Expert-Guided Knowledge Distillation for Semi-Supervised Vessel Segmentation.

In medical image analysis, blood vessel segmentation is of considerable clinical value for diagnosis and surgery. The predicaments of complex vascular structures obstruct the development of the field. Despite many algorithms have emerged to get off the tight corners, they rely excessively on careful annotations for tubular vessel extraction. A practical solution is to excavate the feature information distribution from unlabeled data. This work proposes a novel semi-supervised vessel segmentation framework, named EXP-Net, to navigate through finite annotations. Based on the training mechanism of the Mean Teacher model, we innovatively engage an expert network in EXP-Net to enhance knowledge distillation. The expert network comprises knowledge and connectivity enhancement modules, which are respectively in charge of modeling feature relationships from global and detailed perspectives. In particular, the knowledge enhancement module leverages the vision transformer to highlight the long-range dependencies among multi-level token components; the connectivity enhancement module maximizes the properties of topology and geometry by skeletonizing the vessel in a non-parametric manner. The key components are dedicated to the conditions of weak vessel connectivity and poor pixel contrast. Extensive evaluations show that our EXP-Net achieves state-of-the-art performance on subcutaneous vessel, retinal vessel, and coronary artery segmentations.

SCANet: A Unified Semi-Supervised Learning Framework for Vessel Segmentation.

Automatic subcutaneous vessel imaging with near-infrared (NIR) optical apparatus can promote the accuracy of locating blood vessels, thus significantly contributing to clinical venipuncture research. Though deep learning models have achieved remarkable success in medical image segmentation, they still struggle in the subfield of subcutaneous vessel segmentation due to the scarcity and low-quality of annotated data. To relieve it, this work presents a novel semi-supervised learning framework, SCANet, that achieves accurate vessel segmentation through an alternate training strategy. The SCANet is composed of a multi-scale recurrent neural network that embeds coarse-to-fine features and two auxiliary branches, a consistency decoder and an adversarial learning branch, responsible for strengthening fine-grained details and eliminating differences between ground-truths and predictions, respectively. Equipped with a novel semi-supervised alternate training strategy, the three components work collaboratively, enabling SCANet to accurately segment vessel regions with only a handful of labeled data and abounding unlabeled data. Moreover, to mitigate the shortage of annotated data in this field, we provide a new subcutaneous vessel dataset, VESSEL-NIR. Extensive experiments on a wide variety of tasks, including the segmentation of subcutaneous vessels, retinal vessels, and skin lesions, well demonstrate the superiority and generality of our approach.

Risk stratification system and visualized dynamic nomogram constructed for predicting diagnosis and prognosis in rare male breast cancer patients with bone metastases.

Background: Bone metastases (BM) from malignant tumors could disrupt the balance between osteoclasts and osteoblasts and affect bone homeostasis. Malignant breast cancer (BC) is rare in male patients, and co-occurrence of BM is even rarer. Given its low incidence, there is limited research evaluating risk and prognosis. Despite the widespread application of nomograms to predict uncommon malignancies, no studies have constructed predictive models focusing on the diagnosis and prognosis of male breast cancer with bone metastases (MBCBM). Methods: This study selected all male breast cancer patients (MBC) between 2010 and 2019 in the Surveillance, Epidemiology, and End Results (SEER) database. We used simple and multivariate Logistic regression analyses to identify independent risk factors for BM in MBC patients. Then simple and multivariate Cox regression analyses were employed to determine the independent prognostic factors for overall survival (OS) and cancer-specific survival (CSS) in MBCBM patients. We established and validated three new nomograms based on these independent factors. Result: A total of 4187 MBC patients were included, with 191 (4.56%) having bone metastases at the time of diagnosis. The independent risk factors of BM in MBC patients included age, tumor size, marital status, T stage, and N stage. In MBCBM patients, independent prognostic factors for OS and CSS were both age, T stage, ER status, PR status, and surgery. The concordance index (C-index), the area under the curve (AUC) of the receiver operating characteristic curve (ROC), the calibration curve, and the decision curve analysis (DCA) confirmed that these three nomograms could accurately predict the diagnosis and prognosis of MBCBM patients with excellent discrimination and clinical utility superior to the TNM staging system. We then established two prognostic-based risk stratification systems and three visualized dynamic nomograms that could be applied in clinical practice. Conclusion: In conclusion, this study aimed to establish and validate an accurate novel nomogram to objectively predict the diagnosis and prognosis of MBCBM patients. On this basis, prognostic-based risk stratification systems and visualized dynamic nomograms were constructed to facilitate doctors and patients to quantify individual BM risk probability and survival probability to assist in personalized risk assessment and clinical decision-making.

TrustGWAS: A full-process workflow for encrypted GWAS using multi-key homomorphic encryption and pseudorandom number perturbation.

The statistical power of genome-wide association studies (GWASs) is affected by the effective sample size. However, the privacy and security concerns associated with individual-level genotype data pose great challenges for cross-institutional cooperation. The full-process cryptographic solutions are in demand but have not been covered, especially the essential principal-component analysis (PCA). Here, we present TrustGWAS, a complete solution for secure, large-scale GWAS, recapitulating gold standard results against PLINK without compromising privacy and supporting basic PLINK steps including quality control, linkage disequilibrium pruning, PCA, chi-square test, Cochran-Armitage trend test, covariate-supported logistic regression and linear regression, and their sequential combinations. TrustGWAS leverages pseudorandom number perturbations for PCA and multiparty scheme of multi-key homomorphic encryption for all other modules. TrustGWAS can evaluate 100,000 individuals with 1 million variants and complete QC-LD-PCA-regression workflow within 50 h. We further successfully discover gene loci associated with fasting blood glucose, consistent with the findings of the ChinaMAP project.

Single-Cell Transcriptomics Reveals Killing Mechanisms of Antitumor Cytotoxic CD4+ TCR-T Cells.

T cell receptor-engineered T cells (TCR-Ts) have emerged as potent cancer immunotherapies. While most research focused on classical cytotoxic CD8+ T cells, the application of CD4+ T cells in adoptive T cell therapy has gained much interest recently. However, the cytotoxic mechanisms of CD4+ TCR-Ts have not been fully revealed. In this study, we obtained an MHC class I-restricted MART-127-35-specific TCR sequence based on the single-cell V(D)J sequencing technology, and constructed MART-127-35-specific CD4+ TCR-Ts and CD8+ TCR-Ts. The antitumor effects of CD4+ TCR-Ts were comparable to those of CD8+ TCR-Ts in vitro and in vivo. To delineate the killing mechanisms of cytotoxic CD4+ TCR-Ts, we performed single-cell RNA sequencing and found that classical granule-dependent and independent cytolytic pathways were commonly used in CD4+ and CD8+ TCR-Ts, while high expression of LTA and various costimulatory receptors were unique features for cytotoxic CD4+ TCR-Ts. Further signaling pathway analysis revealed that transcription factors Runx3 and Blimp1/Tbx21 were crucial for the development and killing function of cytotoxic CD4+ T cells. Taken together, we report the antitumor effects and multifaceted killing mechanisms of CD4+ TCR-Ts, and also indicate that MHC class I-restricted CD4+ TCR-Ts could serve as potential adoptive T cell therapies.

Association of PTPRT Mutations with Cancer Metastasis in Multiple Cancer Types.

Metastasis is one of the characteristics of advanced cancer and the primary cause of cancer-related deaths from cancer, but the mechanism underlying metastasis is unclear, and there is a lack of metastasis markers. PTPRT is a protein-coding gene involved in both signal transduction and cellular adhesion. It is also known as a tumor suppressor gene that inhibits cell malignant proliferation by inhibiting the STAT3 pathway. Recent studies have reported that PTPRT is involved in the early metastatic seeding of colorectal cancer; however, the correlation between PTPRT and metastasis in other types of cancer has not been revealed. A combined analysis using a dataset from the genomics evidence neoplasia information exchange (GENIE) and cBioPortal revealed that PTPRT mutation is associated with poor prognosis in pan-cancer and non-small-cell lung cancer. The mutations of PTPRT or "gene modules" containing PTPRT are significantly enriched in patients with metastatic cancer in multiple cancers, suggesting that the PTPRT mutations serve as potential biomarkers of cancer metastasis.

A Novel Proteogenomic Integration Strategy Expands the Breadth of Neo-Epitope Sources.

Tumor-specific antigens can activate T cell-based antitumor immune responses and are ideal targets for cancer immunotherapy. However, their identification is still challenging. Although mass spectrometry can directly identify human leukocyte antigen (HLA) binding peptides in tumor cells, it focuses on tumor-specific antigens derived from annotated protein-coding regions constituting only 1.5% of the genome. We developed a novel proteogenomic integration strategy to expand the breadth of tumor-specific epitopes derived from all genomic regions. Using the colorectal cancer cell line HCT116 as a model, we accurately identified 10,737 HLA-presented peptides, 1293 of which were non-canonical peptides that traditional database searches could not identify. Moreover, we found eight tumor neo-epitopes derived from somatic mutations, four of which were not previously reported. Our findings suggest that this new proteogenomic approach holds great promise for increasing the number of tumor-specific antigen candidates, potentially enlarging the tumor target pool and improving cancer immunotherapy.

Integrating convolution and self-attention improves language model of human genome for interpreting non-coding regions at base-resolution.

Interpretation of non-coding genome remains an unsolved challenge in human genetics due to impracticality of exhaustively annotating biochemically active elements in all conditions. Deep learning based computational approaches emerge recently to help interpret non-coding regions. Here, we present LOGO (Language of Genome), a self-attention based contextualized pre-trained language model containing only two self-attention layers with 1 million parameters as a substantially light architecture that applies self-supervision techniques to learn bidirectional representations of the unlabelled human reference genome. LOGO is then fine-tuned for sequence labelling task, and further extended to variant prioritization task via a special input encoding scheme of alternative alleles followed by adding a convolutional module. Experiments show that LOGO achieves 15% absolute improvement for promoter identification and up to 4.5% absolute improvement for enhancer-promoter interaction prediction. LOGO exhibits state-of-the-art multi-task predictive power on thousands of chromatin features with only 3% parameterization benchmarking against the fully supervised model, DeepSEA and 1% parameterization against a recent BERT-based DNA language model. For allelic-effect prediction, locality introduced by one dimensional convolution shows improved sensitivity and specificity for prioritizing non-coding variants associated with human diseases. In addition, we apply LOGO to interpret type 2 diabetes (T2D) GWAS signals and infer underlying regulatory mechanisms. We make a conceptual analogy between natural language and human genome and demonstrate LOGO is an accurate, fast, scalable, and robust framework to interpret non-coding regions for global sequence labeling as well as for variant prioritization at base-resolution.

Alcohol Consumption and Risk of Atrial Fibrillation: A Dose-Response Meta-Analysis of Prospective Studies.

Background: This study aimed to investigate the dose-response association between alcohol consumption and atrial fibrillation (AF) risk. Methods: PubMed, Embase, Cochrane Library, and Web of Science were systematically searched using keywords related to alcohol and AF from the establishment of databases up to 1 March 2021. Prospective studies examining the impact of alcohol on the risk of AF with hazard ratios (HRs) were included. Restricted cubic spline regression was performed to quantify the dose-response relationship between alcohol consumption and AF risk. Results: Thirteen eligible studies were included in the meta-analysis, with a total of 645,826 participants and 23,079 cases of AF. When compared with non-/seldom-drinkers, the pooled adjusted HRs of AF were 1.30 (95% confidence interval [CI]: 1.20-1.41) and 1.00 (95% CI: 0.96-1.05) for high and low alcohol consumption, respectively. Moderate alcohol intake significantly increased the risk of AF in males (HR, 1.21; 95% CI: 1.10-1.33) but not in females (HR, 1.02; 95% CI: 0.91-1.14). The cubic spline regression analysis illustrated that the risk of AF significantly increased with daily alcohol intake in a Non-linear manner (R2 = 0.64, P = 5.785 × 10-12). Conclusion: This study revealed a Non-linearly positive association between alcohol intake and the risk of AF. Low alcohol intake was not associated with the development of AF, whereas moderate alcohol intake significantly increased the risk of AF in males but not in females. Our meta-analysis highlighted that alcohol consumption should be restricted to a low level to reduce the risk of AF.

Maximum Spreading of Impacting Ferrofluid Droplets under the Effect of Nonuniform Magnetic Field.

This article investigates the maximum spreading of ferrofluid droplets impacting on a hydrophobic surface under nonuniform magnetic fields. A generalized model for scaling the maximum spreading is developed. It is observed that, if the magnetic field strength is zero, a ferrofluid droplet not only demonstrates similar spreading dynamics as the water droplet but also obeys the same scaling law for the maximum spreading factor. Therefore, this article emphasizes the effects of magnetic field strength. In this regard, a dimensionless parameter (Nm) is introduced as the ratio between inertial force and Kelvin force, with an assumption that the kinetic energy mainly transforms to thermal energy. This parameter allows us to rescale all experimental data on a single curve with the Padé approximant, which is applicable to a wide range of impact velocities and magnetic field strengths.

Efficacy and potential mechanisms of Chinese herbal compounds in coronavirus disease 2019: advances of laboratory and clinical studies.

The Coronavirus disease 2019 (COVID-19) pandemic is still spread and has made a severe public health threat around the world. To improve disease progression, emerging Chinese herbal compounds were used in clinical practice and some agents have proven beneficial in treating COVID-19. Here, the relevant literature from basic researches to clinical application were identified and comprehensively assessed. A variety of Chinese herbal compounds have been reported to be effective in improving symptoms and outcomes in patients with COVID-19, particularly together with routine treatment strategy. The pharmacological activities were mainly attributed to the relief of clinical symptoms, inhibition of cytokine storm, and improvement of organ function. Besides, the development of novel antiviral drugs from medicinal herbs were further discussed. The updated laboratory and clinical studies provided the evidence of Chinese herbal compounds such as Lianhua Qingwen prescription, Shufeng Jiedu prescription, and Qingfei Paidu Tang for the relief of COVID-19. However, both of the randomized controlled trials and real world researches need to be done for supporting the evidence including the efficacy and safety in fighting COVID-19.

The Setup and Application of Reference Material in Sequencing-Based Noninvasive Prenatal Testing.

INTRODUCTION: The sequencing-based noninvasive prenatal testing (NIPT) has been successfully integrated into clinical practice and facilitated the early detection of fetal chromosomal anomalies. However, a comprehensive reference material to evaluate and quality control NIPT services from different NIPT providers remains unavailable. METHODS: In this study, we established a set of NIPT reference material consisting of 192 simulated samples. Most of the potential factors influencing the accuracy of NIPT, such as fetal fraction, mosaicism, and interfering substances, were included in the reference material. We compared the performance of chromosomal abnormalities detection on 3 widely used sequencers (NextSeq 500, BGISEQ-500, and Ion Proton) based on the reference material. RESULTS: All 3 sequencers provided highly accurate and reliable results to samples with ≥3.5% fetal fractions and high percentage of mosaicism. CONCLUSIONS: The established reference material can serve as a universal standard quality control for the current and new-coming NIPT providers based on various sequencers.

High-flow hydrogen inhalation might suppresses the immune function of middle-aged participants: a self-controlled study.

Hydrogen inhalation therapy has been proven to be safe and effective in disease treatment in multiple clinical reports, but the gas flow rates used in different studies vary greatly. Since there is no upper limit for the safe concentration of hydrogen, this study tested the effects of high-flow (not high concentration) hydrogen inhalation on immune function. From October 2019 to January 2020, 20 adult participants (31-60 years old) were enrolled in a self-controlled study to check the immune function in peripheral blood lymphocyte subsets before and after a 2-week hydrogen inhalation protocol. The participants inhaled hydrogen for 2 or 4 hours each day. After 2 weeks of hydrogen inhalation, statistically significant changes were observed in follicular helper T cells, helper and cytotoxic T cells, natural killer and natural killer T cells, and gamma delta T cells, generally suggesting a decrease in their proportions. These results show that high-flow hydrogen inhalation has an inhibitory effect on the immune function of healthy participants. The study protocol received ethical approval from the Ethics Committee of Fuda Cancer Hospital, Jinan University on December 7, 2018 (approval No. Fuda20181207).

Morphologic analysis of Chinese lumbar endplate by three-dimensional computed tomography reconstructions for helping design lumbar disc prosthesis.

ABSTRACT: Lumbar disc prostheses have been used increasingly in recent years. The successful design of lumbar disc prostheses depends on accurate morphometric parameters. However, the morphologic dimensions of lumbar endplate area have not been investigated in Chinese population.A total of 1800 lumbar endplates were retrospectively accessed in 150 Chinese adults. Eighteen parameters of each lumbar segment were measured by three-dimensional computed tomography reconstructions from T12/L1 to L5/S1. These obtained parameters were compared between genders, bilateral sides, vertebral segments, and different populations.Endplate length and width increased in general, and there was a significant decrease for length/width ratio from T12 to S1 (P = .03). The average concavity depth of the lower lumbar endplate (2.09 ±â€Š0.93 mm) was usually larger than that of the upper lumbar endplate (1.61 ±â€Š0.74 mm) (P = .02). The percentage of the most concave point of the upper and lower lumbar endplate was 50.01 ±â€Š10.76% and 56.41 ±â€Š9.93%, respectively. Anterior, medium, or posterior intervertebral endplate height was severally 10.01 ±â€Š1.98 mm, 10.46 ±â€Š2.03 mm, and 6.41 ±â€Š1.74 mm, and increased among vertebral segments (P = .01).The intervertebral endplate angle significantly increased from T12-L1 to L5-S1 (P = .01). Parameters displayed significant difference between genders. The morphometric parameters of different populations also showed differences.In conclusion, there is a morphologic discrepancy in dimensions of lumbar endplate regarding genders, vertebral segments, and different populations. It is essential to design the lumbar disc prosthesis suited for Chinese patients specially, for which the morphometric parameters in our study can be utilized.

Two weeks of hydrogen inhalation can significantly reverse adaptive and innate immune system senescence patients with advanced non-small cell lung cancer: a self-controlled study.

Following standard treatments, the traditional model for enhancing anti-tumor immunity involves performing immune reconstitution (e.g., adoptive immune cell therapies or immunoenhancing drugs) to prevent recurrence. For patients with advanced non-small cell lung cancer, we report here on two objectives, the immunosenescence for advanced non-small cell lung cancer and hydrogen gas inhalation for immune reconstitution. From July 1st to September 25th, 2019, 20 non-small cell lung cancer patients were enrolled to evaluate the immunosenescence of peripheral blood lymphocyte subsets, including T cell, natural killer/natural killer T cell and gamma delta T cell. Two weeks of hydrogen inhalation was performed during the waiting period for treatment-related examination. All patients inhaled a mixture of hydrogen (66.7%) and oxygen (33.3%) with a gas flow rate of 3 L/min for 4 hours each day. None of the patients received any standard treatment during the hydrogen inhalation period. After pretreatment testing, major indexes of immunosenescence were observed. The abnormally higher indexes included exhausted cytotoxic T cells, senescent cytotoxic T cells, and killer Vδ1 cells. After 2 weeks of hydrogen therapy, the number of exhausted and senescent cytotoxic T cells decreased to within the normal range, and there was an increase in killer Vδ1 cells. The abnormally lower indexes included functional helper and cytotoxic T cells, Th1, total natural killer T cells, natural killer, and Vδ2 cells. After 2 weeks of hydrogen therapy, all six cell subsets increased to within the normal range. The current data indicate that the immunosenescence of advanced non-small cell lung cancer involves nearly all lymphocyte subsets, and 2 weeks of hydrogen treatment can significantly improve most of these indexes. The study was approved by the Ethics Committee of Fuda Cancer Hospital, Jinan University in China (approval No. Fuda20181207) on December 7th, 2018, and was registered on ClinicalTrials.gov (ID: NCT03818347) on January 24th, 2019.

Performance of copy number variants detection based on whole-genome sequencing by DNBSEQ platforms.

BACKGROUND: DNBSEQ™ platforms are new massively parallel sequencing (MPS) platforms that use DNA nanoball technology. Use of data generated from DNBSEQ™ platforms to detect single nucleotide variants (SNVs) and small insertions and deletions (indels) has proven to be quite effective, while the feasibility of copy number variants (CNVs) detection is unclear. RESULTS: Here, we first benchmarked different CNV detection tools based on Illumina whole-genome sequencing (WGS) data of NA12878 and then assessed these tools in CNV detection based on DNBSEQ™ sequencing data from the same sample. When the same tool was used, the CNVs detected based on DNBSEQ™ and Illumina data were similar in quantity, length and distribution, while great differences existed within results from different tools and even based on data from a single platform. We further estimated the CNV detection power based on available CNV benchmarks of NA12878 and found similar precision and sensitivity between the DNBSEQ™ and Illumina platforms. We also found higher precision of CNVs shorter than 1 kbp based on DNBSEQ™ platforms than those based on Illumina platforms by using Pindel, DELLY and LUMPY. We carefully compared these two available benchmarks and found a large proportion of specific CNVs between them. Thus, we constructed a more complete CNV benchmark of NA12878 containing 3512 CNV regions. CONCLUSIONS: We assessed and benchmarked CNV detections based on WGS with DNBSEQ™ platforms and provide guidelines for future studies.

Quantitative proteomics reveals the regulatory networks of circular RNA BTBD7_hsa_circ_0000563 in human coronary artery.

BACKGROUND: BTBD7_hsa_circ_0000563, which is located on chromosome 14, contains conserved binding sites with miR-155/130a and RNA-binding proteins according to bioinformatic prediction. We investigated the association of BTBD7_hsa_circ_0000563 expression in coronary artery segments with atherosclerotic stenosis and identified the proteome-wide BTBD7_hsa_circ_0000563-regulated proteins in human coronary artery. METHODS: The atherosclerotic grade and extent in coronary artery segments were determined by hematoxylin and eosin staining. BTBD7_hsa_circ_0000563 expression in eight coronary artery segments from one patient was quantified by RT-qPCR assay. A proteomic approach was adopted to reveal significant differences in protein expression between among four groups differing in their BTBD7_hsa_circ_0000563 expression levels. RESULTS: The RT-qPCR assay revealed that coronary artery segments with severe atherosclerotic stenosis had significantly low BTBD7_hsa_circ_0000563 levels. The proteomic analysis identified 49 differentially expressed proteins among the segment groups with different BTBD7_hsa_circ_0000563 expression levels, of which 10 were downregulated and 39 were upregulated with increases in the BTBD7_hsa_circ_0000563 level. The 10 downregulated proteins were P61626 (LYSC_HUMAN), P02760 (AMBP_HUMAN), Q02985 (FHR3_HUMAN), P01701 (LV151_HUMAN), P06312(KV401_HUMAN), P01624 (KV315_HUMAN), P13671 (CO6_HUMAN), P01700(LV147_HUMAN), Q9Y287(ITM2B_HUMAN), and A0A075B6I0 (LV861_HUMAN). The top 10 upregulated proteins were Q92552 (RT27_HUMAN), Q9UJY1(HSPB8_HUMAN), Q9Y235(ABEC2_HUMAN), P19022 (CADH2_HUMAN), O43837(IDH3B_HUMAN), Q9H479(FN3K_HUMAN), Q9UM22(EPDR1_HUMAN), P48681(NEST_HUMAN), Q9NRP0(OSTC_HUMAN), and Q15628(TRADD_HUMAN). CONCLUSION: BTBD7_hsa_circ_0000563 is involved in the atherosclerotic changes in human coronary artery segments. Verification, mechanistic, and function studies are needed to confirm whether patients with coronary artery disease would benefit from such personalized medicine in the future.

Hydrogen therapy can be used to control tumor progression and alleviate the adverse events of medications in patients with advanced non-small cell lung cancer.

Chemotherapy, targeted therapy, and immunotherapy are used against advanced non-small cell lung cancer. A clinically efficacious method for relieving the adverse events associated of such therapies is lacking. Fifty-eight adult patients were enrolled in our trial to relieve pulmonary symptoms or the adverse events of drugs. Twenty patients who refused drug treatment were assigned equally and randomly to a hydrogen (H2)-only group and a control group. According to the results of tumor-gene mutations and drug-sensitivity tests, 10, 18, and 10 patients were enrolled into chemotherapy, targeted therapy, and immunotherapy groups in which these therapies were combined with H2-therapy, respectively. Patients underwent H2 inhalation for 4-5 hours per day for 5 months or stopped when cancer recurrence. Before study initiation, the demographics (except for tumor-mutation genes) and pulmonary symptoms (except for moderate cough) of the five groups showed no significant difference. During the first 5 months of treatment, the prevalence of symptoms of the control group increased gradually, whereas that of the four treatment groups decreased gradually. After 16 months of follow-up, progression-free survival of the control group was lower than that of the H2-only group, and significantly lower than that of H2 + chemotherapy, H2 + targeted therapy, and H2 + immunotherapy groups. In the combined-therapy groups, most drug-associated adverse events decreased gradually or even disappeared. H2 inhalation was first discovered in the clinic that can be used to control tumor progression and alleviate the adverse events of medications for patients with advanced non-small cell lung cancer. This study was approved by the Ethics Committee of Fuda Cancer Hospital of Jinan University on December 7, 2018 (approval No. Fuda20181207), and was registered at ClinicalTrials.gov (Identifier: NCT03818347) on January 28, 2019.

The future of cryoablation: An abscopal effect.

Cryoablation has become a popular modality to treat a variety of malignant tumors in solid organs and soft tissues. In the future, the use of cryoablation should focus on its abscopal effect. The present review discusses the increased immune response triggered by cryoablation alone or by cryoablation combined with immunotherapies, which can improve the immune response and limit immunosuppression. First, cryoablative techniques should be improved to increase the area of necrosis and reduce the area of apoptosis. Second, cryoablation should be combined with immunotherapies, for example, cyclophosphamide, natural killer cells, granulocyte monocyte colony stimulating factor (GM-CSF), cytotoxic T lymphocyte-associated antigen (CTLA)-4, and programmed death receptor 1 (PD)-1 inhibitors. Cryoablation could also be combined with Hydrogen gas molecules, which were shown recently to stimulate peroxisome proliferator activated receptor gamma coactivator (PGC)-1α, thereby promoting mitochondrial function, which might rescue exhausted CD8+ T cells, leading to prolonged progression-free survival and overall survival of patients with advanced colorectal cancer.