Combining single-cell RNA sequencing and population-based studies reveals hand osteoarthritis-associated chondrocyte subpopulations and pathways

Hand osteoarthritis is a common heterogeneous joint disorder with unclear molecular mechanisms and no disease-modifying drugs.In this study,we performed single-cell RNA sequencing analysis to compare the cellular composition and subpopulationspecific gene expression between cartilage with macroscopically confirmed osteoarthritis(n=5)and cartilage without osteoarthritis(n=5)from the interphalangeal joints of five donors.Of 105142 cells,we identified 13 subpopulations,including a novel subpopulation with inflammation-modulating potential annotated as inflammatory chondrocytes.Fibrocartilage chondrocytes exhibited extensive alteration of gene expression patterns in osteoarthritic cartilage compared with nonosteoarthritic cartilage.Both inflammatory chondrocytes and fibrocartilage chondrocytes showed a trend toward increased numbers in osteoarthritic cartilage.In these two subpopulations from osteoarthritic cartilage,the ferroptosis pathway was enriched,and expression of iron overload-related genes,e.g.,FTH1,was elevated.To verify these findings,we conducted a Mendelian randomization study using UK Biobank and a population-based cross-sectional study using data collected from Xiangya Osteoarthritis Study.Genetic predisposition toward higher expression of FTH1 mRNA significantly increased the risk of hand osteoarthritis(odds ratio=1.07,95%confidence interval:1.02–1.11)among participants(n=332668)in UK Biobank.High levels of serum ferritin(encoded by FTH1),a biomarker of body iron overload,were significantly associated with a high prevalence of hand osteoarthritis among participants(n=1241)of Xiangya Osteoarthritis Study(P-for-trend=0.037).In conclusion,our findings indicate that inflammatory and fibrocartilage chondrocytes are key subpopulations and that ferroptosis may be a key pathway in hand osteoarthritis,providing new insights into the pathophysiology and potential therapeutic targets of hand osteoarthritis.

Clinical Effect of Lateral Transforaminal Endoscopic Surgery in the Treatment of Lumbar Disc Herniation

Objective:To analyze the efficacy of lateral transforaminal endoscopic surgery in the treatment of lumbar disc herniation.Methods:A total of 44 patients with lumbar disc herniation,treated in Yancheng No.l People's Hospital from January 2019 to June 2020,were randomly divided into two groups;the 24 patients in group A were treated by lateral transforaminal endoscopic surgery,while the 20 patients in group B were treated by routine lamina fenestration and nucleus pulposus surgery.Results:The curative effect of group A(91.67%)was higher than that of group B(85.0%),P>0.05;there was no significant difference in the angle from straight leg raise between group A and group B(P>0.05);the Oswestry Disability Index(ODI)and the visual analogue scale(VAS)of group A were lower than those of group B(P<0.05);the incision length,intraoperative blood loss,and hospital stay of the patients in group A were better than those in group B,P<0.05.Conclusion:Lateral transforaminal endoscopic surgery can significantly reduce pain,improve symptoms,and help to restore normal function in the early stage for patients with lumbar disc herniation.

Variable Importance Measure System Based on Advanced Random Forest

The variable importance measure(VIM)can be implemented to rank or select important variables,which can effectively reduce the variable dimension and shorten the computational time.Random forest(RF)is an ensemble learning method by constructing multiple decision trees.In order to improve the prediction accuracy of random forest,advanced random forest is presented by using Kriging models as the models of leaf nodes in all the decision trees.Referring to the Mean Decrease Accuracy(MDA)index based on Out-of-Bag(OOB)data,the single variable,group variables and correlated variables importance measures are proposed to establish a complete VIM system on the basis of advanced random forest.The link of MDA and variance-based sensitivity total index is explored,and then the corresponding relationship of proposed VIM indices and variance-based global sensitivity indices are constructed,which gives a novel way to solve variance-based global sensitivity.Finally,several numerical and engineering examples are given to verify the effectiveness of proposed VIM system and the validity of the established relationship.

一体化创伤中心对严重多发伤患者救治质量的影响

目的研究一体化创伤中心对严重多发伤患者救治质量的影响。方法采用回顾性病例对照研究分析2016年1月至2022年12月常州市第二人民医院收治的1286例严重多发伤患者的临床资料,其中男性894例,女性392例;年龄16~80岁,平均(51.9±15.9)岁。损伤严重程度评分(ISS)16~57分,平均(28.0±9.1)分。以我院一体化创伤中心稳定运行后救治的735例患者为观察组,一体化创伤中心成立前及成立初期救治的551例患者为对照组。比较两组患者在创伤救治质量方面的差异。结果观察组的创伤救治质控指标明显优于对照组。结论一体化创伤中心能有效提升严重创伤患者的救治质量,提高救治成功率,值得进一步推广。

WDR62-deficiency Causes Autism-like Behaviors Independent of Microcephaly in Mice

Brain size abnormality is correlated with an increased frequency of autism spectrum disorder(ASD)in offspring.Genetic analysis indicates that heterozygous mutations of the WD repeat domain 62(WDR62)are associated with ASD.However,biological evidence is still lacking.Our study showed that Wdr62 knockout(KO)led to reduced brain size with impaired learning and memory,as well as ASD-like behaviors in mice.Interestingly,Wdr62 Nex-cKO mice(depletion of WDR62 in differentiated neurons)had a largely normal brain size but with aberrant social interactions and repetitive behaviors.WDR62 regulated dendritic spinogenesis and excitatory synaptic transmission in cortical pyramidal neurons.Finally,we revealed that retinoic acid gavages significantly alleviated ASD-like behaviors in mice with WDR62 haploinsufficiency,probably by complementing the expression of ASD and synapse-related genes.Our findings provide a new perspective on the relationship between the microcephaly gene WDR62 and ASD etiology that will benefit clinical diagnosis and intervention of ASD.

The microRNA,miR-29c,participates in muscle development through targeting the YY1 gene and is associated with postmortem muscle pH in pigs

Previous studies indicated that miR-29c is important for muscle development in mice and human,but its role in pigs is unknown.In this study,we detected the expression of miR-29c in Meishan longissimus lumborum(LL)muscle.The results showed that miR-29c was gradually upregulated during development of skeletal muscle in pig.Moreover,the expression of YY1 and Akt3 genes,which were confirmed to be targeted by miR-29c in mice,was decreased along with muscle development.Furthermore,the expression level of miR-29c was significantly higher in adult Meishan pigs than Large White pigs,while the expression of YY1 and Akt3 genes was significantly lower in Meishan pigs.These results indicated that the expression pattern of miR-29c was opposite to that of YY1 and Akt3 genes in pigs.Also,the luciferase assay indicated that miR-29s can target the YY1 gene in pigs.In addition,we identified a T to C mutation in the primary transcript of miR-29c,which was associated with the postmortem muscle pH in pigs.Based on these results,we concluded that miR-29c is also important in skeletal muscle development of pigs.

Nonlinear effects of the finite amplitude ultrasound wave in biological tissues

Nonlinear effects will occur during the transmission of the finite amplitude wave in biological tissues. The theoretical prediction and experimental demonstration of the nonlinear effects on the propagation of the finite amplitude wave at the range of biomedical ultrasound frequency and intensity are studied. Results show that the efficiency factor and effective propagation distance will decrease while the attenuation coefficient increases due to the existence of nonlinear effects. The experimental results coincided quite well with the theory. This shows that the effective propagation distance and efficiency factor can be used to describe quantitatively the influence of nonlinear effects on the propagation of the finite amplitude sound wave in biological tissues.