Although a single nucleotide polymorphism for N-acetyltransferase 10 (NAT10) has been identified in patients with early-onset stroke, the role of NAT10 in ischemic injury and the related underlying mechanisms remains elusive. Here, we provide evidence that NAT10, the only known RNA N4-acetylcytidine (ac4C) modification "writer", is increased in the damaged cortex of patients with acute ischemic stroke and the peri-infarct cortex of mice subjected to photothrombotic (PT) stroke. Pharmacological inhibition of NAT10 with remodelin on Days 3-7 post-stroke or astrocytic depletion of NAT10 via targeted virus attenuates ischemia-induced infarction and improves functional recovery in PT mice. Mechanistically, NAT10 enhances ac4C acetylation of the inflammatory cytokine tissue inhibitor of metalloproteinase 1 (Timp1) mRNA transcript, which increases TIMP1 expression and results in the accumulation of microtubule-associated protein 1 light chain 3 (LC3) and progression of astrocyte autophagy. These findings demonstrate that NAT10 regulates astrocyte autophagy by targeting Timp1 ac4C after stroke. This study highlights the critical role of ac4C in the regulation of astrocyte autophagy and proposes a promising strategy to improve post-stroke outcomes via NAT10 inhibition.

SMARCA4-deficient non small cell lung cancer (SMARCA4-dNSCLC) has recently garnered increasing attention due to its high malignancy and poor prognosis. The literature suggests that in non small cell lung cancer (NSCLC), the loss of SMARCA4 frequently co-occurs with mutations in KRAS, KEAP1, and STK11 rather than in EGFR, ALK, and ROS1. Herein, we present the first documented case of SMARCA4-dNSCLC accompanied with rare mutations of EGFR exon 20 S768I and exon 18 G719X. The patient achieved partial response with afatinib for 17 months. Our case highlights the importance of EGFR mutations in the precision targeted treatment of SMARCA4-dNSCLC.
Humans ; Afatinib/therapeutic use* ; Antineoplastic Agents/therapeutic use* ; Carcinoma, Non-Small-Cell Lung/pathology* ; DNA Helicases/genetics* ; ErbB Receptors/genetics* ; Lung Neoplasms/pathology* ; Mutation ; Nuclear Proteins/genetics* ; Transcription Factors/genetics*

Objective:To investigate the impact of neuroendocrine function on postoperative complications and nutritional status in gastric cancer patients.Methods:Clinical data of 102 gastric cancer patients who underwent radical gastrectomy at the Department of General Surgery, First Affiliated Hospital of Soochow University, from Aug 2021 to Jun 2022 were retrospectively analyzed.Results:Among the 102 gastric cancer patients, 18 (17.6%) suffered from postoperative complications. Univariate analysis indicated that age, BMI, preoperative plasma ghrelin concentration, and preoperative hemoglobin levels were associated with early postoperative complications following radical gastrectomy. Multivariate analysis revealed that age, BMI, and preoperative plasma ghrelin concentration ( P<0.05) were independent risk factors for postoperative complications in gastric cancer patients. Differential analysis of ghrelin concentration demonstrated correlations with hemoglobin levels, skeletal muscle index, albumin, and creatinine, and a positive correlation with the skeletal muscle index. Conclusions:Reduced preoperative neuroendocrine hormone ghrelin concentration is an independent risk factor for postoperative complications in gastric cancer patients. Ghrelin concentration is correlated with the skeletal muscle index in these patients.

Ghrelin is a newly discovered gastrointestinal peptide that is involved in regulating the body's growth,development and energy balance,and plays a key role in the occurrence and progression of malignant tumors,such as cell proliferation,migration,invasion,apoptosis,inflammatory response and vascular disease.Generate immune cell infiltration and so on.Ghrelin affects the progression of gastric cancer by activa-ting NF-κB/p65 and AMPK and other signaling pathways.Ghrelin not only assist in early screening of gastric cancer,but also function a new marker for predicting the prognosis and survival of gastric cancer patients.Ghrelin and its analogs have clinical application value in the treatment of gastric cancer-related syndromes such as cachexia or sarcopenia.

Background and Aims:In recent years,function-preserving proximal gastrectomy with reconstruction has become an important approach for the treatment of early gastric cancer.However,there is no standardized surgical technique,and the short-and long-term outcomes of various new procedures remain unclear.This study was performed to evaluate the safety and short-term efficacy of laparoscopic proximal gastrectomy plus esophagogastrostomy with single-flap technique for early gastric cancer. Methods:The clinical data and follow-up records of 7 patients who underwent laparoscopic proximal gastrectomy with single-flap esophagogastrostomy in the First Affiliated Hospital of Soochow University between December 2021 and December 2022 were retrospectively analyzed.Perioperative safety,postoperative reflux,anastomotic stricture at 6 months,and related nutritional parameters were assessed.The nutrition-related indicators of this group of patients were compared with those of 11 patients who underwent total gastrectomy with Roux-en-Y anastomosis for early gastric cancer during the same period. Results:All 7 patients successfully underwent laparoscopic proximal gastrectomy with single-flap esophagogastrostomy.The average operative time was(212.9±20.6)min,with anastomosis taking(54.7±10.5)min;the mean intraoperative blood loss was(28.6±9.0)mL.No Clavien-Dindo grade Ⅲ or higher complications were observed during hospitalization.None of the patients experienced significant reflux symptoms,although 1 patient developed anastomotic stricture 3 months after operation.There were no statistically significant differences in hemoglobin concentration,albumin level,prealbumin level,total protein concentration,and lymphocyte count between preoperative and 6-month postoperative measurements(all P＞0.05).Compared to patients who underwent total gastrectomy with Roux-en-Y anastomosis,those who had the proximal gastrectomy with single-flap esophagogastrostomy showed a lower percentage decrease in body weight,skeletal muscle area at the third lumbar vertebra(L3),visceral fat area at L3,and hemoglobin concentration at 1 year after operation(all P＜0.05). Conclusion:Laparoscopic proximal gastrectomy with single-flap esophagogastrostomy is a safe and feasible surgical option for early gastric cancer,offering effective anti-reflux outcomes while minimizing the risk of anastomotic stricture.This procedure has a lower impact on postoperative nutritional status compared to total gastrectomy.

Objective    To systematically evaluate the clinical efficacy and adverse reactions of paclitaxel and carboplatin with or without bevacizumab in the treatment of non-small cell lung cancer (NSCLC). Methods    The databases including PubMed, The Cochrane Library, EMbase, CNKI, Wanfang Data, VIP and CBM were searched from inception to October 2022 to collect randomized controlled trials of the clinical efficacy of paclitaxel and carboplatin with or without bevacizumab for the treatment of NSCLC. RevMan 5.4 software was used for meta-analysis. Results    Eight randomized controlled trials were enrolled, involving a total of 1 724 patients. Meta-analysis showed that for the treatment of NSCLC, the disease control rate, overall response rate, 1-year survival rate, and 2-year survival rate were higher in the trial group (paclitaxel and carboplatin combined with bevacizumab) than those in the control group (paclitaxel and carboplatin) (P<0.05); however, the incidences of the adverse reactions, such as leukopenia, hemorrhage, proteinuria and hypertension, etc, were higher in the trial group than those in the control group (P<0.05). There were no statistical differences between the trial group and the control group in the incidences of fatigue, thrombocytopenia, neutropenia or hyponatremia, etc (P>0.05). In addition, the median progression-free survival and overall survival were longer in the trial  group than those in the control group. Conclusion    For the treatment of NSCLC, paclitaxel and carboplatin combined with bevacizumab is superior in terms of disease control, overall response and prolonging patient survival, etc, but will be associated with more adverse reactions.

OX40 is a costimulatory receptor that is expressed primarily on activated CD4⁺, CD8⁺, and regulatory T cells. The ligation of OX40 to its sole ligand OX40L potentiates T cell expansion, differentiation, and activation and also promotes dendritic cells to mature to enhance their cytokine production. Therefore, the use of agonistic anti-OX40 antibodies for cancer immunotherapy has gained great interest. However, most of the agonistic anti-OX40 antibodies in the clinic are OX40L-competitive and show limited efficacy. Here, we discovered that BGB-A445, a non-ligand-competitive agonistic anti-OX40 antibody currently under clinical investigation, induced optimal T cell activation without impairing dendritic cell function. In addition, BGB-A445 dose-dependently and significantly depleted regulatory T cells in vitro and in vivo via antibody-dependent cellular cytotoxicity. In the MC38 syngeneic model established in humanized OX40 knock-in mice, BGB-A445 demonstrated robust and dose-dependent antitumor efficacy, whereas the ligand-competitive anti-OX40 antibody showed antitumor efficacy characterized by a hook effect. Furthermore, BGB-A445 demonstrated a strong combination antitumor effect with an anti-PD-1 antibody. Taken together, our findings show that BGB-A445, which does not block OX40-OX40L interaction in contrast to clinical-stage anti-OX40 antibodies, shows superior immune-stimulating effects and antitumor efficacy and thus warrants further clinical investigation.
Mice ; Animals ; Receptors, Tumor Necrosis Factor/physiology* ; Receptors, OX40 ; Membrane Glycoproteins ; Ligands ; Antibodies, Monoclonal/pharmacology* ; Antineoplastic Agents/pharmacology*

OBJECTIVE: To propose a framework that combines sinogram interpolation with unsupervised image-to-image translation (UNIT) network to correct metal artifacts in CT images. METHODS: The initially corrected CT image and the prior image without artifacts, which were considered as different elements in two different domains, were input into the image transformation network to obtain the corrected image. Verification experiments were carried out to assess the effectiveness of the proposed method using the simulation data, and PSNR and SSIM were calculated for quantitative evaluation of the performance of the method. RESULTS: The experiment using the simulation data showed that the proposed method achieved better results for improving image quality as compared with other methods, and the corrected images preserved more details and structures. Compared with ADN algorithm, the proposed algorithm improved the PSNR and SSIM by 2.4449 and 0.0023 when the metal was small, by 5.9942 and 8.8388 for images with large metals, and by 8.8388 and 0.0130 when both small and large metals were present, respectively. CONCLUSION The proposed method for metal artifact correction can effectively remove metal artifacts, improve image quality, and preserve more details and structures on CT images.
Artifacts ; Algorithms ; Computer Simulation ; Tomography, X-Ray Computed

OBJECTIVE: To compare the ability of the step-by-step approach and the lab-score method in early identification of non-bacterial infection in febrile infants with less than 90 days old. METHODS: A prospective study was conducted. The febrile infants with less than 90 days old hospitalized in the department of pediatrics of Xuzhou Central Hospital from August 2019 to November 2021 were enrolled. The basic data of the infants were recorded. The infants with high risk or low risk of bacterial infection was evaluated by the step-by-step approach and the lab-score method, respectively. The step-by-step approach was based on clinical manifestations, age, blood neutrophil absolute value or C-reactive protein (CRP), urine white blood cells, blood venous blood procalcitonin (PCT) or interleukin-6 (IL-6) to gradually assess the high risk or low risk of bacterial infection in infants with fever. The lab-score method was based on the levels of laboratory indicators such as blood PCT, CRP and urine white blood cells, which were assigned different scores to evaluate the high risk or low risk of bacterial infection in febrile infants according to the total score. Using clinical bacterial culture results as the "gold standard", the negative predictive value (NPV), positive predictive value (PPV), negative likelihood ratio, positive likelihood ratio, sensitivity, specificity, and accuracy of the two methods were calculated. The consistency of the two evaluation methods was tested by Kappa. RESULTS: A total of 246 patients were enrolled in the analysis, and ultimately confirmed by bacterial culture as non-bacterial infections in 173 cases (70.3%), bacterial infection in 72 cases (29.3%), and unclear in 1 case (0.4%). There were 105 cases with low risk evaluated by the step-by-step approach, and 98 cases (93.3%) were ultimately confirmed as non-bacterial infection; 181 cases with low risk evaluated by the lab-score method, and 140 cases (77.4%) were ultimately confirmed as non-bacterial infection. The consistency of the two evaluation methods was poor (Kappa value = 0.253, P < 0.001). The ability of the step-by-step approach in early identification of non-bacterial infection in febrile infants with less than 90 days old was superior to the lab-score method (NPV: 0.933 vs. 0.773, negative likelihood ratio: 5.835 vs. 1.421), but the sensitivity of the former was lower than that of the latter (0.566 vs. 0.809). The ability of the step-by-step approach in early identification of bacterial infection in febrile infants with less than 90 days old was similar to the lab-score method (PPV: 0.464 vs. 0.484, positive likelihood ratio: 0.481 vs. 0.443), but the specificity of the former was higher than that of the latter (0.903 vs. 0.431). The overall accuracy of the step-by-step approach and the lab-score method was similar (66.5% vs. 69.8%). CONCLUSIONS The ability of the step-by-step approach in early identification of non-bacterial infections in febrile infants with less than 90 days old is superior to the lab-score method.
Humans ; Infant ; Child ; Prospective Studies ; Bacterial Infections ; C-Reactive Protein ; Hospitals ; Interleukin-6 ; Procalcitonin

Humans ; Adult ; Serum Albumin, Human ; Consensus ; Cardiac Surgical Procedures ; Thoracic Surgery