Search

Abstract Immunodeficient mice engrafted with either normal or cancerous human cells are widely used in basic and translational research. In particular, NOD/SCID/IL2rg−/− mice can support the growth of various types of human cancer cells. However, the hairs of these mice interfere with the observation and imaging of engrafted tissues. Therefore, novel hairless strains exhibiting comparable immunodeficiency would be beneficial. Recently, the CRISPR/Cas9 system has been used for efficient multiplexed genome editing. In the present study, we generated a novel strain of nude NOD/SCID/IL2rg−/− (NSIN) mice by knocking out Foxn1 from NOD/SCID/IL2rg−/− (NSI) mice using the CRISPR/Cas9 system. The NSIN mice were deficient in B, T, and NK cells and not only showed impaired T cell reconstitution and thymus regeneration after allogeneic bone marrow nucleated cell transplantation but also exhibited improved capacity to graft both leukemic and solid tumor cells compared with NSI, NOG, and NDG mice. Moreover, the NSIN mice facilitated the monitoring and in vivo imaging of both leukemia and solid tumors. Therefore, our NSIN mice provide a new platform for xenograft mouse models in basic and translational research.

In recent years, immunotherapies, such as those involving chimeric antigen receptor (CAR) T cells, have become increasingly promising approaches to non-small-cell lung cancer (NSCLC) treatment. In this study, we explored the antitumor potential of prostate stem cell antigen (PSCA)-redirected CAR T and mucin 1 (MUC1)-redirected CAR T cells in tumor models of NSCLC. First, we generated patient-derived xenograft (PDX) mouse models of human NSCLC that maintained the antigenic profiles of primary tumors. Next, we demonstrated the expression of PSCA and MUC1 in NSCLC, followed by the generation and confirmation of the specificity and efficacy of PSCA- and MUC1-targeting CAR T cells against NSCLC cell lines in vitro. Finally, we demonstrated that PSCA-targeting CAR T cells could efficiently suppress NSCLC tumor growth in PDX mice and synergistically eliminate PSCA+MUC1+ tumors when combined with MUC1-targeting CAR T cells. Taken together, our studies demonstrate that PSCA and MUC1 are both promising CAR T cell targets in NSCLC and that the combinatorial targeting of these antigens could further enhance the antitumor efficacy of CAR T cells.

Abstract Background Bone cement distribution is an important factor affecting pain relief and long-term prognosis of osteoporotic vertebral compression fracture (OVCF) treated with vertebral augmentation. Unilateral percutaneous kyphoplasty (PKP) is the most common procedure, and insufficient bone cement distribution is more common than bilateral PKP. However, effective remedies are remain lack. In this study, sufficient cement distribution was achieved by adjusting the working channel followed by second cement injection as a remedy in cases with insufficient cement distribution, and the purpose was to evaluate the clinical outcomes by a retrospective cohort study. Methods From July 1, 2017 to July 31, 2020, OVCF patients treated with unilateral PKP were included in this retrospective cohort study. According to the bone cement distribution (insufficient cement distribution was confirmed when the cement did not exceed the mid line of the vertebral body in frontal film or/and the cement did not contact the upper/lower vertebral endplates in the lateral film.) and whether second injection was performed during surgery, the patients were divided into three groups. Insufficient group: patients with insufficient cement distribution confirmed by fluoroscopy or postoperative x-ray. Second injection group: patients with insufficient cement distribution was found during the procedure, and second injection was performed to improve the cement distribution. Control group: patients with sufficient cement distribution in one injection. The Primary outcome was cemented vertebrae re-collapse rate. The secondary outcomes included operative time, radiation exposure, cement leakage rate, VAS, ODI, and adjacent vertebral fracture rate. Results There are 34 cases in insufficient group, 45 cases in second injection group, and 241 cases in control group. There was no significant difference in baseline data and follow-up time among the three groups. Primary outcome: The injured vertebrae re-collapse rate of insufficient group was significantly higher than that of second injection group (42.22% vs 20.59%, P = 0.000) and control group (42.22% vs. 18.26%, P = 0.000). Kaplan–Meier survival analysis showed that there was no significant difference in the survival time between second injection group and control group (P = 0.741, Log-rank test), both of which were significant less than that in insufficient group (P = 0.032 and 0.000, respectively). Secondary outcomes: There was no significant difference in VAS score and ODI after operation between second injection group and control group, both of which were superior to those in insufficient group (P = 0.000). At the final follow-up, there was no significant difference in VAS and ODI among the three groups (P > 0.05). The operation time of second injection group was significantly higher than that of insufficient group (53.41 ± 8.85 vs 44.18 ± 7.41, P = 0.000) and control group (53.41 ± 8.85 vs 44.28 ± 7.22, P = 0.000). The radiation exposure of the second injection group was significantly higher than that of insufficient group (40.09 ± 8.39 vs 30.38 ± 6.87, P = 0.000) and control group (40.09 ± 8.39 vs 31.31 ± 6.49, P = 0.000). The cement leakage rate of second injection group (20.59%) was comparable with that of insufficient group (24.44%) and control group (21.26%) (P = 0.877). The length of hospital stay of the second injection group (4.38 ± 1.72) was comparable with that of insufficient group (4.18 ± 1.60) and control group (4.52 ± 1.46) (P = 0.431). Conclusions When cement distribution is insufficient during unilateral PKP, second injection may relieve early pain, reduce the incidence of cemented vertebral re-collapse and adjacent vertebral fracture, without increasing the cement leakage rate, although this procedure may increase the operation time and radiation exposure.

Purpose To compare the clinical efficacy of percutaneous functional spinal unit cementoplasty (PFSUP) and posterior spinal fixation combined with vertebroplasty (PSF + VP) for the treatment of symptomatic chronic osteoporotic vertebral fractures (SCOVFs). Method Thirty-one patients with SCOVFs were included in this retrospective study and divided into PFSUP (n = 14) and PSF + VP (n = 17) groups. Visual analog scores (VAS) and Oswestry Disability Index (ODI) were recorded before and after surgery and at the last follow-up. Besides, the local kyphosis angle (LKA) and sagittal vertical axis (SVA) were measured. The operation duration, number of X-ray exposures, amount of blood loss, bed rest duration, hospitalization duration, and presence of complications were recorded. Result The VAS, ODI, LKA, and SVA after surgery and at the last follow-up were significantly improved in both groups compared to preoperative measurements. The PFSUP group experienced shorter operation duration (78.2 ± 13.1 vs. 124.7 ± 14.7, p

Objective: To assess the efficacy, bleeding pattern, cycle control and safety of a combined oral contraceptive (YAZ) containing drospirenone 3 mg and ethinylestradiol 20 µg in a 24+4-day regimen in China., Methods: This is a multi-center, open, one-label study. Healthy females aged 18-45 years received YAZ for 13 cycles. Following-ups were scheduled during the treatment phase on Day 12-19 of Cycle 1, 4, 7 and 10 and 10-17 days after completing the study. The efficacy variables were the number of unintended pregnancies, bleeding pattern and cycle control. The safety variables were adverse events (AE), lab examinations, physical and gynecological examinations, vital signs and body weights and questionnaires., Results: Four pregnancies occurred among 675 women for 603.78 women-years, resulting in a Pearl index (PI) of 0.7 and adjusted PI of 0.6. The cumulative 1-year pregnancy rate was 0.66%. The mean number of bleeding/spotting days was (26.3 ± 12.4) days in reference period 1 and (15.4 ± 5.5) days in reference period 4. 94.2% (582/618)- 96.8% (538/558) subjects experienced scheduled bleeding. The mean duration of scheduled bleeding decreased from (5.9 ± 3.2) to (5.0 ± 1.6) days. The percentage of women with intermenstrual bleeding decreased from 14.5% (90/621) at Cycle 1 to 2.3% (13/558) at Cycle 12. The common AE relating treatment include nausea (3.4%, 23/675), breast tenderness (1.2%, 8/675), dizzy (1.2%), vagina bleeding (1.2%). No serious AE relating treatment occurred. 85.6% (542/633) subjects were satisfied or very satisfied with the study treatment., Conclusion: YAZ is highly effective, acceptable and safe for Chinese women.