Synthesis and Antifungal Activity of Coumarin Derivatives Containing Hydrazone Moiety.

Plant disease control mainly relies on pesticides. In this study, a series of coumarin derivatives containing hydrazone moiety were designed and synthesized. The synthesized compounds were characterized and used to evaluate the antifungal activity against four pathogens, Botrytis cinerea, Alternaria solani, Fusarium oxysporum, and Alternaria alternata. The results showed that the inhibition rate of some compounds at 100 µg/mL in 96 hours reached around 70 % against A. alternata, higher than that of the positive control. The corresponding EC50 values were found at around 30 µg/mL. Finally, the compound 3 b was screened out with the lowest EC50 value (19.49 µg/mL). The analysis of SEM and TEM confirmed that the compound 3 b can obviously damage the morphological structure of hyphae, resulting in the depletion of the cells by the destruction of morphological matrix and leakage of contents. RNA sequencing showed that compounds 3 b mainly affected the pentose phosphate pathway, which caused to destroy the layer of mitochondrial structure. Molecular docking showed that compounds 3 b fitted the binding pocket of yeast transketolase and interacted with lysine at the hydrazone structure. Our results suggested that the introduction of hydrazone was an effective strategy for the design of novel bioactive compounds.

Jasmonate increases terpene synthase expression, leading to strawberry resistance to Botrytis cinerea infection.

KEY MESSAGE: Jasmonate induced FaTPS1 to produce terpene, and overexpression FaTPS1 led to fruit resistant against B. cinerea infection, FaMYC2 induced FaTPS1 by binding to its promoter that downstream of jasmonate. Jasmonic acid (JA) and its derivatives are associated with plant defence responses against pathogenic organisms. In the present study, a total of 10,631 differentially expressed genes, 239 differentially expressed proteins, and 229 differential metabolites were screened and found to be mainly involved in pathogen perception, hormone biosynthesis and signal transduction, photosynthesis, and secondary metabolism. In strawberry fruits, methyl jasmonate (MeJA) induced FaTPS1 expression and quickly increased the terpene content. Furthermore, FaTPS1 overexpression increased the emission of sesquiterpenes, especially germacrene D, and improved strawberry resistance against Botrytis cinerea infection, although the knockdown of FaTPS1 increased its susceptibility to the same pathogen. Using a yeast one-hybrid assay and transient expression analysis, we demonstrated that FaMYC2 can bind to the G-box element in the promoter region of FaTPS1, thus inducing FaTPS1 expression. MeJA also stimulated FaMYC2 expression and regulated downstream signalling cascades. Moreover, we presented a possible model of the new signalling pathway of MeJA-mediated strawberry resistance to B. cinerea.

A Nomogram Model for Evaluating the Risk of Lymph Node Metastasis in cT2-cT4N0M0 Gastric Cancer Population.

BACKGROUND Neoadjuvant chemotherapy is an important treatment for advanced gastric cancer, but it has been unclear whether neoadjuvant chemotherapy is closely related to lymph node metastasis. Therefore, based on the disease characteristics of the cT2-cT4N0M0 gastric cancer population, this study established a nomogram prediction model of lymph node metastasis risk in this gastric cancer population to help clinicians optimize clinical decision-making. MATERIAL AND METHODS We analyzed the data of 336 patients with advanced gastric cancer with CT imaging stage of cT2-cT4N0M0 admitted to the Third Department of the Fourth Hospital of Hebei Medical University from 2015 to 2021. Combined with the results of univariate and multivariate logistic regression analysis, 7 indicators were selected to establish a nomogram prediction model. The calibration curves, ROC curves, and decision curves were drawn against the nomogram model using R language. RESULTS The results showed that the AUC value of the model and the external validation data set were 0.925 and 0.911, respectively. The P value of the Hosmer-Lemeshow test for the internal validation dataset was 0.082, and the P value of Hosmer-Lemeshow test for the external validation dataset was 0.076.The decision curve results showed that when the threshold probability was 0.1-0.9, this model could benefit patients by predicting the risk of lymph node metastasis in patients with advanced gastric cancer, and formulating appropriate treatment schemes accordingly. CONCLUSIONS This nomogram has shown good discrimination and fit, and can also be combined with imaging examination to screen the populations suitable for neoadjuvant chemotherapy, avoid the risk of misdiagnosis of N staging to the greatest extent, and to assist clinicians to optimize clinical decision-making.

Cystathionine ß-synthase expression correlates with tumor development and poor prognosis in lung squamous cell carcinoma patients.

The purpose of this study was to investigate the correlation between the expression of cystathionine ß-synthase (CBS) in lung squamous cell carcinoma (LUSC) and the microvascular density (MVD) and clinicopathological features. Firstly, the expression status of CBS in diffuse carcinoma and LUSC was searched through the public bioinformatics database. Subsequently, immunohistochemical staining and scoring were performed on tumor tissues and matched normal tissues from 108 LUSC patients to assess CBS expression; the MVD of tumor tissues was also detected. The results showed that CBS was overexpressed in some tumor tissues, including LUSC. Immunohistochemical results showed that the positive expression rate of CBS in tumor tissues (63.0%) was higher than that in normal tissues (17.6%). The expression of CBS was correlated with T (p=0.01), N (p=0.004), TNM (p=0.011) stages, and tumor differentiation degrees (p<0.001), with the increase of T, N, and TNM stages or the decrease of differentiation, the expression level of CBS also increased. In addition, the expression level of CBS was positively correlated with MVD (r=0.6997, p<0.0001). Survival analysis showed that the survival rate of the CBS negative expression group was better than that of the positive expression group (p=0.004). Cox multivariate analysis showed that CBS expression status (p<0.001), T stages (p=0.020), and TNM stages (p=0.021) were independent factors affecting the prognosis of LUSC. In conclusion, the high expression of CBS affects tumor development and is associated with the poor prognosis of LUCS, which may be used as a biomarker to evaluate prognosis and find a new direction for the treatment of LUSC.

Demethylation alters transcriptome profiling of buds and leaves in 'Kyoho' grape.

BACKGROUND: Grape buds and leaves are directly associated with the physiology and metabolic activities of the plant, which is monitored by epigenetic modifications induced by environment and endogenous factors. Methylation is one of the epigenetic regulators that could be involved in DNA levels and affect gene expression in response to stimuli. Therefore, changes of gene expression profile in leaves and bud through inhibitors of DNA methylation provide a deep understanding of epigenetic effects in regulatory networks. RESULTS: In this study, we carried out a transcriptome analysis of 'Kyoho' buds and leaves under 5-azacytidine (5-azaC) exposure and screened a large number of differentially expressed genes (DEGs). GO and KEGG annotations showed that they are mainly involved in photosynthesis, flavonoid synthesis, glutathione metabolism, and other metabolic processes. Functional enrichment analysis also provided a holistic perspective on the transcriptome profile when 5-azaC bound to methyltransferase and induced demethylation. Enrichment analysis of transcription factors (TFs) also showed that the MYB, C2H2, and bHLH families are involved in the regulation of responsive genes under epigenetic changes. Furthermore, hormone-related genes have also undergone significant changes, especially gibberellin (GA) and abscisic acid (ABA)-related genes that responded to bud germination. We also used protein-protein interaction network to determine hub proteins in response to demethylation. CONCLUSIONS: These findings provide new insights into the establishment of molecular regulatory networks according to how methylation as an epigenetic modification alters transcriptome patterns in bud and leaves of grape.

Cooling-field dependence of dipole-induced loop bias.

In ferromagnet/antiferromagnet bilayers and core/shell nanoparticles, an exchange-bias-like loop bias phenomenon in the ferromagnet is observed solely due to the long-range dipolar interactions between ferromagnet and antiferromagnet. With increasing cooling field, the loop bias field may increase from zero in the bilayers or from a negative value in the core/shell nanoparticles to a positive saturated value, depending on the interfacial dipolar interaction and/or ferromagnetic/antiferromagnetic thickness. Using a modified Monte-Carlo method and the Meiklejohn-Bean model, the interfacial dipole fields (up to several teslas) and the domain sizes imprinted on the interfacial antiferromagnet are explicitly calculated to elucidate the cooling field dependence of loop bias, which is governed by distinct mechanisms at the flat and curved interfaces. Finally, through simply discussing the roles of lattice structure, ferromagnetic dipolar interaction, and simulation time, it is evidenced that the dipole-induced loop bias is ubiquitous and applicable for stabilizing a ferromagnet, irrespective of the interface mismatch and the undeterministic diffusion between different ingredients. This work helps us to develop the spintronic devices with nonatomic-contact nanostructure assemblies.

Optical damage resistant Ti-diffused Zr/Er-codoped lithium niobate strip waveguide for high-power 980 nm pumping.

Ti4+-diffused Zr4+/Er3+-codoped LiNbO3 strip waveguide was fabricated on an X-cut LiNbO3 substrate by thermal diffusion in sequence of Er3+, Zr4+ and Ti4+. Secondary ion mass spectrometry study shows that the Ti4+ ions follow a sum of two error functions in the width direction and a Gauss function in the depth direction of the waveguide. Both Er3+ and Zr4+ profiles follow the desired Gauss function, and entirely cover the Ti4+ profile. Optical study shows that the waveguide is TE or TM single mode at 1.5 µm wavelength, and has a loss of 0.3 (0.5) dB/cm for the TM (TE) mode. In the case of 980 nm pumping, the waveguide shows stable 1547 nm signal output under high-power pumping without optical damage observed, and a net gain of 1.1 dB/cm is obtained for the available pump power of 120 mW.

Polarization-insensitive, shallow Ti-diffused near-stoichiometric LiTaO3 strip waveguide for integrated optics.

We report on a Ti-diffused near-stoichiometric (NS) LiTaO3 strip waveguide fabricated by diffusion of an 8 µm wide, 160 nm thick Ti-strip followed by Li-rich vapor transport equilibration. It is found that the waveguide surface caves in ∼60 nm below the crystal surface. X-ray single-crystal diffraction shows that the indentation is due to Ti-induced lattice contraction. Optical studies show that the waveguide is in an NS composition environment, supports TE and TM single-mode propagation at 1.5 µm wavelength, is polarization insensitive, and has a shallow mode field profile and a loss of 0.2/0.3 dB/cm for the TE/TM mode. Secondary ion mass spectrometry analysis shows that the Ti profile follows a sum of two error functions in the width direction and a Gaussian function in the depth direction of the waveguide. With the optimized fabrication condition, the waveguide is promising for developing an optical-damage-resistant device that requires a shallow mode field profile.

Synergistic Construction of Sub-Nanometer Channel Membranes through MOF-Polymer Composites: Strategies and Nanofiltration Applications.

The selective separation of small molecules at the sub-nanometer scale has broad application prospects in the field, such as energy, catalysis, and separation. Conventional polymeric membrane materials (e.g., nanofiltration membranes) for sub-nanometer scale separations face challenges, such as inhomogeneous channel sizes and unstable pore structures. Combining polymers with metal-organic frameworks (MOFs), which possess uniform and intrinsic pore structures, may overcome this limitation. This combination has resulted in three distinct types of membranes: MOF polycrystalline membranes, mixed-matrix membranes (MMMs), and thin-film nanocomposite (TFN) membranes. However, their effectiveness is hindered by the limited regulation of the surface properties and growth of MOFs and their poor interfacial compatibility. The main issues in preparing MOF polycrystalline membranes are the uncontrollable growth of MOFs and the poor adhesion between MOFs and the substrate. Here, polymers could serve as a simple and precise tool for regulating the growth and surface functionalities of MOFs while enhancing their adhesion to the substrate. For MOF mixed-matrix membranes, the primary challenge is the poor interfacial compatibility between polymers and MOFs. Strategies for the mutual modification of MOFs and polymers to enhance their interfacial compatibility are introduced. For TFN membranes, the challenges include the difficulty in controlling the growth of the polymer selective layer and the performance limitations caused by the "trade-off" effect. MOFs can modulate the formation process of the polymer selective layer and establish transport channels within the polymer matrix to overcome the "trade-off" effect limitations. This review focuses on the mechanisms of synergistic construction of polymer-MOF membranes and their structure-nanofiltration performance relationships, which have not been sufficiently addressed in the past.

Constructing an Anion-Braking Separator to Regulate Local Li+ Solvation Structure for Stabilizing Lithium Metal Batteries.

Lithium metal batteries (LMBs) offer significant advantages in energy density and output voltage, but they are severely limited by uncontrollable Li dendrite formation resulting from uneven Li+ behaviors and high reactivity with potential co-solvent plating. Herein, to uniformly enhance the Li behaviors in desolvation and diffusion, the local Li+ solvation shell structure is optimized by constructing an anion-braking separator, hence dynamically reducing the self-amplifying behavior of dendrites. As a prototypal, two-dimensional lithiated-montmorillonite (LiMMT) is blade-coated on the commercial separator, where abundant -OH groups as Lewis acidic sites and electron acceptors could selectively adsorb corresponding FSI- anions, regulating the solvation shell structure and restricting their migration. Meanwhile, the weakened anion mobility delays the time of breaking electrical neutrality, and the Li nucleation density is quantified through the respective experimental, theoretical and spectroscopical results, providing a comprehensive understanding of modifying anion and cation behaviors on dendritic growth suppression. As anticipated, a long Li plating/stripping lifespan up to 1800 h and a significantly increased average Coulombic efficiency of 98.8% are achieved under 3.0 mAh cm-2. The fabricated high-loading Li-LFP or Li-NCM523 full-cells display the cycle durability with enhanced capacity retention of nearly 100%, providing the instructive guide towards realizing dendrite-free LMBs.

[Study of the association between SNP rs7903146(C/T) in TCF7L2 and metabolic syndrome in Chinese Korean and Han populations from Yanbian].

OBJECTIVE: To assess the association between a rs7903146(C/T) polymorphism of TCF7L2 gene and metabolic syndrome (MS), plasma lipoprotein, and plasma adiponectin (PA) in Chinese Korean and Han populations from Yanbian region. METHODS: Polymerase chain reaction and DNA sequencing were used to determine the genotype of rs7903146 in 310 Chinese Korean (190 in case group and 120 in control group) and 344 Chinese Han (255 in case group and 89 in control group). ELIAS was used to test serum insulin (INS) and PA. RESULTS: The frequency of T allele was higher in ethnic Han compared with ethnic Koreans (0.022 vs. 0.008), lower than that of Europeans (0.279) and Africans (0.257), but similar to those of Beijing Chinese and Japanese. For ethnic Korean Chinese, the frequencies of TT and CT genotypes as well as the T allele in patients with EH were significantly higher than those of the control group (P< 0.01), which also showed an increasing trend for both MS and T2DM groups (P=0.09 and P=0.07, respectively). By contrast, for Chinese Han, the frequencies of genotypes and particular allele in patients with MS, T2DM and EH showed no significant difference from those of the control group. For T2DM, EH, and control groups, PA level of individuals with CT or TT genotypes was significantly higher compared with that of the CC genotype (P< 0.05). The TC and LDL-C levels were significantly higher in T2DM, MS and EH groups compared with those of the control group. The PA level was lower in MS group compared with the control group. CONCLUSION: The T allele of SNP rs7903146 of TCF7L2 gene may be a risk factor for EH in Chinese Korean population from Yanbian region. The T allele also affects the PA level; lower PA is a risk factor for MS. The rs7903146 polymorphism showed a racial and ethnic difference.

Biomimetic multifunctional hybrid sponge via enzymatic cross-linking to accelerate infected burn wound healing.

Preparing sponge dressings with stable wet adhesion remains difficult in wound repair, especially in burn wounds with bleeding and large amounts of exudate. In this work, a multifunctional hybrid sponge dressing (DHGT+PHMB+TiO2NPs) with good wet adhesion was developed by combining biomimetic and enzymatic cross-linking reactions. The sponge dressing matrix (DHGT) was prepared by tyrosinase-catalyzed cross-linking of dopamine-modified hyaluronic acid (DOPA-HA) and gelatin. The multifunctional hybrid sponge dressing was obtained by loading polyhexamethylene biguanide (PHMB) and titanium dioxide nanoparticles (TiO2NPs) onto the DHGT matrix. The newly developed sponge dressing exhibited high mechanical properties, good wet adhesion, antibacterial activity, reactive oxygen species (ROS) scavenging, biocompatibility, and excellent hemostasis ability. In vivo studies showed that the multifunctional hybrid sponge dressing could significantly accelerate the healing of infected full-thickness burn wounds by inhibiting bacterial growth, accelerating skin tissue reepithelialization, collagen deposition, and angiogenesis, as well as regulating the expression of inflammatory factors and cytokines.

Diagnostic accuracy of gastric filling ultrasonography in preoperative invasion depth (T stage) of gastric cancer: Meta-analysis.

OBJECTIVE: This study aimed to evaluate the diagnostic value of gastric filling ultrasonography in the preoperative invasion depth (T staging) of gastric cancer. METHODS: We systematically searched several online electronic databases including CNKI, Wanfang Medical Database, VIP, CBM, Pubmed, Embase, Cochrane Library, and Web of Science from January 2010 to December 2021, identifying the study about gastric filling ultrasonography for diagnostic of invasion depth of gastric cancer. Using bivariate mixed effect model to calculate the sensitivity (Sen), specificity (spe), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) with 95% confidence interval (CI). Draw the summary receiver operating characteristic (sROC) curve, likelihood ratio matrix and fagan diagram to evaluate the diagnostic value of gastric filling ultrasonography in the preoperative invasion depth of gastric cancer. Sen analysis and Publication bias tests were performed. RESULTS: This study obtained 21 literatures and the quality were good. The pooled Sen and spe of gastric filling ultrasonography was: T1: 0.63 (95% CI:0.51-0.73), 0.96 (95% CI:0.94-0.98); T2: 0.67 (95% CI:0.62-0.71), 0.90 (95% CI:0.88-0.93); T3: 0.79 (95% CI:0.75-0.82), 0.83 (95% CI:0.80-0.86); T4: 0.80 (95% CI:0.73-0.86), 0.96 (95% CI:0.94-0.97), respectively. In addition, the PLR and NLR of gastric filling ultrasonography was: T1: 16.74 (95% CI:9.98-28.09), 0.39 (95% CI:0.29-0.52); T2: 6.98 (95% CI:5.20-9.38), 0.36 (95% CI:0.31-0.42); T3: 4.65 (95% CI:3.78-5.73), 0.26 (95% CI:0.21-0.31); T4: 18.51 (95% CI:12.77-26.83), 0.20 (95% CI: 0.15-0.29), respectively. The DOR of gastric filling ultrasonography in T1-T4 was: 43.17 (95% CI:20.62-90.41),19.13 (95% CI:12.61-29.03), 18.15 (95% CI:12.86-25.62), 90.63 (95% CI:47.36-173.41), respectively. The sROC curve revealed that the area under the curve (AUC) of T1-T4 was: 0.93, 0.82, 0.87, 0.97, respectively. Sen analysis indicated that the study was steadily. And there is no publication bias in this study. But the study has some heterogeneity. CONCLUSION: Gastric filling ultrasonography is useful for clinical preoperative T staging of gastric cancer, and the result indicate that the accuracy of gastric filling ultrasonography in discriminating T1-T4 is higher than that in discriminating T2 - T3. It can be used as an imaging diagnostic method for preoperative T staging of gastric cancer.

Comparing the efficacy and safety of cement-augmented fenestrated pedicle screws and conventional pedicle screw in surgery for spinal metastases: a retrospective comparative cohort study.

Background: The incidence of cancer patients with bone metastasis is increasing annually. With the advancement of medical treatment for malignant tumors, the survival time of patients with spinal metastases is gradually being prolonged, and adjacent segment vertebral metastases often occur after conventional pedicle screw (CPS) surgery, leading to spinal instability, pain and nerve function injury again, with repeated symptoms. Combined pedicle screw fixation can maintain or reconstruct the spinal stability. This study aimed to investigate the efficacy and safety of cement-augmented fenestrated pedicle screws in the posterior approach for spinal metastases by comparing with CPS. Methods: From January 2017 to August 2019, 52 patients with spinal metastases who underwent separation surgery and internal fixation via posterior approach were retrospectively enrolled. Cases were divided into the cement-augmented pedicle screw (CAPS) group (28 cases) and the CPS group (24 cases). The baseline data [age, gender, surgical sites, surgical segment, Tomita classification, Tomita score, Tokuhashi score, spinal instability neoplastic score (SINS)], surgical information, and local progression-free survival (PFS) time were compared between the two groups. Every patient was followed-up every 3 months with imaging examination. The visual analog scale (VAS) score and Frankel grade of the two groups were recorded before and 3 months after the operation were used to evaluate the efficacy. The operation time, the amount of intraoperative blood loss, the amount of bone cement injected in the pedicle screw group, and the complications of the surgery were recorded to evaluate the safety of CAPS. Results: The baseline characteristics were comparable between the two group. Compared with the CPS group, the CAPS group showed significantly longer operation time (163±20 vs. 138±18 min, P<0.001) and lower VAS scores (2.93±1.33 vs. 4.17±1.34, P=0.002). Adjacent segment vertebral metastasis occurred in 10 cases (2 in the CAPS group and 8 in the CPS group, P=0.017). Internal implant failure occurred in 8 cases (1 in the CAPS group and 7 in the CPS group, P=0.011). Compared with the CPS group, the CAPS group had a significantly longer local PFS time (P<0.05). Conclusions: CAPS could be a safe and effective choice in surgery for spinal metastases with the posterior approach.

Apatinib Functioned as Tumor Suppressor of Synovial Sarcoma through Regulating miR-34a-5p/HOXA13 Axis.

Objective: Synovial sarcoma is a rare malignant tumor. The role of apatinib in synovial sarcoma remains unclear. In this study, we aimed to determine the biological functions and the potential molecular mechanism of action of apatinib in synovial sarcoma. Methods: SW982 cells were stimulated with apatinib. The relative expression of the genes was determined by performing qPCR. Protein levels were evaluated by western blot and immunohistochemistry assays. Proliferation, apoptosis, migration, and invasion of SW982 cells were determined by the CCK-8 assay, clone formation assay, flow cytometry, wound healing, and the transwell assay, respectively. Additionally, SW982 cells were injected into mice to induce synovial sarcoma. Results: Apatinib decreased the proliferation, migration, and invasion but increased the apoptosis of SW982 cells. Apatinib repressed tumor growth in vivo and elevated miR-34a-5p in SW982 cells. The inhibition of miR-34a-5p repressed the reduction of proliferation, migration, and invasion and also the elevation of apoptosis in apatinib-treated SW982 cells. The luciferase activity decreased after cotransfection of the miR-34a-5p mimic and the wild-type HOXA13 vector. Additionally, an increase in miR-34a-5p repressed the levels of HOXA13 mRNA and protein. Moreover, HOXA13 reversed these patterns caused by the inhibition of miR-34a-5p in apatinib-treated SW982 cells. Conclusion: Apatinib elevated miR-34a-5p and reduced HOXA13, leading to a significant decrease in proliferation, migration, and invasion, along with an enhancement of apoptosis in SW982 cells. Apatinib suppressed tumorigenesis and tumor growth in SW982 cells in vivo.

Lithium/Graphene Composite Anode with 3D Structural LiF Protection Layer for High-Performance Lithium Metal Batteries.

Lithium metal batteries (LMBs) are a promising candidate for next-generation energy storage devices. However, the high irreversibility and dead Li accumulation of the lithium metal anode caused by its fragile original solid electrolyte interface (SEI) seriously hinder the practical application of LMBs. Herein, a facile slurry-coating and one-step thermal fluorination reaction method is proposed to construct the 3D structural LiF-protected Li/G composite anode. The existence of a 3D LiF protection layer is convincingly confirmed and the function of the Li/G skeleton is discussed in detail. The 3D structural LiF protection layer results in superior electrochemical performance by improving the utilization of Li and suppressing the accumulation of dead Li in symmetric and full coin cells. Moreover, a 0.85 Ah pouch cell strictly following the parameters of the practical battery industry can work stably for 140 cycles with a gradual internal resistance increase. This novel Li/G composite anode indicates a promising strategy in lithium/carbon composite anodes for LMBs, and the facile thermal fluorination reaction method presented in this paper offers a new method for the construction of a 3D structural protection layer for lithium metal anodes.

Expression and clinical significance of IL-33 and its receptor ST2 in children with obstructive sleep apnea syndrome.

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is characterized by a majority population of respiratory sleep disorders, which consists of simple snoring as well as increased upper airway resistance syndrome. Adenoid hypertrophy has been suggested as the main cause of OSAS in children. The role of interleukin-33 (IL-33) and its receptor suppressor of tumorigenicity 2 (ST2) in a variety of pediatric allergic diseases has been confirmed. We hypothesized that IL-33/ST2 path way might play a pivotal role in the pathogenesis of adenoid hypertrophy-associated OSAS in children. METHODS: A total of 40 children undergoing adenoidectomy due to OSAS in the Otolaryngology of Tianjin Children's Hospital were selected as the study participants. The quantity of IL-33 and ST2 positive cells in adenoids was detected by immunohistochemical (IHC) streptavidin-peroxidase conjugate (SP) method. RESULTS: The IL-33 positive cells were mainly distributed in the submucosa epithelium and vascular endothelium, and expressed in the nucleus and cytoplasm. Meanwhile, ST2 positive cells were primarily observed in the mucosa and expressed in the nucleus and cytoplasm, with a little expression of intercellular substance. There was a positive correlation between the proportion of adenoids in the posterior nostril diameter and the number of IL-33 positive cells. The expression of IL-33 in adenoids was positively correlated with the level of ST2 (r=0.809, P=0.000). The expression of IL-33 in adenoids was positively correlated with the level of eosinophil granulocyte (r=0.859, P=0.000). Moreover, the expression of ST2 in adenoids was positively correlated with the level of eosinophil granulocyte (r=0.814, P=0.000). The number of IL-33 positive cells was significantly higher in the moderate hypoxemia group than that in the mild hypoxemia group (P<0.05). There was no significant difference in the number of ST2 positive cells between the moderate hypoxemia group and mild hypoxemia group (P>0.05). CONCLUSIONS: Both IL-33 and its receptor ST2 were expressed in adenoids of OSAS children. The severity of airway obstruction caused by adenoid hypertrophy was positively correlated with the expression of IL-33.

Successful Treatment of a Patient With Multiple-Line Relapsed Extensive-Stage Small-Cell Lung Cancer Receiving Penpulimab Combined With Anlotinib: A Case Report.

Small-cell lung cancer (SCLC) is a highly malignant, rapidly developing group of diseases with poor biological behavior. Most patients have extensive-stage SCLC (ES-SCLC) when they are first diagnosed. Standard chemotherapy is prone to relapse in a short period of time, and the patients' median overall survival (OS) can reach only 13 months when chemotherapy is given in combination with PD-L1 inhibitors. To date, no studies have verified the efficacy and safety of the composite treatment of ES-SCLC with penpulimab and anlotinib despite some recognized data and advantages related to this regimen. Penpulimab, a novel PD-1 inhibitor with an IgG1 subtype, has a structural modification of the Fc segment which can prevent the immune cells from being phagocytosed or killed and can steadily avoid tumor immune escape. This case report describes a 71-year-old man who had ES-SCLC for 7 years which progressed after receiving standard systemic chemotherapy combined with radiotherapy. The third-line treatment of four cycles of anlotinib and carilizumab was discontinued because of grade 2 immune-related pneumonia despite the efficacy being evaluated as stable disease. After maintaining 22 months of progression-free survival, the patient relapsed and switched to a safer regimen of penpulimab combined with anlotinib to continue the treatment for four cycles. Partial response evaluation was confirmed twice, and the patient remained in good general condition. The combination of penpulimab and anlotinib can positively regulate the therapeutic effect by simultaneously acting on the tumor microenvironment and promoting blood vessel normalization. In general, this case provides support for the successful possibility of a rechallenge with immune checkpoint inhibitors, the better clinical efficacy of cross-line therapy with anlotinib, and the drug safety of penpulimab, suggesting a beneficial therapy for the clinical treatment of ES-SCLC.

Establishment and Validation of a Nomogram Prognostic Model for Epithelioid Hemangioendothelioma.

Background: Epithelioid hemangioendothelioma (EHE) is an ultrarare vascular sarcoma. At present, the epidemiological and clinical characteristics and prognostic factors are still unclear. Our study attempted to describe clinical features, investigate the prognostic indicators, and establish the nomogram prediction model based on the Surveillance, Epidemiology, and End Results (SEER) database for EHE patients. Methods: The patients diagnosed with EHE from 1986 to 2018 were collected from the SEER database and were randomly divided into a training group and a validation group at a ratio of 7 : 3. The Cox proportional hazard models were used to determine the independent factors affecting prognosis and establish a nomogram prognostic model to predict the survival rates for patients with EHE. The accuracy and discriminative ability of the model were measured using the concordance index, receiver operating characteristic curves, and calibration curves. The clinical applicability and application value of the model were evaluated by decision curve analysis. Results: The overall age-adjusted incidence of EHE was 0.31 patients per 1,000,000 individuals, with a statistically significant difference per year. Overall survival at 1, 5, and 10 years for all patients was 76.5%, 57.4%, and 48.2%, respectively. Multivariate Cox regression analysis identified age, tumour stage, degree of tissue differentiation, surgical treatment, chemotherapy, and radiotherapy as independent factors affecting prognosis (P < 0.05). The C-index values for our nomogram model of training group and validation group were 0.752 and 0.753, respectively. The calibration curve was in good agreement with the actual observation results, suggesting that the prediction model has good accuracy. The decision curve analysis indicated a relatively large net benefit. Conclusions: The nomogram model may play an important role in predicting the survival rate for EHE patients, with good concordance and accuracy, and can be applied in clinical practice.

Corrigendum: Successful treatment of a patient with multiple-line relapsed extensive-stage small-cell lung cancer receiving penpulimab combined with anlotinib: A case report.

[This corrects the article DOI: 10.3389/fonc.2022.846597.].