Diabetic nephropathy （DN） is one of the most serious microvascular complications of diabetes and the leading cause of end-stage kidney disease. The onset and progression of DN are linked to the progression of renal fibrosis which is an important pathological feature and final pathological result of various chronic kidney diseases. As a result， therapies against renal fibrosis can help delay the progression of DN. The transforming growth factor-β₁ （TGF-β₁）/Smad signaling pathway is one of the key pathways in renal fibrosis. TGF-β₁， a crucial mediator of renal fibrosis， is highly expressed in the case of fibrosis-associated kidney diseases， and Smads are the main effectors in the TGF-β₁ signal transduction pathway. By activating Smads， TGF-β₁ transports signals from the cytoplasm to the nucleus and regulates the transcription of fibrosis-related target genes， thus exerting the biological effects and promoting the progression of renal fibrosis. In recent years， Chinese medicine has become prominent in the prevention and treatment of DN， and there has been an explosion of research on Chinese medicine in the prevention and treatment of DN through the TGF-β₁/Smad signaling pathway. Based on literature research， this paper reviewed the basic structure of the TGF-β₁/Smad signaling pathway， the relationship with DN， and monomers and extract of Chinese medicine， Chinese patent medicine， and compound Chinese medicine prescriptions in improving and delaying the renal fibrosis based on the TGF-β₁/Smad signaling pathway， and in alleviating inflammatory response and oxidative stress， reducing the accumulation of extracellular matrix， and inhibiting epithelial-mesenchymal transition by regulating the TGF-β₁/Smad signaling pathway. Thereby， this study is expected to provide new mindset for the treatment of DN.

Objective:To explore the curative effect of the "domino" sequential method with prosthesis preservation in the treatment of infection around the prosthesis after limb salvage surgery for bone tumors.Methods:A retrospective analysis of 11 patients with peripheral prosthetic infections after limb salvage surgery with prosthesis preserving "domino" from January 2016 to January 2020 was retrospectively analyzed, including 8 males and 3 females; age 21-74 years old, with an average of 51.8 years old. There were 6 cases of knee prosthesis for distal femoral tumor, 2 cases of proximal tibia knee prosthesis, 2 cases of pelvic prosthesis infection, and 1 case of middle femoral prosthesis. Before the operation, 8 cases had fever, and 2 cases had sinus. Sequential treatment failure is defined as: recurrence of infection. The treatment method is the debridement and lavage of the prosthesis and the systemic combined local application of drug-sensitive antibiotics to evaluate the patient's blood routine, C-reflective protein, erythrocyte sedimentation rate and other indicators, X-ray and CT of the surgical site, and the Musculoskeletal Tumor Society (MSTS) score.Results:The positive rate of microorganism culture was 72.7% (8/11), including 2 cases of Staphylococcus aureus, 1 case of Staphylococcus epidermidis, 1 case of methicillin-resistant Staphylococcus epidermidis, 1 case of methicillin-resistant Staphylococcus aureus, abalone There were 2 cases of Acinetobacter mannifolia and 1 case of Streptococcus degalactiae. The MSTS score before treatment and at the last follow-up after treatment increased from 10.91±2.31 points to 20.73±3.52 points, the difference was statistically significant ( t=7.162, P<0.05). A total of 3 cases of sequential treatment failed to control infection, and the operation success rate was 72.7% (8/11). One case was amputation, one case was long-term replacement of wound dressing, and one case was switched to antibiotic bone cement combined with intramedullary nail reverse double insertion technique to control infection. Conclusion:For bone tumors with clinical infection symptoms less than one month after limb salvage surgery, the use of prosthesis-preserving "domino" sequential method for treatment of prosthetic infections is desirable for early and mid-term clinical efficacy.

Objective:To investigate the alteration of immune microenvironment in giant cell tumor of bone (GCTB) after denosumab treatment from the aspect of immune cellsat single-cell level.Methods:During Nov 2018 and May 2020, fresh tumor excision tissues from GCTB cases were collected and received CyTOF analyses. CyTOF datasets were analyzed and visualized by t-distributed stochastic neighbor embedding (TSNE) method of reduction dimension. The compositions of immune cells in GCTB with or without denosumab treatment were compared. The supernatant of culture medium of ex vivo inoculated primary tumor tissues was harvested to clarify if the culturing supernatant could affect cell growth.Results:A total of 15 primary GCTB cases and three denosumab-treated samples were included in this study and were sent for CyTOF and multicolor FACS assay. GCTB was featured of T-cell and macrophage-like myeloid cell-dominant immune microenvironment. After denosumab treatment, the percentage of T-cells was significantly elevated, while the number of macrophage-like myeloid cells were reduced. Furthermore, the ratio of macrophage-like myeloid cells in total live cells was associated with the treatment period of denosumab. The multinuclear osteoclast like giant cells were characterized by the expression of γδTCR, while most of the intratumoral CD8+ T-cells were activated PD-1+CD69+T-cells. The culturing supernatant of denosumab treatment-free GCTB tissues reinforced cell proliferation in vitro, while this phenomenon was not seen when using denosumab treated tissues.Conclusion:Illustrated the immune cell atlas of GCTB, and preliminarily investigated the potential effects of immune cells on tumor progression in GCTB, providing some theoretical clues for prolonged use of denosumab in unresectable GCTB cases.

Objective:To analyze the surgical techniques, surgical indications and early clinical effects of 3D printed hemipelvic prostheses in the reconstruction of pelvic malignant tumors resected by the sacroiliac joint.Methods:From January 2016 to March 2020, a retrospective analysis of 9 patients with malignant tumors involving pelvis I+II or I+II+III region were treated with sacroiliac joint osteotomy and 3D printed pelvic prosthesis reconstruction. There were 7 males and 2 females; their age was 51.1±10.5 years (range 27-66 years). Among them, 5 cases were chondrosarcoma, 1 case was pleomorphic undifferentiated sarcoma, 2 cases were metastatic renal cell carcinoma, and 1 case was metastatic primitive neuroectodermal tumor. Resection of pelvic area I+II or I+II+III were according to the extent of tumor involvement. During the resection of pelvic I region, osteotomy was done through sacroiliac joint surface, and 3D printed hemipelvic prosthesis that fits the sacral auricular surface was used for reconstruction. Postoperative imaging examination was used to evaluate the acetabular rotation center deviation of the pelvic prosthesis; the International Bone Tumor Society (Musculoskeletal Tumor Society, MSTS) function score was used for functional evaluation; the patient's oncology outcome and postoperative complications were evaluated.Results:All 9 patients successfully completed the operation. The operation time was 3.5-6 hours, with an average of 4.5 hours. The intraoperative blood loss was 800-3 000 ml, with an average of 1 400 ml. 3 patients underwent resection and reconstruction of pelvis I+II area, 4 patients underwent pelvic resection and reconstruction of I+II+III area, 2 patients underwent pelvic I+II+III area combined with proximal femur resection and reconstruction; all patients were followed up. The follow-up time was 6-50 months, with an average of 16 months. At the last follow-up of 9 patients, the MSTS score was 12-26, with an average of 20.2; the postoperative rotation center horizontal displacement distance was 10.67±7.12 mm, and the vertical displacement was 8.56±4.22 mm. One case of metastatic cancer was found to have multiple metastases throughout the body during chemotherapy 3 months after surgery, and died in 7 months after surgery; 1 case of pelvic metastatic renal cell carcinoma developed multiple metastases within one and a half years after surgery, controlled by targeted drugs, and survived with the tumor; the rest seven cases had no recurrence at the surgical site and no distant metastasis was found.Conclusion:The semipelvic prosthesis with 3D printed auricular surface has potential advantages in reconstructing the bone defect of the pelvis I+II or I+II+III area after the sacroiliac joint osteotomy. The short-term efficacy is relatively satisfactory, and the long-term efficacy remains to be further observed.

Objective:To evaluate the effectiveness and safety of intravenous infusion of tranexamic acid combined with local infiltration in reducing the perioperative bleeding of prosthetic replacement surgery after massive tumor resection around the knee joint.Methods:Retrospective analysethe patients treated in our hospital from December 2014 to November 2018 underwent tumor resection and prothesis replacement surgery for tumors around the knee, according to whether intravenous infusion of tranexamic acid combined local infiltration of tranexamic acid in the incision was divided into tranexamic acid group and control group. Statistical analysis of postoperative drainage volume, total blood loss, number of blood transfusion, hemoglobin and fibrinogen level in 3 days after surgery, drug-related side effects, wound complications. The differences between the measurement data of the two groups used independent sample t test to compare; the comparison between the count data groups was by χ2 test. Results:In all 116 patients, preoperative intravenous infusion of tranexamic acid combined with intraoperative local infiltration of tranexamic acid in 26 patients, 90 cases in control group; 39 of the replacement required preoperative chemotherapy, There were 8 cases in the tranexamic acid group. In the tranexamic acid group, there were 23 cases (88.46%) in the distal femur and 3 cases (11.54%) in the proximal tibia, and 59 cases (65.56%) in the proximal femur in control group, and 31 cases (34.44%) of the proximal tibia. The length of the osteotomy is similar, the control group is 14.01±3.26 cm, and the tranexamic acid group is 15.21±4.69 cm. The operation time in control group was 2.57 h, and the tranexamic acid group was 2.34 h. Bleeding volume: the bleeding in control group was 613.33±212.76 ml, and the tranexamic acid group was 440.39±208.48 ml ( t=3.636, P=0.002). There were 54 patients (60%) had blood transfusion in control group, and 15 patients (57.69%) in the tranexamic acid group. There was a significant difference between two groups ( χ2=4.771, P=0.029). The total drainage volume was 623.92±316.87 ml in control group, 468.08±220.74 ml in tranexamic acid group ( t=2.328, P=0.022); estimated total blood loss index: 440.47±194.23 ml in control group, tranexamic acid group: 236.75±116.56 ml ( t=5.046, P=0.000); hemoglobin level in 3 d after surgery, control group: 84.29±11.21 g/L, tranexamic acid group: 92.12±13.66 g/L ( t=-2.951, P=0.004), perioperative blood loss: 866.14±418.68 ml in control group, 586.75±409.93 ml in the tranexamic acid group ( t=2.985, P=0.003). There were significant differences between two groups. All patients were rechecked for coagulation function within 3 days after surgery. The PT time of the patients in the tranexamic acid group was 15.01±1.01 s at 3 d, which is 14.88±0.85 s in control group, and the APTT was 41.18±4.61 s in tranexamic acid group, but approximately 40.77±4.63 s in control group, fibrinogen was 3.26±0.66 g/L and 3.31±1.20 g/L in control group, there is no significant difference between two groups. Conclusion:Local infiltration of tranexamic acid intravenous infusion of tranexamic acid during surgery can significantly reduce the perioperative bleeding volume of limb salvage surgery aroundknee joint and reduce allogeneic blood transfusion.

Objective:To summarize the indications, early functional outcome, complications and precautions of modular reverse shoulder tumor prosthesis in the treatment of proximal humerus tumor.Methods:From September 2018 to October 2019, there were 7 patients with proximal humeral tumor underwent tumor resection and modular reverse shoulder tumor prosthesis replacement in our hospital, including 6 males and 1 female. The average age of the patients was 32 years (14-59 years), including 3 cases of giant cell tumors, 2 cases of osteosarcomas, one case of myeloma and one case of renal cancer metastasis. The prosthesis reconstruction was performed after the removal of the proximal humerus tumor according to malawer type I. Postoperative outpatient follow-up included X-ray of shoulder joint, measurement of shoulder joint activity, functional evaluation using Constant-Murley function score and Musculoskeletal Tumor Society (MSTS) function score.Results:All the 7 patients successfully completed the operation, the operation times were ranged from 125 to 215 min, averaged 158 min; the intraoperative hemorrhage were ranged from 100 to 500 ml, the averaged 257 ml; the length of resected proximal humerus were ranged from 10 to 16 cm, averaged 12 cm. All patients were followed up for 4-17 months, with an average of 8 months. At the last follow-up, the average active abduction of shoulder was 108° (80°-175°), and the average active flexion was 124° (90°-175°). Three patients complained of mild discomfort in the shoulder, the rest of the patients had no pain in the shoulder. Sleep was not affected in all patients, and the hands of seven patients could go over the top of head, and they could live and work normally. In 7 patients, the rotation of shoulder joint was limited, the abduction force of shoulder joint was decreased, the Constant-Murley function score was 72% (59%-78%), and the MSTS function score was 84% (67%-93%). None of the 7 patients had incision infection, hematoma and other related complications. There was one dislocation occurred one month after the operation because the humeral adhesion of deltoid was resected. After open reduction, a larger glenoid ball was used and tension of deltoid muscle was tightened, and no dislocation was found.Conclusion:The combined tumor prosthesis of reverse shoulder has the advantages of simple installation, lower operative requirements compared with the common reverse shoulder prosthesis compounded with allograft, easy to control the length of the prosthesis, and also can achieve satisfactory results.

Objective To evaluate the local recurrence rate,limb function and complications of soft tissue sarcoma of thigh after muscle group resection.Methods Between January 2009 and August 2016,twenty-threepatients who were diagnosed as soft tissue sarcoma for the first time in our hospital,receiving thigh quadriceps muscle group resection,adductor muscle group resection or posterior compartment of the thigh resection were incorporated into this study.Patients who had received surgery of this lesion before,suffered from recurrent soft tissue tumor,had tumor involved multiple muscle groups which could not be resected completely,had sciatic nerve or femoral artery or vein affected by tumor or had distal metastasis were excluded.This retrospective study consisted of 12 male and 11 female.The age ranged from 20-80 with the average of 52.All the patients received CT and MRI of thigh to figure out the size of tumor,the invaded extension of the lesion and the specific muscle group involved.Chest CT scan and ultrasound of bilateral inguinal lymph nodes were arranged to exclude the tumor metastases.After all these examinations were done,needle biopsy with the guidance of CT scan was performed for the pathological diagnosis.The pathology included undifferentiated pleomorphic sarcoma (7 cases),rhabdomyosarcoma (2 cases),primitive neurotodermal tumor (1 case),synovial sarcoma (1 case),leiomyosarcoma (3 cases),fibrosarcoma (5 cases) and liposarcoma (4 cases).Sixpatients received quadriceps muscle group resection,eightpatients received adductor muscle group resection and the other 9 patients received posterior compartment of the thigh resection.Patients with undifferentiated pleomorphic sarcoma,leiomyosarcoma,primitive neurotodermal tumor and synovial sarcoma received postoperative adjuvant chemotherapy.None of patients received radiotherapy.After surgery,drainage tube of negative pressure was placed until the volume of drainage was less than 50 ml within 24 h.The affected thigh was bound up tightly.Intravenous antibiotics were used for 3 days to prevent from postoperative infections.Patients received quadriceps muscle group resection stayed in the bed for 4 weeks.After that they could walk with the protection of orthosis with unbending position.Other patients got out of bed after 2 weeks.All the complications after surgery were recorded.Reexaminations were arranged in 3,6,12 and 24 months after surgery separately.After that,reexamination was arranged every half a year.Chest CT scan was used to detect lung metastasis and ultrasound or MRI was arranged for local recurrence.Lower limb function after surgery was evaluated by MSTS scores.Results All the surgeries of muscle group excision were successfully completed.The duration of surgery ranged 1.5-3.5 h with the average of 2.2 h.The bleeding volume during surgery ranged 100-1 100 mL with the average of 313 mL.The follow-up was a mean of 41 months (range,17-108 months).None was lost to follow-up.The local recurrence rate was 4.3％ (1/23).One patient with undifferentiated pleomorphic sarcoma had positive surgical margin,who received posterior compartment of the thigh resection.Local recurrence occurred 6 months after surgery.Then he received expanded resection.Six patients had distant metastases,five patients for lung metastases,one patient for lung and inguinal lymph node metastases.Of these,five patients had died and one lived with the metastasis.The median MSTS score was 26.3 points (range,14-30 points).Specifically,the median musculoskeletal tumor society (MSTS) score was 28 points (range,21-30 points) for 9 patients with posterior compartment of the thigh resection,twenty-nine points (range,27-30 points) for 8 patients with adductor muscle group resection,and 20.3 points (range,14-24 points) for 6 patients with quadriceps muscle group resection.Five patients had complications,including local recurrence (1 case),hematoma (2 cases) and cutaneous necrosis (2 cases),all of which were settled by reoperation.The rate of complication was 21.7％.Conclusion Muscle group resection is an effective surgical treatment for soft tissue sarcoma of thigh,which could reduce the risk of local recurrence,apart from quadriceps muscle group resection,the other two muscle group resections have limited impact on lower limb function,additionally,thigh muscle group resection is a safe procedure with few complications.

Objective To investigate the clinical charactistics,diagnosis,treatment options and surgical efficacy of spinal osteoblastoma.Methods From May 2007 to May 2016,the clinical manifestations,imaging data,diagnosis,treatment and prognosis of 11 patients with spinal osteoblastoma were retrospectively reviewed.There were 7 males and 4 females.The age ranged from 15 to 44 years old with the average of 27.5 years.Two lesions were involved in cervical spine and 6 lesions were located in thoracic spine.The other 3 cases was in lumbar spine.All patients suffered from local pain.Four patients had neurological deficiency,with 3 suffering radicular pain and 1 suffering incomplete paraplegia (Frankel C).Four patients were staged as Enneking 2 and treated by intralesional curettage.Seven patients were staged as Enneking 3.Accordingly,4 patients were treated by expanded excision with single posterior approach and 1 patient was treated by expanded excision with combined anterior and posterior approach.The other 2 patients were treated by piecemeal total vertebrectomy with single posterior approach.The pain release,neurological recovery and tumor recurrence were evaluated by postoperative follow-up.Results The mean operation time was 3.5 h (range,1.5-7 h) and the average intraoperative blood loss was 800 ml (range,100-3 000 ml).1 patient had cerebrospinal fluid leakage and 2 patients had pleural effusion.No surgical infection was detected in any patient.After surgery,the pain was dramatically relieved in all patients.The radicular pain in 3 patients were relieved and the incomplete paraplegia in 1 patient was recovered to Frankel E.The mean follow-up period was 45.8 months (range,12-117 months).Recurrence occurred in 1 case of cervical 7 and thoracic 1 spine leison 4 years after the surgery.Another expanded excision of the tumor was conducted for this patient and no recurrence was detected till now.No other cases of recurrence were observed.No loosing or breakage of implantation was detected during the follow-up.Conclusion For Enneking 2 leisons,intralesional curettage was effective.For Enneking 3 leisons,the expanded excision or piecemeal total vertebrectomy were recommended.No matter the excision was intralesional or not,the satisfactory results could be achieved if complete tumor excision could be conducted.

Objective To explore the personalized treatment options and clinical results obtained by our hospital for different parts of bone destruction of different degrees of bone giant cell tumor.Methods Retrospective analysis from January 2005 to December 2014,according to the giant bone cell tumor diagnosis and treatment procedures used in thehospital to take wide resection or intralesional curettage and adjuvant therapy for the treatment of primary limb long bone giant cell tumor 281 cases.There were 150 males and 131 females,with overall age from 14 to 71 years and an average of 35.10 yearsold.The distal ulna was 9 cases.The distal radiuswas 26 cases.The proximal humerus was 19 cases.The distal humerus was 2 cases.The proximal femur was 38 cases.The distal femur was 95 cases.The proximal tibiawas 59 cases.The distal tibiawas 10 cases.There were 19 proximal fibula cases,3 distal fibula cases and 1 case of multiple giant cell tumor of bone.We chose curettage and/or adjuvant therapy or wide resection,then with bone cement,allograft or autograft,prostheses to reconstructionaccording to tumor site,the degree of destruction,pathological fractures.The x2 test and Cox regression analysis were used to detect the statistic differences.The KaplanMeier survival analysis was used to count the disease-free survival.The relationship between tumor location,destruction degree,Campanacci grading,pathological fractures,treatment methods at different stages and recurrence were analyzed.Results A total of 281 patients with long bone giant cell tumor were included in the follow-up study,including 37 pathological fracture and 244 non-fracture.According to the author's giant cell tumor diagnosis and treatment process,122 patients received a wide resection,159 cases were treated with curettage ± adjuvant therapy.23 patients had postoperative recurrence,the recurrence rate was 8.19％.The recurrence time after operation ranged from 9 to 75 months (average 30.95 months).There was no significant difference between the recurrence rate of lesions around the knee and other parts (x2=0.370,P=0.240).In the non-pathologic fracture group,the recurrence rate was significantly lower in the large section compared with curettage surgery (x2=9.393,P=0.002).Of the patients with intralesional surgery,126 patients reconstructed with cement and 28 patients reconstructed with autograft/allograft bone to rebuild mechanical stability.There were 14 recurrence cases (14/126,11.11％) in the bone cement group and 8 recurrence cases (8/28,28.57％) in the bone graft group.The recurrence rate in the bone cement group was significantly lower than that in the simple bone graft group (x2=5.846,P=0.017).The patients with lesion less than 50％,4 had recurrences (4/55,7.27％),12 recurrences occurred (12/76,15.79％) in more than 50％ and less than 75％ of the cross-sections,and if the lesion was more than 75％ cross-sectional area,4 cases of recurrence (4/113,3.54％).There was no significant difference in the proportion of bone destruction between different cross-sections in affecting tumor recurrence.The recurrence rate of Campanacci Grade Ⅲ patients was significantly higher than that of Campanacci Grade Ⅱ patients with curettage surgery (x2=9.909,P=0.002).Only 1 of the patients with pathological fracture had recurrence (1/37,2.70％),the recurrence rate was significantly lower than that the curettage group (x2=11.972,P=0.001).Among the early patients,79 cases (63.71％) were cured by surgery and 17 cases were relapsed,while in the last 5 years 80 cases (50.96％) were cured by surgery and 6 cases were relapsed,In two different periods,the curettage recurrence rate was significantly decreased (x2=9.246,P=0.003).Conclusion By selecting personalized treatment options for different patients,it is possible to increase the proportion of patients who maintain their knee joints while reducing the local recurrence rate,providing doctors and patients with a choice of treatment options.

Objective: To evaluate the efficacy and safety of maintenance therapy with reduced dose of rhTPO in the patients with primary immune thrombocytopenia (ITP) who attained stable platelet (PLT) counts after daily administration of rhTPO. Methods: Treatment was started with a daily administration of rhTPO (300 U/kg) for 2 consecutive weeks. Patients who attained stable PLT≥50×10⁹/L were enrolled to maintenance therapy starting with every other day administration of rhTPO, then adjusted dose interval to maintain platelet count (30-100) ×10⁹/L. Results: A total of 91 eligible patients were enrolled. Fourteen patients discontinued the study due to noncompliance (12/14) and investigator decision (2/14) . Among 77 patients who completed the study, 38 patients with the administration of rhTPO at every other day or less could maintain PLT≥30×10⁹/L for 12 weeks. The percentage of patients with a platelet response (PLT≥30×10⁹/L) at 4^th week, 8^th week and 12^th week of maintain therapy was 92.6% (63/68) , 82.7% (43/52) and 85.0% (34/40) , respectively. Median platelet counts remained in the range of (70-124) ×10⁹/L. The overall incidence of rhTPO-related adverse events was 7.7%. All the adverse events were generally mild. Conclusion Extending the dose interval of rhTPO is feasible to maintain stable platelet count in the patients with ITP, but the optimal dose interval is uncertain and might vary with individuals.