Lenalidomide Enhances CAR-T Cell Activity Against Solid Tumor Cells.

Chimeric antigen receptor (CAR) T-cell immunotherapy still faces many challenges in the treatment of solid tumors, one of which is T-cell dysfunction or exhaustion. Immunomodulator lenalidomide may improve CAR T-cell function. In this study, the effects of lenalidomide on CAR T-cell functions (cytotoxicity, cytokine secretion, and cell proliferation) were investigated. Two different CAR T cells (CD133-specific CAR and HER2-specific CAR) were prepared, and the corresponding target cells including human glioma cell line U251 CD133-OE that overexpress CD133 and human breast cancer cell line MDA-MB-453 were used for functional assay. We found that lenalidomide promoted the killing of U251 CD133-OE by CD133-CAR T cells, the cytokine secretion, and the proliferation of CD133-CAR T cells. Lenalidomide also enhanced the cytotoxicity against MDA-MB-453 and the cytokine secretion of HER2-CAR T cells but did not affect their proliferation significantly. Furthermore, lenalidomide may regulate the function of CAR T cells by inducing the degradation of transcription factors Ikaros and Aiolos.

Galunisertib enhances chimeric antigen receptor-modified T cell function.

Chimeric antigen receptor (CAR) T cell therapy still faces the challenge of immunosuppression when treating solid tumors. TGF-ß is one of the critical factors in the tumor microenvironment to help tumors escape surveillance by the immune system. Here we tried using the combination of a small molecule inhibitor of TGF-ß receptor I, Galunisertib, and CAR T cells to explore whether Galunisertib could enhance CAR T cell function against solid tumor cells. In vitro experiments showed Galunisertib could significantly enhance the specific cytotoxicity of both CD133- and HER2-specific CAR T cells. However, Galunisertib had no direct killing effect on target cells. Galunisertib significantly increased the cytokine secretion of CAR T cells and T cells that do not express CAR (Nontransfected T cells). Galunisertib did not affect the proliferation of T cells, the antigen expression on target cells and CD69 on CAR T cells. We found that TGF-ß was secreted by T cells themselves upon activation, and Galunisertib could reduce TGF-ß signaling in CAR T cells. Our findings can provide the basis for further preclinical and clinical studies of the combination of Galunisertib and CAR T cells in the treatment of solid tumors.

Dynamic changes and characterization of the protein and carbohydrate fractions of native grass grown in Inner Mongolia during ensiling and the aerobic stage.

OBJECTIVE: To improve the utility of native grass resources as feed in China, we investigated the dynamics of protein and carbohydrate fractions among Inner Mongolian native grasses, during ensiling and the aerobic stage, using the Cornell Net Carbohydrate and Protein System. METHODS: Silages were prepared without or with lactic acid bacteria (LAB) inoculant. We analyzed the protein and carbohydrate fractions and fermentation quality of silages at 0, 5, 15, 20, 30, and 60 d of ensiling, and the stability at 0.5, 2, 5, and 10 d during the aerobic stage. RESULTS: Inner Mongolian native grass contained 10.8% crude protein (CP) and 3.6% water-soluble carbohydrates (WSC) on a dry matter basis. During ensiling, pH and CP and WSC content decreased (p<0.05), whereas lactic acid and ammonia nitrogen (N) content increased (p<0.05). Non-protein N (PA) content increased significantly, whereas rapidly degraded true protein (PB1), intermediately degraded true protein (PB2), total carbohydrate (CHO), sugars (CA), starch (CB1), and degradable cell wall carbohydrate (CB2) content decreased during ensiling (p<0.05). At 30 d of ensiling, control and LAB-treated silages were well preserved and had lower pH (<4.2) and ammonia-N content (<0.4 g/kg of fresh matter [FM]) and higher lactic acid content (>1.0% of FM). During the aerobic stage, CP, extract ether, WSC, lactic acid, acetic acid, PB1, PB2, true protein degraded slowly (PB3), CHO, CA, CB1, and CB2 content decreased significantly in all silages, whereas pH, ammonia-N, PA, and bound true protein (PC) content increased significantly. CONCLUSION: Control and LAB-treated silages produced similar results in terms of fermentation quality, aerobic stability, and protein and carbohydrate fractions. Inner Mongolian native grass produced good silage, nutrients were preserved during ensiling and protein and carbohydrate losses largely occurred during the aerobic stage.

Health literacy of COVID-19 and its associated factors in Inner Mongolia Autonomous Region / 中华健康管理学杂志

Objective:To investigate the status of Corona Virus Disease 2019 (COVID-19) health literacy and associated factors in Inner Mongolia Autonomous Region.Methods:Based on the multi-stage stratified sampling method, the questionnaire survey of health literacy of COVID-19 were carried out in 55 599 local residents from12 prefecture-level cities of Inner Mongolia Autonomous Region between March 10 and 15, 2020. The questionnaire in details included not only knowledge, attitude and behavior, but also mental health, their scores were calculated using Decimal method. A ≥80% of the correct answer rate of the survey content was regarded as qualified for health literacy. There were 51 722 (93.0%) valid questionnaires, according to the ratio of medical staff to non-medical staff, 32 529 questionnaires were selected for analysis. The health literacy level was defined according to the proportion of qualified people.The credibility and availability of the questionnaires were evaluated by Cronbach′s α coefficient and KMO test. The associated factors were analyzed by Pearson χ 2 test and logistic regression. Results:In Inner Mongolia Autonomous Region, the whole level of health literacy of COVID-19 was 85.7%, and their scores were (26.30±2.48). Knowledge, attitude, and behavioral literacy levels were 61.6%, 95.6%, and 96.8%, respectively. Compared with the population of 15-25 years old, the health literacy level of 46-65 years old was the highest ( OR=2.00, 95% CI: 1.78-2.24). The health literacy level of medical staff group ( OR=2.54, 95% CI: 1.30-4.95) was far higher than the non-medical staff group; the population with college or above education level ( OR=10.22, 95% CI: 9.19-11.36) was significantly higher than the population with education level below college. The degree of anxiety was negatively correlated with education level. Conclusions:The health literacy level of COVID-19 in residents in Inner Mongolia Autonomous Region is relatively high, but the level of knowledge literacy needs to be improved. The main factors affecting the health literacy of COVID-19 among Inner Mongolia residents are age, occupation and education level.

Association between blood lipid indices and bone mineral density in a physical examination population / 中华健康管理学杂志

Objective This study aimed to explore the association between blood lipid indices and bone mineral density (BMD).Methods A total of 2,396 individuals (1 198 males and 1 198 females,average age 55.24±12.12 years) who underwent physical examination between April 2015 and April 2016 at the medical examination center of the Inner Mongolia Autonomous Region People's Hospital were recruited.The blood lipid indices,including high-density lipoprotein cholesterol (HDL-C),low-density lipoprotein cholesterol (LDL-C),total cholesterol (TC),and triglycerides,were collected,and BMD at the total hip and its sub-regions was measured.The association between lipid indices and BMD was analyzed using SPSS 16.0 software,with adjustment for the covariates of age,sex,height,and weight.The association between blood lipid indices and BMD was then tested by linear regression analysis.Results Regression analysis demonstrated that in the combined sample with both sexes,HDL-C was negatively associated with total and sub-region BMD (regression coefficients,-0.11 to-0.06;all P＜0.01).LDL-C was negatively associated with femur neck BMD (regression coefficient,-0.01;P=0.01) and Ward's triangle BMD (regression coefficient,-0.01;P＜0.01).TC was negatively associated with trochanter BMD,femoral neck BMD,and Ward's triangle BMD (beta coefficients,-0.02 to-0.01;P＜0.05).In the female group,TC was positively associated with trochanter BMD (regression coefficient,0.06;P＜0.01).In the male group,both LDL-C and TC were negatively associated with femoral neck BMD (regression coefficients,-0.05 and-0.04,respectively;P＜0.05).Conclusion While blood lipid indices are associated with sub-region and total hip BMD,the association pattern and magnitude vary according to body region and sex.

Growth performance, apparent digestibility, and N balance in Mongolian lambs and hoggs fed diets supplemented with a Chinese traditional herbal medicine complex.

We evaluated the effects of dietary supplementation with Chinese traditional herbal medicine (CTHM) on the growth performance, apparent digestibility, and nitrogen balance in Mongolian lambs and hoggs. The CTHM used as a dietary supplement consisted of 30% pine needles, 20% mugwort, 40% garlic, and 10% Astragalus mongholicus on a dry matter (DM) basis. The basal diet was prepared from corn stover, corn grain, wheat bran, rapeseed meal, shell meal, dicalcium phosphate, salt, vitamin premix, and mineral premix. In total, 16 Mongolian lambs (20.75 kg initial body weight [BW]) and 16 hoggs (33.81 kg initial BW) were allocated randomly to one of two treatments, the basal diet without and with CTHM, with the group receiving CTHM fed 98.5% basal diet + 1.5% CTHM complex on a DM basis. Lamb and hogg growth trials showed that CTHM supplementation improved the final live weight, gain, and feed conversion ratio (p < 0.01). A digestibility trial showed that the diet with CTHM improved the digestibility of DM, organic matter (OM), crude protein (CP), and neutral detergent fiber in lambs and hoggs. Finally, CTHM supplementation decreased (p < 0.0001) fecal and urinary nitrogen and increased (p = 0.0004) nitrogen (N) retention. Overall, the addition of CTHM to the diets of lambs and hoggs has beneficial effects on growth.

Bone regeneration effects of platelet-rich fibrin used alone in sinus floor elevation / 中国组织工程研究

BACKGROUND: As a blood concentrate rich in growth factors and fibrin, platelet-rich fibrin (PRF) is able to significantly promote bone regeneration. PRF mixed with bone substitutes is commonly used to repair bone defects in oral maxillofacial region. But it remains controversial whether PRF as a sole material in sinus floor elevation can produce enough new bone tissues.OBJECTIVE: To evaluate the osteogenic potential of PRF as a sole grafting material in sinus floor elevation by means of an animal model.METHODS: Twelve healthy adult mongrel dogs aged 12-18 months were selected and randomized into three groups (groups A, B and C), with four dogs in each group. Upper first molars on both side of each dog were extracted 12 weeks prior to sinus floor elevation and simultaneous implants placement. Different materials were used to fill in the space between the sinus membrane and implant. Groups A, B and C were filled with PRF, autologus bone particles and autologus blood clot respectively. After 12 weeks, specimens were harvested to analyze the new bone formation by gross observation, X-ray examination and histological evaluation.RESULTS AND CONCLUSION: New bone formation was found to embrace all the implants close to the bony sinus floor, and the tips of all implants were free from bone coverage. The new bone height of groups A, B and C were (3.135±0.288),(3.218±0.345), and (1.898±0.157) mm, respectively. The new bone density of groups A, B and C were (65.06±5.88),(75.34±8.18), and (56.92±4.95) g/cm3, respectively. There were significant differences between the new bone height in groups A and C as well as in groups B and C (P < 0.05). Also, significant differences were found between the new bone density in groups A and B, B and C, A and C (P < 0.05). Within the confine of this experiment, it is feasible to use PRF as a sole grafting material in the sinus floor elevation to generate new bone, but the new bone volume is limited.

The relationship between adipocyte fatty acid binding protein and lower limb vascular disease in the elderly with type 2 diabetes / 中华老年医学杂志

Objective To explore the relationship between adipocyte fatty acid binding protein (A-FABP) and lower limb vascular disease (LLVD) in the elderly with type 2 diabetes(T2DM).Methods Bilateral lower limb vessels were checked by the High Resolution Color Doppler in all the subjects,including 40 healthy subjects as control (group A),126 T2DM patients.42 T2DM patients had no LLVD (group B),40 had mild LLVD (group C),and 44 had severe LLVD (group D).The levels of plasma A-FABP,blood glucose,lipid profiles,HOMA-IR,hypersensitive C reactive protein (hs CRP),and e-glomerular filtration rate were determined.Results The levels of plasma A-FABP were in the following ascending order of group A(4.5± 1.7)μg/L＜group B(6.1±2.1)μg/L＜group C (7.2 ± 2.3)μg/L ＜ group D (8.4 ± 3.2)μg/L (P＜ 0.01).A-FABP levels elevated along with the decrease of ABI and the increase of L IMT.Multiple logistic regression analysis showed that A FABP levels was main influencing factor of lower limb vascular disease (LLVD) in the elderly with type 2 diabetes.LDL C,HbA1c,HOMR-IR,hs-CRP were the predictive factors for the plasma A-FABP levels in the elderly with T2DM after multiple stepwise regression analysis.Conclusions For elder T2DM patients,the level of plasma A FABP is correlated with the degree of LLVD,and plays an important role in the progress of LLVD.