A Survey on the Knowledge, Attitudes, Behaviors and Influencing Factors of Caregivers for Newborns With COVID-19 in Chongqing, China.

OBJECTIVE: This study aimed to investigate the healthcare knowledge, attitudes, and behaviors of primary caregivers of newborns with coronavirus disease 2019 (COVID-19) during the pandemic in Chongqing, China, and analyze the influencing factors. METHODS:  The study included primary caregivers of COVID-19 newborns hospitalized in our institution from December 2022 to January 2023. A questionnaire survey was initiated to assess the caregivers' health-care knowledge, attitudes, and behaviors for COVID-19 and the influencing factors. The data were analyzed statistically. RESULTS: A total of 195 caregivers were included, one for each infant with COVID-19. The questionnaire consisted of three dimensions. For the knowledge dimension, the top scoring items were wearing masks in public spaces (4.92 ± 0.087), strengthening hand hygiene (4.83 ± 0.164), and frequent ventilation in living environment (4.62 ± 0.331) in order; for the attitude dimension, the top three scoring items were wearing masks in public spaces (4.85 ± 0.353), strengthening hand washing and disinfection (4.72 ± 0.450), and regular ventilation (4.49 ± 0.501). For the behavior dimension, the top three were confidence in winning the challenge of the pandemic (4.71 ± 0.480), standardized wearing of masks in public spaces/confined spaces (4.68 ± 0.589), and high satisfaction with community epidemic prevention measures (4.67 ± 0.496). Among the influencing factors, fear of COVID-19 was the independent risk indicator for the caregivers' anxiety (OR = 38.085, 95% CI = 14.383-100.664) and fear of COVID-19 (OR = 8.170, 95%CI = 2.156-30.957) and fever (OR = 10.213, 95% CI = 1.972-52.892) were the independent risk indicators for depression. CONCLUSION:  The study shows a key link between caregiver knowledge, attitudes, behaviors, and neonatal COVID-19 infection, with a gap between knowledge, attitudes, and behaviors. Caregivers, especially those dealing with premature infants, worried about mother-to-child transmission and experienced multiple births, face significant psychological stress during this phase of the pandemic.

A new alkaloid and two organic acids from Portulaca oleracea L. and their bioactivities.

A new alkaloid, identified as 1-benzyl-2-nitroso-1,2,3,4-tetrahydroisoquinoline-6,7-diol, named oleraisoquinoline (1), and five organic acids and two esters, identified as 5-(hydroxymethyl)furan-2-carboxylic acid (2), 1H-pyrrole-2,5-dicarboxylic acid (3), (7E,10E)-octadeca-7,10-dienoic acid (4), (10E,13E)-octadeca-10,13-dienoic acid (5), (7E,10E)-hexadeca-7,10-dienoic acid (6), methyl tridecanoate (7) and methyl (9E,12E)-octadeca-9,12-dienoate (8), were isolated from Portulaca oleracea L., among which compounds 2 and 4‒7 were isolated for the first time. Moreover, the anti-inflammatory activities of compounds 1‒3 were studied, especially, compound 1 presented good inhibitory effects on the production of inflammatory factors IL-1ß and TNF-α.

Preparation and anti-triple-negative breast cancer cell effect of a nanoparticle for the codelivery of paclitaxel and gemcitabine.

Amphiphilic polymers (HA-ANI) were prepared by grafting hyaluronic acid (HA) and 6-(2-nitroimidazole)hexylamine (ANI) and then self-assemble in water to form nanoparticles (NPs) that could be loaded with paclitaxel (PTX) and gemcitabine (GEM) by dialysis. Infrared spectroscopy and 1H-NMR indicated the successful synthesis of HA-ANI. Three different ratios of NPs were prepared by adjusting the ratios of hydrophilic and hydrophobic materials, and the particle size decreased as the ratio of hydrophilic materials increased. When HA:ANI = 2.0:1, the nanoparticles had the smallest size distribution, good stability and near spherical shape and had high drug loading and encapsulation rates. In vitro release experiments revealed that NADPH could accelerate the drug release from NPs. Cellular uptake rate reached 86.50% at 6 h. The toxic effect of dual drug-loaded nanoparticles (P/G NPs) on MDA-MB-231 cells at 48 h was stronger than that of the free drug. The AO/EB double-staining assay revealed that a large number of late apoptotic cells appeared in the P/G NPs group, and the degree of cell damage was significantly stronger than that of the free drug group. In the cell migration assay, the 24 h-cell migration rate of the P/G NPs group was 5.99%, which was much lower than that of the free group (13.87% and 17.00%). In conclusion, MDA-MB-231 cells could effectively take up P/G NPs, while the introduction of the nano-codelivery system could significantly enhance the toxicity of the drug to MDA-MB-231 cells as well as the migration inhibition effect.

The relationship between the PICC tip position and weight gain, length growth of premature infants under ultrasonography: a correlation analysis study.

Objective: This study aimed to analyze the correlation between PICC tip position and weight/length changes in preterm infants in different positions using ultrasonography. Methods: The study is a prospective before and after self-control clinical trial. The study analyzed the distance between the PICC tip and the entrance of the heart under ultrasonography for premature infants who underwent PICC insertion. The infants were positioned and tracked weekly, and their weight and length were recorded. The Spearman rank correlation test was used to analyze the relationship between the displacement distance of the PICC tip under ultrasonography in different positions and weight/length changes. Results: A total of 202 premature infants were included in the study, and 100% of them experienced changes in the PICC tip position. During the first week, 134 (66.33%) cases in a flexed position and 153 (75.74%) cases in a straight position showed displacement of the catheter toward the heart. The displacement distance of the tip during catheter retention was significantly correlated with weight change (rs = 0.681/0.661, P < 0.05) and length change (rs = 0.629/0.617, P < 0.05). In the third and fifth weeks, weight increased by 451 ± 178 and 750 (715-975) g, length increased by 1.50 (1.00-2.12) and 3.00 (2.00-3.70) cm, the catheter moved 1.27 ± 0.89 and 2.23 ± 0.95 cm, respectively, in a flexed position. Conclusion: The PICC tip position in preterm infants is influenced by weight and length changes. It is crucial to use ultrasonography to track and locate the catheter within the first week of placement and to increase the frequency of catheter localization starting from the third and fifth weeks. The flexed position is recommended during catheter localization.

Tumor Microenvironment Responsive Nanomicelle with Folic Acid Modification Co-Delivery of Doxorubicin/Shikonin for Triple Negative Breast Cancer Treatment.

Triple negative breast cancer (TNBC), which has poor prognosis, easily develops drug resistance and metastasizes. In general, those TNBC characteristics are related to a high activation of the epithelial-mesenchymal transition (EMT) pathway, which is inhibited by shikonin (SKN). Therefore, the synergistic therapy of SKN and doxorubicin (DOX) will increase anti-tumor efficacy and reduce metastasis. In this study, we prepared the folic acid-linked PEG nanomicelle (NM) grafted with the DOX (denoted as FPD) to load the SKN. We prepared the SKN@FPD NM according to the effective ratio of dual drugs, where the drug loadings of DOX and SKN were 8.86 ± 0.21% and 9.43 ± 0.13%, with 121.8 ± 1.1 nm of its hydrodynamic dimension and 6.33 ± 0.16 mV of zeta potential, respectively. The nanomaterials significantly slowed down the release of DOX and SKN over 48 h, leading to the release of pH-responsive drugs. Meanwhile, the prepared NM inhibited the activity of MBA-MD-231 cells in vitro. Further in vitro study revealed that the SKN@FPD NM increased the DOX uptake and significantly reduced the metastasis of MBA-MD-231 cells. Overall, these active-targeting NMs improved the tumor-targeting of small molecular drugs and effectively treated TNBC.

Sorafenib/2800Z Co-Loaded into Cholesterol and PEG Grafted Polylysine NPs for Liver Cancer Treatment.

The treatment of liver cancer remains challenging due to the low responsiveness of advanced cancer to therapeutic options. Sorafenib is the first line chemotherapeutic drug for advanced liver cancer but is frequently associated with severe side effects lead to discontinuation of chemotherapy. We previously developed a specific SIRT7 inhibitor 2800Z, which suppressed tumor growth and enhanced the chemosensitivity of sorafenib. In this study, we constructed polylysine polymer nanoparticles modified with cholesterol and GSH-sensitive PEG (mPssPC) to load sorafenib (SOR) and the SIRT7 inhibitor 2800Z to form dual-loaded NPs (S2@PsPCs) to reduce the toxicity and increase efficacy of sorafenib in liver cancer. The average size of S2@PsPC NPs was approximately 370 nm and the zeta potential was approximately 50-53 mV. We found that the release of the drugs exhibited pH sensitivity and was significantly accelerated in an acid release medium simulating the tumor environment. In addition, S2@PsPC NPs inhibited the proliferation and induced apoptosis of liver cancer cells in vitro. An in vivo study further revealed that S2@PsPCs showed high specificity to the liver cancer but low affinity and toxicity to the main organs including the heart, kidneys, lungs, and liver. Our data thus further approved the combination of a SIRT7 inhibitor and sorafenib for the treatment of liver cancer and provided new drug delivery system for targeted therapy.

Lactobacillus rhamnosus TR08 Improves Dyslipidemia in Mice Fed with a High Fat Diet by Regulating the Intestinal Microbiota, Reducing Systemic Inflammatory Response, and Promoting Sphingomholipid Metabolism.

Dysbiosis is a crucial manifestation of dyslipidemia; however, oral supplementation of probiotic modulates the intestinal commensal composition. The protective mechanism of probiotics against hyperlipidemia is still under investigation. To elucidate the hypolipidemic effect of Lactobacillus rhamnosus TR08 through the analysis of gut microbiota and lipid metabolomics, we investigated changes in gut microbiota and lipid metabolomic phenotypes in mice by real time quantitative PCR and untargeted metabolomics analysis. High fat diet-induced dyslipidemia mice were orally administered with TR08 for 8 weeks. The proinflammatory cytokines (interleukin-2 and interferon-γ) levels in spleen and aortic wall injury in the mice fed with a high-fat diet were inhibited after treatment with TR08 at 1 × 108 CFU per day per mouse. TR08 also reshaped the gut microbiota with increases of the relative abundances of Bifidobacterium and Bacteroides, reduced the abundance of the pro-pathogen bacterial Enterococcus, increased the serum level of short chain fatty acids (SCFAs) contents, and promoted sphingomholipid metabolic pathway. The results indicated that TR08 could improve the intestinal microbiota of mice to increase the production of SCFAs, and then play the anti-inflammation induced by hyperlipidemia and reduce the inflammatory injury of blood vessel wall. Therefore, TR08 can potentially be used as a hypolipidemic effect probiotic in further interventions.

Comparison of bedside ultrasonography and bedside chest radiography in neonatal peripherally inserted central catheters: A before and after self-control study.

Objective: This study aimed to compare the applications of bedside ultrasonography (US) and bedside chest radiography (CR) in positioning peripherally inserted central venous catheter (PICC) at Neonatal Intensive Care Units (NICUs). Methods: The study is a prospective before and after self-control clinical trial. A consecutive series of 181 neonate patients were finally enrolled for PICC placement. CR, followed by US, was used to evaluate and readjust the sites of catheter tips. The imaging capability for PICC key structures, fluctuation of the measured data, measurement of tip-to-atrium distance, operation time, infants' body temperature changes, and direct expenses of the two imaging modalities were obtained and compared. Results: (1) Comparison in viewing PICC key structures: the display rate of catheter tip, SVC-and-right-atrium junction, IVC-and-right-atrium junction and tip-to-atrium distance is 99.47%, 100%, 100% and 99.47% for US and 100%, 98.42%, 97.37% and 95.79% for CR, respectively. (2) Fluctuation of the measured data by US and CR: the tip-to-atrium distance measured by US is 0.631 (0.435-0.820) cm, and that measured by CR is 0.593 (0.210-0.825) cm. US showed a narrower range of datum variance. (3) Consistency between US and CR: for consistency analysis, the Kappa coefficient (κ) was 0.843 (P < 0.05), showing their favorable consistency. (4) Comparison of operation time and infants' body temperature drop: for a CR exam, the time period taken was significantly longer than that of US (59.7 ± 26.33 vs. 79.6 ± 28.06, P < 0.001); and CR operations caused a significant babies' body temperature drop compared to US (0.14 ± 0.11 vs. 0.34 ± 0.19, P < 0.001). (5) Comparison of the direct expenses: the total cost for CR positioning was significantly higher than that for US (¥153.99 vs. ¥143, P = 0.026). Conclusion: US exhibited superior traits to CR in the positioning of PICC tip. It could be promising for routine use in NICU.

LncRNA TM1-3P Regulates Proliferation, Apoptosis and Inflammation of Fibroblasts in Osteoarthritis through miR-144-3p/ONECUT2 Axis.

OBJECTIVE: This study explores LncRNA TM1-3P effects on the proliferation, apoptosis, and inflammatory response of fibroblasts in osteoarthritis (OA) and its underlying mechanism. METHODS: Bioinformatics was performed to analyze OA disease-related genes, miRNA profiles, and function. The targeted regulation of LncRNA TM1-3P and miR-144-3p, ONECUT2 and miR-144-3p were analyzed by dual luciferase reporter gene assay, RNA Binding Protein Immunoprecipitation (RIP), and RNA pull down. Histopathological morphology of the knee joint was observed by hematoxylin-eosin (HE) and Annona Red O/Fast Green. The expressions of mRNAs and proteins were detected by RT-qPCR, Western blot, and immunohistochemistry. Unpaired T test was used between groups, and the one-way analysis of variance of repeated measurement data was applied for multi-group comparison, following Tukey's post-test. RESULTS: ONECUT2 and Smurf2 genes were significantly elevated in the osteoarthritis group compared with the normal group (P < 0.001, P < 0.001). Expressions of ONECUT2 and LncRNA TM1-3P were increased, and expression of miR-144-3p was decreased in interleukin (IL)-1ß-induced human fibroblast synovial cells (hFSCs) (mRNA: 1.06 ± 0.24 vs. 3.29 ± 0.73, proteins: 0.22 ± 0.03 vs. 0.46 ± 0.22, 1.23 ± 0.22 vs. 3.76 ± 0.73, 1.06 ± 0.25 vs. 0.37 ± 0.13, P < 0.01, P < 0.001, P < 0.01, P < 0.05). Overexpression of miR-144-3p down-regulated the ONECUT2 expression, reduced cell proliferation, promoted apoptosis in hFSCs induced by IL-1ß (mRNA: 0.89 ± 0.14 vs. 0.15 ± 0.01, P < 0.05; proteins: 0.46 ± 0.01 vs. 0.23 ± 0.01, P < 0.001; CCK8: 1.88 ± 0.07 vs. 1.65 ± 0.07; P < 0.05; EDU: 55.82 ± 1.44 vs 40.57 ± 2.24, P < 0.05; apoptosis: 10.57 ± 0.79 vs 16.36 ± 0.35, P < 0.0001). Overexpression of LncRNA TM1-3P up-regulated the expression of ONECUT2, promoted cell proliferation, and inhibited apoptosis (mRNA: 0.9 ± 0.09 vs 1.94 ± 0.12, P < 0.05; proteins: 0.61 ± 0.05 vs 0.76 ± 0.03, P > 0.05; CCK8: 2.07 ± 0.05 vs 2.47 ± 0.06; P < 0.01; EDU: 52.67 ± 1.17 vs 60.06 ± 3.24, P < 0.05; apoptosis: 10.57 ± 0.79 vs 16.36 ± 0.35, P < 0.001), which were reversed by the overexpression of miR-144-3p treatment (mRNA: 1.82 ± 0.07 vs 0.31 ± 0.07, P < 0.0001; proteins: 0.74 ± 0.02 vs 0.35 ± 0.01, P < 0.01; CCK8: 2.41 ± 0.01 vs 1.67 ± 0.02; P < 0.0001; EDU: 66.85 ± 2.86 vs 44.68 ± 1.97, P < 0.0001; apoptosis: 7.19 ± 0.19 vs 13.36 ± 0.53, P < 0.0001). Silencing LncRNA TM1-3P attenuated the injury of knee joint tissue, down-regulated the expression of ONECUT2, Smurf2, IL-1ß, IL-6, TNF-α, and improved the expression of Rap1 in rats (0.71 ± 0.04 vs 0.48 ± 0.02, 0.68 ± 0.06 vs 0.36 ± 0.02, 0.74 ± 0.03 vs 0.49 ± 0.04, 0.78 ± 0.01 vs 0.54 ± 0.03, 0.68 ± 0.02 vs 0.4 ± 0.04, 0.24 ± 0.01 vs 0.4 ± 0.03, P < 0.05, P < 0.05, P < 0.05, P < 0.01, P < 0.01, P < 0.05). CONCLUSION: LncRNA TM1-3P improved inflammation and damage of knee joints in OA rats through miR-144-3p/ONECUT2 axis, providing a new theoretical basis for gene therapy of OA.

A Survey of the Practice Status Quo of Ultrasound-Guided ECC Tip Location for Neonatal Patients in 31 Provinces of China.

Objective: To investigate the status quo of implementing ultrasound (US)-guided epicutaneo-caval catheters (ECC) tip location for neonatal patients in 31 provinces. Methods: The convenience sampling method was used to investigate the nursing managers and ECC (or intravenous therapy) nurses of 91 hospitals in 31 provinces from October 29 to November 10, 2021. Results: The survey involved a total of 182 medical staff, including 91 managers and 91 nurses, and 91 institutions, including 22 children's hospitals, 49 general hospitals and 21 maternal and child health care hospitals. Sixteen hospitals (17.6%) carried out US-guided ECC for neonatal patients; 176 subjects (96.7%) of the 91 hospitals had known about or heard of the technology of US-guided ECC. The low awareness of operators of the tip location of ECC catheters in children under ultrasound guidance (OR = 2.690, 95% CI = 1.163-6.221), limited conditions in existing wards (OR = 2.953, 95% CI = 1.285-6.790), and insufficient funds (OR = 2.836, 95% CI = 1.149-7.004) were the independent risk factors responsible for the failure to carry out ultrasonic-guided location of ECC tips in newborns. Conclusion: The popularity of neonatal US-guided ECC location was seriously hindered by factors such as a low awareness rate of the project, the low qualification certification rate of the nursing staff, a flawed performance allocation system, and the lack of a professional team, among other factors.

A Study of Hydrophobically Modified Pullulan Nanoparticles with Different Hydrophobic Densities on the Effect of Anti-Colon Cancer Cell Efficiency.

To discuss the effect of hydrophobic groups of a polymer on the structural properties and function of polymer nanoparticles (NPs), we grafted chenodeoxycholic acid (CDCA) with pullulan (PU) to form hydrophobically modified PU (PUC). Three PUC polymers, namely, PUC-1, PUC-2, and PUC-3, with different degrees of substitution were designed by changing the feed ratio of CDCA and PU. 1H-NMR spectra showed that the PUC polymer was successfully synthesized, and the degrees of hydrophobic substitution for PUC-1, PUC-2, and PUC-3 were calculated to be 10.66%, 13.92%, and 16.94%, respectively. The PUC NPs were prepared by the dialysis method and were shown to be uniformly spherical by transmission electron microscopy (TEM). The average sizes were about (220±10) nm, (203±7) nm, and (163±6) nm under dynamic light scattering (DLS) for PUC-1 NPs, PUC-2 NPs, and PUC-3 NPs, respectively. Drug release experiments showed that the three PUC/DOX NPs exhibited good sustained release. At 48 h, the IC50 of doxorubicin in inhibiting colon cancer HCT116 cells was 0.0904 µg/mL. A cell study showed that PUC-3/DOX NPs had the highest uptake efficiency by HCT116 cells with the most cytotoxicity and inhibited the migration of HCT116 cells with the highest efficiency. The structural properties and function of polymer NPs were closely related to the hydrophobic groups in the polymer, and NPs with higher hydrophobicity showed a smaller size, higher drug capacity, and greater cell efficiency.

Preparation of ICA-loaded mPEG-ICA nanoparticles and their application in the treatment of LPS-induced H9c2 cell damage.

Hydrophilic polyethylene glycol monomethyl ether (mPEG) was grafted onto Icariin (ICA) by succinic anhydride to form a polyethylene glycol-Icariin (mPEG-ICA) polymer. The structure of the polymer was characterized by Fourier transform infrared spectroscopy (FT-IR) and nuclear magnetic resonance spectroscopy (NMR). mPEG-ICA nanoparticles loaded with ICA were prepared by physical embedding of ICA by dialysis. The particle size was determined to be (220 ± 13.7) nm, and the ζ potential was (2.30 ± 1.33) mV by dynamic light scattering (DLS). Under a transmission electron microscope (TEM), the nanoparticles were spherical, and the morphology was regular. In the medium with pH 7.4, the drug release rate of mPEG-ICA nanoparticles reached (52.80 ± 1.70)% within 72 h. At pH 6.8, the cumulative drug release of nanoparticles reached (75.66 ± 0.17)% within 48 h. Treatment of the nanoparticles with LPS-treated H9c2 cells maintained cell viability, reduced LDH release and exerted antiapoptotic effects. Moreover, ICA-loaded mPEG-ICA nanoparticles significantly decreased the mRNA expression of the myocardial inflammatory cytokines TNF-α, IL-1ß and IL-6M. In conclusion, ICA-loaded mPEG-ICA nanoparticles protected against LPS-induced H9c2 cell injury.

Two amide glycosides from Portulaca oleracea L. and its bioactivities.

Two novel amide glycosides, named oleraciamide E (1) and oleraciamide F (2), were isolated from the Portulaca oleracea L. Their structures were determined by means of 1D and 2D NMR spectroscopic and UHPLC-ESI-TOF-MS methods. Oleraciamide E (1) exhibited anticholinesterase activity with IC50 values of 52.43 ± 0.33 µM, and presented scavenging activity in 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical quenching assay, with the IC50 values of 24.64 ± 0.33 µM.

Brain-Targeted Polysorbate 80-Emulsified Donepezil Drug-Loaded Nanoparticles for Neuroprotection.

Most Alzheimer's disease drugs do not work efficiently because of the blood-brain barrier. Therefore, we designed a new nanopreparation (PS-DZP-CHP): cholesterol-modified pullulan (CHP) nanoparticle with polysorbate 80(PS) surface coverage, as donepezil (DZP) carrier to realize brain tissue delivery. By size analysis and isothermal titration calorimetry, we chose the optimal dosing ratio of the drug with nanomaterials (1:5) and designed a series of experiments to verify the efficacy of the nanoparticles. The results of in vitro release experiments showed that the nanoparticles can achieve continuous drug release within 72 h. The results of fluorescence observation in mice showed a good brain targeting of PS-DZP-CHP nanoparticles. Furthermore, the nanoparticle can enhance the drug in the brain tissue concentration in mice. DZP-CHP nanoparticles were used to pretreat nerve cells with Aß protein damage. The concentration of lactate dehydrogenase was determined by MTT, rhodamine 123 and AO-EB staining, which proved that DZP-CHP nanoparticles had a protective effect on the neurotoxicity induced by Aß25-35 and were superior to free donepezil. Microthermal perpetual motion meter test showed that PS-DZP-CHP nanoparticles have an affinity with apolipoprotein E, which may be vital for this nanoparticle targeting to brain tissue.

Artemisinin Derivatives Inhibit Non-small Cell Lung Cancer Cells Through Induction of ROS-dependent Apoptosis/Ferroptosis.

Non-small cell lung cancer (NSCLC) is one of the major cancer-related causes of morbidity and mortality worldwide. Despite the progress in lung cancer treatment, there is still an urgent need to discover novel therapeutic agents for NSCLC. Natural products represent a rich source of bioactive compounds. Through a natural compound library screening assay, we found that a group of anti-insect drugs had significant inhibitory effect on the proliferation of NSCLC cells. Among the anti-insect drugs, two derivatives of artemisinin, i.e., artesunate (ART) and dihydroartemisinin (DHA), a group of well-known anti-malarial drugs, have been shown to possess selective anti-cancer properties. Mechanistically, we found that ART and DHA induced apoptosis of A549 cells as evidenced by decreased protein level of VDAC and increased caspase 3 cleavage. Furthermore, cystine/glutamate transporter (xCT), a core negative regulator of ferroptosis, was downregulated by ART and DHA. The mRNA level of transferrin receptor (TFRC), a positive regulator of ferroptosis, was upregulated by ART and DHA. ART/DHA-induced apoptosis and ferroptosis in NSCLC cells were partly reversed by N-Acetyl-L-cysteine (NAC), a ROS scavenger, and ferrostatin-1, a ferroptosis inhibitor, respectively. These results suggest that artemisinin derivatives have anti-NSCLC activity through induction of ROS-dependent apoptosis/ferroptosis. Our findings provide the experimental basis for the potential application of artemisinin derivatives as a class of novel therapeutic drugs for NSCLC.

A home-based, post-discharge early intervention program promotes motor development and physical growth in the early preterm infants: a prospective, randomized controlled trial.

BACKGROUND: The implementation of early intervention (EI) in medical settings is time-consuming and resource-intensive, which limits its extensive use. In 2018, the Chinese Eugenics Association developed a home-based, post-discharge EI program. This study aims at evaluating the impact of this EI program on neurodevelopment and physical growth of early preterm infants. METHODS: This study was a prospective, partially blinded, randomized controlled trial (RCT), followed by an open phase. A total of 73 infants born at 28+ 0 ~ 31+ 6 weeks' gestation who were admitted to the Children's Hospital of Chongqing Medical University between December 1, 2019, and June 31, 2020, were enrolled. Another 33 infants were retrospectively recruited as the reference group. Thirty-seven infants randomized in the first early intervention, then standard care (EI-SC) group performed a 30-day EI during RCT period, while 36 infants allocated to SC-EI group were given EI in the following open phase. The test of infant motor performance (TIMP), development quotient (DQ), and anthropometric measures (length, weight, head circumference) were measured at the baseline (T0), termination of the RCT (T1), and termination of the open phase (T2). Repeated measures analysis was performed for comparison among groups. RESULTS: From T0 to T1, both groups had significant improvements in all outcome measures (all p < 0.001). A 30-day EI program was more effective in improving TIMP than standard care (from 53.12 ± 8.79 to 83.50 ± 11.85 in EI-SC group vs from 50.52 ± 8.64 to 75.97 ± 13.44 in SC-EI group, F = 4.232, p = 0.044). EI-SC group also had greater improvements in length, weight, and head circumference than SC-EI group (all p < 0.05). From T0 to T2, there was no significant difference regarding the improvements in all outcomes between the groups (all p > 0.05). At the endpoint of T2, the EI-SC and SC-EI group had similar TIMP and anthropometric measures, but much higher than the reference group (all p < 0.05). CONCLUSIONS: These findings demonstrated that a home-based, post-discharge EI program in this study was a practical approach to promote motor development and physical growth in early preterm infants. TRIAL REGISTRATION: CHICTR, CTR1900028330, registered December 19, 2019, https:// http://www.chictr.org.cn/showproj.aspx?proj=45706.

Two new amide alkaloids from Portulaca oleracea L. and their anticholinesterase activities.

Two new amide alkaloids, identified as 5,6-dihydroxy-3,4-dihydroisoquinolin-1(2H)-one, named oleraciamide G (1) and (E)-1-(5-hydroxy-6-((3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)-1H-indol-1-yl)-3-(4-hydroxyphenyl)prop-2-en-1-one, named oleraindole D (2) were obtained from Portulaca oleracea L. Their structures were determined by spectroscopic methods, including the 1 D and 2 D NMR, high-resolution electrospray ionization time-of-flight mass spectrometry. In addition, compounds 1 and 2 presented anticholinesterase activities with IC50 values of 65.71 ± 0.15 µM and 58.78 ± 0.36 µM, respectively.

Ultrasound-assisted bottom-up synthesis of Ni-graphene hybrid composites and their excellent rhodamine B removal properties.

In this paper, a facile one-pot bottom-up approach has been developed for the rapid preparation (≤5 min) of graphene nanostructures and Ni-graphene hybrid composites. Under the aid of ultrasonic irradiation, the graphene nanostructures were prepared via reducing hexachloro-benzene(C6Cl6) with sodium (Na) in non-polar organic solvent n-tetradecane (C14H30). On the basis of this route, the Ni-graphene hybrid composites were easily synthesized by adding Ni nanoparticles (NPs) into reaction system. The whole reaction was carried out at low temperature (100-120 °C) and in air atmosphere. Despite the absence of nitrogen protection, the result from surface analysis still shows a relatively high C/O ratio (10:1). The effect of the Ni NPs content and size on the specific surface area (SSA) of the products is also investigated. The synthesized samples exhibit large SSA, which is significantly affected by the Ni NPs content rather than their size. The adsorption performances of the samples are evaluated for the removal of organic dyes such as rhodamine B (RhB) from aqueous solutions. The testing results show great adsorption capacity (qmax = 963.04 mg g-1), rapid adsorption rate (~99.88%, 2 min), high adsorption efficiency (>99.7%) and good chemical stability in a wide pH range (3-13), high salt tolerance (>80 mg mL-1), and good recyclability (>99.5%, 20 cycles).

Synergistically Enhanced Inhibitory Effects of Pullulan Nanoparticle-Mediated Co-Delivery of Lovastatin and Doxorubicin to Triple-Negative Breast Cancer Cells.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer that is prone to drug resistance and difficult to treat. In this study, we grafted water-soluble pullulan with lovastatin (LV) to develop a novel amphiphilic conjugate, pullulan-encapsulated LV (PLV). The PLV conjugate was synthesized with three different ratios of pullulan to LV and characterized by Fourier transform infrared (FTIR). The degree of substitution (DS) of LV in terms of molar ratio was 7.87%, 3.58%, and 3.06% for PLV (1/2), PLV (1/3), and PLV (1/4), respectively, by proton NMR analysis. We selected the PLV (1/2) conjugate to prepare doxorubicin (DXR)-loaded PLV nanoparticles (PLV/DXR NPs) because of its superior properties. The average size and zeta potential for PLV (1/2) NPs were 177.6 nm and - 11.66 mV, respectively, determined by dynamic light scattering, and those for PLV/DXR NPs were 225.6 nm and - 10.51 mV, respectively. In vitro drug release profiling showed that PLV/DXR NPs sustainably released DXR within 72 h, which was more robust at pH 5.4 (97.90%) than pH 7.4 (76.15%). In the cytotoxicity study, PLV/DXR NPs showed greater inhibition of proliferation of TNBC MDA-MB-231 than non-TNBC MDA-MB-453 cells (IC50 0.60 vs 11.05 µM). FITC-loaded PLV/DXR NPs were prepared to investigate cellular uptake: both cell lines showed a time-dependent uptake of NPs, but the number of NPs entering MDA-MB-231 cells was greater than that entering the MDA-MB-453 cells. Pullulan-based NP co-delivery of LV and DXR could efficiently inhibit TNBC cells, which may help in designing a powerful drug delivery system for treating TNBC.

Prognostic value of biomarkers EpCAM and αB-crystallin associated with lymphatic metastasis in breast cancer by iTRAQ analysis.

BACKGROUND: Metastasis is responsible for the majority of deaths in a variety of cancer types, including breast cancer. Although several factors or biomarkers have been identified to predict the outcome of patients with breast cancer, few studies have been conducted to identify metastasis-associated biomarkers. METHODS: Quantitative iTRAQ proteomics analysis was used to detect differentially expressed proteins between lymph node metastases and their paired primary tumor tissues from 23 patients with metastatic breast cancer. Immunohistochemistry was performed to validate the expression of two upregulated (EpCAM, FADD) and two downregulated (NDRG1, αB-crystallin) proteins in 190 paraffin-embedded tissue samples. These four proteins were further analyzed for their correlation with clinicopathological features in 190 breast cancer patients. RESULTS: We identified 637 differentially regulated proteins (397 upregulated and 240 downregulated) in lymph node metastases compared with their paired primary tumor tissues. Data are available via ProteomeXchange with identifier PXD013931. Furthermore, bioinformatics analysis using GEO profiling confirmed the difference in the expression of EpCAM between metastases and primary tumors tissues. Two upregulated (EpCAM, FADD) and two downregulated (NDRG1, αB-crystallin) proteins were associated with the progression of breast cancer. Obviously, EpCAM plays a role in the metastasis of breast cancer cells to the lymph node. We further identified αB-crystallin as an independent biomarker to predict lymph node metastasis and the outcome of breast cancer patients. CONCLUSION: We have identified that EpCAM plays a role in the metastasis of breast cancer cells to the lymph node. αB-crystallin, a stress-related protein that has recently been shown to be important for cell invasion and survival, was identified as a potential prognostic biomarker to predict the outcome of breast cancer patients.