To address the challenges faced by current brain midline segmentation techniques, such as insufficient accuracy and poor segmentation continuity, this paper proposes a deep learning network model based on a two-stage framework. On the first stage of the model, prior knowledge of the feature consistency of adjacent brain midline slices under normal and pathological conditions is utilized. Associated midline slices are selected through slice similarity analysis, and a novel feature weighting strategy is adopted to collaboratively fuse the overall change characteristics and spatial information of these associated slices, thereby enhancing the feature representation of the brain midline in the intracranial region. On the second stage, the optimal path search strategy for the brain midline is employed based on the network output probability map, which effectively addresses the problem of discontinuous midline segmentation. The method proposed in this paper achieved satisfactory results on the CQ500 dataset provided by the Center for Advanced Research in Imaging, Neurosciences and Genomics, New Delhi, India. The Dice similarity coefficient (DSC), Hausdorff distance (HD), average symmetric surface distance (ASSD), and normalized surface Dice (NSD) were 67.38 ± 10.49, 24.22 ± 24.84, 1.33 ± 1.83, and 0.82 ± 0.09, respectively. The experimental results demonstrate that the proposed method can fully utilize the prior knowledge of medical images to effectively achieve accurate segmentation of the brain midline, providing valuable assistance for subsequent identification of the brain midline by clinicians.
Humans ; Brain/diagnostic imaging* ; Deep Learning ; Image Processing, Computer-Assisted/methods* ; Algorithms ; Magnetic Resonance Imaging/methods* ; Neural Networks, Computer

Amoenucles A-F (1-6), six previously undescribed nucleoside derivatives, and two known analogs (7 and 8) were isolated from the culture of Aspergillus amoenus TJ507. Their structures were elucidated through spectroscopic analysis, single-crystal X-ray crystallography, and chemical reactions. Notably, 3 and 4 represent the first reported instances of nucleosides with an attached pyrrole moiety. Of particular significance, the absolute configuration of the sugar moiety of 1-4 was determined using nuclear magnetic resonance (NMR), electric circular dichroism (ECD) calculations, and a hydrolysis reaction, presenting a potentially valuable method for confirming nucleoside structures. Furthermore, 1, 2, and 5-8 exhibited potential tumor necrosis factor α (TNF-α) inhibitory activities, which may provide a novel chemical template for the development of agents targeting autoimmune and inflammatory diseases.
Aspergillus/chemistry* ; Tumor Necrosis Factor-alpha/antagonists & inhibitors* ; Molecular Structure ; Nucleosides/isolation & purification* ; Crystallography, X-Ray ; Animals ; Humans ; Mice ; Magnetic Resonance Spectroscopy

Hepatic ischemia/reperfusion injury (IRI) remains a critical complication contributing to graft dysfunction following liver surgery. As part of an ongoing search for hepatoprotective natural products, five previously unreported homoadamantane-type polycyclic polyprenylated acylphloroglucinols (PPAPs), named hyperhomanoons A-E (1-5), and one known analog, hypersampsone O (6), were isolated from Hypericum patulum. Among these, compound 6 demonstrated potent protective effects against CoCl₂-induced hypoxic injury in hepatocytes. Furthermore, in a murine model of hepatic IRI induced by vascular occlusion, pretreatment with 6 markedly alleviated liver damage and reduced hepatocyte apoptosis. This study is the first to identify PPAPs as promising scaffolds for the development of therapeutic agents targeting hepatic IRI, underscoring their potential as lead compounds in drug discovery efforts for ischemic liver diseases.
Reperfusion Injury/prevention & control* ; Animals ; Hypericum/chemistry* ; Phloroglucinol/administration & dosage* ; Mice ; Humans ; Male ; Liver/blood supply* ; Apoptosis/drug effects* ; Molecular Structure ; Protective Agents/pharmacology* ; Hepatocytes/drug effects* ; Mice, Inbred C57BL ; Liver Diseases/drug therapy*

Objective:To investigate the clinical diagnosis, treatment, and genetic variations of neonates with congenital hyperinsulinism (CHI).Methods:The clinical data of CHI newborns admitted to the Provincial Hospital Affiliated to Shandong First Medical University from September 2018 to April 2022 were retrospectively analyzed.Results:Four cases of CHI were included, three of whom were full-term infants and all were macrosomic, while one was a premature infant. One infant was born to a mother with gestational diabetes mellitus, and 1 had a family history of hypoglycemia. All the 4 patients presented with weak response, 3 with drowsiness, 1 with hypotonia and 1 with convulsions. Cranial MRI indicated abnormal signals in the occipital lobe cortex in 1 case. Gene sequencing revealed homozygous variation c.799C>G in KCNJ11 gene for 1 case, and heterozygous variations c.4477C>T, c.3540C>G, c.683G>A and c.4536C>A in ABCC8 gene for 3 cases respectively and all these variations were identified as pathogenic mutations. Notably, the c.799C>G variant in KCNJ11 gene as well as the c.3540C>G and c.4536C>A variants in ABCC8 gene were reported for the first time. Among infants with ABCC8 gene variations, two showed no response to diazoxide treatment while one patient with KCNJ11 gene variation responded effectively. The parents of the patient with hypoglycemic brain injury gave up treatment. Three other cases were discharged from hospital after improvement and followed up to 1 year old. 2 patients had stable blood glucose after ceasing medication, and 1 patient still required intermittent oral glucose to maintain normal blood glucose level.Conclusions:CHI can lead to hypoglycemic brain injury. Clinically, infants large for gestational age or with a family history of diabetes and hypoglycemia should be monitored for blood glucose early after birth, to identify CHI as early as possible and actively treat it. Different gene variants have different therapeutic responses.

Objective:To investigate the association between congenital hypothyroidism (CH) and the adverse outcomes during hospitalization in very low birth weight infants (VLBWI).Methods:This prospective, multicenter observational cohort study was conducted based on the data from the Sino-northern Neonatal Network (SNN). Data of 5 818 VLBWI with birth weight <1 500 g and gestational age between 24-<37 weeks that were admitted to the 37 neonatal intensive care units from January 1 st, 2019 to December 31 st, 2022 were collected and analyzed. Thyroid function was first screened at 7 to 10 days after birth, followed by weekly tests within the first 4 weeks, and retested at 36 weeks of corrected gestational age or before discharge. The VLBWI were assigned to the CH group or non-CH group. Chi-square test, Fisher exact probability method, Wilcoxon rank sum test, univariate and multivariate Logistic regression were used to analyze the relationship between CH and poor prognosis during hospitalization in VLBWI. Results:A total of 5 818 eligible VLBWI were enrolled, with 2 982 (51.3%) males and the gestational age of 30 (29, 31) weeks. The incidence of CH was 5.5% (319 VLBWI). Among the CH group, only 121 VLBWI (37.9%) were diagnosed at the first screening. Univariate Logistic regression analysis showed that CH was associated with increased incidence of extrauterine growth retardation (EUGR) ( OR=1.31(1.04-1.64), P<0.05) and retinopathy of prematurity (ROP) of stage Ⅲ and above ( OR=1.74(1.11-2.75), P<0.05). However, multivariate Logistic regression analysis showed no significant correlation between CH and EUGR, moderate to severe bronchopulmonary dysplasia, grade Ⅲ to Ⅳ intraventricular hemorrhage, neonatal necrotizing enterocolitis in stage Ⅱ or above, and ROP in stage Ⅲ or above ( OR=1.04 (0.81-1.33), 0.79 (0.54-1.15), 1.15 (0.58-2.26), 1.43 (0.81-2.53), 1.12 (0.70-1.80), all P>0.05). Conclusion:There is no significant correlation between CH and in-hospital adverse outcomes, possibly due to timely diagnosis and active replacement therapy.

Objective     To exploring the effectiveness of perioperative application of new surgical clinical classification and staging for myasthenia gravis (MG) in reducing the incidence of postoperative myasthenic crisis (MC). Methods     The clinical data of patients with generalized MG admitted to the Comprehensive Treatment Center for Myasthenia Gravis of Henan Provincial People’s Hospital from January 2018 to June 2022 were retrospectively analyzed, who were scored with myasthenia gravis-activities of daily living (MG-ADL) score and quantification of the myasthenia gravis (QMG) score at the first visit, 1 day before surgery, and 3 days after surgery. The patients were divided into a group A (typeⅡ) and a group B (typeⅢ+Ⅳ+Ⅴ) by the new surgical clinical classification and staging of MG according to the disease progression process, and all patients underwent expanded thoracoscopic thymus (tumor) resection after medication and other interventions to control symptoms in remission or stability. The incidence of MC and the efficiency rate after surgery were analyzed. The normal distribution method and percentile method were used to calculate the unilateral 95% reference range of the QMG score and MG-ADL score. Results     Finally 126 patients were enrolled, including 62 males and 64 females, aged 13-71 years, with an average age of 46.00±13.00 years. There were 95 patients in the group A and 31 patients in the group B, and the differences of the preoperative baseline data between the two groups were not statistically significant (P>0.05). The incidence of postoperative MC was 1.05% (1/95) in the group A and 3.23%(1/31) in the group B (P>0.05). The effective one-sided 95% reference range of the QMG score and MG-ADL score 1 day before surgery was 0-7.75 and 0-5.00, and there was no postoperative death in both groups. Conclusion     The new surgical clinical classification and staging of MG can guide the timing of surgery, which can benefit patients undergoing surgery for MG and greatly reduce the incidence of postoperative MC.

Objective    To investigate the expression of α7 nicotinic acetylcholine receptor (α7 nAChR) in thymocytes of patients with myasthenia gravis (MG) and its effect on cytokine secretion and T cell proliferation. Methods    Patients with MG who underwent expanded thoracoscopic thymectomy in the Comprehensive Diagnosis and Treatment Center of the Henan Provincial People’s Hospital from June 2021 to June 2022 were selected and allocated to a MG group. Patients who underwent partial thymectomy to expose the surgical field during the cardiac disease surgery from June 2021 to September 2022 in the Department of Adult Cardiac Surgery of Fuwai Huazhong Cardiovascular Hospital were selected as the control group. Thymic single cell suspensions were prepared from MG and control groups, and the expression of α7 nAChR in thymocytes of the two groups was detected by real-time polymerase chain reaction and Western blotting. Then CD3/CD28 monoclonal antibody coupled with magnetic beads was used to induce T cell activation, and the levels of cytokines interferon-gamma (IFN-γ), tumor necrosis factor-α (TNF-α), interleukin-4 (IL-4), IL-6, IL-10, IL-17, and IL-21 in thymocytes of the two groups were detected by enzyme-linked immunosorbent assay (ELISA). The activated T cells of the MG group were divided into a blank control group, an α7 nAChR antagonist group, and an α7 nAChR agonist group according to different treatment methods. After 72 hours of culture, IFN-γ, TNF-α, IL-4, IL-6, IL-10, IL-17, and IL-21 expression levels in the culture supernatant were measured by ELISA. Afterwards, CD4-PE and CD8-APC antibodies were added, and the proliferation of T cell subsets was detected by flow cytometry. Results    A total of 10 MG patients were collected, including 3 males and 7 females with an average age of 19.25±6.28 years; and 15 control patients were collected, including 6 males and 9 females with an average age of 26.18±6.77 years. Compared with the control group, the mRNA and protein levels of α7 nAChR in the thymocytes of MG group were decreased, and the expression levels of IFN-γ, TNF-α, IL-4, IL-6 and IL-21 in the supernatant were increased (P<0.05), but there was no statistical difference in the expression of IL-10 and IL-17 (P>0.05). The cell-culture experiment showed that compared with the blank control group, the levels of IFN-γ, TNF-α, IL-6 and IL-21 secreted by T cells in the α7 nAChR antagonist group were increased (P<0.05), while they were decreased in the α7 nAChR agonist group (P<0.05). There was no statistical difference in the secretion levels of IL-4, IL-10 or IL-17 among the three groups (P>0.05). CD4+ T and CD8+ T cells in the α7 nAChR agonist group were significantly less than those in the blank control group and α7 nAChR antagonist group (P<0.001), while they were significantly more in the α7 nAChR antagonist group than those in the blank control group (P<0.001). Conclusion    The expression of α7 nAChR in thymocytes of MG patients is decreased, and α7 nAChR may be involved in the inflammatory response in thymocytes and thus in thymic function.

Healthcare Big Data and its driven real-world study (RWS) have increasingly become important sources of evidence for medical decision-making.Drawing on successful international experiences, China′s neonatal-perinatal field has established national or regional neonatal collaboration networks to conduct various forms of clinical scientific researches, continuously improving the treatment and care level for preterm infants.How to construct a scientific clinical research methodology system based on clinical issues in China′s neonatal field and reliable real-world data is currently a pressing issue that needs to be addressed.This article discussed the methodological exploration for advancing neonatal clinical scientific research through regional collaboration networks.

Background::Endoscopic resection is increasingly used in the treatment for early gastric cancer (EGC); however, about 15% of endoscopic submucosal dissection (ESD) cases report non-curative resection. The efficacy of different remedial interventions after non-curative ESD for EGC remains controversial. This meta-analysis aimed to compare the long-term outcomes of additional surgery and non-gastrectomy treatment for EGC patients who underwent non-curative ESD.Methods::All relevant studies published up to October 2021 were systematically searched in the PubMed, Web of Science, and Embase databases. The medical subject headings terms "early gastric cancer," "gastrectomy," "endoscopic submucosal dissection," and their related free keywords were used to search relevant articles without restrictions on regions, publication types, or languages. The Newcastle–Ottawa Quality Assessment Scale was used to evaluate the quality of the included studies. Odds ratios (ORs) with 95% confidence intervals (CIs) of 5-year overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS) and hazard ratios (HRs) with 95% CIs of OS were calculated using a random- or fixed-effects model.Results::This meta-analysis included 17 retrospective cohort studies with 5880 patients, of whom 3167 underwent additional surgery and 2713 underwent non-gastrectomy. We found that patients receiving additional gastrectomy had better 5-year OS (OR = 3.63, 95% CI = 3.05–4.31), DSS (OR = 3.22, 95% CI = 2.22–4.66), and DFS (OR = 4.39, 95% CI = 1.78–10.82) outcomes than those receiving non-gastrectomy treatments. The pooled HR also showed that gastrectomy following non-curative ESD significantly improved OS (HR = 0.40, 95% CI = 0.33–0.48). In addition, elderly patients benefited from additional surgery in consideration of the 5-year OS (HR = 0.54, 95% CI= 0.41–0.72).Conclusions::Compared with non-gastrectomy treatments, additional surgery offered better long-term survival outcomes for patients with EGC who underwent non-curative ESD.

Objective To investigate the composition and pathological subtypes of thyroid cancer in patients with thyroid nodule surgery in Guiyang in recent 8 years, and to analyze their influencing factors. Methods A retrospective pathological analysis of 4 262 thyroid surgery cases in Affiliated Hospital of Guizhou Medical University during the 2009-2016 to investigate the proportion of thyroid cancer and pathological subtype. The iodine content of salt was reduced at the end of 2012 in Guiyang. 2009-2012 as the pre down-regulation group(n＝1 572), 2013-2016 as the after down-regulation group ( n＝2 690), then comparative analysis before and after the adjustment of the iodine content of salt composition of thyroid cancer and changes of pathological subtype was performed. Results From 2009 to 2016, the proportion of thyroid cancer were 17.08%, 17.52%,15.65%, 18.58%, 19.80%, 29.35%, 35.34%, and 48.33%, increased year by year (P＜0.05). Thyroid microcarcinoma were 2.14%, 4.74%, 3.40%, 3.65%, 3.80%, 7.03%, 9.10%, and 25.95%(P＜0.05). The constituent ratio of thyroid cancer after adjustment of salt iodine content was higher than before. Papillary thyroid carcinoma is the main pathological subtype before and after adjustment of salt iodine content. The proportion of female patients was higher than that of males. The age of patients with thyroid cancer after adjustmen was higher than before ( P＜0. 05). Conclusions In the past 8 years, the constituent ratio of thyroid cancer and thyroid microcarcinoma in Guiyang increased year by year. The reason may be related to the increase of radiation in the environment, the improvement of medical level and the higher detection rate of thyroid microcarcinoma. The relationship between iodine nutrition and thyroid cancer needs to be further studied.[Key words] Thyroid cancer; Thyroid microcarcinoma; Thyroid papillary carcinoma; Pathological type;Iodized salt; Iodine nutrition