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Background Continuous renal replacement therapy (CRRT) has been considered as an adjuvant therapy for sepsis. However, the novel biomarker to evaluate the benefits of CRRT is limited. The aim of this study was to explore the novel biomarkers involved in the impact of CRRT in pediatric sepsis. Methods The serum proteomic profiles on the 7th day after CRRT (CRRT 7th day) compared with before CRRT (CRRT 1st day) was determined in 3 children with sepsis as a discovery set. The screened candidates were confirmed in the validation cohort including patients received CRRT (CRRT group) and without CRRT (non-CRRT group). We defined that pediatric sequential organ failure assessment score (pSOFA) in pediatric patients with sepsis decreased by 2 points or more on the CRRT 1st day compared with CRRT initiation as CRRT responders. The changes of serum biomarkers were compared between CRRT responders and CRRT non-responders. Moreover, correlation analysis was further conducted in pediatric sepsis. Results A total of 145 differentially expressed proteins were found according to the serum proteomics profiles. By visualizing the interaction between the differential proteins, 6 candidates (Lysozyme C [LYZ], Leucine-rich alpha-2-glycoprotein [LRG1], Fibromodulin [FMOD], Alpha-1-antichymotrypsin [SERPINA3], L-selectin [SELL], Monocyte differentiation antigen CD14 [CD14]) were screened. In the validation cohort, serum levels of LYZ and LRG1 showed a higher trend on the CRRT 7th day than that on the 1st day in the non-CRRT group. However, the changes in levels of LYZ and LRG1 on the 7th day was significant in the CRRT group (p = 0.016, p = 0.009, respectively). Moreover, the levels of LYZ and LRG1 on the CRRT 7th day in the CRRT group were significantly higher than that in the non-CRRT group (p Conclusion Elevated serum LYZ and LRG1 levels are associated with clinical benefits of CRRT during sepsis.

Multiple organ dysfunction syndrome (MODS) with secondary hemophagocytic lymphohistiocytosis (SHLH) causes significant mortality. We aimed to identify the predictor factors for death in pediatric patients with SHLH-associated MODS receiving continuous renal replacement therapy (CRRT).This multicentered nested case-control study was conducted from 2016 to 2020. The characteristics were compared between survivors and non-survivors. Logistic regression was applied to identify the risk factors for death. The cutoff values were assessed by receiver operating characteristics curves.Fifty two patients were enrolled in this study. Interleukin-6 level (p = 0.018) and the number of organ dysfunction (p = 0.047) were independent risk factors for death. The cutoff value of 13.12 pg/ml interleukin-6 and three organs dysfunction at CRRT initiation presented a high sensitivity and specificity.The number of organ dysfunction and interleukin-6 at CRRT initiation are independent risk factors for death in pediatric patients with SHLH-associated MODS.

Background: Bone was the most common site of metastasis in prostate cancer(PCa) patients and was correlated with poor prognosis and increasing economicalburden. Studies were limited on the prognostic prediction for metastatic PCapatients with the assistance of neural network. Methods: Four convolutional neural network (CNN) models were developed andevaluated to predict overall survival (OS) of PCa patients with bone metastasis.All the CNN models were first trained with 64 samples and evaluated with 10samples, two models used only bone scan images and two models used both bonescan images and clinical parameters (CPs). Predictions of the best models werecompared with those of two urology surgeons on 20 test samples. Results: Our best models could predict OS of PCa patients with bone metastasiswith AUC = 0.8022 by using only bone scan images and AUC = 0.8132 by usingboth bone scan image and CPs on 20 test samples. When the sensitivities(specificities) set equal to average level of urology surgeons, their specificities(sensitivities) were 0%(7.2%) and 30.77%(7.7%) higher, which showedsignificant advantages of CNN models. Conclusion: The CNN models were suitable to predict OS in PCa patients withbone metastasis using bone scan images and CPs. Our models showed betterperformance in terms of accuracy and stability than urology surgeons. Keywords: Bone Metastasis; Bone Scan; Convolutional Neural Network;Prostate Cancer; Overall Survival

Objective: Peritumoral stiffness of lesions measured by shear-wave elastography (SWE) can improve the diagnostic specificity of the conventional ultrasound(US) in breast cancer. Our aim was to develop dual-modal CNN models based on combining US images and SWE of peritumoral region to improve prediction of breast cancer. Materials and Methods: We retrospectively collected US images and SWE data of 1271 BI-RADS-4 breast lesions from 1116 female patients (mean age ± standard deviation, 45.40 ± 9.65 years). The lesions were divided into three subgroups based on the maximum diameter (MD): ≤15 mm; >15 mm and ≤25 mm; >25 mm. We recorded lesion stiffness (SWV1) and 5-point average stiffness of the peritumoral tissue (SWV5). Based on the segmentation of different widths of peritumoral tissue (0.5 mm, 1.0 mm, 1.5 mm, 2.0 mm) and internal SWE image of the lesions, CNN models were built using PP-LiteSeg and EfficientNet-B0 architecture. All single-parameter CNN models, dual-modal CNN models, and quantitative SWE parameters inthe training cohort (971 lesions) and the validation cohort (300 lesions) were assessed by receiver operating characteristic (ROC) curve. Results: The dual-modal CNN models based on the combination of US and SWE segmentation images had better diagnostic performance than the quantitative SWE parameters, US CNN model, and SWE CNN models in predicting breast cancer (P < 0.001 for all). The US + 1.0 mm SWE model achieved the highest area under the ROC curve (AUC) in the subgroup of lesions with MD ≤15 mm in both the training (0.94) and the validation cohorts (0.91). In the subgroups with MD between 15 and 25 mm and above 25 mm, the US + 2.0 mm SWE model achieved the highest AUCs in both the training cohort (0.96 and 0.95, respectively) and the validation cohort (0.93 and 0.91, respectively). Conclusion: The dual-modal CNN models based on the combination of US images and peritumoral region SWE images allow accurate prediction of breast cancer.

Terpenoids constitute the largest class of natural products with complex structures, essential functions, and versatile applications. Creation of new building blocks beyond the conventional five-carbon (C

Background Reactive lymphocytes are substantial components of germinoma, which are believed to be related to the favorable prognosis of this intracranial tumor and better response to immunotherapy. However, the mechanisms managing the recruitment of lymphocytes are poorly understood. High endothelial venules (HEVs) are specialized blood vessels that play key roles in lymphocyte trafficking in Lymph nodes. These vessels are associated with lymphocytes infiltration in chronic inflammatory diseases and various malignant tumors, but their distribution and implications in germinoma are unknown. Methods This study investigated the presence and distribution of HEVs in 42 germinomas by immunohistochemical staining of peripheral node addressin (PNAd) and transmission electron microscopic examination. The correlation of the densities of HEVs with the extent of T and B lymphocytes infiltration and several clinicopathological characteristics were also analyzed to determine whether HEVs are responsible for lymphocytes recruitment and their roles in anti-tumor immunity in germinoma. Results PNAd-positive HEVs were detected in 31% (13/42) of germinomas, and their presence correlated with abundant infiltrating CD3 + T cells, CD20 + B cells and CD8 + Cytotoxic T Lymphocytes (p = 0.0410, 0.0023, 0.0061, respectively). Higher HEVs density was also correlated with several clinicopathological parameters, which are recognized indicators for favorable prognosis in germinomas, including typical tumor location (p = 0.0093), lower tumor cell content (P = 0.0428), and younger age at diagnosis (p = 0.0121). Furthermore, bioinformatics analysis showed HEVs-associated genes mainly enriched in immune-related Gene Ontology terms, including innate immune response, inflammatory response, and B cell receptor signaling pathway. The xCell analysis revealed that germinomas with higher HEVs enrichment scores had increased levels of the immune score, microenvironment score, dendritic cells, CD8 + central memory T-cells, CD4 + memory T-cells, and B-cells. Conclusion Our findings indicate that HEVs could contribute to lymphocytes recruitment in germinomas, thus may serve as a predictor of favorable prognosis and better response to immunotherapy in this intracranial tumor.

Background Recently, the International System for Reporting Serous Fluid Cytopathology (TIS) has been established, with an aim to standardize reporting and guide clinical decision making. Methods The cytological and clinicopathological data of pleural effusions were retrieved from the pathology database and electronic medical records. All specimens were evaluated and reclassified in accordance with the TIS recommendations. Finally, the risk of malignancy (ROM) and performance parameters were measured. Results A total of 2454 pleural effusion specimens were included, among which 30 (1.2%), 1670 (68.1%), 151 (6.2%), 54 (2.2%) and 549 (22.4%) patients were classified into non-diagnostic (ND), negative for malignancy (NFM), atypia of undetermined significance (AUS), suspicious for malignancy (SFM) and malignancy (MAL) groups, respectively. The most commonly diagnosed malignancies were lung cancer (48.4%), ovary cancer (10.2%), breast cancer (7.5%), and 21.3% unknown primary site (UPS). Among the 36 UPS patients, the most common site of origin was lung (36.1%), followed by ovary (13.9%) and breast (11.1%) via immunocytochemistry of cell block. The calculated ROM values were 26.7%, 12%, 62.3%, 77.8% and 100% for ND, NFM, AUS, SFM and MAL groups, respectively. When considering MAL as the only positive group, the diagnostic accuracy, sensitivity, specificity, positive and negative predictive values were determined to be 95.2%, 81.9%, 100%, 100% and 93.6%, respectively. Conclusion The newly proposed TIS is an easy-to-master, user-friendly, and standardized classification system, especially when applying on pleural effusions. An adequate serous sample, application of immunocytochemistry, review of cytomorphological data and past medical history could enhance the accuracy of cytological diagnosis.

Biliary tract cancer (BTC) is an uncommon and aggressive neoplasm, with most patients presenting in an advanced stage. Systemic chemotherapy is the limited treatment available but is unsatisfactory, while targeted therapy is still awaiting validation from clinical trials. Given the potential effect of immune checkpoint inhibitors (ICIs) in the treatment of BTC, this review aims to summarize the evidence-based benefits and predictive biomarkers for using inhibitors of cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) ligand, or programmed cell death protein-1 and its ligand (PD-1 and PD-L1) as monotherapy or combined with other anti-tumor therapies, while also pointing out certain pitfalls with the use of ICIs which need to be addressed.

We investigated the expression and biological function of retinoic acid inducible gene I (RIG-I) in esophageal squamous cell carcinoma (ESCC). Materials and methods: An immunohistochemical analysis was performed on 86 pairs of tumor tissue and adjacent normal tissue samples of patients with ESCC. We generated RIG-I-overexpressing ESCC cell lines KYSE70 and KYSE450, and RIG-I- knockdown cell lines KYSE150 and KYSE510. Cell viability, migration and invasion, radioresistance, DNA damage, and cell cycle were evaluated using CCK-8, wound-healing and transwell assay, colony formation, immunofluorescence, and flow cytometry and Western blotting, respectively. RNA sequencing was performed to determine the differential gene expression between controls and RIG-I knockdown. Tumor growth and radioresistance were assessed in nude mice using xenograft models. RIG-I expression was higher in ESCC tissues compared with that in matched non-tumor tissues. RIG-I overexpressing cells had a higher proliferation rate than RIG-I knockdown cells. Moreover, the knockdown of RIG-I slowed migration and invasion rates, whereas the overexpression of RIG-I accelerated migration and invasion rates. RIG-I overexpression induced radioresistance and G2/M phase arrest and reduced DNA damage after exposure to ionizing radiations compared with controls; however, it silenced the RIG-I enhanced radiosensitivity and DNA damage, and reduced the G2/M phase arrest. RNA sequencing revealed that the downstream genes DUSP6 and RIG-I had the same biological function; silencing DUSP6 can reduce the radioresistance caused by the overexpression of RIG-I. RIG-I knockdown depleted tumor growth in vivo, and radiation exposure effectively delayed the growth of xenograft tumors compared with the control group. RIG-I enhances the progression and radioresistance of ESCC; therefore, it may be a new potential target for ESCC-targeted therapy.

We report the discovery, via a unique high-throughput screening strategy, of a novel bioactive anticancer compound: Thiol Alkylating Compound Inducing Massive Apoptosis (TACIMA)-218. We demonstrate that this molecule engenders apoptotic cell death in genetically diverse murine and human cancer cell lines, irrespective of their p53 status, while sparing normal cells. TACIMA-218 causes oxidative stress in the absence of protective antioxidants normally induced by Nuclear factor erythroid 2–related factor 2 activation. As such, TACIMA-218 represses RNA translation and triggers cell signaling cascade alterations in AKT, p38, and JNK pathways. In addition, TACIMA-218 manifests thiol-alkylating properties resulting in the disruption of redox homeostasis along with key metabolic pathways. When administered to immunocompetent animals as a monotherapy, TACIMA-218 has no apparent toxicity and induces complete regression of pre-established lymphoma and melanoma tumors. In sum, TACIMA-218 is a potent oxidative stress inducer capable of selective cancer cell targeting.

Objective This study assessed whether ultrasonic speckle-tracking imaging (STI) could help evaluate right ventricular systolic function in repaired Tetralogy of Fallot (TOF) with different pulmonary artery branch angles. Methods We retrospectively evaluated 64 patients who underwent surgery for TOF and 60 normal children. The angle between the left pulmonary artery and main pulmonary artery was measured using echocardiography and computed tomography angiography (CTA). Furthermore, STI was used to record the global longitudinal strain of the four-chamber view (GLS4), the global longitudinal strain of the two-chamber view (GLS2), and the global longitudinal strain of the right ventricle (RVGLS). Results The GLS4, GLS2, and RVGLS values in the TOF groups with different pulmonary artery branch angles were significantly lower than those in the control group. Furthermore, the GLS2 and RVGLS values were significantly lower for angles of 90-100° and 100°). Multivariate linear regression analyses revealed that pulmonary regurgitation and the angle between the left and main pulmonary arteries were two important factors affecting RVGLS. The Bland-Altman consistency test revealed good agreement regarding the pulmonary artery branch angles measured using echocardiography and CTA. Conclusion In patients with TOF, the RVGLS was lower for acute left pulmonary artery angulation than for round and blunt left pulmonary artery angulation. The angle of the pulmonary artery branches was an important factor affecting RVGLS. Echocardiography can be used to measure the angle of the pulmonary artery branches, which provides valuable information for surgical correction of pulmonary artery morphology.

Ischemia-induced neuronal death leads to serious lifelong neurological deficits in ischemic stroke patients. Histone deacetylase 6 (HDAC6) is a promising target for neuroprotection in many neurological disorders, including ischemic stroke. However, the mechanism by which HDAC6 inhibition protects neurons after ischemic stroke remains unclear. Here, we discovered that genetic ablation or pharmacological inhibition of HDAC6 reduced brain injury after ischemic stroke by increasing macrophage migration inhibitory factor (MIF) acetylation. Mass spectrum analysis and biochemical results revealed that HDAC6 inhibitor or aspirin treatment promoted MIF acetylation on the K78 residue. MIF K78 acetylation suppressed the interaction between MIF and AIF, which impaired MIF translocation to the nucleus in ischemic cortical neurons. Moreover, neuronal DNA fragmentation and neuronal death were impaired in the cortex after ischemia in MIF K78Q mutant mice. Our results indicate that the neuroprotective effect of HDAC6 inhibition and aspirin treatment results from MIF K78 acetylation; thus, MIF K78 acetylation may be a therapeutic target for ischemic stroke and other neurological diseases.

Background: Advanced glycation end product receptor (RAGE) acts as the receptor of pro-inflammatory ligands and highly expressed in alveolar epithelial cells (AECs). Autophagy in AECs has received much attention nowadays. However, the role between autophagy and RAGE in the pathogenesis of acute lung injury remains unclear. Therefore, the aim of this study is to explore whether RAGE activation signals take part in disfunction of alveolar epithelial barrier through autophagic death.Methods: We established the acute lung injury animal model using C57BL/6 and ager genes knockout (ager -/- mice) mice. A549 cells were treated with siRNA to reduce ager gene expression. Autophagy was inhibited by 3-methyladenine. Lung injury was assessed by histopathological examination. Cell viability was estimated by cell counting kit-8. The serum and bronchoalveolar lavage fluid (BALF) of IL-6, IL-8 and soluble RAGE (sRAGE) evaluated by ELISA, further studied the involvement of RAGE signals, autophagy and apoptosis by western blots, immunohistochemistry, immunofluorescence, transmission electron microscopy and TUNEL test.Results: The expression of RAGE was promoted by LPS, which was associated with activation of autophagy both in mice lungs and A549 cells. sRAGE in the BALF presented a positive correlation with inflammatory factors, inflammation and apoptosis in lungs were alleviated in ager-/- mice than wild-type controls. Persistently activated autophagy contributed to cells apoptosis, while blocking autophagy by 3-MA protects from lung damage, ager knockdown inhibited LPS-induced autophagy and attenuated lung injury. RAGE knockdown by siRNA in A549 cells significantly suppressed LPS-induced autophagy activation and apoptosis. The expression of RAGE activates the downstream STAT3 signaling pathway. Conclusion: RAGE plays an essential role in the pathogenesis of AECs injury, RAGE inhibition alleviates LPS-induced lung injury via directly suppressing autophagic apoptosis of alveolar epithelial cells.

Background The 5-α reductase inhibitors (5-ARIs) are the first-line drug managing benign prostatic hyperplasia (BPH). Unfortunately, some patients showed no responses to 5-ARIs therapy, even suffering from worse symptoms. Although the decreased expression of 5-α reductase type 2(SRD5A2) in BPH tissues might explain the 5-ARIs therapy failure, the mechanisms underlying SRD5A2 decreased remained unelucidated. Objectives To investigate the mechanisms of microRNA regulating the variable expression of SRD5A2 resulting in treatment failure of 5-ARIs. Materials and methods The expression of SRD5A2 and microRNAs in BPH tissues and prostate cells were detected by immunohistochemistry, western blotting, and quantitative real-time PCR (qRT-PCR). Dual-luciferase reporter assay was performed to confirm that microRNA directly combine to SRD5A2 mRNA. The apoptosis of prostatic cells was detected by flow cytometry. Results 13.6%, 28.8%, and 57.6% of BPH tissues showed negative, weak, and strong positive SRD5A2 expression, respectively. Normal human prostatic epithelial cell line RWPE-1 strongly expressed SRD5A2, whereas the immortalized human prostatic epithelial cell line BPH-1 weakly expressed SRD5A2. miR-1199-5p expression level in BPH-1 was remarkably higher than that in RWPE-1(P༜0.001), and miR-1199-5p expression was significantly upregulated in BPH tissues with negative SRD5A2 expression than those with positive SRD5A2 expression. After miR-1199-5p mimics transfection, SRD5A2 expression was decreased markedly in RWPE-1 cells, whereas after miR-1199-5p inhibitor transfection, SRD5A2 expression increased in BPH-1 cells. Dual-luciferase reporter assay showed that miR-1199-5p could bind the 3’ untranslated region of SRD5A2. Additionally, miR-1199-5p could decrease the sensibility of finasteride (100 µM) on RWPE-1 cells. Conclusion Our results demonstrate that SRD5A2 expression varied in BPH tissues and miR-1199-5p might be one of the several factors contributing to differential SRD5A2 expression in BPH patients.

Summary Here, we report a high-performance catalyst Cu@Na-Beta, prepared via a unique method to embed 2∼5 nm Cu nanoparticles in crystalline particles of Na-Beta zeolite, for CO2 hydrogenation to ethanol as the only organic product in a traditional fixed-bed reactor. The ethanol yield in a single pass can reach ∼14% at 300°C, ∼12,000 mL·gcat−1·h−1, and 2.1 MPa, corresponding to a space-time yield of ∼398 mg·gcat−1·h−1. The key step of the reaction is considered as the rapid bonding of CO2∗ with surface methyl species at step sites of Cu nanoparticles to CH3COO∗ that converts to ethanol in following hydrogenation steps. The points of the catalyst seemed to be that the irregular copper nanoparticles stuck in zeolitic frameworks offer high density of step sites and the intimate surrounding of zeolitic frameworks strongly constrain the CO2 reactions at the copper surface and block by-products, such as methanol, formic acid, and acetyl acid.

Background Describe the outcome of adenovirus pneumonia in a pediatric intensive care unit (PICU) over a 3-year period, to identify the risk factors that may be associated with worse outcome. Methods A retrospective observational study was performed in the PICU of children’s hospital in Shanghai from July 2016 to June 2019. Sixty-seven children over 29 days to 14 years old with adenovirus pneumonia who were admitted to PICU with acute hypoxemic respiratory failure were included in this study. The primary outcome was hospital mortality, and secondary outcomes were hospital and PICU length of stay (LOS), and risk factors of worse outcome. Results Of 67 children with severe adenovirus pneumonia, the hospital mortality was 16.42% (11/67) and 28-day mortality was 14.93% (10/67). Median Pediatric Risk of Mortality III (PRISM III) score at admission was 13 (interquartile range [IQR], 10–15). Median PICU LOS stay was 11 days (8-18d) and hospital LOS was 22 days (16-31d). Among children with extracorporeal membrane oxygenation (n = 9), 6 cases survived and 3 cases died. The patients who need renal replacement therapy, neuromuscular blockade, parenteral nutrition, and packed red blood cell perfusion had higher hospital mortality (p < 0.001, p = 0.041, p = < 0.001, p = 0.012, respectively). Multivariate logistic analysis indicated that liver dysfunction and nosocomial infection were associated with high risk of mortality. Conclusions The hospital mortality of adenovirus pneumonia in our PICU was 16.42%. Patients complicated liver dysfunction and co-infection & nosocomial infection were associated with poor outcome.

Solfeggio is an important basic course for music majors, and audio recognition training is one of the important links. With the improvement of computer performance, audio recognition has been widely used in smart wearable devices. In recent years, the development of deep learning has accelerated the research process of audio recognition. However, there is a lot of sound interference in music teaching environment, which leads to the performance of the audio classifier that cannot meet the actual demand. In order to solve this problem, an improved audio recognition system based on YOLO-v4 is proposed, which mainly improves the network structure. First, Mel frequency cepstrum number is used to process the original audio and extract the corresponding features. Then, try to apply the YOLO-v4 model in the field of deep learning to the field of audio recognition and improve it by combining with the spatial pyramid pool module to strengthen the generalization ability of data in different audio formats. Second, the stacking method in ensemble learning is used to fuse the independent submodels of two different channels. Experimental results show that compared with other deep learning technologies, the improved YOLO-v4 model can improve the performance of audio recognition, and it has better performance in processing data of different audio formats, which shows better generalization ability.

Sepsis is extremely heterogeneous pathology characterized by complex metabolic changes. Fibroblast growth factor 19 (FGF19) is a well-known intestine-derived inhibitor of bile acid biosynthesis. However, it is largely unknown about the roles of FGF19 in improving sepsis-associated metabolic disorder and organ injury. In the present study, mice were intravenously injected recombinant human FGF19 daily for 7 days followed by lipopolysaccharide (LPS) administration. At 24 hours after LPS stimuli, sera were collected for metabolomic analysis. Ingenuity pathway analysis (IPA) network based on differential metabolites (DMs) was conducted. Here, metabolomic analysis revealed that FGF19 pretreatment reversed the increase of LPS-induced fatty acids. IPA network indicated that altered linoleic acid (LA) and gamma-linolenic acid (GLA) were involved in the regulation of oxidative stress and mitochondrial function and were closely related to reactive oxygen species (ROS) generation. Further investigation proved that FGF19 pretreatment decreased serum malondialdehyde (MDA) levels and increased serum catalase (CAT) levels. In livers, FGF19 suppressed the expression of inducible NO synthase (iNOS) and enhanced the expression of nuclear factor erythroid 2-related factor 2 (NRF2) and hemeoxygenase-1 (HO-1). Finally, FGF19 pretreatment protected mice against LPS-induced liver, ileum, and kidney injury. Taken together, FGF19 alleviates LPS-induced organ injury associated with improved serum LA and GLA levels and oxidative stress, suggesting that FGF19 might be a promising target for metabolic therapy for sepsis.

Background Optimal intraoperative positive end expiratory pressure (PEEP) improves patient outcomes. The pulse-oximetry has been used to determine the lung opening and closing pressures. Therefore, we hypothesized that intraoperative optimal PEEP obtained by titrating inspiratory oxygen fraction (FiO2) guided with pulse-oximetry could improve perioperative oxygenation. Methods Forty-six males undergoing elective robotic assisted laparoscopic prostatectomy were randomly assigned to either optimal PEEP (Group O, n=23) or control with fixed PEEP of 5 cmH2O (Group C, n=23). Optimal PEEP, defined as the PEEP with lowest FiO2 or 0.21 to maintain SpO2≥ 95%, was obtained in both groups after placing the patients in Trendelenburg position and peritoneal insufflation. Patients in Group O maintained the optimal PEEP and in Group C maintained PEEP of 5cmH2O intraoperatively. Both groups were extubated in a sitting position once the extubation criteria met. The primary outcome was the partial arterial oxygen pressure (PaO2)/inspiratory oxygen fraction (FiO2) prior to extubation. Secondary outcome was the incidence of postoperative hypoxemia (SpO2༜92% on room-air after extubation) in post-operative care unit. Results The median optimal PEEP was 16 cm H2O [inter-quartile range, 12-18]. The PaO2/FiO2prior to extubation was significantly higher in Group O than that in Group C (77.0±4.9kPa vs.60.6±5.9kPa, p=0.04); PaO2/FiO2 was also significantly higher in Group O 30minutes after extubation (57.6±1.9 vs. 46.6±1.8kPa, p=0.01). The incidence of hypoxemia on room air in the post-operative care unit was significantly lower in the Group O than in the Group C (1/23, or 4.3% vs. 7/23 or 30.4%, p =0.02). Conclusions Intraoperative optimal PEEP can be achieved by titration of FiO2 guided with SpO2. Maintaining intraoperative optimal PEEP improves intraoperative oxygenation and reduces the incidence of post-operative hypoxemia. Trial registration : Chinese Clinical Trial Registry identifier: ChiCTR2100051010. Prospectively registered on 10 September, 2021

Qiangji Decoction (QJD), a classic formula, has been widely used to treat brain aging–related neurodegenerative diseases. However, the mechanisms underlying QJD’s improvement in cognitive impairment of neurodegenerative diseases remain unclear. In this study, we employed D-galactose to establish the model of brain aging by long-term D-galactose subcutaneous injection. Next, we investigated QJD’s effect on cognitive function of the model of brain aging and the mechanisms that QJD suppressing neuroinflammation as well as improving neurodegenerative changes and hippocampal neuron apoptosis. The mice of brain aging were treated with three different dosages of QJD (12.48, 24.96, and 49.92 g/kg/d, respectively) for 4 weeks. Morris water maze was used to determine the learning and memory ability of the mice. HE staining and FJB staining were used to detect the neurodegenerative changes. Nissl staining and TUNEL staining were employed to detect the hippocampal neuron apoptosis. The contents of TNF-α, IL-1β, and IL-6 in the hippocampus were detected by using ELISA. Meanwhile, we employed immunofluorescence staining to examine the levels of GFAP and IBA1 in the hippocampus. Besides, the protein expression levels of Bcl-2, Bax, caspase-3, cleaved caspase-3, AMPKα, p-AMPKα-Thr172, SIRT1, IκBα, NF-κB p65, p-IκBα-Ser32, and p-NF-κB p65-Ser536 in the hippocampus of different groups were detected by Western blot (WB). Our findings showed that the QJD-treated groups, especially the M-QJD group, mitigated learning and memory impairments of the model of brain aging as well as the improvement of neurodegenerative changes and hippocampal neuron apoptosis. Moreover, the M-QJD markedly attenuated the neuroinflammation by regulating the AMPK/SIRT1/NF-κB signaling pathway. Taken together, QJD alleviated neurodegenerative changes and hippocampal neuron apoptosis in the model of brain aging via regulating the AMPK/SIRT1/NF-κB signaling pathway.

Kang-Xin Wang,1,&ast; Ting-Yun Cui,1,&ast; Xu-Dong Yang,2 Guo-Qun Wang,1 Qiu-Sheng Jiang,2 Hui Sun,1 Nan-Yuan Jiang,1 Xiao-Min Yong,3 Chuan-Bing Shi,4 Yong-Bin Ding,2 Xiao-Feng Chen,1,5,&ast; Yue-Yu Fang1,&ast; 1Department of Oncology, Pukou Branch Hospital of Jiangsu Province Hospital (Nanjing Pukou Central Hospital), Nanjing, 211800, People’s Republic of China; 2Department of General Surgery, Pukou Branch Hospital of Jiangsu Province Hospital (Nanjing Pukou Central Hospital), Nanjing, 211800, People’s Republic of China; 3Department of Radiology, Pukou Branch Hospital of Jiangsu Province Hospital (Nanjing Pukou Central Hospital), Nanjing, 211800, People’s Republic of China; 4Department of Pathology, Pukou Branch Hospital of Jiangsu Province Hospital (Nanjing Pukou Central Hospital), Nanjing, 211800, People’s Republic of China; 5Department of Oncology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 210029, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yue-Yu FangDepartment of Oncology, Pukou Branch Hospital of Jiangsu Province Hospital (Nanjing Pukou Central Hospital), No. 166 Shanghe Street, Pukou District, Nanjing, 211800, People’s Republic of ChinaEmail Fyymmy091120@163.comXiao-Feng ChenDepartment of Oncology, The First Affiliated Hospital with Nanjing Medical University, Pukou Branch Hospital of Jiangsu Province Hospital (Nanjing Pukou Central Hospital), No. 300 Guangzhou Road, Nanjing, 210029, People’s Republic of ChinaEmail chenxiaofengnjmu@163.comBackground: The standard treatment for advanced gastric/gastroesophageal junction cancer (AGC/GEJC) is palliative chemotherapy combined with targeted therapy. The SOX regimen (S-1 plus oxaliplatin) is recommended as neoadjuvant or palliative first-line chemotherapy in Asian patients. Apatinib, an oral VEGFR tyrosine kinase inhibitor, is associated with additional survival benefit as third- or subsequent-line therapy. However, the median overall survival time of AGC/GEJC is only 8– 11 months in the West and 13– 17 months in East Asia/Japan, even with the application of anti-angiogenic agents. Hence, the multimodal and individual management of patients is challenging standards to improve prognosis, including the preferential use of low-dose anti-angiogenic drugs and immunotherapy, as well as the application of multi-disciplinary treatment (MDT)-directed conversion therapy.Methods/Design: This single-center study was designed to combine low-dose apatinib with camrelizumab plus the SOX regimen in diagnosed potentially resectable and initially unresectable AGC/GEJC. This a prospective, open-label, single-arm, dose escalation and extension phase Ib clinical trial, conducted in Jiangsu Province Hospital, beginning from June 2020. All patients will first receive this combined regimen (3 weeks/cycle) for at most eight cycles, then apatinib and camrelizumab in maintenance therapy until disease progression, intolerable toxicity, death, a maximum 2 years of treatment or discontinuation for any reason. Follow-up and evaluation will be carried out regularly. If surgery is allowed by MDT discussions, oral apatinib will be discontinued during the last preoperative cycle. The primary endpoints are the objective response rate and maximum tolerated dose according to the Response Evaluation Criteria In Solid Tumors (RECIST) criteria (version 1.1) and the Common Terminology Criteria for Adverse Events (CTCAE) criteria (version 5.0).Discussion: This study will assess the response and side effects of AGC/GEJC patients in the use of low-dose apatinib combined with camrelizumab and the SOX regimen, and this combined therapy is expected to be a feasible and optimized first-line treatment option. In addition, this study will provide robust evidence and novel ideas for conversion therapy.Trial Registration: ChiCTR.gov.cn: ChiCTR2000034109.Keywords: clinical trial, AGC/GEJC, low-dose apatinib, camrelizumab, SOX regimen, protocol

Herein, X-ray photoelectron spectrometer (XPS), angle-resolved XPS (ARXPS), and atomic force microscopy (AFM) are used to study the surface changes of Ta2O5 bombarded by Ar+ ions with different energies. The results reveal that the Ar+ bombardment of Ta2O5 leads to a preferential sputtering of O atoms, which results in an imbalance in the Ta/O ratio on the material surface; and the formation of an “altered layer” composed of Ta2O5, Ta1+, Ta2+, Ta3+, and Ta4+. The Ta/O ratio increases from 0.34 to 0.55 with the sputtering time; however, it does not vary with ion energy. Before reaching a steady-state, the thickness of the altered layer increases with the sputtering time; however, after reaching a steady-state, the thickness of the altered layer does not exceed 3 nm. Concurrently, it increases with increasing sputtering energy. Further, AFM measurements reveal that low-energy Ar+ bombardment leads to a slight increased surface roughness, which does not exceed the initial value (0.41 nm) by 25%.