To introduce and analyze guideline terminology related to clinical question formulation, evidence retrieval and appraisal, and recommendation development.

Astrocytes are the largest glial population in the mammalian brain. However, we have a minimal understanding of astrocyte development, especially fate specification in different regions of the brain. Through lineage tracing of the progenitors of the third ventricle (3V) wall via in-utero electroporation in the embryonic mouse brain, we show the fate specification and migration pattern of astrocytes derived from radial glia along the 3V wall. Unexpectedly, radial glia located in different regions along the 3V wall of the diencephalon produce distinct cell types: radial glia in the upper region produce astrocytes and those in the lower region produce neurons in the diencephalon. With genetic fate mapping analysis, we reveal that the first population of astrocytes appears along the zona incerta in the diencephalon. Astrogenesis occurs at an early time point in the dorsal region relative to that in the ventral region of the developing diencephalon. With transcriptomic analysis of the region-specific 3V wall and lateral ventricle (LV) wall, we identified cohorts of differentially-expressed genes in the dorsal 3V wall compared to the ventral 3V wall and LV wall that may regulate astrogenesis in the dorsal diencephalon. Together, these results demonstrate that the generation of astrocytes shows a spatiotemporal pattern in the developing mouse diencephalon.
Mice ; Animals ; Astrocytes ; Neuroglia/physiology* ; Diencephalon ; Brain ; Neurons ; Mammals

Conventional chemotherapy based on cytotoxic drugs is facing tough challenges recently following the advances of monoclonal antibodies and molecularly targeted drugs. It is critical to inspire new potential to remodel the value of this classical therapeutic strategy. Here, we fabricate bisphosphonate coordination lipid nanogranules (BC-LNPs) and load paclitaxel (PTX) to boost the chemo- and immuno-therapeutic synergism of cytotoxic drugs. Alendronate in BC-LNPs@PTX, a bisphosphonate to block mevalonate metabolism, works as both the structure and drug constituent in nanogranules, where alendronate coordinated with calcium ions to form the particle core. The synergy of alendronate enhances the efficacy of paclitaxel, suppresses tumor metastasis, and alters the cytotoxic mechanism. Differing from the paclitaxel-induced apoptosis, the involvement of alendronate inhibits the mevalonate metabolism, changes the mitochondrial morphology, disturbs the redox homeostasis, and causes the accumulation of mitochondrial ROS and lethal lipid peroxides (LPO). These factors finally trigger the ferroptosis of tumor cells, an immunogenic cell death mode, which remodels the suppressive tumor immune microenvironment and synergizes with immunotherapy. Therefore, by switching paclitaxel-induced apoptosis to mevalonate metabolism-triggered ferroptosis, BC-LNPs@PTX provides new insight into the development of cytotoxic drugs and highlights the potential of metabolism regulation in cancer therapy.

Objective Data mining technology was used to mine the medication rules of the prescriptions used in the treatment of pediatric atopic dermatitis by Chinese medical master XUAN Guo-Wei.Methods The medical records of effective cases of pediatric atopic dermatitis treated by Professor XUAN Guo-Wei at outpatient clinic were collected,and then the medical data were statistically analyzed using frequency statistics,association rule analysis and cluster analysis.Results A total of 242 prescriptions were included,involving 101 Chinese medicinals.There were 23 commonly-used herbs,and the 16 high-frequency herbs(frequency＞100 times)were Glycyrrhizae Radix et Rhizoma,Saposhnikoviae Radix,Glehniae Radix,Perillae Folium,Ophiopogonis Radix,Cynanchi Paniculati Radix et Rhizoma,Microctis Folium,Dictamni Cortex,Scrophulariae Radix,Coicis Semen,Cicadae Periostracum,Lilii Bulbus,Rehmanniae Radix,Kochiae Fructus,Sclerotium Poriae Pararadicis,and Euryales Semen.The analysis of the medicinal properties showed that most of the herbs were sweet and cold,and mainly had the meridian tropism of the spleen,stomach and liver meridians.The association rule analysis yielded 24 commonly-used drug combinations and 20 association rules.Cluster analysis yielded 2 core drug combinations.Conclusion For the treatment of pediatric atopic dermatitis,Professor XUAN Guo-Wei focuses on the clearing,supplementing and harmonizing therapies,and the medication principle of"supporting the healthy-qi to eliminate the pathogen,and balancing the yin and yang"is applied throughout the treatment.

Objective To identify inflammation-related genes in atrial fibrillation(AF)and explore the possible role and mechanism of these genes and infiltrating immune cells in the development of AF.Methods A series of bioinformatics analysis combined with machine learning algorithms to identify biomarkers of AF,the receiver operating characteristic(ROC)curves were used to verify the prediction and diagnostic value of key genes,and Spearman correlation analysis was used to clarify the correlation between key genes and infiltrating immune cells.Results 593 differential genes(| log2(fold change,FC)|>1,P<0.05),7 immune cell subtypes(P<0.05)were selected,190 immune-related differential genes were obtained,3 biomarkers(IGF1,PTGS 2 and PPARG),and the correlation analysis showed that 3 markers were significantly associated with infiltrating immune cells(P<0.05).Conclusion IGF1,PTGS2 and PPARG are inflammation-related genes of AF,which are speculated to be closely related to the process and pathway of immune cell infiltration.

Protein as the allergens could lead to allergy. In addition, a widespread class of allergens were known as glycans of N-glycoprotein. N-glycoprotein contained oligosaccharide linked by covalent bonds with protein. Recently,studies implicated that allergy was associated with glycans of heterologous N-glycoprotein found in food, inhalants, insect toxins, etc. The N-glycan structure of N-glycoprotein allergen has exerted an influence on the binding between allergens and IgE, while the recognition and presentation of allergens by antigen-presenting cells (APCs) were also affected. Some researches showed thatN-glycan structure of allergen was remodeled by N-glycosidase, such as cFase I, gpcXylase, as binding of allergen and IgE partly decreased. Thus, allergic problems caused by N-glycoproteins could potentially be solved by modifying or altering the structure ofN-glycoprotein allergens, addressing the root of the issue. Mechanism of N-glycans associated allergy could also be elaborated through glycosylation enzymes, alterations of host glycosylation. This article hopes to provide a separate insight for glycoimmunology perspective, and an alternative strategy for clinical prevention or therapy of allergic diseases.

【Objective】 To analyze the effect of sample hemolysis on ELISA test results in blood screening laboratory, so as to determine the acceptable tolerance of hemolysis specific to laboratory test items and detection system, and provide reference for the formulation of tolerance standard of sample hemolysis. 【Methods】 Negative and weakly positive (S/CO was about 2) samples with different hemolysis degrees were tested by several commonly used domestic reagents for HBsAg, HIV Ag/Ab, anti-HCV and anti-TP, respectively. The effects of various degrees of hemolysis on the test results of negative and weakly positive samples for each item were analyzed. 【Results】 1) Hemolysis had no effect on the test results (reactive/non-reactive) of negative and weakly positive samples for HBsAg, anti-HCV and anti-TP ELISA items; 2) Hemolysis affected the test results (reactive/non-reactive) of negative and weakly positive samples for HIV Ag/Ab ELISA item. A tolerance of Hb 2 g/L was taken as the acceptable hemolysis degree for HIV Ag/Ab ELISA item. 【Conclusion】 In this study, the acceptable tolerance of hemolytic samples for corresponding test items and detection system in our laboratory were determined. The influence of hemolysis on ELISA test result is related to the reagent, equipment, environment and other factors, therefore the acceptable tolerance of hemolysis should be determined scientifically and reasonably based on the specific evaluation of each laboratory.

Objective:To explore the value of salivary gland imaging based on deep learning and Delta radiomics in assessing salivary gland injury after 131I treatment in post-thyroidectomy thyroid cancer patients. Methods:A retrospective analysis on 223 patients (46 males, 177 females, age(47.7±14.0) years ) with papillary thyroid cancer, who underwent total thyroidectomy and 131I treatment in Affiliated Hospital of Guilin Medical University between December 2019 and January 2022, was conducted. All patients underwent salivary gland 99Tc mO 4- imaging before and after 131I therapy. The patients were categorized according to salivary gland function based on 99Tc mO 4- imaging results (normal salivary gland vs salivary gland injury), and divided into training and test sets in a ratio of 7∶3. A ResNet-34 neural network model was trained using images at the time of maximum salivary gland radioactivity and those based on background radioactivity counts for structured image feature data. The Delta radiomics approach was then used to subtract the image feature values of the two periods, followed by feature selection through t-test, correlation analysis, and the least absolute shrinkage and selection operator( LASSO) algorithm, to develop logistic regression (LR), support vector machine (SVM), and K-nearest neighbor (KNN) predictive models. The diagnostic performance of 3 models for salivary gland function on the test set was compared with that of the manual interpretation. The AUCs of the 3 models on the test set were compared (Delong test). Results:Among the 67 cases of the test set, the diagnostic accuracy of 3 physicians were 89.6%(60/67), 83.6%(56/67), and 82.1%(55/67) respectively, with the time required for diagnosis of 56, 74 and 55 min, respectively. The accuracies of LR, SVM, and KNN models were 91.0%(61/67), 86.6%(58/67), and 82.1%(55/67), with the required times of 12.5, 15.3 and 17.9 s, respectively. All 3 radiomics models demonstrated good classification and predictive capabilities, with AUC values for the training set of 0.972, 0.965, and 0.943, and for the test set of 0.954, 0.913, and 0.791, respectively. There were no significant differences among the AUC values for the test set ( z values: 0.72, 1.18, 1.82, all P>0.05). Conclusion:The models based on deep learning and Delta radiomics possess high predictive value in assessing salivary gland injury following 131I treatment after surgery in patients with thyroid cancer.

OBJECTIVE To study material basis of Xianglian Pill(XLP)in vivo and in vitro using UPLC-Q-TOF-MS/MS technique,and to qualitatively analyze the main components of Xianglian Pill as well as the prototypical components and metabolites that were absorbed into the blood.METHODS A Thermo Accucore C18 column(2.1 mm×100 mm,2.6 μm)was used with 0.1%formic acid in water(A)-acetonitrile(B)as the mobile phase in a gradient elution mode,the column temperature was 40℃,and the flow rate was 0.4 mL·min-1 with the injection volume of 4 μL.The mass spectrometry information was collected by using the electros-pray ionization(ESI)ion source in the positive-negative ion scan mode.RESULTS By analyzing the precise relative molecular mass,retention times,secondary fragments and other mass spectrometry information of the components,and comparing them with the mass spectrometry information of the corresponding control products and relevant literature information,a total of 75 chemical compo-nents were finally identified in the extract of Xianglian Pill,including alkaloids,sesquiterpenoids,flavonoids,limonins and organic acids.In addition,16 prototypical components and 15 metabolites were identified in the plasma of the mice after the administration of the drug.Most of the prototypical components found in the plasma were alkaloids,and the metabolic pathways of these components in vivo were mainly hydroxylation,demethylation,reduction,hydrolysis,hydrogenation and glucuronidation.CONCLUSION The method can be used for the rapid identification of the external and internal components of Xianglian Pill,and its analytical results lay the foundation for further basic research on the pharmacological substances.

Objective To establish a method for determining hydrogen sulfide(H2S)in blood and apply it to practical cases.Methods A delute solution was achieved by adding 0.8 mL saturated borax solution into 0.2 mL blood sample was diluted with.1 mL acetonitrile solution containing 0.1％formic acid was then taken in a test tube,followed by adding 0.1 mL dilute solution and 0.1 mL thiozine aqueous solution(1％).After thorough mixing,the mixture was left to stand for 30 minutes.Subsequently,the sample was subjected to liquid chromatography-tandem mass spectrometry(LC-MS/MS)analysis after centrifugation and membrane filtration.Results The results showed that H2S exhibited good linearity within the concentration range of 10～2 000 ng/mL,with the R2 value of 0.998 5.The detection limit was 5 ng/mL,and the quantification limit was 10 ng/mL.In three cases of H2S poisoning,sulfur ions were detected in the blood of the deceased individuals,with concentrations ranging from 0.17 to 0.56 μg/mL.Conclusion For the first time,this study established a LC-MS/MS method for determining H2S in blood,which can meet the detection needs of H2S poisoning cases.