BACKGROUND: Epidermal growth factor receptor (EGFR) sensitive mutation is one of the effective targets of targeted therapy for non-small cell lung cancer (NSCLC). However, due to the difficulty of obtaining some primary tissues and the economic factors in some underdeveloped areas, some patients cannot undergo traditional genetic testing. The aim of this study is to establish a machine learning (ML) model using non-invasive peripheral blood markers to explore the biomarkers closely related to EGFR mutation status in NSCLC and evaluate their potential prognostic value. METHODS: 2642 lung cancer patients who visited Jiangsu Cancer Hospital from November 2016 to May 2023 were retrospectively enrolled and finally 175 NSCLC patients with complete follow-up data were included in the study. The ML model was constructed based on peripheral blood indicators and divided into training set and test set according to the ratio of 8:2. Unsupervised learning algorithms were used for clustering blood features and mutual information method for feature selection, and an ensemble learning algorithm based on Shapley value was designed to calculate the contribution of each feature to the model prediction result. The receiver operating characteristic (ROC) curve was used to evaluate the predictive ability of the model. RESULTS: Through the feature extraction and contribution analysis of the predictive results of the interpretable ML model based on the Shapley value, the top ten indicators with the highest contribution were: pathological type, phosphorus, eosinophils, monocyte count, activated partial thromboplastin time, potassium, total bilirubin, sodium, eosinophil percentage, and total cholesterol. The area under the curve (AUC) of the model was 0.80. In addition, patients with hyponatremia and squamous cell carcinoma group had a poor prognosis (P<0.05). CONCLUSIONS The interpretable model constructed in this study provides a new approach for the prediction of EGFR mutation status in NSCLC patients, which provides a scientific basis for the diagnosis and treatment of patients who cannot undergo genetic testing.
Humans ; Carcinoma, Non-Small-Cell Lung/diagnosis* ; Machine Learning ; Lung Neoplasms/diagnosis* ; Male ; Female ; Mutation ; Middle Aged ; ErbB Receptors/genetics* ; Prognosis ; Aged ; Retrospective Studies ; Adult ; Biomarkers, Tumor/genetics*

Objective To investigate the application efficiency and potential of CT radiomics in differentiating malignant and benign sub-centimeter solid pulmonary nodules. Methods A retrospective study was performed on the sub-centimeter ( ≤ 10 mm) solid pulmonary nodules detected by enhanced CT in our hospital from March 2020 to January 2023. Malignancy was confirmed by surgical pathology, and benignity was confirmed by surgical pathology or follow-up. Lesions were manually segmented and radiomic features were extracted. The feature dimension was reduced via feature correlation analysis and least absolute shrinkage and selection operator (LASSO). The 5-fold cross validation was used to validate the model. Support vector machine, logistic regression, linear classification support vector machine, gradient boosting, and random forest models were established for CT radiomics. Receiver operating characteristic curves were drawn. Delong test was used to compare the diagnostic performance of the five classifiers. The optimal model was selected and compared to radiologists with medium and high seniority. Results A total of 303 nodules, 136 of which were malignant, were examined. Radiomics models were established after feature extraction and selection. On test set, the areas under the receiver operating characteristic curves of support vector machine, logistic regression, linear classification support vector machine, random forest, and gradient boosting models were 0.922 (95%CI: 0.893, 0.950), 0.910 (95%CI: 0.878, 0.942), 0.905 (95%CI: 0.872, 0.938), 0.899 (95%CI: 0.865, 0.933), and 0.896 (95%CI: 0.862, 0.930), respectively. Delong test indicated no significant differences in the performance of the five radiomics models, and the support vector machine model showed the highest accuracy and F1 score. The support vector machine model showed significantly higher diagnostic accuracy as compared to radiologists (83.8% vs. 55.4%, P < 0.001). Conclusion The radiomics models achieved high diagnostic efficiency and may help to reduce the uncertainty in diagnosis of malignant and benign sub-centimeter solid nodules by radiologists.

Objective:The clinical manifestations, types of gene mutations, therapeutic effects and prognostic characteristics of 15 children with cblC type methylmalonic acidemia (MMA) and hydrocephalus were analyzed to improve the clinical understanding of the disease, so as to provide a basis for the treatment of the disease.Methods:From April 2015 to January 2019, 15 patients with MMA and hydrocephalus in Department of Pediatric Surgery, Peking University First Hospital were enrolled, and all gene detection showed clbC type.All the 15 patients underwent ventriculoperitoneal shunt.After surgery, the clinical manifestations and imaging findings were applied as the basis to adjust the pressure of the diverter valve appropriately.Clinical data and gene mutation characteristics of 15 children with cblC type and hydrocephalus were retrospectively analyzed, and the therapeutic effects and prognosis were summarized and analyzed as well.Results:There were 8 males (53.3%) and 7 females (46.7%), aged from 2 to 33 months.All the cases were followed up from 11 to 55 months, without death case and serious postoperative complications of hydroce-phalus.The head circumference of 3 cases (20.0%) was in the normal range, 1 case (6.7%) was greater than the normal range, and 11 cases (73.3%) were less than the normal range.Four patients (26.7%) were transferred to the pediatric intensive care unit after surgery.c.609G>A mutation was the most common in this study, with 7 cases (46.7%) of c. 609G>A homozygous mutation, and 5 cases (33.3%) of c. 609G>A heterozygous mutation.Clinical symptoms of intracranial hypertension were relieved or disappeared.The head circumference progressive enlargement was stopped.The anterior fontanelle tension greatly decreased, all " setting-sun" sign of eyes disappeared, and vision loss and hearing loss were better compared with the pre-operation.Four cases (26.7%) displayed normal intelligence and exercise, and 11 cases (73.3%) were left with mild to severe psychomotor retardation.During the follow-up pe-riod, the head CT showed that the ventricle was remarkably narrowed, and interstitial brain edema obviously improved.Conclusions:Ventriculoperitoneal shunt in the treatment of cblC type MMA with hydrocephalus has positive effects.The head circumference of most cblC type MMA with hydrocephalus is less than the normal range.c.609 G>A is the most common mutation in cblC type MMA with hydrocephalus.Perioperative " metabolic crisis" can result in serious complications.

Objective:To explore the effect of adhesion molecule nectin-1 expression on epileptic seizure and mossy fiber sprouting.Methods:(1) Adult male SD rats were randomly divided into control group ( n=6), empty vector group ( n=6) and lentivirus interfered group ( n=24), and rats in the lentivirus interfered group were further divided into 4 subgroups ( n=6) according to the time points of lentivirus injection (3, 7, 14 and 30 d after injection). The protein expression of nectin-1 in the hippocampus of rats was detected by Western blotting. (2) Another 12 male SD rats were randomly selected and divided into lentivirus epilepsy group ( n=6) and empty vector epilepsy group ( n=6). Lentivirus and empty lentivirus vector were injected into the hippocampus of the above two groups respectively, and then, pilocarpine epilepsy models were kindled; the behavior changes of these rats were recorded, and changes of mossy fiber sprouting in the hippocampus were observed by Timm staining. Results:(1) There were significant differences in hippocampal nectin-1 protein expressions in each group ( F=76.120, P=0.000); the nectin-1 expression in the 7, 14, and 30 d subgroups was significantly decreased as compared with that in the control group and empty vector group ( P<0.05). (2) The results of behavior changes showed that the times required for the lentivirus epilepsy group to be kindled successfully ([34.33±2.38] min) were significantly longer than those for the empty vector epilepsy group ([24.50±2.06] min, t=7.650, P=0.000). In terms of seizure level, the seizure level of rats in the lentivirus epilepsy group was significantly lower at each time point within one h modeling than that of rats in the empty vector epilepsy group ( P<0.05). After kindling, the time of spontaneous seizure appeared in the lentivirus epilepsy group was significantly longer than that in the empty vector epilepsy group, and the frequencies of spontaneous seizure in the lentivirus epilepsy group were significantly decreased as compared with those in the empty vector epilepsy group ( P<0.05). Timm staining scores in the lentivirus epilepsy group (3.500±0.224) were significantly lower than those in the empty vector epilepsy group (4.667±0.211, t=9.289, P=0.000). Conclusion:Inhibition of nectin-1 expression in hippocampal area of epileptic rats can delay the occurrence of epilepsy and reduce the frequencies of spontaneous seizures of epileptic rats, whose mechanism may be related to the reduction of nectin-1 in the formation of mossy fiber sprouting in abnormal neural circuits of hippocampal area.

With literature of professor CHEN Yinglong such as Medical Notes of Doctor CHEN Yinglongfor Taiwan Compatriots,the'experience of doctor CHEN Yinglong treating common diseases in Fujian and Tai-wan is summarized. The diseases in the paper are constipation, retention of urine, asthma, vec6rdia, bi syndromeinsomnia, thoracic obstruction, pediatric obesity and freckle of face, etc. It is discovered that professor CHENYinglong treated diseases with combination of acupuncture and medication and accurate acupoints according to thefeature of climate in Fujian and Taiwan.
Acupuncture Points ; Acupuncture Therapy ; history ; Asthma ; therapy ; Constipation ; therapy ; History, 20th Century ; Humans ; Taiwan

Objective To establish a high-performance induction culture system for Raw264.7 cells to differentiate into osteoclasts(OC)invitro by improving the cell culture program.Methods The Raw264.7 cells were cultured withα-MEM medium containing 50 μg · L-1 M-CSF, 100 μg · L-1 RANKL, and 1 × 10-8 mol · L-1 1α,25-(OH)2 D3 in 5% CO2 for 12 d at 37℃. The cells were digested transiently every time before the medium was changed after every three days. The morphologic changes of the Raw264.7 cells were observed by inverted microscope.The maturation and phagotrophic function of OC were identified by HE,TRAP,FITC-phalloidin staining and immunofluorescence.Results The cells remained to grow in single layers all the time in most areas of the well during the whole induction by the improved culture program. The observation results of inverted microscope and HE staining showed that the growth area of the polykaryotic OC reached to 70% of the well on day 1 2. FITC-phalloidin staining showed that in the maturation of the OC, the cluster-shaped podosomes in the pseudopodia gradually transformed into rings,which finally fused to form a large belt surrounding the periphery of the cytoplasm. The calcitionin receptor (CTR) expressed by OC was markedly enhanced compared with the precursor cells by immunofluroescence staining,and a large number of red granules appeared in the cytoplasm of OC with TRAP staining on day 1 2. These results comfirmed that the obtained OC were maturated and owned phagotrophic function. Conclusion A high-performance induction culture system for Raw264. 7 cells to differentiate into OC in vitro induced by combination of 50μg · L-1 M-CSF, 100 μg · L-1 RANKL,and 1 × 10-8 mol·L-1 1α,25-(OH)2 D3 is established by improving the cell culture program.

Objective To assess the safety and efficacy of endoscopic retrograde cholangiopancreatography (ERCP) for pancreaticobiliary diseases in children. Methods Data of 9 patients younger than 14 years who underwent ERCP at between November 2004 and May 2010 were indentified through a computer database search. Therapeutic methods, success rate and procedure-related complications were evaluated.Results A total of 9 patients underwent 17 ERCP procedures under anesthesia, including 16 therapeutic and 1 diagnostic procedure. The success rate was 94. 1% (16/17) and the complication rate was 11.8%(2/17), including 1 mild pancreatitis and 1 peri-pancreatic infection. Conclusion ERCP is an important tool with high safety and efficacy for diagnosis and treatment of pancreaticobiliary diseases in children.

Objective To probe the relationship between the expression of TL1A and the level of IFN-γ secreted by T cells in the acute stage of Guillain-Barre syndrome (GBS). Methods ① Six-week female Bal b/c mice were immunized by purified recombinant human soluble TNF-like molecular 1A (rhsTL1A) protein. The polyclonal antibody against rhsTL1A was identified by immunofluorescence using human umbilical vein epithelial cells (HUVEC). ② To detect the biologic activity of rhsTL1A, the peripheral blood mononuclear cells (PBMC) from the healthy donors were separated by Ficoll gradient centrifugation and were seeded on 96-well plates with medium containing 2 μg/ml PHA (control group), 2 μg/ml PHA + 25 ng/ml rhsTL1 A, 2 μg/ml PHA + 100 ng/ml rhsTL1A and 2 μg/ml PHA + 400 ng/ml rhsTLlA respectively. T cell proliferation assay was carried out using ~3H-TdR. ③ IFN-γ productions in the sera of the children with GBS in the acute stage were detected by ELISA. ④ The ratio of CD_3~+ TL1A~+ T cells to CD_3~+ T cells in the peripheral blood of the children with GBS in acute stage was detected with flow, cytometry. ⑤PBMC from the children in acute GBS were separated and cultured in the environment adding 2 μg/ml PHA and 400 ng/ml rhsTL1A in vitro. Then, the IFN-γ in the supernatant was determined by ELISA kit after 72 hours. Results ① hTL1A A expressed by eukaryotic HUVECs was recognized by rhsTL1 A polyclonal antiserum. ② The result of T cell proliferation assay showed that SI of 25 ng/ml rhTL1A, 100 ng/ml rhTL1A A and 400 ng/ml rhTL1A group was increased compared with control group. The SI of 2 μg/ml PHA +400 ng/ml rhsTL1 A group was the highest (2. 65) among them. ③ IFN-γ productions in the sera of the children with GBS in the acute stage ((102. 25±22. 17) pg/ml) were increased significantly compared with healthy control ((28.75 ± 1.31) pg/ml, t = 3. 309, P < 0. 05). ④ The ratio of CD_3~+ TL1A~+ T cells to CD_3~+ T cells in the peripheral blood of the children with GBS in acute stage (18.22%± 1.83%) was enhanced significantly compared with healthy control (5. 17% ±0. 48%, t = 6. 884, P < 0. 01). ⑤ PBMC both in healthy control and the acute GBS secreted more IFN-γ markedly ((43.56± 4.41) pg/ml and (180.64 ± 38.39) pg/ml) after being incubated in 2 μg/ml PHA and 400 ng/ml rhsTL1A (t =4. 523 and 2. 600, P <0. 01 and 0. 05 respectively). Moreover, PBMC in acute GBS secreted more IFN-γ, than that of the healthy group markedly (t = 3. 545, P < 0. 05). Conclusions ① The mouse antiserum recognizing rhsTL1A is successfully obtained. ② In this study, 400 ng/ml rhsTL1A promotes the proliferation of T cells activated by 2 μg/ml PHA, indicating that rhsTL1A has biological activity. ③ The expression of hTL1A of activated T cells in the peripheral blood of the children with acute GBS is up-regulated. These TL1A proteins promote the secretion of IFN-γ through binding to their receptors DR_3.

Objective:To probe into the long-term effect of La(NO3)3 fed orally on gast ric mucosa of rats.Methods:The gastric mucosa of rats was studied after La(NO3)3 was administe red orally for a long-term,by the use of ordinary histological technology and m orphometry.Results:In the groups of 20 mg·kg-1 and 10 mg·kg-1,the cytopl asma of more parietal cells lying in the top of the gastric gland was loose.Proporti on of cell types of the gastric gland was related to the doses. The acid mucus l evel of the mucous neck cells of male rats in the groups of 20 mg·kg-1 an d 10 m·kg-1 decreased. In the groups of 2 mg2kg-1, 0.2 mg·kg -1 and 0.1 mg*kg-1,the acid mucus level of the mucous neck cells of both male and female rats increased.Conclusion:La(NO3)3 fed orally for a long-term could injure gastric muc osa in higher dose (20 mg·kg-1,10 mg·kg-1) but promote the protect ive action of the gastric mucosa in lower dose (0.2 mg·kg-1,0.1 mg·kg- 1).