OBJECTIVE To investigate the ameliorative effect and potential mechanism of imperatorin （IMP） on doxorubicin （DOX） resistance in breast cancer. METHODS The effects of maximum non-toxic concentration （100 μg/mL） of IMP combined with different concentrations of DOX （12.5， 25， 50， 75， 100 μg/mL） on the proliferation of MCF-7/DOX cells were determined by MTT method. MCF-7/DOX cells were divided into blank control group （1‰ dimethyl sulfoxide）， DOX group （50 μg/mL）， IMP+DOX group （100 μg/mL IMP+50 μg/mL DOX） and IMP group （100 μg/mL）. mRNA and protein expressions of multidrug resistance protein 1 （MDR1） and multidrug resistance-associated protein 1 in each group were measured. The relevant pathways and targets involved in the improvement of DOX resistance in breast cancer cells by IMP were screened and validated by using transcriptome sequencing technology， along with gene ontology （GO） enrichment analyses and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses. RESULTS Compared with DOX alone， the combination of IMP and DOX reduced the half inhibitory concentration of DOX on MCF-7/DOX cells from 81.965 μg/mL to 43.170 μg/mL， the reverse fold was 1.90， and the mRNA expression of MDR1 was significantly down-regulated （P＜0.05）. The results of GO enrichment analyses and KEGG pathway enrichment analyses indicated that the reversal of DOX resistance in breast cancer by IMP was mainly associated with the regulation of biological processes such as detoxification， multiple biological processes， and cell killing. The main pathway involved was the p53 signaling pathway， and the key targets mainly included constitutively photomorphogenic protein 1 （COP1）， cyclin E1 （CCNE1）， growth arrest and DNA damage-inducible protein 45A E-mail：tangxilan1983@163.com （GADD45A） and GADD45B. The results of the verification experiments showed that compared with DOX group， there was a trend of up-regulation of COP1 mRNA， and significant down- regulation of CCNE1， GADD45A， and GADD45B mRNA expression in IMP+DOX group （P＜0.05）. CONCLUSIONS The effect of IMP in ameliorating DOX resistance in breast cancer is related to its regulation of COP1， CCNE1， GADD45A and GADD45B targets in the p53 signaling pathway.

Background::Atopic dermatitis (AD) affects approximately 10% of adults worldwide. CM310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 signaling. This trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe AD.Methods::This multicenter, randomized, double-blind, placebo-controlled, phase 2b trial was conducted in 21 medical institutions in China from February to November 2021. Totally 120 eligible patients were enrolled and randomized (1:1:1) to receive subcutaneous injections of 300 mg CM310, 150 mg CM310, or placebo every 2 weeks for 16 weeks, followed by an 8-week follow-up period. The primary endpoint was the proportion of patients achieving ≥75% improvement in the Eczema Area and Severity Index (EASI-75) score from baseline at week 16. Safety and pharmacodynamics were also studied.Results::At week 16, the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups (70% [28/40] for high-dose and 65% [26/40] for low-dose) than that in the placebo group (20%[8/40]). The differences in EASI-75 response rate were 50% (high vs. placebo, 95% CI 31%–69%) and 45% (low vs. placebo, 95% CI 26%–64%), with both P values <0.0001. CM310 at both doses also significantly improved the EASI score, Investigator’s Global Assessment score, daily peak pruritus Numerical Rating Scale, AD-affected body surface area, and Dermatology Life Quality Index compared with placebo. CM310 treatment reduced levels of thymus and activation-regulated chemokine, total immunoglobulin E, lactate dehydrogenase, and blood eosinophils. The incidence of treatment-emergent adverse events (TEAEs) was similar among all three groups, with the most common TEAEs reported being upper respiratory tract infection, atopic dermatitis, hyperlipidemia, and hyperuricemia. No severe adverse events were deemed to be attributed to CM310. Conclusion::CM310 at 150 mg and 300 mg every 2 weeks demonstrated significant efficacy and was well-tolerated in adults with moderate-to-severe AD.Trial Registration::ClinicalTrials.gov, NCT04805411.

Objective To investigate the inhibitory effect of aumolertinib combined with anlotinib on proliferation of non-small cell lung cancer(NSCLC)cells.Methods CCK-8 assay,colony formation assay,and flow cytometry were used to assess the effect of different concentrations of aumolertinib or anlotinib on proliferation,survival,and apoptosis of PC-9 and HCC827 cells,and their synergistic effect was evaluated using the SynergyFinder model.In PC-9 and HCC827 cells treated with aumolertinib combined with anlotinib,the changes in cell invasion and migration abilities were assessed with Transwell assay,and the expressions of apoptosis-and invasion/migration-related proteins(Bax,Bcl-2,E-cadherin,vimentin,MMP2,and MMP9)and the key PI3K-Akt pathway proteins were detected using Western blotting.Results In PC-9 cells,the IC50 of aumolertinib and anlotinib was 1.701 μmol/L and 4.979 μmol/L,respectively,with a synergy score(ZIP)of 19.112;in HCC827 cells,their IC50 was 2.961 μmol/L and 7.934 μmol/L,respectively,with a ZIP of 12.325.Compared with aumolertinib and anlotinib used alone,their combined treatment more strongly inhibited the proliferation and survival,enhanced apoptosis and suppressed invasion and migration abilities of PC-9 and HCC827 cells.Western blotting showed that in both PC-9 and HCC827 cells,the combined treatment significantly upregulated the expressions of E-cadherin and Bax proteins,downregulated the expressions of Bcl-2,vimentin,MMP2,and MMP9 proteins,and reduced phosphorylation levels of PI3K and Akt.Conclusion Aumolertinib combined with anlotinib can effectively inhibit NSCLC cell proliferation by downregulating the PI3K-Akt pathway,suggesting a potentially new option for NSCLC treatment.

Objective To investigate the inhibitory effect of aumolertinib combined with anlotinib on proliferation of non-small cell lung cancer(NSCLC)cells.Methods CCK-8 assay,colony formation assay,and flow cytometry were used to assess the effect of different concentrations of aumolertinib or anlotinib on proliferation,survival,and apoptosis of PC-9 and HCC827 cells,and their synergistic effect was evaluated using the SynergyFinder model.In PC-9 and HCC827 cells treated with aumolertinib combined with anlotinib,the changes in cell invasion and migration abilities were assessed with Transwell assay,and the expressions of apoptosis-and invasion/migration-related proteins(Bax,Bcl-2,E-cadherin,vimentin,MMP2,and MMP9)and the key PI3K-Akt pathway proteins were detected using Western blotting.Results In PC-9 cells,the IC50 of aumolertinib and anlotinib was 1.701 μmol/L and 4.979 μmol/L,respectively,with a synergy score(ZIP)of 19.112;in HCC827 cells,their IC50 was 2.961 μmol/L and 7.934 μmol/L,respectively,with a ZIP of 12.325.Compared with aumolertinib and anlotinib used alone,their combined treatment more strongly inhibited the proliferation and survival,enhanced apoptosis and suppressed invasion and migration abilities of PC-9 and HCC827 cells.Western blotting showed that in both PC-9 and HCC827 cells,the combined treatment significantly upregulated the expressions of E-cadherin and Bax proteins,downregulated the expressions of Bcl-2,vimentin,MMP2,and MMP9 proteins,and reduced phosphorylation levels of PI3K and Akt.Conclusion Aumolertinib combined with anlotinib can effectively inhibit NSCLC cell proliferation by downregulating the PI3K-Akt pathway,suggesting a potentially new option for NSCLC treatment.

Objective To establish a quality control method for detecting impurities in chloral hydrate raw materials, improve the quality standards and control limits of raw materials. Methods The determination methods of chloroform and halogenated carboxylic acid in chloral hydrate were established to monitor the change of impurities in chloral hydrate through stability. Results The research and establishment of chloroform and halogenated carboxylic acid methods met the requirements of relevant regulations for analytical methodology verification, which could accurately detect four impurities in raw materials and preparations by one method. Conclusion The study provides technical support for the improvement and optimization of the quality standards of chloral hydrate and preparations. It is very necessary to implement the impurity monitoring in preparation research and production process by the chloral hydrate impurity detection and the stability comparison of this product at high temperature and light, which could largely promote the safety of medication.

This study aimed to observe the protective effect of momordicine I, a triterpenoid compound extracted from momordica charantia L., on isoproterenol (ISO)-induced hypertrophy in rat H9c2 cardiomyocytes and investigate its potential mechanism. Treatment with 10 μM ISO induced cardiomyocyte hypertrophy as evidenced by increased cell surface area and protein content as well as pronounced upregulation of fetal genes including atrial natriuretic peptide, β-myosin heavy chain, and α-skeletal actin; however, those responses were markedly attenuated by treatment with 12.5 μg/ml momordicine I. Transcriptome experiment results showed that there were 381 and 447 differentially expressed genes expressed in comparisons of model/control and momordicine I intervention/model, respectively. GO enrichment analysis suggested that the anti-cardiomyocyte hypertrophic effect of momordicine I may be mainly associated with the regulation of metabolic processes. Based on our transcriptome experiment results as well as literature reports, we selected glycerophospholipid metabolizing enzymes group VI phospholipase A 2 (PLA2G6) and diacylglycerol kinase ζ (DGK-ζ) as targets to further explore the potential mechanism through which momordicine I inhibited ISO-induced cardiomyocyte hypertrophy.Our results demonstrated that momordicine I inhibited ISO-induced upregulations of mRNA levels and protein expressions of PLA2G6 and DGK-ζ. Collectively, momordicine I alleviated ISO-induced cardiomyocyte hypertrophy, which may be related to its inhibition of the expression of glycerophospholipid metabolizing enzymes PLA2G6 and DGK-ζ.

Malnutrition in liver cirrhosis is associated with ascites, hepatic encephalopathy, infection, and other complications even death. To date, the hazard and disease burden of malnutrition in cirrhosis patients have been severely underestimated. This review summarized the most recent advancement in the field and discussed the techniques and methodologies in detection and evaluation of malnutrition in cirrhosis patients, nutritional support therapy, and future research directions and clinical care of the patients.

New threats posed by the emerging circulating variants of SARS-CoV-2 highlight the need to find conserved neutralizing epitopes for therapeutic antibodies and efficient vaccine design. Here, we identified a receptor-binding domain (RBD)-binding antibody, XG014, which potently neutralizes β-coronavirus lineage B (β-CoV-B), including SARS-CoV-2, its circulating variants, SARS-CoV and bat SARSr-CoV WIV1. Interestingly, antibody family members competing with XG014 binding show reduced levels of cross-reactivity and induce antibody-dependent SARS-CoV-2 spike (S) protein-mediated cell-cell fusion, suggesting a unique mode of recognition by XG014. Structural analyses reveal that XG014 recognizes a conserved epitope outside the ACE2 binding site and completely locks RBD in the non-functional "down" conformation, while its family member XG005 directly competes with ACE2 binding and position the RBD "up". Single administration of XG014 is effective in protection against and therapy of SARS-CoV-2 infection in vivo. Our findings suggest the potential to develop XG014 as pan-β-CoV-B therapeutics and the importance of the XG014 conserved antigenic epitope for designing broadly protective vaccines against β-CoV-B and newly emerging SARS-CoV-2 variants of concern.
Angiotensin-Converting Enzyme 2 ; Antibodies, Neutralizing ; Antibodies, Viral ; COVID-19 ; Epitopes ; Humans ; SARS-CoV-2/genetics* ; Spike Glycoprotein, Coronavirus/genetics*

Objective:To explore the status and influencing factors of incontinence-associated dermatitis among elderly inpatients in 52 hospitals nationwide, and to analyze the nursing of elderly inpatients with incontinence, so as to provide a reference for clinical intervention.Methods:On March 31, 2021, convenience sampling was used to select 14 675 elderly inpatients from 52 hospitals across the country as the research object. The self-designed Incontinence-associated Dermatitis Questionnaire for Elderly Inpatients was used to collect general demographic data, health status, incontinence, and skin nursing. Binomial Logistic regression was used to investigate the influencing factors of incontinence-associated dermatitis in elderly inpatients.Results:Among 14 675 elderly inpatients, the prevalence rates of xerosis cutis, incontinence and incontinence-associated dermatitis were 38.78% (5 691/14 675) , 11.06% (1 623/14 675) and 1.91% (280/14 675) , respectively. The prevalence of mild, moderate and severe incontinence-associated dermatitis were 1.27% (186/14 675) , 0.55% (81/14 675) , and 0.09% (13/14 675) , respectively. Among the nursing of 1 623 elderly inpatients with incontinence, the items with low implementation rate were the use neutral lotion to clean skin (14.17%, 230/1 623) , use of skin protectant after moisturizing (17.68%, 287/1 623) , moisturizing after cleansing the skin (28.90%, 469/1 623) . The results of binomial Logistic regression analysis showed that xeroderma, fecal incontinence, urinary and fecal incontinence, ≥2 kinds of combined medication, and hospital stay >30 days were risk factors for incontinence-associated dermatitis in elderly inpatients.Conclusions:The risk factors of incontinence-associated dermatitis in elderly inpatients mainly include xerosis cutis, type of incontinence, ≥2 kinds of combined medication, and hospital stay >30 days.

Objective: To investigate the effect of metformin on the expressions of activating transcription factor-6(ATF6)and Caspase12 in hippocampus of type 2 diabetic rats. Methods: GK male rats with random blood glucose≥11.1 mmol/L were orally administrated with normal saline(DM group)and metformin(MET group, 85 mg·kg^-1·d^-1)for 8 weeks(n=10 each group). Wistar male rats were selected as normal contorl group(NC, n=10). After 8 weeks of continuous medication, body weight and fasting plasma glucose(FPG)were measured, and the morphology of HE stained cells and the expressions of ATF6 and Caspase12 by immunohistochemistry staining in the CA1 area of hippocampus were detected. Results: Compared with NC group, the body weight of DM and MET groups decreased(P<0.05), but there was no significant difference between DM and MET groups(P>0.05). In comparison with NC group, FPG levels in DM and MET groups were markedly increased(P<0.05)while FPG level in MET group was significantly lower than that in DM group(P<0.05). The normal nerve cells in the CA1 region of hippocampal were lower in DM and MET groups than those in NC group, especially in DM group. The protein expressions of ATF6 and Caspase12 in DM and MET groups were higher than that in NC group(all P<0.05), and the expressions of the two protein in MET group were significantly decreased as compared with DM group(P<0.05). Conclusion Metformin reduces the expressions of ATF6 and Caspase12 in hippocampus of type 2 diabetic rats, which may be related to its protective effect on brain. (Chin J Endocrinol Metab, 2018, 34: 594-597)