BACKGROUND: Neoadjuvant therapeutic strategies play a pivotal role in the comprehensive treatment of non-small cell lung cancer (NSCLC). However, lung squamous cell carcinoma (SCC) generally exhibits a more favorable response to neoadjuvant therapy compared with lung adenocarcinoma (ADC). The aim of this study is to elucidate how baseline cancer-associated fibroblasts (CAFs) and tumor-associated endothelial cells (TAECs) influence the differential therapeutic outcomes of neoadjuvant treatment in SCC versus ADC. METHODS: We retrospectively collected pretreatment biopsy samples from 104 patients with stage II-III NSCLC who underwent neoadjuvant chemotherapy (NAC) or neoadjuvant chemoimmunotherapy (NAIC) at Shandong Cancer Hospital between January 1, 2018 and December 31, 2023. Tissue microarrays were constructed using an automated arrayer, and multiplex immunofluorescence staining (α-SMA/CD31/CK/DAPI) was performed to identify CAFs (α-SMA+/CK-) and TAECs (CD31+/CK-). Quantitative analyses included CAFs and TAECs densities, the nearest neighbor distance (NND) between CAFs and TAECs, and their spatial proximity (30 μm). Differences in major pathological response (MPR) between groups, defined as residual viable tumor cells ≤10% in resected specimens after neoadjuvant therapy, were assessed using the χ² test. The Mann-Whitney U test was applied to analyze intergroup differences in quantitative indicators, and receiver operating characteristic (ROC) curve analysis was conducted to evaluate the predictive performance of immune-related markers for MPR in the NAIC cohort. RESULTS: Among the 104 NSCLC patients who received neoadjuvant therapy, 35 underwent NAIC and 69 received NAC. Overall, patients with SCC were more likely to achieve MPR compared with those with ADC (50.0% vs 22.4%, P=0.006). This trend persisted in the NAIC subgroup (72.7% vs 30.8%, P=0.038), whereas no significant difference in MPR rates was observed between SCC and ADC in the NAC subgroup. At baseline, prior to NAIC or NAC, programmed cell death ligand 1 (PD-L1)/programmed cell death 1 (PD-1) expression, CAFs and TAECs densities, CAFs-TAECs NND, and CAFs-TAECs proximity (30 μm) showed no significant differences between SCC and ADC. In patients with SCC receiving NAIC, baseline PD-L1/PD-1 expression, CAFs density, and TAECs density showed not significant differences between MPR and NMPR groups. However, the CAFs-TAECs distance was significantly greater in the MPR group (NND: 31.2 vs 24.7 μm, P=0.038), and the number of TAECs within 30 μm of CAFs was significantly lower (proximity: 1.1 vs 3.6, P=0.038). Univariate Cox regression analysis indicated that low TAECs density was associated with MPR following NAIC (OR=36.00, 95%CI: 2.68-1486.88, P=0.019). Furthermore, ROC analysis demonstrated that baseline CAFs-TAECs NND and proximity (30 μm) exhibited strong predictive performance for MPR in SCC patients treated with NAIC, with an area under the curve (AUC) of 0.893, sensitivity of 0.857, and specificity of 1.000. CONCLUSIONS CAFs are more spatially distant from TAECs and more prone to MPR after NAIC in SCC, which may be related to the reduced interaction of CAFs with TAECs and reduced tumor-associated angiogenesis.
Humans ; Lung Neoplasms/therapy* ; Neoadjuvant Therapy ; Male ; Female ; Middle Aged ; Retrospective Studies ; Endothelial Cells/drug effects* ; Aged ; Cancer-Associated Fibroblasts/drug effects* ; Immunotherapy ; Carcinoma, Squamous Cell/drug therapy* ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Adult

With the rapid development of population aging in various countries around the world,the health and elderly care industry has been paid high attention.The standardization of smart health and elderly care technology and services is particularly important.This paper firstly reviewed the policies related to healthy elderly care in China.By analyzing the industrial standards and provincial standards issued,this paper focused on the policies proposed by the Shanghai Municipal Government for the standardization of smart health and elderly care,as well as the researches on the standard system and the construction of standard families.Shanghai group standards in the field of smart health and elderly care were summarized,including the guidelines for the construction of standard systems,elderly care service platforms,community elderly cafeterias,portable health monitoring terminals,indoor sports services,and home-based elderly care safety monitoring.A series of case analyses of the standardized implementation of the above aspects were also provided.Through standardization research and practice in recent years,it has been fully demonstrated that the standard research plays an important leading role in the field of smart health and elderly care.

Objective To construct a prokaryotic expression vector of of the long QT syndrome(LQTS)associated C-terminal lobe of calmodulin(CaM)mutant E141G(C-lobeE141G)and to identify the expression,purification,and activity of C-lobeE141G.Methods A cDNA fragment was inserted into a PGEX-6p-3 plasmid vector and transferred into Escherichia coli BL21 receptor cells,and glutathione-S-trans-ferase(GST)fusion protein was induced by isopropyl thio-β-D galactoside(IPTG).Glutathione-Sepharose 4B beads were used to separate and purify GST-C-lobeE141G.After removing the GST label with protease,the purity and concentration of purified C-lobeE141G were detected using SDS-PAGE and BCA,respectively.The activity of purified C-lobeE141G was detected using the GST pull-down method and patch clamp technique.Results GST-C-lobeE141G fusion protein was highly expressed,and C-lobeE141G with high purity and concentration was obtained.The purified C-lobeE141G protein not only bound to CaV1.2 calcium channels,but also rescued the channel activity from run-down in the ventricular myocytes of rat hearts.Conclusion This study successfully constructed a prokaryotic expression vector of C-lobeE141G,which provides a material basis for the study of the mechanism of LQTS mediated by C-lobe mutations in CaM.

Objective To observe the value of lumbar spine bone marrow MR T1 mapping radiomics for predicting clinical risk of acute lymphoblastic leukemia(ALL)in children.Methods Lumbar bone marrow T1 mappings were prospectively acquired from 77 newly diagnosed ALL children.The volume of interest(VOI)of L3 vertebral body was segmented using 3D Slicer software and 2 060 radiomics features were extracted,and the best features were screened.The children were divided into training and testing sets at the ratio of 8:2.Logistic regression(LR),support vector machine(SVM)and random forest(RF)were used to established radiomics models based on the best features,respectively,which were trained in training set and verified in testing set.The clinical risk was evaluated according to newly diagnosed risk and the response to chemotherapy after MR examination.Receiver operating characteristic(ROC)curve was drawn,and the area under the curve(AUC)was calculated to evaluate the efficacy of each model for predicting clinical risk of ALL in children.Results There were 52 cases in low-medium risk group and 25 in high risk group.The training set consisted of 44 cases of low-medium risk and 17 of high risk,while the testing set consisted of 8 cases of low-medium risk and 8 of high risk.Twelve best features were selected to establish radiomics models.The sensitivity and accuracy of RF model in training set were both 100％,but its sensitivity(50.00％)and accuracy(75.00％)in testing set were both low,which indicating overfitting.The AUC(0.95)of LR model was slightly higher than that of SVM model(0.92)in testing set,but no significantly difference was found(P＞0.05),and the accuracy of these two models was consistent.Conclusion Both lumbar bone marrow T1 mapping LR and SVM radiomics models could be used to predict clinical risk of ALL in children,and LR model had better predictive efficacy.

Purpose To establish and validate an ultrasound-based radiomics nomogram for predicting ipsilateral axillary lymph node metastasis in stage T1 breast cancer.Materials and Methods 443 stage T1 breast cancer patients in the First Affiliated Hospital of Wannan Medical College from January 2012 to June 2021 were retrospectively collected.All patients were randomly divided into training(n=310)and validation(n=133)group.ITK-SNAP was used to delineate the tumor margins,and Pyradiomics software was used to extract features.Image omics models and Rad-scores were constructed after feature screening.Clinical model,radiomics model and combined diagnostic models were developed,with the combined model's nomogram constructed.The models'predictive values were assessed via receiver operating characteristic curves.Results Multivariate Logistic regression analysis showed that the positive axillary ultrasonography,high echo halo and abundant internal blood supply were the independent risk factors of axillary lymph node metastasis.Then the clinical model was constructed,and imaging omics model was also constructed by feature screening.The combined model,which incorporated clinical and imaging features,demonstrated superior predictive performance.In the training group,the area under the curve for the combined model was 0.822,which was significantly higher than that of the clinical model(0.765)and radiomics model(0.723)(P=0.002 1,P=0.001 8).In the validation group,the area under the curve for the combined model was 0.846,outperforming the imaging omics model(0.686,P=0.001 8)and the clinical model(0.783),though the latter difference was not statistically significant(P=0.111 3).Conclusion Ultrasound-based radiomics combined diagnostic model effectively predicts ipsilateral axillary lymph node metastasis in stage T1 breast cancer,demonstrating high clinical predictive efficiency.

Objective To compare the general conditions， clinical characteristics， and polysomnographic features of patients before， around， and after menopause.Methods Participants were divided into premenopausal， perimenopausal， and postmenopausal groups by the age of 45 years and 55 years. General conditions， clinical characteristics， and polysomnographic indicators were compared across these groups.Results A total of 316 patients before， around， and after menopause were included in this study. There were no significant between-group differences in the body mass index， smoking and alcohol consumption rates， sleep latency， sleep duration， sleep efficiency， and the durations and proportions of deep and light sleep. The perimenopausal and postmenopausal groups showed significantly increased nocturnal awakenings and significantly decreased nocturnal oxygen saturation compared with the premenopausal group. The apnea-hypopnea index （AHI） differed significantly between the three groups， showing an increasing trend.Conclusion Changes in reproductive status do not alter objective sleep duration and efficiency， and subjective perception contributes more to sleep disturbances around menopause. Changes in nocturnal sleep continuity， the AHI， and nocturnal minimum oxygen saturation suggest complex neuro-molecular mechanisms underlying the effects of hormonal variations on sleep in women.
Perimenopause

Humans ; Nitric Oxide ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Lung Neoplasms ; Lung ; Nitric Oxide Synthase ; Macrophages, Alveolar ; Pulmonary Alveoli

OBJECTIVE: To explore the clinical features and genetic etiology for a neonate with Smith-Magenis syndrome (SMS). METHODS: Copy number variation sequencing (CNV-seq) was applied to the neonate and his parents, and the genotype-phenotype correlation was analyzed. RESULTS: On the second day after birth, the neonate had presented with pathological jaundice and immunodeficiency. Cranial MRI revealed ventricular enlargement and enlargement of cisterna magna. At 3 months, the infant has presented with square face, prominent forehead, deep-set eyes, hypertelorism, palpebral fissure upward and button noses. Genetic testing showed that he had carried a 2.9 Mb deletion in 17p11.2 region, seq[GRCh37] del(17)(p11.2)(chr17:16 836 379-19 880 992). The same deletion was not found in either parent. CONCLUSION SMS is mostly diagnosed in child and adulthood, but rarely in neonates. For neonates with SMS, the neurological and behavioral abnormalities have not been shown, but pathological jaundice, CNS abnormalities and immune deficiency may be the characteristics, which require attention of neonatal physicians.
Adult ; Chromosome Deletion ; Chromosomes, Human, Pair 17 ; DNA Copy Number Variations ; Genetic Testing ; Humans ; Infant, Newborn ; Intellectual Disability/genetics* ; Male ; Phenotype ; Smith-Magenis Syndrome/genetics*

Fruquintinib is an effective, highly selective and oral VEGFR 1, 2 and 3 tyrosine kinase inhibitor. It was discovered and developed by Hutchison MediPharma for the treatment of solid tumors. In September 2018, fruquintinib received its first global approval in China for use in the treatment of metastatic colorectal cancer (CRC) patients who have failed at least two prior systemic anti-neoplastic therapies. Clinical studies have shown that it has the advantages of low off-target toxicity, good drug resistance and strong curative effect. This article reviews the molecular structure, mechanism of action, pharmacokinetics, clinical efficacy and safety of fruquintinib, as well as its potential clinical applications in other tumor types.

Objective:To explore the effect of group visits on health condition among follow-up patients with chronic heart failure.Methods:Totally 126 outpatient follow-up patients with heart failure were divided into intervention group and control group by random number table from 2018 to 2019. The intervention group consisted of 63 cases and control group consisted of 59 cases. The intervention lasted 6 months. The intervention group received group visits, while the control group received routine outpatient follow-up. Medication adherence, quality of life and heart failure related indicators were evaluated at baseline and after 6 months of intervention.Results:At 6 months after intervention, the scores of medication adherence, total quality of life, body, emotion and others dimensions of the intervention group were (5.79±1.38), (30.11±8.22), (12.65±5.53), (5.24±4.57) and (12.22±4.76) points. These scores of the control group were (5.31±1.09), (37.26±9.02), (15.87±5.21), (7.03±5.14), (14.36±5.54) points. The differences between the two groups were statistically significant ( t values were -4.581-2.161, P<0.05 or 0.01). The BNP and proportion of New York Heart Association (NYHA) I the intervention group were (180.87±174.92) ng/L and 84.1% (53/63). These indicators of the control group were (351.02±268.13) ng/L and 67.8% (40/59). The differences between the two groups were statistically significant ( t value was -4.177, χ2 value was 4.484, P<0.01 or 0.05). Conclusions:Group visits program is an effective management mode to provide intensive patient education and foster peer support, improving medication adherence and quality of life of follow-up patients with heart failure.