Breast milk is the optimal natural food for newborns. However， some newborns cannot receive maternal breast milk due to reasons such as mother-infant separation or insufficient lactation. The establishment of human milk banks （HMB） can effectively address these issues， thereby increasing the breastfeeding rate among hospitalized newborns and improving their quality of survival. However， HMB in China is still in the development and improvement stage. Its implementation involves a series of ethical issues， such as informed consent， privacy protection， economic incentives， quality and safety， and fair resource distribution， which hinder HMB’s widespread promotion. Therefore， discussing the ethical dilemmas faced by the widespread establishment of HMB in China’s hospitals and analyzing coping strategies are crucial for improving the breastfeeding rate of newborns. This paper deeply analyzed and sorted out the ethical issues and challenges currently faced by HMB in China， and proposed corresponding strategies， including “ensuring informed consent and voluntary participation of both donors and recipients，” “protecting the privacy of donors and recipients，” “establishing an ethics-based moral incentive and social support system，” “strictly controlling quality and safety issues”， and “developing fair and rational policies，” aiming to provide a reference solution for addressing ethical concerns in the establishment and operation of HMB.

Objective: To investigate the correlation between tumor size, tumor location, and prognosis in patients with early-stage endometrial cancer (EC) receiving adjuvant radiotherapy. Methods: Data of patients who had been treated for stage I–II EC from March 1999 to September 2017 in 13 tertiary hospitals in China was screened. Cox regression analysis was performed to investigate associations between tumor size, tumor location, and other clinical or pathological factors with cancer-specific survival (CSS) and distant metastasis failurefree survival (DMFS). The relationship between tumor size as a continuous variable and prognosis was demonstrated by restricted cubic splines. Prognostic models were constructed as nomograms and evaluated by Harrell’s C-index, calibration curves and receiver operating characteristic (ROC) curves. Results: The study cohort comprised 805 patients with a median follow-up of 61 months and a median tumor size of 3.0 cm (range 0.2–15.0 cm). Lower uterine segment involvement (LUSI) was found in 243 patients (30.2%). Tumor size and LUSI were identified to be independent prognostic factors for CSS. Further, tumor size was an independent predictor of DMFS. A broadly positive relationship between poor survival and tumor size as a continuous variable was visualized in terms of hazard ratios. Nomograms constructed and evaluated for CSS and DMFS had satisfactory calibration curves and C-indexes of 0.847 and 0.716, respectively. The area under the ROC curves for 3- and 5-year ROC ranged from 0.718 to 0.890. Conclusion Tumor size and LUSI are independent prognostic factors in early-stage EC patients who have received radiotherapy. Integrating these variables into prognostic models would improve predictive ability.

Fetal arachnoid cyst is a common central nervous system malformation. Prenatal imaging manifestations are prone to confusion with other intracranial cysts. This study comprehensively reviews the literature on fetal arachnoid cysts, including the anatomical foundations, pathogenesis, imaging characteristics, and differential diagnosis. Additionally, the pregnancy management and prognosis of this disease are summarized in this article.

Objective:To investigate the role of speckle-type POZ(pox virus and zinc finger protein) protein (SPOP) in enterovirus 71 (EV71) infection.Methods:Immunoprecipitation analysis was employed to examine the impact of SPOP on the ubiquitin level of EV71 non-structural protein 2A protease (2A pro), while the phosphorylation level of IFR3 protein was assessed through Western blot. Cells were either overexpressed or knockdown of SPOP, followed by infection with EV71. RT-qPCR was utilized to analyze the transcription level of IFN-β, and the transcription level and protein level of EV71 structural protein VP1 were determined using RT-qPCR and Western blot, respectively. Results:The inhibition of EV71 infection in RD cells was observed following transfection with HA-SPOP. Additionally, it was found that the ubiquitin level of EV71-2A pro increased in a gradient-dependent manner. Subsequent transfection with shSPOP plasmid for endogenous SPOP knockdown resulted in a dose-dependent decrease in the levels of melanoma differentiation-associated gene 5 (MDA5), mitochondrial antiviral signaling (MAVS), and p-IRF3. Conversely, transfection with HA-SPOP plasmid led to a dose-dependent increase in the levels of MDA5, MAVS, and p-IRF3. The expression of SPOP, whether high or low, had an impact on the expression of IFN-β in cells. Additionally, the levels of VP1 mRNA or protein were found to be inhibited or increased. Conclusions:SPOP plays a role in increasing the ubiquitination level of EV71-2A pro, which in turn promotes the phosphorylation level of IRF3 and secretion of IFN-β. This effect is achieved by inhibiting the cleavage of 2A pro against key molecules MAVS and MDA5 in the RLR signaling pathway, ultimately leading to the inhibition of EV71 replication.

Ischemic stroke,with a high disability and mortality rate,seriously endangers human health.Pathological process of ischemic stoke involves participations of various cells such as microglia and astrocytes.Among them,microglia,as innate immune cells in central nervous system(CNS),play an important role whether in physiological or pathological states.Triggering receptor expressed on myeloid cells 2(TREM2)is an immunoglobulin like receptor mainly existing on microglia in CNS,and can bind to a variety of ligands,which can negatively regulate autoimmunity and inflammation.In addition,TREM2 can mainly play an important role in process of proliferation,phagocytosis,survival and expressions of inflammatory factors.This article focused on biological characteristics of TREM2 on microglia,corresponding ligands and its signaling pathways,discussing regulation of TREM2 in ischemic stroke and its potential therapeutic effects,in order to provide an new target for prevention and treatment of ischemic stroke.

Objective To analyze the medication rule of Traditional Chinese Medicine(TCM)in treating diabetes nephropathy(DN)and to explore the interaction between core components and key targets.Methods Based on the ancient and modern medical case cloud platform,the medication rules of TCMs and the drug pairs with the highest frequency in treating DN were summarized.Then the network pharmacology approach was utilized to analyze the pharmacodynamic material basis and mechanisms of the highest frequency-drug pairs.The potential targets were predicted by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)databases.TTD,DISGENET,and GENECARD databases were used to obtain the related targets of DN and screen out the potential targets for DN.In order to clarify the relationships between the active ingredients,the core targets,and pathways,STRING and Cytoscape 3.7.1 software were used to construct the protein-protein interaction(PPI)network and core drugs-ingredients-targets-disease interaction network,DAVID database was screened for Kyoto Encyclopedia of Genes and Gnomes(KEGG)enrichment analysis of core targets.Sybyl 2.1 software and biofilm interference verify the combined capacity between the core ingredients and key targets.Results Among 183 prescriptions,Astragali Radix had the highest use frequency and average dose,43 times and 37 g,respectively,followed by Salviae miltiorrhizae Radix and Poria cocos.To find the core combined with the highest confidence in association analysis was astragalus,salvia miltiorrhiza,and tuckahoe.Correlation analysis indicates that the core combination with the highest confidence was Astragali Radix-Salviae miltiorrhizae Radix-Poria cocos.Network pharmacologic showed 89 potential targets and 15 key signaling pathways for the treatment of DN by the drug pair.TNF signaling pathway,Nod-like receptor signaling pathway,and MAPK signaling pathway were disease-related pathways,and IL-6,TNF,and vascular endothelial growth factor A(VEGFA)were core targets.Isorhamnetin and quercetin of the drug pair had high binding ability with IL6,the scores were 8.2 and 7.4,respectively,and the dissociation constants(KD)were 5.6×10-5 mol·L-1 and 6.8×10-5 mol·L-1,respectively.Conclusion This study preliminarily finds the prescription rule of treating DN with Astragali Radix-Salviae miltiorrhizae Radix-Poria cocos as the core drug pair,isorhamnetin,and quercetin are probably the main active compounds of this drug pair in DN treatment,which provides a basis for clinical treatment and drug discovery of DN.

Background::The association and its population heterogeneities between low-density lipoprotein cholesterol (LDL-C) and all-cause and cardiovascular mortality remain unknown. We aimed to examine the dose-dependent associations of LDL-C levels with specific types of cardiovascular disease (CVD) mortality and heterogeneities in the associations among different population subgroups.Methods::A total of 2,968,462 participants aged 35-75 years from China Health Evaluation And risk Reduction through nationwide Teamwork (ChinaHEART) (2014-2019) were included. Cox proportional hazard models and Fine-Gray subdistribution hazard models were used to estimate associations between LDL-C categories (<70.0, 70.0-99.9, 100.0-129.9 [reference group], 130.0-159.9, 160.0-189.9, and ≥190.0 mg/dL) and all-cause and cause-specific mortality.Results::During a median follow-up of 3.7 years, 57,391 and 23,241 deaths from all-cause and overall CVD were documented. We observed J-shaped associations between LDL-C and death from all-cause, overall CVD, coronary heart disease (CHD), and ischemic stroke, and an L-shaped association between LDL-C and hemorrhagic stroke (HS) mortality ( P for non-linearity <0.001). Compared with the reference group (100.0-129.9 mg/dL), very low LDL-C levels (<70.0 mg/dL) were significantly associated with increased risk of overall CVD (hazard ratio [HR]: 1.10, 95% confidence interval [CI]: 1.06-1.14) and HS mortality (HR: 1.37, 95% CI: 1.29-1.45). Very high LDL-C levels (≥190.0 mg/dL) were associated with increased risk of overall CVD (HR: 1.51, 95% CI: 1.40-1.62) and CHD mortality (HR: 2.08, 95% CI: 1.92-2.24). The stronger associations of very low LDL-C with risk of CVD mortality were observed in individuals with older age, low or normal body mass index, low or moderate 10-year atherosclerotic CVD risk, and those without diagnosed CVD or taking statins. Stronger associations between very high LDL-C levels and all-cause and CVD mortality were observed in younger people. Conclusions::People with very low LDL-C had a higher risk of all-cause, CVD, and HS mortality; those with very high LDL-C had a higher risk of all-cause, CVD, and CHD mortality. On the basis of our findings, comprehensive health assessment is needed to evaluate cardiovascular risk and implement appropriate lipid-lowering therapy for people with very low LDL-C.

ObjectiveTo study the effects of Buyang Huanwutang on the skeletal muscle injuries in type 2 diabetes mellitus from mitochondrial transport， glucose metabolism， oxidative stress， and inflammation. MethodA total of 60 SPF-grade male C57BL/6J mice were selected in this study. The mouse model of type 2 diabetes mellitus was established with a high-fat diet combined with intraperitoneal injection of streptozotocin. The mice were assigned by the random number table method into blank control， model， high-， medium-， and low-dose （86.5， 43.2， 21.6 g·kg^-1， respectively） Buyang Huanwutang， and metformin （150 mg·kg^-1） groups， 10 mice in each group. During the experiment period， blood glucose and other indicators of mice were measured regularly. At the end of the experiment， skeletal muscle samples were collected and frozen in 4% paraformaldehyde and -80 ℃， respectively. Blood samples were sent for examination. The skeletal muscle was stained with hematoxylin-eosin. The levels of inflammation indicators and reactive oxygen species （ROS） were determined by enzyme-linked immunosorbent assay. The expression of mitochondrial proteins was determined by Western blot and immunohistochemistry. ResultCompared with the blank control group， the model group showcased increased fasting blood glucose， water intake， and food intake （P<0.01） and decreased body weight （P<0.01）. Compared with the model group， metformin and Buyang Huanwutang reduced the fasting blood glucose， water intake， and food intake （P<0.05， P<0.01） and increased the body weight （P<0.01）. Compared with the blank control group， the model group showed rising levels of tumor necrosis factor-alpha （TNF-α）， interleukin-6 （IL-6）， and ROS （P<0.01）， which were decreased by metformin and Buyang Huanwutang （P<0.05， P<0.01）. The skeletal muscle fibers in the model group were generally atrophic and thin， which suggested atrophy and morphological changes of the skeletal muscle， while metformin and Buyang Huanwutang alleviated the pathological changes of the skeletal muscle and restored the morphology of fiber bundles. Compared with the blank control group， the modeling down-regulated the expression of the mitofusin2 （Mfn2） （P<0.01）， which was up-regulated by metformin and Buyang Huanwutang （P<0.05， P<0.01）. Compared with the blank control group， the modeling up-regulated the expression of the dynamin-related protein （Drp1） （P<0.01）， which were down-regulated by metformin and Buyang Huanwutang （P<0.01）. ConclusionBuyang Huanwutang can improve the body weight and attenuate the pathological changes of the skeletal muscle， reduce fasting blood glucose， food intake， and water intake， lower the levels of TNF-α， IL-6， and ROS， down-regulate the expression of Drp1， and up-regulate the expression of Mfn2 in the mouse model of type 2 diabetes mellitus.

Objective To observe the value of habitat model based on lung CT for predicting brain metastasis(BM)of lung adenocarcinoma with epidermal growth factor receptor(EGFR)mutation.Methods Data of plain lung CT of 198 lung adenocarcinoma patients with EGFR-mutant were retrospectively analyzed.The patients were divided into training set(n=138)and test set(n=60)at the ratio of 7∶3,and further divided into BM subgroup and non-BM subgroup in each set.Then a logistic regression(LR)clinical model was constructed using variables being statistically different between subgroups in training set.For features extracted from tumor and subregion of tumor,radiomics models and habitat models were constructed based on random forest,Gaussian process(GP)and support vector machine(SVM)algorithms,and the best radiomics and habitat models with generalization ability were screened.LR combined model was constructed based on the predicted values of the best radiomics and habitat models with generalization ability,as well as the clinical model.Then receiver operating characteristic curves were drawn,and the area under the curves(AUC)were calculated to evaluate the efficacy of each model for predicting BM of lung adenocarcinoma with EGFR-mutant.Spearman correlation analysis was performed to observe the correlations between Ki-67 and habitat features of lung adenocarcinoma with EGFR-mutant.Results AUC of LR clinical model,GP radiomics model,SVM habitat model and LR combined model for predicting BM of lung adenocarcinoma with EGFR-mutant was 0.700,0.726,0.801 and 0.834 in training set,0.754,0.600,0.715 and 0.848 in test set,respectively.AUC of LR combined model was higher than that of LR clinical model in training set(P＜0.001),also higher than that of GP radiomics model in test set(P=0.010).Compared with GP radiomics model and SVM habitat model,the performance of LR combined model was significantly and positively improved in training set(integrated discrimination improvement index[IDI]=8.60%,8.55%,both P＜0.001).Ki-67 level of EGFR-mutant lung adenocarcinoma was lowly and positively correlated with habitatmap_original_glszm_lalgle extracted from habitat map(│rs│=0.201,P=0.004).Conclusion The habitat model based on lung CT could be used to predict BM of lung adenocarcinoma with EGFR-mutant effectively.

Multiple myeloma bone disease(MBD)is a common clinical complication in patients with multiple myeloma(MM),and the occurrence of bone-related events seriously affects the quality of survival and prognosis of patients.The pathogenesis of MBD involves an imbalance in physiologic bone remodeling:overactivation of osteoclasts,suppression of osteoblasts,and multiple cell-cytokine interactions in the microenvironment,including osteoblasts,bone marrow stromal cells,and immune cells.The current treatment of MBD is based on standard antimyeloma therapy to control tumor progression,along with the use of bone-related drugs act-ing on bone remodeling within the indications.To prevent bone destruction.In order to prevent bone destruction,it is essential to in-duce new bone formation to repair the existing lesions while resisting bone resorption,and a variety of novel bone-targeting drugs are currently demonstrating anti-osteopathic effects in preclinical and clinical trials.This article summarizes new advances in the mecha-nisms of bone remodeling and treatment of MBD.