Objective To find the effects of varus degree on the early metabolic changes of the lateral compartment cartilage in knees with medial unicompartmental osteoarthritis by detecting glycosaminoglycan (GAG) in varus knees.Methods From June 2016 to December 2017,twenty middle-aged volunteers without osteoarthritis or coronal deformities were recruited as the control group.Sixty patients diagnosed as medial unicompartmental osteoarthritis were recruited as the osteoarthritis group.The patients were further divided into four groups according to the degrees of varus angle,namely 2°-5° varus group,5°-10° varus group,10°-15° varus group and ＞15° varus group with 15 patients in each group.Delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) was performed in all participants.The dGEMRIC indices (T1Gd) representing GAG content were calculated in the weight-bearing femoral cartilage (wbFC),the posterior non-weight-bearing femoral cartilage (pFC),the lateral femoral cartilage (FC,wbFC+pFC) and the tibial cartilage (TC) in the lateral compartment by using Matlab 7.1 and MRIMapper software.Results T1Gd of wbFC,pFC,FC and TC were 400.3±51.5 ms,393.6±57.9 ms,397.5±52.3 ms and 448.6±62.5 ms in the control group,391.8±41.5 ms,407.2±43.8 ms,400.1±37.8 ms and 461.3±41.6 ms in 2°-5° varus group and 386.9±57.1 ms,401.3±73.5 ms,397.7±59.6 ms and 438.9±42.8 ms in 5°-10° varus group.There was no significant difference among the above three groups in T1Gd in any of the analyzed cartilage regions (P＞0.05).In 10°-15° varus group,T1Gd of wbFC,pFC,FC and TC were 380.1±45.5 ms,385.5±76.6 ms,384.0±53.5 ms and 400.2±43.8 ms,respectively.Although T1Gd of wbFC,pFC and FC in 10°-15° varus group were similar with that in the control group,2°-5° varus group and 5°-10° varus (P＞0.05),T1Gd of TC in 10°-15° varus group decreased significantly (P＜0.05).In addition,T1Gd of wbFC,pFC,FC and TC in ＞15° varus groupwere 327.7±54.3 ms,340.1±33.0 ms,334.9±36.0 ms and 363.6±48.6 ms,respectively.T1Gd of all regions of interest in ＞15° varus group were significantly lower than that informer four groups (P＜0.05).Conclusion In medial unicompartmental knee osteoarthritis,there is a relationship between varus degree and GAG content of the lateral compartment cartilage.If varus angle ≤10°,the GAG content of the lateral compartment cartilage was similar with the similar aged subjects without osteoarthritis.If varus angle ＞ 10°,GAG content of the lateral compartment decreases significantly.

Immune checkpoint inhibitors (ICIs) have demonstrated unparalleled clinical responses and revolutionized the paradigm of tumor treatment, while substantial patients remain unresponsive or develop resistance to ICIs as a single agent, which is traceable to cellular metabolic dysfunction. Although dysregulated metabolism has long been adjudged as a hallmark of tumor, it is now increasingly accepted that metabolic reprogramming is not exclusive to tumor cells but is also characteristic of immunocytes. Correspondingly, people used to pay more attention to the effect of tumor cell metabolism on immunocytes, but in practice immunocytes interact intimately with their own metabolic function in a way that has never been realized before during their activation and differentiation, which opens up a whole new frontier called immunometabolism. The metabolic intervention for tumor-infiltrating immunocytes could offer fresh opportunities to break the resistance and ameliorate existing ICI immunotherapy, whose crux might be to ascertain synergistic combinations of metabolic intervention with ICIs to reap synergic benefits and facilitate an adjusted anti-tumor immune response. Herein, we elaborate potential mechanisms underlying immunotherapy resistance from a novel dimension of metabolic reprogramming in diverse tumor-infiltrating immunocytes, and related metabolic intervention in the hope of offering a reference for targeting metabolic vulnerabilities to circumvent immunotherapeutic resistance.
Humans ; Neoplasms/pathology* ; Immunotherapy/methods* ; Immune Checkpoint Inhibitors/therapeutic use*