We aimed to evaluate the role of extracorporeal shockwave therapy (ESWT) in improving osteonecrosis of the femoral head (ONFH). We searched studies focusing on the role of ESWT in ONFH using PubMed, Embase, the Cochrane Library, WanFang, VIP, and CNKI databases updated up to July 28, 2017, without language restriction. Standardized mean difference (SMD) values and 95% confidence intervals (95% CIs) were pooled to compare the pain score and Harris hip score for ESWT treatment and other treatment strategies. Four articles, including 230 ONFH patients, were eligible for the meta-analysis. No significant differences were found in the pain score (SMD = − 1.0104; 95% CI − 2.3279–0.3071) and Harris hip score (SMD = 0.3717; 95% CI − 0.3125–1.0559) between the two groups before treatment. After treatment, significant differences were found between the experimental and control groups in the pain score (SMD = − 2.1148; 95% CI − 3.2332–0.9965) and Harris hip score (SMD = 2.1377; 95% CI 1.2875–2.9880). There were no significant differences in pain score before and after treatment between the two groups (SMD = − 0.7353; 95% CI − 2.1272–0.6566), but significant differences were found in the Harris hip score (SMD = 1.2969; 95% CI 0.7171–1.8767). For patients at an early stage, ESWT may be safe and effective for relief of pain and improvement of motor function.

To probe into the mechanism of the Chinese herbs with functions of reinforcing kidney and supplementing qi for preventing knee osteoarthritis of the rabbit. Totally 72 healthy Japan long-ear white rabbits, aged 4 months, were randomly divided into 6 groups, blank group (A), model group (B), high dose Chinese herb group (C), middle dose Chinese herb group (D), small dose Chinese herb group (E), aminoglucose hydrochloride capsule control group (F), 12 rabbits in each group. All the rabbits in the groups, except the group A, were fixed with plaster cast for six weeks to establish rabbit knee osteoarthritis. At the same time of modeling, the different doses of Juanbi Capsules and aminoglucose hydrochloride capsule were administrated intragastrically in the group C, D, E, F, respectively, for 4 weeks, for preventive treatment. In the group B, the rabbit was administrated intragastrically with equal volume of normal saline to the medication groups, twice each day, in the morning and the evening, and in the group A, nothing was administrated. After modeling for 6 weeks, the joint fluid was taken and TNF-alpha, IL-1 and IL-6 contents were detected with ELISA method, and the articular cartilage was taken for macroscopic and microscopic examinations. In all the preventive treatment groups, the articular cartilage color changed to varying degrees with formation of osteophyte and bone cyst, superficial erosion on the chondral articular surface, and the cartilage defect reached to the mid layer in a part of specimens with cartilage exfoliation, but which in the extent were significantly lower than those in the model group. There were significant differences between the group A and B in TNF-alpha, IL-1 and IL-6 contents in the joint fluid (P < 0.05), indicating that the modeling is successful; and there were significant differences as group B compared with the group C,D, E, F, showing that TNF-alpha , IL-1 and IL-6 contents are decreased in all the medication groups; and significant differences between group C, D, E suggests that the increase of Chinese herb doses strengthened the effect of reducing TNF-alpha, IL-1 and IL-6 contents in joint fluid. The Juanbi Capsule prevents osteoarthritis possibly through decreasing serum TNF-alpha, IL-1 and IL-6 contents.

Osteoarthritis (OA) is an increasingly prevalent disease affecting synovial joints, which includes joint degeneration, inflammation, and joint pain. The activation of nucleotide‐binding and oligomerization domain‐like receptor containing protein 3 (NLRP3) could promote synovial inflammation. Previous studies have shown that electroacupuncture (EA) has potential anti‐inflammatory effect. However, the effect of EA treatment on OA remains unclear. The aim of this study was to investigate the effect of applied EA on OA and joint pain and its relationship with NLRP3 inflammasome. The Hartley guinea pigs with naturally occurring OA at age 18 months were chosen as the OA model and treated with EA for 4 weeks. Mechanical allodynia was quantified by using von Frey filaments. The expression of NLRP3 inflammasome and the downstream proinflammatory factors in the cartilage tissue were quantified. Our results showed that EA treatment significantly reduces mechanical allodynia, improves the articular cartilage structure, and decreases the fibrillation on the cartilage surface in guinea pigs with spontaneous osteoarthritis. Moreover, we also found that EA treatment attenuates the NLRP3 inflammasome activation and suppresses the protein expression levels of caspase‐1 and IL‐1β in the cartilage tissue. Our findings suggest that EA treatment attenuates OA and joint pain by suppressing NLRP3 inflammasome activation and support further investigation of the potential therapeutic tactics.

The objective of this study was to evaluate whether apolipoprotein gene polymorphisms confer susceptibility to osteonecrosis of the femoral head (ONFH). The relevant literature was screened from databases of Pubmed, Embase, Wanfang, Weipu and China National Knowledge Internet (CNKI) until May, 2017. In addition, odds ratio (OR) and its corresponding 95% confidence interval (CI) were used as a measure of effect size for calculating effect size. Totally, six case-control studies were included in this meta-analysis. It revealed that ApoB-C7623T polymorphism frequency was increased in ONFH group than in control group under three genetic models, including allele model (T vs. C, OR = 4.5149, 95% CI: 1.6968–12.0134); additive model (TC vs. CC, OR = 6.2515, 95% CI: 2.0939–18.6640); and dominant model (TT + TC vs. CC, OR = 5.4998, 95% CI: 1.9246–15.7163). In addition, the increased risk of ONFH were related to ApoA1-rs1799837 polymorphism under additive model (AA vs. GG, OR = 1.4175, 95% CI: 1.0522–1.9096) and recessive model (AA vs. GG + AG, OR = 1.7727, 95% CI: 1.3399–2.3452). However, four ApoB rs1042031, rs693, 3’-VNTR and G12619A polymorphisms under the all genetic models were not associated with susceptibility to ONFH. The T allele and TC genotype of ApoB-C7623T and AA genotype of ApoA1-rs1799837 may contribute to increase the risk of ONFH.

Background CD24 is a small glycosylphosphatidylinositol (GPI)-anchored glycoprotein overexpressed on multiple types of cancers including lymphoma, breast cancer, ovarian cancer, where it reportedly regulates cell migration, invasion, proliferation and immune escape.¹ Apart from being viewed as a tumor-associated antigen (TAA), CD24 was recently found to suppress tumor phagocytosis by delivering a ‘don’t-eat-me’ signal via binding to Siglec-10 expressed on tumor-associated macrophages.² We hypothesize that selective tumor targeting of the CD24-Siglec-10 pathway by anti-CD24 mAb may represent a novel therapeutic approach to enhance anti-cancer immunity while avoiding potential on-target off-tumor toxicity. Methods We immunized mice with the extracellular portion of human CD24 purified from both the E. coli and 293T expression systems and screened for hCD24-binding hybridomas by ELISA. We evaluated the affinity of binders by SPR and selective tumor cell binding over normal cells by FACS. We profiled lead antibodies in ADCC and ADCP co-culture studies and in in vivo tumor cell efficacy models. We humanized the best clone in silico and affinity matured it by saturation mutation. We determined the epitope of the lead candidate (NXA01) by overlapping peptide blocking and co-crystallography studies. Results With an affinity of 1.5 nM as determined by SPR, NXA01 bound to hCD24 on tumor cells such as NALM6 and MDA-MB-468 but not to normal human granulocytes or B cells. This tumor selectivity was related to preferential binding of NXA01 to aglycosylated or hypogylcosylated hCD24 as enzymatic deglycosylation of normal cells restored binding. NXA01 blocked hCD24-Siglec10 interaction with an EC50 of 8 nM and as a result enhanced ADCP activity of tafasitamab (anti-CD19). NXA01 could also mediate direct killing of NALM6 and MDA-MB-468 cells through both ADCC and ADCP at EC50s of <10 nM, but it spared normal B cells in a tumor/normal mixed cell culture, further indicating tumor selectivity. Finally, NXA01 treatment significantly inhibited the growth of MC38-hCD24, NALM6 and MDA-MB-468 tumor cells in vivo with maximal inhibition of 104%, 105% and 51%, respectively. Conclusions NXA01 is a potential best-in-class CD24 blocking antibody that exhibits selective tumor binding and strong anti-tumor activity in vitro and in vivo. The dual mechanism of ADCC and macrophage checkpoint blockade makes NXA01 a good candidate for monotherapy as well as a combination partner with other TAA or immune-oncological drugs. IND-enabling studies are ongoing for NXA01. References Altevogt P, Sammar M, Hüser L, Kristiansen G. Novel insights into the function of CD24: A driving force in cancer. Int. J. Cancer. 2021;148:546–559 Barkal AA, Brewer RE, Markovic M, et al. CD24 signalling through macrophage Siglec-10 is a target for cancer immunotherapy. Nature. 2019;572:392–396.