. Conclusion The velocity and deceleration of crash have impact on the injury character of animal, and the main injury organs are the thorax and abdomen in traffic injury of front crash in rabbits.

Objective To investigate the changes of cervical vagal efferent discharge induced by lipopolysaccaride in rats. Methods Ten rats were randomly divided into two groups, receiving lipopolysaccaride (5 mg/kg) or normal saline through intravenous injection. Frequency of cervical vagal efferent discharge was recorded at 30 min, 1, 2 and 4 h after the injection. Results The frequency of cervical vagal efferent discharge was significantly increased after LPS injection (P

Objective To develop a device for stretch-induced injury to cultured cells and measure the injury parameters.It makes possible to observe the changes of cell configuration and function directly after injury. Methods The device was developed based on aero-dynamical principle,and consisted of mini-type air compressor,electromagnetic valve,pressure transmitter,PGA amplifier,A/D converter and computer.The computer can accurately control the injury parameters.A new method and device were first introduced to measure the deformation rate and deformation degree of silastic membrance in the stretch induced cultured cell injury process.The device controlled by the computer was used to cause the astrocyte injury.The degree of cell injury was assessed qualitatively by electron microscopy,and quantitatively by lactate dehydrogenase(LDH) enzyme release and trypan blue staining.Results The experiment results showed that the injury of different levels could be reproduced by our device under the injury parameters we set.Conclusion The injury device and the measuring system meet the requirements of our design.The results suggested that the new device and the method were much better than those reported in foreign literature.It has the advantages of simple and convenient manipulation,high precision and real-time processing.It can be used for the cell-level experiment research.