Clinical evaluation of augmented reality-based 3D navigation system for brachial plexus tumor surgery.

BACKGROUND: Augmented reality (AR), a form of 3D imaging technology, has been preliminarily applied in tumor surgery of the head and spine, both are rigid bodies. However, there is a lack of research evaluating the clinical value of AR in tumor surgery of the brachial plexus, a non-rigid body, where the anatomical position varies with patient posture. METHODS: Prior to surgery in 8 patients diagnosed with brachial plexus tumors, conventional MRI scans were performed to obtain conventional 2D MRI images. The MRI data were then differentiated automatically and converted into AR-based 3D models. After point-to-point relocation and registration, the 3D models were projected onto the patient's body using a head-mounted display for navigation. To evaluate the clinical value of AR-based 3D models compared to the conventional 2D MRI images, 2 senior hand surgeons completed questionnaires on the evaluation of anatomical structures (tumor, arteries, veins, nerves, bones, and muscles), ranging from 1 (strongly disagree) to 5 (strongly agree). RESULTS: Surgeons rated AR-based 3D models as superior to conventional MRI images for all anatomical structures, including tumors. Furthermore, AR-based 3D models were preferred for preoperative planning and intraoperative navigation, demonstrating their added value. The mean positional error between the 3D models and intraoperative findings was approximately 1 cm. CONCLUSIONS: This study evaluated, for the first time, the clinical value of an AR-based 3D navigation system in preoperative planning and intraoperative navigation for brachial plexus tumor surgery. By providing more direct spatial visualization, compared with conventional 2D MRI images, this 3D navigation system significantly improved the clinical accuracy and safety of tumor surgery in non-rigid bodies.

Loss of Paip1 causes translation reduction and induces apoptotic cell death through ISR activation and Xrp1.

Regulation of protein translation initiation is tightly associated with cell growth and survival. Here, we identify Paip1, the Drosophila homolog of the translation initiation factor PAIP1, and analyze its role during development. Through genetic analysis, we find that loss of Paip1 causes reduced protein translation and pupal lethality. Furthermore, tissue specific knockdown of Paip1 results in apoptotic cell death in the wing imaginal disc. Paip1 depletion leads to increased proteotoxic stress and activation of the integrated stress response (ISR) pathway. Mechanistically, we show that loss of Paip1 promotes phosphorylation of eIF2α via the kinase PERK, leading to apoptotic cell death. Moreover, Paip1 depletion upregulates the transcription factor gene Xrp1, which contributes to apoptotic cell death and eIF2α phosphorylation. We further show that loss of Paip1 leads to an increase in Xrp1 translation mediated by its 5'UTR. These findings uncover a novel mechanism that links translation impairment to tissue homeostasis and establish a role of ISR activation and Xrp1 in promoting cell death.

Qishen Yiqi dropping pills improve cardiomyocyte hypertrophy via the lncRNA TINCR/miR-193b-3p/RORA axis.

Background: This study was designed to explore the therapeutic effect and mechanism of action of Qishen Yiqi dropping pills (QYDP) in chronic heart failure (CHF) via a long non-coding RNA (lncRNA)-microRNA (miRNA)-messenger RNA (mRNA) axis. Here, the mechanism of action of the lncRNA terminal differentiation-induced non-coding RNA (TINCR), miR-193b-3p, and RAR-related orphan receptor A (RORA) mRNA was analyzed in an angiotensin (Ang) II-induced H9C2 cardiomyocyte hypertrophy model treated with QYDP. Methods: Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to analyze the gene expression changes of lncRNA, miRNA, and mRNA in H9C2 induced by QYDP on Ang II. The Gene Expression Omnibus (GEO) was used to analyze differentially expressed genes (DEGs) potentially affecting CHF progression. Cell Counting Kit-8 (CCK-8) was used to analyze the effect of QYDP on the proliferation of H9C2, RNA pull-down was used to analyze the binding of lncRNA and miRNA, and dual luciferase was used to analyze the targeting of miRNA and lncRNA or mRNA. Results: Ang II induced TINCR and RORA downregulation, miR-193b-3p upregulation, and hypertrophy in the H9C2 cardiomyocytes, which were alleviated by QYDP. In contrast, TINCR inhibition reversed the effects of QYDP by increasing miR-193b-3p expression and downregulating RORA expression. According to subsequent double luciferase and RNA pull-down experiments, TINCR adsorbed miR-193b-3p by acting as a competitive endogenous RNA sponge and miR-193b-3p directly targeted RORA. Lastly, we showed that the Ang-II-induced inhibition of TINCR and RORA expression and promotion of cardiac hypertrophy were both reversed by a TINCR overexpression plasmid (ov-TINCR), whereas the effects of ov-TINCR were suppressed by a miR-193b-3p mimic. Conclusions: Administration of QYDP improves Ang II-induced H9C2 cardiomyocyte hypertrophy and increase cell proliferation rate through the TINCR/miR-193b-3p/RORA axis.

Arthroscopy-assisted partial trapeziectomy combined with ligament reconstruction for thumb carpometacarpal joint osteoarthritis: A different technique.

Background: There is no consensus on the best surgery option for thumb carpometacarpal osteoarthritis (CMC OA). The traditional method has the risk of large trauma, obvious metacarpal subsidence, and decreased stability. The aim of this study is to introduce a different technique to restore the function and stability of the first carpal metacarpal joint with minimal trauma, rapid pain relief, reduced complications, and the clinical outcomes in the long-term follow-up was evaluated and statistically analyzed. Methods: This was a retrospective study of 10 patients with a mean age of 51.8 years. The surgery consisted of removing partial trapezium through arthroscopy, reconstructing the stability with flexor carpi radialis suspension and tendon interposition. The subjective assessment included visual analog scale (VAS) of pain, quick disabilities of the arm, shoulder, and hand (Quick-DASH) score, and patient satisfaction. The range of motion, grip strength, pinch strength, and radiographic assessment, which can reflect stability of the thumb, were objectively evaluated and statistically analyzed. Results: Ten patients were monitored at a mean follow-up of 6.8 years. The mean grip strength improved significantly from 16.64 to 22.57 kg after surgery. Pinch strength improved significantly from 3.72 to 5.71 kg on average. The Kapandji score improved significantly from 5.7 to 8.6 on average. 80% (8/10) of the patients were satisfied with this surgery. On objective indicators, the VAS score decreased significantly from 6.4 to 1.3 on average. The mean Quick-DASH score improved significantly from 6.1 to 28.9. Postoperative x-ray showed slight subsidence and dislocation of the first metacarpal in two patients and did not affect the function by measurement. Conclusion: Arthroscopy-assisted partial trapezium resection combined with ligament reconstruction could be a workable and promising surgical technique in patients with thumb CMC OA. It can offer the advantages of minimizing surgical injury by preserving the first carpal metacarpal joint capsule to protect its stability, with a rapid pain relief, function improvement, and satisfactory results in patients' clinical measurements.

Qishen Yiqi dropping pills improve isoproterenol-induced cardiomyocyte hypertrophy by regulating X-inactive specific transcript (XIST) expression in rats.

Background: This study aimed to explore the potential mechanism of Qishen Yiqi dropping pills (QYDPs) in the treatment of chronic heart failure (CHF) by regulating the expression of lncRNAs during CHF. Methods: Differences in the expression of the long non-coding RNA (lncRNA), X-inactive specific transcript (XIST), in an isoproterenol (ISO)-induced cardiomyocyte hypertrophy model treated with QYDPs was analyzed by reverse transcription quantitative polymerase chain reaction (RT-qPCR). A cell counting kit-8 (CCK8) assay, flow cytometry (FCM), and enzyme linked immunosorbent assay (ELISA) were used to analyze the protective effects of QYDPs on the proliferation rate, apoptosis, myocardial enzyme, oxidative stress, and inflammation of cardiomyocytes, as well as the molecular mechanism of XIST. Results: Our results showed that in the ISO-induced cardiomyocyte hypertrophy model, XIST expression and apoptosis were increased, the cell proliferation rate was decreased, and myocardial enzyme levels increased [i.e., increased lactate dehydrogenase (LDH) and creatine kinase (CK) levels]. Furthermore, cellular oxidative stress [i.e., increased malondialdehyde (MDA) levels and decreased superoxide dismutase (SOD) levels] and inflammatory response [i.e., increased interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α protein secretion] were also promoted. QYDP treatment effectively mitigated the effects of ISO induction. Subsequently, we found that suppressing XIST expression reversed the effect of ISO induction, whereas overexpression (ov) of XIST enhanced the effect of ISO induction. Finally, this study confirmed that QYDP treatment improved the ISO-induced decrease in proliferation, apoptosis, and promotion of oxidative stress and inflammatory response in cardiomyocytes, whereas ov of XIST partially negated the effect of QYDPs. Conclusions: QYDPs protected H9c2 cells from ISO-induced damage by downregulating XIST expression.

Lactylation-driven METTL3-mediated RNA m6A modification promotes immunosuppression of tumor-infiltrating myeloid cells.

Tumor-infiltrating myeloid cells (TIMs) are crucial cell populations involved in tumor immune escape, and their functions are regulated by multiple epigenetic mechanisms. The precise regulation mode of RNA N6-methyladenosine (m6A) modification in controlling TIM function is still poorly understood. Our study revealed that the increased expression of methyltransferase-like 3 (METTL3) in TIMs was correlated with the poor prognosis of colon cancer patients, and myeloid deficiency of METTL3 attenuated tumor growth in mice. METTL3 mediated m6A modification on Jak1 mRNA in TIMs, the m6A-YTHDF1 axis enhanced JAK1 protein translation efficiency and subsequent phosphorylation of STAT3. Lactate accumulated in tumor microenvironment potently induced METTL3 upregulation in TIMs via H3K18 lactylation. Interestingly, we identified two lactylation modification sites in the zinc-finger domain of METTL3, which was essential for METTL3 to capture target RNA. Our results emphasize the importance of lactylation-driven METTL3-mediated RNA m6A modification for promoting the immunosuppressive capacity of TIMs.

Admission Neutrophil-Lymphocyte Ratio Predicts Rebleeding Following Aneurismal Subarachnoid Hemorrhage.

OBJECTIVE: The relationship between neutrophil-lymphocyte ratio (NLR) and the occurrence of rebleeding in aneurysmal subarachnoid hemorrhage (aSAH) is poorly understood. Our study aimed to investigate the association between NLR on admission and rebleeding following aSAH. METHODS: Clinical and laboratorial data from patients with aSAH were retrospectively collected, including leukocyte, neutrophil, lymphocyte, and NLR. Univariate and multivariate analyses were performed to assess for the association of NLR with rebleeding. We performed propensity-score matching analyses to correct imbalances in patient characteristics between the rebleeding group and nonrebleeding group. RESULTS: Rebleeding occurred in 30 of 716 (4.19%) patients with aSAH in this cohort. Patients with rebleeding had significantly higher NLR comparing with patients without rebleeding (11.27 vs. 5.5; P < 0.05) in the univariate analysis. In the multivariate analysis, NLR was considered as a risk factor of rebleeding (odds ratio, 0.283; 95% confidence interval, 0.130-0.620; P = 0.002), as well as Fisher grade (odds ratio, 0.353, 95% confidence interval, 0.151-0.824; P = 0.016). The area under the curve of the NLR and combined NLR-Fisher grade model was 0.702 and 0.744 (sensitivity was 39.94%, and specificity was 100%) for predicting rebleeding, respectively. After propensity-score matching, the optimal cutoff value for NLR as a predictor for rebleeding following aSAH was determined as 5.4 (sensitivity was 83.33%, and the specificity was 63.33%). CONCLUSIONS: Higher NLR predicts the occurrence of rebleeding and poor outcome, and NLR combined with Fisher grade significantly improves the prediction of rebleeding following aSAH.

Effects of Frozen Stromal Vascular Fraction on the Survival of Cryopreserved Fat Tissue.

BACKGROUND: Nowadays, the use of cryopreserved fat tissue for soft tissue augmentation is common, except for its unpredictable fat graft absorption, and the toxicity of the cryoprotective agent remains a limitation. In this study, the effects of freezing stored fat tissue without a cryoprotector, and the addition of the stromal vascular fraction (SVF) on the survival of cryopreserved transplants was studied. METHODS: Lipoaspirates from six donors were processed and cryopreserved at - 20 °C, - 80 °C and - 196 °C, respectively. The authors evaluated the lipoaspirates in vitro, on the basis of fat tissue and SVF viability after cryopreservation. In vivo fat grafting was performed in nude mice. Six trenches were injected on the backs of mice. Cryopreserved tissues (- 20 °C, - 80 °C and - 196 °C) were injected on the right side, and the other side received the SVF combination. At 4 and 8 weeks after transplantation, the authors examined the weight, volume and morphology of the tissue and analyzed histochemical staining and immunohistochemistry (i.e., DIL, CD31 and VWF) to evaluate the survival of the fat grafts. RESULTS: After cryopreservation without the cryoprotective agent, adipose tissue maintained its morphology better in - 80 °C than - 20 °C and - 196 °C. SVF cells can retain their adhesive and proliferative properties after cryopreservation. Although cryopreservation caused damage to fat tissue, all explants showed intact adipocytes and vascular ingrowth. Most of all, the - 80 °C group had less graft resorption and fibrosis than the other temperature groups. There was increased survival of fat grafts in the SVF group compared with the control group. CONCLUSION: In this study, the authors demonstrated that the storage temperature of - 80 °C was promising for 3 months of adipose tissue cryopreservation without a cryoprotective agent, and SVF could increase the survival rate of cryopreserved fat tissue. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Nuclease-functionalized poly(styrene-b-isobutylene-b-styrene) surface with anti-infection and tissue integration bifunctions.

Hydrophobic thermoplastic elastomers, e.g., poly(styrene-b-isobutylene-b-styrene) (SIBS), have found various in vivo biomedical applications. It has long been recognized that biomaterials can be adversely affected by bacterial contamination and clinical infection. However, inhibiting bacterial colonization while simultaneously preserving or enhancing tissue-cell/material interactions is a great challenge. Herein, SIBS substrates were functionalized with nucleases under mild conditions, through polycarboxylate grafts as intermediate. It was demonstrated that the nuclease-modified SIBS could effectively prevent bacterial adhesion and biofilm formation. Cell adhesion assays confirmed that nuclease coatings generally had no negative effects on L929 cell adhesion, compared with the virgin SIBS reference. Therefore, the as-reported nuclease coating may present a promising approach to inhibit bacterial infection, while preserving tissue-cell integration on polymeric biomaterials.