Self-adaptive pyroptosis-responsive nanoliposomes block pyroptosis in autoimmune inflammatory diseases.

Nanoliposomes have a broad range of applications in the treatment of autoimmune inflammatory diseases because of their ability to considerably enhance drug transport. For their clinical application, nanoliposomes must be able to realize on-demand release of drugs at disease sites to maximize drug-delivery efficacy and minimize side effects. Therefore, responsive drug-release strategies for inflammation treatment have been explored; however, no specific design has been realized for a responsive drug-delivery system based on pyroptosis-related inflammation. Herein, we report a pioneering strategy for self-adaptive pyroptosis-responsive liposomes (R8-cardiolipin-containing nanoliposomes encapsulating dimethyl fumarate, RC-NL@DMF) that precisely release encapsulated anti-pyroptotic drugs into pyroptotic cells. The activated key pyroptotic protein, the N-terminal domain of gasdermin E, selectively integrates with the cardiolipin of liposomes, thus forming pores for controlled drug release, pyroptosis, and inflammation inhibition. Therefore, RC-NL@DMF exhibited effective therapeutic efficacies to alleviate autoimmune inflammatory damages in zymosan-induced arthritis mice and dextran sulfate sodium-induced inflammatory bowel disease mice. Our novel approach holds great promise for self-adaptive pyroptosis-responsive on-demand drug delivery, suppressing pyroptosis and treating autoimmune inflammatory diseases.

Rapid scanning method for SICM based on autoencoder network.

Scanning Ion Conductance Microscopy (SICM) enables non-destructive imaging of living cells, which makes it highly valuable in life sciences, medicine, pharmacology, and many other fields. However, because of the uncertainty retrace height of SICM hopping mode, the time resolution of SICM is relatively low, which makes the device fail to meet the demands of dynamic scanning. To address above issues, we propose a fast-scanning method for SICM based on an autoencoder network. Firstly, we cut under-sampled images into small image lists. Secondly, we feed them into a self-constructed primitive-autoencoder super-resolution network to compute high-resolution images. Finally, the inferred scanning path is determined using the computed images to reconstruct the real high-resolution scanning path. The results demonstrate that the proposed network can reconstruct higher-resolution images in various super-resolution tasks of low-resolution scanned images. Compared to existing traditional interpolation methods, the average peak signal-to-noise ratio improvement is greater than 7.5823 dB, and the average structural similarity index improvement is greater than 0.2372. At the same time, using the proposed method for high-resolution image scanning leads to a 156.25% speed improvement compared to traditional methods. It opens up possibilities for achieving high-time resolution imaging of dynamic samples in SICM and further promotes the widespread application of SICM in the future.

Acute cardiac tamponade following thoracoscopic lobectomy: a case report and literatures review.

Thoracoscopic lobectomy is a common surgical procedure for the treatment of lung cancer. With the continuous development of surgical techniques and medical devices, complications after thoracoscopic lobectomy are less and less, and cardiac tamponade is even rarer. This case is a 62-year-old woman who underwent thoracoscopic left upper lobectomy for a left upper lobe nodule. The patient developed acute cardiac tamponade on postoperative day 2, and symptoms resolved after pericardiocentesis. However, 20 h later, the patient underwent emergency surgery for re-developed acute cardiac tamponade, which was found to be a coronary tear. A review of the literature suggested that cardiac tamponade is more common in left lung surgery than right lung surgery. Pericardiocentesis can resolve initial acute cardiac tamponade, but pericardiotomy may be urgently needed after recurrence.

Investigating the effects of solution viscosity on the stability and success rate of SECCM imaging.

Due to the capability of simultaneously detecting the morphology and electrochemical information of samples and limiting the electrochemical reaction to a range approximately the size of the inner diameter of the pipette tip opening, scanning electrochemical cell microscopy (SECCM) enables higher precision local electrochemical measurement and surface material delivery and has been demonstrating unique advantages and broad application prospects. However, the meniscus droplet at the pipette tip of SECCM is equivalent to the opening radius of the pipette tip, which is usually tens of nanometers to hundreds of nanometers. The tiny meniscus droplet makes it susceptible to evaporation and crystallization, which increases the likelihood of the pipette colliding with the sample during the scanning process, resulting in the failure of scanning. In this paper, the influence of solution viscosity on the shape variation of the droplet at the tip during the movement of the pipette of SECCM was studied by finite element analysis. It is proved that the increase of solution viscosity is helpful in reducing the shape variation of the droplet at the tip during the movement of the pipette. Then scanning experiments were carried out using a flat Au substrate and Au substrates with rounded triangle and rounded rectangular convex structures as the samples. According to the experimental results, increasing solution viscosity improves scanning success rates and scanning quality and effectively lowers the MSE of the scanning results. The experimental results also show that SECCM can image at a higher speed when the solution's viscosity increases since the deformation of the droplet at the tip is less than with a typical solution.

A Redox Homeostasis Modulatory Hydrogel with GLRX3+ Extracellular Vesicles Attenuates Disc Degeneration by Suppressing Nucleus Pulposus Cell Senescence.

Characterized by nucleus pulposus (NP) cell senescence and extracellular matrix (ECM) degradation, disc degeneration is a common pathology for various degenerative spinal disorders. To date, effective treatments for disc degeneration are absent. Here, we found that Glutaredoxin3 (GLRX3) is an important redox-regulating molecule associated with NP cell senescence and disc degeneration. Using a hypoxic preconditioning method, we developed GLRX3+ mesenchymal stem cell-derived extracellular vehicles (EVs-GLRX3), which enhanced the cellular antioxidant defense, thus preventing reactive oxygen species (ROS) accumulation and senescence cascade expansion in vitro. Further, a disc tissue-like biopolymer-based supramolecular hydrogel, which was injectable, degradable, and ROS-responsive, was proposed to deliver EVs-GLRX3 for treating disc degeneration. Using a rat model of disc degeneration, we demonstrated that the EVs-GLRX3-loaded hydrogel attenuated mitochondrial damage, alleviated the NP senescence state, and restored ECM deposition by modulating the redox homeostasis. Our findings suggested that modulation of redox homeostasis in the disc can rejuvenate NP cell senescence and thus attenuate disc degeneration.

Exosome-laden injectable self-healing hydrogel based on quaternized chitosan and oxidized starch attenuates disc degeneration by suppressing nucleus pulposus senescence.

Disc degeneration is the common pathology underlying various degenerative spinal disorders and currently there is no effective cure. Here, we found nucleus pulposus (NP) cell senescence was closely associated with the severity of disc degeneration, and exosomes (Exos) derived from mesenchymal stem cells (MSCs) ameliorated NP cell senescence and promoted extracellular matrix (ECM) deposition. As chitosan-based hydrogels have been widely used as vehicles to deliver Exos due to their prominent antibacterial capacity, biocompatibility, and biodegradability, we developed an Exos-laden hydrogel based on quaternized chitosan (QCS) and oxidized starch (OST) to treat disc degeneration. The synthesized QCS-OST hydrogel is injectable, self-healing, biocompatible, and demonstrated desirable pore size, injectable properties, and sustainable release of Exos. In a rat model of disc degeneration, the QCS-OST/Exos hydrogel was able to rejuvenate NP cell senescence, promote ECM remodeling, and partially restore the structures of NP and annulus fibrosis. Our findings suggested that the novel QCS-OST/Exos hydrogel is an effective therapeutic strategy for treating disc degeneration via alleviating NP cell senescence.

HECTD1-Mediated Ubiquitination and Degradation of Rubicon Regulates Autophagy and Osteoarthritis Pathogenesis.

OBJECTIVE: Osteoarthritis (OA) is one of the most common degenerative joint diseases and is associated with autophagy suppression. However, the molecular mechanism of autophagy regulation in the context of OA is not fully understood. In this study, we sought to determine the role that HECTD1 plays in the pathogenesis of OA. METHODS: We used RNA sequencing analysis to explore the differential expression of E3 ubiquitin ligase genes in healthy human cartilage and human cartilage affected by OA. Using surgery- and aging-induced OA mouse models, we comprehensively analyzed the function of the screened gene Hectd1 in the development of OA; furthermore, we dissected the mechanism by which HECTD1 regulates autophagy and OA progression using a combination of molecular biologic, cell biologic, and biochemical approaches. RESULTS: HECTD1 was significantly down-regulated in human OA cartilage samples compared to healthy cartilage samples. Overexpression of HECTD1 in mouse joints alleviated OA pathogenesis, whereas conditional depletion of Hectd1 in cartilage samples aggravated surgery- and aging-induced OA pathogenesis. Mechanistically, HECTD1 bound to Rubicon and ubiquitinated Rubicon at lysine residue 534, which targets Rubicon for proteasomal degradation. More importantly, HECTD1-mediated Rubicon degradation regulated chondrocyte autophagy, leading to mitigation of stress-induced chondrocyte death and the subsequent progression of OA. CONCLUSION: HECTD1 plays a crucial role in the pathogenesis of OA, in that HECTD1 regulates chondrocyte autophagy by ubiquitinating and targeting Rubicon for proteasomal degradation.

Synergistically targeting synovium STING pathway for rheumatoid arthritis treatment.

Rheumatoid arthritis (RA) is a common autoimmune disease leading to pain, disability, and even death. Although studies have revealed that aberrant activation of STING was implicated in various autoimmune diseases, the role of STING in RA remains unclear. In the current study, we demonstrated that STING activation was pivotal in RA pathogenesis. As the accumulation of dsDNA, a specific stimulus for STING, is a feature of RA, we developed a spherical polyethyleneimine-coated mesoporous polydopamine nanoparticles loaded with STING antagonist C-176 (PEI-PDA@C-176 NPs) for treating RA. The fabricated NPs with biocompatibility had high DNA adsorption ability and could effectively inhibit the STING pathway and inflammation in macrophages. Intra-articular administration of PEI-PDA@C-176 NPs could effectively reduce joint damage in mice models of dsDNA-induced arthritis and collagen-induced arthritis by inhibiting STING pathway. We concluded that materials with synergistic effects of STING inhibition might be an efficacious strategy to treat RA.

Scavenging of reactive oxygen species can adjust the differentiation of tendon stem cells and progenitor cells and prevent ectopic calcification in tendinopathy.

Tendinopathy is a common disorder that leads to pain and impaired quality of life. Recent studies revealed that osteogenic differentiation of tendon stem/progenitor cells (TSPCs) played an important role in the pathogenesis of tendon calcification and tendinopathy. In this study, we found that the growth hormone-releasing hormone agonist (GA) can prevent matrix degradation and osteogenic differentiation in TSPCs. As oxidative stress is a key factor in the osteogenic differentiation of TSPCs, we used bovine serum albumin/heparin nanoparticles (BHNPs), which have biocompatibility and drug loading capacity, to scavenge reactive oxygen species (ROS) and achieve sustained release of GA at the site of inflammation. The newly developed BHNPs@GA had a synergetic effect on reducing ROS production in TSPCs. In addition, BHNPs@GA effectively inhibited tendon calcification and promoted collagen formation in a rat model of tendinopathy. Focusing on the ROS underlying the differentiation and dedifferentiation of TSPCs, this work demonstrated that sustained release of GA targeting ROS and ectopic ossification is a practical therapeutic strategy for treating tendinopathy. STATEMENT OF SIGNIFICANCE: Osteogenic differentiation of tendon stem/progenitor cells (TSPCs) plays an important role in the pathogenesis of ectopic calcification in tendinopathy. In this study, we found that growth hormone-releasing hormone agonist (GA) can reduce reactive oxygen species (ROS) production and adjust TSPCs differentiation. Bovine serum albumin/heparin nanoparticles (BHNPs) were developed to encapsulate GA and achieve sustained release of GA at the site of inflammation. The developed compound, BHNPs@GA, with a synergistic effect of inhibiting ROS and thus, can effectively adjust TSPCs differentiation, inhibit tendon calcification, and promote collagen formation in tendinopathy. This study highlighted the role of ROS underlying the differentiation and dedifferentiation of TSPCs in tendinopathy, and findings may help to identify new therapeutic targets and develop novel strategy for treating tendinopathy.

Feasibility and oncological outcomes of video-assisted thoracic surgery versus thoracotomy for pathologic N2 disease in non-small cell lung cancer: A comprehensive systematic review and meta-analysis.

This meta-analysis aimed to evaluate the feasibility and oncological outcomes between video-assisted thoracic surgery (VATS) and thoracotomy for non-small cell lung cancer (NSCLC) patients with pathologic N2 (pN2) disease. Data for analysis included short-term outcomes and long-term outcomes. We calculated the weighted mean differences (WMDs) for continuous data and the results of overall survival (OS) and disease free survival (DFS) were pooled using the hazard ratios (HRs) with 95% confidence intervals (CIs). Heterogeneity was assessed using the Q-test and I2 -test. Sensitivity analysis was performed to further examine the stability of pooled HRs and WMDs. In the pooled analyses of 10 eligible studies, results showed that VATS for NSCLC patients with pN2 disease yielded significantly less blood loss (WMD = -61.43; 95% confidence intervals [CI], [-87.69, -35.18]; p < 0.001), less post-operation hospital stay (WMD, -1.62; 95% CI, [-2.96, -0.28]; p = 0.02), and comparable operation time (WMD,  -8.32; 95% CI, [-23.88, 7.23]; p = 0.29), post-operation complication rate (risk ratio [RR], 0.95; 95% CI, [0.78, 1.15]; p = 0.59), chest tube duration to thoracotomy (WMD, -0.64; 95% CI, [-1.45, 0.17]; p = 0.12), extent of lymph node dissection (WMD, -1.46; 95% CI, [-3.87, 0.95]; p = 0.23) and 1-year OS (HR, 1.30; 95% CI, [0.96, 1.76]; p = 0.09) than thoracotomy. However, VATS may improve 3-year OS (HR, 1.26; 95% CI, [1.12, 1.42]; p = 0.0002) and yield comparable 1-year DFS (HR, 1.14; 95% CI, [0.89, 1.46]; p = 0.32) and 3-year DFS (HR, 1.03; 95% CI, [0.88, 1.22]; p = 0.70) for NSCLC patients with pN2 disease than thoracotomy. VATS could yield less surgical trauma and improve post-operative recovery than thoracotomy. Moreover, VATS may improve the oncological outcomes of those patients.

A network meta-analysis for efficacies and toxicities of different concurrent chemoradiotherapy regimens in the treatment of locally advanced non-small cell lung cancer.

BACKGROUND: Concurrent chemoradiotherapy (CCRT) has become the cornerstone of treatment for patients with locally advanced non-small cell lung cancer (LA-NSCLC). The aim of this study was to compare the efficacies and toxicities of different CCRT regimens in the treatment of LA-NSCLC by adopting a network meta-analysis (NMA). METHODS: An exhaustive search of PubMed, EMBASE, Web of Science, and the Cochrane Central Register of Controlled Trials (CENTRAL) was conducted to identify relevant studies from inception to October 1, 2020. Direct and indirect evidence was combined to calculate the odds radios (ORs) and 95% confidence intervals (CIs), as well as to plot the surface under the cumulative ranking (SUCRA) curves. Cluster analyses were adopted to compare the efficacies and toxicities of different CCRT regimens according to the similarity of 2 variables. Publication bias was detected by comparison-adjusted funnel plots. RESULTS: Twenty-two studies were enrolled in this NMA, including 18 regimens: CCRT (cisplatin + etoposide), CCRT (carboplatin + paclitaxel), CCRT (pemetrexed + carboplatin), CCRT (pemetrexed + cisplatin), CCRT (docetaxel + cisplatin), CCRT (S-1 + cisplatin), CCRT (mitomycin + vindesine + cisplatin), CCRT (cisplatin + vinorelbine), CCRT (cisplatin), CCRT (etoposide + cisplatin + amifostine), RT, CCRT (5-FU), CCRT (paclitaxel + cisplatin), CCRT (irinotecan + carboplatin), CCRT (nedaplatin), CCRT (carboplatin + etoposide), CCRT (paclitaxel), and CCRT (carboplatin). The results indicated that the regimens with CCRT (cisplatin + etoposide), CCRT (carboplatin + paclitaxel), CCRT (pemetrexed + cisplatin), CCRT (S-1 + cisplatin), and CCRT (cisplatin + vinorelbine) had relatively better efficacies compared with other regimens. As for toxicities of different CCRT regimens, the CCRT (carboplatin + paclitaxel), CCRT (pemetrexed + cisplatin), and CCRT (docetaxel + cisplatin) were relatively lower. CONCLUSIONS: Our study demonstrated that CCRT (pemetrexed + cisplatin) and CCRT (carboplatin + paclitaxel) might be the best options for the treatment of LA-NSCLC, and CCRT (pemetrexed + cisplatin) had the highest 3-year overall survival (OS) rate.

Wedge Resection vs. Stereotactic Body Radiation Therapy for Clinical Stage I Non-small Cell Lung Cancer: A Systematic Review and Meta-Analysis.

Background: Whether wedge resection or stereotactic body radiation therapy (SBRT) has better effectiveness in treatment of clinical stage I non-small cell lung cancer (NSCLC) patients remains unclear. Here we conducted the first meta-analysis to directly compare the survival outcomes of clinical stage I NSCLCs treated with wedge resection and SBRT. Methods: We systematically searched studies from PubMed, Embase, and Corchrane Library up to October 1, 2021. Data for analysis mainly included overall survival (OS) and disease-free survival (DFS), which were obtained directly from the text results or calculated from the Kaplan-Meier survival curve. We used the standard random-effect model test (DerSimonian and Laird method) to analyze the pooled hazard ratios (HRs) and 95% confidence intervals (CIs). The Q-test and I 2-test were used to assess heterogeneity. The stability of pooled HRs was examined by sensitivity analysis. Results: Six retrospective studies with a total of 11,813 clinical stage I NSCLCs who received wedge resection or SBRT were included. The results showed that patients receiving wedge resection had a significantly better OS (HR = 1.20, 95% CI = [1.07, 1.34], P = 0.002) than those with SBRT, but no significant difference of DFS (HR 1.53, 95% CI = [0.83-2.83], P = 0.17) was observed. There was no significant heterogeneity during our analysis, but there may be potential publication bias among these studies. Conclusions: Our meta-analysis showed that clinical stage I NSCLCs treated with wedge resection had superior OS than those treated with SBRT. However, more prospective clinical trials should be well-designed to evaluate the optimal treatment modality of early-stage NSCLCs.

Clinicopathological and prognostic significance of NM23 expression in patients with non-small cell lung cancer: A systematic review and meta-analysis.

BACKGROUND: There is a heated debate on the clinicopathological features and prognostic significance with non-metastasis 23 (NM23) expression in patients with non-small cell lung cancer (NSCLC). Thus, we conducted this meta-analysis to evaluate the clinicopathological features and prognostic significance of NM23 for NSCLC patients. METHODS: Pubmed, Embase, and Web of Science were exhaustively searched to identify relevant studies published prior to March, 2020. Odds radios (ORs) and hazard radios with 95% confidence intervals (CIs) were calculated to summarize the statistics of clinicopathological and prognostic assessments. Q-test and I2-statistic were utilized to assess heterogeneity across the included studies. We also performed subgroup analyses and meta-regression analyses to identify the source of heterogeneity. Publication bias was detected by Begg and Egger tests. Sensitivity analysis was used to value the stability of our results. All the data were analyzed using statistical packages implemented in R version 4.0.5. RESULTS: Data from a total of 3170 patients from 36 studies were extracted. The meta-analysis revealed that low expression of NM23 was correlated with higher risk of NSCLC (OR = 4.35; 95% CI: 2.76-6.85; P < .01), poorer tumor node metastasis (TNM) staging (OR = 1.39; 95% CI: 1.01-1.90; P = .04), poorer differentiation degree (OR = 1.37; 95% CI: 1.01-1.86; P = .04), positive lymph node metastasis (OR = 1.83; 95% CI: 1.22-2.74; P < .01), lung adenocarcinoma (OR = 1.45; 95% CI: 1.20-1.75; P < .01), and poorer 5-year overall survival (OS) rate (hazard radio = 2.33; 95%CI: 1.32-4.11; P < .01). The subgroup analyses and meta-regression analyses suggested that the "Publication year", "Country", "Sample size", and "Cutoff value" might be the source of heterogeneity in TNM staging, differentiation degree, and lymph node metastasis. Both Begg test and Egger test verified that there were publication bias in 5-year OS rate. Sensitivity analysis supported the credibility of the results. CONCLUSION: The reduced NM23 expression is strongly associated with higher risk of NSCLC, higher TNM staging, poorer differentiation degree, positive lymph node metastasis, lung adenocarcinoma, and poorer 5-year OS rate in NSCLC patients, which indicated that NM23 could serve as a biomarker predicating the clinicopathological and prognostic significance of NSCLC.

Scanning Electrochemical Cell Microscopy Platform with Local Electrochemical Impedance Spectroscopy.

Local electrochemical impedance spectroscopy (LEIS) has been a versatile technology for characterizing local complex electrochemical processes at heterogeneous surfaces. However, further application of this technology is restricted by its poor spatial resolution. In this work, high-spatial-resolution LEIS was realized using scanning electrochemical cell microscopy (SECCM-LEIS). The spatial resolution was proven to be ∼180 nm based on experimental and simulation results. The stability and reliability of this platform were further verified by long-term tests and Kramers-Kronig transformation. With this technology, larger electric double-layer capacitance (Cdl) and smaller interfacial resistance (Rt) were observed at the edges of N-doped reduced graphene oxide, as compared to those at the planar surface, which may be due to the high electrochemical activity at the edges. The established SECCM-LEIS provides a high-spatial approach for study of the interfacial electrochemical behavior of materials, which can contribute to the elucidation of the electrochemical reaction mechanism at material surfaces.

Identification of potential diagnostic and prognostic biomarkers for LUAD based on TCGA and GEO databases.

Accumulating evidence has demonstrated that gene alterations play a crucial role in LUAD development, progression, and prognosis. The present study aimed to identify the hub genes associated with LUAD. In the present study, we used TCGA database to screen the hub genes. Then, we validated the results by GEO datasets. Finally, we used cBioPortal, UALCAN, qRT-PCR, HPA database, TCGA database, and Kaplan-Meier plotter database to estimate the gene mutation, gene transcription, protein expression, clinical features of hub genes in patients with LUAD. A total of 5930 DEGs were screened out in TCGA database. Enrichment analysis revealed that DEGs were involved in the transcriptional misregulation in cancer, viral carcinogenesis, cAMP signaling pathway, calcium signaling pathway, and ECM-receptor interaction. The combining results of MCODE and CytoHubba showed that ADCY8, ADRB2, CALCA, GCG, GNGT1, and NPSR1 were hub genes. Then, we verified the above results by GSE118370, GSE136043, and GSE140797 datasets. Compared with normal lung tissues, the expression levels of ADCY8 and ADRB2 were lower in LUAD tissues, but the expression levels of CALCA, GCG, GNGT1, and NPSR1 were higher. In the prognosis analyses, the low expression of ADCY8 and ADRB2 and the high expression of CALCA, GCG, GNGT1, and NPSR1 were correlated with poor OS and poor PFS. The significant differences in the relationship of the expression of 6 hub genes and clinical features were observed. In conclusion, 6 hub genes will not only contribute to elucidating the pathogenesis of LUAD and may be potential therapeutic targets for LUAD.

New MR-based measures for the evaluation of age-related lumbar paraspinal muscle degeneration.

PURPOSE: Although signal intensity on T2W axial images is sensitive in detection of fatty infiltration to assess paraspinal muscle degeneration, it is affected by inhomogeneities of magnetic fields and individual variabilities. The purpose of this study was to propose reference adjusted signal measures on T2W axial images and determine their capacities in reflecting age-related lumbar paraspinal muscle degeneration. METHODS: Lumbar MR images of 421 population-based subjects (177 men and 244 women, mean age 53.1 years, range 19.8-87.9 years) were studied. A custom software Spine Explore (Tulong 2.0) was used to automatically obtain paraspinal measurements of multifidus, erector spinae and psoas major. FCSA/TCSA was defined as functional cross-sectional area relative to total cross-sectional area of paraspinal muscle. Two new signal measures were canal-adjusted and cerebrospinal fluid (CSF)-adjusted signal, defined as the ratio between mean signal measurements and the mean signal of the canal and CSF. RESULTS: The raw signal measurements of the paraspinal muscles were weakly correlated to age (r = 0.28-0.39, P < 0.001). When the signal of canal (r = 0.43-0.59, P < 0.001) or CSF (r = 0.45-0.61, P < 0.001) was used as reference, the correlations substantially increased. Signal measurements of three paraspinal muscles, adjusted or not, were strongly associated with Goutallier score (ρ = 0.60-0.65, P < 0.001) and FCSA/TCSA (r = -0.64 to -0.82, P < 0.001). Greater Goutallier score was associated with greater age (r = 0.38-0.60, P < 0.001), while Lumbar indentation value (LIV) not. CONCLUSION: On routine T2W axial MR images the adjusted signal measurements using an internal reference of CSF or canal can better reflect age-related degenerative changes in the paraspinal muscles.

Analysis and improvement of positioning reliability and accuracy of theta pipette configuration for scanning ion conductance microscopy.

Scanning ion conductance microscopy (SICM) as an emerging non-contact scanning probe microscopy technique and featuring its strong in-situ detectability for soft and viscous samples, is increasingly used in biomedical and materials related studies. In SICM measurements, employing theta pipette as SICM probe to scan sample is an effective method to extend the applications of SICM for multi-parameter measurement. There are two crucial but still unclear issues that influence the reliability and accuracy of the usage of theta pipette in the SICM measurements, which are the safe feedback threshold and the horizontal measurement offset. In this work, aiming at the theta pipette configuration of SICM, we systematically investigated the two issues of the theta pipette by both finite element method (FEM) simulation and SICM experiments. The FEM analysis results show that the safe feedback threshold of the one side barrel of the theta pipette is above 99.5%, and the horizontal measurement offset is ~0.53 times of the inner radius of the probe tip. Based on this, we proposed an improved scanning method used by the theta pipette to solve the reliability and accuracy problems caused by the feedback threshold too close to the reference current (100%) and the measurement offset error at the tip radius level. Then through testing the polydimethylsiloxane (PDMS) samples with different embossed patterns with the improved method of SICM, we can conclude that the improved method can enhance the scanning reliability by adding the double barrels approaching process and increase the positioning accuracy by compensating an offset distance. The theoretical analysis and the improved scanning method in this work demonstrate more property and usage details of the theta pipette, and further improve the reliability and accuracy of the diversified multifunctional applications of the theta pipette for SICM to meet the increasingly complex and precise research needs.

The sequence of pulmonary vessels ligation during lobectomy for non-small cell lung cancer: A systematic review and meta-analysis.

OBJECTIVES: The effects of ligating the pulmonary vein first or pulmonary artery first during lobectomy on the long-term survival of patients with non-small cell lung cancer (NSCLC) remain controversial. We conducted the first systematic review and meta-analysis to determine the association between different sequences of vessel ligation during lobectomy and the prognosis of patients with NSCLC. METHODS: Literature retrieval was performed by systematically searching Embase, PubMed and Web of Science to identify relevant articles published from the inception of each database to November 2020. The overall survival (OS) and disease-free survival (DFS) of patients treated with vein-first ligation versus those treated with artery-first ligation during lobectomy were analyzed. A standard fixed-effect model test (Mantel-Haenszel method) was used to calculate pooled hazard ratios (HRs) and 95% confidence intervals (CIs). Heterogeneity was assessed using the Q-test and I2-test. Sensitivity analysis was performed to further examine the stability of pooled HRs. RESULTS: Five studies with a total of 1109 patients receiving lobectomy, including one randomized controlled trial and four retrospective studies, were included in this meta-analysis. The results showed that patients with vein-first ligation had a significantly better OS (HR 1.25, 95% CI 1.03-1.50; P = 0.02) and DFS (HR 1.54, 95% CI 1.16-2.04; P = 0.003) than those with artery-first ligation during lobectomy. Significant heterogeneity and publication bias were not observed during analysis. CONCLUSION: Our meta-analysis indicates that vein-first ligation may improve the prognosis of NSCLC patients receiving lobectomy. Therefore, vein-first ligation is recommended during lobectomy for patients with non-small cell lung cancer whenever possible.

A Deep-Learning-Based, Fully Automated Program to Segment and Quantify Major Spinal Components on Axial Lumbar Spine Magnetic Resonance Images.

OBJECTIVE: The paraspinal muscles have been extensively studied on axial lumbar magnetic resonance imaging (MRI) for better understanding of back pain; however, the acquisition of measurements mainly relies on manual segmentation, which is time consuming. The study objective was to develop and validate a deep-learning-based program for automated acquisition of quantitative measurements for major lumbar spine components on axial lumbar MRIs, the paraspinal muscles in particular. METHODS: This study used a cross-sectional observational design. From the Hangzhou Lumbar Spine Study, T2-weighted axial MRIs at the L4-5 disk level of 120 participants (aged 54.8 years [SD = 15.0]) were selected to develop the deep-learning-based program Spine Explorer (Tulong). Another 30 axial lumbar MRIs were automatically measured by Spine Explorer and then manually measured using ImageJ to acquire quantitative size and compositional measurements for bilateral multifidus, erector spinae, and psoas muscles; the disk; and the spinal canal. Intersection-over-union and Dice score were used to evaluate the performance of automated segmentation. Intraclass coefficients and Bland-Altman plots were used to examine intersoftware agreements for various measurements. RESULTS: After training, Spine Explorer (Tulong) measures an axial lumbar MRI in 1 second. The intersections-over-union were 83.3% to 88.4% for the paraspinal muscles and 92.2% and 82.1% for the disk and spinal canal, respectively. For various size and compositional measurements of paraspinal muscles, Spine Explorer (Tulong) was in good agreement with ImageJ (intraclass coefficient = 0.85 to approximately 0.99). CONCLUSION: Spine Explorer (Tulong) is automated, efficient, and reliable in acquiring quantitative measurements for the paraspinal muscles, the disk, and the canal, and various size and compositional measurements were simultaneously obtained for the lumbar paraspinal muscles. IMPACT: Such an automated program might encourage further epidemiological studies of the lumbar paraspinal muscle degeneration and enhance paraspinal muscle assessment in clinical practice.