Objective This study aims to investigate the expression, phenotypic changes, and mechanisms of action of guanylate-binding protein 2 (GBP2) in the process of silica-induced pulmonary fibrosis. Methods The expression and localization of GBP2 in silicotic lung tissue were detected by immunohistochemical staining and immunofluorescence. An in vitro cell model was constructed, and methods such as Western blot and real-time quantitative reverse transcription polymerasechain reaction were utilized to investigate the function of GBP2 in different cell lines following silica stimulation. The mechanism of action of GBP2 in various cell lines was elucidated using Western blot analysis. Results GBP2 was highly expressed in the lung tissue of patients with silicosis. Immunohistochemical staining and immunofluorescence have revealed that GBP2 was localized in macrophages and epithelial cells. In vitro cell experiments demonstrated that silicon dioxide stimulated THP-1 cells to activate the c-Jun pathway through GBP2, promoting the secretion of inflammatory factors and facilitating the occurrence of M2 macrophage polarization. In epithelial cells, GBP2 promoted the occurrence of epithelial to mesenchymal transition (EMT) by upregulating Krueppel-like factor 8 (KLF8). Conclusion GBP2 not only activates c-Jun in macrophages to promote the production of inflammatory factors and the occurrence of M2 macrophage polarization, but also activates the transcription factor KLF8 in epithelial cells to induce EMT, collectively promoting the progression of silicosis.
Humans ; Silicosis/genetics* ; Macrophages/cytology* ; Epithelial Cells/pathology* ; GTP-Binding Proteins/physiology* ; Epithelial-Mesenchymal Transition ; Disease Progression ; Cell Line ; Male

Objectives:To investigate the early related factors for hepatic insufficiency after hemihepatectomy and to construct and validate a nomogram model.Methods:This is a retrospective cohort study.There were 207 patients with liver tumor who underwent hemihepatectomy in the Department of Hepatobiliary Surgery, Cancer Hospital, Chinese Academy of Medical Sciences from October 2016 to December 2022. Using the random number method, patients were randomly divided into a model group( n=166) and a validation group( n=41) according to an 4∶1 ratio. There were 118 males and 48 females in the modeling group,with an age ( M(IQR)) of 59.0(13.3) years (range: 22.0 to 81.0 years),42 patients in the group with postoperative liver insufficiency and 124 patients in the group without postoperative liver insufficiency. There were 32 males and 9 females in the validation group, with an age of 54.0(19.0) years (range: 25.0 to 81.0 years). The first results of the peripheral blood test of patients within 24 hours after surgery were collected,and the independent related factors for incomplete postoperative liver function were determined by multivariate Logistic regression analysis,and related factors of postoperative incomplete liver function were screened by best subset selection. A nomogram model of the related factors of postoperative hepatic insufficiency after hemihepatectomy was constructed using R software,validated by internal and external validation of the model. Results:Multivariate logistic regression analysis showed that elevated D-dimer level and decreased antithrombin Ⅲ (AT-Ⅲ) activity within 24 hours after surgery were independent related factors for the development of postoperative hepatic insufficiency in hemihepatectomized patients. The results of the best subset selection showed that ALT, D-dimer, and AT-Ⅲ activity levels within 24 hours postoperatively were the most relevant factors for postoperative hepatic insufficiency. The R software was applied to build a nomogram prediction model based on the above three indicators in the model set, and the receiver operating characteristic(ROC) curve of the model showed an area under the curve of 0.803 and the calibration curve showed a U-index of -0.012 for the model( P=0.977). The results of the clinical decision analysis and the clinical impact curve indicated that the model had good clinical utility. The internal validation results of the Bootstrap method suggested that the model had reasonable consistency. The area under the ROC curve of the validation group model was 0.806, suggesting that the model had a good generalization prediction ability. Conclusions:The levels of ALT, D-dimer, and AT-Ⅲ activity within 24 hours after hemihepatectomy are valuable indicators for predicting liver insufficiency after hemihepatectomy. The nomogram model is reliable and can be used as an indicator for close postoperative monitoring.

Objectives:To investigate the early related factors for hepatic insufficiency after hemihepatectomy and to construct and validate a nomogram model.Methods:This is a retrospective cohort study.There were 207 patients with liver tumor who underwent hemihepatectomy in the Department of Hepatobiliary Surgery, Cancer Hospital, Chinese Academy of Medical Sciences from October 2016 to December 2022. Using the random number method, patients were randomly divided into a model group( n=166) and a validation group( n=41) according to an 4∶1 ratio. There were 118 males and 48 females in the modeling group,with an age ( M(IQR)) of 59.0(13.3) years (range: 22.0 to 81.0 years),42 patients in the group with postoperative liver insufficiency and 124 patients in the group without postoperative liver insufficiency. There were 32 males and 9 females in the validation group, with an age of 54.0(19.0) years (range: 25.0 to 81.0 years). The first results of the peripheral blood test of patients within 24 hours after surgery were collected,and the independent related factors for incomplete postoperative liver function were determined by multivariate Logistic regression analysis,and related factors of postoperative incomplete liver function were screened by best subset selection. A nomogram model of the related factors of postoperative hepatic insufficiency after hemihepatectomy was constructed using R software,validated by internal and external validation of the model. Results:Multivariate logistic regression analysis showed that elevated D-dimer level and decreased antithrombin Ⅲ (AT-Ⅲ) activity within 24 hours after surgery were independent related factors for the development of postoperative hepatic insufficiency in hemihepatectomized patients. The results of the best subset selection showed that ALT, D-dimer, and AT-Ⅲ activity levels within 24 hours postoperatively were the most relevant factors for postoperative hepatic insufficiency. The R software was applied to build a nomogram prediction model based on the above three indicators in the model set, and the receiver operating characteristic(ROC) curve of the model showed an area under the curve of 0.803 and the calibration curve showed a U-index of -0.012 for the model( P=0.977). The results of the clinical decision analysis and the clinical impact curve indicated that the model had good clinical utility. The internal validation results of the Bootstrap method suggested that the model had reasonable consistency. The area under the ROC curve of the validation group model was 0.806, suggesting that the model had a good generalization prediction ability. Conclusions:The levels of ALT, D-dimer, and AT-Ⅲ activity within 24 hours after hemihepatectomy are valuable indicators for predicting liver insufficiency after hemihepatectomy. The nomogram model is reliable and can be used as an indicator for close postoperative monitoring.

Objective:To investigate the factors related to hypothyroidism induced by programmed death(PD)-1 treatment in elderly patients with cancer.Methods:A total of 193 older patients(≥60 years old)with advanced solid tumors who received PD-1 treatment between January 2018 and January 2021 at the Department of Oncology of Xiangyang Central Hospital were included in this study.The patients were divided into two groups based on whether they were diagnosed with hypothyroidism after PD-1 treatment: the hypothyroidism group(36 cases)and the non-hypothyroidism group(157 cases).The clinical data of both groups, including age, gender, Eastern Cooperative Oncology Group performance status(ECOG PS), PD-1 inhibitors, thyroid function, and thyroid antibody, were compared to analyze the risk factors associated with hypothyroidism.Results:Among the 193 patients, 36(18.7%)were diagnosed with hypothyroidism.The study found no significant differences between the two groups in terms of age, gender, ECOG PS, tumor type, and PD-1 type(all P>0.05).However, significant differences were observed in the baseline levels of thyroid stimulating hormone(TSH)and thyroid antibody subgroups(both P<0.05).The results of multivariate Logistic regression analysis revealed that the presence of baseline anti-thyroid peroxidase antibody(TPOAb)( OR=20.256, 95% CI: 5.709-71.868, P<0.001), the presence of both baseline thyroglobulin antibody(TGAb)and TPOAb( OR=5.853, 95% CI: 1.475-23.227, P=0.012), and an increase in baseline TSH levels( OR=3.065, 95% CI: 1.049-8.959, P=0.041)were identified as risk factors for hypothyroidism induced by PD-1 treatment.On the other hand, there was no significant association between the presence of baseline TGAb and the occurrence of hypothyroidism( OR=1.373, 95% CI: 0.353-5.341, P=0.648). Conclusions:The incidence rate of hypothyroidism induced by PD-1 inhibitors is high among elderly patients with cancer.Additionally, the risk of hypothyroidism is higher in patients with elevated baseline TSH and positive TPOAb.Therefore, it is crucial to remain vigilant for the occurrence of hypothyroidism during PD-1 treatment.Timely diagnosis and treatment of hypothyroidism are necessary to minimize the incidence of adverse events.

This article is a summary of the Second China Breast Milk Science Conference, which was held in Beijing from August 5 to 7, 2022, with the theme of "Data sharing, method sharing and science sharing". The purpose of the conference is to summarize the latest progress in breast milk research, identify the unresolved issues, and jointly discuss the direction of future breast milk research. Firstly, we summarize the contents and purpose of breast milk scientific research and prospect of breast milk science. The second part focuses on the research status of breast milk composition and its health effects, and puts forward the future research direction. The third section focuses on the health effects of breastfeeding and scientific support and key aspects of breastfeeding promotion actions. The fourth part elaborates the specific methods of current scientific research of breast milk and emphasize the importance of method standardization and the idea of future methodological research. The fifth part consists of the strategy of feeding infants with medical conditions and ways to better promote the growth and development of these infants. The last part introduces the innovation, deficiencies, and future research directions of infant formula production technology in China. This conference demonstrate the importance of multidisciplinary communication, discussions and collaborations in clinical medicine, nutrition, perinatal health, food science, and policy-making in the scientific research of breast milk, and provides guidance for future multidisciplinary research on the physiology of lactation, the composition of breast milk, breastfeeding, and infants and young children nutrition.

Background/Aims: Colorectal cancer (CRC) patients often exhibit peritoneal metastasis, which negatively impacts their prognosis. CD31 and D2-40 have recently been suggested to be predictors of breast cancer prognosis, but their role in colorectal peritoneal metastasis (CRPM) remains unknown. Methods: The expression profiles of CD31 and D2-40 were analyzed in CRC patients with or without CRPM and in CRC cell lines with increasing metastatic potential. Overexpression and short hairpin RNA knockdown assays were performed in CRC cells, and the effects of these alterations on epithelial-mesenchymal transition (EMT) in vitro, growth of xenograft tumors in vivo, and peritoneal metastasis potential in a mouse model of CRPM were examined. Results: The expressions of CD31 and D2-40 were upregulated in CRC tumor tissues and was elevated further in tumor tissues from patients with CRPM. CD31 and D2-40 expression levels exhibited increasing trends parallel to the EMT potential of CRC cells. CD31 and D2-40 are essential for CRC cell EMT in vitro as well as for xenograft tumor growth and peritoneal metastasis in vivo. Conclusions CD31 and D2-40 contribute to CRPM by promoting EMT and may serve as prognostic markers and therapeutic targets for CRC, particularly in patients with peritoneal metastasis.

Human milk is the optimal food for infants. We described the history of human milk research both in China and abroad, the gap between domestic and international research, and the future direction in this area. Human milk needs to be studied as a biological system in the future. Reference values for human milk components of Chinese healthy mother-infant dyad should be established. Factors associated with human milk components variations and relationships between human milk components and maternal and child health also need to be investigated to achieve the best nutrition and health status for mother and child pairs.

【Objective】 To investigate the feasibility of using surface electromyography （SEMG） for the detection of abnormal muscle response （AMR） in patients with hemifacial spasm （HFS）. 【Methods】 We retrospectively reviewed the clinical data of HFS patients who underwent microvascular decompression （MVD） in our hospital between June 2019 and December 2020. Patients who received both surface electrode （preoperative） and needle electrode （intraoperative） detection of AMR were included. SEMG recorded from two stimulation-recording sites， namely， zygomatic-mentalis and mandibular marginal-orbicularis oculi， was selected for analyzing the characteristics of AMR. The positive rates of AMR detected by these two kinds of electrodes were comprehensively compared. 【Results】 Totally 77 patients were included in this study. When detected with surface electrodes， the positive rate， latency and amplitude of AMR recorded at zygomatic-mentalis oculi were 90.9% （70/77）， （10.87±1.86） ms and （202.8±47.4） μV， and at mandibular marginal-orbicularis oculi were 92.2% （71/77）， （10.41±1.83） ms and （211.1±54.1） μV， respectively. AMR was detected in 74 patients （96.1%） with surface electrodes. There was no significant difference in positive rate， latency and amplitude of AMR between these two stimulation-recording methods. When detected with needle electrodes， the positive rate of AMR recorded at zygomatic-mentalis oculi was 98.7% （76/77）， which was significantly higher than the rate 89.6% （69/77） recorded at mandibular marginal-orbicularis oculi （P=0.016）. The latency and amplitude of AMR recorded at zygomatic-mentalis were （10.63±1.39） ms and （83.5±27.2） μV， and at mandibular marginal-orbicularis oculi were （10.31±1.18） ms and （58.6±21.4） μV. There was no significant difference in latency between the two stimulation-recording methods， but the amplitude recorded at mandibular marginal-orbicularis oculi was significantly lower （P=0.041）. AMR was detected in 76 patients （98.7%） with needle electrodes. There was no significant difference in the detection rate of AMR between surface electrodes and needle electrodes （P=0.500）， the results were moderately consistent （Kappa=0.490， P<0.001）. 【Conclusion】 The detection efficiency of surface electrodes for AMR is similar to that of needle electrode. With its non-invasive characteristic， the surface electrode can be routinely used for electrophysiological evaluation of HFS.

Objective:To investigate the definition and influencing factors of early recurrence after resection for synchronous colorectal cancer liver metastases (sCRLM).Methods:Patients with sCRLM in Department of Hepatobiliary Surgery, Cancer Hospital, Chinese Academy of Medical Sciences from December 2008 to December 2016 were included. Restricted cubic spline was used to determine the correlations between the time of recurrence and the long-term prognosis. The univariable and multivariable Cox was performed to measure the feasibility of recurrence within 6 months as the early recurrence. Then apply logistic regression, support vector machine, decision tree, random forest, artificial neural network and XGBoost, these machine learning algorithm to comprehensively rank the importance of every clinicopathological variable to early recurrence, and according to the comprehensively ranks, we introduced variables into the multivariable logistic regression model and observed the receiver operating characteristic curve (ROC) of the logistic regression model, based on the ROC area under curve, Akaike information criterion, and Bayesian information criterion, we identified the best performed variable combination and introduced them into the multivariate logistic regression analysis to confirm the independent risk factors for early recurrence. Subsequently, inverse probability weighting (IPTW) was performed on the therapy-associated independent risk factor to evaluate and validate its influence on the early recurrence of sCRLM patients after reducing the standardized mean difference of all covariates.Results:A total of 228 sCRLM patients who received resection were enrolled and followed up from 2.10 to 108.57 months. There were 142 males and 86 females, aged (55.89±0.67) years old. In 170 (74.6%) patients with recurrence, restricted cube analysis determined that the hazard ratio (HR) of disease free survival (DFS) and overall survival (OS) satisfies a linear relationship ( P<0.05), and Cox analysis indicated that 6 months as the time cutoff for defining early recurrence was feasible ( HR=3.405, 95% CI: 2.098-5.526, P<0.05). Early recurrence was occurred in 93 (40.79%) patients. The survival rate of patients in early recurrence group was significantly lower than that in the late recurrence group ( HR=3.405, 95% CI: 2.098-5.526, P<0.05, and the 5-year survival rate was 14.0% vs 52.0%). Comprehensive analysis of 6 machine learning algorithms identified that the total number of lymph node dissection >22 ( OR=0.258, 95% CI: 0.132-0.506, P<0.05) is an independent protective factor for early recurrence, while the number of liver metastases>3 ( OR=4.715, 95% CI: 2.467-9.011, P<0.05) and postoperative complications ( OR=2.334, 95% CI: 1.269-4.291, P<0.05) are independent risk factors. Finally, the IPTW analysis fully reduced the influence of covariate confounding influence via causal inference to prove lymph node dissection associated with early recurrence (IPTW OR=0.29, P<0.05), benefiting the DFS (IPTW HR=0.4887, P<0.05), but without influence on OS (IPTW HR=0.6951, P>0.05). Conclusion:Six months after sCRLM as the definition of early recurrence, it has significant feasibility. The long-term survival of patients with early recurrence is poor. The independent influencing factors of early recurrence after sCRLM are the total number of lymph node dissection, the number of liver metastases and postoperative complications disease.