Liver diseases cannot be easily detected in the early stage， and although invasive diagnostic methods， such as liver biopsy， are relatively accurate， they tend to have a low degree of acceptance， which greatly limits the improvement in diagnosis and treatment techniques for liver diseases. Therefore， it is of great importance to search for new biomarkers and therapeutic targets. As an emerging biomarker for liquid biopsy， tRNA-derived small RNA （tsRNA） is abnormally expressed in various liver diseases including viral hepatitis， fatty liver disease， liver injury， and liver cancer， and it can affect the development and progression of liver diseases by regulating the biological functions such as gene expression， epigenetic regulation， and protein translation. This article reviews the origin， classification， and biological function of tsRNA， as well as the research advances in tsRNA as biomarkers and potential therapeutic targets for liver diseases， so as to provide ideas for the early diagnosis and treatment of liver diseases.

Objective:To investigate the clinical efficacy of haploidentical high-dose in vitro non-T-cell-depleted peripheral blood hematopoietic stem cell transplantation (haplo-HDPSCT) in treating adult patients with Ph + acute lymphoblastic leukemia (Ph + ALL) . Method:This retrospective analysis was conducted on the clinical efficacy of 25 adult patients with Ph + ALL who underwent haplo-HDPSCT from July 2011 to June 2022 at our hospital. Results:This study included 25 patients with a median age of 27 (16-61) years, consisting of 12 males and 13 females. CR1 and ≥CR2 before transplantation were found in 23 and 2 cases, positive and negative minimal residual lesions were observed in 8 and 17 cases, and myeloablative conditioning and reduced-intensity conditioning were reported in 21 and 4 cases, respectively. Hematopoietic function was restored in all 25 patients after stem cell infusion. Of the 25 patients who underwent transplantation, 16 developed acute graft-versus-host disease (aGVHD). The cumulative incidence rates of Ⅱ-Ⅳ and Ⅲ-Ⅳ aGVHD were (40.4±11.3) % and (4.8±4.6) %, respectively. Four patients experienced relapse after transplantation, the cumulative relapse rates at 1 and 2 years after transplantation were (4.0±3.9) % and (14.5±7.9) %, respectively. The 2-year overall survival rate after transplantation was (81.3±8.5) % and the disease-free survival rate was (77.1±9.1) %.Conclusion:This study reveals that the unique haplo-HDPSCT protocol achieves good clinical efficacy in Ph + ALL treatment.

Objective:To investigate the clinical efficacy of haploidentical high-dose in vitro non-T-cell-depleted peripheral blood hematopoietic stem cell transplantation (haplo-HDPSCT) in treating adult patients with Ph + acute lymphoblastic leukemia (Ph + ALL) . Method:This retrospective analysis was conducted on the clinical efficacy of 25 adult patients with Ph + ALL who underwent haplo-HDPSCT from July 2011 to June 2022 at our hospital. Results:This study included 25 patients with a median age of 27 (16-61) years, consisting of 12 males and 13 females. CR1 and ≥CR2 before transplantation were found in 23 and 2 cases, positive and negative minimal residual lesions were observed in 8 and 17 cases, and myeloablative conditioning and reduced-intensity conditioning were reported in 21 and 4 cases, respectively. Hematopoietic function was restored in all 25 patients after stem cell infusion. Of the 25 patients who underwent transplantation, 16 developed acute graft-versus-host disease (aGVHD). The cumulative incidence rates of Ⅱ-Ⅳ and Ⅲ-Ⅳ aGVHD were (40.4±11.3) % and (4.8±4.6) %, respectively. Four patients experienced relapse after transplantation, the cumulative relapse rates at 1 and 2 years after transplantation were (4.0±3.9) % and (14.5±7.9) %, respectively. The 2-year overall survival rate after transplantation was (81.3±8.5) % and the disease-free survival rate was (77.1±9.1) %.Conclusion:This study reveals that the unique haplo-HDPSCT protocol achieves good clinical efficacy in Ph + ALL treatment.

Objective:To evaluate the efficacy of 3D printed individualised prosthesis in treating bone and joint defects in upper limbs remained after earlier microsurgical repairs.Methods:From June 2019 to September 2021, 12 patients were treated in the Institute of Orthopaedic Trauma of PLA, the 80th Group Army Hospital for bone and joint defects in upper limb that had been remained after earlier repairs with soft tissue flaps. The defects were: 1 in completely severed wrist, 2 defects of digit metacarpal bone, 4 defects of interphalangeal joint, 4 defects of bones in radiocarpal joint and 1 defect of lunate bone. The area of soft tissue defect ranged from 1.5 cm×3.0 cm to 12.0 cm×18.0 cm, and the length of bone defects ranged from 2.5 to 8.5(average 3.64) cm. For incompletely severed and completely severed limbs, replantation of severed limbs (digits) were performed in the primary surgery and the repair of soft tissue defects were performed in the second stage surgery. The remaining defects of bone and joint were reconstructed by 3D printed individualised prostheses in the third stage surgery. Finger soft tissue defects were covered with a local flap in the primary surgery, and bone and joint defects were reconstructed with a 3D printed prosthesis in the second surgery. Finger soft tissue defects were covered with a local flap in the first phase, and bone and joint defects were reconstructed with a 3D printed prosthesis in the second phase. After the surgery, the bone integration between the broken end of the bone joint defect and the prosthesis was determined based on the X-ray results and the Paley fracture healing score standard. Simultaneously measured the Total Active Motion(TAM) of the forearm and hand joints. At 1, 2, 3, 6, 9 and 12 months after hospital discharge. Follow-up X-ray examinations were taken followed by examinations on the recovery of soft tissues and bones. The upper limb function was graded according to the Evaluation Trial Standards of Upper Limb Partial Functional of Hand Surgery of Chinese Medical Association.Results:Postoperative follow-up at outpatient clinic lasted for 6 to 26 months, with an average of 11.5 months. All flaps were free from necrosis and infection, also there was no infection in bones and joints. According to the Paley fracture healing scale, 10 patients were in excellent and 2 in good. In addition, according to the Evaluation Trial Standards of Upper Limb Partial Functional of Hand Surgery of Chinese Medical Association, 5 patients achieved upper limb function in excellent, 5 in good and 2 in fair. The ranges of motion of the affected wrists were 30°-42°(average 37.3°) for the implanted prostheses of distal end of radius and the radial shaft. Wrist flexion 40° to 55°(average 43.5°). The range of motion of finger and wrist was 60° to 70°(average 65.7°) with a metacarpal and phalangeal bone prosthesis.Conclusion:3D printed individually customised prostheses are safe, accurate and effective in repair of the remained bone and joint defects in upper limbs after primary and early stages of microsurgical flap repairs. It can effectively restore anatomical structures of bone and joint in upper limbs.

Gallic Acid/pharmacology* ; Humans ; Senotherapeutics ; Stem Cells

Objective: To analyze the efficacy of HLA-haploidentical peripheral hematopoietic stem cell transplantation (haplo-PBSCT) following reduced intensity conditioning (RIC) regimen to treat the patients with hematological malignancies who were older than 50 years old. Methods: Eighteen patients with hematological malignancies over 50 years were enrolled, including 8 male and 10 female patients. The median age of all patients was 52 (range: 50–66) years. Of them, 8 patients had acute myeloid leukemia (AML) , 2 chronic myelocytic leukemia (CML) , 5 myelodysplastic syndrome (MDS) , 2 acute lymphoblastic leukemia (ALL) , and 1 aggressive natural killer cell leukemia (ANKL) . All patients received fludarabine, cytarabine and melphalan with rabbit anti-human thymocyte globulin (FAB+rATG regimen) and transplanted with high dose non-T cell-depleted peripheral hematopoietic stem cells from donors. Enhanced graft versus host disease (GVHD) prophylaxis and infection prevention were administered. Results: Fifteen days after transplantation, 16 patients achieved complete donor chimerism. One of them rejected the donor graft completely at thirty days after transplantation, and the other 2 patients had mixed chimerism 15 days after transplantation and converted to complete recipient chimerism at 30 days after transplantation. The cumulative incidence of acute GVHD (aGVHD) was 61.1% (95%CI49.6%-72.6%) . The incidence of grade Ⅱ-Ⅳ aGVHD was 35.4% (95%CI 21.1%-49.7%) , whereas grade III-IV was 13.8% (95%CI 4.7%-22.9%) . The 2-year cumulative incidence of chronic GVHD (cGVHD) rate was estimated at 38.2% (95%CI 25.5%-50.9%) . Patients were followed-up for a median of 14.5 months (range, 3-44 months) . The Kaplan Meier estimates of 2-year overall survival (OS) and disease-free survival (DFS) was 72.6% (95%CI 60.1%-85.1%) and 63.7% (95%CI 49.2%-78.2%) , respectively. The 2-year cumulative incidence of relapse and non-relapse-mortality (NRM) was 31.2% (95%CI 16.5%-45.9%) and 12.5% (95%CI 4.2%-20.8%) , respectively. Conclusion RIC-haplo-PBSCT protocol can achieve better results in patients with hematologic malignancies over 50 years old.

Objective To observe clinical curative effect of the FLAG regimen combined donor lymphocyte infusion after granulocyte colony stimulating factor(G‐CSF) mobilization(G‐DLI) ,for the acute myeloid leukemia (AML) of allogeneic Peripheral blood hematopoietic stem cell trans‐plantation (allo‐HSCT) after recurrence of hematology .Methods For the patients with recur‐rence after allo‐HSCT ,giving the FLAG regimen chemotherapy when the WBC dropped to the lowest point ,followed by giving G‐DLI that infusion peripheral blood stem cell from the original donors ,to observe curative effect and survival situation .And searched the literature review through the PubMed etc .Results Through FLAG regimen combined G‐DLI ,3 cases of relapse after transplan‐tation again obtained complete remission (CR) .Case 1 :disease‐free survival (DFS) was 13 month and overall survival(OS) was 23 months after G‐DLI .The patient has been the central recurrence and remission in bone marrow ,he was dead after 23 months due to multipleorgan function failure .He occurred Ⅱ acute GVHD in Skin and Ⅰ acute GVHD in liver after G‐DLI and obtained effective control ,not chronic GVHD .Case 2 :DFS and OS were 12 months and 13 months ,as bone marrow relapse again and giving up treat‐ment ,so died a month later .Respectively ,he has limitations chronic GVHD in skin after G‐DLI .Case 3:DFS was 16 months after G‐DLI since the disease‐free survival ,had limitations GVHD in skin that was control for given small dose of immunosuppressive drugs .Conclusion Joint FLAG scheme and G‐DLI may be one of the effective treatment of postoperative recurrence of allo‐HSCT .

Objective To observe the effect of simvastatin on bone metastasis of breast cancer in nude mice model.Methods Sixty mice were divided into three groups randomly with 20 in each group.Mice were inoculated with MDA-MB-231 cells into the left cardiac ventricle.After 7 days,mice were treated with either simvastatin,saline,or nothing twice per week for 19 days.The area of osteolytic metastases was subsequently measured in long bones of all mice using an image analysis system.After sacrifice,parathyroid hormone-related protein (PTHrP) concentrations in bone marrow from all mice were determined using a two-site immunoradiometric assay.Osteoclast number expressed per millimeter of tumor/bone interface was assessed using an OsteoMeasure System.Measured data were compared with analysis of variance,and P ＜ 0.05 for the difference was statistically significant.Results The area of osteolytic lesions was significantly lower in mice treated with simvastatin compared with mice receiving saline and no treatment (0.51 ±0.18 mm2 vs 2.13 ± 1.24 mm2 vs 2.29 ± 1.22 mm2 ; F =15.600,P =0.002 ; F =15.673,P =0.001).In addition,treatment with simvastatin decreased the concentrations of PTHrP in bone marrow plasma (0.98 ±0.20 pmol/L vs 2.11 ±0.31 pmoL/L vs 1.99 ± 0.29 pmol/L; F =61.469,P ＜ 0.001 ; F =58.274,P ＜ 0.001) and the osteoclast numbers per millimeter of tumor/bone interface (4.00 ± 1.73 vs 11.40 ±4.93 vs 10.91 ± 3.87 ; F =17.820,P =0.001 ; F =17.184,P =0.002) compared with controls.Conclusion Simvastatin may reduce the production of PTHrP of breast cancer cells,which suppresses the development of destructive bone lesions as well as the growth of breast cancer cells in bone.

OBJECTIVETo study the clinical features of acute graft-versus-host disease (aGVHD) and its risk factors for the related HLA-haploidentical non T cell-depleted in vitro peripheral hematopoietic stem cell transplantation (RHNT-PBSCT).

METHODSFrom July 2002 to December 2012, 104 patients who underwent the RHNT-PBSCT were enrolled to analyze the incidences, location and its risk factors of aGVHD, compared with those of the 103 patients who received the HLA-matched sibling non T cell-depleted in vitro PBSCT (MSNT-PBSCT) in the same period.

RESULTS(1)The cumulative incidence of aGVHD in the RHNT-PBSCT group was significantly higher than the MSNT-PBSCT group [(56.2±4.7)% vs (34±3.6)%, P<0.05], but the cumulative incidences of II-IV and III-IVgrade aGVHD had no significant difference between the two groups[(39.5±2.9)% vs (21.2±5.4)%, P>0.05; (12.6±4.1)% vs (10.8±2.4)%, P>0.05]. (2)The cumulative incidence of cutaneous aGVHD was significantly higher in RHNT-PBSCT group than that in MSNT-PBSCT group [(42.3±3.2)% vs (17.5±2.3)%, P<0.05]. The cumulative incidences of liver and gastrointestinal aGVHD between the two groups had no significant difference [(7.7±2.1)% vs (12.6±3.4)%, P>0.05; (16.3±4.5)% vs (10.3±2.5)%, P>0.05]. (3)The 3-year disease free survival (DFS) and overall survival(OS) of RHNT-PBSCT group and MSNT-PBSCT group were (63±5.5)%, (65.2±4.7)% and (74.2±5.4)%, (77.4±5)% respectively, without significance (P=0.078, P=0.052). (4)aGVHD occurrence with HLA haplotype (P=0.003) and matched loci (P=0.002) were significantly correlated by univariate analysis. Multivariate analysis showed that only the HLA typing is a risk factor for aGVHD (HR=1.891, P=0.03).

CONCLUSIONAlthough the incidence of total aGVHD in RHNT-PBSCT protocol is higher than that in MSNT-PBSCT, but there was no significance in severe aGVHD and cutaneous aGVHD was the common type, which indicates that RHNT-PBSCT protocol is feasible.

Disease-Free Survival ; Graft vs Host Disease ; Haplotypes ; Hematopoietic Stem Cell Transplantation ; Histocompatibility Testing ; Humans ; In Vitro Techniques ; Incidence ; Peripheral Blood Stem Cell Transplantation ; Risk Factors ; Siblings ; T-Lymphocytes

Objective Evaluate data of 1270 cases with free flap transplant,to find the problems in the process of operation,and then to analyse its causes and how to prevent and solve it,as well as providing reference for clinical colleagues. Methods To study 1270 cases of free flaps,musculocutaneous flap and perforator flap who was treated in our hospital from October 2000 to October 2010 retrospectively. A total of 722 cases of the group were followed-up 6 months to 5 years. To detective and search the problems and imperfection from designing,harvesting,tranfer,to the management and function of donor site after free flap transplantion.And also to analysis the couse of problems and operation failure,discuss the conclude of and to provide advisable measure. Results Total 1270 free flaps were transplanted successfully except 64 can-celled or failured for some reason, the success rate was 95.0％, the postopertive necrosis rate was 3.8％.Seventy-six cases were encountered vascular complications venous crisis in 42,arterial crisis in 38.Fifty-five cases were saved successfully without surgery,and 15 cases survived completely by vessel explorative operation. Five cases were partial necrosis and 7 cases necrosis. The rate of postoperative infection of emergency cases and chronic one were 4.7％ (682 cases)and 8.8％(588 cases) which show the infective incidence of latter was higher than former. In addition, there were many other problems were found such as distal flaps necrosis,contracture,deformation,impairment function of doner site,etc. Conclusion Preventing and management timely to vessle crisis is the key to flap suvive. The principle of dissecting flap should be followed strictly,and control the indications of modified processing during flap harvest,keep the proper flap tension were technical requirements in flap transplantion. Right way of donor site closed and management of insufficient timely were equally important to prevent and solve to complications and dysfunction.