Mixed Reality Combined with Three‐Dimensional Printing Technology in Total Hip Arthroplasty: An Updated Review with a Preliminary Case Presentation

Three‐dimensional (3D) printing technology, virtual reality, and augmented reality technology have been used to help surgeons to complete complex total hip arthroplasty, while their respective shortcomings limit their further application. With the development of technology, mixed reality (MR) technology has been applied to improve the success rate of complicated hip arthroplasty because of its unique advantages. We presented a case of a 59‐year‐old man with an intertrochanteric fracture in the left femur, who had received a prior left hip fusion. After admission to our hospital, a left total hip arthroplasty was performed on the patient using a combination of MR technology and 3D printing technology. Before surgery, 3D reconstruction of a certain bony landmark exposed in the surgical area was first performed. Then a veneer part was designed according to the bony landmark and connected to a reference registration landmark outside the body through a connecting rod. After that, the series of parts were made into a holistic reference registration instrument using 3D printing technology, and the patient's data for bone and surrounding tissue, along with digital 3D information of the reference registration instrument, were imported into the head‐mounted display (HMD). During the operation, the disinfected reference registration instrument was installed on the selected bony landmark, and then the automatic real‐time registration was realized by HMD through recognizing the registration landmark on the reference registration instrument, whereby the patient's virtual bone and other anatomical structures were quickly and accurately superimposed on the real body of the patient. To the best of our knowledge, this is the first report to use MR combined with 3D printing technology in total hip arthroplasty.     

TGFβ promotes YAP‐dependent AXL induction in mesenchymal‐type lung cancer cells

The acquisition of chemoresistance remains a major cause of cancer mortality due to the limited accessibility of targeted or immune therapies. However, given that severe alterations of molecular features during epithelial‐to‐mesenchymal transition (EMT) lead to acquired chemoresistance, emerging studies have focused on identifying targetable drivers associated with acquired chemoresistance. Particularly, AXL, a key receptor tyrosine kinase that confers resistance against targets and chemotherapeutics, is highly expressed in mesenchymal cancer cells. However, the underlying mechanism of AXL induction in mesenchymal cancer cells is poorly understood. Our study revealed that the YAP signature, which was highly enriched in mesenchymal‐type lung cancer, was closely correlated to AXL expression in 181 lung cancer cell lines. Moreover, using isogenic lung cancer cell pairs, we also found that doxorubicin treatment induced YAP nuclear translocation in mesenchymal‐type lung cancer cells to induce AXL expression. Additionally, the concurrent activation of TGFβ signaling coordinated YAP‐dependent AXL expression through SMAD4. These data suggest that crosstalk between YAP and the TGFβ/SMAD axis upon treatment with chemotherapeutics might be a promising target to improve chemosensitivity in mesenchymal‐type lung cancer.

Abbreviations

AUC

area under the curve

AXL

AXL receptor tyrosine kinase

BCL2

B‐cell lymphoma 2

CTD2

cancer target discovery and development

CTGF

connective tissue growth factor

DEG

differentially expressed genes

DOXO

doxorubicin

EMT

epithelial–mesenchymal transition

Eto

etoposide

FDA

Food and Drug Administration

ITGB3

integrin beta‐3

MAPK

mitogen‐activated protein kinase

MMP2

matrix metalloproteinase‐2

MMP9

matrix metalloproteinase‐9

mRNA

messenger RNA

NF‐κB

nuclear factor kappa‐light‐chain‐enhancer of activated B cells

SBE

SMAD binding element

SERPINE1

serpin family E member 1

siRNA

small interfering RNA

ssGSEA

single‐sample gene set enrichment analysis

TCGA

The Cancer Genome Atlas

TGFβ

transforming growth factor beta

YAP

Yes‐associated protein

YAP8SA

mutants of inhibitory phosphorylation site at eight serine to Alanine of YAP

ZEB1

zinc finger E‐box binding homeobox 1

ZEB2

zinc finger E‐box‐binding homeobox 2

     

HIV-negative children’s experiences and opinions towards parental HIV disclosure: a qualitative study in China

In HIV/AIDS research, few studies to date have evaluated ways to improve parental HIV disclosure practices using feedback from HIV-negative children who have recently experienced this event. We conducted semi-structured in-depth interviews with 20 children (aged 6–15) who were partially to fully aware of their parents’ HIV status in rural Guangxi, China. Of the 20 children, eight children who were of older age (11.38 years in average) endorsed parental HIV disclosure, five discouraged it and seven expressed uncertainty. Children’s different experiences and attitudes towards disclosure were seen to be associated with their family dynamics (especially the parent–child relationship), social support and care, experiences of stigma and discrimination, psychosocial suffering, comprehension of the disease and the children’s age. Our study contributes to building a child-centered comprehensive understanding for Chinese parental HIV disclosure. It is imperative that counselors and community advocates assess and help parents achieve optimal readiness preceding disclosure of their illness to their HIV-negative children.     

Health-Related Quality of Life in KEYNOTE-010: a Phase II/III Study of Pembrolizumab Versus Docetaxel in Patients With Previously Treated Advanced,Programmed Death Ligand 1–Expressing NSCLC

Introduction

In the phase II/III KEYNOTE-010 study (ClinicalTrials.gov, NCT01905657), pembrolizumab significantly prolonged overall survival over docetaxel in patients with previously treated, programmed death ligand 1–expressing (tumor proportion score ≥ 1%), advanced NSCLC. Health-related quality of life (HRQoL) results are reported here.

Deferoxamine promotes recovery of traumatic spinal cord injury by inhibiting ferroptosis

Ferroptosis is an iron-dependent novel cell death pathway. Deferoxamine, a ferroptosis inhibitor, has been reported to promote spinal cord injury repair. It has yet to be clarified whether ferroptosis inhibition represents the mechanism of action of Deferoxamine on spinal cord injury recovery. A rat model of Deferoxamine at thoracic 10 segment was established using a modified Allen's method. Ninety 8-week-old female Wistar rats were used. Rats in the Deferoxamine group were intraperitoneally injected with 100 mg/kg Deferoxamine 30 minutes before injury. Simultaneously, the Sham and Deferoxamine groups served as controls. Drug administration was conducted for 7 consecutive days. The results were as follows:(1) Electron microscopy revealed shrunken mitochondria in the spinal cord injury group.(2) The Basso, Beattie and Bresnahan locomotor rating score showed that recovery of the hindlimb was remarkably better in the Deferoxamine group than in the spinal cord injury group.(3) The iron concentration was lower in the Deferoxamine group than in the spinal cord injury group after injury.(4) Western blot assay revealed that, compared with the spinal cord injury group, GPX4, xCT, and glutathione expression was markedly increased in the Deferoxamine group.(5) Real-time polymerase chain reaction revealed that, compared with the Deferoxamine group, mRNA levels of ferroptosis-related genes Acyl-CoA synthetase family member 2(ACSF2) and iron-responsive element-binding protein 2(IREB2) were up-regulated in the Deferoxamine group.(6) Deferoxamine increased survival of neurons and inhibited gliosis. These findings confirm that Deferoxamine can repair spinal cord injury by inhibiting ferroptosis. Targeting ferroptosis is therefore a promising therapeutic approach for spinal cord injury.