Synergistic Photothermal Therapy and Chemotherapy Enabled by Tumor Microenvironment-Responsive Targeted SWCNT Delivery.

As a novel therapeutic approach, photothermal therapy (PTT) combined with chemotherapy can synergistically produce antitumor effects. Herein, dithiodipropionic acid (DTDP) was used as a donor of disulfide bonds sensitive to the tumor microenvironment for establishing chemical bonding between the photosensitizer indocyanine green amino (ICG-NH2) and acidified single-walled carbon nanotubes (CNTs). The CNT surface was then coated with conjugates (HD) formed by the targeted modifier hyaluronic acid (HA) and 1,2-tetragacylphosphatidyl ethanolamine (DMPE). After doxorubicin hydrochloride (DOX), used as the model drug, was loaded by CNT carriers, functional nano-delivery systems (HD/CNTs-SS-ICG@DOX) were developed. Nanosystems can effectively induce tumor cell (MCF-7) death in vitro by accelerating cell apoptosis, affecting cell cycle distribution and reactive oxygen species (ROS) production. The in vivo antitumor activity results in tumor-bearing model mice, further verifying that HD/CNTs-SS-ICG@DOX inhibited tumor growth most significantly by mediating a synergistic effect between chemotherapy and PTT, while various functional nanosystems have shown good biological tissue safety. In conclusion, the composite CNT delivery systems developed in this study possess the features of high biocompatibility, targeted delivery, and responsive drug release, and can achieve the efficient coordination of chemotherapy and PTT, with broad application prospects in cancer treatment.

Rack1 regulates B-cell development and function by binding to and stabilizing the transcription factor Pax5.

The transcription factor Pax5 activates genes essential for B-cell development and function. However, the regulation of Pax5 expression remains elusive. The adaptor Rack1 can interact with multiple transcription factors and modulate their activation and/or stability. However, its role in the transcriptional control of B-cell fates is largely unknown. Here, we show that CD19-driven Rack1 deficiency leads to pro-B accumulation and a simultaneous reduction in B cells at later developmental stages. The generation of bone marrow chimeras indicates a cell-intrinsic role of Rack1 in B-cell homeostasis. Moreover, Rack1 augments BCR and TLR signaling in mature B cells. On the basis of the aberrant expression of Pax5-regulated genes, including CD19, upon Rack1 deficiency, further exploration revealed that Rack1 maintains the protein level of Pax5 through direct interaction and consequently prevents Pax5 ubiquitination. Accordingly, Mb1-driven Rack1 deficiency almost completely blocks B-cell development at the pro-B-cell stage. Ectopic expression of Pax5 in Rack1-deficient pro-B cells partially rescues B-cell development. Thus, Rack1 regulates B-cell development and function through, at least partially, binding to and stabilizing Pax5.

Mechanochemical generation of aryne.

Mechanical force is unique in promoting unusual reaction pathways and especially for the generation of reactive intermediates sometimes inaccessible to other forms of activation. The mechanochemical generation of reactive species could find application in synthetic and materials chemistry alike. However, the nature of these reactive intermediates has been mostly limited to radicals or carbenes. Here, we present a new mechanophore that generates a reactive aryne intermediate upon dissociation of a benzocyclobutene (BCB) core via a force-promoted retro [2 + 2] cycloaddition.

Comprehensive analysis of PHF5A as a potential prognostic biomarker and therapeutic target across cancers and in hepatocellular carcinoma.

OBJECTIVE: Cancer is a predominant cause of death globally. PHD-finger domain protein 5 A (PHF5A) has been reported to participate in various cancers; however, there has been no pan-cancer analysis of PHF5A. This study aims to present a novel prognostic biomarker and therapeutic target for cancer treatment. METHODS: This study explored PHF5A expression and its impact on prognosis, tumor mutation burden (TMB), microsatellite instability (MSI), functional status and tumor immunity across cancers using various public databases, and validated PHF5A expression and its correlation with survival, immune evasion, angiogenesis, and treatment response in hepatocellular carcinoma (HCC) using bioinformatics tools, qRT-PCR and immunohistochemistry (IHC). RESULTS: PHF5A was differentially expressed between tumor and corresponding normal tissues and was correlated with prognosis in diverse cancers. Its expression was also associated with TMB, MSI, functional status, tumor microenvironment, immune infiltration, immune checkpoint genes and tumor immune dysfunction and exclusion (TIDE) score in diverse malignancies. In HCC, PHF5A was confirmed to be upregulated by qRT-PCR and IHC, and elevated PHF5A expression may promote immune evasion and angiogenesis in HCC. Additionally, multiple canonical pathways were revealed to be involved in the biological activity of PHF5A in HCC. Moreover, immunotherapy and transcatheter arterial chemoembolization (TACE) worked better in the low PHF5A expression group, while sorafenib, chemotherapy and AKT inhibitor were more effective in the high expression group. CONCLUSIONS: This study provides a comprehensive understanding of the biological function of PHF5A in the carcinogenesis and progression of various cancers. PHF5A could serve as a tumor biomarker related to prognosis across cancers, especially HCC, and shed new light on the development of novel therapeutic targets.

Construction and validation of a prognostic and therapeutic cuproptosis- and immune-related gene signature in hepatocellular carcinoma.

Background: Abnormal accumulation of copper could induce cell death and tumor growth, and affect tumor immune escape by regulating programmed cell death ligand 1 (PD-L1) expression. This study aims to establish and verify a risk signature based on cuproptosis- and immune-related genes (CIRGs) for hepatocellular carcinoma (HCC) management. Methods: HCC RNA-seq and clinical data were obtained from open databases. Least absolute shrinkage and selection operator (LASSO) and Cox regression analyses were utilized to screen CIRGs and develop a risk signature. The signature's value for clinical applications, functional enrichment, tumor mutation burden (TMB), and immune profile analyses were investigated systematically. Results: A risk signature was developed utilizing seven CIRGs, and it performed well in predicting the prognosis of HCC patients in both the training and external validation cohorts. The model's risk score was discovered to be related to important clinical features. Top 15 mutated genes in HCC were significantly different among different risk groups. High-risk patients showed higher TMB, and high TMB was closely identified with a poorer prognosis. Immune profile analyses showed that immune infiltration level was higher in low-risk patients than high-risk patients, and the level of immune checkpoint genes expression varied significantly between patients in two different risk groups. Low-risk patients responded well to immunotherapy treatment, whereas high-risk patients were more sensitive to sorafenib, doxorubicin, gemcitabine and AKT (also known as protein kinase B) inhibitors. Conclusions: The established risk signature based on CIRGs can not only well predict the prognosis of HCC patients but is also promising in evaluating TMB and treatment response to immunotherapy, targeted therapy and chemotherapy, which has the potential to assist in the clinical management of HCC.

Development of a nomogram to predict 30-day mortality in patients with post-infarction ventricular septal rupture.

Ventricular septal rupture (VSR) is a mechanical complication of acute myocardial infarction (AMI), and its mortality has not decreased significantly in recent decades. However, no clinical model has been developed to predict short-term mortality in patients with post-infarction VSR (PIVSR). This study aimed to develop a nomogram to predict the 30-day mortality by using the clinical characteristics of hospitalized patients with PIVSR. The least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression analysis was used to construct a nomogram by R. The model was evaluated by the area under the curve (AUC), calibration curve and decision curve analysis (DCA). The bootstrap method was used to validate the model internally. As a result, a nomogram was constructed by using six variables, including CRRT, mechanical ventilation, PPCI, WBC, PASP and methods of treatment. The AUC of the prediction model was 0.96 (0.93, 0.98). The prediction model was well calibrated. The DCA showed that if the threshold probability was between 15% and 95%, the nomogram model would provide a net benefit. The well-constructed and evaluated nomogram can be beneficial to clinicians to predict the risk of death within 30 days in patients with PIVSR.

RACK1 enhances STAT3 stability and promotes T follicular helper cell development and function during blood-stage Plasmodium infection in mice.

CD4+ T cells are central mediators of protective immunity to blood-stage malaria, particularly for their capacity in orchestrating germinal center reaction and generating parasite-specific high-affinity antibodies. T follicular helper (Tfh) cells are predominant CD4+ effector T cell subset implicated in these processes, yet the factors and detailed mechanisms that assist Tfh cell development and function during Plasmodium infection are largely undefined. Here we provide evidence that receptor for activated C kinase 1 (RACK1), an adaptor protein of various intracellular signals, is not only important for CD4+ T cell expansion as previously implied but also plays a prominent role in Tfh cell differentiation and function during blood-stage Plasmodium yoelii 17XNL infection. Consequently, RACK1 in CD4+ T cells contributes significantly to germinal center formation, parasite-specific IgG production, and host resistance to the infection. Mechanistic exploration detects specific interaction of RACK1 with STAT3 in P. yoelii 17XNL-responsive CD4+ T cells, ablation of RACK1 leads to defective STAT3 phosphorylation, accompanied by substantially lower amount of STAT3 protein in CD4+ T cells, whereas retroviral overexpression of RACK1 or STAT3 in RACK1-deficient CD4+ T cells greatly restores STAT3 activity and Bcl-6 expression under the Tfh polarization condition. Further analyses suggest RACK1 positively regulates STAT3 stability by inhibiting the ubiquitin-proteasomal degradation process, thus promoting optimal STAT3 activity and Bcl-6 induction during Tfh cell differentiation. These findings uncover a novel mechanism by which RACK1 participates in posttranslational regulation of STAT3, Tfh cell differentiation, and subsequent development of anti-Plasmodium humoral immunity.

Diagnóstico prenatal de clorhidrorrea congénita: reporte de caso / Prenatal diagnosis of congenital chloride diarrhea: A case report

La clorhidrorrea congénita es un trastorno genético infrecuente pero importante caracterizado por una alteración grave del balance hidroelectrolítico como resultado de un defecto en la absorción intestinal de cloruros. Los niños afectados presentan diarrea persistente, deshidratación y malnutrición; el control médico y del desarrollo son complejos. Mejorar la detección prenatal es esencial para facilitar la atención del paciente, las intervenciones tempranas y el asesoramiento genético informado. Sin embargo, a pesar de los avances de la medicina, la naturaleza compleja y la escasa frecuencia de esta entidad, constituyen un desafío para la detección prenatal. En este estudio, se reporta el caso de una embarazada donde los estudios por imágenes de resonancia magnética fetales identificaron en forma efectiva las características típicas de la clorhidrorrea congénita. Se proveen conocimientos sobre las complejidades del diagnóstico y se sugieren caminos para las estrategias de detección temprana de esta enfermedad.

Congenital chloride diarrhea (CCD) is a rare but significant genetic disorder characterized by severe electrolyte imbalances resulting from impaired intestinal chloride absorption. Affected children experience persistent diarrhea, dehydration, and malnutrition, complicating medical and developmental care. The enhancement of prenatal detection is crucial for improved patient management, early interventions, and informed genetic counseling. However, despite advancements in medicine, the complex nature and rarity of CCD make prenatal detection challenging. In this study, we report a fetal case where prenatal magnetic resonance imaging (MRI) effectively identified the distinctive characteristics of CCD, providing insights into the complexities of diagnosis and suggesting avenues for enhanced early detection strategies.

Mussel-Mimetic Hydrogel Coating with Anticoagulant and Antiinflammatory Properties on a Poly(lactic acid) Vascular Stent.

Biodegradable stents are the most promising alternatives for the treatment of cardiovascular disease nowadays, and the strategy of preparing functional coatings on the surface is highly anticipated for addressing adverse effects such as in-stent restenosis and stent thrombosis. Yet, inadequate mechanical stability and biomultifunctionality limit their clinical application. In this study, we developed a multicross-linking hydrogel on the polylactic acid substrates by dip coating that boasts impressive antithrombotic ability, antibacterial capability, mechanical stability, and self-healing ability. Gelatin methacryloyl, carboxymethyl chitosan, and oxidized sodium alginate construct a double-cross-linking hydrogel through the dynamic Schiff base chemical and in situ blue initiation reaction. Inspired by the adhesion mechanism employed by mussels, a triple-cross-linked hydrogel is formed with the addition of tannic acid to increase the adhesion and antibiofouling properties. The strength and hydrophilicity of hydrogel coating are regulated by changing the composition ratio and cross-linking degree. It has been demonstrated in tests in vitro that the hydrogel coating significantly reduces the adhesion of proteins, MC3T3-E1 cells, platelets, and bacteria by 85% and minimizes the formation of blood clots. The hydrogel coating also exhibits excellent antimicrobial in vitro and antiinflammatory properties in vivo, indicating its potential value in vascular intervention and other biomedical fields.

PTEN deficiency induces an extrahepatic cholangitis-cholangiocarcinoma continuum via aurora kinase A in mice.

BACKGROUND & AIMS: The PTEN-AKT pathway is frequently altered in extrahepatic cholangiocarcinoma (eCCA). We aimed to evaluate the role of PTEN in the pathogenesis of eCCA and identify novel therapeutic targets for this disease. METHODS: The Pten gene was genetically deleted using the Cre-loxp system in biliary epithelial cells. The pathologies were evaluated both macroscopically and histologically. The characteristics were further analyzed by immunohistochemistry, reverse-transcription PCR, cell culture, and RNA sequencing. Some features were compared to those in human eCCA samples. Further mechanistic studies utilized the conditional knockout of Trp53 and Aurora kinase A (Aurka) genes. We also tested the effectiveness of an Aurka inhibitor. RESULTS: We observed that genetic deletion of the Pten gene in the extrahepatic biliary epithelium and peri-ductal glands initiated sclerosing cholangitis-like lesions in mice, resulting in enlarged and distorted extrahepatic bile ducts in mice as early as 1 month after birth. Histologically, these lesions exhibited increased epithelial proliferation, inflammatory cell infiltration, and fibrosis. With aging, the lesions progressed from low-grade dysplasia to invasive carcinoma. Trp53 inactivation further accelerated disease progression, potentially by downregulating senescence. Further mechanistic studies showed that both human and mouse eCCA showed high expression of AURKA. Notably, the genetic deletion of Aurka completely eliminated Pten deficiency-induced extrahepatic bile duct lesions. Furthermore, pharmacological inhibition of Aurka alleviated disease progression. CONCLUSIONS: Pten deficiency in extrahepatic cholangiocytes and peribiliary glands led to a cholangitis-to-cholangiocarcinoma continuum that was dependent on Aurka. These findings offer new insights into preventive and therapeutic interventions for extrahepatic CCA. IMPACT AND IMPLICATIONS: The aberrant PTEN-PI3K-AKT signaling pathway is commonly observed in human extrahepatic cholangiocarcinoma (eCCA), a disease with a poor prognosis. In our study, we developed a mouse model mimicking cholangitis to eCCA progression by conditionally deleting the Pten gene via Pdx1-Cre in epithelial cells and peribiliary glands of the extrahepatic biliary duct. The conditional Pten deletion in these cells led to cholangitis, which gradually advanced to dysplasia, ultimately resulting in eCCA. The loss of Pten heightened Akt signaling, cell proliferation, inflammation, fibrosis, DNA damage, epigenetic signaling, epithelial-mesenchymal transition, cell dysplasia, and cellular senescence. Genetic deletion or pharmacological inhibition of Aurka successfully halted disease progression. This model will be valuable for testing novel therapies and unraveling the mechanisms of eCCA tumorigenesis.

GJ Express: an improvement initiative to decrease sedation and anesthesia for gastrojejunostomy tube exchanges.

BACKGROUND: Overuse of sedation and anesthesia causes delays in gastrojejunostomy tube (GJ) exchanges, increased risk of complications, unnecessary use of resources, preventable hospital admissions, and an adverse impact on patient and family experience. Our hospital was over-utilizing sedation and anesthesia, and we aimed to decrease this use from 78% to 20% within two years. METHODS: An interdisciplinary quality improvement team comprehensively evaluated current processes for GJ tube exchanges through a retrospective chart review for baseline data with prospective time series analysis after improvement implementation. The primary outcome measure was the percentage of pediatric patients that utilized sedation or anesthesia for routine GJ tube exchanges. RESULTS: A statistical process control p-chart was used to calculate and show changes over time for patients (n = 45 patients average). The median percent of pediatric GJ tube exchanges performed with sedation or anesthesia decreased from 77.8% to 11.3%. Most patients (76%) were covered by Medicaid programs; with low reimbursement rates, decreased anesthesiologist billing revenue does not have a negative financial impact. CONCLUSIONS: An interprofessional improvement initiative that engaged patients and families, incorporated pediatric-specific staff services, and developed systematic weaning was associated with a significant decrease in the overuse of sedation and anesthesia for GJ tube exchanges. IMPACT: We believe that this work is highly relevant and impactful for medical centers caring for children who require gastrojejunostomy tubes, an increasingly common approach to management of children with feeding issues. There is very little literature available on the use of sedation or anesthesia for changing these tubes. While large children's medical centers in the USA usually do not utilize sedation or anesthesia, there are likely many serious outliers, especially when children receive care outside of a pediatric specific institution. This paper brings awareness to this serious issue and provides information about how we changed care to achieve higher patient safety and lower medical costs.

Research on the antipruritic active ingredients of Mikania micrantha.

Mikania micrantha is a perennial liana of the genus Mikania of the Asteraceae family. It is a commonly used medicine in South America for treating fever, malaria, dysentery, snake bites, etc. Because of its strong adaptability and ability to inhibit the growth of its associated plants, Mikania micrantha is considered an invasive species in China and is known as a plant killer. Preliminary studies have shown that Mikania micrantha has an antipruritic effect, but the antipruritic active substance is not yet clear. In this study, a 4-aminopyridine-induced itching model in mice was used to determine the antipruritic effects of petroleum ether, ethyl acetate, ethanol extraction site, and Mikania micrantha volatile oil. GC-MS was used to analyze the components of the antipruritic fractions, combined with mice itch-causing models to study the antipruritic effects of ß-caryophyllene and humulene. The safety of ß-caryophyllene was preliminarily evaluated through the acute toxicity test of mice skin. The ethyl acetate and volatile oil of Mikania micrantha have apparent antipruritic effects. Humulene and ß-caryophyllene have a quantitative-effective relationship to inhibit itching in mice. The acute toxicity test of mouse skin showed that ß-caryophyllene has no acute toxicity. This study indicated that the main antipruritic active ingredients of Mikania micrantha are ß-caryophyllene and humulene.

Prenatal diagnosis of congenital chloride diarrhea: A case report. / Diagnóstico prenatal de clorhidrorrea congénita: reporte de caso.

Congenital chloride diarrhea (CCD) is a rare but significant genetic disorder characterized by severe electrolyte imbalances resulting from impaired intestinal chloride absorption. Affected children experience persistent diarrhea, dehydration, and malnutrition, complicating medical and developmental care. The enhancement of prenatal detection is crucial for improved patient management, early interventions, and informed genetic counseling. However, despite advancements in medicine, the complex nature and rarity of CCD make prenatal detection challenging. In this study, we report a fetal case where prenatal magnetic resonance imaging (MRI) effectively identified the distinctive characteristics of CCD, providing insights into the complexities of diagnosis and suggesting avenues for enhanced early detection strategies.

La clorhidrorrea congénita es un trastorno genético infrecuente pero importante caracterizado por una alteración grave del balance hidroelectrolítico como resultado de un defecto en la absorción intestinal de cloruros. Los niños afectados presentan diarrea persistente, deshidratación y malnutrición; el control médico y del desarrollo son complejos. Mejorar la detección prenatal es esencial para facilitar la atención del paciente, las intervenciones tempranas y el asesoramiento genético informado. Sin embargo, a pesar de los avances de la medicina, la naturaleza compleja y la escasa frecuencia de esta entidad, constituyen un desafío para la detección prenatal. En este estudio, se reporta el caso de una embarazada donde los estudios por imágenes de resonancia magnética fetales identificaron en forma efectiva las características típicas de la clorhidrorrea congénita. Se proveen conocimientos sobre las complejidades del diagnóstico y se sugieren caminos para las estrategias de detección temprana de esta enfermedad.

Recycling Waste Glyceroborate to Aqueous Lubricant for Tribological Applications.

The present study attempts to explore the direct recyclability of glyceroborate from medicine pharmaceutical production wastewater into an aqueous lubricant instead of conventional waste processing methods from the tribological view. In order to determine the tribological feasibility, the physicochemical properties of crude pharmaceutical wastewater are investigated and compared with those of pure glycerol to access their potential lubrication properties. The results demonstrated that the crude pharmaceutical wastewater has better friction-reducing and antiwear properties under the same working conditions. Besides outstanding lubricating properties, the friction-induced formation of borate tribo-film and intermediate FeOOH compound favors lowering of the shear stress between the rubbing surfaces. This finding better provides an alternative to transform glyceroborate from medicine pharmaceutical production wastewater after simple distillation processing to a potential aqueous lubricant.

A Novel Strategy for Whole-Cell Biotransformation Enabling Simultaneous l-Phenyllactic Acid Production and Coenzyme Regeneration.

l-Phenyllactic acid (l-PLA) is a small molecular organic acid that exhibits a powerful capacity for inhibition against foodborne pathogens. In this work, we developed a new cost-effective and environmentally friendly process for the biosynthesis of l-PLA. This strategy designed a novel whole-cell biotransformation system employing two heterologous enzymes, namely, phenylalanine dehydrogenase (PheDH) and l-hydroxyisocaproate dehydrogenase (l-HicDH). The novelty of this strategy lies in the first-time utilization of these two enzymes, which not only enables cascade catalysis for the production of l-PLA but also facilitates the regeneration of the coenzymes (NAD+/NADH) using only two enzymes rather than introducing more heterologous enzymes to the system. Consequently, this strategy can effectively simplify the biosynthesis process of l-PLA and minimize production costs. The initial l-PLA yield using this process achieved 2.53 ± 0.07 g/L. Furthermore, through meticulous optimization of the parameters for inducible enzyme expression and l-PLA biosynthesis, the l-PLA yield was successfully increased to 4.68 ± 0.04 g/L with a yield rate of 64.54 ± 0.29%. Moreover, this novel strategy is versatile in the biosynthesis of other organic acids, which can be achieved by easily modulating the combinations of substrates and enzymes.

Facile construction of drugs loaded lipid-coated calcium carbonate as a promising pH-Dependent drug delivery system for thyroid cancer treatment.

To develop innovative drug delivery carriers for controllable release and cancer-targeted delivery of therapeutic agents to accomplish efficient cancer chemotherapy. Herein we effectively fabricated CaCO3 primarily loaded biotin (BT) and directly the self-assembly of oxaliplatin (Pt (IV)) prodrugs form in liposomes. The acquired BT-Pt (IV)@PEG/CaCO3 with outstanding biological stability displays rapid pH-mediated degradations, thus allowing the effective pH-responsive delivery of BT. In vitro, anticancer assays proved that BT-Pt (IV)@PEG/CaCO3 effectively kills the thyroid cancer cells (B-CPAP and FTC-133). The biochemical staining assays investigated the morphological changes of thyroid cancer after treatment with nanoparticles. The DNA fragmentation of the cells was assessed by utilizing the comet assay. BT-Pt (IV)@PEG/CaCO3 increased ROS levels and caused mitochondrial membrane potential and DNA damage, which resulted in apoptosis. Due to its versatile drug-loading capability, this research demonstrates that CaCO3 liposomal formulation is a biocompatible and reliable substrate for establishing pH-mediated drug delivery methods and promising for possible therapeutic application.

Development and validation of novel immune-inflammation-based clinical predictive nomograms in HER2-negative advanced gastric cancer.

Purpose: To explore the predictive value of multiple immune-inflammatory biomarkers including serum VEGFA and systemic immune-inflammation index (SII) in HER2-negative advanced gastric cancer (AGC) and establish nomograms for predicting the first-line chemotherapeutic efficacy, progression-free survival (PFS) and overall survival (OS) of patients with this fatal disease. Methods: From November 2017 to April 2022, 102 and 34 patients with a diagnosis of HER2-negative AGC at the First Affiliated Hospital of Bengbu Medical College were enrolled as development and validation cohorts, respectively. Univariate and multivariate analyses were performed to evaluate the clinical value of the candidate indicators. The variables were screened using LASSO regression analysis. Predictive models were developed using significant predictors and are displayed as nomograms. Results: Baseline VEGFA expression was significantly higher in HER2-negative AGC patients than in nonneoplastic patients and was associated with malignant serous effusion and therapeutic efficacy (all p<0.001). Multivariate analysis indicated that VEGFA was an independent predictor for first-line therapeutic efficacy and PFS (both p<0.01) and SII was an independent predictor for first-line PFS and OS (both p<0.05) in HER2-negative AGC patients. The therapeutic efficacy model had an R2 of 0.37, a Brier score of 0.15, and a Harrell's C-index of 0.82 in the development cohort and 0.90 in the validation cohort. The decision curve analysis indicated that the model added more net benefits than VEGFA assessment alone. The PFS/OS models had Harrell's C-indexes of 0.71/0.69 in the development cohort and 0.71/0.62 in the validation cohort. Conclusion: The established nomograms integrating serum VEGFA/SII and commonly available baseline characteristics provided satisfactory performance in predicting the therapeutic efficacy and prognosis of HER2-negative AGC patients.

Antitumor activity of a whey peptide-based enteral diet in C26 colon tumor-bearing mice.

The antitumor effects of a whey peptide-based enteral diet, whose main components are whey peptides and yogurt fermented by Lactobacillus delbureckii subsp. bulgaricus 2038 and Streptococcus thermophilus 1131, were investigated in mice. Our results indicated that the tumor weight in C26 carcinoma-transplanted mice was significantly smaller at day 16 post-implantation in the whey peptide-based enteral diet group (1.36 ± 0.54 g) than in the control group (1.83 ± 0.89 g) (p < 0.05). The whey peptide-based enteral diet group exhibited higher tumor cell apoptosis, lower cell proliferation, and inactive angiogenesis indicating by higher degree of TUNEL, lower positive rates of Ki-67, VEGF, and CD34 than control group. It also attenuated inflammatory cell infiltration of spleen and liver as indicated by the decreased spleen index (10.89 ± 2.06 vs. 12.85 ± 2.92, p < 0.05) and increased liver index (58.09 ± 11.37 vs. 53.19 ± 6.67, p < 0.05) in the whey peptide-based enteral diet group than the control diet group. These results proved the inhibitory effect of the whey peptide-based enteral diet on tumor growth, which might be attributed to the whey peptides component. PRACTICAL APPLICATION: A whey peptide-based enteral diet (MEIN® ), containing cheese whey and multiple nutrients, was selected to verify the anti-tumor effect by animal experiments. The tumor weight growth, tumor cell proliferation, inflammatory cell infiltration of spleen and liver in tumor model mice was significantly attenuated by the whey peptide-based enteral diet, that might be attributed to its whey peptides component. These results provided an additive direction for cancer therapy and need a further study including clinical trials.

Changes in process and outcome for ST elevation myocardial infarction in central China from 2011 to 2018.

BACKGROUND: Limited data are available on the changes in the quality of care for ST elevation myocardial infarction (STEMI) during China's health system reform from 2009 to 2020. This study aimed to assess the changes in care processes and outcome for STEMI patients in Henan province of central China between 2011 and 2018. METHODS: We compared the data from the Henan STEMI survey conducted in 2011-2012 ( n = 1548, a cross-sectional study) and the Henan STEMI registry in 2016-2018 ( n = 4748, a multicenter, prospective observational study). Changes in care processes and in-hospital mortality were determined. Process of care measures included reperfusion therapies, aspirin, P2Y12 antagonists, ß-blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and statins. Therapy use was analyzed among patients who were considered ideal candidates for treatment. RESULTS: STEMI patients in 2016-2018 were younger (median age: 63.1 vs . 63.8 years) with a lower proportion of women (24.4% [1156/4748] vs . 28.2% [437/1548]) than in 2011-2012. The composite use rate for guideline-recommended treatments increased significantly from 2011 to 2018 (60.9% [5424/8901] vs . 82.7% [22,439/27,129], P <0.001). The proportion of patients treated by reperfusion within 12 h increased from 44.1% (546/1237) to 78.4% (2698/3440) ( P <0.001) with a prolonged median onset-to-first medical contact time (from 144 min to 210 min, P <0.001). The use of antiplatelet agents, statins, and ß-blockers increased significantly. The risk of in-hospital mortality significantly decreased over time (6.1% [95/1548] vs . 4.2% [198/4748], odds ratio [OR]: 0.67, 95% confidence interval [CI]: 0.50-0.88, P = 0.005) after adjustment. CONCLUSIONS: Gradual implementation of the guideline-recommended treatments in STEMI patients from 2011 to 2018 has been associated with decreased in-hospital mortality. However, gaps persist between clinical practice and guideline recommendation. Public awareness, reperfusion strategies, and construction of chest pain centers need to be further underscored in central China.

Fluoxetine partially alleviates inflammation in the kidney of socially stressed male C57 BL/6 mice.

Stress-related illnesses are linked to the onset and progression of renal diseases and depressive disorders. To investigate stress-induced changes in the renal transcriptome associated with the development of depressive behaviors, we generated here a chronic social defeat stress (CSDS) model of C57 BL/6 male mice and then performed RNA sequencing of the kidneys to obtain an inflammation-related transcriptome. Administration of the antidepressant drug fluoxetine (10 mg·kg-1 ·day-1 ) during CSDS induction could partially alleviate renal inflammation and reverse CSDS-induced depression-like behaviors. Moreover, fluoxetine also modulated gene expression of stress-related hormone receptors, including prolactin and melanin-concentrating hormone. These results suggest that CSDS can induce gene expression changes associated with inflammation in the kidney of C57 BL/6 male mice, and this inflammation can be treated effectively by fluoxetine.