Two doses of fosaprepitant included prophylactic treatment for the three-day cisplatin-based chemotherapy induced nausea and vomiting.

PURPOSE: Neurokinin 1 receptor antagonists included prophylactic treatment was recommended for patients who receive one-day cisplatin chemotherapy. It is unclear whether the prolonged administration of fosaprepitant is effective for three-day cisplatin-based chemotherapy induced nausea and vomiting (CINV). We aim to explore the prophylactic antiemetic efficacy and safety of two doses of fosaprepitant included regimen in the patients receiving multiple-day cisplatin chemotherapy. METHODS: This randomized, parallel-group, open-labelled study was conducted in nine hospitals between February 2021 and February 2023. Patients diagnosed as lung cancer and chemotherapy naive were screened. Eligible participants were scheduled to be treated with highly emetogenic chemotherapy regimen which including three days of cisplatin. Then they were randomly divided into the experimental group (two doses of fosaprepitant, Group 2DF) and the control group (one dose of fosaprepitant, Group C). The primary endpoints included the safety and the average none CINV days (NCDs). This study was registered on the website of chictr.org.cn, number ChiCTR2100042665. RESULTS: Overall, 204 participants were randomly assigned, and 198 patients were analyzed. No statistical difference in adverse events was found between the two groups. All treatment-related adverse effects for fosaprepitant observed were of grade 1-2. The average NCDs of Group 2DF was significantly more than Group C (18.21 ± 3.40 days vs 16.14 ± 5.20 days, P = 0.001). Furthermore, the better life function score was achieved in Group 2DF according to FLIE questionnaire. CONCLUSION: The administration of two-dose fosaprepitant was safe and more effective than one dose in protecting patients from CINV induced by three-day cisplatin included chemotherapy.

Efficacy and safety of EGFR-TKI combined with WBRT vs. WBRT alone in the treatment of brain metastases from NSCLC: a systematic review and meta-analysis.

Background: The efficacy and safety of combining epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) with whole-brain radiotherapy (WBRT) for treating brain metastases in non-small cell lung cancer patients remains to be determined. Methods: A systematic search was conducted using databases including PubMed, Embase, Web of Science, Cochrane, Wanfang, and China National Knowledge Infrastructure (CNKI), aiming to identify relevant clinical studies on the treatment of brain metastases originating from non-small cell lung cancer through the combination of EGFR-TKI and WBRT. Statistical analysis was performed utilizing Stata 17.0 software, covering clinical studies published until March 1, 2023. Results: This analysis incorporated 23 randomized controlled trials (RCTs), involving a total of 2,025 patients. Of these, 1,011 were allocated to the group receiving both EGFR-TKI and WBRT, while 1,014 were assigned to the WBRT alone group. The findings reveal that the combination of EGFR-TKI and WBRT significantly improves the intracranial objective remission rate (RR = 1.57, 95% CI: 1.42-1.74, p < 0.001), increases the intracranial disease control rate (RR = 1.30, 95% CI: 1.23-1.37, p < 0.001), and enhances the 1-year survival rate (RR = 1.48, 95% CI: 1.26-1.73, p < 0.001). Additionally, this combined treatment was associated with a significant survival advantage (RR = 1.48, 95% CI: 1.26-1.73, p < 0.001) and a reduced incidence of adverse effects (RR = 0.65, 95% CI: 0.51-0.83, p < 0.001), particularly with respect to nausea and vomiting (RR = 0.54, 95% CI: 0.37-0.81, p = 0.002) and myelosuppression (RR = 0.59, 95% CI: 0.40-0.87, p = 0.008). However, no statistically significant differences were observed for diarrhea (RR = 1.15, 95% CI: 0.82-1.62, p = 0.418), and skin rash (RR = 1.35, 95% CI: 0.88-2.07, p = 0.164). Conclusion: In contrast to WBRT alone, the combination of EGFR-TKI and WBRT significantly improves intracranial response, enhancing the objective response rate, disease control rate, and 1-year survival rate in NSCLC patients with brain metastases. Moreover, aside from mild cases of rash and diarrhea, there is no statistically significant increase in the incidence of additional adverse effects. Based on the comprehensive evidence collected, the use of third-generation EGFR-TKI combined with WBRT is recommended as the preferred treatment for NSCLC patients with brain metastases, offering superior management of metastatic brain lesions. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/#, CRD42023415566.

Diet and lifestyle behaviours simultaneously act on frailty: it is time to move the threshold of frailty prevention and control forward.

BACKGROUND: To analyse the association among the simultaneous effects of dietary intake, daily life behavioural factors, and frailty outcomes in older Chinese women, we predicted the probability of maintaining physical robustness under a combination of different variables. METHODS: The Fried frailty criterion was used to determine the three groups of "frailty", "pre-frailty", and "robust", and a national epidemiological survey was performed. The three-classification decision tree model was fitted, and the comprehensive performance of the model was evaluated to predict the probability of occurrence of different outcomes. RESULTS: Among the 1,044 participants, 15.9% were frailty and 50.29% were pre-frailty; the overall prevalence first increased and then decreased with age, reaching a peak at 70-74 years of age. Through univariate analysis, filtering, and embedded screening, eight significant variables were identified: staple food, spices, exercise (frequency, intensity, and time), work frequency, self-feeling, and family emotions. In the three-classification decision tree, the values of each evaluation index of Model 3 were relatively average; the accuracy, recall, specificity, precision, and F1 score range were between 75% and 84%, and the AUC was also greater than 0.800, indicating excellent performance and the best interpretability of the results. Model 3 takes exercise time as the root node and contains 6 variables and 10 types, suggesting the impact of the comprehensive effect of these variables on robust and non-robust populations (the predicted probability range is 6.67-93.33%). CONCLUSION: The combined effect of these factors (no exercise or less than 0.5 h of exercise per day, occasional exercise, exercise at low intensity, feeling more tired at work, and eating too many staple foods (> 450 g per day) are more detrimental to maintaining robustness.

Highly robust supramolecular polymer networks crosslinked by a tiny amount of metallacycles.

Supramolecular polymeric materials have exhibited attractive features such as self-healing, reversibility, and stimuli-responsiveness. However, on account of the weak bonding nature of most noncovalent interactions, it remains a great challenge to construct supramolecular polymeric materials with high robustness. Moreover, high usage of supramolecular units is usually necessary to promote the formation of robust supramolecular polymeric materials, which restrains their applications. Herein, we describe the construction of highly robust supramolecular polymer networks by using only a tiny amount of metallacycles as the supramolecular crosslinkers. A norbornene ring-opening metathesis copolymer with a 120° dipyridine ligand is prepared and self-assembled with a 60° or 120° Pt(II) acceptor to fabricate the metallacycle-crosslinked polymer networks. With only 0.28 mol% or less pendant dipyridine units to form the metallacycle crosslinkers, the mechanical properties of the polymers are significantly enhanced. The tensile strengths, Young's moduli, and toughness of the reinforced polymers reach up to more than 20 MPa, 600 MPa, and 150 MJ/m3, respectively. Controllable destruction and reconstruction of the metallacycle-crosslinked polymer networks are further demonstrated by the sequential addition of tetrabutylammonium bromide and silver triflate, indicative of good stimuli-responsiveness of the networks. These remarkable performances are attributed to the thermodynamically stable, but dynamic metallacycle-based supramolecular coordination complexes that offer strong linkages with good adaptive characteristics.

Role of regulatory T cells in mouse lung development.

Regulatory T cells (Tregs) constitute a specialized subset of T cells with dual immunoregulatory and modulatory functions. Recent studies have reported that Tregs mediate immune responses and regulate the development and repair processes in non-lymphoid tissues, including bone and cardiac muscle. Additionally, Tregs facilitate the repair and regeneration of damaged lung tissues. However, limited studies have examined the role of Tregs in pulmonary development. This study aimed to evaluate the role of Tregs in pulmonary development by investigating the dynamic alterations in Tregs and their hallmark cellular factor Forkhead box P3 (Foxp3) at various stages of murine lung development and establishing a murine model of anti-CD25 antibody-induced Treg depletion. During the early stages of murine lung development, especially the canalicular and saccular stages, the levels of Treg abundance and expression of Foxp3 and transforming growth factor-ß (TGF-ß) were upregulated. This coincided with the proliferation period of alveolar epithelial cells and vascular endothelial cells, indicating an adaptation to the dynamic lung developmental processes. Furthermore, the depletion of Tregs disrupted lung tissue morphology and downregulated lung development-related factors, such as surfactant protein C (SFTPC), vascular endothelial growth factor A (VEGFA) and platelet endothelial cell adhesion molecule-1 (PECAM1/CD31). These findings suggest that Tregs promote murine lung development.

The genetic landscape and phenotypic spectrum of GAA-FGF14 ataxia in China: a large cohort study.

BACKGROUND: An intronic GAA repeat expansion in FGF14 was recently identified as a cause of GAA-FGF14 ataxia. We aimed to characterise the frequency and phenotypic profile of GAA-FGF14 ataxia in a large Chinese ataxia cohort. METHODS: A total of 1216 patients that included 399 typical late-onset cerebellar ataxia (LOCA), 290 early-onset cerebellar ataxia (EOCA), and 527 multiple system atrophy with predominant cerebellar ataxia (MSA-c) were enrolled. Long-range and repeat-primed PCR were performed to screen for GAA expansions in FGF14. Targeted long-read and whole-genome sequencing were performed to determine repeat size and sequence configuration. A multi-modal study including clinical assessment, MRI, and neurofilament light chain was conducted for disease assessment. FINDINGS: 17 GAA-FGF14 positive patients with a (GAA)≥250 expansion (12 patients with a GAA-pure expansion, five patients with a (GAA)≥250-[(GAA)n (GCA)m]z expansion) and two possible patients with biallelic (GAA)202/222 alleles were identified. The clinical phenotypes of the 19 positive and possible positive cases covered LOCA phenotype, EOCA phenotype and MSA-c phenotype. Five of six patients with EOCA phenotype were found to have another genetic disorder. The NfL levels of patients with EOCA and MSA-c phenotypes were significantly higher than patients with LOCA phenotype and age-matched controls (p < 0.001). NfL levels of pre-ataxic GAA-FGF14 positive individuals were lower than pre-ataxic SCA3 (p < 0.001) and similar to controls. INTERPRETATION: The frequency of GAA-FGF14 expansion in a large Chinese LOCA cohort was low (1.3%). Biallelic (GAA)202/222 alleles and co-occurrence with other acquired or hereditary diseases may contribute to phenotypic variation and different progression. FUNDING: This study was funded by the National Key R&D Program of China (2021YFA0805200 to H.J.), the National Natural Science Foundation of China (81974176 and 82171254 to H.J.; 82371272 to Z.C.; 82301628 to L.W.; 82301438 to Z.L.; 82201411 to L.H.), the Innovation Research Group Project of Natural Science Foundation of Hunan Province (2020JJ1008 to H.J.), the Key Research and Development Program of Hunan Province (2020SK2064 to H.J.), the Innovative Research and Development Program of Development and Reform Commission of Hunan Province to H.J., the Natural Science Foundation of Hunan Province (2024JJ3050 to H.J.; 2022JJ20094 and 2021JJ40974 to Z.C.; 2022JJ40783 to L.H.; 2022JJ40703 to Z.L.), the Project Program of National Clinical Research Center for Geriatric Disorders (Xiangya Hospital, 2020LNJJ12 to H.J.), the Central South University Research Programme of Advanced Interdisciplinary Study (2023QYJC010 to H.J.) and the Science and Technology Innovation Program of Hunan Province (2022RC1027 to Z.C.). D.P. holds a Fellowship award from the Canadian Institutes of Health Research (CIHR).

HM_ADET: a hybrid model for automatic detection of eyelid tumors based on photographic images.

BACKGROUND: The accurate detection of eyelid tumors is essential for effective treatment, but it can be challenging due to small and unevenly distributed lesions surrounded by irrelevant noise. Moreover, early symptoms of eyelid tumors are atypical, and some categories of eyelid tumors exhibit similar color and texture features, making it difficult to distinguish between benign and malignant eyelid tumors, particularly for ophthalmologists with limited clinical experience. METHODS: We propose a hybrid model, HM_ADET, for automatic detection of eyelid tumors, including YOLOv7_CNFG to locate eyelid tumors and vision transformer (ViT) to classify benign and malignant eyelid tumors. First, the ConvNeXt module with an inverted bottleneck layer in the backbone of YOLOv7_CNFG is employed to prevent information loss of small eyelid tumors. Then, the flexible rectified linear unit (FReLU) is applied to capture multi-scale features such as texture, edge, and shape, thereby improving the localization accuracy of eyelid tumors. In addition, considering the geometric center and area difference between the predicted box (PB) and the ground truth box (GT), the GIoU_loss was utilized to handle cases of eyelid tumors with varying shapes and irregular boundaries. Finally, the multi-head attention (MHA) module is applied in ViT to extract discriminative features of eyelid tumors for benign and malignant classification. RESULTS: Experimental results demonstrate that the HM_ADET model achieves excellent performance in the detection of eyelid tumors. In specific, YOLOv7_CNFG outperforms YOLOv7, with AP increasing from 0.763 to 0.893 on the internal test set and from 0.647 to 0.765 on the external test set. ViT achieves AUCs of 0.945 (95% CI 0.894-0.981) and 0.915 (95% CI 0.860-0.955) for the classification of benign and malignant tumors on the internal and external test sets, respectively. CONCLUSIONS: Our study provides a promising strategy for the automatic diagnosis of eyelid tumors, which could potentially improve patient outcomes and reduce healthcare costs.

Performance of Subcutaneous Implantable Cardioverter Defibrillator (S-ICD) in Chinese Population with Primary Prevention Indications: A Prospective Observational Cohort Study.

BACKGROUND International studies have shown that use of a subcutaneous implantable cardioverter defibrillator (S-ICD) could reduce lead-related complications while maintaining adequate defibrillation performance; however, data from the Chinese population or other Asian groups are limited. MATERIAL AND METHODS SCOPE is a prospective, multicenter, observational cohort study. Two hundred patients with primary prevention indication for sudden cardiac death (SCD), who are candidates for S-ICD, will be enrolled. From the same population, another 200 patients who are candidates for transvenous implantable cardioverter defibrillator (TV-ICD) will be enrolled after being matched for age, sex, SCD high-risk etiology (ischemic cardiomyopathy, and non-ischemic cardiomyopathy, ion channel disease, and other) and atrial fibrillation in a 1: 1 ratio with enrolled S-ICD patients. All the patients will be followed for 18 months under standard of care. RESULTS The primary endpoint is proportion of patients free from inappropriate shock (IAS) at 18 months in the S-ICD group. The lower 95% confidence bound of the proportion will be compared with a performance goal of 90.3%, which was derived from the previous meta-analysis. The comparisons between S-ICD and TV-ICD on IAS, appropriate shock, and complications will be used as secondary endpoints without formal assumptions. CONCLUSIONS This is the first prospective multicenter study focusing on the long-term performance of S-ICD in a Chinese population. By comparing with the data derived from international historical studies and a matched TV-ICD group, data from SCOPE will allow for the assessment of S-ICD in the Chinese population in a contemporary real-world implantation level and programming techniques, which will help us to further modify the device implantation and programming protocol in this specific population in the future.

Exploring the relationship between intestinal microbiota and immune checkpoint inhibitors in the treatment of non-small cell lung cancer: insights from the "lung and large intestine stand in exterior-interior relationship" theory.

Objective: This study is aim to discern the Traditional Chinese Medicine (TCM) syndrome classifications relevant to immunotherapy sensitive in non-small cell lung cancer (NSCLC) patients, and to delineate intestinal microbiota biomarkers and impact that wield influence over the efficacy of NSCLC immunotherapy, grounded in the TCM theory of "lung and large intestine stand in exterior-interior relationship." Methods: The study cohort consisted of patients with advanced NSCLC who received treatment at the Oncology Department of Chengdu Fifth People's Hospital. These patients were categorized into distinct TCM syndrome types and subsequently administered immune checkpoint inhibitors (ICIs), specifically PD-1 inhibitors. Stool specimens were collected from patients both prior to and following treatment. To scrutinize the differences in microbial gene sequences and species of the intestinal microbiota, 16S rRNA amplicon sequencing technology was employed. Additionally, peripheral blood samples were collected, and the analysis encompassed the assessment of T lymphocyte subsets and myeloid suppressor cell subsets via flow cytometry. Subsequently, alterations in the immune microenvironment pre- and post-treatment were thoroughly analyzed. Results: The predominant clinical manifestations of advanced NSCLC patients encompassed spleen-lung Qi deficiency syndrome and Qi-Yin deficiency syndrome. Notably, the latter exhibited enhanced responsiveness to ICIs with a discernible amelioration of the immune microenvironment. Following ICIs treatment, significant variations in microbial abundance were identified among the three strains: Clostridia, Lachnospiraceae, and Lachnospirales, with a mutual dependency relationship. In the subset of patients manifesting positive PD-L1 expression and enduring therapeutic benefits, the study recorded marked increases in the ratios of CD3+%, CD4+%, and CD4+/CD8+ within the T lymphocyte subsets. Conversely, reductions were observed in the ratios of CD8%, Treg/CD4+, M-MDSC/MDSC, and G-MDSC/MDSC. Conclusion: The strains Clostridia, Lachnospiraceae, and Lachnospirales emerge as potential biomarkers denoting the composition of the intestinal microbiota in the NSCLC therapy. The immunotherapy efficacy of ICIs markedly accentuates in patients displaying durable treatment benefits and those expressing positive PD-L1.

Stimuli-triggered multilayer films in response to temperature and ionic strength changes for controlled favipiravir drug release.

The block copolymer micelles and natural biopolymers were utilized to form layer-by-layer (LbL) films via electrostatic interaction, which were able to effectively load and controllably release favipiravir, a potential drug for the treatment of coronavirus epidemic. The LbL films demonstrated reversible swelling/shrinking behavior along with the manipulation of temperature, which could also maintain the integrity in the structure and the morphology. Due to dehydration of environmentally responsive building blocks, the drug release rate from the films was decelerated by elevating environmental temperature and ionic strength. In addition, the pulsed release of favipiravir was observed from the multilayer films under the trigger of temperature, which ensured the precise control in the content of the therapeutic reagents at a desired time point. The nanoparticle-based LbL films could be used for on-demandin vitrorelease of chemotherapeutic reagents.

Two way workable microchanneled hydrogel suture to diagnose, treat and monitor the infarcted heart.

During myocardial infarction, microcirculation disturbance in the ischemic area can cause necrosis and formation of fibrotic tissue, potentially leading to malignant arrhythmia and myocardial remodeling. Here, we report a microchanneled hydrogel suture for two-way signal communication, pumping drugs on demand, and cardiac repair. After myocardial infarction, our hydrogel suture monitors abnormal electrocardiogram through the mobile device and triggers nitric oxide on demand via the hydrogel sutures' microchannels, thereby inhibiting inflammation, promoting microvascular remodeling, and improving the left ventricular ejection fraction in rats and minipigs by more than 60% and 50%, respectively. This work proposes a suture for bidirectional communication that acts as a cardio-patch to repair myocardial infarction, that remotely monitors the heart, and can deliver drugs on demand.

Advanced Generation Therapeutics: Biomimetic Nanodelivery System for Tumor Immunotherapy.

Tumor immunotherapy is a safe and effective strategy for precision medicine. However, immunotherapy for most cancer cases still ends in failure, with the root causes of the immunosuppressive and extraordinary heterogeneity of the solid tumors microenvironment. The emerging biomimetic nanodelivery system provides a promising tactic to improve the immunotherapy effect while reducing the adverse reactions on nontarget cells. Herein, we summarize the relationship between tumor occurrence and tumor immune microenvironment, mechanism of tumor immune escape, immunotherapy classification (including adoptive cellular therapy, cytokines, cancer vaccines, and immune checkpoint inhibitors) and recommend target cells for immunotherapy first, and then emphatically introduce the recent advances and applications of the latest biomimetic nanodelivery systems (e.g., immune cells, erythrocytes, tumor cells, platelets, bacteria) in tumor immunotherapy. Meanwhile, we separately summarize the application of tumor vaccines. Finally, the predictable challenges and perspectives in a forward exploration of biomimetic nanodelivery systems for tumor immunotherapy are also discussed.

Left Bundle Branch Pacing for Heart Failure and Left Bundle Branch Block Patients With Mildly Reduced and Preserved Left Ventricular Ejection Fraction.

BACKGROUND: Left bundle branch block (LBBB) may induce or aggravate heart failure (HF). Few data are available on patients with HF and LBBB with mildly reduced ejection fraction (HFmrEF; left ventricular ejection fraction [LVEF] 40%-50%) and those with preserved EF (HFpEF. LVEF ≥ 50%). We aimed to assess the long-term outcomes of left bundle branch pacing (LBBP) on cardiac function and remodelling in patients with LBBB and symptomatic HFmrEF and HFpEF. METHODS: Nonischemic cardiomyopathy (NICM) patients with HFmrEF and HFpEF (LVEF from 40% to 60% as defined with the use of echocardiography) with LBBB who successfully underwent LBBP (n = 50) were prospectively included from 4 centres. Patient characteristics and echocardiographic and lead parameters were recorded at implantation and during follow-ups of 1, 3, 6, and 12 months. RESULTS: All patients completed 1-year follow up. The LVEF was significantly improved from 46.5 ± 5.2% at baseline to 60.0 ± 6.1% (n = 50; P < 0.001) after 1-year follow up. Higher ΔLVEF and super-response rate were observed in the HFmrEF group (n = 30) than in the HFpEF group (n = 20). CONCLUSIONS: LBBP improved symptoms and reversed remodelling in patients with LBBB and symptomatic HF at 1-year follow-up. Improvement occurred even in HFpEF patients, and the resynchronisation effect was better in HFmrEF group.

Cobalt-Nanoparticles-Decorated 3D Porous Nitrogen-Doped Carbon Network for Electrocatalytic Nitrite Reduction to Ammonia.

Electrocatalytic nitrite (NO2-) reduction offers the potential to synthesize high-value ammonia (NH3) while simultaneously removing NO2- pollution from aqueous solutions, but it requires high-efficiency catalysts to drive the complex six-electron reaction. Herein, cobalt-nanoparticle-decorated 3D porous nitrogen-doped carbon network (Co@NC) is proven as a high-efficiency catalyst for the selective electroreduction of NO2- to NH3. Such Co@NC attains a large NH3 yield of 922.7 µmol h-1 cm-2 and a high Faradaic efficiency of 95.4% under alkaline conditions. Furthermore, it shows remarkable electrochemical stability during cyclic electrolysis.

A Hierarchical CuO Nanowire@CoFe-Layered Double Hydroxide Nanosheet Array as a High-Efficiency Seawater Oxidation Electrocatalyst.

Seawater electrolysis has great potential to generate clean hydrogen energy, but it is a formidable challenge. In this study, we report CoFe-LDH nanosheet uniformly decorated on a CuO nanowire array on Cu foam (CuO@CoFe-LDH/CF) for seawater oxidation. Such CuO@CoFe-LDH/CF exhibits high oxygen evolution reaction electrocatalytic activity, demanding only an overpotential of 336 mV to generate a current density of 100 mA cm-2 in alkaline seawater. Moreover, it can operate continuously for at least 50 h without obvious activity attenuation.

Electrical Synchrony Optimization for Left Bundle Branch Area Pacing in Patients With Bradycardia and Heart Failure.

Left bundle branch area pacing (LBBAP) has emerged as a promising physiological pacing modality. This study was designed to investigate the acute impact of the atrioventricular delay (AVD) on cardiac electrical characteristics and identify an optimal range of AVDs for LBBAP to achieve electrical atrioventricular and interventricular synchrony. Patients indicated for ventricular or biventricular pacing were studied during routine follow-ups at least 3 months after LBBAP implantation. Patients were excluded if they had a complete AV block or persistent atrial fibrillation. AVD was programed from 40 to 240 ms or until intrinsic conduction occurred. Optimal AVD was determined by the electrocardiography criteria, including QRS duration, reduced R-wave in lead V1, reduced notching or slurring in lateral leads, and more desirable precordial QRS transition. A total of 38 patients (age 68.7 ± 10.3 years; 16 male (42%); 18 dual-chamber pacemakers and 20 cardiac resynchronization therapy devices; average follow-up period 15.1 ± 10.2 months) were included. The fusion of LBBAP and intrinsic right ventricular conduction occurred in 21 patients with corresponding optimal AVD determined. A great proportion (∼85%) of the optimal AVDs ranged from 50% to 80% of the observed atrium-to-left bundle branch-sensing (A-LBBS) intervals. The linear correlation between the optimal AVD and corresponding A-LBBS interval (optimal AVD = 0.84 × [A-LBSs interval] - 36 ms) produced R = 0.86 and p <0.0001. In conclusion, AVD selection during LBBAP greatly impacted the ventricular electrical characteristics and the optimal AVD was linearly correlated with the corresponding A-LBBS interval.

Prebiotics Modulate Gut Microbiota-mediated T-cell Immunity to Enhance the Inhibitory Effect of Sintilimab in Lewis Lung Adenocarcinoma Model Mice.

BACKGROUND: Sintilimab (Sin) helps the body to restore the anti-tumor response of T lymphocytes. However, in clinical use, the treatment process is more complicated due to adverse effects and different dosing regimens. It is not clear whether prebiotics (PREB) have a potentiating effect on Sin for lung adenocarcinoma, and this study intends to investigate the inhibitory effect, safety and possible mechanism of Sin combined with PREB on lung adenocarcinoma from animal experiments. METHODS: Lewis lung adenocarcinoma cells were inoculated into the right axilla of mice subcutaneously to prepare the Lewis lung cancer mouse model and treated in groups. The volume of transplanted tumors was measured, the histopathology of the liver and kidney of mice was observed by H&E staining, the levels of ALT, AST, UREA, CREA, WBC, RBC, and HGB in blood were analyzed biochemically; the ratio of T-cell subpopulations in blood, spleen, and bone marrow was detected by flow cytometry, the expression of PD-L1 in tumor tissue was detected by immunofluorescence staining, and 16S rRNA to analyze the diversity of fecal flora. RESULTS: Sin inhibited tumor growth and regulated immune cell homeostasis in lung adenocarcinoma mice, but liver and kidney histopathology showed different degrees of damage after Sin treatment, while the addition of PREB reduced liver and kidney damage in lung adenocarcinoma mice and promoted Sin's regulation of immune cells. In addition, the beneficial effects of Sin were associated with changes in intestinal flora diversity. CONCLUSION: The mechanism by which Sintilimab combined with prebiotics inhibits tumor volume and regulates immune cell subpopulation balance in lung adenocarcinoma mice may be related to gut microbes.

Case Report: Advanced pulmonary sarcomatoid carcinoma with adrenal gland metastasis after sintilimab combined with anlotinib treatment.

Background: Pulmonary sarcomatoid carcinoma (PSC) is a rare subtype of non-small-cell lung cancer (NSCLC), which is resistant to conventional chemotherapy and radiotherapy with a poor prognosis. The MET inhibitor may be effective for the patients with MET exon 14 skipping mutation. This mutation was not detected in this patient. However, the PD-L1 TPS 60%, KRAS and TP53 mutations were detected in this patient could benefited from immunotherapy. The anlotinib is a novel multitarget antiangiogenic drug that could be effective for advanced non-small-cell lung cancer and some sarcoma patients. We report a patient with advanced pulmonary sarcomatoid carcinoma successfully treated with immunotherapy combined with antiangiogenic drugs. Case summary: A 75-year-old male was admitted to the hospital in July 2020 because of productive cough for more than three months. The patient was diagnosed with advanced pulmonary sarcomatoid carcinoma with adrenal gland metastasis (cT4N3M1b, stage IVA) was treated in our hospital. Genetic testing revealed KRAS P.L19F mutation (abundance 19.12%) and NFEE2L2 P.E82G mutation (abundance 14.84%); TP53 P.S183 mutation (abundance 26.97%), TMB(Tumor Mutational Burden) 30.91 muts/Mb, MSS, and PD-L1 (Daco 22C3) TPS 60% were also detected. We administrated sintilimab combined with anlotinib treatment, a PD-1 inhibitor with antiangiogenic drug. The patient achieved a favorable outcome with tolerable adverse effects. Conclusion: Sintilimab combined with anlotinib treatment may lead to a favorable outcome for patients with advanced pulmonary sarcomatoid carcinoma.

Recurrent trichilemmal carcinoma of the periorbital region treated with IMRT radiotherapy: A case report and a review of literature.

RATIONALE: Trichilemmal carcinoma (TLC) is a rare malignant cutaneous adnexal tumor usually accept surgery. This report describes an elderly patient with recurrence TLC of the periorbital region after surgery who was subsequently treated with IMRT radiotherapy. After 2-years follow-up visit, there was no progress or metastasis. INTRODUCTION: TLC is a rare malignant cutaneous adnexal tumor. It usually occurs on sun-exposed areas in elderly people but rarely occurs in the periorbital region. Most cases accept surgery or micrographic Mohs surgery. Recurrence or metastasis of this neoplasm was seldom reported in the medical literature after enough tumor-free margin surgery. And radiotherapy was seldom reported in the treatment for patients of TLC. PATIENT CONCERNS: Here we report an elderly patient with recurrence TLC of the periorbital region after surgery who was subsequently treated with radiotherapy with a total dose of 66 Gy. Two years later, the patient was admitted head, neck, chest, abdomen CT scan, and no progress or metastasis was detected after 2-years follow-up. DIAGNOSIS: Trichilemmal carcinoma of the periorbital region. INTERVENTIONS: We describe the clinical characteristics, pathological features, and choice of examination methods of a patient with TLC in the periorbital region. And we use the radical radiotherapy to treat this case. OUTCOMES: There are no progress or metastasis after 2-years follow-up. CONCLUSION: Radiotherapy is a good option for patients with TLC if the patient refuses surgery or fails to achieve a satisfactory tumor-free margin or relapses after surgery.

Immediate early response 3 gene promotes aggressive progression and autophagy of AML by negatively regulating AKT/mTOR.

BACKGROUND: Immediate early response 3 (IER3) plays a vital role in many tumors. This study aims to explore the function and mechanism of IER3 in Acute myeloid leukemia (AML). METHODS: The expression of IER3 in AML was performed by bioinformatics analysis. CCK-8 proliferation assay, flow cytometry cycle assay, clone formation assay, and tumorigenic ability were used to investigate the effect of IER3 on AML cells. Unbiased label-free quantitative proteomics and label-free quantitative phosphoproteomics analysis were performed. The regulatory relationship between SATB1(Special AT-rich sequence binding protein 1) and IER3 was investigated by Real time-PCR, Western blot, Chromatin immunoprecipitation (CHIP), and PCR. RESULTS: The result indicated that the prognosis of the high IER3 expression group was significantly worse than that of the low expression group. CCK-8 assay showed that IER3 enhanced the proliferation ability. Cell cycle analysis showed IER3 could promote HL60 cells to enter the S phase of DNA synthesis from the quiescent phase. IER3 could stimulate HEL cells to enter mitosis. Clone-formation experiments suggested that IER3 enhanced clonogenic ability.IER3 promoted the tumorigenesis of AML. Further experimental investigation revealed that IER3 promoted autophagy and induced the occurrence and development of AML by negatively regulating the phosphorylation activation of AKT/mTOR pathway. SATB1 was found to bind to the promoter region of IER3 gene and negatively regulate its transcription. CONCLUSION: IER3 could promote the development of AML and induce autophagy of AML cells by negatively regulating the phosphorylation and activation of AKT/mTOR. By the way, SATB1 may negatively target regulates IER3 transcription.