T-cell engager(TCE) bridges T cells to target cells via dual-targeting, activating specific cytotoxicity of T cells,revolutioni-zing oncology and autoimmune therapies. In the field of hematological tumor treatment, TCE drug CD19/CD3 bispecific antibody Blinatumomab improves outcomes in relapsed/refractory B-cell malignancies. For solid tumors, cha llenges include antigen off-target toxicity and immunosuppressive microenvironments(such as insufficient T-cell infiltration and enrichment of inhibitory factors). Strategies prioritize high-specificity targets [such as delta-like protein 3(DLL3) and claudin 18.2(CLDN18.2)], exemplified by Tarlatamab that has been approved for small cell lung cancer. In the field of autoimmune disease treatment, TCE can accurately deplete pathological cell subsets [such as CD3/CD19 for B/pre-plasma cells,CD3/B-cell maturation antigen(BCMA)for plasma cells], breaking through the limitations of traditional therapies. In this paper, the mechanism of TCE drugs, the role of CD3 as a signal hub in TCE targeted therapy and the research progress on TCE drugs are reviewed in order to provide references for optimizing the clinical transformation pathway of TCE and developing a new generation of immune reprogramming technology.

BACKGROUND:Psoralen has a strong anti-osteoporotic activity and may have a restorative effect on chemotherapy-induced osteoporosis. OBJECTIVE:To explore the restorative effect of psoralen on the osteogenic differentiation of bone marrow mesenchymal stem cells in mice inhibited by cyclophosphamide and its mechanism. METHODS:C57BL/6 mouse bone marrow mesenchymal stem cells were isolated and cultured.Effect of psoralen on viability of bone marrow mesenchymal stem cells was detected by MTT assay.Osteogenic induction combined with alkaline phosphatase staining was used to determine the optimal dose of psoralen to restore the osteogenic differentiation of bone marrow mesenchymal stem cells inhibited by cyclophosphamide.The mRNA expression levels of Runx2,alkaline phosphatase,Osteocalcin,osteoprotegerin,and Wnt/β-catenin signaling pathway-related genes Wnt1,Wnt4,Wnt10b,β-catenin,and c-MYC were measured by RT-qPCR at different time points under the intervention with psoralen.The protein expression of osteogenic specific transcription factor Runx2 and Wnt/β-catenin signaling pathway related genes Active β-catenin,DKK1,c-MYC,and Cyclin D1 was determined by western blot assay at different time points under the intervention with psoralen. RESULTS AND CONCLUSION:(1)There was no significant effect of different concentrations of psoralen on the viability of bone marrow mesenchymal stem cells.The best recovery of the inhibition of osteogenic differentiation of bone marrow mesenchymal stem cells caused by cyclophosphamide was under the intervention of psoralen at a concentration of 200 μmol/L.(2)Psoralen reversed the reduction in osteogenic differentiation marker genes Runx2,alkaline phosphatase,Osteocalcin and osteoprotegerin mRNA expression and Runx2 protein expression in bone marrow mesenchymal stem cells caused by cyclophosphamide conditioned medium.(3)Psoralen reversed the decrease in Wnt/β-catenin pathway-related genes Wnt4,β-catenin,c-MYC mRNA and Active β-catenin,c-MYC,and Cyclin D1 protein expression and the increase in DKK1 protein expression in bone marrow mesenchymal stem cells caused by cyclophosphamide conditioned medium.(4)The results showed that cyclophosphamide inhibited osteogenic differentiation of bone marrow mesenchymal stem cells in mice,and psoralen had a restorative effect on it.The best intervention effect was achieved at a concentration of 200 μmol/L psoralen,and this protective effect might be related to the activation of Wnt4/β-catenin signaling pathway by psoralen.

Objective To summarize the application experiences and curative efficacies of single lung transplantation assisted by extracorporeal circulation with coated lung ,centrifugal pump and coated pipe .Methods Retrospective analysis was conducted for clinical data of 6 adult patients with respiratory insufficiency undergoing single lung transplantation .The changes of hemodynamics and oxygenation before and after adjuvant treatment were observed ,the effects of adjuvant evaluated and the experiences of application summarized .Results The hemodynamic parameters post-assistance significantly improved as compared with that pre-assistance and pulmonary arterial pressure dropped from (56 ± 15 ) to (45 ± 13 ) mmHg with statistically significant differences . Arterial blood gas parameters significantly improved .PO2 spiked from (47 ± 12) to (68 ± 9) mmHg and PCO2 declined from (65 ± 14) to (55 ± 12)mmHg .And there were statistically significant differences .All patients were discharged successfully .Conclusions The simple extracorporeal membrane oxygenation system of coated lung , centrifugal pump and coated pipe during routine extracorporeal circulation may guarantee the operative safety of single lung transplantation and provide a new therapeutic option .

BACKGROUND:Osteoporosis caused by chemotherapy has become one of the serious side effects that impact the skeletal system. Icarin shows a strong anti-osteoporosis activity, which can have protective effect on osteoporosis induced by chemotherapy. OBJECTIVE: To study the protective effect and mechanism of icarin against cyclophosphamide-induced obstacle of mouse bone marrow mesenchymal stem cels differentiating into osteoblasts. METHODS:MTT assay and alkaline phosphatase (ALP) staining were used to determine the optimal protective concentration of icarin against cyclophosphamide-induced obstacle of mouse bone marrow mesenchymal stem cels differentiating into osteoblasts. mRNA expressions of osteoblast-specific transcription factors, OC, ALP, Runx2, and Wnt/β-catenin signaling pathway target genes, β-catenin, C-Myc, cyclin D1, were determined using RT-PCR method at different time after intervention with the optimal concentration of icarin. Expressions of Runx2, β-catenin, c-Myc, cyclin D1 regulated by the optimal concentration of icarin were detected using western blot assay at the protein level. RESULTS AND CONCLUSION:Cel viability and ALP activity decreased significantly in the cyclophosphamide group compared with the control group, but there was no significant difference in cel viability between icarin group and cyclophosphamide group. Icarin at 100 μmol/L showed the best protective effect against cyclophosphamide-induced obstacle of osteogenic differentiation of bone marrow mesenhymal stem cels. Compared with the control group, cyclophosphamide chemotherapy reduced the expressions of ALP, OC, Runx2 at mRNA level and Runx2 at protein level, weakened the expressions ofβ-catenin, cyclin D1 at mRNA level and active β-catenin, Cyclin D1, c-myc at protein level, and increased the expression of DKK1. Compared with the cyclophosphamide group, 100 μmol/L icarin increased the expression of osteoblast-specific transcription factors and Wnt/β-catenin signaling pathway genes at mRNA and protein levels, and reduced the expression of DKK1 protein. These results show that cyclophosphamide can lead to osteogenic differentiation disorder of mouse bone marrow mesenchymal stem cels, and in contrast, icarin shows a protective effect and its optimal intervention concentration is 100 μmol/L. Additionaly, the protective roleof icarin is probably related to activation of Wnt/β-catenin signal pathway.

Objective To isolate and purify VacA protein secreted by Helicobacter pylori or recombinant VacA , and to investigate the effect of VacA-induced cell vacuolar change and apoptosis .Methods VacA proteins were separated and pu-rified from the culture supernatant of H.pylori ( ATCC26695 ) or from the split products of genetically engineered bacteria (pQE30-VacA-E.coli M15) expressing recombinant VacA.The VacA protein obtained was acidified and then incubated with AGS cells for 24 h at different final concentrations of 5 and 10 ng/ml before the vacuolar change and apoptosis of AGS cells were detected via microscopy and flow cytometry assay , respectively .Results H.pylori-secreted VacA and recombi-nant VacA were successfully separated and purified .The H.pylori-secreted VacA significantly induced the vacuolar change and apoptosis of AGS cells (P<0.01) while the recombinant VacA did not.Conclusion H.pylori-secreted VacA protein can effectively induce cell vacuolar change and apoptosis, but recombinant VacA can not, suggesting that the purified VacA protein secreted by H.pylori can be used to explore VacA-induced pathogenesis.

Objective To investigate the correlation between Helicobacter pylori (HP) infection-associated gastritis and the ap-optotic genes in gastric mucosa .Methods Forty-five patients with chronic gastritis were registrated in our study from November 2013 to December 2014 .HP infection status in the patients was detected by using urease test and 13C-urea breath test .The degree of gastritis in the gastric mucosa with HP infection was confirmed via histopathology .qRT-PCR was used to measure the mRNA ex-pressions of Bax ,Bak and Bcl-2 in the gastric mucosa with HP infection and matched normal gastric mucosa .Person analysis was used to assess the correlation between the HP infection-associated gastritis and the mRNA expressions of Bax ,Bak and Bcl-2 in the gastric mucosa .Results Forty-five patients with HP infection in antrum and 45 patients (100% ) with chronic antrum gastritis were identified ,including 28 patients (62 .2% ) with light gastritis ,16 patients (35 .6% ) with moderate gastritis ,1 patient (2 .0% ) with severe gastritis .9 patients (20 .0% )with metaplasia ,5 patients(11 .1% ) with low grade intraepithelial neoplasms .The urease tests were negative in the gastric body of 45 patients ,6 patients (13 .3% )were mild chronic gastritis in the body ;Patient with meta-plasia and intrapithelial gastritis was not found .The Bax expression in the HP-infected gastric mucosa was markedly increased when compared with the normal gastric mucosa (P< 0 .01) ,and positively correlated with the degree of gastritis (P< 0 .01) , whereas the expressions of Bak and Bcl-2 have no significantly deferences bttween two groups(P>0 .05) .Conclusion HP infec-tion-associated gastritis positively correlated with the expressions of apoptotic genes in gastric mucosa ,suggesting that HP infection might result in increasing the Bax expression and further enhancing the cell apoptosis .

Objective To investigate the morbidity of soldiers stationed on an island ,analyze the relationship betweendiseases and the environment,and to provide an effective method for disease prevention and treatment .Method Data ofoutpatients from troops stationed on an island between September 2012 and August 2013 were statistically investigatedaccording to the classification of diseases.The cause of disease was analyzed .In addition,90 soldiers stationed on an islandwere randomly selected to investigate their response to heat and humidity and parts susceptible to skin diseases viaquestionnaires and talks.Results A total of 789 cases of disease were identified,including 226 cases of upper respiratorytract infection,118 cases of orthopedic-related diseases,90 cases of traumatic diseases,88 cases of oral diseases,74 casesof digestive system diseases,62 cases of skin diseases,53 cases of ENT diseases,41 cases of urinary tract infection,and37 cases of anorectal diseases.The top five responses to heat and humidity were sweating,thirst,body fatigue,dizzinessand profuse sweating.The most susceptible part to skin diseases was the feet ,followed by the cheek,crotch,back andneck.Conclusion The epidemiological characteristics of diseases on this island are significant,and medical supportshould be focused on improving the overall level of hospital treatment.

OBJECTIVETo compare therapeutic effects of red-hot needle therapy and filiform needle therapy on nodules of breast of the type of stagnation of liver-qi and phlegm coagulation.

METHODSSix hundred cases were randomly divided into a treatment group and a control group, 300 cases in each group. The treatment group were treated with red-hot needle pricking at the proliferative parts and Ashi points as main, and the control group with filiform needle therapy.

RESULTSIn the treatment group, 240 cases were cured, 58 cases improved and 2 cases were not cured with an effective rate of 99.3%; and in the control group, 113 cases were cured, 165 cases improved and 22 were not cured with an effective rate of 92.7%, with a significant difference between the two groups (P = 0.001).

CONCLUSIONThe therapeutic effect of red-hot needle therapy is better than that of filiform needle therapy on nodules of breast of the type of stagnation of liver-qi and phlegm coagulation.

ObjectiveTo investigate rational surgical therapy for patients aged at 70 and up suffering from cardiac cancer. Methods 79 cases admitted from 1991 to 2000 were treated by transabdominal total gastrectomy with a radical resection rate of 73% and palliative resection rate of 19%. Results The average age was 74 6 years with a ratio of male to female of 4 6∶1. The average course of the disease was 3 1 months, and only 1 (2%) case got early diagnosis,while the misdiagnosis rate was 54%. Postoperative complication rate was 38%, mortality rate was 3%. Conclusions With the preoperative concurrent disease properly managed and the operation appropriately performed senile patients with cardiac cancer could also be managed successfuly as young patients .

[Objective] To investigate the influence of injection of substance P (SP) and its antagonist into locus ceruleus on electroacupuncture of Neiguan for acute myocardial ischemia (AMI). [Methods] Rabbit model of AMI was set up by ligating left ventricular branch of coronary artery. Forty-nine rabbits were allocated to five groups: Group A (the control group), Group B (electroacupuncture of Neiguan), Group C (injection of SP), Group D (electroacupuncture of Neiguan and injection of SP) and Group E (electroacupuncture of Neiguan and injection of SP antagonist) . Locus ceruleus was located by cerebral stereotaxic apparatus. Dynamic changes of ST segment of electrocardiogram and morphological feature of myocardium were observed. [ Results ] Injection of SP promoted the recovery of AMI and enhance the effect of electroacupuncture of Neiguan for AMI. However, the above effects were counteracted by the injection of SP antagonist. [Conclusion] SP plays an important role in reducing the damage of AMI on electroacupuncture of Neiguan and may serve as an important mediator for the connection of Neiguan and the heart.