Coupling Postsynthetic High-Temperature Oxidative Thermolysis and Thermal Rearrangements in Isoreticular Zinc MOFs.

Herein, we report coupling in situ high temperature postsynthetic modifications (PSMs) in metal-organic frameworks (MOFs). Thermo-reactive propargyloxy-functionalized zinc IRMOFs (isoreticular metal-organic frameworks) prepared from 2-(prop-2-yn-1-yloxy)-[1,1'-biphenyl]-4,4'-dicarboxylic acid (H2bpdcOCH2CCH) were investigated for their high-temperature postsynthetic rearrangement (PSR) chemistry to heterocyclic chromenes and benzofurans and then coupled to solid-gas reactions with molecular oxygen. The selectivity for the initial molecular rearrangements was found to be inverted in the porous MOF environment compared to conventional melt reactions of the ester compound Me2bpdcOCH2CCH and proceeded far more easily than the solid-state transformation from H2bpdcOCH2CCH, showing the potential of MOFs to give rise to different chemistry. The major oxidative process was thermolysis of the chromene ring with a minor pathway of allylic-type oxidation to give heterocyclic chromenone functionality. The sequence was also successful on a series of two-component multivariate IRMOF frameworks prepared from thermo-reactive H2bpdcOCH2CCH and thermo-resistant H2bpdcOMe linkers, demonstrating that these reactions can be used with known crystal engineering strategies. All transformations were fully compatible with the requirements to maintain MOF crystallinity and porosity as evidenced by surface area analysis and X-ray powder diffraction measurements. This work contributes to establishing the feasibility of high-temperature solid-gas manifolds for MOF PSM.

Activation of p38 mitogen-activated protein kinase pathway by lipopolysaccharide aggravates postoperative ileus in colorectal cancer patients.

BACKGROUND AND AIM: Patients undergoing abdominal surgery can develop postoperative ileus (POI). Inflammation of the intestinal muscularis following intestinal manipulation may be caused by displaced bacteria or lipopolysaccharide (LPS). The aim of this study was to investigate the relationship between gut microbiota, LPS, and POI in colorectal cancer (CRC) patients and explore underlying mechanisms of LPS-triggered POI. METHODS: Sixty CRC patients undergoing colorectal resection were included. Bacterial communities from fecal samples were characterized by 16S rRNA gene sequencing, and fecal LPS levels were determined by Limulus amebocyte lysate assay. Mice were used to mechanistically investigate the causal relationship between microbiota, LPS, and POI. RESULTS: We discovered that CRC patients who developed prolonged POI (PPOI) had a unique pro-inflammatory gut microbial composition during the perioperative period. The highest proportions of Gram-negative bacteria at the genus level were Escherichia-Shigella and Bacteroides; the abundance of Escherichia-Shigella was higher throughout the perioperative period. Fecal LPS levels were significantly higher in patients with PPOI. In mice treated with an antibiotic cocktail, intestinal muscularis inflammation and intestinal dysfunction were significantly improved. Inflammation and dysfunction were significantly reduced in mice treated with polymyxin B, but were worsened by treatment with LPS. Moreover, LPS upregulated p38 phosphorylation in mice, and treatment with an inhibitor of p38 (SB203580) significantly alleviated intestinal inflammation and dysmotility. CONCLUSION: Lipopolysaccharide increases intestinal muscularis inflammation via activation of p38 signaling, which aggravates POI. Removing bacterial sources of LPS during the perioperative period is promising for the prophylactic treatment of PPOI.

Gut microbiota from nCAL patients promotes colon anastomotic healing by inducing collagen synthesis in epithelial cells.

BACKGROUND AND AIMS: Colon anastomotic leak (CAL) is considered one of the most feared and serious postoperative complications in colorectal cancer (CRC) patients, with no effective prevention strategies to date. Based on previous studies, gut microbiota is associated with anastomotic healing, but its ability to effectively promote anastomotic healing remains largely unknown. METHODS: We performed a clinical study to analyze the gut microbiota profiling in CRC patients who developed CAL and those who did not (nCAL) using 16S-rRNA-based next-generation sequencing (NGS). To investigate these changes in an in vivo model, we performed fecal microbiota transplantation in a colon anastomosis rat experimental model to elucidate the causal effect between gut microbiota and anastomotic healing. Notably, RNA-seq in the anastomotic tissue of the latter experimental model was utilized to discover the potential molecular mechanism. RESULTS: Our analysis implicated that gut microbiota profiling was profoundly different between CAL and nCAL patients. Strikingly, the rat experimental model transplanted with fecal microbiota derived from nCAL patients demonstrated enhanced anastomotic healing properties. Moreover, collagen synthesis, EMT, and TGF-ß/Smad signaling pathways were upregulated in the same rats. Concordantly, we discovered that the better anastomotic healing profiling displayed in gut microbiota derived from nCAL patients is dependent on the TGF-ß/Smad-induced EMT in vitro and in vivo. CONCLUSIONS: Collectively, our clinical study identified the postoperative gut microbiota profile is associated with CAL in CRC patients. On the contrary, fecal microbiota from nCAL patients promotes anastomotic healing via TGF-ß/Smad-induced EMT, with subsequent collagen synthesis and enhanced anastomosis healing.

Chiral covalent organic frameworks: design, synthesis and property.

Covalent organic frameworks (COFs) are constructed using reticular chemistry with the building blocks being connected via covalent bonds and have emerged as a new series of porous materials for multitudinous applications. Most COFs reported to date are achiral, and only a small fraction of COFs with chiral nature are reported. This review covers the recent advances in the field of chiral COFs (CCOFs), including their design principles and synthetic strategies, structural studies, and potential applications in asymmetric catalysis, enantioselective separation, and chiral recognition. Finally, we illustrate the remaining challenges and future opportunities in this field.

Metal-Diamidobenzoquinone Frameworks via Post-Synthetic Linker Exchange.

Metal-organic frameworks with amidic linkers often exhibit exceptional physical properties, but, owing to their strong metal-nitrogen bonds, are exceedingly challenging to isolate through direct synthesis. Here, we report a route to access metal-diamidobenzoquinone frameworks from their dihydroxobenzoquinone counterparts via postsynthetic linker exchange. The parent compounds (Me2NH2)2[M2L3] (M = Zn, Mn; H2L = 2,5-dichloro-3,6-dihydroxo-1,4-benzoquinone) undergo linker exchange upon exposure to a solution of monodeprotonated 2,5-diamino-3,6-dibromo-1,4-benzoquinone or 2,5-diamino-3,6-dichloro-1,4-benzoquinone, proceeding through single-crystal-to-single-crystal reactions. The presence of both types of linker in the resulting frameworks is confirmed by a combination of NMR, Raman, and energy-dispersive X-ray (EDX) spectroscopies. Moreover, the extent of linker exchange in the Zn frameworks is quantified using 13C NMR spectroscopy, and spatially resolved EDX spectroscopy reveals the two types of linker to be homogeneously distributed within a crystal. Finally, we propose a tentative mechanism of linker exchange based on pKa measurements, considerations of framework solubility, and powder X-ray diffraction analysis. This work provides the first method to exchange organic linkers with different donor atoms in metal-organic frameworks and in doing so demonstrates exchange between linkers with donor atoms differing in acidity by a remarkable 11 units of pKa. Together, these results offer a potentially general synthetic strategy toward new materials with exotic metal-linker coordination modes.

Spin Crossover in Iron(III) Quinolylsalicylaldiminates: The Curious Case of [Fe(qsal-F)2](Anion).

A family of iron(III) spin crossover complexes with different counteranions, [Fe(qsal-F)2]A (qsal-F = 4-fluoro-2-[(8-quinolylimino)methyl]phenolate; A = PF6- 1, OTf- 2, NO3- 3, ClO4- 4, BF4- 5, or NCS- 6) have been prepared. All compounds are isostructural and crystallize (triclinic P1̅ space group) with two independent iron(III) centers (Fe1 and Fe2) in the asymmetric unit. No solvent molecules are found in the crystal lattice, allowing us to directly probe the relative influence of anion variation on the spin crossover characteristics. The crystal packing is governed by three types of π-π interactions (type A, type B, and type C), which form undulating 1D chains. Additional interactions (π-F, C-H···O/F, and P4AE) connect the neighboring chains to form a complex supramolecular network. Hirshfeld surface analysis supports these findings. The anions are located between the cationic [Fe(qsal-F)2]+ chains; hence, similar interchain distances (dchain) are observed irrespective of the anion. However, the interplane distances (dplane) are influenced by the crystal packing and increase proportionally with the anion size. Magnetic studies reveal that smaller anions tend to stabilize the low-spin state (NO3- 3, ClO4- 4, and BF4- 5), while larger anions (PF6- 1 and OTf- 2) exhibit lower transition temperatures (Tonset for 1 = 200 K and T for 2 = 190 K) and gradual spin crossovers. The anomaly is 6, where, despite having the smallest anion, it exhibits the lowest transition temperature with magnetic hysteresis in the first step (T1/2↑ = 170 K and T1/2↓ = 157 K). This suggests the size, shape, and supramolecular connectivity of the anion all influence the magnetic properties.

Harnessing Structural Dynamics in a 2D Manganese-Benzoquinoid Framework To Dramatically Accelerate Metal Transport in Diffusion-Limited Metal Exchange Reactions.

Postsynthetic metal exchange represents a powerful synthetic method to generate metal-organic frameworks (MOFs) that are not accessible through direct synthesis, yet it is often hampered by slow reaction kinetics and incomplete exchange. While studies of metal exchange reactions have primarily focused on the transmetalation process, transport of exogenous metal ions into the framework structure represents a critical yet underexplored process. Here, we employ X-ray crystallography, electron microscopy, and energy dispersive X-ray spectroscopy to comprehensively examine the transport of Co2+ and Zn2+ ions during postsynthetic metal exchange reactions within the 2D manganese-benzoquinoid framework (Et4N)2[Mn2L3] (H2L = 3,6-dichloro-2,5-dihydroxy-1,4-benzoquinone). These studies reveal that exogenous metal ions diffuse primarily through the 1D channel along the crystallographic c axis, and this transport represents the rate-determining step. In addition, the Mn framework exhibits reversible dynamic structure behavior, contracting upon desolvation and then rapidly restoring its original structure and full volume upon resolvation. When conducting metal exchange reactions using a partially desolvated sample, these structural dynamics lead to acceleration of metal transport by up to 2000-fold, improve product purity, and give exchange of a larger fraction of metal sites. Finally, upon performing metal exchange using full-solvated crystals, an intermediate product can be isolated that constitutes a unique example of a 2D material with a gradient vertical heterostructure.

Formation of a Highly Reactive Cobalt Nanocluster Crystal within a Highly Negatively Charged Porous Coordination Cage.

Earth-abundant first-row transition-metal nanoclusters (NCs) have been extensively investigated as catalysts. However, their catalytic activity is relatively low compared with noble metal NCs. Enhanced catalytic activity of cobalt NCs can be achieved by encapsulating Co NCs in soluble porous coordination cages (PCCs). Two cages, PCC-2a and 2b, possess almost identical cavity in shape and size, while PCC-2a has five times more net charges than PCC-2b. Co2+ cations were accumulated in PCC-2a and reduced to ultra-small Co NCs in situ, while for PCC-2b, only bulky Co particles were formed. As a result, Co NCs@PCC-2a accomplished the highest catalytic activity in the hydrolysis of ammonium borane among all the first-row transition-metals NCs. Based on these results, it is envisioned that confining in the charged porous coordination cage could be a novel route for the synthesis of ultra-small NCs with extraordinary properties.

Modulating the Performance of an Asymmetric Organocatalyst by Tuning Its Spatial Environment in a Metal-Organic Framework.

Systematically tuning the spatial environment around the active sites of synthetic catalysts is a difficult challenge. Here, we show how this can be accomplished in the pores of multicomponent metal-organic frameworks. This relies on embedding a catalytic unit in a pore of the MUF-77 framework and then tuning its environment by introducing different functional groups to the surrounding linkers. This approach benefits from the structural regularity of MUF-77, which places each component in a precise location to circumvent disorder. Prolinyl groups, which are catalytically competent toward asymmetric aldol reactions, were selected as the catalytic unit. Since every prolinyl group is positioned in an identical environment, correlations between the pore architecture and the activity of these single-site catalysts can be elucidated. Systematic engineering of the pore structure, which is achieved by installing modulator groups on the framework linkers, impacts on the reaction rate and the enantiomeric excess of the aldol products. Furthermore, the spatial environment around the proline catalyst can override its innate stereochemical preference to dictate the preferred enantiomer of the reaction product. These results offer a new way to design three-dimensional active site environments for synthetic catalysts.

Triple-Stranded Cluster Helicates for the Selective Catalytic Oxidation of C-H Bonds.

Triple-stranded cluster helicates with heptametallic dicubane cores are synthesized by entrapping metals in the cavities of linear triple helicates based on a C2-symmetrical hexadentate Schiff-base ligand of ortho-substitued biphenol. The helicates are stable in both the solution and solid states, and the copper species could selectively catalyze the oxidation of C-H bonds of alkanes to ketones.

Systematic ligand modulation enhances the moisture stability and gas sorption characteristics of quaternary metal-organic frameworks.

Complex metal-organic frameworks (MOFs) that maintain high structural order promise sophisticated and tunable properties. Here, we build on our strategy of using combinations of structurally distinct ligands to generate a new isoreticular series of ordered quaternary Zn4O-carboxylate MOFs. Rational design of the framework components steers the system toward multicomponent MOFs and away from competing phases during synthesis. Systematic ligand modulation led to the identification of a set of frameworks with unusually high stability toward water vapor. These frameworks lose no porosity after 100 days' exposure to ambient air or 20 adsorption-desorption cycles up to 70% relative humidity. Across this series of frameworks, a counterintuitive relationship between the length of pendant alkyl groups and framework stability toward water vapor emerges. This phenomenon was probed via a series of gas and vapor adsorption experiments together with Grand Canonical Monte Carlo (GCMC) simulations, and could be rationalized on the basis of the propensity of the frameworks to adsorb water vapor and the proximity of the adsorbed water molecules to the water-sensitive metal clusters. Systematic variation of the pore volume and topography also tunes the CO2 and CH4 gas adsorption behavior. Certain of these materials display increases in their adsorption capacities of 237% (CO2) and 172% (CH4) compared to the parent framework.

Programmed pore architectures in modular quaternary metal-organic frameworks.

To generate metal-organic frameworks (MOFs) that are complex and modular yet well ordered, we present a strategy employing a family of three topologically distinct linkers that codes for the assembly of a highly porous quaternary MOF. By introducing substituted analogues of the ligands, a set of eight isoreticular frameworks is delivered, with the MOF structure systematically varied while the topology is maintained. To combat randomness and disorder, the substitution patterns of the ligands are designed to be compatible with their crystallographic site symmetries. MOFs produced in this way feature "programmed pores"--multiple functional groups compartmentalized in a predetermined array within a periodic lattice--and are capable of complex functional behavior. In these examples unconventional CO2 sorption trends, including capacity enhancements close to 100%, emerge from synergistic effects. Future PP-MOFs may be capable of enzyme-like heterogeneous catalysis and ultraselective adsorption.

A novel cuproptosis-related lncRNA prognostic signature in thyroid cancer.

Aims: We aimed to investigate the value of cuproptosis-related lncRNA in screening out high-risk thyroid cancer patients. Materials & methods: RNA sequencing data of thyroid cancer were obtained from The Cancer Genome Atlas. A cuproptosis-related lncRNA signature was constructed by using Cox regression. Results: Four cuproptosis-related lncRNAs were used to construct a survival prognosis model for thyroid cancer. The receiver operating characteristic curve showed that the area under the curve reached 0.830 at 1 year, 0.790 at 3 years and 0.824 at 5 years. Conclusion: The model may help to screen out thyroid cancer patients at high risk, and thus develop more appropriate treatment strategies.

The incidence of thyroid cancer (TC) is increasing and in most patients the standard treatment is effective. However, a regional recurrence or distant metastasis is observed in some patients with aggressive TC. Hence, finding reliable biomarkers to predict patients at risk of recurrence or distant metastasis and formulating effective treatment strategies have important clinical significance. In this study, we proposed a novel prediction model for TC patients. The model may help to screen out TC patients at risk of local recurrence or distant metastasis, and thus develop more appropriate treatment strategies.

Efficacy and safety of Jinhua Qinggan granules in the treatment of coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis.

OBJECTIVE: To evaluate, using meta-analysis, the efficacy and safety profile of Jinhua Qinggan granules (JHQG) in the treatment of novel coronavirus pneumonia. METHODS: We screened multiple publication databases (PubMed, Embase, The Cochrane Library, Web of Science, CNKI, WanFang, and VIP), using parameters designed to identify articles detailing randomized controlled trials relating to the treatment of novel coronavirus pneumonia with JHQG. The inclusion period for each search was the point of database inception to November 2022. Each piece of literature identified in our initial screening was independently reviewed by 2 researchers, who extracted the relevant data and evaluated the bias risk associated with the study. The data was split in 2: the control group (containing patients who had received routine treatment or placebo) and the experimental group (containing patients treated with JHQG). The meta-analysis was performed using Revman 5.4 software. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS: Four articles were selected for this study and combined included a total of 582 patients, which were subdivided into experimental (n = 347) and control (n = 235) groups. The results showed that treatment with JHQG could significantly: enhance the improvement rate of primary symptoms [relative ratio (RR) = 1.26,95% confidence interval (CI) (1.07, 1.49), P = .007] and fever [RR = 1.48, 95% CI (1.07, 2.04), P = .02]; decrease the viral nucleic acid in patients with coronavirus disease 2019 (COVID-19) [RR = 2.04, 95% CI (1.15, 3.62), P = .02] and reduce the progression of pneumonia [RR = 0.34, 95% CI (0.17, 0.67), P = .002]. However, there was no significant difference between the 2 groups with regards to: the improvement rate of cough, nausea and vomiting, fatigue, computed tomography, or frequency of adverse reactions. CONCLUSIONS: Current evidence indicates that JHQG is effective in treating COVID-19, increasing the rate of improvement for fever, increasing the negative rate of viral nucleic acid in patients with COVID-19 and reducing the aggravation rate of pneumonia. These conclusions need to be verified by further rigorous studies, as the existing results were limited by the number and quality of the included studies.

Traditional Chinese Medicine Based Acupoint Application for Asthma Treatment in Children: A Meta-Analysis and Systematic Review.

Objective: By conducting a systematic review of the efficacy of acupoint application on children with asthma. Methods: We searched Chinese databases (CNKI, VIP, and Wanfang) and English databases (PubMed, Embase, and Cochrane Library) for studies from the establishment of the database to October 2021. The included literature studies were randomized control studies investigating the treatment of asthma in children by acupoint application. The primary outcomes included the cure rate, the resolution time of cough, and the resolution time of wheezing. The secondary outcomes included pulmonary function and interleukins. Stata 15 and RevMan 5.4 were used to analyze the extracted data. Results: A total of 24 related studies were included containing 2716 cases. The meta-analysis showed that TCM group was superior to control group in terms of cure rate, pulmonary function (FEV1), and resolution time of wheezing in children with asthma [RR = 1.26,95% (1.21,1.31), P < 0.05; SMD = 0.81, 95%CI (0.05,1.56), P < 0.05; WMD = -1.40, 95%CI (-1.75, -1.05), P < 0.05]. Conclusions: The present study shows that acupoint application is an effective treatment for children with asthma in China, especially in alleviating wheezing and improving quality of life.

Challenges and opportunities for chiral covalent organic frameworks.

As highly versatile crystalline porous materials, covalent organic frameworks (COFs) have emerged as an ideal platform for developing novel functional materials, attributed to their precise tunability of structure and functionality. Introducing chiral functional units into frameworks produces chiral COFs (CCOFs) with chiral superiorities through chirality conservation and conversion processes. This review summarises recent research progress in CCOFs, including synthetic methods, chiroptical characterisations, and their applications in asymmetric catalysis, chiral separation, and enantioselective recognition and sensing. Challenges and limitations are discussed to uncover future opportunities in CCOF research.

Randomized Clinical Trial: Probiotics Alleviated Oral-Gut Microbiota Dysbiosis and Thyroid Hormone Withdrawal-Related Complications in Thyroid Cancer Patients Before Radioiodine Therapy Following Thyroidectomy.

Background: Thyroid hormone withdrawal (THW) in postoperative thyroid cancer patients who need always accompanied by complications (e.g., dyslipidemia and constipation). At present, there are no effective and safe means to alleviate these complications. Purpose: We aimed to assess the oral-gut microbiota profiles in THW patients then investigate whether probiotics could alleviating alleviate THW related complications and investigate whether these therapeutic effects were associated with the oral-gut microbiota state. Methods: Fifty eligible thyroid carcinoma patients undergoing thyroidectomy were randomly assigned to receive probiotics or placebo during THW. Complications were assessed through validated questionnaires and plasma lipid indicators. The complex probiotics preparation was composed of Bifidobacterium infantis, Lactobacillus acidophilus, Enterococcus faecalis, and Bacillus cereus. Results: Probiotics alleviated lack of energy, constipation, weight gain, and dry mouth and decreased the levels of fecal/serum LPS and plasma lipid indicators (total cholesterol, triglycerides, low-density lipoprotein, and apolipoprotein A) (P < 0.05). Gut and oral microbial diversity were significantly decreased after THW, while an increased microbial dysbiosis index (MDI) was observed. Probiotics distinctly restored the gut and oral microbial diversity. Increased Holdemanella, Enterococcus, and Coprococcus_2, while decreased Fusobacterium, Eubacterium_ruminantium_group, Ruminococcus_1, and Parasutterella in the gut were found after probiotics intervention. Lack of energy, constipation, weight gain, and dyslipidemia were seen to be related to the above microbiota. In addition, probiotics reduced oral Prevotella_9, Haemophilus, Fusobacterium, and Lautropia, which were positively correlated with the occurrence of dry mouth. Conclusion: Probiotics reduce the incidence of complications in patients after THW, which may be related to modifying the oral and gut microbiota. Clinical Trial Registration: [https://clinicaltrials.gov/], identifier America Clinical Trial Registry NCT03574051.

Controlled n-Doping of Naphthalene-Diimide-Based 2D Polymers.

2D polymers (2DPs) are promising as structurally well-defined, permanently porous, organic semiconductors. However, 2DPs are nearly always isolated as closed shell organic species with limited charge carriers, which leads to low bulk conductivities. Here, the bulk conductivity of two naphthalene diimide (NDI)-containing 2DP semiconductors is enhanced by controllably n-doping the NDI units using cobaltocene (CoCp2 ). Optical and transient microwave spectroscopy reveal that both as-prepared NDI-containing 2DPs are semiconducting with sub-2 eV optical bandgaps and photoexcited charge-carrier lifetimes of tens of nanoseconds. Following reduction with CoCp2 , both 2DPs largely retain their periodic structures and exhibit optical and electron-spin resonance spectroscopic features consistent with the presence of NDI-radical anions. While the native NDI-based 2DPs are electronically insulating, maximum bulk conductivities of >10-4  S cm-1 are achieved by substoichiometric levels of n-doping. Density functional theory calculations show that the strongest electronic couplings in these 2DPs exist in the out-of-plane (π-stacking) crystallographic directions, which indicates that cross-plane electronic transport through NDI stacks is primarily responsible for the observed electronic conductivity. Taken together, the controlled molecular doping is a useful approach to access structurally well-defined, paramagnetic, 2DP n-type semiconductors with measurable bulk electronic conductivities of interest for electronic or spintronic devices.

Development and validation of survival nomograms in colorectal cancer patients with synchronous liver metastases underwent simultaneous surgical treatment of primary and metastatic lesions.

Colorectal cancer patients with synchronous liver metastases (CRSLM) can be treated by simultaneous surgery, that is the primary tumor and liver metastasis are removed at the same time. However, criteria for simultaneous surgery are underwent continuously modified and expanded. An appropriate selection of adequate candidates for simultaneous surgery is vital to get best benefits. A retrospective study including CRSLM patients underwent simultaneous surgical treatment was conducted. CRSLM patients from SEER database were screened as development set, while CRSLM patients in Harbin (China) were enrolled as validation set. Overall survival (OS) and cancer-specific survival (CSS) were applied as end-point. Variables were screen by LASSO-Cox regression, then Cox regression was applied to construct 1-, 3- and 5-year OS, and CSS nomograms. Nomograms were compared to TMN stage for survival prediction and evaluated by concordance indexes (C-indexes), Time-dependent receiver operating characteristic (ROC) curves, Decision Curve Analysis (DCA). 1347 and 112 CRSLM patients were included in the development set and validation set respectively. Nine factors were found associated with OS and CSS, i.e., Age, Primary Site, Differentiation grade, Histology type, T stage, N stage, Tumor size, Chemotherapy, CEA. Compared to the TNM stage, OS nomogram in development set and validation set got C-indexes values of 0.701 vs 0.641, 0.670 vs 0.557 respectively. Meanwhile, compared to the TNM stage, CSS nomogram in development set and validation set got C-indexes values of 0.704 vs 0.649, 0.677 vs 0.569 respectively. AUC values of the OS and CSS nomograms were higher than the TNM stage, DCA showed the OS and CSS nomograms got more clinical net benefit than the TNM stage, in both the development set and validation set. Our nomograms for predicting survival might be helpful to identify the right CRSLM patients who can get most benefit from simultaneous surgery.

Tectorigenin inhibits inflammation and pulmonary fibrosis in allergic asthma model of ovalbumin-sensitized guinea pigs.

OBJECTIVES: The aim of this study was to evaluate the effect of tectorigenin on treating allergic asthma model of guinea pigs and investigate the underlying mechanisms. METHODS: Allergic asthma model of guinea pigs was established by sensitizing with ovalbumin (OVA). Then OVA-sensitized guinea pigs were injected with 10 mg/kg tectorigenin, 25 mg/kg tectorigenin or dexamethasone to investigate the effect of tectorigenin. KEY FINDINGS: High dose of tectorigenin effectively decreased the number of coughs, the number of inflammatory cells and the levels of pro-inflammatory factors. Moreover, tectorigenin could inhibit pulmonary fibrosis in guinea pigs sensitized with OVA. In addition, the functions of tectorigenin were realized through downregulating profibrotic factors of transforming growth factor (TGF)-ß1, phosphorylated (p)-Smad2/3 and Smad4, upregulating fibrosis-inhibitor of Smad7 and decreasing pro-inflammatory factors of vascular endothelial growth factor A (VEGFA), tumour necrosis factor-α (TNF-α), Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), p-inhibitor of nuclear factor-kappa B (NF-κB) kinase ß (p-IKKß) and NF-κB. CONCLUSIONS: Tectorigenin could inhibit pulmonary fibrosis and airway inflammation through TGF-ß1/Smad signalling pathway and TLR4/NF-κB signalling pathway. Therefore, tectorigenin might be a promising medicine to treat allergic asthma.