A virulent milRNA inhibits host immunity by silencing a host receptor-like kinase MaLYK3 and facilitates infection by Fusarium oxysporum f. sp. cubense.

MicroRNA-like RNAs (milRNAs) play a significant role in the infection process by plant-pathogenic fungi. However, the specific functions and regulatory mechanisms of fungal milRNAs remain insufficiently elucidated. This study investigated the function of Foc-milR138, an infection-induced milRNA secreted by Fusarium oxysporum f. sp. cubense (Foc), which is the causal agent of Fusarium wilt of banana. Initially, through precursor gene knockout and phenotypic assessments, we confirmed that Foc-milR138 acts as a virulent milRNA prominently upregulated during the early stages of Foc infection. Subsequent bioinformatic analyses and transient expression assays in Nicotiana benthamiana leaves identified a host receptor-like kinase gene, MaLYK3, as the direct target of Foc-milR138. Functional investigations of MaLYK3 revealed its pivotal role in triggering immune responses of N. benthamiana by upregulating a suite of resistance genes, bolstering reactive oxygen species (ROS) accumulation and callose deposition, thereby fortifying disease resistance. This response was markedly subdued upon co-expression with Foc-milR138. Expression pattern analysis further verified the specific suppression of MaLYK3 by Foc-milR138 during the early root infection by Foc. In conclusion, Foc secretes a virulent milRNA (Foc-milR138) to enter the host banana cells and inhibit the expression of the plant surface receptor-like kinase MaLYK3, subverting the disease resistance activated by MaLYK3, and ultimately facilitating pathogen invasion. These findings shed light on the roles of fungal milRNAs and their targets in resistance and pathogenicity, offering promising avenues for the development of disease-resistant banana cultivars.

Evaluation of immune and pyroptosis status in a model of sepsis-induced secondary pneumonia.

In recent years, researchers have focused on studying the mechanism of sepsis-induced immunosuppression, but there is still a lack of suitable animal models that accurately reflect the process of sepsis-induced immunosuppression. The aim of this study was to evaluate the immune status at various stages in a model of sepsis-induced secondary pneumonia and to demonstrate whether pyroptosis is one of the modes of immune cell death in sepsis. Firstly, we established a sepsis model in C57BL/6J mice using cecal ligation and puncture (CLP). The surviving mice were treated with a 40 µL suspension of P.aeruginosa (Pa) under anesthesia on day 4 post-CLP to establish a sepsis-induced secondary pneumonia model. Secondly, routine blood tests, serum ALT and PCT levels, gross lung specimens, and H&E staining of the lung and liver tissues were used to assess the successful establishment of this model. Serum levels of TNF-α and IL-6, the CD4+/CD8+ratio in blood, H&E staining of the spleen, and immunohistochemistry of CD4 and CD8 in the spleen were detected to evaluate the immune status of the model mice. Finally, the expression levels of pyroptosis-related proteins in the spleen were detected by Western blot. The expression of GSDMD was assessed using immunohistochemistry, and pyroptosis was directly observed through transmission electron microscopy. The experimental results above confirmed the successful construction of the model for sepsis-induced secondary pneumonia, demonstrating its ability to reflect sepsis-induced immunosuppression. Moreover, the expression of pyroptosis-related proteins, immunohistochemical GSDMD, and transmission electron microscopy of the spleen showed that pyroptosis was one of the modes of immune cell death in sepsis.

Acutalibacter caecimuris sp. nov., Acutalibacter intestini sp. nov. and Neglectibacter caecimuris sp. nov., three novel species of the family Oscillospiraceae isolated from caecal contents of C57BL/6J mice.

The intestines of mice are colonized by diverse, as-yet-uncultivated bacteria. In this report, we describe the isolation, culture, genotypic and phenotypic characterization, as well as taxonomic classification of three novel anaerobic bacterial strains derived from the caecal contents of C57BL/6J male mice. According to the phenotypic and genotype-based polyphasic taxonomy, we propose three novel species within the family Oscillospiraceae. They are Acutalibacter caecimuris sp. nov. (type strain M00118T=CGMCC 1.18042T=KCTC 25739T), Acutalibacter intestini sp. nov. (type strain M00204T=CGMCC 1.18044T=KCTC 25741T) and Neglectibacter caecimuris sp. nov. (type strain M00184T=CGMCC 1.18043T=KCTC 25740T).

Zero-profile implant system versus novel plate systems after ACDF for comparison of sagittal balance parameters and clinical efficacy analysis.

BACKGROUND: The zero-profile implant system (Zero-P) and conventional plates have been widely used in anterior cervical discectomy and fusion (ACDF) to treat cervical spondylosis. The purpose of this study was to compare the effects of the application of Zero-P and new conventional plates (ZEVO, Skyline) in ACDF on the sagittal imaging parameters of cervical spondylosis patients and to analyze their clinical efficacy. METHODS: We conducted a retrospective study on 119 cervical spondylosis patients from January 2018 to December 2021, comparing outcomes between those receiving the Zero-P device (n = 63) and those receiving a novel conventional plate (n = 56, including 46 ZEVO and 10 Skyline plates) through ACDF. Cervical sagittal alignment was assessed pre- and postoperatively via lateral radiographs. The Japanese Orthopedic Association (JOA), Neck Disability Index (NDI), and visual analog scale (VAS) scores were recorded at baseline, after surgery, and at the 2-year follow-up to evaluate patient recovery and intervention success. RESULTS: There were significant differences in the postoperative C0-C2 Cobb angle and postoperative sagittal segmental angle (SSA) between patients in the novel conventional plate group and those in the Zero-P group (P < 0.05). Postoperatively, there were significant changes in the C2‒C7 Cobb angle, C0‒C2 Cobb angle, SSA, and average surgical disc height (ASDH) compared to the preoperative values in both patient groups (P < 0.05). Dysphagia in the immediate postoperative period was lower in the Zero-P group than in the new conventional plate group (0% in the Zero-P group, 7.14% in the novel conventional plate group, P = 0.046), and the symptoms disappeared within 2 years in both groups. There was no statistically significant difference between the two groups in terms of complications of adjacent spondylolisthesis (ASD) at 2 years postoperatively (3.17% in the Zero-P group, 8.93% in the novel conventional plate group; P = 0.252). According to the subgroup analysis, there were significant differences in the postoperative C2‒C7 Cobb angle, C0‒C2 Cobb angle, T1 slope, and ASDH between the ZEVO group and the Skyline group (P < 0.05). Compared with the preoperative scores, the JOA, NDI, and VAS scores of all groups significantly improved at the 2-year follow-up (P < 0.01). According to the subgroup analysis, the immediate postoperative NDI and VAS scores of the ZEVO group were significantly better than those of the Skyline group (P < 0.05). CONCLUSION: In ACDF, both novel conventional plates and Zero-P can improve sagittal parameters and related scale scores. Compared to the Zero-P plate, the novel conventional plate has a greater advantage in correcting the curvature of the surgical segment, but the Zero-P plate is less likely to produce postoperative dysphagia.

A Computational and Chemical Design Strategy for Manipulating Glycan-Protein Recognition.

Glycans are complex biomolecules that encode rich information and regulate various biological processes, such as fertilization, host-pathogen binding, and immune recognition, through interactions with glycan-binding proteins. A key driving force for glycan-protein recognition is the interaction between the π electron density of aromatic amino acid side chains and polarized C─H groups of the pyranose (termed the CH-π interaction). However, the relatively weak binding affinity between glycans and proteins has hindered the application of glycan detection and imaging. Here, computational modeling and molecular dynamics simulations are employed to design a chemical strategy that enhances the CH-π interaction between glycans and proteins by genetically incorporating electron-rich tryptophan derivatives into a lectin PhoSL, which specifically recognizes core fucosylated N-linked glycans. This significantly enhances the binding affinity of PhoSL with the core fucose ligand and enables sensitive detection and imaging of core fucosylated glycans in vitro and in xenograft tumors in mice. Further, the study showed that this strategy is applicable to improve the binding affinity of GafD lectin for N-acetylglucosamine-containing glycans. The approach thus provides a general and effective way to manipulate glycan-protein recognition for glycoscience applications.

The effect of physical therapy and mechanical stimulation on dysfunction of lower extremities after total pelvic exenteration in cervical carcinoma patient with rectovesicovaginal fistula induced by radiotherapy: a case report.

BACKGROUND: Total pelvic exenteration is the ultimate solution for rectovesicovaginal fistula caused by radiation therapy, yet total pelvic exenteration frequently causes intraoperative complications and postoperative complications. These complications are responsible for the dysfunction of lower extremities, impaired quality of life, and even the high long-term morbidity rate, thus multidisciplinary cooperation and early intervention for prevention of complications are necessary. Physical therapy was found to reduce the postoperative complications and promote rehabilitation, yet the effect on how physiotherapy prevents and treats complications after total pelvic exenteration and pelvic lymphadenectomy remains unclear. CASE PRESENTATION: A 50-year-old Chinese woman gradually developed perianal and pelvic floor pain and discomfort, right lower limb numbness, and involuntary vaginal discharge owing to recurrence and metastasis of cervical cancer more than half a year ago. Diagnosed as rectovesicovaginal fistula caused by radiation, she received total pelvic exenteration and subsequently developed severe lower limb edema, swelling pain, obturator nerve injury, and motor dysfunction. The patient was referred to a physiotherapist who performed rehabilitation evaluation and found edema in both lower extremities, right inguinal region pain (numeric pain rate scale 5/10), decreased temperature sensation and light touch in the medial thigh of the right lower limb, decreased right hip adductor muscle strength (manual muscle test 1/5) and right hip flexor muscle strength (manual muscle test 1/5), inability actively to adduct and flex the right hip with knee extension, low de Morton mobility Index score (0/100), and low Modified Barthel Index score (35/100). Routine physiotherapy was performed in 2 weeks, including therapeutic exercises, mechanical stimulation and electrical stimulation as well as manual therapy. The outcomes showed that physiotherapy significantly reduced lower limb pain and swelling, and improved hip range of motion, motor function, and activities of daily living, but still did not prevent thrombosis. CONCLUSION: Standardized physical therapy demonstrates the effect on postoperative complications after total pelvic exenteration and pelvic lymphadenectomy. This supports the necessity of multidisciplinary cooperation and early physiotherapy intervention. Further research is needed to determine the causes of thrombosis after standardized intervention, and more randomized controlled trials are needed to investigate the efficacy of physical therapy after total pelvic exenteration.

Foraminoplasty Performed with a Trephine and a New Tool in Transforaminal Endoscopic Lumbar Discectomy: A Single-Center Retrospective Study.

OBJECTIVE: Foraminoplasty is an important step in transforaminal endoscopic lumbar discectomy (TELD). A trephine is widely used in foraminoplasty. However, foraminoplasty using a trephine alone sometimes fails to remove the resected bone, resulting in the bone remaining in the foramen or spinal canal, which can potentially cause neurological irritation or injury. The objective of this study is to introduce a self-designed tool, referred to as an anchoring drill, for use with a trephine in foraminoplasty in TELD and to evaluate its advantages. METHODS: A retrospective review was performed to identify patients who underwent L4-5 TELD between January 2019 to January 2022. Foraminoplasty was performed in all patients. Depending on whether the anchoring drill was used or not, patients were divided into two groups. Surgery-related parameters and complications were reviewed. Visual analog scale (VAS) and Japanese Orthopaedic Association (JOA) scores were also assessed for all patients. SPSS statistical software was used for statistical calculation. RESULTS: A total of 100 patients were included (55 in the anchoring drill group and 45 in the trephine group). The incidence of residual bone fragments after foraminoplasty of the anchoring drill group was 9.09%, which was lower than that of the trephine group, at 33.33% (p < 0.05). The mean endoscopic operation time of the anchoring drill group was shorter than that of the trephine group (p < 0.05). The mean fluoroscopy time and duration of foraminoplasty showed no significant differences between the two cohorts. The total perioperative complication incidence was lower in the anchoring drill group, in which the neural irritation incidence showed a significant difference (anchoring drill group: 3.64%, trephine group: 17.78%, p < 0.05). VAS and JOA scores were significantly improved after the operation for all patients (p < 0.001), however, no statistical differences were found between the two groups at each follow-up visit. CONCLUSION: The combination of a trephine with an anchor drill was demonstrated to be safe and effective in foraminoplasty in TELD, improving the success rate of foraminoplasty and reducing neurological complications compared to using trephine alone.

Ovarian cancer disease burden decreased in the United States from 1975 to 2018: A joinpoint and age-period-cohort analysis.

Ovarian cancer (OC) is the leading cause of gynecological cancer-related deaths in the United States. The purpose of this study was to evaluate long-term trends in OC incidence and incidence-based mortality rates (IBM) in the U.S. from 1975 to 2018 and to assess the effects of age, period, and cohort factors on OC incidence and mortality using an age-period-cohort model. We obtained data from the U.S. OC incidence/mortality data from the Surveillance, Epidemiology, and End Results database from 1975 to 2018. Joinpoint regression analysis was used to determine long-term trends and transitions, and an age-period-cohort model was used to quantify the effects of age, period, and cohort parameters on incidence and mortality. In addition, 1990 to 2019 U.S. OC data obtained from the Global Burden of Disease study served as a potential validation set. Between 1975 and 2018, 80,622 new cases of OC and 60,218 deaths from OC were reported in the U.S. The average annual percent change for OC incidence was -1.33 (95% CI: -1.64 to -1.02, P < .001), with a significant decrease in incidence at a rate of 7.80% (95% CI: -11.52 to -3.92) per year from to 2015-2018. IBM reached its peak for the U.S. population in 1994, with an age-standardized mortality rate of 6.38 (per 100,000 people). IBM rose first, peaked in 1986, and then declined at a rate of 0.39% (95% CI: -0.66 to -0.12) and 2.48% (95% CI: -3.09 to -1.85) per year from to 1986-2007 and 2007-2018, respectively. In addition, age-period-cohort model analysis showed the highest risk of OC incidence in 1980 to 1984 and the highest risk of OC death in 1985-1989. This study reported a significant decline in OC morbidity and mortality in the U.S. since 1986. In addition, this study analyzed the changes in trends in OC incidence and mortality by race/ethnicity in the U.S. Monitoring trends in OC incidence and mortality by race/ethnicity can help in the development of targeted prevention and treatment measures.

Construction and immune evaluation of the recombinant duck adenovirus type 3 delivering capsid protein VP1 of the type 1 duck hepatitis virus.

Adenovirus serves as an excellent viral vector and is employed in vector vaccine research. Duck hepatitis A virus type 1 (DHAV1) and duck adenovirus type 3 (DAdV3) cause significant economic losses in the Chinese duck industry. In this study, we found an excellent exogenous gene insertion site in DAdV3 genome of CH-GD-12-2014 strain, within 3 intergenic regions (IGR). Subsequently, we generated a recombinant duck adenovirus named rDAdV3-VP1-188, which exhibits excellent replication characteristics and immunogenicity of DAdV3 and DHAV1. Animal experiments showed that rDAdV3-VP1-188 can provide 100% protection against the DAdV3 and 80% protection against DHAV1. These results showed that rDAdV3-VP1-188 could induce protection against DAdV3 and DHAV1 in ducks, thus indicating the feasibility of DAdV3 as a vector for the development of avian vector vaccines. These insights contribute to the further development of DAdV3 vectors and other adenovirus vectors.

New treatment insights into pancreatic acinar cell carcinoma: case report and literature review.

Pancreatic acinar cell carcinoma (PACC) is a rare pancreatic malignancy with unique clinical, molecular, and morphologic features. The long-term survival of patients with PACC is substantially better than that of patients with ductal adenocarcinoma of the pancreas. Surgical resection is considered the first choice for treatment; however, there is no standard treatment option for patients with inoperable disease. The patient with metastatic PACC reported herein survived for more than 5 years with various treatments including chemotherapy, radiotherapy, antiangiogenic therapy and combined immunotherapy.

SETD2-H3K36ME3: an important bridge between the environment and tumors.

Epigenetic regulation plays an important role in the occurrence, development and treatment of tumors. The histone methyltransferase SET-domain-containing 2 (SETD2) plays a key role in mammalian epigenetic regulation by catalyzing histone methylation and interacting with RNA polymerase II to mediate transcription elongation and mismatch repair. As an important bridge between the environment and tumors, SETD2-H3K36me3 plays an important role in the occurrence and development of tumors. Many tumors, including renal cancer, gastric cancer, lung cancer, are closely related to SETD2 gene mutations. As a key component of common tumor suppressor mechanisms, SETD2-H3K36me3is an important target for clinical disease diagnosis and treatment. Here, we reviewed the structure and function of the SETD2 and how SETD2-H3K36me3 functions as a bridge between the environment and tumors to provide an in-depth understanding of its role in the occurrence and development of various tumors, which is of great significance for future disease diagnosis and treatment.

Chromium-Doped Nickel Oxide and Nickel Nitride Mediate Selective Electrocatalytic Oxidation of Sterol Intermediates Coupled with H2 Evolution.

Replacing the oxygen evolution reaction (OER) with the thermodynamically favorable electrooxidation of organics is considered a promising approach for the simultaneous production of hydrogen (H2 ) and high-value chemicals. However, exploring and optimizing efficient electrocatalysts remains a challenge for large-scale production of value-added steroid carbonyl and H2 . Herein, Cr-NiO/GF and Cr-Ni3 N/GF (GF: graphite felt) electrocatalysts were designed as anode and cathode for the production of steroid carbonyls and H2 , respectively. The cooperative Cr-NiO and ACT (4-acetamido-2,2,6,6-tetramethyl-1-piperidine-N-oxyl) electrocatalyst can be extended to the electrooxidation of a series of steroid alcohols to the corresponding aldehydes. Additionally, Cr-Ni3 N displays superior electrocatalytic activity for hydrogen evolution reaction (HER), with a low overpotential of 35 mV to deliver 10 mA cm-2 . Furthermore, the system coupled with anodic electrooxidation of sterol and cathodic HER exhibited excellent performance with high space-time yield of 48.85 kg m-3 h-1 for steroid carbonyl and 1.82 L h-1 for H2 generation in a two-layer stacked flow cell. Density Functional Theory (DFT) calculations indicated that Cr doping effectively stabilizes ACTH on the NiO surface, and ACTH molecule could be captured via the ketonic oxygen interaction with Cr, resulting in excellent electrocatalytic activity. This work develops a novel approach to the rational design of efficient electrocatalysts for the simultaneous production of H2 and large-scale value-added pharmaceutical carbonyl intermediates.

Clinical Outcomes and Radiologic Parameters of Endoscopic Lumbar Interbody Fusion Using a Novel Nerve Baffle with a Minimum 1-year Follow-up.

OBJECTIVE: Since endoscopic lumbar interbody fusion procedure has established, the insertion of cage requires a large working tube, which may lead to nerve root irritation. A novel nerve baffle was used for endoscopic lumbar interbody fusion (ELIF) and its short-term outcomes were analyzed. METHODS: A total of 62 patients (32 cases in tube group, 30 cases in baffle group) with lumbar degenerative diseases who underwent endoscopic lumbar fusion surgery from July 2017 to September 2021 were retrospectively analyzed. Clinical outcomes were measured using pain visual analogue scale (VAS), Oswestry disability index (ODI), Japanese Orthopedic Association Scores (JOA), and complications. Perioperative blood loss was calculated using the Gross formula. Radiologic parameters included lumbar lordosis, surgical segmental lordosis, cage position, and fusion rate. RESULTS: There were significant differences in VAS, ODI, and JOA scores postoperatively, 6 months after operation, and at the last follow-up (P < 0.05) within the 2 groups. The VAS and ODI score and hidden blood loss were significantly lower (P < 0.05) for the baffle group. There was no significant difference in lumbar lordosis and segmental lordosis (P > 0.05). Postoperative disc height was significantly higher than preoperative and follow-up disc heights (P < 0.05) for both groups. There was no statistical difference in fusion rate and cage position parameters or subsidence rate. CONCLUSIONS: Endoscopic lumbar interbody fusion using the novel baffle has more advantages in nerve protection and hidden blood loss reduction than traditional ELIF with working tube. Compared with the working tube procedure, it has similar or even better short-term clinical outcomes.

Hidden Blood Loss and Its Possible Risk Factors in Full Endoscopic Lumbar Interbody Fusion.

BACKGROUND: Full endoscopic lumbar interbody fusion (Endo-LIF) is a representative recent emerging minimally invasive operation. The hidden blood loss (HBL) in an Endo-LIF procedure and its possible risk factors are still unclear. METHODS: The blood loss (TBL) was calculated by Gross formula. Sex, age, BMI, hypertension, diabetes, ASA classification, fusion levels, surgical approach type, surgery time, preoperative RBC, HGB, Hct, PT, INR, APTT, Fg, postoperative mean arterial pressure, postoperative heart rate, Intraoperative blood loss (IBL), patient blood volume were included to investigate the possible risk factors by correlation analysis and multiple linear regression between variables and HBL. RESULTS: Ninety-six patients (23 males, 73 females) who underwent Endo-LIF were retrospective analyzed in this study. The HBL was 240.11 (65.51, 460.31) mL (median [interquartile range]). Fusion levels (p = 0.002), age (p = 0.003), hypertension (p = 0.000), IBL (p = 0.012), PT (p = 0.016), preoperative HBG (p = 0.037) were the possible risk factors. CONCLUSION: Fusion levels, younger age, hypertension, prolonged PT, preoperative HBG are possible risk factors of HBL in an Endo-LIF procedure. More attention should be paid especially in multi-level minimally invasive surgery. The increase of fusion levels will lead to a considerable HBL.

Progress in the clinical application of immune checkpoint inhibitors in small cell lung cancer.

Small cell lung cancer (SCLC) is a refractory cancer with poor prognosis due to its aggressive malignancy and high rates of metastasis, recurrence and drug resistance. These characteristics have also greatly impeded the identification of new treatment methods and drugs. The traditional model of SCLC treatment that has been reliant on platinum combined with etoposide for decades has been superseded by the emergence of immune checkpoint inhibitors (ICIs), which have shown significant therapeutic effects and broad application prospects as a monotherapy. This has led to the evaluation of ICIs with different mechanisms of action and their use in combination with radiotherapy or a variety of molecular targeted drugs to achieve synergy, complementary advantages, and reduce adverse reactions. Here, we review the progress in the use of ICIs as a monotherapy or in combination therapy for SCLC and consider the current limitations of these approaches as well as prospects for future developments.

Increased iron deposition in nucleus accumbens associated with disease progression and chronicity in migraine.

BACKGROUND: Migraine is one of the world's most prevalent and disabling diseases. Despite huge advances in neuroimaging research, more valuable neuroimaging markers are still urgently needed to provide important insights into the brain mechanisms that underlie migraine symptoms. We therefore aim to investigate the regional iron deposition in subcortical nuclei of migraineurs as compared to controls and its association with migraine-related pathophysiological assessments. METHODS: A total of 200 migraineurs (56 chronic migraine [CM], 144 episodic migraine [EM]) and 41 matched controls were recruited. All subjects underwent MRI and clinical variables including frequency/duration of migraine, intensity of migraine, 6-item Headache Impact Test (HIT-6), Migraine Disability Assessment (MIDAS), and Pittsburgh Sleep Quality Index (PSQI) were recorded. Quantitative susceptibility mapping was employed to quantify the regional iron content in subcortical regions. Associations between clinical variables and regional iron deposition were studied as well. RESULTS: Increased iron deposition in the putamen, caudate, and nucleus accumbens (NAC) was observed in migraineurs more than controls. Meanwhile, patients with CM had a significantly higher volume of iron deposits compared to EM in multiple subcortical nuclei, especially in NAC. Volume of iron in NAC can be used to distinguish patients with CM from EM with a sensitivity of 85.45% and specificity of 71.53%. As the most valuable neuroimaging markers in all of the subcortical nuclei, higher iron deposition in NAC was significantly associated with disease progression, and higher HIT-6, MIDAS, and PSQI. CONCLUSIONS: These findings provide evidence that iron deposition in NAC may be a biomarker for migraine chronicity and migraine-related dysfunctions, thus may help to understand the underlying vascular and neural mechanisms of migraine. TRIAL REGISTRATION: ClinicalTrials.gov, number NCT04939922.

ROS Scavenging Graphene-Based Hydrogel Enhances Type H Vessel Formation and Vascularized Bone Regeneration via ZEB1/Notch1 Mediation.

The regeneration strategy for bone defects is greatly limited by the bone microenvironment, and excessive reactive oxygen species (ROS) seriously hinder the formation of new bone. Reduced graphene oxide (rGO) is expected to meet the requirements because of its ability to scavenge free radicals through electron transfer. Antioxidant hydrogels based on gelatine methacrylate (GM), acrylyl-ß-cyclodextrin (Ac-CD), and rGO functionalized with ß-cyclodextrin (ß-CD) are developed for skull defect regeneration, but the mechanism of how rGO-based hydrogels enhance bone repair remains unclear. In this work, it is confirmed that the GM/Ac-CD/rGO hydrogel has good antioxidant capacity, and promotes osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and angiogenesis of human umbilical vein endothelial cells (HUVECs). The rGO-based hydrogel affects ZEB1/Notch1 to promote tube formation. Furthermore, two-photon laser scanning microscopy is used to observe the ROS in a skull defect. The rGO-based hydrogel promotes type H vessel formation in a skull defect. In conclusion, the hydrogel neutralizes ROS in the vicinity of a skull defect and stimulates ZEB1/Notch1 to promote the coupling of osteogenesis and angiogenesis, which may be a possible approach for bone regeneration.

Competing risk analysis of cardiovascular death in breast cancer: evidence from the SEER database.

Background: Cardiovascular disease (CVD) is the leading cause of death for all non-cancer deaths among breast cancer (BC) patients. The aim of this study was to investigate the risk of cardiovascular mortality (CVM) in patients with BC. Methods: Patients diagnosed with primary BC between 2010 and 2018 were identified through the Surveillance, Epidemiology and End Results (SEER) database. The standardized mortality ratio (SMR) for CVD was calculated to compare the CVM of BC patients with that of the general population. Multivariate competing risk models were performed to identify predictors of CVM in BC patients. Results: Overall, 399,014 BC patients were included from the SEER database, of whom 7,023 (1.8%) suffered death from CVD. The significantly higher overall SMR of CVM was observed in BC patients [SMR =4.84, 95% confidence interval (CI): 4.72-4.95]. Multivariate competing risk regression analysis revealed that age, race, American Joint Committee on Cancer (AJCC) stage, year of diagnosis, estrogen receptor (ER) status, progesterone receptor (PR) status, human epidermal growth factor receptor 2 (HER2) status, BC subtype, surgery, chemotherapy, radiation therapy, and median household income as independent predictors of CVM in BC patients. Conclusions: Compared to the general population, BC patients have a higher risk of experiencing CVM during the follow-up period after diagnosis. Early detection and intervention of cardiovascular risk factors would improve overall survival (OS) of BC patients.

Analysis of prognostic factors and establishment of prediction model of lung adenocarcinoma based on SEER database.

Background: Few models have been developed to predict survival outcomes for lung adenocarcinoma (LUAD). In this study, we aimed to establish a nomogram for the prediction of cancer-specific survival (CSS) in LUAD patients which can be further developed as a convenient web-based calculator. Methods: We performed a retrospective analysis of 50,007 LUAD patients selected from the Surveillance, Epidemiology, and End Result (SEER) 18 registry database. To enhance the reliability of the analysis, the patients' data were further randomly divided into the training cohort (70%) and validation cohort (30%). The optimal age cut-off points were determined using X-tile software, and patients were divided into three age groups: 10-72, 73-79, and 80-99 years. We selected independent prognostic factors from 17 variables by Cox regression, and plotted a visual nomogram to predict the 1-, 3-, and 5-year CSS. The predictive performance of the nomogram was evaluated through the concordance index (C-index), calibration curve and receiver operating characteristic (ROC) curve. To facilitate CSS forecast, a web-based calculator has subsequently been developed. Results: We selected sex, age, race, marital status, N stage, tumor size, surgery, radiotherapy, chemotherapy, and metastasis (bone, brain, liver, and lung) as independent prognostic factors. The C-index was 0.779 [95% confidence interval (CI): 0.775-0.783] in the training set prediction model, and 0.782 (95% CI: 0.778-0.786) in the validation set. ROC analysis showed that area under the curve (AUC) values were 0.700, 0.733 and 0.669 for the 1-, 3- and 5-year CSS in the training set and 0.700, 0.744 and 0.669 in the validation set, respectively. In the nomogram calibration curve, there was strong correlation between the observed and predictive values. A web-based calculator can be accessed at: https://hjhlovelfb.shinyapps.io/DynNomapp/. Conclusions: This nomogram model has good predictive power and can help clinicians identify LUAD patients at high risk of cancer-related death. This nomogram is expected to be a precise and personalized tool for predicting the prognosis of patients with LUAD.

Establishment and validation of a prognostic nomogram for extrahepatic cholangiocarcinoma.

Simple summary: Accurately estimate the prognosis of patients with ECCA is important. However, the TNM system has some limitations, such as low accuracy, exclusion of other factors (e.g., age and sex), and poor performance in predicting individual survival risk. In contrast, a nomogram-based clinical model related to a comprehensive analysis of all risk factors is intuitive and straightforward, facilitating the probabilistic analysis of tumor-related risk factors. Simultaneously, a nomogram can also effectively drive personalized medicine and facilitate clinicians for prognosis prediction. Therefore, we construct a novel practical nomogram and risk stratification system to predict CSS in patients with ECCA. Background: Accurately estimate the prognosis of patients with extrahepatic cholangiocarcinoma (ECCA) was important, but the existing staging system has limitations. The present study aimed to construct a novel practical nomogram and risk stratification system to predict cancer-specific survival (CSS) in ECCA patients. Methods: 3415 patients diagnosed with ECCA between 2010 and 2015 were selected from the SEER database and randomized into a training cohort and a validation cohort at 7:3. The nomogram was identified and calibrated using the C-index, receiver operating characteristic curve (ROC), and calibration plots. Decision curve analysis (DCA), net reclassification index (NRI), integrated discrimination improvement (IDI) and the risk stratification were used to compare the nomogram with the AJCC staging system. Results: Nine variables were selected to establish the nomogram. The C-index (training cohort:0.785; validation cohort:0.776) and time-dependent AUC (>0.7) showed satisfactory discrimination. The calibration plots also revealed that the nomogram was consistent with the actual observations. The NRI (training cohort: 1-, 2-, and 3-year CSS:0.27, 0.27,0.52; validation cohort:1-,2-,3-year CSS:0.48,0.13,0.34), IDI (training cohort: 1-, 2-, 3-year CSS:0.22,0.18,0.16; validation cohort: 1-,2-,3-year CSS:0.18,0.16,0.17), and DCA indicated that the established nomogram significantly outperformed the AJCC staging system (P<0.05) and had better recognition compared to the AJCC staging system. Conclusions: We developed a practical prognostic nomogram to help clinicians assess the prognosis of patients with ECCA.