Effect analysis of brentuximab vedotin monotherapy and brentuximab vedotin combined with chemotherapy in treatment of relapsed or refractory lymphoma / 白血病·淋巴瘤

Objective:To investigate the safety, efficacy and survival of brentuximab vedotin (BV) monotherapy and BV combined with chemotherapy for relapsed or refractory lymphoma.Methods:A total of 47 patients with relapsed or refractory Hodgkin's lymphoma (HL) in First Medical Center of PLA general Hospital and Fourth Medical Center of PLA General Hospital from October 2011 to December 2018 were admitted, including 35 cases (BV monotherapy group) and 12 cases (BV combined with chemotherapy group); there were 8 cases of relapsed or refractory anaplastic large cell lymphoma (ALCL), 4 cases in BV monotherapy group and 4 cases in BV combined with chemotherapy group. The safety, clinical efficacy and survival of two neoplasms in different groups were compared.Results:For relapsed or refractory HL, the objective remission rate (ORR) and complete remission rate (CRR) was 67.7% (21/31) and 16.1% (5/31), and the median progressive-free survival (PFS) time was 3.5 months (1.5-24.0 months) in BV monotherapy group; ORR and CRR was 81.8% (9/11) and 27.3% (3/11), and median PFS time was 5.5 months (2.0 - 24.0 months) in BV combined with chemotherapy group; there was no statistical difference in ORR and CRR between the both groups (χ 2 = 0.788, P = 0.375; χ 2 = 0.654, P = 0.419). There were 4 cases in BV monotherapy group for ALCL, of which 3 could be evaluated for efficacy, including 1 case of complete remission (CR) and 1 case of partial remission (PR); there were 4 cases in BV combined with chemotherapy group for ALCL, of which 4 could be evaluated for efficacy, including 2 cases of CR and 2 cases of PR. The common adverse events in BV monotherapy group were anemia, leukopenia, thrombocytopenia, fever, elevated transaminase, fatigue, nausea, peripheral neuritis and cough. Grade ≥3 adverse events were mainly anemia, thrombocytopenia and leukopenia. The common adverse events of BV combined with chemotherapy group were similar to those of BV monotherapy group, and there were significant differences in bone marrow suppression (thrombocytopenia, leukopenia) between the two groups (all P < 0.05). Conclusions:The clinical efficacy of BV combined with chemotherapy is better than that of BV monotherapy in treatment of relapsed or refractory lymphoma, and the survival time is prolonged. The adverse reaction of BV combined with chemotherapy is mainly manifested in bone marrow suppression, and the safety and tolerability of patients are acceptable.

Phase I study of chimeric antigen receptor modified T cells in treating HER2-positive advanced biliary tract cancers and pancreatic cancers

This phase I clinical trial (NCT01935843) is to evaluate the safety, feasibility, and activity of chimeric antigen receptor-engineered T cell (CART) immunotherapy targeting human epidermal growth factor receptor 2 (HER2) in patients with advanced biliary tract cancers (BTCs) and pancreatic cancers (PCs). Eligible patients with HER2-positive (>50%) BTCs and PCs were enrolled in the trial. Well cultured CART-HER2 cells were infused following the conditioning treatment composed of nab-paclitaxel (100-200 mg/m) and cyclophosphamide (15-35 mg/kg). CAR transgene copy number in the peripheral blood was serially measured to monitor the expansion and persistence of CART-HER2 cells in vivo. Eleven enrolled patients received 1 to 2-cycle CART-HER2 cell infusion (median CAR T cell 2.1 × 10/kg). The conditioning treatment resulted in mild-to-moderate fatigue, nausea/vomiting, myalgia/arthralgia, and lymphopenia. Except one grade-3 acute febrile syndrome and one abnormal elevation of transaminase (>9 ULN), adverse events related to the infusion of CART-HER2 cells were mild-to-moderate. Post-infusion toxicities included one case of reversible severe upper gastrointestinal hemorrhage which occurred in a patient with gastric antrum invaded by metastasis 11 days after the CART-HER2 cell infusion, and 2 cases of grade 1-2 delayed fever, accompanied by the release of C-reactive protein and interleukin-6. All patients were evaluable for assessment of clinical response, among which 1 obtained a 4.5-months partial response and 5 achieved stable disease. The median progression free survival was 4.8 months (range, 1.5-8.3 months). Finally, data from this study demonstrated the safety and feasibility of CART-HER2 immunotherapy, and showed encouraging signals of clinical activity.

Effect of brentuximab vedotin combined with chlormethine hydrochloride on the treatment of 6 patients with relapsed and refractory Hodgkin lymphoma / 中华血液学杂志

<p><b>OBJECTIVE</b>To observe the clinical efficacy and side effects of brentuximab vedotin (BV) plus chlormethine hydrochloride (CH) in patients with relapsed and refractory Hodgkin lymphoma (HL) after failure with BV alone.</p><p><b>METHODS</b>From March, 2014 to December, 2014, 6 patients who failed with BV monotherapy were enrolled in this study. The chemotherapy regimen consisted of BV (1.2-1.8 mg/kg, iv. gtt, d1) and CH (6 mg/m2, iv. gtt, d1) was given for 3 weeks as one course, and all patients received about 3-8 courses of chemotherapy, with an median of 4 courses. Clinical efficacy and adverse events were assessed and observed by radiographic examination and serological detection.</p><p><b>RESULTS</b>Among 6 patients, the overall response rate was 100% with 2 complete remission and 4 partial remission. The main adverse events were grade I (2 patients) and IV (2 patients) bone marrow depression, grade II (2 patients)gastrointestinal reaction, grade I (1 patient) increase of transaminase and myocardial enzyme and grade I (1 patient) mouth ulcers.</p><p><b>CONCLUSION</b>The combination of BV and CH in the treatment of relapsed and refractory HL after failure with BV alone was high effective and the toxicities were well tolerable.</p>

Clinical significance of triple-phase bone scintigraphy in diagnosing peri-prosthetic infection following hip arthroplasty / 中国组织工程研究

BACKGROUND: Aseptic loosening and infection are difficult to diagnose due to their similar clinical manifestations following total hip replacement.There lacks routine examinations or gold standard to diagnose peri-prosthetic infection.OBJECTIVE: To evaluate the clinical effectiveness of technetium-99m-labelled triphase isotope scinitigraphy in the diagnosis of peri-prosthetic infection following total hip arthroplasty.METHODS: A total of 11 patients with suspected peri-prosthetic infection were selected,with continuous hip pain,prosthesis loosening and abnormal serum indexes,including 7 males and 4 females,with an average age of 63.8(53-74)years.The average time of prosthesis usage was 14.5(0.5-30)years.The technetium 99m-labelled bone scintigraphy images were obtained to observe the density variation of the infection region during the blood flow phase,blood pool phase and late phase and compared with normal lateral limb.Time-radioactive uptake curve was made using software to analyze the diagnostic results.In addition,the diagnostic value of the triple-phase bone scinitigraphy was analyzed using the intraoperative frozen section results(neutrophil < 5 under 10 high power visual fields: no infection).RESULTS AND CONCLUSION: Of 11 patients,2 cases showed negative result of triple-phase bone scinitigraphy,and intraoperative frozen section analysis showed < 5 polymorphonuclear cells per high-power field,who underwent one-stage revision surgery; 8 displayed positive result of tdple-phase bone scinitigraphy,and intraoperative frozen section analysis showed > 5polymorphonuclear cells per high-power field,who underwent two-stage revision surgery; 1 case showed negative result of triple-phase bone scinitigraphy but intraoperative frozen section analysis showed > 5 polymorphonuclear cells per high-power field,who also underwent two-stage revision surgery.Results show that positive results of triple-phase bone scintigraphy were related to peri-prosthetic infection,which has great value for revision surgery in combination with histopathological examination.

Clinical analysis of elder patients with invasive fungal infections of gerontal hematological malignant / 白血病·淋巴瘤

Objective To explore the clinical characteristics of the elder patients with the invasive fungal infections (IFI) in gerontal hematological malignant. Methods 38 patients with IFI during Jan 2000 to October 2007 were enrolled to analyze retrospectively. Results A total of 38 cases of gerontal hematological malignancies were diagnosed IFI. Occurrence of IFI correlated with agranulocytosis persistence >5 days, broad - spectrum antibiotics using >7 days, complicating diabetes, the hospitalized day longer than 20 days,chemotherapy scheme combined with glucocorticoids. IFI clinical manifestation varied with different infection sites and different fungal species. Lung was the frequently fungal infection site(25 cases, 65.8 %). The most common fungal subtypes were Candida albicans (14 strains, 38.9 %) and aspergillus (7 strains, 19.4 %).Although amphotericin B and itraconozole were adopted to treat IFI, but there were still 10 cases of patients died because of severe respiratory failure. Conclusion Elder patients with gerontal hematological malignant with a marked increasing mortality of IFI, prognosis was poor. Morbidity concerned with many factors, early prophylaxis or empiric antifungal treatment should be adopt.

Experimental research for position accuracy of caput femoris center in total knee replacement navigation surgery / 生物医学工程学杂志

Finding the position of caput femoris center by exact and fast method is a key technique in total knee replacement navigation surgery. A method for finding the position of caput femoris center is described in this paper. The main idea is abstracting this problem to a geometrical model in which the center of a sphere can be easily worked out with a few known spherical points. Experiments show that the method is feasible and the precision satisfies the requirements of navigation surgery.

Comparison of MRI versus stress radiograph in imagiological diagnosis of the anteromedial osteoarthritis knees / 中国矫形外科杂志

0.05)respectively.[Conclusion]The technique of radiographic assessment to define the anteromedial OA of the knee is not easy to perform,but it can be used,by well trained doctors,in the most knee OA cases with high accuracy.The MR imaging gives more information about cartilage defects and can be used in some doubted cases.

Study on estrogen receptor of adult human osteoblasts / 中西医结合学报

OBJECTIVE: To examine estrogen receptor (ER) in osteoblasts from adult human and to elucidate the mechanism of estrogen in modulating bone metabolism. METHODS: The cultured osteoblasts were harvested from bone chips by modified sequential digestive enzyme release and immunohistochemical assay of ER in osteoblasts were carried out in three groups of female adults: normal control (group 1), patients with moderate osteoporosis (group 2) and patients with serious osteoporosis (group 3). The percentages of ER-positive osteoblasts from the three groups were compared by t test. RESULTS: The brown marks that indicate ER were found in nuclei and plasma of the osteoblasts, and the percentages of ER-positive osteoblasts among three groups were significantly different. CONCLUSION: ERs exist in nuclei and plasma of the osteoblasts. Estrogen may modulate bone metabolism through binding ER in nuclei and plasma of the osteoblasts. The reduction of ER of osteoblasts may play an important role in the pathogenesis of postmenopausal osteoporosis.

Culture of human osteoclasts / 中西医结合学报

To establish a stable, useful culture system for human osteoclasts and to investigate the effect of osteoblasts on the differentiation, proliferation and activation of osteoclasts so as to provide a base for the studies on prevention and treatment of osteolysis and osteoporosis.

Osteogenic potential of rabbit marrow stromal stem cells cultured in vitro: a histochemical and scanning electron microscopic study / 中华创伤杂志(英文版)

<p><b>OBJECTIVE</b>To further investigate the osteogenic potential of rabbit marrow stromal stem cells cultured in vitro.</p><p><b>METHODS</b>Rabbit marrow stromal stem cells were isolated by density gradient centrifugation method and amplified in the flasks, using the osteogenic inducing conditions (OGC) as the culture media. The osteogenic potential of marrow stromal stem cells were investigated by means of bone-seeking fluorescence (tetracycline) labelling, Alizarin red S (ARS) staining, Alcian blue-Sirius red (AS) staining, and scanning electron microscope.</p><p><b>RESULTS</b>After being passaged, the marrow stromal stem cells increased in number, became confluent and formed multi-layer structure. The stromal stem cells excreted innumerable tiny granules, heaping up on the cell body and merging gradually into foggy substances. These foggy substances kept on enlarging and formed round, oval, or flake-like nodules. These nodules revealed bright golden yellow fluorescence under fluorescence microscope when labelled with tetracycline. Histochemical study with specific new bone staining with ARS revealed positive calcium reaction, both denoting that they were newly formed bone tissues. After they were stained with AS, collagen and acid mucopolysaccharide were shown. Under scanning electron microscope, three types of cells with different configurations were found. They were globular cells, spindle-shaped cells and polygonal or polygonal cells. Granules were excreted from the cells and heaped up on the cell body. Needle-shaped and irregularly rectangular crystals also appeared and agglomerated with the granules to form nodules and trabecula-like or flake-like structures.</p><p><b>CONCLUSIONS</b>Sequence of events of bone formation by rabbit marrow stromal stem cells cultured in vitro is fully depicted and confirmed, which provides the foundation for further investigating the mechanisms of osteoblast differentiation from marrow stromal stem cells and the possible application in orthopaedics.</p>

The recent advance in joint replacement / 中华创伤骨科杂志

Total hip and knee replacements, which have developed for abou t forty years, have been widely used as effective surgical treatments for severe hip and knee diseases. This article discusses the recent advance in techniques of hip and knee replacement Chiefly in the aspects of hip or knee prosthesis des ign, improvement of materials and surgical techniques. In total hip replacement, second-generation cementing technique, new types of metal-on-metal prosthesi s and minimally invasive technique have been applied to enhance the stability, r educe the wear rate and facilitate the functional recovery. In knee replacement, mobile bearing and high flexion are great advancements made in design. The comp uter-aided operational technique has greatly improved the replacement.

Advances in treatment of nonunion and delayed union of fractures / 中华创伤骨科杂志

Nonunion or delayed union remains one of the major complicatio ns of fractures. Repair of fractures involves a sequence of dynamic events which ultimately restore the integrity of bone and its biomechanical properties, incl uding such methods as surgery, internal fixation, bone grafting, external fixati on, electrical stimulation, ultrasound, and high-energy extracorporeal shock wa ve. The preferred management of nonunion and delayed union is autologous bone gr afting. However, the supply of suitable bone is limited and it often results in additional morbidity to the donor site. Recently some advances have been made in the therapeutic principle for nonunion or delayed union. It is aimed at providi ng non-invasion, less complication, and safe treatment. This article introduces the development of some effective and safe therapies for nonunion or delayed un ion.

Diagnosis and treatment of glenoid labrum injury of the shoulder with arthroscopy / 中华骨科杂志

Objective To discuss the practical significance and clinical therapeutic effects of shoulder arthroscopy technique in the diagnosis and treatment of glenoid labrum injury. Methods In order to have an accurate diagnosis of glenoid labrum injury of the shoulder, X-ray, arthrography, MRI and arthrog-raphy and arthroscopy techniques were used respectively for thirty-six cases of glenoid labrum injury. Under shoulder arthroscopy, the injured glenoid labrum was partially resected in twenty-eight patients affected with single glenoid labrum injury. The injured glenoid labrum of five SLAP cases were treated with debridement under shoulder arthroscopy, and then the affected shoulder was immobilized by zero-degree traction. The injured glenoid labrum of three Bankart cases also underwent debridement under shoulder arthroscopy, and then treated with improved Bristow operation through limited incision. Results After 2-year follow-up, according to the standard criterion of U. S. Michasel Reese Medical Center, the total pain score and the total joint function score were 75 and 25 respectively; the patients' average score was 65 and 20 postoperatively, compared with 35 and 10 preoperatively. The clinical symptoms of all these cases were greatly improved and the unstable symptoms disappeared postoperatively in eight SLAP injury or Bankart injury patients and they all returned their preoperative activities. Conclusion Glenoid labrum is one of the most frequent parts of shoulder joint to be injured. Shoulder arthroscopy is a necessary and effective advanced technique for a definite diagnosis and treatment of glenoid labrum injury. There is some difficulty to carry out operation with arthroscopy and some specific instruments, however, it is necessary for the surgeon to understand and handle the technique.

Repair of articular cartilage by using induced autogeneic mesenchymal cells derived from bone marrow in rabbits / 中华骨科杂志

Objective To observe the tissus implanted into the damaged articular cartilage of rabbits with induced autogeneic mesenchymal cells. Methods The autologous mesenchymal cells derived from bone marrow of New Zealand rabbits were harvested. With basic fibroblast growth factor(bFGF， 25 ng/ml) and transforming growth factor beta 1(TGF-? 1， 2 ng/ml)， the cells were induced and expanded in cell culture. The induced cells with absorbable gelatin sponge as a carrier were then implanted into the damaged articular cartilage in rabbits as experimental group. The absorbable gelatin sponge without cells were served as control. Specimens were harvested at the end of 4, 12 and 24 week after implantation, and were stained with toluidine blue. Results By RT- PCR, it was confirmed that there was expression of typeⅡ procollagen mRNA in the induced mesenchymal cell. After implantation, it was difficult to macroscopically distinguish the repaired tissues from the normal cartilaginous tissue in the experimental group in 24 weeks. While the defect of articular cartilage was filled with white and swampy tissue in the control group at the same time. Histologically, the defective area of the articular cartilage was replaced by the formation of neo- cartilage which showed positive staining of toluidine blue in 4 weeks in the experimental group. The neo- cartilage was modeled to normal cartilage tissues in 12 weeks and was similar to the surrounding cartilage in 24 weeks. But in the control group, the defect of articular cartilage was not repaired by cartilage tissue at every stage and were replaced by fibrocartilage which was shown weakly positive staining of toluidine blue in 24 weeks. Conclusion The transplant of the induced autogeneic mesenchymal cells derived from bone marrow might promote repair of articular cartilage, and restore its structure and function.

Biological Study of Hydroxyapatite Gradient Coatings / 中国矫形外科杂志

Objective: To estimate the biological characteristics of HA gradient coating in vivo.Method:We inserted coated and uncoated implants in bilateral femur of loading area in dogs.Result:Histological findings demonstrated that HA coated implants bind the host bone tightly and the amount and velocity of the new bone formation are more than the uncoated implants.The mean interface shear strength between HA gradient coated implants were greater than those of uncoated implants (p<0.01).Conclusion:The results of this study confirms that HA gradient coatings can has its practical value in orthopeadics fields.