Regulatory T Cells Induced by Single-Peptide Liposome Immunotherapy Suppress Islet-Specific T Cell Responses to Multiple Antigens and Protect from Autoimmune Diabetes.

Ag-specific tolerizing immunotherapy is considered the optimal strategy to control type 1 diabetes, a childhood disease involving autoimmunity toward multiple islet antigenic peptides. To understand whether tolerizing immunotherapy with a single peptide could control diabetes driven by multiple Ags, we coencapsulated the high-affinity CD4+ mimotope (BDC2.5mim) of islet autoantigen chromogranin A (ChgA) with or without calcitriol (1α,25-dihydroxyvitamin D3) into liposomes. After liposome administration, we followed the endogenous ChgA-specific immune response with specific tetramers. Liposome administration s.c., but not i.v., induced ChgA-specific Foxp3+ and Foxp3- PD1+ CD73+ ICOS+ IL-10+ peripheral regulatory T cells in prediabetic mice, and liposome administration at the onset of hyperglycemia significantly delayed diabetes progression. After BDC2.5mim/calcitriol liposome administration, adoptive transfer of CD4+ T cells suppressed the development of diabetes in NOD severe combined immunodeficiency mice receiving diabetogenic splenocytes. After BDC2.5mim/calcitriol liposome treatment and expansion of ChgA-specific peripheral regulatory T cells. IFN-γ production and expansion of islet-specific glucose-6-phosphatase catalytic subunit-related protein-specific CD8+ T cells were also suppressed in pancreatic draining lymph node, demonstrating bystander tolerance at the site of Ag presentation. Thus, liposomes encapsulating the single CD4+ peptide, BDC2.5mim, and calcitriol induce ChgA-specific CD4+ T cells that regulate CD4+ and CD8+ self-antigen specificities and autoimmune diabetes in NOD mice.

A Case of Hypophosphatemia due to Oncogenic Osteomalacia in a Patient with Natural Killer T-Cell Lymphoma.

INTRODUCTION: Oncogenic osteomalacia (Onc-Ost) is a paraneoplastic phenomenon characterized by hypophosphatemia due to elevated fibroblast growth factor-23 (FGF-23). Onc-Ost has been previously reported in patients with germ line mesenchymal tumors and solid organ malignancies. This is the first report of aggressive natural killer (NK) T-cell lymphoma presenting as Onc-Ost. CASE DESCRIPTION: A 33-year-old Vietnamese female with active hepatitis B and Mycobacterium avium complex, on ongoing therapy with tenofovir disoproxil, azithromycin, and ethambutol, presented with persistent fevers and developed refractory hypophosphatemia. Workup confirmed severe renal phosphate wasting. Tenofovir disoproxil was initially suspected; however, presence of isolated phosphaturia without Fanconi syndrome and persistence of hypophosphatemia despite discontinuation of medication led to clinical suspicion of Onc-Ost. Elevated FGF-23 warranted further workup, leading to a definitive diagnosis of clinically subtle NK T-cell lymphoma. Chemotherapy was initiated; however, patient continued to deteriorate clinically and expired. CONCLUSION: Along with commonly reported germ line mesenchymal tumors and solid malignancies, NK T-cell lymphoma can also present as Onc-Ost. Timely detection of associated tumors and subsequent antitumor therapy would likely reverse hypophosphatemia and improve clinical outcomes.

Tunable Nanosensor Based on Fano Resonances Created by Changing the Deviation Angle of the Metal Core in a Plasmonic Cavity.

In this paper, a type of tunable plasmonic refractive index nanosensor based on Fano resonance is proposed and investigated. The sensor comprises a metal-insulator-metal (MIM) nanocavity with a center-deviated metal core and two side-coupled waveguides. By carefully adjusting the deviation angle and distance of the metal core in the cavity, Fano resonances can be obtained and modulated. The Fano resonances can be considered as results induced by the symmetry-breaking or geometric effect that affects the field distribution intensity at the coupling region between the right waveguide and the cavity. Such a field-distribution pattern change can be regarded as being caused by the interference between the waveguide modes and the cavity modes. The investigations demonstrate that the spectral positions and modulation depths of Fano resonances are highly sensitive to the deviation parameters. Furthermore, the figure of merit (FOM) value is calculated for different deviation angle. The result shows that this kind of tunable sensor has compact structure, high transmission, sharp Fano lineshape, and high sensitivity to the change in background refractive index. This work provides an effective method for flexibly tuning Fano resonance, which has wide applications in designing on-chip plasmonic nanosensors or other relevant devices, such as information modulators, optical filters, and ultra-fast switches.

Electro-optical coupling of a circular Airy beam in a uniaxial crystal.

This paper investigates theoretically and numerically on the electro-optical coupling (EOC) for a circular Airy beam (CAB) propagating along the optical axis of a uniaxial crystal after deducing the wave coupling equations of EOC. For a circularly polarized incident CAB, EOC can be used to generate vortex beam by coupling the incident left-handed component into the right-handed vortex component with a vortex topological charge of 2. What's more, EOC plays important role in enhancing or suppressing the abrupt autofocusing, the most important property of CABs, for both left-handed and right-handed components. Near the focal plane, EOC can result in electrically controllable optical "needle" and "cage", which shall be interesting in micromanipulation. In addition, EOC can influence or even forbid the exchange between spin angular momentum (SAM) and orbit angular momentum (OAM). For a linearly polarized incident CAB, its two Cartesian field components of the beam cannot only couple their powers to each other, but also lead to the changes of the intensity pattern and polarization distributions. The polarization state becomes spatially inhomogeneous, and possesses vortex phase with a topological charge of 2 during propagation. EOC presents a new way to control an Airy beam fast and efficiently.

Propagation dynamics of a circular Airy beam in a uniaxial crystal.

This paper investigates theoretically and numerically the propagation characteristics of a circular Airy beam (CAB) in a uniaxial crystal in detail. The beam loses its boundary cylindrical symmetry during propagation because of the medium anisotropy, although it propagates along the optical axis. This effect of anisotropy on the propagating beam becomes increasingly evident with the increase of the propagation distance. Another main influential factor of the propagation characteristics is the ratio of the extraordinary refractive index to the ordinary refractive index (ne/no). The more the value deviates from 1, the worse the symmetry of the beam intensity distribution becomes. The polarization becomes notably complicated, but possesses a vortex state with a topological charge of 2 during propagation. The abruptly autofocusing characteristic, the most important property of CABs, also appears when the crystal length is long enough, which is greatly different from that characteristic in isotropic media. This work is helpful for the design of optical devices based on uniaxial crystals for beams with some special wavefronts.

Association of Serum Free Light Chain Level with Long-Term Kidney Function in Patients with Newly Diagnosed Multiple Myeloma.

INTRODUCTION: Multiple myeloma (MM) frequently involves the kidneys, resulting in acute, subacute, or chronic kidney disease (CKD). Patient- and treatment-related factors are associated with the long-term development of CKD. The aim of our study was to examine the association of serum free light chain (FLC) levels, measured at the time of diagnosis of MM, and CKD at subsequent follow-up. METHODS: Patients with newly diagnosed MM were identified using cancer registries at five hospitals. The primary outcome was low eGFR (<60 mL/min/1.73 m2) or dialysis dependence and a secondary composite outcome of low eGFR, dialysis dependence, or death at the last follow-up, up to 12 months from diagnosis. Logistic regression analyses were performed. RESULTS: A total of 149 patients met the inclusion criteria. Patients with an FLC level above the median had a higher frequency of hypertension (54% vs. 81%; p < 0.001), hyperlipidemia (37% vs. 56%; p = 0.018), low eGFR at the time of diagnosis (43% vs. 66%; p = 0.006), and a higher MM stage (p = 0.018). On multivariable analyses, after adjustment for several covariates, serum FLC level (per each 100 mg/L) was independently associated with low eGFR or dialysis dependence at follow-up (adjusted odds ratio [aOR] 1.021; 95% CI: 1.002, 1.041; p = 0.033). This association persisted for the composite outcome of low eGFR, dialysis dependence, or death (aOR 1.034; 95% CI: 1.006, 1.063; p = 0.018). DISCUSSION/CONCLUSION: Higher serum FLC level measured at the time of MM diagnosis is independently associated with CKD at up to 12 months of follow-up.

Development and interpretation of a multimodal predictive model for prognosis of gastrointestinal stromal tumor.

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal original tumor in gastrointestinal (GI) tract and is considered to have varying malignant potential. With the advancement of computer science, radiomics technology and deep learning had been applied in medical researches. It's vital to construct a more accurate and reliable multimodal predictive model for recurrence-free survival (RFS) aiding for clinical decision-making. A total of 254 patients underwent surgery and pathologically diagnosed with GIST in The First Hospital of China Medical University from 2019 to 2022 were included in the study. Preoperative contrast enhanced computerized tomography (CE-CT) and hematoxylin/eosin (H&E) stained whole slide images (WSI) were acquired for analysis. In the present study, we constructed a sum of 11 models while the multimodal model (average C-index of 0.917 on validation set in 10-fold cross validation) performed the best on external validation cohort with an average C-index of 0.864. The multimodal model also reached statistical significance when validated in the external validation cohort (n = 42) with a p-value of 0.0088 which pertained to the recurrence-free survival (RFS) comparison between the high and low groups using the optimal threshold on the predictive score. We also explored the biological significance of radiomics and pathomics features by visualization and quantitative analysis. In the present study, we constructed a multimodal model predicting RFS of GIST which was prior over unimodal models. We also proposed hypothesis on the correlation between morphology of tumor cell and prognosis.

GSTT1 null genotype contributes to increased risk of gastric cancer in Chinese population: evidence from a meta-analysis.

Previous studies suggested glutathione S-transferase T1 (GSTT1) null genotype might be a candidate genetic polymorphism with a role in the susceptibility to gastric cancer, but studies form Chinese population reported controversial findings. Thus, a meta-analysis was performed to clarify the effect of GSTT1 null genotype on gastric cancer risk in Chinese population. Eligible studies were searched in Medline, Embase, and China National Knowledge Infrastructure databases. Between-study heterogeneity was assessed using the I (2) statistic. Odds ratios (OR) with the corresponding 95 % confidence intervals (95 % CI) were pooled to assess the association. Twenty case-control studies involving a total of 3,204 gastric cancer cases and 5,462 controls were finally included in the meta-analysis. Meta-analysis of all 20 studies showed that GSTT1 null genotype was associated with an elevated risk of gastric cancer in Chinese population (OR=1.26, 95 % CI 1.09-1.46, P OR=0.002). The cumulative meta-analysis showed a trend of a more obvious association between GSTT1 null genotype and risk of gastric cancer in Chinese population as information accumulated gradually. Sensitivity analysis by omitting individual study, in turns, did not materially alter the pooled ORs. This meta-analysis provides a strong evidence for the significant association between GSTT1 null genotype and gastric cancer risk in Chinese population, and GSTT1 null genotype contributes to increased risk of gastric cancer.

The Interplay between RNA Editing Regulator ADAR1 and Immune Environment in Colorectal Cancer.

An abnormality in the regulation of adenosine deaminase acting on RNA (ADAR) enzymes, which catalyzed adenosine-to-inosine (A-to-I) RNA editing, was closely associated with the highly aggressive biologic behavior and poor prognosis in many malignancies. In the present study, we aimed to investigate the relationship among transcript factors-microRNAs regulatory network, immune environment, and ADAR gene in colorectal carcinoma (CRC). The association among the expression levels of ADAR mRNA and copy number variation, methylation, and mutation status were comprehensively analyzed using cBioPortal, Wanderer, and UALCAN databases in CRC datasets. ADAR-transcript factors (TFs) and ADAR-miRNA regulation networks were constructed by Cistrome Cancer and miRWalk2.0, respectively. The full network and subnetworks for ADAR coexpression genes were constructed using the STRING database and visualized by the MCODE module of the Cytoscape app. The relationship between ADAR mRNA expression and the abundance of infiltrating immune cells in CRC patients was explored by the Tumor Immune Estimation Resource, CIBERSORT, and single-gene gene set enrichment analysis (GSEA). ADAR mRNA was elevated and was a cancer essential gene in CRC. ADAR mRNA and transcripts P110 were significantly elevated in CRC compared to normal controls. Low-level methylation in the promoter region and high copy number amplification of ADAR were responsible for high levels of ADAR mRNA expression. ADAR coexpression genes were mainly involved in immunoregulation, especially T-lymphocyte activation. Hub genes, including CD2, CD274, and FASLG, were also significantly upregulated in the ADAR-high group compared to the control group. Besides, M1 macrophages were enriched in the ADAR-high group compared to the control group. This study demonstrated that ADAR, a new essential gene, was involved in the immune regulator and was a novel immune treatment target in CRC.

Identification and analysis of methylation signature genes and association with immune infiltration in pediatric acute myeloid leukemia.

BACKGROUND: Acute myeloid leukemia (AML) is a common leukemia with low cure rate and poor prognosis among pediatric patients. The regulation of AML immune microenvironment and methylation remains to be explored. Pediatric and adult AML patients differ significantly in epigenetic factors, and the efficiency of treatment modalities varies between the two groups of patients. METHODS: We collected mRNA, miRNA and DNA methylation data from pediatric AML patients across multiple databases. Differentially expression genes were identified, and a gene-miRNA regulatory network was constructed. Prognostic risk models were established by integrating LASSO and Cox regression, and a nomogram was generated. Based on this model, we investigated tumor-infiltrating immune cells and cell communication, analyzing the biological functions and pathways associated with prognostic factors. Furthermore, the relationships between all prognostic factors and gene modules were explored, and the impact of these factors on treatment modalities was determined. RESULTS: We developed an efficient prognostic risk model and identified HOXA9, SORT1, SH3BP5, mir-224 and mir-335 as biomarkers. We validated these findings in an external dataset and observed a correlation between age and risk in pediatric patients. AML samples with lower risk scores have a better prognosis and higher expression of immune-upregulated biomarkers, and have lower immune scores. Furthermore, we detected discrepancies in immune cell infiltration and interactions between high- and low-risk group samples, which affected the efficacy of immunotherapy. We evaluated all prognostic factors and predicted the effect of immunotherapy and medicine. CONCLUSION: This study comprehensively investigated the role of methylation signature genes in pediatric AML at the level of genomes and transcriptomes. The research aims to enhance the risk stratification, prognosis evaluation and assessment of treatment effectiveness of AML patients. This study also highlight the uniqueness of pediatric AML and foster the development of new immunotherapy and targeted therapy strategies.

α2,6-Sialylation promotes hepatocellular carcinoma cells migration and invasion via enhancement of nSmase2-mediated exosomal miRNA sorting.

Exosomes have a critical role in the intercellular communication and metastatic progression of hepatocellular carcinoma (HCC). Recently, our group showed that α2, 6-sialylation played an important role in the proliferation- and migration-promoting effects of cancer-derived exosomes. However, the molecular basis remains elusive. In this study, the mechanism of α2, 6-sialylation-mediated specific microRNAs (miRNA) sorting into exosomes was illustrated. We performed miRNA profiling analysis to compare exosomes from HCC cell lines that differ only in α2, 6-sialylation status. A total of 388 differentially distributed miRNAs were identified in wild-type and ß-galactoside α2, 6-sialyltransferase I (ST6Gal-I) knockdown MHCC-97H cells-derived exosomes. Neutral sphingomyelinase-2 (nSmase2), an important regulator mediating the sorting of exosomal miRNAs, was found to be a target of ST6Gal-I. The reduction of α2, 6-sialylation could impair the activity of nSmase2, as well as the nSmase2-dependent exosomal miRNAs sorting. This α2,6-sialylation-dependent sorting exerted an augmentation of motility on recipient HCC cells. Our data further demonstrated that α2,6-sialylation-mediated sorting of exosomal miR-100-5p promoted the migration and invasion of recipient HepG2 cells via the PI3K/AKT signaling pathway. The cellular metastasis-related gene CLDN11 was confirmed as a direct target of exosomal miR-100-5p, which elevated the mobility of recipient HCC cells. In conclusion, our results showed that α2,6-sialylation modulates nSmase2-dependent exosomal miRNAs sorting and promotes HCC progression.

Male Breast Cancer: An Updated Review of Epidemiology, Clinicopathology, and Treatment.

Male breast cancer (MaBC) is a rare clinical entity, which makes up approximately 1% of all breast cancers. However, the incidence of MaBC has been steadily increasing over the past few decades. The risk factors for MaBC include age, black race, family history of breast cancer, genetic mutations, liver cirrhosis, and testicular abnormalities. The majority of patients with MaBC present with painless lumps, and about half of the patients have at least one lymph node involved at the time of diagnosis. The treatment of MaBC models that of female breast cancer (FeBC), but this is mainly due to lack of prospective studies for MaBC patients. The treatment modality includes surgery, adjuvant radiation, endocrine therapy, and chemotherapy. However, there are some distinct features of MaBC, both clinically and molecularly, that may warrant a different clinical approach. Ongoing multinational effort is required, to conduct clinical trials for MaBC, or the inclusion of MaBC patients in FeBC trials, to help clinicians improve care for MaBC patients.

Propagation Characteristics of Circular Airy Vortex Beams in a Uniaxial Crystal along the Optical Axis.

Circular airy vortex beams (CAVBs) have attracted much attention due to their "abruptly autofocusing" effect, phase singularity, and their potential applications in optical micromanipulation, communication, etc. In this paper, we numerically investigated the propagation properties of circular airy beams (CABs) imposed with different optical vortices (OVs) along the optical axis of a uniaxial crystal for the first time. Like other common beams, a left-hand circular polarized (LHCP) CAVB, propagating along the optical axis in a uniaxial crystal, can excite a right-hand circular polarized (RHCP) component superimposed with an on-axis vortex of topological charge (TC) number of 2. When the incident beam is an LHCP CAB imposed with an on-axis vortex of TC number of l = 1, both of the two components have an axisymmetric intensity distribution during propagation and form hollow beams near the focal plane because of the phase singularity. The phase pattern shows that the LHCP component carries an on-axis vortex of TC number of l = 1, while the RHCP component carries an on-axis vortex of TC number of l = 3. With a larger TC number (l = 3), the RHCP component has a larger hollow region in the focal plane compared to the LHCP component. We also studied cases of CABs imposed with one and two off-axis OVs. The off-axis OV makes the CAVB's profile remain asymmetric throughout the propagation. As the propagation distance increases, the off-axis OVs move near the center of the beam and overlap, resulting in a special intensity and phase distribution near the focal plane.

Long-term outcomes and clinical safety of expanded indication early gastric cancer treated with endoscopic submucosal dissection versus surgical resection: a meta-analysis.

BACKGROUND AND AIMS: Endoscopic submucosal dissection (ESD) remains an investigational issue for early gastric cancer (EGC) with expanded indications owing to the risk of lymph node metastasis. In this study, we aimed to evaluate the clinical outcomes and safety of ESD versus surgical resection (SR) for EGC with expanded indications. METHODS: The systematic review selected studies from PubMed, Embase, Cochrane and Web of Science databases from 2010 to 2020, and compared survival and clinical safety data of ESD with those of surgical resection for EGC with expanded indications. The fixed-effects or random-effects model was used to calculate the differences between the two groups. To assess the validity of the eligible studies, risk of bias was measured using the Newcastle-Ottawa Quality Assessment Scale. RESULTS: Nine retrospective studies were used to calculate the differences in survival and clinical safety data between the two groups for EGC with expanded indications. Differences were not significant between the groups in terms of age, sex, tumour size, tumour histology or lesion morphology. Regarding tumour site, tumours located in the L area (the lower third of the stomach) were more likely to be found in the ESD group. With regard to metachronous and synchronous carcinomas, there was a significant difference favouring SR treatment (metachronous: OR=0.12, 95% CI=0.05 to 0.25, p<0.00001; synchronous: OR=0.11, 95% CI=0.02 to 0.46, p=0.003). Adverse event data were identified in six studies showing a significant difference favouring ESD treatment (ESD vs SR, OR=0.49, 95% CI=0.34 to 0.72. p=0.002). Additionally, six studies evaluating 5-year overall survival showed no significant differences between the two groups (HR=1.22, 95% CI=0.66 to 2.25, p=0.53). With regard to 5-year disease-free survival, patients with expanded indication EGC undergoing SR showed better survival (ESD vs SR, HR=3.29, 95% CI=1.60 to 6.76, p=0.001). CONCLUSION: ESD provided favourable results for patients with EGC with expanded indications regarding clinical outcomes and safety in retrospective studies. Further, to detect synchronous or metachronous lesions, endoscopic surveillance should be performed following ESD. However, the included studies were observational, some did not have adequate adjustment for confounding factors and their results lacked generalisability due to their origin. Thus, further related randomised controlled trials are urgently encouraged. PROSPERO REGISTRATION NUMBER: CRD42021251068.

Screening Protein Prognostic Biomarkers for Stomach Adenocarcinoma Based on The Cancer Proteome Atlas.

The objective was to construct a prognostic risk model of stomach adenocarcinoma (STAD) based on The Cancer Proteome Atlas (TCPA) to search for prognostic biomarkers. Protein data and clinical data on STAD were downloaded from the TCGA database, and differential expressions of proteins between carcinoma and para-carcinoma tissues were screened using the R package. The STAD data were randomly divided into a training set and a testing set in a 1:1 ratio. Subsequently, a linear prognostic risk model of proteins was constructed using Cox regression analysis based on training set data. Based on the scores of the prognostic model, sampled patients were categorized into two groups: a high-risk group and a low-risk group. Using the testing set and the full sample, ROC curves and K-M survival analysis were conducted to measure the predictive power of the prognostic model. The target genes of proteins in the prognostic model were predicted and their biological functions were analyzed. A total of 34 differentially expressed proteins were screened (19 up-regulated, 15 down-regulated). Based on 176 cases in the training set, a prognostic model consisting of three proteins (COLLAGEN VI, CD20, TIGAR) was constructed, with moderate prediction accuracy (AUC=0.719). As shown by the Kaplan-Meier and survival status charts, the overall survival rate of the low-risk group was better than that of the high-risk group. Moreover, a total of 48 target proteins were identified to have predictive power, and the level of proteins in hsa05200 (Pathways in cancer) was the highest. According to the results of the Univariate and multivariate COX analysis, tri-protein was identified as an independent prognostic factor. Therefore, the tri-protein prognostic risk model can be used to predict the likelihood of STAD and guide clinical treatment.

A Novel Approach for Measurement of Free-Form Optical Elements with Digital Holographic Microscopy.

Free-form optical elements face significant challenges in high-precision measurement due to their high complexity and non-rotational symmetry. Digital holographic microscopy (DHM), as one of the methods for the measurement of free-form optical elements, has promising applications due to its ultra-high precision and non-destructive and fast characteristics. Therefore, we have designed a novel measurement method that combines transmission DHM and reflection DHM to obtain thickness information and surface information of elements to deduce the 3D structure. With this method, we completed the measurement of a free-form optical element. The DHM system we built has recorded holograms under 4× and 20× objectives and successfully recovered the 3D surface shape of the element. The measurements are consistent with the designed and manufactured parameters, demonstrating the unique advantages of DHM for measuring special types of optical elements.

Novel Necroptosis-Related Gene Signature for Predicting Early Diagnosis and Prognosis and Immunotherapy of Gastric Cancer.

Necroptosis is a kind of programmed necrosis, which is different from apoptosis and pyroptosis. Its molecular mechanism has been described in inflammatory diseases. Gastric cancer (GC) is one of the most common malignancies worldwide with the third highest mortality. However, the role of necroptosis in the occurrence and progression of GC remains largely unexplored. Therefore, we investigated necroptosis-related genes (NRGs) by analyzing public transcriptomic data from GC samples. Our results indicate that 83 of 740 NRGs are dysregulated in GC tissues. Next, we identified necroptosis-associated early diagnosis and prognostic gene signatures for GC using machine learning. 2-NRGs (CCT6A and FAP) and 4-NRGs (ZFP36, TP53I3, FAP, and CCT6A), respectively, can effectively assess the risk of early GC (AUC = 0.943) and the prognosis of GC patients (AUC = 0.866). Through in-depth analysis, we were pleasantly surprised to find that there was a significant correlation between the 4-NRGs and GC immunotherapy effect and immune checkpoint inhibitors (ICIs), which could be used for the evaluation of immunosuppressants. Finally, we identified the core gene FAP, and established the relationship between FAP and ICIs in GC. These findings could provide a new target for immunotherapy for GC and a more effective treatment scheme for GC patients.

D2 lymphadenectomy with complete mesogastrium excision vs. conventional D2 gastrectomy for advanced gastric cancer.

BACKGROUND: The complete mesogastrium excision (CME) based on D2 radical gastrectomy is believed to significantly reduce the local-regional recurrence compared with D2 radical gastrectomy in advanced gastric cancer, and it is widely used in China. This study aimed to explore whether D2 + CME is superior to D2 on surgical outcomes during gastrectomy from Chinese data. METHODS: Feasible studies comparing the D2 + CME (D2 + CME group) and D2 (D2 group) published up to March 2020 are searched from electronic databases. The data showing surgical and complication outcomes are extracted to be pooled and analyzed. RESULTS: Fourteen records including 1352 patients were included. The D2 + CME group had a shorter mean operative time (weighted mean difference [WMD] = -16.72 min, 95% confidence interval [CI]: -26.56 to -6.87 min, P   <  0.001), lower mean blood loss (WMD = -39.08 mL, 95% CI: -49.94 to -28.21 mL, P  < 0.001), higher mean number of retrieved lymph nodes (WMD = 2.13, 95% CI: 0.58-3.67, P  = 0.007), shorter time to first flatus (WMD = -0.31 d, 95% CI: -0.53 to - 0.10 d, P  = 0.005), and postoperative hospital days (WMD = -1.09, 95% CI: -1.92 to -0.25, P  = 0.010) than the D2 group. Subgroup analysis suggested that the advantages from the D2 + CME group were obvious in traditional open radical gastrectomy, proximal gastrectomy, and distal gastrectomy compared with D2 group. The evaluations of post-operative complications showed that the patients who underwent D2 + CME had a lower incidence of post-operative complications than the patients who underwent D2 surgery alone (relative risk [RR] = 0.65, 95% CI: 0.45-0.87, P  = 0.003). The D2 radical gastrectomy plus CME improved 3-year overall survival (OS) (RR = 1.16, 95% CI: 1.02-1.32, P  = 0.020) and lowered the local recurrence rate (RR = 0.51, 95% CI: 0.28-0.94, P  = 0.030). The patients undergoing laparoscopic surgery or total gastrectomy had more significant advantages compared between D2 + CME and D2 groups in 3-year OS. CONCLUSION: The data from China show that D2 radical gastrectomy plus CME are reliable procedures and safety compared to D2 radical gastrectomy with faster recovery, lower risk, and better prognosis.

A genetically encoded fluorescent biosensor for monitoring ATP in living cells with heterobifunctional aptamers.

Visualizing the dynamics of ATP in living cells is key to understanding cellular energy metabolism and related diseases. However, the live-cell applications of current methods are still limited due to challenges in biological compatibility and sensitivity to pH. Herein, a novel label-free fluorescent " turn-on " biosensor for monitoring ATP in living bacterias and mammalian cells was developed. This biosensor (Broc-ATP) employed heterobifunctional aptamers to detect ATP with high sensitivity in vitro. In our system, a very useful tandem method was established by combining four Broc-ATPs with 3 × F30 three-way junction scaffold to construct an intracellular biosensor that achieves sufficient fluorescence to respond to intracellular ATP. This intracellular biosensor can be used for sensitive and specific dynamic imaging of ATP in mammalian cells. Hence, this genetically encoded biosensor provides a robust and efficient tool for the detection of intracellular ATP dynamics and 3 × F30 tandem method expands the application of heterobifunctional aptamers in mammalian cells.

Screening of miRNAs as Prognostic Biomarkers for Colon Adenocarcinoma and Biological Function Analysis of Their Target Genes.

We constructed a prognostic risk model for colon adenocarcinoma (COAD) using microRNAs (miRNAs) as biomarkers. Clinical data of patients with COADs and miRNA-seq data were from TCGA, and the differential expression of miRNAs (carcinoma vs. para-carcinoma tissues) was assessed using R software. COAD data were randomly divided into Training and Testing Sets. A linear prognostic risk model was constructed using Cox regression analysis based on the Training Set. Patients were classified as high-risk or low-risk according to the score of the prognostic model. Survival analysis and receiver operating characteristic (ROC) curves were used to evaluate model performance. The gene targets in the prognostic model were identified and their biological functions were analyzed. Analysis of COAD and normal cell lines using qPCR was used to verify the model. There were 134 up-regulated and 140 down-regulated miRNAs. We used the Training Set to develop a prognostic model based on the expression of seven miRNAs. ROC analysis indicated this model had acceptable prediction accuracy (area under the curve=0.784). Kaplan-Meier survival analysis showed that overall survival was worse in the high-risk group. Cox regression analysis showed that the 7-miRNA Risk Score was an independent prognostic factor. The 2,863 predicted target genes were mainly enriched in the MAPK, PI3K-AKT, proteoglycans in cancer, and mTOR signaling pathways. For unknown reasons, expression of these miRNAs in cancerous and normal cells differed somewhat from model predictions. Regardless, the 7-miRNA Risk Score can be used to predict COAD prognosis and may help to guide clinical treatment.