Predictive Value of Ultrasound Imaging Characteristics and a BRAF V600E Nomogram for Central Lymph Node Metastasis Risk in Papillary Thyroid Microcarcinoma.

Objective: The objective of this study was to construct and validate a nomogram for preoperatively identifying central lymph node metastasis (CLNM) in patients with papillary thyroid microcarcinoma (PTMC) using ultrasound imaging characteristics and the BRAF V600E gene mutation. Methods: A retrospective data analysis was conducted on 216 PTMC patients who underwent surgery at our facility between February 2016 and June 2022. Univariate and multivariate analyses examined the relationship between CLNM and clinicopathological traits, the BRAF V600E mutation, and ultrasound imaging characteristics. The area under the curve (AUC) was calculated, and receiver operating characteristic (ROC) curves were constructed to assess the predictive efficacy of the model in both the training and validation sets. Calibration curves were generated to evaluate the agreement between predicted and observed outcomes. Decision curve analysis (DCA) was performed to assess the clinical suitability of the model. A nomogram was developed to illustrate the predicted likelihood of CLNM. Results: The incidence rate of CLNM was found to be 38.4% (83/216 patients). Logistic univariate and multivariate analyses revealed that the BRAF V600E mutation, patient age less than 45 years, tumor size greater than 5 mm, thyroid capsule invasion, and presence of microcalcification in the tumor were independent risk factors for CLNM. The model demonstrated high exclusionary performance with AUC values of 0.88 and 0.877 in the training and validation cohorts, respectively. The calibration curve and DCA confirmed the accuracy of the predicted outcomes and the clinical value of the nomogram. Conclusions: A model incorporating ultrasound imaging characteristics and the BRAF V600E mutation can effectively predict the risk of central lymph node metastasis in patients with papillary thyroid microcarcinoma before surgery. The identified risk factors, including tumor size greater than 5 mm3, BRAF V600E mutation, patient age less than 45 years, nodule capsule invasion, and presence of microcalcification, can aid in surgical decision-making. The nomogram provides a valuable tool for clinicians to assess the likelihood of CLNM in PTMC patients.

Curcumin combined with arsenic trioxide in the treatment of acute myeloid leukemia: network pharmacology analysis and experimental validation.

PURPOSE: This study aimed to evaluate the effects of curcumin by co-administration of arsenic trioxide (As2O3) in acute myeloid leukemia (AML) treatment, using network pharmacology and experimental validation. METHODS: Using Pubchem database, Traditional Chinese Medicine Information Database (TCMID) database, and Swiss target prediction database to predict compound-related targets, AML-associated targets were determined using GeneCards and Online Mendelian Inheritance in Man (OMIM) databases. We identify overlapping common targets by comparing Compounds-related and AML-associated targets and using these targets to perform GO and KEGG functional enrichment analyses. Subsequently, these targets were input into the STRING database, and we used Cytoscape to construct protein-protein interaction (PPI) network. Finally, we used KG1-a cells and the AML mouse model to measure the anti-leukemia effects of curcumin and As2O3 and their combination. RESULTS: Compounds and targets screening hinted that 85 intersection targets were predicted in the curcumin treatment of AML, 75 targets in the As2O3 treatment of AML, and 48 targets in the curcumin combined with the As2O3 treatment of AML. GO and KEGG analyses indicated that the top 10 enriched biological processes and top 20 pathways implicated in the therapeutic effects of curcumin and As2O3 on AML, respectively. In addition, network pharmacology screening revealed STAT3, TP53, EP300, MAPK1, and PIK3CA as the top five genes in PPI network of curcumin treatment of AML and TP53, MAPK3, MAPK1, STAT3, and SRC as the top five genes in PPI network of As2O3 treatment of AML. Moreover, the in vitro experiment demonstrated that curcumin combined with As2O3 inhibited proliferation and induced apoptosis in KG1-a cells, and this effect is more substantial than curcumin or As2O3 alone. Mechanistically, the curcumin combined with As2O3 significantly down-regulated the protein expression of JAK2, STAT3, and Bcl-2, and up-regulated the levels of P53, P27, and Bax. In the mouse model, the survival time of mice in each administration group was drawn out to varying degrees, with the most significant prolongation in the curcumin combined with the As2O3 group. CONCLUSION: Our results suggested that curcumin and As2O3 combination therapy exerts more significant anti-leukemia effects in the treatment of AML than curcumin or As2O3 monotherapy by up-regulating p53 pathway and down-regulating the JAK2/STAT3 pathway.

[Preadmission follow-up condition of neonates hospitalized due to severe hyperbilirubinemia after discharge from the department of obstetrics and influencing factors for follow-up compliance: a multicenter investigation]. / äº§ç§‘å‡ºé™¢åŽå› ä¸¥é‡é«˜èƒ†çº¢ç´ è¡€ç—‡ä½é™¢æ–°ç”Ÿå„¿å ¥é™¢å‰éšè®¿æƒ å†µåŠéšè®¿ä¾ä»Žæ€§å½±å“å› ç´ çš„å¤šä¸­å¿ƒè°ƒæŸ¥.

OBJECTIVES: To investigate the preadmission follow-up condition of neonates hospitalized due to severe hyperbilirubinemia after discharge from the department of obstetrics and the influencing factors for follow-up compliance. METHODS: A multicenter retrospective case-control study was performed for the cases from the multicenter clinical database of 12 units in the Quality Improvement Clinical Research Cooperative Group of Neonatal Severe Hyperbilirubinemia in Jiangsu Province of China from January 2019 to April 2021. According to whether the follow-up of neonatal jaundice was conducted on time after discharge from the department of obstetrics, the neonates were divided into two groups: good follow-up compliance and poor follow-up compliance. The multivariate logistic regression model was used to identify the influencing factors for follow-up compliance of the neonates before admission. RESULTS: A total of 545 neonates with severe hyperbilirubinemia were included in the study, with 156 neonates (28.6%) in the good follow-up compliance group and 389 (71.4%) in the poor follow-up compliance group. The multivariate logistic regression analysis showed that low gestational age at birth, ≥10% reduction in body weight on admission compared with birth weight, history of phototherapy of siblings, history of exchange transfusion of siblings, Rh(-) blood type of the mother, a higher educational level of the mother, the use of WeChat official account by medical staff to remind of follow-up before discharge from the department of obstetrics, and the method of telephone notification to remind of follow-up after discharge were associated with the increase in follow-up compliance (P<0.05). CONCLUSIONS: Poor follow-up compliance is observed for the neonates with severe hyperbilirubinemia after discharge from the department of obstetrics, which suggests that it is necessary to further strengthen the education of jaundice to parents before discharge and improve the awareness of jaundice follow-up. It is recommended to remind parents to follow up on time by phone or WeChat official account.

Identification of chloramination disinfection by-products from phenylalanine in tap drinking water.

Phenylalanine (Phe) is widely present in natural water and serves as a precursor of disinfection by-products (DBPs). We reported the identification of chloramination DBPs from Phe in drinking water using ultra-high performance liquid chromatography (UHPLC) coupled with complementary high-resolution quadrupole time-of-flight (QTOF) and triple quadrupole (tQ) tandem mass spectrometry (MS/MS). In the chloraminated Phe water solution, sixteen new DBPs in a total of seventeen were identified based on their accurate mass, MS/MS spectra and 35Cl/37Cl isotopic patterns. Three of these DBPs were verified as benzamide, phenylacetamide, and p-hydroxyphenylacetamide with their standards, while the others were chlorinated derivatives of Phe, hydrazone, amidine, amide and peroxide, in which the unique structures of these DBPs were rarely reported. Their stability and formation process were investigated as well. Furthermore, a method consisting of solid phase extraction (SPE) and UHPLC-MS/MS using dynamic multiple reaction monitoring (dMRM) was developed to investigate these DBPs in authentic waters. Phe, benzamide, phenylacetamide, and N-Cl-2-phenylacetimidamide were detected in chlorinated tap water. Compared with the other identified DBPs, these three DBPs were exceptionally stable and could be formed in wide formation conditions. Our work not only provided ideas for the identification of new chloramination DBPs, but also demonstrated that some DBPs usually generated in the chloramination disinfection process could also be found in the chlorinated drinking water.

Effects of Qinghuang Powder on Acute Myeloid Leukemia Based on Network Pharmacology, Molecular Docking, and In Vitro Experiments.

Qinghuang powder (QHP) is a traditional Chinese herbal medicine. This is a unique formula that is frequently used to treat malignant hematological diseases such as acute myeloid leukemia (AML) in modern clinical practice. An approach of network pharmacology and experimental validation were applied to investigate the pharmacological mechanisms of QHP in AML treatment. First, public databases for target genes known to be associated with AML are searched and compared to the target genes of the active compounds in QHP. Second, AML-associated genes and QHP target genes are compared to identify overlapping enriched genes, and these were used to predict selected target genes that may be implicated in the effects of QHP on AML. Additionally, we conducted functional enrichment analyses, such as gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The significantly enriched pathway associated with potential target proteins was the PI3K-Akt signaling pathway, suggesting that these potential target proteins and pathways may mediate the beneficial biological effects of QHP on AML. All these following genes were found to occur in the compounds-target-pathway networks: AKT1, MAPK1, MAPK3, PIK3CG, CASP3, CASP9, TNF, TGFB1, MAPK8, and TP53. Then, based on the molecular docking studies, it was suggested that the active compound isovitexin can fit into the binding pockets of the top candidate QHP-AML target proteins (PIK3CG). Subsequently, based on the prediction by network pharmacology analysis, both in vitro AML cells and western blot experiments were performed to validate the curative role of QHP. QHP exerted its antitumor activity on AML in vitro, as it inhibits cells proliferation, reduced the expression of Bcl-2 protein, and downregulated the PI3K-Akt signaling pathway. In conclusion, these results revealed that QHP could treat AML via a "multicomponent, multitarget, multipathway" regulatory network. Furthermore, our study also demonstrated that the combination of network pharmacology with the experimental study is effective in discovering and identifying QHP in the treatment of AML and its underlying pharmacological mechanisms.

Effect of Daiqin phlegm-expelling pill on development of inflammation in rats with chronic obstructive pulmonary disease induced by lipopolysaccharide and smoke.

OBJECTIVE: To investigate the effect of Daiqin phlegm-expelling pill, prepared with Traditional Chinese Medicine (TCM), on the development of inflammation in Sprague-Dawley (SD) rats with chronic obstructive pulmonary disease (COPD) induced by lipopolysaccharide (LPS) and smoke, and to identity the possible underlying mechanism. METHODS: Sixty male rats were divided into 6 groups (healthy control group, untreated group, Daiqin phlegm-expelling pill low, middle and high dose, and ambroxol hydrochloride tablet group). COPD was established in SD rats by sootiness and tracheal instillation with LPS. The rats were treated with Daiqin phlegm-expelling pill at the indicated doses for 28 d, the inflammatory cells in bronchoalveolar lavage fluid (BALF), the concentration of tumor necrosis factor-α (TNF-α), interleukin (IL)-8 and IL-6 in blood and the inflammation in lung were evaluated. RESULTS: The number of inflammatory cells in the BALF and TNF-α, IL-8 and IL-6 level in plasma were significantly reduced in rats with COPD when treated with Daiqin phlegm-expelling pill or ambroxol hydrochloride tablet, compared with those without any treatment. The Daiqin phlegm-expelling pill treated rats with COPD had a attenuated inflammation in lung tissue, compared with the untreated group. CONCLUSION: Daiqin phlegm-expelling pill can significantly restrain the airway inflammation in rats with LPS-smoke induced COPD.