Tetrahedral DNA nanostructures synergize with MnO2 to enhance antitumor immunity via promoting STING activation and M1 polarization

Stimulator of interferon genes (STING) is a cytosolic DNA sensor which is regarded as a potential target for antitumor immunotherapy. However, clinical trials of STING agonists display limited anti-tumor effects and dose-dependent side-effects like inflammatory damage and cell toxicity. Here, we showed that tetrahedral DNA nanostructures (TDNs) actively enter macrophages to promote STING activation and M1 polarization in a size-dependent manner, and synergized with Mn2+ to enhance the expressions of IFN-β and iNOS, as well as the co-stimulatory molecules for antigen presentation. Moreover, to reduce the cytotoxicity of Mn2+, we constructed a TDN-MnO2 complex and found that it displayed a much higher efficacy than TDN plus Mn2+ to initiate macrophage activation and anti-tumor response both in vitro and in vivo. Together, our studies explored a novel immune activation effect of TDN in cancer therapy and its synergistic therapeutic outcomes with MnO2. These findings provide new therapeutic opportunities for cancer therapy.

Coating with flexible DNA network enhanced T-cell activation and tumor killing for adoptive cell therapy

Adoptive cell therapy (ACT) is an emerging powerful cancer immunotherapy, which includes a complex process of genetic modification, stimulation and expansion. During these

Lateral rectus abdominis approach combined with presacral decompression for old Denis type II sacral fractures complicated with upper sacral plexus injury / 中华创伤杂志

Objective:To investigate the clinical effect of lateral rectus abdominis approach combined with presacral decompression for surgical treatment of old Denis type II sacral fractures complicated with upper sacral plexus injury.Methods:A retrospective case series study was performed on the clinical data of 9 patients with old Denis type II sacral fractures complicated with upper sacral plexus injury (L 4-S 1) admitted to Zhongnan Hospital of Wuhan University from June 2010 to December 2016. There were 6 males and 3 females, aged (33.1±7.5)years (range, 15-58 years). Embolization of internal iliac artery and preimplantation of abdominal aortic balloon were performed 2 hours before operation under the guidance of digital subtraction angiography (DSA). Surgery was performed using a single lateral rectus abdominis approach combined with presacral decompression. The operation time, intraoperative blood loss and full weight-bearing time were recorded. The visual analogue scale (VAS) and European QOL Five Dimensional health scale (EQ-5D) were compared before and after operation. The Gibbons' impairment scale was used to assess neurological function. X-ray and CT scan were used to observe internal fixation and fracture healing. The complications during and after operation were recorded. Results:The patients were followed up for 24-52 months [(35.2±5.2)months]. The operation time was (2.9±0.6)hours. The intraoperative bleeding was (573±138)ml, and the full weight-bearing time was (11.6±1.2)weeks. X-ray and CT scan showed bone healing in all patients at the latest follow-up. The VAS and EQ-5D scale improved from preoperative (7.8±0.6)points and (0.34±0.07)points to the final follow-up of (0.8±0.3)points and (0.81±0.05)points ( P<0.05). According to Gibbons classification, 8 patients were grade I and 1 patient was grade II one year after operation ( P<0.01). Namely, the radiation pain of lower extremities was significantly improved in all patients, among which 8 patients showed pain disappeared and completely returned to normal and 1 patient showed residual numbness and hypoesthesia of the affected limbs. No major complications (eg, iatrogenic lumbosacral plexus injury, vital blood vessels or pelvic organs injury) occurred during the operation. During the follow-up period, only one patient developed traumatic hip arthritis and underwent total hip arthroplasty 6 months after operation. Fractures of the remaining patients were healed well without complications like infection, pressure ulcer or implant failure. Conclusions:For old Denis type II sacral fractures complicated with upper sacral plexus injury, lateral rectus abdominis approach combined with presacral decompression can fully decompress the upper sacral plexus nerve, relieve pain, and promote functional rehabilitation, with low incidence of complications. It is an alternative surgical method for the treatment of old Denis type II sacral fractures complicated with upper sacral plexus injury.

Lateral rectus abdominis approach versus posteromedian sacrum approach for unstable sacral fracture complicated with lumbosacral plexus injury / 中华创伤骨科杂志

Objective To compare the lateral rectus abdominis approach versus posteromedian sacrum approach in the surgical treatment of unstable sacral fracture complicated with lumbosacral plexus injury.Methods From June 2010 to December 2014,33 unstable sacral fractures complicated with lumbosacral plexus injury were treated at Department of Orthopaedics,Spinal and Pelvic Surgery Center,Zhongnan Hospital.Of them,24 were fresh and 9 obsolete.The lateral rectus abdominis approach was adopted in 17 patients and the posteromedian sacrum approach in 16.All the patients received surgical treatment within 2 to 12 weeks (average,4.5 weeks) after injury.The 2 groups were compared in terms of operation time,bleeding volume,complications,weight-bearing time,visual analogue scale (VAS),European QOL Five Dimensional health scale (EQ-5D) and lumbosacral injury classification and severity scale (LSICS).Results The 2 groups were compatible due to their insignificant differences in baseline data (P ＞ 0.05).Their follow-up time ranged from 17 to 37 months (average,26.8 months).Perioperatively,infection and necrosis of the lumbosacral incision appeared in 2 patients and iatrogenic injury to the lumbosacral plexus in 3 patients.All the other incisions healed well without major complications like infection,pressure ulcer or implant failure.There were no significant differences between the 2 groups in operation time (235.8± 72.0 minutes versus 318.0 ± 64.7 minutes),intraoperative bleeding volume (558.8 ± 125.7 mL versus 734.0 ±98.0 mL),weight-bearing time (9.4 ±2.4 weeks versus 11.3 ±2.3 weeks),postoperative complications,VAS(1.1 ±0.6 points versus 1.0 ±0.6 points),EQ-5D (0.82 ±0.09 points versus 0.78 ±0.06 points) or LSICS (P ＞ 0.05).The final follow-ups revealed significant improvements in VAS,EQ-5D and LSICS in all the patients (P ＜ 0.05).Conclusion The lumbosacral plexus can be well decompressed via both the lateral rectus abdominis approach and the posteromedian sacrum approach,leading to satisfactory clinical outcomes.

The application of CAR-T cell therapy in hematological malignancies: advantages and challenges

Chimeric antigen receptor T cell (CAR-T cell) therapy is a novel adoptive immunotherapy where T lymphocytes are engineered with synthetic receptors known as chimeric antigen receptors (CAR). The CAR-T cell is an effector T cell that recognizes and eliminates specific cancer cells, independent of major histocompatibility complex molecules. The whole procedure of CAR-T cell production is not well understood. The CAR-T cell has been used predominantly in the treatment of hematological malignancies, including acute lymphoblastic leukemia, chronic lymphocytic leukemia, lymphoma, and multiple myeloma. Solid tumors including melanoma, breast cancer and sarcoma offer great promise in CAR-T cell research and development. CD19 CAR-T cell is most commonly used, and other targets, including CD20, CD30, CD38 and CD138 are being studied. Although this novel therapy is promising, there are several disadvantages. In this review we discuss the applications of CAR-T cells in different hematological malignancies, and pave a way for future improvement on the effectiveness and persistence of these adoptive cell therapies.

Applications of one-stage total spondylectomy by anterior and posterior approaches for solitary plasmacytoma of cervical spine / 中国修复重建外科杂志

Objective: To investigate the feasibility of one-stage total spondylectomy by anterior and posterior approaches for treating solitary plasmacytoma (SP) of cervical spine.

Medical education reform and practice under the background of holistic integrated medicine / 中华医学教育探索杂志

With the development of specialization and specialist differentiation of modem medicine,the developing mode of "reducing and specializing" has promoted the explosive growth of medical knowledge.Meanwhile,the medical practice based on medical knowledge is being fragmented,and medical activities are gradually moving away from the'people-oriented'core value.Therefore,current medical modality needs to be transformed into a "holistic medicine" stage,which also requires reforms of medical personnel cultivation,including the emphasizes of holistic view as well as multidisciplinary integration.Medical schools are exploring paths to achieve holistic medicine-oriented education and training of students.Currently,the concept of holistic medicine have begun to permeate in medical curriculum design and teaching method innovationand yet needs to befurther deepened in understanding and practicing the essence of the holistic medical modality in the future.

Research progress concerning the sinus tarsal approach for treatment of calcaneal fractures / 中华创伤骨科杂志

Treatment of calcaneal fractures has always been the focus of many clinical researchers.The goals of traditional surgical treatment are not only to restore the integrity of calcaneal articular surface but also to reconstruct the anatomy of the calcaneus.More importantly,we need to reduce postoperative soft tissue swelling and incidence of postoperative complications.In recent years,scholars have reported satisfactory clinical efficacy and prognosis resulting from a sinus tarsal approach for treatment of calcaneal fractures.This paper reviews the latest research progress concerning the sinus tarsal approach for treatment of calcaneal fractures at home and abroad,intending to provide helpful information for the clinical surgeons.

Treatment research and new progress of early-onset scoliosis / 中国组织工程研究

BACKGROUND:Early-onset scoliosis is a kind of disease that seriously affects the growth of children’s spine and development of cardiorespiratory function. The treatment of the disease has always been the focus of many clinical researchers.OBJECTIVE:To analyze the therapy for early-onset scoliosis and explore the spinal fusion, spinal non-fusion, conventional growth rod technology and magnetic control ed growth rod technology of early-onset scoliosis. METHODS:We retrieved PubMed, CENTRAL, EMbase, the ISI Web of Knowledge Databases, VIP, CNKI, CBM and Wanfang Database for related studies published from inception of the database to March 2016. The key words were“scoliosis, growing rod, complications”. The included 54 studies were analyzed and discussed. RESULTS AND CONCLUSION:For these children of early-onset scoliosis, we should not only maintain the correction of spine deformities, but also protect the ability of spine growth, keeping the normal cardiopulmonary function. In addition to conventional (non-surgical) treatment, there are surgical treatment (such as spinal fusion and growing rod technique) and magnetical y control ed growing rod, a new technology for the treatment of early-onset scoliosis. A comprehensive understanding of the effect of surgical treatment on the spine growth and cardiopulmonary function of children with early-onset scoliosis wil help to prevent the occurrence of related complications, so as to obtain a better therapeutic effect.

Alterations of CD4+CD8+T cells in peripheral blood of patients with tuberculosis and its clinical sig- nificance / 中华微生物学和免疫学杂志

Objective To characterize CD4+CD8+double-positive T ( DPT) cells in PBMCs from patients with tuberculosis(TB).Methods PBMCs were isolated from peripheral blood samples collected from patients with TB and healthy subjects.The subsets and percentages of CD4+T, CD8+T and DPT cells in PBMCs were determined by flow cytometry.Cell surface markers ( CD45RO, CCR7 and CD25 ) and intracellular cytokines ( IFN-γand TNF-α) were detected directly and after ESAT-6/PPD stimulation.Re-sults Patients with TB showed a significantly increased DPT cells as compared with the cured individuals and healthy subjects (P<0.005).The levels of DPT cells were gradually decreased down to normal upon the treatment of pharmacotherapy.DPT cells expressed higher levet of CD25 than CD4+T and CD8+T cells ( P<0.005 ) . DPT cells could express more IFN-γand TNF-αupon the stimulation of ESAT-6/PPD (P<0.005).The analysis of memory phenotype indicated that DPT cells were memory T cells.Conclusion DPT cells in peripheral blood of the patients with tuberculosis played a critical role in protective immunity against tuberculosis.The alterations of DPT cells in PBMCs during the period of pharmacotherapy might be a potential indicator for the prognosis of pulmonary tuberculosis.

Establishment and application of a tandem affinity purification system of innate immune regulatory protein PKR / 中华微生物学和免疫学杂志

Objective To establish a tandem affinity purification(TAP) system of innate immune-regulatory protein PKR and analyze PKR function, for the future screen and identification of novel PKR-interaction proteins. Methods PKR gene was amplified by PCR, and then cloned into a mammalian expression vector pcTAP-A. Recombinant pcTAP-PKR was transfected into PKR knock-down(PKRkd) HeLa cells by LipofectAMINE 2000,and the PKR overexpressed HeLa cells were harvested for mitogen-activated protein kinases(MAPK) activation analysis. Cell extracts of PKR overexpressed cells were purified using TAP kit and examined by Western blot. Results Cal modulin resin(CBP) and streptavidin resin(SBP) tagged PKR was detected in PKRkd HeLa cells as early as 24 h upon transfection with pcTAP-PKR, and its expression decreased at later time points. The overexpression of PKR was autophosphorylated, and thus involved in the regulation of MAPK actviation. After small-scale TAP kit purification, PKR protein was detectable by Western blot. Conclusion We have successfully established a TAP system that over-expresses functional PKR, providing a useful tool for the future study on the identification of PKR interacting proteins.