N-acetyl-p-aminophenol （APAP） is an antipyretic analgesic commonly used in clinical practice， and APAP overdose can cause severe liver injury and even death. In recent years， the incidence rate of APAP-induced liver injury （AILI） tends to increase， and it has become the second most common cause of liver transplantation worldwide. Autophagy is a highly conserved catabolic process that removes unwanted cytosolic proteins and organelles through lysosomal degradation to achieve the metabolic needs of cells themselves and the renewal of organelles. A large number of studies have shown that autophagy plays a key role in the pathophysiology of AILI， involving the mechanisms such as APAP protein conjugates， oxidative stress， JNK activation， mitochondrial dysfunction， inflammatory response and apoptosis. This article elaborates on the biological mechanism of autophagy in AILI， in order to provide a theoretical basis for the treatment of AILI and the development of autophagy regulators.

The incidence rate of drug-induced liver injury （DILI） is increasing year by year with unknown mechanisms， and the treatment methods for DILI mainly include drugs， liver support systems， and liver transplantation， all of which have certain limitations. Therefore， the search for safer and more effective treatment methods has become a research hotspot at present. Studies have shown that mesenchymal stem cells and their exosomes can alleviate liver injury by reducing liver inflammation， promoting hepatocyte proliferation and regeneration， inhibiting the apoptosis of hepatocytes， improving oxidative stress， and regulating immunity. This article briefly reviews the role of mesenchymal stem cells and their exosomes in the treatment of DILI， so as to provide a reference for further research.

Autoimmune hepatitis(AIH)is a type of chronic hepatitis caused by the attack of hepatocytes by the autoimmune system,and with the prolongation of disease course,it may gradually progress to liver cirrhosis and even hepatocellular carcinoma.Although great achievements have been made in the understanding and treatment of AIH,its etiology and pathogenesis still remain unclear.T cells play a crucial role in the development and progression of AIH,and by focusing on follicular helper T cells,this article elaborates on the research advances in follicular helper T cells in AIH,in order to provide new ideas and strategies for the clinical treatment of AIH.

Objective To observe the value of isotropic volumetric MRI for displaying perineural spread(PNS)of cranial nerve(CN)in nasopharyngeal carcinoma.Methods Eighty-seven patients with pathologically proven nasopharyngeal carcinoma were prospectively enrolled.MR scanning,including three-dimensional liver acquisition with volume acceleration-flexible(3D LAVA_Flex)image,T2WI with fat suppression(T2WI-FS),T1WI,contrast enhancement(CE)T1WI-FS of nasopharynx and neck region were performed.The displaying rates of CN PNS were evaluated and compared between 3D LAVA Flex and T2WI-FS,T1WI,CE-T1WI-FS at patient level,CN group level and neural level,respectively.Results The displaying rate of CN PNS in all 87 nasopharyngeal carcinoma patients by 3D LAVA_Flex sequence was 49.43％(43/87),higher than that of conventional MRI(30/87,34.48％,P=0.001).Among 59 patients with advanced nasopharyngeal carcinoma diagnosed with conventional sequences,the displaying rate of CN PNS was 71.19％(42/59)by 3D LAVA-Flex sequence,higher than that of conventional MRI(30/59,50.85％,P=0.001).At both patient level and posterior CN level,significant differences of the displaying rate of CN PNS were found between 3D LAVA-Flex sequence and T2WI-FS,T1WI,CE-T1WI-FS,while at CN level,the displaying rates of mandibular nerve PNS,CN Ⅸ-Ⅺ PNS in jugular foramen(P＜0.05)and CN Ⅸ-Ⅻ PNS in carotid space of 3D LAVA_Flex sequence were all significantly higher than that of T2WI-FS,T1WI and CE-T1WI-FS(all P＜0.05),of PNS of CN Ⅲ-Ⅴ in cavernous sinus were higher than that of T2WI-FS(P＜0.05),while of PNS of hypoglossal nerve were significantly higher than that of T2WI-FS and T1WI(both P＜0.05).Conclusion 3D LAVA_Flex sequence could be used to effectively display CN PNS of nasopharyngeal carcinoma.

Following concerted efforts for over 7 decades, great achievements have been gained in the national schistosomiasis control program of China. Currently, China is moving towards the stage of schistosomiasis elimination, when the major task is to make full use of available resources to improve schistosomiasis surveillance and response to sustainably consolidate gained schistosomiasis control achievements and prevent re-emerging schistosomiasis. There is therefore an urgent need for optimization of interventions for schistosomiasis elimination. Based on analysis of socioeconomic features at different stages of the national schistosomiasis control program in China, this review discusses the relationship between the needs of assessment of schistosomiasis elimination interventions and the optimized strategy of schistosomiasis elimination at different stages of the national schistosomiasis control program using a marginal benefit approach and proposes the optimized schistosomiasis elimination strategy that allows the highest marginal benefit with currently available schistosomiasis elimination costs, so as to provide the optimal strategic pathway to schistosomiasis elimination and facilitate the achievement of the targets set in Healthy China 2030.

Programmed death-1 and programmed death-ligand 1(PD-1/PD-L1)are regulatory immune checkpoint molecules that inhibit T cell activation and,therefore,play an important role in tumor immunotherapy.In recent years,increasing numbers of targeted therapeutic agents have been developed,but single immune checkpoint blockers cannot completely inhibit tumor occurrence,and tumor escape sporadically occurs.Consequently,combination therapy of targeted drugs is considered a useful method to inhibit tumorigenesis and tumor development.T cell immunoglobulin and immunoreceptor tyrosine-based inhibition motif(ITIM)domain(TIGIT)is an inhibitory type 1 poliovirus receptor that has recently been a hotspot of targeted drug therapy research.It has been shown that the combination therapy of TIGIT plus PD-1/PD-L1 can reduce tumor escape and inhibit tumorigenesis more effectively.Therefore,this review summarizes and discusses the progress on the dual blockade of TIGIT and PD-1/PD-L1 pathways in tumor immunotherapy to provide a theoretical basis for tumor im-munotherapy.

Objective:To design 3D printed prosthesis in an individualized way and explore the short-term clinical efficacy of reconstruction of segmental defect after resection of bone tumor in lower extremities with 3D-printed prosthesis.Methods:From January 2017 to June 2019, 6 patients with lower limb bone tumor who met the inclusion criteria were recruited, including 3 males and 3 females, aged 8.67±1.11 years (range 6-11 years). All 6 cases were primary bone tumors, and the Enneking stages were all IIB, including 3 cases of left tibial tumors, 2 cases of right tibial tumors, and 1 case of right femoral tumor. These 3D-printed prostheses were designed based on the preoperative imaging data. The mechanical stability of the prosthesis was evaluated by three-dimensional finite element analysis. After tumor resection, the 3D-printed prosthesis was installed and fixed to reconstruct the segmental bone defect. All patients were clinically followed up and evaluated by imaging regularly after operation. The functional status was assessed by the Musculoskeletal Tumor Society (MSTS) score. Oncology results and complications were recorded in detail.Results:All operations were successfully performed, including 3 cases underwent left tibial tumor resection, 2 cases underwent right tibial tumor resection, and 1 case underwent right femoral tumor resection. The length of the bone defect after tumor resection was 18.19±3.74 cm, the average operation time was 165.83±54.17 min, and the average intraoperative bleeding was 233.33±133.33 ml. These finite element analysis data show that the overall stress of these prostheses are lower than the maximum mechanical strength of the corresponding materials. These 3D printed prostheses match well with the excision defect and meet the expected effect. There were no adverse reactions during the operation. The mean follow-up period was 16.83±7.17 months. At the last follow-up, all patients survived without tumor recurrence or metastasis. Postoperative imaging results showed that all the implants were stable without complications such as peripheral infection, aseptic loosening, prosthesis fracture. These 3D-printed prostheses composite resulted in substantial bone integration at follow-up. The average MSTS score was 83.67%±9.11%.Conclusion:The individualized 3D printed prosthesis can be used to reconstruct the bone defect after the resection of osteosarcoma in the lower extremities, and the clinical efficacy was satisfactory in the short-term follow-up.

Objective To explore the feasibility and clinical efficacy of long-segmental bone defects after en bloc tumor resection of lower limb segment with composite of titanium alloy 3D printed prosthesis and vascularized fibular autograft and bioceramics.Methods 5 patients with lower extremity tumor (1 high grade chondrosarcoma,1 Ewing sarcoma,1 single metastatic tumor and 2 osteosarcoma) were treated by en bloc resection and precise reconstruction with segmental 3D-printed,custom-made prosthesis from August 2015 to November 2016,which composed of 1 male and 4 females,ranged from 16 to 56 years old,the average was 32± 19.3 years old.Three-dimensional computed tomography reconstructed images of patients' tumors were built before surgery.Custom-made prostheses were manufactured based on the patients' reconstructed images with micro-pores on the surface.After en bloc tumor resection with the help of osteotomy guide plate,the defects were reconstructed with 3D-printed,custom-made prostheses.Vascularized fibular autografts were put inside the prostheses,and the interval space among them was filled with bioceramics.Results All the 5 cases were performed surgical planning before the surgery with prosthesis and guide plate were designed at the same time.After verification of the finite element analysis SLM (2 cases) and the EBM (3 cases) were used to process prosthesis,and were designed into porous sharp with 210.98±66.16 mm in length and 26 901.76±12 903.96 mm3 in volume.Then the prosthesis would be cleaned and sterilized.All 5 operation were proceeded according to the plan of preoperative.The intra-operative guide plate were installed on the bone surface stably.The bone cutting was guided according to the plan of preoperative.By intra-operative frozen pathological examination,there were no malignant tissues in near and far marrow cavity.Unfolded fibular flap with 168.75±49.07 mm in length and porous tricalcium phosphate particle composite implants with 10±4.08 g were used in 4 cases and bone cement was used in 1 cases of metastatic tumor.The average operation time was 261±85 min and average blood loss was 540±182 ml.After a mean follow-up time of 6.4 months (1-15 months),all 5 cases survived with no local recurrence and pulmonary metastasis tumor.2 cases with vascular pedicle fibular transplant confirmed the survival of fibula via bone scan 3 months after operation.All cases were no infection,fractures,prosthesis loosening,except broken screw in 1 case.The Musculoskeletal Tumor Society (MSTS) 93 score was 17-26.Conclusion Long segment tubular titanium alloy 3D printed prosthesis with vascularized fibular autograft and bioceramics could reconstruct the segmental defects caused by tumor resection.

Objective To analyze the image and histological results of the combined use of allograft/extracorporeally frozen tumor-bearing bone and vascularized fibular flap for the reconstruction of bony defects following tumor resection,guiding clinical practice.Methods From March 2007 to June 2013,we enrolled 63 patients who had combinative biological reconstruction after bone tumor resection (11 in humerus,22 in femur,21 in tibia,4 in calcaneus).There were 36 male and 27 female in this series.The average age at time of operation was 20 years,ranging from 9 to 48 years.The follow-up ranged from 16 to 102 months with average of 48 months.We investigated the X-ray and CT images for all patients and histological findings of two patients.Patients were assessed functionally with the Musculoskeletal Tumor Society 93 score.Results Three patients with local soft tissue recurrence and one patient with infection underwent amputation.The survival of construct was 93.6％.Bone union achieved in all cases with the average MSTS score of 92.8％.Bone union ranged from 11 to 28 months in allograft group and 9 to 14 months in devitalized tumor bearing bone group.Significant difference of bone union time was found between two groups (Z=-3.638,P=0.000).Viability of the fibular grafts was verified in 58 of 63 patients (92％).Three types of images were observed in complex.Osteopenia and spongy change in fibula were found in 51 patients (81％) with stable fixation of the complex.Five complexes with failed blood supply of fibula and stable fixation revealed no density change of fibula,small amount of callous formation and relative delayed union.In seven complexes (11％) with unstable complex due to patients' incompliance,fibula reacted with dense hypertrophy and microfracture.Fusion of grafts with amount of callus was obviously observed.Union at allograft-host bone junctions occurred by residual host bone-derived external callus and fibular-derived internal callus that bridged the junction and filled the gap between abutting cortices.Callus from fibular graft was mature than that from periosteum of residual host bone.Internal repair was observed at the internal surface of the allografts.Fibula showed significant spongy changes.Conclusion Recycled tumor-bearing bone in combined with fibular flap is a reliable reconstruction as an alternative to traditional Capanna technique.The survival of the fibula is a cornerstone in success of complex reconstruction.Sponginess of fibula and internal repair of allograft compromise the intensity of complex,necessitating the strong instrumentation during reconstruction.

Objective To evaluate the prognostic effects of treatment of giant cell tumor of axis by tumor resection associated with biological reconstruction and internal fixation.Methods From 2009 to 2013,5 patients that had giant cell tumor of axis underwent combined anterior and posterior surgery program.The posterior use pedicle screw system to stabilize the cervical spine,then the anterior use stemocleidomastoid inner edge of the mandibular angle approach to reveal the axis.When the cortex of vertebrae was relatively complete,.When the cortical bone was destroyed,vertebra was resected and the ilium was taken to reconstruct the defect.Adjuvant radiotherapy and diphosphate treatment was used postoperatively.Regular follow-up for X-ray,3D CT and MRI examination were done to observe the tumor recurrence,healing of biological reconstruction and function of cervical vertebra.Results The follow-up time was 12-60 months.No recurrence of the tumor was observed in all patients.The 3 patients accepted beta-TCP implanting after curettage was observed with fuzzy internal structure 3 months after surgery,and the grafted bone fusion can be found 12 months after surgery.The 2 ilium grafted patients can be found with bone fusion with the adjacent vertebrae 6 months after surgery.The bend and stretch function of cervical vertebrae of the 5 patients returned to normal after 3months.The biological healing of bone graft,cervical stability and activity were satisfied.The local pain and neurological symptoms were relieved.Conclusion Anterior and posterior surgery program in combination with biological reconstruction and adjuvant radiotherapy provide an excellent option for treatment of giant cell tumor of axis.The dens could be retained to keep the function of occipital cervical when the odontoid bone cortex is not destructed.