BACKGROUND:Adjustable piezoelectric effect can promote tissue regeneration and repair.Piezoelectric materials are widely used in weight-bearing tissue engineering. OBJECTIVE:To prepare a piezoelectric film material that can promote bone regeneration,and to explore its structural characterization,electrical output performance,biocompatibility,and effect of electrical output on osteogenic differentiation of rabbit bone marrow mesenchymal stem cells. METHODS:Using poly-3-hydroxybutyrateco/4-hydroxybutyrate(P34HB)as raw material,barium calcium stannate titanate powder(Ba0.94Ca0.06Sn0.08Ti0.92O3,BCST)was added according to mass ratios of 0%,5%,10%,15%,and 20%.Dichloromethane was added to solve P34HB,and the thickness of 150-200 μm BCST/P34HB piezoelectric film was prepared by vacuum drying method.After polarization in the oil bath,the surface morphology,crystal phase composition,piezoelectric coefficient and open circuit voltage were tested.The effect of BCST/P34HB electrical output at 110 Hz and 0.25 N force on the proliferation and osteogenic differentiation of rabbit bone marrow mesenchymal stem cells was tested. RESULTS AND CONCLUSION:(1)Scanning electron microscopy,X-ray diffraction,water contact angle,piezoelectric coefficient and electrical output performance tests showed that when the mass ratio of BCST increased to 20%,the BCST/P34HB piezoelectric film had good piezoelectric properties(d33=5.9 pC/N)and electrical output performance(180 mV),which was closer to the suitable range of 500 mV for electrical stimulation.(2)Live and dead staining showed that on the first day of co-culture,15%group and 20%group showed less red fluorescence.On the 5th day of culture,the number of green fluorescence in each group was significantly higher than that on the first day,and the red fluorescence was not observed in the 10%,15%and 20%groups,and only a small amount of red fluorescence was observed in the 0%and 5%groups.(3)On the 1st,3rd and 5th days of co-culture with rabbit bone marrow mesenchymal stem cells,Almar blue staining exhibited that the number of cells in each group showed an increasing trend with the increase of time.On the 5th day of culture,the number of cells in the 20%group was significantly more than that in the 0%group(P<0.05).(4)On day 10 of osteogenic induction,alkaline phosphatase staining results showed that the positive rate of the 20%group was significantly higher than that of the 0%group(P=0.000 1).On day 21,alizarin red staining and quantitative analysis of calcium nodules showed a similar trend to alkaline phosphatase staining.Compared with the 0%group,the 15%group and 20%group showed significant differences(P<0.01,P<0.000 1).(5)The results showed that 20%BCST/P34HB films had good piezoelectric properties,electrical output properties,biocompatibility and the ability of promoting osteogenic differentiation of bone marrow mesenchymal stem cells.

Objective To establish the ultra-high performance liquid chromatography(UPLC)chromatographic fingerprint of Notopterygii Rhizoma et Radix;To determine the contents of ferulic acid,nodakenin,ammijin,notopterol,isoimperatorin and volatile oil of Notopterygii Rhizoma et Radix from different producing areas;To provide reference for quality evaluation of Notopterygii Rhizoma et Radix.Methods Waters BEH C18 chromatographic column(2.1 mm×150 mm,1.7 μm)was used,with mobile phase acetonitrile-0.02%formic acid aqueous solution gradient elution,flow rate 0.25 mL/min,column temperature 25℃,detection wavelength 330 nm,injection volume 2 μL.UPLC fingerprints of 25 batches of Notopterygii Rhizoma et Radix were established,and the similarity analysis and chemometrics analysis were carried out.The contents of ferulic acid,nodakenin,ammijin,notopterol and isoimperatorin were determined simultaneously,and the contents of volatile oil was determined by steam distillation method.Results Totally 23 common fingerprint peaks were calibrated,11 known components were identified.According to the results of the cluster analysis and principal component analysis,25 batches of Notopterygii Rhizoma et Radix samples were divided into 3 categories,and the 6 potential differential components were screened out by orthogonal partial least squares-discriminant analysis(OPLS-DA).The results showed that the contents of notopterol and volatile oil from Sichuan Province were higher than those from Gansu Province and Qinghai Province.Conclusion The method established in the study is accurate and reliable,which can provide scientific basis and reference for the quality evaluation and control of Notopterygii Rhizoma et Radix.

Objective:To investigate the clinical efficacy of three-dimensional speckle tracking imaging in the dynamic evaluation of left ventricular systolic function in patients with pregnancy-induced hypertension.Methods:50 patients with pregnancy-induced hypertension, who received prenatal examination in Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine from July 2019 to June 2020 and finally gave birth, were included in the observation group. An additional 50 healthy pregnant women who concurrently received prenatal examination were included as controls. All participants underwent routine echocardiography and three-dimensional speckle tracking imaging examinations. Parameters related to left ventricular systolic function were recorded. Routine echocardiography parameters and three-dimensional speckle tracking imaging parameters were compared between the observation and control groups.Results:There were no significant differences in routine echocardiography parameters (including heart rate, left ventricular end-diastolic diameter, interventricular septum thickness in end-diastole, left ventricular posterior wall thickness in diastole, and left ventricular ejection fraction) between before treatment, after treatment, and 3 months after delivery in the observation group, and between observation and control groups before treatment (all P > 0.05). The absolute values of left ventricular global longitudinal strain (LVGLS) [(-18.41 ± 2.23)% vs. (-26.03 ± 2.79)%], left ventricular global circumferential strain (LVGCS) [(31.29 ± 3.09)% vs. (37.45 ± 3.68)%], left ventricular global radial strain (LVGRS) [(-19.37 ± 2.19)% vs. (-24.59 ± 2.74)%], and left ventricular global area peak systolic strain (LVGAS) [(-26.61 ± 3.18)% vs. (-39.23 ± 3.96)%] measured before treatment were significantly lower in the observation group than in the control group ( t = 6.31 -14.87, all P < 0.05). The absolute values of LVGLS, LVGCS, LVGRS, and LVGAS in the observation group were significantly higher after treatment [(-24.79 ± 2.68)%, (35.94 ± 3.25)%, (-22.48 ± 2.41)%, (-37.54 ± 3.38)%] and 3 months after delivery [(-25.64 ± 2.72)%, (36.63 ± 3.47)%, (-23.91 ± 2.69)%, (-38.49 ± 3.64)%] than before treatment ( t = 4.08 - 10.59, P < 0.05). There were no significant differences in LVGLS, LVGCS, LVGRS, and LVGAS between observation group and control groups at each time point studied ( t = 0.47 - 1.19, P = 0.182 - 0.652 > 0.05). The absolute svalues of LVGLS, LVGCS, LVGRS and LVGAS in patients with pregnancy-induced hypertension were positively correlated with left ventricular ejection fraction values ( r = 0.638 - 0.775, P = 0.009 - 0.041 < 0.05). Conclusion:Three-dimensional speckle tracking imaging can be used to dynamically evaluate the impairment of left ventricular systolic function in patients with pregnancy-induced hypertension. This technique helps guide early intervention and prognosis evaluation and has a high clinical application value.

Mandibular defects caused by injuries, tumors, and infections are common and can severely affect mandibular function and the patient's appearance. However, mandible reconstruction with a mandibular bionic structure remains challenging. Inspired by the process of intramembranous ossification in mandibular development, a hierarchical vascularized engineered bone consisting of angiogenesis and osteogenesis modules has been produced. Moreover, the hierarchical vascular network and bone structure generated by these hierarchical vascularized engineered bone modules match the particular anatomical structure of the mandible. The ultra-tough polyion complex has been used as the basic scaffold for hierarchical vascularized engineered bone for ensuring better reconstruction of mandible function. According to the results of in vivo experiments, the bone regenerated using hierarchical vascularized engineered bone is similar to the natural mandibular bone in terms of morphology and genomics. The sonic hedgehog signaling pathway is specifically activated in hierarchical vascularized engineered bone, indicating that the new bone in hierarchical vascularized engineered bone underwent a process of intramembranous ossification identical to that of mandible development. Thus, hierarchical vascularized engineered bone has a high potential for clinical application in mandibular defect reconstruction. Moreover, the concept based on developmental processes and bionic structures provides an effective strategy for tissue regeneration.
Bone Regeneration ; Bone Transplantation/methods* ; Hedgehog Proteins ; Humans ; Mandible/surgery* ; Osteogenesis

Objective:To investigate the long term efficacy and side effects of a donor-derived CD19 chimeric antigen receptor (CAR) T-cell (HI19α-4-1BB-ζ CAR-T) therapy in the treatment of patients with relapsed B-cell acute lymphoblastic leukemia (B-ALL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) .Methods:A total of 9 subjects with relapsed B-ALL post allo-HSCT received donor-derived CD19 CAR-T therapy from July 2017 to May 2020. All subjects were infused with donor CD3-positive T cells after lymphodepletion chemotherapy, and a median dose of CAR-T cells was 1.79 (range, 0.86-3.53) ×10 6/kg. Results:①All subjects achieved complete remission and MRD-negative at 28-42 d post CAR-T cells infusion. ②Cytokine releasing syndrome (CRS) occurrd in all subjects and was grade 3 in 2, grade 2 in 4, grade 1 in 3 cases respectively. Four subjects developed immune effector cell-associated neurotoxicity syndrome (ICANS) , which was grade 2 in 1, grade 1 in 3. One subject developed grade IV acute graft-versus-host disease (GVHD) , and side effects were all controllable. ③Four subjects relapsed at a median period of 8.6 (4.6-19.3) months, 2 subjects died of disease progression after receiving chemotherapy and another one also died of disease progression 14 months after a second transplant, only 1 subject achieved complete remission after CD22 CAR-T cell therapy. Until last follow-up date, 6 subjects were leukemia-free and achieved complete donor chimerism. The estimated 1-year and 2-year leukemia-free survival (LFS) rate was 63.5% and 50.8%, with a median LFS of 18.1 months. ④After a median follow-up of 25.1 (range, 6.9-36.7) months, the estimated 2-year and 2.5-year OS rate were 87.5% and 52.5%, respectively.Conclusion:The donor-derived CD19 CAR-T cell therapy obtain a high remission rate in relapsed B-ALL patients post allo-HSCT with tolerable side effects, half subjects survived more than 2 years without disease recurrence, though long-term efficacy requires further observation. Chinese Clinical Trial Registry: ChiCTR1900025419

Objective:To analyze the clinical manifestations and laboratory features in patients with myeloid neoplasms complicated with clonal T large granular lymphocyte (T-LGL) proliferation.Methods:The clinical data of 5 patients with myeloid neoplasms complicated with clonal T-LGL proliferation from November 2017 to November 2018 in Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College were analyzed retrospectively.Results:The median age was 60 years old. All patients had a history of abnormal peripheral blood cell counts for over 6 months. The absolute lymphocyte count in peripheral blood was less than 1.0×10 9/L. In addition to the typical T-LGL phenotype, the immunophenotype was heterogenous including CD4 +CD8 - in 2 patients, the other 3 CD4 -CD8 +. Four patients were αβ type T cells, the other one was γδ type. STAT3 mutation was detected in 1 patient by next-generation sequencing, the other 4 cases were negative. Conclusions:Clonal T-LGL proliferation with myeloid neoplasm develops in an indolent manner, mainly in elderly patients. Hemocytopenia is the most common manifestation. The diagnosis of T-LGL proliferation does not have specific criteria, that it should be differentiated from other T cell proliferative disorders, such as T-cell clones of undetermined significance. STAT3 or STAT5b mutation may help distinguish.

OBJECTIVETo investigate the myeloperoxidase (cMPO) expression pattern by flow cytometry (FCM) in patients with acute myeloid leukemia (AML) and its role in classifying AML.

METHODSEight- color multiparametric FCM with CD45/SSC gating was used to determine the cMPO expression in 502 AML patients.

RESULTSThe positive rate of cMPO in all patients was 58.0%, in which the proportion of normal positivity, dim positivity and partial positivity was 21.5%, 34.1% and 2.4%, respectively. The remaining case (42.0%) were all negative. In AML with t (15;17）(q22;q12)/PMLRARα, the positive rate was the highest (100%) and the intensity was similar to that of the normal granular leukocytes, followed by AML with t (8;21（q22;q22/RUNX1-RUNX1T1, the positive rate was 91.4% and the intensity was mostly dim. AML with minimal differentiation and acute megakaryoblastic leukemia were all cMPO negative. The positive rates of cMPO in the remaining subtypes were between 22.7% and 76.2%.

CONCLUSIONThe positive rate and intensity of cMPO were significantly different among different subtypes of AML.

Objective To introduce the technique of metal-on-metal hip resurfacing arthroplasty,evaluate its preliminary clinical results and review the factors which affect the results.Methods From January 2006 to October 2010,104 patients (116 hips) with osteonecrosis of the femoral head,hip osteoarthritis,hip dyplasia,or ankylosing spondylitis were treated with the total hip resurfacing arthroplasty.Among them,59 patients (66 hips) were male,and 45 patients (50 hips) were female,with an average age of 39.7 years (range,16-67 years).Standard operation technique was performed for all patients with Conserve Plus prosthesis.Each patient was followed up at 1 month,3 months,6 months,1 year postoperatively.Results Three patients (4 hips) were lost,so 101 patients (112 hips) were followed up for an average period of 33 months (range,9-66 months).The average Harris hip score was improved significantly from 37.6±6.3 preoperatively to 91.3±5.3 at final follow-up; 104 hips were excellent,7 hips were good,1 hip was poor,and the excellent and good rate was 99.1％.At final follow-up,the average abduction angle of the acetabutar cup was 42.7°(range,36°-55°); the average femoral prothesis stem-shaft angle was 138.5° (range,132°-146°).Two patients presented with heterotopic ossification (Brook Ⅲ and Brook Ⅱ ).One patient presented with prothesis dislocation,which healed after being treated with manual reduction.There was no femoral neck fracture,infection,or prosthesis loosening.Conclusion With strict patient selection criteria and optimized technique,the short-term results of metal-on-metal hip resurfacing arthroplasty are satisfactory.

Objective To investigate the methods of diagnosis and treatment of pediatric and hebetic adrenocorticotropic hormone ( ACTH) secreting pituitary microadenoma. Methods The data of 10 patients with ACTH secreting pituitary microadenoma were retrospectively analysed. ACTH secreting pituitary microadenoma was diagnosed by clinical manifestations, biochemical and imaging findings, and 5 patients underwent bilateral inferior petrosal sinus sampling ( BIPSS). Transsphenoidal surgery was performed on all the patients under microscope, and the tumor specimens were detected by immunohistochemistry. Results Immunohistochemical examination revealed that ACTH was positive in 8 cases and negative in 2 cases. Patients were followed up for 12 to 63 months, 7 cases (70%) were cured, one (10%) achieved remission, and the other two (20%) experienced recurrence. Conclusion BIPSS is helpful in the diagnosis and localization of pediatric and hebetic ACTH pituitary microadenoma, and transsphenoidal surgery is the optimal choice of treatment.