The Benefit of the Optimized Formula of Yinxieling in Psoriasis Vulgaris via Regulation on Autophagy Based on microRNA Expression Profile and Network Pharmacology Analysis.

Background: Psoriasis is a widespread chronic, immune-mediated skin disease with frequent recurrences, and is extremely harmful to the physical and mental health of patients, causing enormous suffering and exerting considerable economic burdens on the health care system as a whole. In more than a decade of clinical use, the optimized formula of Yinxieling (PSORI-CM01) has consistently demonstrated its effectiveness for treating psoriasis. However, its underlying mechanism remains largely unexplored. Methods: The network pharmacology analysis was conducted to predict the mechanism and protective effect of PSORI-CM01 in treating psoriasis. Subsequently, we collected blood samples from 21 patients with psoriasis as part of a randomized, double-blind, and double-dummy clinical trial for microRNA expression profiling. Finally, it was experimentally confirmed that PSORI-CM01 improved psoriasis by regulating miR-20a-3p and miR-3184-3p expression. Results: As a result of the network pharmacology analysis, PSORI-CM01 improved psoriasis through the regulation of autophagy, cellular apoptosis, cellular proliferation, and anti-inflammatory processes. In the target-miRNA regulatory network, these key targets were mainly associated with the regulation of hsa-miR-20a-3p, hsa-miR-155-5p, has-miR-3184-3p, hsa-miR-328-3p and hsa-miR-124-3p. Based on the microRNA expression profiling results, the PSORI-CM01 treatment group exhibited five up-regulated genes and 16 down-regulated genes compared with the healthy control group. In particular, miR-20a-3p and miR-3184-3p were the primary differentially expressed microRNAs, and they were significantly enriched in the signaling pathways involving autophagy, apoptosis, proliferation, and anti-inflammation. Further experiments confirmed that PSORI-CM01 effectively regulates miR-20a-3p and miR-3184-3p, resulting in increased autophagy. Conclusion: We demonstrated by combining network pharmacology and clinical studies of miRNA expression profiles in PBMCs that PSORI-CM01 effectively modulated miR-20a-3p and miR-3184-3p, leading to an increase in autophagy and a decrease in keratinocyte proliferation.

Pathomics and single-cell analysis of papillary thyroid carcinoma reveal the pro-metastatic influence of cancer-associated fibroblasts.

BACKGROUND: Papillary thyroid carcinoma (PTC) is globally prevalent and associated with an increased risk of lymph node metastasis (LNM). The role of cancer-associated fibroblasts (CAFs) in PTC remains unclear. METHODS: We collected postoperative pathological hematoxylin-eosin (HE) slides from 984 included patients with PTC to analyze the density of CAF infiltration at the invasive front of the tumor using QuPath software. The relationship between CAF density and LNM was assessed. Single-cell RNA sequencing (scRNA-seq) data from GSE193581 and GSE184362 datasets were integrated to analyze CAF infiltration in PTC. A comprehensive suite of in vitro experiments, encompassing EdU labeling, wound scratch assays, Transwell assays, and flow cytometry, were conducted to elucidate the regulatory role of CD36+CAF in two PTC cell lines, TPC1 and K1. RESULTS: A significant correlation was observed between high fibrosis density at the invasive front of the tumor and LNM. Analysis of scRNA-seq data revealed metastasis-associated myoCAFs with robust intercellular interactions. A diagnostic model based on metastasis-associated myoCAF genes was established and refined through deep learning methods. CD36 positive expression in CAFs can significantly promote the proliferation, migration, and invasion abilities of PTC cells, while inhibiting the apoptosis of PTC cells. CONCLUSION: This study addresses the significant issue of LNM risk in PTC. Analysis of postoperative HE pathological slides from a substantial patient cohort reveals a notable association between high fibrosis density at the invasive front of the tumor and LNM. Integration of scRNA-seq data comprehensively analyzes CAF infiltration in PTC, identifying metastasis-associated myoCAFs with strong intercellular interactions. In vitro experimental results indicate that CD36 positive expression in CAFs plays a promoting role in the progression of PTC. Overall, these findings provide crucial insights into the function of CAF subset in PTC metastasis.

The Prognostic Value and Potential Immune Mechanisms of lncRNAs Related to Immunogenic Cell Death in Papillary Thyroid Carcinoma.

Background: Long non-coding RNAs (lncRNAs) associated with immunogenic cell death (ICD) play a pivotal role in tumorigenesis and offer prognostic insights for papillary thyroid carcinoma (PTC) patients. This study delves into the impact of ICD-related lncRNAs on the prognosis of PTC. Methods: PTC samples were accessed from The Cancer Genome Atlas-Thyroid carcinoma database (TCGA-THCA) and consensus cluster analysis to elucidate the influence of ICD-related lncRNA expression. To gauge the prognostic significance of these lncRNAs, we developed a prognostic model. Additionally, we conducted GO and KEGG enrichment analyses, assessed immune cell infiltration (ICI) using CIBERSORT and ssGSEA, examined immune checkpoint expression, tumor mutation burden (TMB), tumor microenvironment (TME), T-cell dysfunction and exclusion (TIDE), TCIA, and drug sensitivity across various groups. A comprehensive suite of in vitro experiments, encompassing EdU labeling, wound scratch assays, Transwell assays, and flow cytometry, were conducted to elucidate the regulatory role of LINC00924 in two PTC cell lines, BCPAP and TPC1, transfected with LINC00924 overexpression plasmids. Results: Two distinct clusters demonstrated varying TME, BRAF, NRAS, and ICI characteristics, suggesting potential immune mechanisms in PTC. Our prognostic model identified seven lncRNAs: SRRM2-AS1, AC008556.1, BHLHE40-AS1, EGOT, AL39066.1, LINC00924, and PICART1. The expression of ICD-related lncRNAs correlated with progression-free interval (PFI) in PTC patients. Overexpression of LINC00924 significantly reduced cell proliferation, migration, and invasion, while augmenting apoptosis in PTC cells. Conclusion: Our findings highlight the potential of ICD-related lncRNAs as prognostic biomarkers for PFI in PTC. In vitro experiments suggest a protective role of LINC00924 in PTC progression.

The Influence of Electroluminescent Inhomogeneous Phase Addition on Enhancing MgB2 Superconducting Performance and Magnetic Flux Pinning.

As a highly regarded superconducting material with a concise layered structure, MgB2 has attracted significant scientific attention and holds vast potential for applications. However, its limited current-carrying capacity under high magnetic fields has greatly hindered its practical use. To address this issue, we have enhanced the superconducting performance of MgB2 by incorporating inhomogeneous phase nanostructures of p-n junctions with electroluminescent properties. Through temperature-dependent measurements of magnetization, electronic specific heat, and Hall coefficient under various magnetic fields, we have confirmed the crucial role of inhomogeneous phase electroluminescent nanostructures in improving the properties of MgB2. Experimental results demonstrate that the introduction of electroluminescent inhomogeneous phases effectively enhances the superconducting performance of MgB2. Moreover, by controlling the size of the electroluminescent inhomogeneous phases and optimizing grain connectivity, density, and microstructural uniformity, we can further improve the critical temperature (TC) and flux-pinning capability of MgB2 superconducting materials. Comprehensive studies on the physical properties of MgB2 superconducting structures added with p-n junction electroluminescent inhomogeneous phases also confirm the general effectiveness of electroluminescent inhomogeneous phases in enhancing the performance of superconducting materials.

DNMT3L inhibits hepatocellular carcinoma progression through DNA methylation of CDO1: insights from big data to basic research.

BACKGROUND: DNMT3L is a crucial DNA methylation regulatory factor, yet its function and mechanism in hepatocellular carcinoma (HCC) remain poorly understood. Bioinformatics-based big data analysis has increasingly gained significance in cancer research. Therefore, this study aims to elucidate the role of DNMT3L in HCC by integrating big data analysis with experimental validation. METHODS: Dozens of HCC datasets were collected to analyze the expression of DNMT3L and its relationship with prognostic indicators, and were used for molecular regulatory relationship evaluation. The effects of DNMT3L on the malignant phenotypes of hepatoma cells were confirmed in vitro and in vivo. The regulatory mechanisms of DNMT3L were explored through MSP, western blot, and dual-luciferase assays. RESULTS: DNMT3L was found to be downregulated in HCC tissues and associated with better prognosis. Overexpression of DNMT3L inhibits cell proliferation and metastasis. Additionally, CDO1 was identified as a target gene of DNMT3L and also exhibits anti-cancer effects. DNMT3L upregulates CDO1 expression by competitively inhibiting DNMT3A-mediated methylation of CDO1 promoter. CONCLUSIONS: Our study revealed the role and epi-transcriptomic regulatory mechanism of DNMT3L in HCC, and underscored the essential role and applicability of big data analysis in elucidating complex biological processes.

Diagnosis, Treatment, and Associated Factors Among Patients with HCV Infection - Jiangsu Province, China, 2004-2020.

What is already known on this topic?: The global efforts to address the hepatitis C virus (HCV) are progressing, but there are still significant gaps in the diagnosis and treatment of HCV, leading to an increasing number of deaths related to HCV. What is added by this report?: An extensive investigation was conducted to assess HCV RNA diagnosis, treatment uptake, and associated factors among individuals infected with HCV within Jiangsu Province. The study encompassed a large geographical area and utilized a substantial sample size. What are the implications for public health practice?: Implementing focused interventions to improve the timely diagnosis of HCV RNA and increase the uptake of HCV treatment could effectively reduce the future burden of HCV-related health problems, deaths, and healthcare expenses. This is essential for achieving the global target of eliminating hepatitis C.

Upregulation of SLAMF8 aggravates ischemia/reperfusion-induced ferroptosis and injury in cardiomyocyte.

BACKGROUND: Myocardial infarction (MI) is a cardiovascular diseases, that seriously threatens human life. Signaling lymphocytic activation molecule family member 8 (SLAMF8) has been discovered to regulate the development and function of many immune cells. However, there are limited reports on SLAMF8 in the field of cardiopathy, and its regulatory role also remains unclear. METHODS: The mRNA and protein expressions of genes were examined through RT-qPCR and western blot. The infarct size in heart was assessed through TTC staining. The pathological section of heart tissue was evaluated through HE staining. The iron, Fe2+, MDA and SOD levels were assessed through the corresponding commercial kits. The ROS level was detected through Immunofluorescence (IF) staining. The cell viability and cell apoptosis were assessed through MTT assay and flow cytometry. RESULTS: Through GEO (GSE84796) database, SLAMF8 exhibited higher expression in heart failure patients. Furthermore, the ischemia/reperfusion SD rat (ischemia/reperfusion, I/R treatment) and H9C2 cell (hypoxia/reoxygenation, H/R treatment) models were set up. The mRNA and protein levels of SLAMF8 were upregulated in ischemia/reperfusion SD rat and H9C2 cell models. In addition, SLAMF8 inhibition alleviated ischemia/reperfusion-induced myocardial injury in SD rats. Moreover, SLAMF8 suppression inhibited ischemia/reperfusion-induced ferroptosis and oxidative stress. Further experiments were performed in H/R stimulated H9C2 cells, and the results showed that SLAMF8 knockdown alleviated H/R-induced cardiomyocyte death, ferroptosis and oxidative stress in H/R-induced cardiomyocyte. Lastly, SLAMF8 activated the TLR4/NOX4 pathway in I/R treated-SD rats or H/R treated-H9C2 cells. CONCLUSION: SLAMF8 aggravated ischemia/reperfusion-induced ferroptosis and injury in cardiomyocyte. This discovery may provide a useful bio-target for MI treatment.

Green-Light GaN p-n Junction Luminescent Particles Enhance the Superconducting Properties of B(P)SCCO Smart Meta-Superconductors (SMSCs).

Superconducting materials exhibit unique physical properties and have great scientific value and vast industrial application prospects. However, due to limitations, such as the critical temperature (TC) and critical current density (JC), the large-scale application of superconducting materials remains challenging. Chemical doping has been a commonly used method to enhance the superconductivity of B(P)SCCO. However, satisfactory enhancement results have been difficult to achieve. In this study, we introduce green-light GaN p-n junction particles as inhomogeneous phases into B(P)SCCO polycrystalline particles to form a smart meta-superconductor (SMSC) structure. Based on the electroluminescence properties of the p-n junction, the Cooper pairs were stimulated and strengthened to enhance the superconductivity of B(P)SCCO. The experimental results demonstrate that the introduction of inhomogeneous phases can indeed enhance the critical temperature TC, critical current density JC, and complete diamagnetism (Meissner effect) of B(P)SCCO superconductors. Moreover, when the particle size of the raw material of B(P)SCCO is reduced from 30 to 5 µm, the grain size of the sintered samples also decreases, and the optimal doping concentration of the inhomogeneous phases increases from 0.15 wt.% to 0.2 wt.%, further improving the superconductivity.

Reliability, Validity, and Identification Ability of a Commercialized Waist-Attached Inertial Measurement Unit (IMU) Sensor-Based System in Fall Risk Assessment of Older People.

Falls are a prevalent cause of injury among older people. While some wearable inertial measurement unit (IMU) sensor-based systems have been widely investigated for fall risk assessment, their reliability, validity, and identification ability in community-dwelling older people remain unclear. Therefore, this study evaluated the performance of a commercially available IMU sensor-based fall risk assessment system among 20 community-dwelling older recurrent fallers (with a history of ≥2 falls in the past 12 months) and 20 community-dwelling older non-fallers (no history of falls in the past 12 months), together with applying the clinical scale of the Mini-Balance Evaluation Systems Test (Mini-BESTest). The results show that the IMU sensor-based system exhibited a significant moderate to excellent test-retest reliability (ICC = 0.838, p < 0.001), an acceptable level of internal consistency reliability (Spearman's rho = 0.471, p = 0.002), an acceptable convergent validity (Cronbach's α = 0.712), and an area under the curve (AUC) value of 0.590 for the IMU sensor-based receiver-operating characteristic (ROC) curve. The findings suggest that while the evaluated IMU sensor-based system exhibited good reliability and acceptable validity, it might not be able to fully identify the recurrent fallers and non-fallers in a community-dwelling older population. Further system optimization is still needed.

Remodeling the tumor immune microenvironment via siRNA therapy for precision cancer treatment.

How to effectively transform the pro-oncogenic tumor microenvironments (TME) surrounding a tumor into an anti-tumoral never fails to attract people to study. Small interfering RNA (siRNA) is considered one of the most noteworthy research directions that can regulate gene expression following a process known as RNA interference (RNAi). The research about siRNA delivery targeting tumor cells and TME has been on the rise in recent years. Using siRNA drugs to silence critical proteins in TME was one of the most efficient solutions. However, the manufacture of a siRNA delivery system faces three major obstacles, i.e., appropriate cargo protection, accurately targeted delivery, and site-specific cargo release. In the following review, we summarized the pharmacological actions of siRNA drugs in remolding TME. In addition, the delivery strategies of siRNA drugs and combination therapy with siRNA drugs to remodel TME are thoroughly discussed. In the meanwhile, the most recent advancements in the development of all clinically investigated and commercialized siRNA delivery technologies are also presented. Ultimately, we propose that nanoparticle drug delivery siRNA may be the future research focus of oncogene therapy. This summary offers a thorough analysis and roadmap for general readers working in the field.

Comparative transcriptome analysis reveals candidate genes related to the sex differentiation of Schisandra chinensis.

Schisandra chinensis is a monoecious plant with unisex flowers. The fruit of S. chinensis is of high medical with economic value. The yield of S. chinensis fruit is related to the ratio of its female and male flowers. However, there is little research on its floral development and sex differentiation. To elucidate the possible mechanism for the sex differentiation of S. chinensis, we collected 18 samples of female and male flowers from three developmental stages and performed a comparative RNA-seq analysis aimed at identifying differentially expressed genes (DEGs) that may be related to sex differentiation. The results showed 936, 7179, and 6890 differentially expressed genes between female and male flowers at three developmental stages, respectively, and 466 candidate genes may play roles in sex differentiation. KEGG analysis showed genes involved in the flavonoid biosynthesis pathway and DNA replication pathway were essential for the development of female flowers. 51 MADS-box genes and 10 YABBY genes were identified in S. chinensis. The DEGs analysis indicated that MADS-box and YABBY genes were strongly related to the sex determination of S. chinensis. RT-qPCR confirmed the RNA-seq results of 20 differentially expressed genes, including three male-biased genes and 17 female-biased genes. A possible regulatory model of sex differentiation in S. chinensis was proposed according to our results. This study helps reveal the sex-differentiation mechanism of S. chinensis and lays the foundation for regulating the male-female ratio of S. chinensis in the future.

Platelet-mimetic nano-sensor for combating postoperative recurrence and wound infection of triple-negative breast cancer.

Tumor recurrence mainly triggered by tumor residual cells significantly contributes to mortality following breast tumor resection, and meanwhile post-surgical bacterial wound infections may accelerate tumor recurrence due to a series of infection-related complications. In this study, a nano-sensor system, Van-ICG@PLT, is constructed by a membrane camouflage and small molecule drug self-assembly strategy. This nano-sensor harnesses the innate tropism of platelets (PLT) to deliver vancomycin (Van) and indocyanine green (ICG) to surgical incisions, effectively eliminating both residual tumor cells and bacterial infections. Our findings demonstrate that Van-ICG@PLT preferentially accumulates at surgical wound. Under near-infrared (NIR) laser irradiation, Van-ICG@PLT exhibits significant cytotoxicity against 4T1 cells. Additionally, it is found to significantly promote ROS production thus inhibiting Staphylococcus aureus (S. aureus) growth, underscoring the synergistic benefits of phototherapy in combination with antibiotic treatment. In the 4T1 post-surgery recurrence mice model, Van-ICG@PLT is shown to efficiently ablate tumors in tumor-bearing mice (tumor inhibition rate of about 83%), and it demonstrates an excellent anti-infective effect in mice abscess models. Taken together, Van-ICG@PLT represents a promising paradigm in post-surgical adjuvant therapy (PAT). Its dual benefit in inhibiting cancer growth and promoting antibacterial activity makes Van-ICG@PLT a valuable addition to the existing arsenal of therapeutic options available for breast cancer patients.

Non-flammable solvent-free liquid polymer electrolyte for lithium metal batteries.

As a replacement for highly flammable and volatile organic liquid electrolyte, solid polymer electrolyte shows attractive practical prospect in high-energy lithium metal batteries. However, unsatisfied interface performance and ionic conductivities are two critical challenges. A common strategy involves introducing organic solvents or plasticizers, but this violates the original intention of security design. Here, an electrolyte concept called liquid polymer electrolyte without any small molecular solvents is proposed for safe and high-performance batteries, based on the design of a room-temperature liquid-state brush-like polymer as the sole solvent of lithium salts. This liquid polymer electrolyte is non-flammable and exhibits high ionic conductivity (1.09 [Formula: see text] 10-4 S cm-1 at 25 °C), significant lithium dendrite suppression, and stable long-term cycling over a wide operating temperature range ( ≥ 1000 cycles at 60 °C and 90 °C). Moreover, the pouch cell can resist thermal abuse, vacuum environment, and mechanical abuse. This electrolyte and design strategy are expected to provide enlightening ideas for the development of safe and high-performance polymer electrolytes.

Blinatumomab as salvage therapy in patients with relapsed/refractory B-ALL who have failed/progressed after anti-CD19-CAR T therapy.

BACKGROUND: Anti-CD19 chimeric antigen receptors (CARs) T-cell therapy has been shown to have excellent efficacy in patients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (ALL). But many patients are refractory to anti-CD19-CAR T-cell therapy or relapse again. METHODS: Five patients with R/R B-ALL did not respond to anti-CD19-CAR T-cell therapy or had a disease progression again after CAR-T cell therapy. They received a salvage therapy of Blinatumomab. The clinical response, CD19 expression on ALL cells, the proportion of CD3+ T cells, level of cytokine levels of interleukin-6 (IL-6), hematological toxicity, grade of cytokine release syndrome (CRS), and immune effector cell-associated neurotoxic syndrome (ICANS) were observed in salvage therapy of Blinatumomab. RESULTS: Four patients obtained CR/CRi, even in patients without high expression of CD19 in B-ALL cells, while the other patient received NR after Blinatumomab therapy. The CD19 expression on ALL cells, the proportion of CD3+ T cells, and CD3+CD8+ T cells were deficient in Pt 5, who obtained PR in Blinatumomab therapy. One patient (Pt 3) was diagnosed with grade 0 hematological toxicity. The other four patients were diagnosed with grades 2-3 of hematological toxicity. The CRS was grade 0/one patient, grade 1/three, and grade 2/one. The ICANS was grade 0/four patients, grade 1/one. Rhizopus microsporus pneumonia and cryptococcal encephalopathy in two patients were controlled during Blinatumomab therapy. CONCLUSIONS: Blinatumomab could be an effective and safe salvage therapy in patients with R/R B-ALL who failed/progressed after anti-CD19-CAR T therapy, even in R/R B-ALL patients without high expression of CD19 in B-ALL cells, patients with CNS leukemia or co-infection.Key messagesSome R/R B-ALL patients did not respond to anti-CD19 CAR T-cell therapy or had a disease progression again. Effective and safe salvage therapy for such patients remains to be explored.Blinatumomab could be an effective and safe salvage therapy in patients with R/R B-ALL who failed/progressed after anti-CD19-CAR T therapy, even in patients without high expression of CD19 in B-ALL cells.Blinatumomab could be an effective and safe salvage therapy in patients with R/R B-ALL who failed/progressed after anti-CD19-CAR T therapy, even in patients with CNS leukemia or co-infection.

Effectiveness and diurnal variations of vegetative environmental buffers (VEBs) for mitigating NH3 and PM emissions from poultry houses.

Air pollutants from poultry production, such as ammonia (NH3) and particulate matter (PM), have raised concerns due to their potential negative impacts on human health and the environment. Vegetative environmental buffers (VEBs), consisting of trees and/or grasses planted around poultry houses, have been investigated as a mitigation strategy for these emissions. Although previous research demonstrated that VEBs can reduce NH3 and PM emissions, these studies used a limited number of samplers and did not examine concentration profiles. Moreover, the differences between daytime and nighttime emissions have not been investigated. In this study, we characterized emission profiles from a commercial poultry house using an array with multiple sampling heights and explored the differences between daytime and nighttime NH3 and PM profiles. We conducted three sampling campaigns, each with ten sampling events (five daytime and five nighttime), at a VEB-equipped poultry production facility. NH3 and PM samples were collected downwind from the ventilation tunnel fans before, within, and after the VEB. Results showed that ground-level concentrations beyond the VEB decreased to 8.0% ± 2.7% for NH3, 13% ± 4% for TSP, 13% ± 4% for PM10, and 2.4% ± 2.8% for PM2.5 of the original concentrations from the exhaust tunnel fan, with greater reduction efficiency during daytime than nighttime. Furthermore, pollutant concentrations were positively intercorrelated. These findings will be valuable for developing more effective pollutant remediation strategies in poultry house emissions.

The effect of ginsenosides on liver injury in preclinical studies: a systematic review and meta-analysis.

Background: Liver injury is a severe liver lesion caused by various etiologies and is one of the main areas of medical research. Panax ginseng C.A. Meyer has traditionally been used as medicine to treat diseases and regulate body functions. Ginsenosides are the main active components of ginseng, and their effects on liver injury have been extensively reported. Methods: Preclinical studies meeting the inclusion criteria were retrieved from PubMed, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), and Wan Fang Data Knowledge Service Platforms. The Stata 17.0 was used to perform the meta-analysis, meta-regression, and subgroup analysis. Results: This meta-analysis included ginsenosides Rb1, Rg1, Rg3, and compound K (CK), in 43 articles. The overall results showed that multiple ginsenosides significantly reduced alanine aminotransferase (ALT) and aspartate aminotransferase (AST), affected oxidative stress-related indicators, such as superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), glutathione peroxidase (GSH-Px), and catalase (CAT), and reduced levels of inflammatory factor, such as factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6). Additionally, there was a large amount of heterogeneity in the meta-analysis results. Our predefined subgroup analysis shows that the animal species, the type of liver injury model, the duration of treatment, and the administration route may be the sources of some of the heterogeneity. Conclusion: In a word, ginsenosides have good efficacy against liver injury, and their potential mechanisms of action target antioxidant, anti-inflammatory and apoptotic-related pathways. However, the overall methodological quality of our current included studies was low, and more high-quality studies are needed to confirm their effects and mechanisms further.

Esophageal stenting with minimally-invasive surgical intervention for delayed spontaneous esophageal perforation.

Background: Spontaneous esophageal perforation is a challenging surgical emergency with significant morbidity and mortality, and timely primary repair carries good outcomes. However, direct repair for a delayed spontaneous esophageal perforation is not always feasible and is associated with high mortality. Esophageal stenting can provide therapeutic benefits in the management of esophageal perforations. In this study, we review our experience with placing esophageal stents in combination with minimally-invasive surgical drainage to treat delayed spontaneous esophageal perforations. Methods: We retrospectively analyzed patients with delayed spontaneous esophageal perforations between September 2018 and March 2021. All patients were treated using a hybrid approach, including esophageal stenting across the gastroesophageal junction (GEJ) to reduce continued contamination, gastric decompression with extraluminal sutures to prevent stent migration, early enteral nutrition, and aggressive minimally-invasive thoracoscopic debridement and drainage of infected material. Results: There were 5 patients with delayed spontaneous esophageal perforation treated with this hybrid approach. The mean duration between symptoms and diagnosis was 5 days, and the interval between symptoms and esophageal stent insertion was 7 days. The median time to oral nutrition and to esophageal stent removal was 43 and 66 days. There was no stent migration or hospital mortality. Three patients (60%) had postoperative complications. All patients were successfully resumed on oral nutrition with esophageal preservation. Conclusions: A hybrid approach combining endoscopic esophageal stent placement with extraluminal sutures to prevent stent migration, thoracoscopic decortication with chest tube drainage, gastric decompression, and jejunostomy tube placement for early nutrition was feasible and effective in the treatment of delayed spontaneous esophageal perforations. This technique offers a less invasive treatment approach for a challenging clinical problem which has traditionally carried a high rate of morbidity and mortality.

A single-cell transcriptome atlas profiles early organogenesis in human embryos.

The early window of human embryogenesis is largely a black box for developmental biologists. Here we probed the cellular diversity of 4-6 week human embryos when essentially all organs are just laid out. On the basis of over 180,000 single-cell transcriptomes, we generated a comprehensive atlas of 313 clusters in 18 developmental systems, which were annotated with a collection of ontology and markers from 157 publications. Together with spatial transcriptome on embryonic sections, we characterized the molecule and spatial architecture of previously unappreciated cell types. Combined with data from other vertebrates, the rich information shed light on spatial patterning of axes, systemic temporal regulation of developmental progression and potential human-specific regulation. Our study provides a compendium of early progenitor cells of human organs, which can serve as the root of lineage analysis in organogenesis.

Esophageal cancer-related gene 4 inhibits gastric cancer growth and metastasis by upregulating Krüppel-like factor 2 expression.

Background: There are a large number of people suffering from gastric cancer (GC) worldwide, so the study of biomarkers for GC is urgently needed. This study aimed to investigate the role of esophageal cancer-related gene 4 (ECRG4) in the growth, metastasis, and prognosis of GC and the possible underlying mechanism. Methods: The expression of ECRG4 was detected in GC tissues by quantitative polymerase chain reaction (PCR), Western blot, and immunohistochemistry. The relationships between ECRG4 expression and clinicopathological parameters of patients with GC were statistically analyzed, and Kaplan-Meier prognosis and survival curves of the patients were plotted. ECRG4 was overexpressed in the human gastric adenocarcinoma cell line (AGS) and human GC cell line 27 (HGC27), and the in vivo effects of ECRG4 overexpression on the growth, invasion, and metastasis of GC were analyzed and verified in nude mice. To identify the downstream transcription factors potentially regulated by ECRG4, ribonucleic acid (RNA) sequencing and differential gene expression analysis were performed on ECRG4-overexpressing cells. Quantitative PCR, Western blot, and immunohistochemistry were used to detect the expression of the downstream transcription factors targeted by ECRG4 in GC. Results: The ECRG4 mRNA and protein expression levels were low in GC tissues and were associated with a poor prognosis. Least absolute shrinkage and selection operator (LASSO) Cox regression and Kaplan-Meier survival analyses showed that patients with low ECRG4 expression had worse prognosis and survival. Overexpression of ECRG4 inhibited the proliferation, metastasis, and invasion of GC cells. RNA sequencing analysis showed that overexpression of ECRG4 induced the upregulation of Krüppel-like factor 2. Conclusions: Our findings show that ECRG4 promotes GC progression via Krüppel-like factor 2 signaling and highlight ECRG4 as a potential GC biomarker and therapeutic target.

Correlation of 3'-phosphoadenosine-5'-phosphosulfate synthase 1 (PAPSS1) expression with clinical parameters and prognosis in esophageal squamous cell carcinoma.

BACKGROUND: In recent years, 3'-phosphoadenosine-5'-phosphosulfate synthase 1 (PAPSS1) has been found to be highly expressed in some cancers and significantly associated with prognosis. Nevertheless, the role of PAPSS1 in esophageal squamous cell carcinoma (ESCC) is poorly understood. METHODS: In this study, PAPSS1 expression in ESCC samples was researched through real-time quantitative polymerase chain reaction (qPCR), immunohistochemistry (IHC), and western blot (WB) techniques. siRNA technology was then used to inhibit PAPSS1 expression in ESCC cells, and cytologic tests were conducted to research gene affection on cell apoptosis, proliferation, and migration. Then, the expression of Bcl2, Ki67, and Snail was detected using qPCR and WB tests. These experimental data were analyzed by GraphPad software, where the P-value<0.05 was statistically significant. RESULTS: The results showed that PAPSS1 expression level in ESCC tissues was higher than in the adjacent tissues. The data also showed that PAPSS1 was significantly correlated with N stage, and that the patients with high expressions had longer survival time. After transfection for 48 hours, the cell apoptosis rate of siRNA-PAPSS1 transfected groups decreased significantly, whereas the cell proliferation rate and migration ability increased relative to the control. At the same time, the expression levels of Bcl2, Ki67 and Snail were all upregulated by siRNA-PAPSS1. PAPSS1, however, was suppressed. CONCLUSIONS: PAPSS1 may be an ESCC suppressor gene, and its specific molecular mechanism in ESCC needs to be further studied.