OBJECTIVE: To analyze the clinical and genetic characteristics of a Chinese pedigree affected with congenital Isolated growth hormone deficiency (IGHD). METHODS: A pedigree presenting with Pituitary stalk interruption syndrome (PSIS) (including the proband, his two younger sisters and both parents) who had visited the Capital Institute of Pediatrics Affiliated to Capital Medical University in September 2020 was selected as the study subject. Clinical data were collected. Peripheral blood samples were collected from the proband and his family members. Following the extraction of genomic DNA, whole-exome sequencing (WES) was carried out, and candidate variants were validated by Sanger sequencing. The pathogenicity of the candidate variants was classified based on guidelines from the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of the Institute Pediatrics of Capital Medical University (Ethics No.: SHERLL2025033). RESULTS: The proband and one younger sister (Ⅱ3) presented with growth retardation, short stature, and a doll-like facies. Another younger sister (Ⅱ2) and both parents had normal heights and appearance. Sanger sequencing confirmed that the proband and his younger sister (Ⅱ3) both harbored compound heterozygous variants of the GHRHR gene, namely c.776C>A (p.T259K) and c.1166G>A (p.R389Q). The other younger sister (Ⅱ2) and the parents were heterozygous carriers. The c.1166G>A (p.R389Q) variant was unreported previously. Based on the guidelines from the ACMG, it was classified as variant of uncertain significance (PM2_Supporting+BP4). Bioinformatics analysis indicated a deleterious effect on the protein function. CONCLUSION Variants of the GHRHR gene probably underlay the pathogenesis of IGHD in this pedigree. Above finding has provided a basis for the clinical diagnosis and genetic counseling for this family.
Child ; Female ; Humans ; Male ; China ; Dwarfism, Pituitary/genetics* ; Exome Sequencing ; Human Growth Hormone/deficiency* ; Mutation ; Pedigree ; Receptors, Neuropeptide/genetics* ; Receptors, Pituitary Hormone-Regulating Hormone/genetics* ; East Asian People/genetics*

Objective To investigate the correlation between single nucleotide polymorphisms(SNPs)of the EGF gene,including rs11569017(A>T),rs2237051(A>G),rs3733625(C>T),and rs4444903(A>G),and the risk of non-small cell lung cancer(NSCLC)in a Han population of Yunnan.Methods A total of 439 patients with NSCLC and 520 healthy controls were recruited in Yunnan Province between January 2022 and December 2023.Genotyping of four SNP loci in the EGF gene was performed using TaqMan probes,followed by analysis of allele,genotype,genetic model,and haplotype distribution frequencies between NSCLC and control groups.Stratified analyses were further conducted based on NSCLC pathological types and clinical stages.Results The rs2237051 locus showed significant differences in allele(P=0.011)and genotype(P=0.042)frequencies between the squamous cell carcinoma(SCC)group and the control group.The frequency of the A allele was lower in the SCC group than in the control group(OR=0.71,95%CI 0.54～1.85),but there was no difference after Bonferroni correction(P>0.0125).Under the log-additive model,the rs2237051-2G/G+A/G genotype was associated with an increased risk of SCC(P=0.01;OR=1.42,95%CI 1.08～1.86).However,the association lost statistical significance after Bonferroni correction(P>0.0125).The haplotype rs11569017-rs2237051-rs3733625-rs4444903 has no difference between the two groups(P>0.0125).The stratified analysis revealed no significant associations between the genetic loci and different disease stages(P>0.0125).Conclusion In the Yunnan Han population,the individuals carrying the rs2237051-A allele of the EGF gene have a significantly lower risk of squamous lung cancer,but further functional experiments are needed to verify the protective mechanism.

Ultra-high dose rate radiotherapy (dose rate ≥40 Gy/s), spearheading a revolution in radiation oncology through its unique " FLASH effect", demonstrates remarkable efficacy in eradicating tumors while concomitantly mitigating damage to normal tissues. This special issue compiles cutting-edge research, offering multi-dimensional insights into its biological mechanisms. At the molecular level, FLASH achieves targeted tumor killing by differentially regulating endoplasmic reticulum stress, cell cycle arrest patterns, programmed cell death, and energy metabolism reprogramming. FLASH irradiation may induce a transient oxygen depletion, creating a hypoxic window that facilitates the efficient scavenging of free radicals within normal tissues. Various animal studies have consistently validated FLASH's capacity to significantly alleviate both acute and long-term radiation injuries while potently suppressing tumor growth. Concurrently, advancements in physics and dosimetry have addressed the core challenges of precise delivery and measurement of ultra-high dose rates, in order to clear critical hurdles for clinical translation. In summary, FLASH radiotherapy has established a solid foundation, spanning from mechanistic elucidation to technological innovation. Its clinical translation now urgently demands the advancement of high-quality, standardized research, with the ultimate goal of safely and precisely harnessing the highly promising FLASH effect for patient benefit, thereby achieving a transformative leap in both therapeutic efficacy and quality of life for cancer patients undergoing radiotherapy.

AIM:To investigate the therapeutic effects of botulinum toxin A(BTXA)injection versus strabismus surgery in the treatment of acute acquired comitant esotropia(AACE).METHODS:Patient records of AACE cases treated at First People's Hospital of Nantong from January 2019 to September 2023 were retrospectively analyzed in this study. Patients were categorized into either strabismus surgery or BTXA injection groups based on treatment modality. Further stratification was performed according to preoperative deviation angles [>35 prism diopters(PD)vs ≤35 PD] and age(≥18 years adult group vs <18 years adolescent group). The baseline patient characteristics were collected, deviation angles at multiple timepoints before and after treatment were measured, and stereopsis test results were documented. Through comparative analysis of therapeutic outcomes across subgroups, we systematically evaluated the efficacy of different treatment approaches.RESULTS:A total of 43 AACE patients were included. At the final follow-up, both the surgery and BTXA injection groups showed a statistically significant decrease in deviation angle compared to pretreatment measurements(P<0.001). Significant differences were noted between the two groups in terms of the cure rate of strabismus and the recovery rate of stereopsis(P<0.05). For patients with deviations >35 PD, surgery yielded significantly better outcomes than injection therapy in postoperative angle, success rate, and stereopsis recovery(P<0.05). Similarly, in patients aged ≥18 years, surgical treatment was superior to injections in reducing strabismus angle, improving success rates, and restoring stereopsis(P<0.05).CONCLUSION:Both BTXA injection and strabismus surgery demonstrate therapeutic efficacy in AACE. Surgical treatment demonstrated superior efficacy compared to BTXA injection therapy, particularly in patients with deviations >35 PD and those aged ≥18 years. For patients with angles ≤35 PD or under 18 years, BTXA injection remains a viable treatment option.

Ultra-high dose rate radiotherapy (dose rate ≥40 Gy/s), spearheading a revolution in radiation oncology through its unique " FLASH effect", demonstrates remarkable efficacy in eradicating tumors while concomitantly mitigating damage to normal tissues. This special issue compiles cutting-edge research, offering multi-dimensional insights into its biological mechanisms. At the molecular level, FLASH achieves targeted tumor killing by differentially regulating endoplasmic reticulum stress, cell cycle arrest patterns, programmed cell death, and energy metabolism reprogramming. FLASH irradiation may induce a transient oxygen depletion, creating a hypoxic window that facilitates the efficient scavenging of free radicals within normal tissues. Various animal studies have consistently validated FLASH's capacity to significantly alleviate both acute and long-term radiation injuries while potently suppressing tumor growth. Concurrently, advancements in physics and dosimetry have addressed the core challenges of precise delivery and measurement of ultra-high dose rates, in order to clear critical hurdles for clinical translation. In summary, FLASH radiotherapy has established a solid foundation, spanning from mechanistic elucidation to technological innovation. Its clinical translation now urgently demands the advancement of high-quality, standardized research, with the ultimate goal of safely and precisely harnessing the highly promising FLASH effect for patient benefit, thereby achieving a transformative leap in both therapeutic efficacy and quality of life for cancer patients undergoing radiotherapy.

Objective By comparing the changes in cerebral blood flow,neuronal morphology in brain tissue,and the levels of serum oxidation and inflammatory factors in models of cerebral hypoperfusion,three experimental rat models were assessed for their suitability as subjects of studies on the mechanisms and therapeutic drugs of cerebrovascular diseases and neurodegenerative diseases.Methods A total of 88 male SD rats were randomly divided into a sham operation group(n=16),classic bilateral common carotid artery occlusion group(classic 2-VO group,n=24),modified 2-VO group(n=24),and intraluminal thread technique group(n=24).Bilateral common carotid artery ligation was performed on the classic 2-VO group,while blood was drawn from the common carotid artery before ligation in the modified 2-VO group(1 mL/100 g).Middle cerebral artery occlusion was performed on the intraluminal thread technique group.In the sham operation groups of the first two models,the common carotid artery was separated but not ligated,while the proximal end of the common carotid artery and the external carotid artery were ligated;in addition,the bolt thread was not inserted in the sham group of the intraluminal thread technique group.Cerebral blood flow,infarct volume,serum inflammatory factor levels,hematoxylin and eosin-stained morphology,and ultrastructure of the hippocampal tissue were assessed at 1,3,and 7 days after the operations.Results Laser speckle interferometry showed a decrease in cerebral blood flow of the modified 2-VO group that was more obvious than that of the other two groups.On day 7,only the modified 2-VO group still had significant differences in cerebral blood flow compared with the sham group,and it remained in a state of hypoperfusion(cerebral blood flow decreased by 30％compared with that before the operation).TTC staining showed that infarcts in the striata of the three groups gradually increased with time after the operation;4 rats(about 26.7％)in the modified 2-VO group and 10 rats(about 66.7％)in the intraluminal thread technique group had infarcts in both the cortex and striatum.ELISA showed that the levels of inflammatory factors,such as TNF-α,IL-1 β,and hs-CRP,in the three groups were increased after the operations,and levels of the pro-oxidation factor ROS were also increased.In contrast,levels of the antioxidant factor SOD decreased.On postoperative day 7,there was no significant difference in the hs-CRP of the classic 2-VO and intraluminal thread technique groups compared with that of the sham group.However,the modified 2-VO group still exhibited significant differences in all the above indicators compared with the sham group.Hematoxylin and eosin staining showed that the modified 2-VO group had more severe damage to the hippocampal CA1 and CA3 regions compared with the other groups.Transmission electron microscopy demonstrated that the modified 2-VO group showed more severe damage to the mitochondrial and endoplasmic reticulum in the hippocampal region compared with the other groups.Conclusions A cerebral hypoperfusion model was successfully established.Compared with the classic 2-VO and intraluminal thread techniques,the modified 2-VO method can induce more complete cerebral hypoperfusion and more severe neural damage within the same time frame,resembling the pathological state of human cerebral hypoperfusion more closely.

Alzheimer's disease (AD) is an irreversible neurodegenerative disorder that damages patients' memory and cognitive abilities. Therefore, the diagnosis of AD holds significant importance. The interactions between regions of interest (ROIs) in the brain often involve multiple areas collaborating in a nonlinear manner. Leveraging these nonlinear higher-order interaction features to their fullest potential contributes to enhancing the accuracy of AD diagnosis. To address this, a framework combining nonlinear higher-order feature extraction and three-dimensional (3D) hypergraph neural networks is proposed for computer-assisted diagnosis of AD. First, a support vector machine regression model based on the radial basis function kernel was trained on ROI data to obtain a base estimator. Then, a recursive feature elimination algorithm based on the base estimator was applied to extract nonlinear higher-order features from functional magnetic resonance imaging (fMRI) data. These features were subsequently constructed into a hypergraph, leveraging the complex interactions captured in the data. Finally, a four-dimensional (4D) spatiotemporal hypergraph convolutional neural network model was constructed based on the fMRI data for classification. Experimental results on the Alzheimer's Disease Neuroimaging Initiative (ADNI) database demonstrated that the proposed framework outperformed the Hyper Graph Convolutional Network (HyperGCN) framework by 8% and traditional two-dimensional (2D) linear feature extraction methods by 12% in the AD/normal control (NC) classification task. In conclusion, this framework demonstrates an improvement in AD classification compared to mainstream deep learning methods, providing valuable evidence for computer-assisted diagnosis of AD.
Humans ; Alzheimer Disease/diagnostic imaging* ; Neural Networks, Computer ; Magnetic Resonance Imaging/methods* ; Neuroimaging/methods* ; Diagnosis, Computer-Assisted ; Brain ; Cognitive Dysfunction

Objective:To explore the influencing factors of frailty in elderly patients with coronary heart disease (CHD), and to compare and analyze the value of different frailty scales in screening elderly patients with coronary heart disease.Methods:Using cross-sectional research methods，elderly patients with coronary heart disease from November 2019 to January 2020 in the Department of Cardiology of a tertiary hospital in Zhenjiang City were selected as the research objects. The frailty status of the patients was evaluated by the frailty index scale, and the patients were divided into frailty group (54 cases) and non-frailty group (149 cases) according to the evaluation results. F-test was used for the comparison between measurement data groups conforming to normal distribution, and χ 2 test or exact probability method was used for the comparison of counting data. Multivariate Logistic regression was used to analyze the main influencing factors of elderly patients with coronary heart disease. The correlation and consistency of clinical frail scale, frail scale and frail index were compared and analyzed were analyzed by Spearman correlation and Kappa test. ROC curve was used to analyze the sensitivity, specificity and the area under the working characteristic curve. Results:The age ((78.96±6.78) years), the percentage of monocytes >10% (31.48% (17/54)), the specific index for coronary heart disease ≥4 points (57.41% (31/54)), Barthel index <100 points (85.19% (46/54)), the mini nutritional assessment scale <24 points (66.67% (36/54)) of the patients in the frail group was higher than these in non-frail group ((73.94±5.89) years old, 12.08%(18/149), 7.38%(11/149), 22.15%(33/149), 14.77%(22/149)), the differences were statistically significant (statistical values were t=5.15, χ 2=10.46, χ 2=60.45, χ 2=66.26, χ 2=52.32; P values were <0.001,0.001,<0.001,<0.001,<0.001,respectively). The results of multivariate Logistic regression analysis showed that the percentage of monocytes >10% ( OR=5.927, 95% CI:1.854-18.947), the mini nutritional assessment scale <24 ( OR=7.026, 95% CI:2.660-18.555),the specific index for coronary heart disease ≥4 points ( OR=3.333, 95% CI:1.889-26.850,) and Barthel index <100 points ( OR=15.649, 95% CI:5.403-45.321) are the main effects of frailty in elderly patients with coronary heart disease factors ( P values were 0.003,<0.001,<0.001, and <0.001, respectively). Taking the frailty index as the gold standard, the sensitivity of the clinical frailty scale and FRAIL scale were 85.19% and 85.19%, respectively, and the specificity was 90.60% and 94.63%, respectively, with no significant difference (χ 2 values were 0.000 and 1.767; all P>0.05). The Kappa of the clinical frailty scale scale was <0.75, while the Kappa of the FRAIL scale was >0.75. The consistency of the frail scale with the gold standard was better than that of the clinical frailty scale scale. Conclusion:The percentage of monocytes, the specific index for coronary heart disease, the mini nutritional assessment scale and Barthel index are the main factors affecting the frailty of elderly patients with coronary heart disease. Taking the frailty index score as the standard, the consistency between the screening results of frail scale and frailty index score is better than that of clinical frailty scale scale, which has clinical application value.

Osteosarcoma is a kind of primary malignant tumor of bone originated from mesenchymal tissue, which mainly occurs in children and adolescents, and presents the characteristics of high malignancy, rapid growth, early metastasis and poor prognosis. Currently, most of the studies at home and abroad mainly focused on therapeutic procedures. However, reliable predictors are essential for monitoring disease changes, guiding treatment and evaluating prognosis. In recent years, the research on prognosis related genes of osteosarcoma has become a new hotspot. Its abnormal expression affects the progress, invasion and metastasis of osteosarcoma cells, and plays an important role in drug resistance and chemotherapy of osteosarcoma. This paper briefly summarizes the abnormal expression of genes related to the prognosis of osteosarcoma: miRNAs, Incrna, CircRNA, ErbB gene family and the imbalance of oncogenes and immune related genes, and fully understands their characteristics, in order to provide a new direction and possible new drug treatment target for the early diagnosis and treatment of osteosarcoma patients, so as to improve the prognosis of osteosarcoma patients.

Neutrophils are predominant leukocytes in the circulation, which are essential for killing invading pathogens via the activation of effector responses and the production of reactive oxygen species (ROS), also named as "oxidative burst." When infected, activated neutrophils fight bacteria, fungi, and viruses through oxidative burst, phagocytosis, degranulation, and the production of neutrophil extracellular traps (NETs) in a neutrophil death process named as "NETosis" (Mutua and Gershwin, 2021). NETs, consisting of DNA fibers decorated with modified histones and numerous antimicrobial proteins from cytoplasmic granules and the nucleus, can either be beneficial or detrimental (Mutua and Gershwin, 2021). Several pathways can lead to this death process. In response to various stimuli, NETosis traps and clears pathogens, facilitating phagocytosis by other neutrophils and phagocytes. However, excessive NETosis often results in disease due to increasing the pro-inflammatory response and perpetuating the inflammatory condition (Hellebrekers et al., 2018; Hidalgo et al., 2019; Klopf et al., 2021). Accordingly, inhibiting aberrant NETosis may alleviate the severity of various autoimmune and inflammatory diseases.
DNA ; Extracellular Traps/metabolism* ; Neutrophils/metabolism* ; Reactive Oxygen Species/metabolism* ; Respiratory Burst