Objective:To identify XMA09,a broadly neutralizing antibody against severe acute respiratory syndrome coronavi-rus 2(SARS-CoV-2),and to explore the potential mechanism of XMA09 to broadly neutralize variants of SARS-CoV-2,so as to pro-vide a reference for vaccine design and broadly neutralizing antibody screening against SARS-CoV-2.Methods:XMA09 protein was expressed and purified by ExpiCHO expression system and Protein A chromatography column.The key amino acid sites on receptor binding domain(RBD)recognized by XMA09 were identified by Cryo-EM,and the affinity of XMA09 to Spike protein of SARS-CoV-2 and its variants was detected by indirect ELISA and Surface Plasmon Resonance(SPR).The pseudovirus neutralization assay based on vesicular stomatitis virus(VSV)was used to detect the neutralization ability of XMA09 to wild-type and variants of SARS-CoV-2.Results:In this study,it was found that the epitopes recognized by XMA09 were conservative,who has an excellent binding ability to Spike protein of many kinds of variants,and could neutralize the variants of concern(VOCs),including the widespread BA.4/5.Conclusion:XMA09 is a broadly neutralizing antibody,which has the potential to be used as a therapeutic antibody against SARS-CoV-2,and can provide reference for broad-spectrum vaccine design and antibody drug development against SARS-CoV-2.

Osteoarthritis (OA), in which M1 macrophage polarization in the synovium exacerbates disease progression, is a major cause of cartilage degeneration and functional disabilities. Therapeutic strategies of OA designed to interfere with the polarization of macrophages have rarely been reported. Here, we report that SHP099, as an allosteric inhibitor of src-homology 2-containing protein tyrosine phosphatase 2 (SHP2), attenuated osteoarthritis progression by inhibiting M1 macrophage polarization. We demonstrated that M1 macrophage polarization was accompanied by the overexpression of SHP2 in the synovial tissues of OA patients and OA model mice. Compared to wild-type (WT) mice, myeloid lineage conditional Shp2 knockout (cKO) mice showed decreased M1 macrophage polarization and attenuated severity of synovitis, an elevated expression of cartilage phenotype protein collagen II (COL2), and a decreased expression of cartilage degradation markers collagen X (COL10) and matrix metalloproteinase 3 (MMP3) in OA cartilage. Further mechanistic analysis showed thatSHP099 inhibited lipopolysaccharide (LPS)-induced Toll-like receptor (TLR) signaling mediated by nuclear factor kappa B (NF-κB) and PI3K-AKT signaling. Moreover, intra-articular injection of SHP099 also significantly attenuated OA progression, including joint synovitis and cartilage damage. These results indicated that allosteric inhibition of SHP2 might be a promising therapeutic strategy for the treatment of OA.

The abnormal thyroid function in the duration of drug treatment has attracted increasing attention, these drugs included traditional drugs, such as glucocorticoid, nonsteroidal anti-inflammatory drug, iodine agent, etc.; also included new types of drugs, such as immune checkpoint inhibitors. The possible reasons causing abnormality of thyroid biomarkers included drugs′ toxicity on thyroid, drug-drug interaction affecting synthetic thyroid hormones therapy, and drug′s interference on biomarkers′ measurement. This article focused on the influence and mechanisms of common drugs on the regulation, synthesis, release, transport and metabolism of thyroid hormones. Here also briefly introduced the mechanism of drug-drugs interaction on the effect of synthetic thyroid hormone; the interference and mechanism of some drugs on the laboratory measurement was also included. The aim of this article was to strengthen clinician′s understanding on drug-induced thyroid diseases and to be alert to drugs′ interference on the in-vitro measurement of biomarkers.

The abnormal thyroid function in the duration of drug treatment has attracted increasing attention, these drugs included traditional drugs, such as glucocorticoid, nonsteroidal anti-inflammatory drug, iodine agent, etc.; also included new types of drugs, such as immune checkpoint inhibitors. The possible reasons causing abnormality of thyroid biomarkers included drugs′ toxicity on thyroid, drug-drug interaction affecting synthetic thyroid hormones therapy, and drug′s interference on biomarkers′ measurement. This article focused on the influence and mechanisms of common drugs on the regulation, synthesis, release, transport and metabolism of thyroid hormones. Here also briefly introduced the mechanism of drug-drugs interaction on the effect of synthetic thyroid hormone; the interference and mechanism of some drugs on the laboratory measurement was also included. The aim of this article was to strengthen clinician′s understanding on drug-induced thyroid diseases and to be alert to drugs′ interference on the in-vitro measurement of biomarkers.

Objective:To explore the role of virtual reduction and design of 3D printed guide template in assisting reduction and internal fixation of comminuted patellar fractures.Methods:A retrospective study was conducted of 12 patients who had been treated for closed patellar fractures from March 2016 to April 2019 at Department of Orthopaedics, Jiangxi Provincial People's Hospital. They were 8 males and 4 females with an average age of 35.4 years (from 22 to 51). All their fractures were type 34-C3 (more than 3 fragments) according to the AO/OTA classification. Their preoperative CT data were imported into software Mimics to print a full patella, upper and lower halves of the patella, and a guide template for reduction. During operation, bone fragments were first temporarily fixated with a fine Kirschner wire after combined together with the assistance of reduction templates for upper and lower hemi-patellas. Next, the whole patella was precisely reset and definitely fixated using patellar ring ligation and tension band wire with the assistance of the reduction guide template for full patellar. Recorded were operation time, fluoroscopic frequency, and visual analogue scale (VAS), knee range of motion (ROM) and knee function B?stman scores at the last follow-up.Results:In this group of patients, operation time averaged 90 minutes (from 75 to 120 minutes), fluoroscopic frequency 4.5 times (from 3 to 8 times), follow-up duration 19 weeks (from 16 to 22 weeks), and fracture healing time 14 weeks (from 11 to 17 weeks). At their last follow-up, X-ray showed good patellar morphology, fine internal fixation positions and an average VAS pain scores of 0.3 (from 0 to 1), their knee joints could be fully straightened, their knee ROM averaged 130°(from 100° to 138°), and their knee B?stman scores 28.8 points (from 21 to 30 points), giving 9 excellent and 3 good cases.Conclusion:3D printed reduction guide templates can significantly improve the efficiency and quality of surgical reduction in comminuted patella fractures, enhancing fixation strength and facilitating early and full range exercise of the knee joint to achieve excellent recovery.

OBJECTIVE: To analyze the accuracy and positive rate of ultrasound-guided fine-needle aspiration (US-FNA) cytology for detecting suspected thyroid cancer nodules of different sizes. METHODS: A total of 591 patients with 594 suspected malignant thyroid nodules received examinations with US-FNA cytology. Based on their size, the nodules were divided into group I (4-5 mm), group II (6-10 mm), group III (>10 mm). With the results of pathology as the standard, we analyzed the results of US-FNA cytology for detecting thyroid carcinoma in terms of its accuracy, indeterminate rate, positive predictive value and negative predictive value for nodules of different sizes. RESULTS: The positive rates in group I, group II and group III were 39.2% (40/102), 48.2% (172/357) and 65.2% (88/135), respectively, similar between groups I and II (=0.107) and differed significantly between groups I and III (=0.000) and between groups II and III (=0.001). The accuracy, indeterminate rate, positive predictive value and negative predictive value in the 3 groups were 95.5% (21/22), 97.1% (100/103), and 94.4% (51/54); 2.9% (3/102), 2.8% (10/357), and 1.5% (2/135); 100%, 100%, and 98%; 66.7%, 57.1%, and 33.3%, respectively, showing no significant differences among the 3 groups. CONCLUSIONS The size of the thyroid nodules can affect the positive rate but does not have significant effects on the accuracy, indeterminate rate, positive predictive value or negative predictive value of US-FNA cytology.
Biopsy, Fine-Needle ; Humans ; Retrospective Studies ; Thyroid Neoplasms ; Thyroid Nodule ; Ultrasonography, Interventional

Objective To explore the anatomic basis for and clinical outcomes of the internal fixation which preserves the pronator quadratus (PQ) for distal radius fractures.Methods Twenty cadaveric specimens of adult upper extremity were used for this study (14 males and 6 females).The radial and ulnar lengths of PQ,the distal and proximal widths of PQ,the distances from the distal end of PQ to the articular surface of the distal radius and to the transverse line of the wrist,and the width of the bony tunnel of PQ were dissected and measured to study the anatomical features of PQ.A retrospective study was conducted of the 18 distal radius fractures which had been treated from March 2015 to March 2017 by internal fixation with T-shaped anatomic locking compression plate (LCP) with PQ preserved.They were 8 males and 10 females,with an average age of 52.7 years (range,from 28 to 65 years).According to the AO classification,there were 8 cases of type 23-A,5 ones of type 23-B and 5 ones of type 23-C1.The functional outcomes of the wrist were assessed using the Cooney scoring system at the last follow-ups.Results The PQ muscle was flat and like a right angle trapezoid with rich blood vessels.The radial and ulnar lengths of PQ were about 4.60 cm and 4.46 cm;the distal and proximal widths of PQ were about 4.41 cm and 4.48 cm;the distance from the distal end of PQ to the transverse line of the wrist was about 3.61 cm;the widths of the distal and proximal bony tunnels were about 3.08 cm and 1.91 cm.The 18 patients were followed up for 6 to 36 months (average,11.5 months).Bone union was achieved in all the patients after a mean time of 2.5 months (range,from 2 to 3 months).The mean Cooney score for the wrist function was 97.7 (range,from 95 to 100) at the last follow-up,yielding an excellent rate of 100％.Conclusions The transverse line of the distal radius fracture is located between 1/4 and 1/2 of the distal PQ.The bony tunnel of PQ is wide enough.It is feasible to preserve the distal PQ muscle in the internal fixation of distal radius fractures of types 23-A,23-B and 23-C1,because it may lead to rapid recovery of the patients and satisfactory wrist function.

Human epidermal growth factor receptor 2 (HER2) proteins are overexpressed in a high proportion of gastric cancer (GC) cases and affect the maintenance of cancer stem cell (CSC) subpopulations, which are used as targets for the clinical treatment of patients with HER2-positive GC. Despite improvements in survival, numerous HER2-positive patients fail treatment with trastuzumab, highlighting the need for more effective therapies. In this study, we generated a novel type of genetically modified human T cells, expressing a chimeric antigen receptor (CAR), and targeting the GC cell antigen HER2, which harbors the CD137 and CD3ζ moieties. Our findings show that the expanded CAR-T cells, expressing an increased central memory phenotype, were activated by the specific recognition of HER2 antigens in an MHC-independent manner, and effectively killed patient-derived HER2-positive GC cells. In HER2-positive xenograft tumors, CAR-T cells exhibited considerably enhanced tumor inhibition ability, long-term survival, and homing to targets, compared with those of non-transduced T cells. The sphere-forming ability and in vivo tumorigenicity of patient-derived gastric cancer stem-like cells, expressing HER2 and the CD44 protein, were also inhibited. Our results support the future development and clinical application of this adoptive immunotherapy in patients with HER2-positive advanced GC.
Animals ; Humans ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasms, Experimental ; immunology ; pathology ; therapy ; Receptor, ErbB-2 ; immunology ; Receptors, Antigen, T-Cell ; immunology ; Stomach Neoplasms ; immunology ; pathology ; therapy ; Tumor Cells, Cultured

Objective To investigate the value of integrin αvβ3 targeted microSPECT/CT imaging with 99 Tcm-3P4-RGD2 as a radiotracer in tumor anti-angiogenesis therapy .Methods Animal models bearing glioma and prostate cancer xenografts were established by subcutaneously injecting tumor cells U87MG and PC-3 in nude mice.Anti-angiogensis therapy with Avastin was administered via intraperitoneal injection when the tumor diameter reached 6 to 7 mm while saline was served as control group . MicroSPECT/CT imaging was performed with 99 Tcm-3P4-RGD2 as radiotracer one day before and 3, 5, 10, 15 days after Avastin administration .Tumor volume and tumor uptake of 99 Tcm-3P4-RGD2 , expressed as percentage of injected dose (%ID) or %ID per gram (%ID/g) were measured and calculated based on microSPECT/CT.Mice basic condition was monitored and tumor xenograft was harvested in one tumor bearing nude mouse after its sacrifice at each imaging time point .Results Tumor volume of U87MG glioma in the administration group was significantly smaller than that of non-administration control group at 10 d after Avastin adminstration ( t=5.81, P<0.05), while no significance was observed between the administration group and its control group of PC-3 tumor (P >0.05).The uptake of 99Tcm-3P4-RGD2 (%ID/g) in U87MG group was higher than that in PC-3 group before Avastin administration ( t=10.48, P<0.05), and it decreased to a value less than control ( t =3.26, P <0.05) at 3 d after Avastin administration and continually reduced at longer time after administration .PC-3 tumor had less uptake of 99 Tcm-3P4-RGD2 in both Avastin administration group and its control group .The pathologic results revealed on that the decrease of tumor integrin β3 expression in U87MG treatment group was mainly on the endothelial cells of the neovessel .Linear relationship was verified between tumor uptake (%ID/g ) and integrin β3 expression (y=0.499 1x-0.243 8, R2 =0.811 7).Conclusions Complete inhibition of integrin is demonstrated early after Avastin administration .99 Tcm-3P4-RGD2 microSPECT/CT imaging, assessing the expression level of integrin αvβ3 level by quantification of tumor uptake of 99 Tcm-3P4-RGD2 , is probably an important method to reflect the early therapeutic effect of tumor anti -angiogensis .

BACKGROUND:Fibroblast-like synoviocytes (FLS) in the synovial lining layer are related to the cell proliferation, invasion, migration and apoptosis as well as bone resorption in rheumatoid arthritis. OBJECTIVE:To compare the migration and invasion abilities of FLS (MH7A) in rheumatoid arthritis and normal FLS (HFLS). METHODS:The capacities of cell migration and invasion were evaluated by Transwell cell migration and invasion assays. The primers of the indicated microRNAs were designed and synthesized, and the expression levels of miRNAs were determined by real-time PCR according to the SYBR?PrimeScript?miRNA RT-PCR Kit instruction. RESULTS AND CONCLUSION:MH7A possessed stronger migration and invasion abilities than HFLS. Compared with HFLS, obviously upregulated miR-132, -155, -203, -223 and -124, and significantly downregulated miR-15a, -16, 18a, -19a, -26a and -146a were found in MH7A. These findings suggest that the differentially expressed 11 kinds of rheumatoid arthritis-associated miRNAs participate in the pathogenesis of rheumatoid arthritis probably by enhancing the migration and invasion capacities of MH7A.