[Efficacy and safety analysis of the zanubrutinib-based bridging regimen in chimeric antigen receptor T-cell therapy for relapsed/refractory diffuse large B-cell lymphoma].

Objective: To further elucidate the clinical efficacy and safety of a combination regimen based on the BTK inhibitor zebutanil bridging CD19 Chimeric antigen receptor T cells (CAR-T cells) in the treatment of relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL) . Methods: Twenty-one patients with high-risk r/r DLBCL were treated with a zanubrutinib-based regimen bridging CAR-T between June 2020 and June 2023 at the Department of Hematology, Tongji Hospital, Tongji University and the Second Affiliated Hospital of Zhejiang University, and the efficacy and safety were retrospectively analyzed. Results: All 21 patients were enrolled, and the median age was 57 years (range: 38-76). Fourteen patients (66.7%) had an eastern cooperative oncology group performance status score (ECOG score) of ≥2. Eighteen patients (85.7%) had an international prognostic index (IPI) score of ≥3. Three patients (14.3%) had an IPI score of 2 but had extranodal infiltration. Fourteen patients (66.7%) had double-expression of DLBCL and seven (33.3%) had TP53 mutations. With a median follow-up of 24.8 (95% CI 17.0-31.6) months, the objective response rate was 81.0%, and 11 patients (52.4%) achieved complete remission. The median progression-free survival (PFS) was 12.8 months, and the median overall survival (OS) was not reached. The 1-year PFS rate was 52.4% (95% CI 29.8% -74.3%), and the 1-year OS rate was 80.1% (95% CI 58.1% -94.6%). Moreover, 18 patients (85.7%) had grade 1-2 cytokine-release syndrome, and two patients (9.5%) had grade 1 immune effector cell-associated neurotoxicity syndrome. Conclusion: Zanubrutinib-based combination bridging regimen of CAR-T therapy for r/r DLBCL has high efficacy and demonstrated a good safety profile.

[Efficacy and safety of fourth-generation CD19 CAR-T expressing IL7 and CCL19 along with PD-1 monoclonal antibody for relapsed or refractory large B-cell lymphoma].

Objective: This study systematically explore the efficacy and safety of fourth-generation chimeric antigen receptor T-cells (CAR-T), which express interleukin 7 (IL7) and chemokine C-C motif ligand 19 (CCL19) and target CD19, in relapsed or refractory large B-cell lymphoma. Methods: Our center applied autologous 7×19 CAR-T combined with tirelizumab to treat 11 patients with relapsed or refractory large B-cell lymphoma. The efficacy and adverse effects were explored. Results: All 11 enrolled patients completed autologous 7×19 CAR-T preparation and infusion. Nine patients completed the scheduled six sessions of tirolizumab treatment, one completed four sessions, and one completed one session. Furthermore, five cases (45.5%) achieved complete remission, and three cases (27.3%) achieved partial remission with an objective remission rate of 72.7%. Two cases were evaluated for disease progression, and one died two months after reinfusion because of uncontrollable disease. The median follow-up time was 31 (2-34) months, with a median overall survival not achieved and a median progression-free survival of 28 (1-34) months. Two patients with partial remission achieved complete remission at the 9th and 12th months of follow-up. Therefore, the best complete remission rate was 63.6%. Cytokine-release syndrome and immune effector cell-associated neurotoxicity syndrome were controllable, and no immune-related adverse reactions occurred. Conclusion: Autologous 7×19 CAR-T combined with tirelizumab for treating relapsed or refractory large B-cell lymphoma achieved good efficacy with controllable adverse reactions.

[Current status and research advances on drug sedation and analgesia in burn children].

Children are high-risk groups of burns, with unique physiological, psychological, and anatomical states, and the management of anxiety and pain for burn children are extremely challenging. Non-pharmacological interventions are very important for pain management in burn children, but are often inadequate for treating pain and anxiety, so pharmacological sedation and analgesia are necessary. This article reviewed the clinical treatment and research progress in this field in the past 10 years at home and abroad, including the pain assessment of burn children, monitoring in sedative and analgesic treatment, main therapeutic drugs and research progress, and some controversies in clinical practice. Besides, some suggestions have been put forward for clinical reference.

[Clinical randomized controlled trial on influence of recombinant human growth hormone on the immune function of younger children with severe burn injuries].

Objective: To preliminarily investigate the influence of recombinant human growth hormone (rhGH) on the immune function of younger children with severe burn injuries. Methods: A total of 30 younger children with severe burn injuries, conforming to the study criteria, were admitted to our hospital from July 2016 to July 2018. They were enrolled in the prospective, randomized, double-blinded, controlled trial and divided into group rhGH [n=15, 10 boys and 5 girls, aged (22±10) months] and control group [n=15, 8 boys and 7 girls, aged (21±7) months] according to the random number table. The patients in control group received anti-shock, anti-infection, and wound caring therapies, etc. On the basis of above-mentioned treatment, the patients in group rhGH were subcutaneously injected with rhGH once every night before bedding, with a dosage of 0.2 IU·kg(-1)·d(-1), from the 3rd day post injury for 7 consecutive days. Before and on the 3rd and 7th day of rhGH treatments, the fasting peripheral venous blood was collected from patients in both groups. Blood glucose level was detected by glucometer. Percentages of CD4(+) T lymphocytes, CD8(+) T lymphocytes, CD3(+) T lymphocytes, CD19(+) B lymphocytes, and ratio of CD4(+) T lymphocytes to CD8(+) T lymphocytes were determined by flow cytometer. Mass concentration of serum immune globulin (Ig) A, IgG, and complement C3 were detected by enzyme-linked immunosorbent assay. Data were processed with Fisher's exact probability test, independent sample t test, analysis of variance for repeated measurement and Bonferroni correction, and Mann-Whitney U test. Results: (1) The blood glucose levels of children in the two groups were similar before and on the 3rd and 7th day of rhGH treatment (t=0.474, 1.652, 1.997, P>0.05). The glucose levels of children in group rhGH on the 3rd and 7th day of rhGH treatment [(6.9±1.0) and (7.7±1.1) mmol/L] were significantly higher than (5.9±0.9) mmol/L before rhGH treatment (P<0.05). The glucose level of children in control group on the 7th day of rhGH treatment was significantly higher than that before rhGH treatment (P<0.05). (2) The percentages of CD4(+) T lymphocytes of children in group rhGH before rhGH treatment and on the 7th day of rhGH treatment were (35.1±2.0)% and (38.5±2.2)%, which were close to (36.2±2.0)% and (33.6±2.2)% in control group, respectively (t=0.371, 1.553, P>0.05). The percentages of CD4(+) T lymphocytes of children in group rhGH on the 7th day of rhGH treatment[(44.7±2.2)%] was significantly higher than (36.5±2.2)% in control group (t=2.624, P<0.05). The percentage of CD4(+) T lymphocytes of children in group rhGH on the 7th day of rhGH treatment was significantly higher than that before rhGH treatment (P<0.05). The percentages of CD4(+) T lymphocytes of children in control group on the 3rd and 7th day of rhGH treatment were both close to the percentage before rhGH treatment (P>0.05). (3) The percentage of CD8(+) T lymphocytes of children in group rhGH on the 3rd day of rhGH treatment was significantly lower than that in control group (t=2.107, P<0.05). (4) The ratio of CD4(+) T lymphocytes to CD8(+) T lymphocytes of children in group rhGH on the 7th day of rhGH treatment (2.36±0.20) was significantly higher than 1.72±0.20 in control group (t=2.285, P<0.05). The ratio of CD4(+) T lymphocytes to CD8(+) T lymphocytes of children in group rhGH on the 7th day of rhGH treatment was significantly higher than 2.04±0.19 before rhGH treatment (P<0.05). (5) The percentages of CD3(+) T lymphocytes and CD19(+) B lymphocytes of children in the two groups were similar before and on the 3rd and 7th day of rhGH treatment (t=1.913, 0.552, 1.327, 1.465, 1.587, 0.407, P>0.05). The percentages of CD3(+) T lymphocytes of children in group rhGH on the 3rd and 7th day of rhGH treatment were significantly higher than the percentage before rhGH treatment (P<0.05). (6) The mass concentration of serum IgA, complement C3, and IgG of children in the two groups was similar before and on the 3rd and 7th day of rhGH treatment (t=-1.596, -0.100, 1.263, -0.220, 1.378, 1.631, Z=0.228, 0.519, 1.182, P>0.05). The mass concentration of serum IgA and complement C3 of children in group rhGH on the 3rd and 7th day of rhGH treatment was significantly higher than that before rhGH treatment(P<0.05). Conclusions: rhGH has little effect on humoral immunity of younger children with severe burn injuries with limited influence on CD19(+) B lymphocyte, mass concentration of serum IgA, IgG, and complement C3. It may improve the cellular immunity function mainly through promoting the release of CD4(+) T lymphocyte, reducing the release of CD8(+) T lymphocyte. It can be used in clinical treatment of younger children with severe burn injuries.

[Expression of gamma-aminobutyric acid type A receptor beta3 subunit in murine cleft palate induced by 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin].

Objective: To investigate the expression of gamma-aminobutyric acid type A receptor beta3 subunit (GABRB3) on cleft palate in C57BL/6J mice induced by 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD). Methods: Sixty C57BL/6J pregnant mice on gestation day (GD) 10.5 were divided into two groups: one group was administered through gastric tubes one dose of 28 µg/kg TCDD (experimental group) and the other group was administered through gastric tubes one dose of 5.6 ml/kg corn oil (control group). Embryos were removed by cesarean section from pregnant mice during the palatal formation stage (GD 13.5-17.5) and the palatal tissue studied in morphological and histological observation. The relative mRNA and protein expression of GABRB3 was measured by real-time quantitative PCR and Western blotting. Localization of GABRB3 protein was measured by immunohistochemistry or immunofluorescence. Results: The incidence of cleft palate at GD17.5 was 100% in experimental group and there was no cleft palate occurred in the control group (0); elevation of palatine processes in experimental group was completed on GD15.5 which was clearly delayed by a day compared with that in control group. On GD14.5-GD17.5, the mRNA expression (0.561±0.073, 0.728±0.104, 0.782±0.137, 0.686±0.145) and protein expression (0.288±0.013, 0.404±0.017, 0.399±0.012, 0.307±0.010) in the experimental group were significantly lower than the control group mRNA expression (0.818±0.088, 0.865±0.086, 1.021±0.054, 1.163±0.179) and protein expression (0.481±0.017, 0.456±0.009, 0.474±0.016, 0.529±0.015)(P<0.05). Immunohistochemistry and immunofluorescence showed that GABRB3 was mainly expressed in the mesenchymal cells and medial edge epithelium. Conclusions: TCDD delayed palatal shelf elevation and eventually led to cleft palate may be associated with a decrease in GABRB3. GABRB3 may play an important role in the elevation and fusion phases of the palate development.

Effect of rituximab combined with chemotherapy on the expression of serum exosome miR-451a in patients with diffuse large b-cell lymphoma.

OBJECTIVE: The aim of this study was to investigate the influence of rituximab combined with chemotherapy on the expression of serum exosome micro ribonucleic acid 451a (miR-451a) in patients with diffuse large B-cell lymphoma (DLBCL), and to explore the possible underlying mechanism. PATIENTS AND METHODS: 89 DLBCL patients (DLBCL group) receiving rituximab combined with chemotherapy were enrolled in this study. Meanwhile, 48 healthy controls (control group) were enrolled as well. Serum samples were collected from all patients before and after treatment, respectively. At the same time, blood samples of healthy people were collected, and serum exosome was extracted. Real-Time fluorescence-quantitative Polymerase Chain Reaction (qRT-PCR) was applied to measure the expression level of serum exosome miR-451a. Receiver operating characteristics (ROC) curve was used to evaluate the diagnostic efficiency of miR-451a. Statistical Product and Service Solutions (SPSS) 22.0 was employed for statistical analysis. Two-sided 95% confidence interval (CI) was used for all tests, and p<0.05 was considered statistically significant. RESULTS: The expression level of miR-451a in the DLBCL group was significantly lower than that of the control group. The area under the ROC curve (AUC) for the diagnostic efficacy of serum exosome miR-451a for DCBCL was 0.7147. After treatment, the level of serum exosome miR-451a in patients was significantly increased, whereas was still lower than the normal level. The AUC of ROC for evaluating the effect of serum exosome miR-451a in DCBCL was 0.8038. CONCLUSIONS: Serum exosome miR-451a has moderate diagnostic efficiency for DLBCL. Moreover, miR-451a can act as an indicator for evaluating the efficacy of rituximab combined with chemotherapy in the DLBCL treatment.

Sequential therapy with "vacuum sealing drainage-artificial dermis implantation-thin partial thickness skin grafting" for deep and infected wound surfaces in children.

OBJECTIVE: To evaluate the efficacy of a "vacuum sealing drainage (VSD) - artificial dermis implantation (ADI) - thin partial thickness skin grafting (TSG)" sequential therapy for deep and infected wounds in children. MATERIALS AND METHODS: Fifty-three pediatric patients with deep and infected wounds were treated with sequential VSD-ADI-TSG therapy. The efficacy of this treatment was compared with that of the surgical debridement-change dressings-thin partial thickness skin grafting previously performed on 20 patients. Survival of tissue grafts, color and flexibility, subcutaneous fullness and scar formation of the graft site were examined and compared. RESULTS: The sequential therapy combined the advantages of the VSD treatment, in reducing tissue necrosis and infection on the wound surfaces and promoting the growth of granulation tissue, with the enhancement of grafting by artificial dermis. Compared with the 20 controls, skin grafted on the artificial dermis was more smooth and glossy, while the textures of the region were more elastic, and the scars were significantly lighter in Vancouver scale. CONCLUSION: The sequential VSD-ADI-TSG therapy is a simple and effective treatment for children with deep and infected wounds. LEVEL OF EVIDENCE: IV.

[Comparison study between biological vision and computer vision].

The development and bearing of biology vision in structure and mechanism were discussed, especially on the aspects including anatomical structure of biological vision, tentative classification of reception field, parallel processing of visual information, feedback and conformity effect of visual cortical, and so on. The new advance in the field was introduced through the study of the morphology of biological vision. Besides, comparison between biological vision and computer vision was made, and their similarities and differences were pointed out.

[Geometrical dummy used for ergonomic evaluation on early stage cockpit conceptual design].

Objective. Basing on the need of cockpit ergonomic design, to set up a geometrical dummy. Method. Surface partition of the dummy, source of the curved face data, express of the curved face, degree of freedom of the human joint, coordinate system of the parts, position of the human segment centroid and weight of the human segment were cleared up first, then geometrical dummy was displayed with three-dimensional software. Result. The geometrical dummy could simulate some basic body movements and postures for ergonomic analysis. Conclusion. The geometrical dummy was suitable for present study and engineering design.

[A study on physical characteristics of porous plates for water sublimator].

Objective. To investigate the development method of porous plate, the key part of water sublimator, and its main physical characteristics. Method. Technical parameters of porous plates used in water sublimator were analyzed. On the basis of this, porous plates made of different materials were developed by making use of sintered powder technology. A tester for testing the physical characteristics of porous plate was designed. All around physical characteristic tests for porous plates were conducted. Result. Main factors affecting performance of porous plates were tested. These provided basis for performance test of sublimator, established porous plate criterion and optimized porous plate. Conclusion. Porous plates developed by making use of sintered powder technology could meet requirements of performance of water sublimator.

[Heat transfer analysis of liquid cooling garment used for extravehicular activity].

Brief description was given about the construction and function of the LCG (liquid cooling garment) used for EVA (extravehicular activity). The heat convection was analyzed between ventilating gas and LCG, the heat and mass transfer process was analyzed too, then a heat and mass transfer mathematical model of LCG was developed. Thermal physiological experimental study with human body wearing LVCG (liquid cooling and ventilation garment) used for EVA was carried out to verify this mathematical model. This study provided a basis for the design of liquid-cooling and ventilation system for the space suit.

Human movement characteristics of target acquisition.

Objective. This paper deals with the problem of human movement characteristics of target acquisition. Method. A hypothetical model was posed by using experimental data. Result. The conception of final target size was put forward, an equation for calculating the movement time of target acquisition was obtained, and a new definition of index of difficulty was given. Conclusion. Analysis of experimental data showed that this equation could give a better description of target acquisition in a wide range.

[Research progress of thermal control system for extravehicular activity space suit].

New research progress of thermal control system for oversea Extravehicular Activity (EVA) space suit is presented. Characteristics of several thermal control systems are analyzed in detail. Some research tendencies and problems are discussed, which are worthwhile to be specially noted. Finally, author's opinion about thermal control system in the future is put forward.

[The present status and development of thermal control system of spacesuits for extravehicular activity].

With the extension of extravehicular activity (EVA) duration, the need for more effective thermal control of EVA spacesuits is required. The specific schemes investigated in heat sink system for EVA are discussed, including radiator, ice storage, metal hydride heat pump, phase-change storage/radiator and sublimator. The importance and requirements of automatic thermal control for EVA are also discussed. Existed automatic thermal control for EVA are reviewed. Prospects of further developments of thermal control of spacesuits for EVA are proposed.