Exploring the formation mechanism of ferulic acid/hydroxypropyl-ß-cyclodextrin inclusion complex: spectral analyses and computer simulation.

BACKGROUND: The biological functions of ferulic acid (FA) have garnered significant interest but its limited solubility and stability have led to low bioavailability. Hydroxypropyl-ß-cyclodextrin (HP-ß-CD), with its distinctive hollow structure, offers the potential for encapsulating hydrophobic molecules. The formation of an inclusion complex between FA and HP-ß-CD may therefore be a viable approach to address the inherent limitations of FA. To investigate the underlying mechanism of the FA/HP-ß-CD inclusion complex formation, a combination of spectral analyses and computer simulation was employed. RESULTS: The disappearance of the characteristic peaks of FA in Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) confirmed the formation of an inclusion complex between FA and HP-ß-CD. Thermogravimetry-derivative thermogravimetry (TG-DTG) studies demonstrated that the thermal stability of FA was enhanced due to the encapsulation of FA within HP-ß-CD. Molecular dynamics simulation also provided evidence that FA successfully penetrated the HP-ß-CD cavity, primarily driven by van der Waals interactions. The formation of the complex resulted in more compact HP-ß-CD structures. The bioavailability of FA was also strengthened through the formation of inclusion complexes with HP-ß-CD. CONCLUSIONS: The findings of this study have contributed to a deeper understanding of the interactions between FA and HP-ß-CD, potentially advancing a delivery system for FA and enhancing the bioavailability of insoluble active components. © 2024 Society of Chemical Industry.

[Degradation of Ciprofloxacin by Activating Peroxymonosulfate with Sludge Biochar].

Sludge biochar(BC), which was prepared by the pyrolysis of waste-activated sludge at 450℃, was applied for peroxymonosulfate(PMS) activation to construct a BC/PMS system for ciprofloxacin(CIP) degradation. The physical and chemical properties of BC were studied using scanning electron microscopy(SEM), an energy dispersive spectrometer(EDS), a Fourier transform infrared spectrometer(FTIR), X-ray diffraction(XRD), a Zeta potential analyzer, and electron paramagnetic resonance spectroscopy(EPR). The effects of BC dosage, PMS dosage, initial pH value, and inorganic anions on CIP removal in the BC/PMS system were investigated. Further, the degradation mechanism of the BC/PMS system was speculated through the free radical quenching experiment and X-ray photoelectron spectroscopy(XPS) analysis. The results showed that the CIP degradation rate was 49.09% at a BC dosage of 1.0 g·L-1, PMS of 3.0 mmol·L-1, CIP of 20 mg·L-1, and pH of 6.0 in 120 min. SO42- and NO3- had no obvious effect on the removal of CIP in the BC/PMS system, whereas HCO3- and Cl-could inhibit CIP degradation significantly. The CIP removal in the BC/PMS system was attributed to the common function of the radical pathway dominated by ·OH and SO4-· and the non-radical pathway dominated by 1O2. The CIP degradation pathway mainly included piperazine ring opening and hydroxylation reaction.

Diagnostic value of contrast-enhanced ultrasonography in the preoperative evaluation of lymph node metastasis in papillary thyroid carcinoma: a single-center retrospective study.

BACKGROUND: Contrast-enhanced ultrasound (CEUS) has been recently used for the assessment of cervical lymph node metastasis (LNM) to guide surgical operation in patients with papillary thyroid carcinoma (PTC). However, the specificity and sensitivity of CEUS reported from previous studies are not consistent. The objective of this study was to evaluate the diagnostic value of CEUS for the metastasis of cervical lymph nodes in PTC patients based on data from one regional central hospital. METHODS: The diagnostic value of CEUS in preoperative LNM of PTC patients was concluded by comparing the results of CEUS on lymph node status with postoperative pathology examination. In addition, this study conducted hierarchical analysis of PTC patients to explore whether tumor size, different lymph node regions, and Hashimoto's thyroiditis influence the assessment of CEUS. RESULTS: This research study ultimately enrolled 965 PTC patients, including 266 males and 699 females with a mean age of 42.27 ± 11.34 years. A total of 527 patients were considered clinical-node negative, and 438 were clinical-node positive before surgery. The specificity, sensitivity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of CEUS in the assessment of LNM in PTC patients were 56.00%, 71.00%, 57.06%, 69.76% and 62.59%, respectively. For central and lateral lymph nodes, the accuracy of CEUS in PTC patients was 49.43% and 54.30%, respectively. In addition, it was shown that the accuracy of CEUS in PTC patients with Hashimoto's thyroiditis (HT) slightly decreased to 58.44%, and the accuracy of CEUS in PTC patients with non-HT in turn increased to 64.17%. The accuracy of CEUS in non-papillary thyroid microcarcinoma (PTMC) and PTMC patients was 65.68% and 61.24%, respectively. The accuracy of CEUS in predicting central LNM was significantly different between PTC patients with or without HT (P < 0.001) in this study but not for lateral lymph nodes (P = 0.114). CONCLUSION: The accuracy of CEUS in the assessment of LNM in PTC is not consistently satisfactory, especially for central lymph nodes, small tumor diameters, or patients with HT. More diagnostic technologies for abnormal lymph nodes should be considered in PTC patients.

Development and validation of a nomogram prediction model for hypertension-diabetes comorbidity based on chronic disease management in the community.

PURPOSE: ​Develop and validate a nomogram prediction model for hypertension-diabetes comorbidities based on chronic disease management in the community. PATIENTS AND METHODS: The nomogram prediction model was developed in a cohort of 7200 hypertensive patients at a community health service center in Hongshan District, Wuhan City. The data were collected from January 2022 to December 2022 and randomly divided into modeling and validation groups at a 7:3 ratio. The Lasso regression model was used for data dimensionality reduction, feature selection, and clinical test feature construction. Multivariate logistic regression analysis was used to build the prediction model. RESULTS: The application of the nomogram in the verification group showed good discrimination, with an AUC of 0.9205 (95% CI: 0.8471-0.9527) and a good calibration effect. Decision curve analysis demonstrated that the predictive model was clinically useful. CONCLUSION: This study presents a nomogram prediction model that incorporates age, waist-height ratio and elevated density lipoprotein cholesterol (HDL-CHOLESTEROL), which can be used to predict the risk of codeveloping diabetes in hypertensive patients.

A novel non-invasive exhaled breath biopsy for the diagnosis and screening of breast cancer.

BACKGROUND: Early detection is critical for improving the survival of breast cancer (BC) patients. Exhaled breath testing as a non-invasive technique might help to improve BC detection. However, the breath test accuracy for BC diagnosis is unclear. METHODS: This multi-center cohort study consecutively recruited 5047 women from four areas of China who underwent BC screening. Breath samples were collected through standardized breath collection procedures. Volatile organic compound (VOC) markers were identified from a high-throughput breathomics analysis by the high-pressure photon ionization-time-of-flight mass spectrometry (HPPI-TOFMS). Diagnostic models were constructed using the random forest algorithm in the discovery cohort and tested in three external validation cohorts. RESULTS: A total of 465 (9.21%) participants were identified with BC. Ten optimal VOC markers were identified to distinguish the breath samples of BC patients from those of non-cancer women. A diagnostic model (BreathBC) consisting of 10 optimal VOC markers showed an area under the curve (AUC) of 0.87 in external validation cohorts. BreathBC-Plus, which combined 10 VOC markers with risk factors, achieved better performance (AUC = 0.94 in the external validation cohorts), superior to that of mammography and ultrasound. Overall, the BreathBC-Plus detection rates were 96.97% for ductal carcinoma in situ, 85.06%, 90.00%, 88.24%, and 100% for stages I, II, III, and IV BC, respectively, with a specificity of 87.70% in the external validation cohorts. CONCLUSIONS: This is the largest study on breath tests to date. Considering the easy-to-perform procedure and high accuracy, these findings exemplify the potential applicability of breath tests in BC screening.

Efficiency and mechanism of the degradation of ciprofloxacin by the oxidation of peroxymonosulfate under the catalysis of a Fe3O4/N co-doped sludge biochar.

A novel and recyclable composite material, Fe3O4/N co-doped sludge biochar (FNBC), was developed from original sludge biochar (BC) and found to have excellent stability and superior catalytic capacity during the ciprofloxacin (CIP) degradation under the action of peroxymonosulfate (PMS). In the FNBC/PMS system, an approximately complete removal of CIP was achieved within 60 min under the condition of 1.0 g/L FNBC, 3.0 mM PMS, and 20 mg/L CIP, which was about 2.08 times of that in BC/PMS system (48.01%). Besides, FNBC/PMS system could effectively remove CIP under the influence of wide pH (2.0-10.0) or inorganic ions compared with BC/PMS system. Moreover, it was found that there were radical produced under the effect of Fe element, defects, functional groups, pyridinic N and pyrrolic N and non-radical caused by graphitic N, carbon atoms next to the iron atoms and better adsorption capacity in the FNBC/PMS system. It was observed that the contribution of hydroxyl radical (•OH), sulfate radical (SO4•-) and singlet oxygen (1O2), which were the main reactive oxygen species, during the CIP degradation, were 75.80%, 11.49% and 10.26%, respectively. Furthermore, total organic carbon (TOC) variation was analyzed and the degradation pathway of CIP was speculated. The application of this material could combine the recycling of sludge with the effective degradation of refractory organic pollutant, providing an environmentally friendly and economic method.

Research progress on social withdrawal in children / 中国学校卫生

Abstract@#Social withdrawal is a kind of behavioral inhibition in social situations, which may increase the risk for maladjustment, internalizing and externalizing problems, interfering with psychological development and healthy growth. With the deepening understanding in sociology of development, child social withdrawal has gradually received extensive attention from scholars across the world. Understanding the phenomenon of child social withdrawal is important for in depth follow up research. Based on the literature review, the paper aims to summarize the types, mechanisms and influencing factors of social withdrawal in children, in order to provide scientific basis for formulating prevention strategies and early intervention programs in the future.

Clinical considerations of CDK4/6 inhibitors in HER2 positive breast cancer.

Deregulation of cell cycles can result in a variety of cancers, including breast cancer (BC). In fact, abnormal regulation of cell cycle pathways is often observed in breast cancer, leading to malignant cell proliferation. CDK4/6 inhibitors (CDK4/6i) can block the G1 cell cycle through the cyclin D-cyclin dependent kinase 4/6-inhibitor of CDK4-retinoblastoma (cyclinD-CDK4/6-INK4-RB) pathway, thus blocking the proliferation of invasive cells, showing great therapeutic potential to inhibit the spread of BC. So far, three FDA-approved drugs have been shown to be effective in the management of advanced hormone receptor positive (HR+) BC: palbociclib, abemaciclib, and ribociclib. The combination strategy of CDK4/6i and endocrine therapy (ET) has become the standard therapeutic regimen and is increasingly applied to advanced BC patients. The present study aims to clarify whether CDK4/6i can also achieve a certain therapeutic effect on Human epidermal growth factor receptor 2 positive (HER2+) BC. Studies of CDK4/6i are not limited to patients with estrogen receptor positive/human epidermal growth factor receptor 2 negative (ER+/HER2-) advanced BC, but have also expanded to other types of BC. Several pre-clinical and clinical trials have demonstrated the potential of CDK4/6i in treating HER2+ BC. Therefore, this review summarizes the current knowledge and recent findings on the use of CDK4/6i in this type of BC, and provides ideas for the discovery of new treatment modalities.

Adsorption and oxidation of ciprofloxacin by a novel layered double hydroxides modified sludge biochar.

In this study, biochar derived from municipal sludge (SBC) was modified by CoFe-Layered double hydroxides (CoFe-LDH), and used as adsorbent and oxidant for the removal of ciprofloxacin (CIP) for the first time. Under the optimal conditions, the CIP removal rate is increased by 24% compared with the single SBC, while the removal rates of total organic carbon and total nitrogen in the modified one are increased by 24% and 27%, respectively. Mechanism investigation suggested that the specific surface area and adsorption sites of modified biochar increased, and more CIP was adsorbed to the composite surface and then oxidized by more environmental persistent free radicals contained in the CoFe-LDH@SBC, when the adsorbed CIP molecules was oxidized and degraded, the adsorption sites can be freed and thus new CIP could be adsorbed to the CoFe-LDH@SBC. In addition, the plausible degradation pathways of CIP were proposed according to high-performance liquid chromatography-mass spectrometry and density functional theory calculation. It not only reveals that CoFe-LDH@SBC has the high ability of adsorption and oxidation for CIP removal but also sheds novel insight into the application of biochar.

DrABC: deep learning accurately predicts germline pathogenic mutation status in breast cancer patients based on phenotype data.

BACKGROUND: Identifying breast cancer patients with DNA repair pathway-related germline pathogenic variants (GPVs) is important for effectively employing systemic treatment strategies and risk-reducing interventions. However, current criteria and risk prediction models for prioritizing genetic testing among breast cancer patients do not meet the demands of clinical practice due to insufficient accuracy. METHODS: The study population comprised 3041 breast cancer patients enrolled from seven hospitals between October 2017 and 11 August 2019, who underwent germline genetic testing of 50 cancer predisposition genes (CPGs). Associations among GPVs in different CPGs and endophenotypes were evaluated using a case-control analysis. A phenotype-based GPV risk prediction model named DNA-repair Associated Breast Cancer (DrABC) was developed based on hierarchical neural network architecture and validated in an independent multicenter cohort. The predictive performance of DrABC was compared with currently used models including BRCAPRO, BOADICEA, Myriad, PENN II, and the NCCN criteria. RESULTS: In total, 332 (11.3%) patients harbored GPVs in CPGs, including 134 (4.6%) in BRCA2, 131 (4.5%) in BRCA1, 33 (1.1%) in PALB2, and 37 (1.3%) in other CPGs. GPVs in CPGs were associated with distinct endophenotypes including the age at diagnosis, cancer history, family cancer history, and pathological characteristics. We developed a DrABC model to predict the risk of GPV carrier status in BRCA1/2 and other important CPGs. In predicting GPVs in BRCA1/2, the performance of DrABC (AUC = 0.79 [95% CI, 0.74-0.85], sensitivity = 82.1%, specificity = 63.1% in the independent validation cohort) was better than that of previous models (AUC range = 0.57-0.70). In predicting GPVs in any CPG, DrABC (AUC = 0.74 [95% CI, 0.69-0.79], sensitivity = 83.8%, specificity = 51.3% in the independent validation cohort) was also superior to previous models in their current versions (AUC range = 0.55-0.65). After training these previous models with the Chinese-specific dataset, DrABC still outperformed all other methods except for BOADICEA, which was the only previous model with the inclusion of pathological features. The DrABC model also showed higher sensitivity and specificity than the NCCN criteria in the multi-center validation cohort (83.8% and 51.3% vs. 78.8% and 31.2%, respectively, in predicting GPVs in any CPG). The DrABC model implementation is available online at http://gifts.bio-data.cn/ . CONCLUSIONS: By considering the distinct endophenotypes associated with different CPGs in breast cancer patients, a phenotype-driven prediction model based on hierarchical neural network architecture was created for identification of hereditary breast cancer. The model achieved superior performance in identifying GPV carriers among Chinese breast cancer patients.

[Efficacy of ultrasound-guided vacuum-assisted Mammotome excision for management of benign breast diseases: analysis of 1267 cases].

OBJECTIVE: To assess the clinical value of ultrasound-guided vacuum-assisted Mammotome (MMT) system for surgical resection of benign breast disease. METHODS: This retrospective study was conducted among 1267 patients who underwent minimally invasive surgery with ultrasound-guided MMT system for benign breast disease at our center between January, 2009 and January, 2014. The resection rate, incidence of complication, recurrence rate, patients' satisfaction, clinical follow-up results and risk factors were analyzed. The patients were followed up at 1 month, 6 months and every 6 months thereafter for up to 2 years with a median follow-up of 22 months. RESULTS: Of the total of 1267 patients, 1259 (99.36%) had complete resection of the breast lesions, and residual lesions were found in 8 cases 1 month after the operation. The resection rate was significantly associated with lesion size (P=0.003) but not with the patients'age, pathology, BI-RADS classification, or the number or location of the lesions (P>0.05). Eighty-nine (7.02%) patients showed postoperative complications, and hematoma occurred in 70 (5.52%) patients after the operation. The complication rate was significantly associated with the number and location of lesions (P=0.000) but not with age, pathology, BI-RADS classification or the lesion size (P>0.05). A total of 193 (15.23%) patients had recurrence after the operation, including 65 (5.13%) with in situ recurrence and 128 (10.1%) with new lesions. The recurrence rate was significantly associated with the number and size of lesions (P=0.000) but not with age, pathology, BI-RADS classification or location of lesions(P>0.05). Six patients were not satisfied with the appearance of the incision, and the overall satisfaction rate of the patients was 99.52%. CONCLUSION: s Ultrasound-guided vacuum-assisted MMT excision is a safe and effective procedure for benign breast disease with a low surgical complication rate, a high resection rate and a low recurrence rate. This technique results in good postoperative appearance for treatment of benign and high-risk breast lesions, especially multiple benign breast lesions.

A novel UPLC-MS/MS method for simultaneous quantification of rhein, emodin, berberine and baicalin in rat plasma and its application in a pharmacokinetic study.

BACKGROUND: Dahuang Huanglian Xiexin Decoction (DHXD) is a classical formula in traditional Chinese medicines. In this study, a novel UPLC-MS/MS method was developed for the simultaneous quantification of rhein, emodin, berberine and baicalin, the major bioactive compounds of DHXD in rat plasma. RESULTS: The method possessed high sensitivity and ultrashort analysis time (7 min). Linearity, accuracy, precision and extraction recovery of four analytes were all satisfactory. The method was then successfully applied in a pharmacokinetic study of four bioactive components after a single oral administration of DHXD extract to rats. CONCLUSION: The method was applicable for simultaneous bioanalysis of rhein, emodin, berberine and baicalin.