Objective To explore the appropriate nursing care of acute hyperlipidemic pancreatitis and increase nursing level.Methods The clinical data of 3 cases of hyperlipidemic pancreatitis misdiagnosed as acute appendicitis were analyzed retrospectively and the nursing experience was summarized.Results The blood sample of all 3 cases represented dramatically high level of serum triglyceride (14.1～61.0 mmol/L).Obvious inducing factors were observed in one case.Besides upper abdominal symptom and physical sign continued in spite of the right lower abdominal discomfort,ascites was discovered by early B-ultrasound.There was no significant increase of serum or urine amylase.After correct diagnosis,all of the 3 cases recovered well by close observation,mental nursing,anti-hyperlipidemic nursing,drainage nursing and health education.Conclusions The knowledge of hyperlipidemic pancreatitis should be well understood during nursing practice.Comprehensive nursing evaluation and close observation can help doctors to analyze and estimate the disease.Integrated nursing techniques can accelerate the recovery of the patients.Health education,anti-hyperlipidemic therapy,and removal of the inducing factors are the keys of prevention.

Objective To investigate the diagnostic and prognostic value of serum exosomal exocirc_0023461 in coronary artery disease(CAD)related acute myocardial infarction(AMI).Methods From December 2019 to January 2022,383 patients with CAD related AMI(AMI group),200 pa-tients with chronic stable CAD but no AMI(control group),and 200 healthy individuals identified with physical examination(healthy group)were recruited in our hospital.The serum exocirc_0023461 level was determined by real-time quantitative fluorescence polymerase chain reaction.The correlation of serum exosomal circ_0023461 level with clinicopathological features and oxida-tive stress indicators was analyzed.Results The serum level of exocirc_0023461 was significantly higher in the AMI group than the control group and healthy group[3.54(1.39,9.82)vs 0.86(0.62,1.23)and 0.65(0.41,0.79),P＜0.01].ROC curve analysis showed that when the serum level of exocirc_0023461 ≥1.31,its AUC value for the diagnosis of AMI was 0.857(95％CI:0.827-0.887),with a sensitivity and specificity of 78.90％and 83.50％,respectively.Kaplan-Meier survival curve displayed that the survival time was significantly shorter in the high level AMI patients without MACE than those with low level(X2=19.390,Plog rank＜0.01).Multivariate Cox regression analysis revealed that age,peripheral artery disease and serum exocirc_0023461 were independent predictors of MACE occurrence in AMI patients during follow-up(P＜0.05,P＜0.01).Pearson correlation analysis indicated that serum exocirc_0023461 level was negatively correlated with serum GPX and SOD levels(r=-0.395,r=-0.193,P＜0.01),and positively correlated with serum MDA level(r=0.194,P＜0.01).Conclusion Serum exocirc_0023461 may be a potential biomarker for the diagnosis and prognosis of CAD-related AMI,and its mechanism seems to be associated with its regulating oxidative stress and thus affecting myocardial injury.

Objective To investigate the social support needs of medical staff in Guangzhou during the post-COVID-19 period,providing a basis for relevant departments to offer targeted social support for medical staff in Guangzhou and improve their of occupational quality of life.Methods A cross-sectional survey was conducted,employing a combination of quota and conven-ience sampling to select subjects,eligible medical staff were invited to complete an online questionnaire.Results The social sup-port with a total score of 20 for medical staff in Guangzhou scored 9(7,11).Among the dimensions of social support,media sup-port scored the lowest.Social support as a whole scored with statistically significant differences across groups of different age,ed-ucational background,and job position(all P＜0.05).The median score was the lowest for those under 25 years,for those with a college degree or below,and highest among administrative staff,with other positions showing equal median score.The five di-mensions of social support ranked on the top concerning the total number of the respondents included patients'understanding and trust for medical staff(93.03％),increasing in salaries and benefits(86.06％),accurate policy promotion and public opinion guidance by media(83.41％),attention to the living conditions of medical staff by media(80.29％),and enhanced regulation of false reporting and inappropriate commentary by media(76.92％).Medical staff under the age of 25 had a high need for pa-tients'following doctor's advice,and medical staff with a collegiate degree or below had a high need for family members or friends to care about their physical and mental health.The five strongest needs for social support ranked on the top concerning the total number of respondents included understanding and trust from patients(75.72％),increased salaries and benefits(53.85％),assistance with household matters by family or friends(42.55％),correct policy promotion and public opinion guidance by media(34.62％),and attention to the living conditions of medical staff from media(33.41％).Conclusion Social support for medical staff in Guangzhou are at a relatively low level,indicating a need for social support from all levels of society.

OBJECTIVETo develop animal models and methodologies for assay of pseudoallergy induced by injectable drugs.

METHODRats cutaneous anaphylactoid reaction model was developed by intravenous injection of 0. 6% Evans blue(EB) followed by intracutaneous injection of test substance solutions 50 microL. Diameters of subcutaneous blue spots and EB exudation were assayed.

RESULTRat anaphylactoid reaction was characterized as vascular hyperpermeability which was measured by diameters of blue spots inside the skin and the EB exudation of the blue spots. Compound 48/80 caused severe bluing and EB exudation in the skin by inducing obvious vascular hyperpermeability which indicated that it can induce rat skin pseudoallergy. Normal saline or 5% glucose injection showed no obvious reactions. The rat pseudoallergy model was validated by intracutaneous injections of western drug injections and Chinese medicine.

CONCLUSIONRats could be developed into skin pseudoallergy model for preclinical safety evaluation of injectable drugs. The pseudoallergy reaction in this model is of high clinic consistency, sensitivity, reproducibility, and maneuverability. The model is suitable for the evaluation for pseudoallergy induced by injectable products prepared from Chinese materia medica This model can also be used for safety assay and quality control in manufacturing process, spot checking of marketed products, screening of allergen as well as studying of pseudoallergy mechanism.

Animals ; Disease Models, Animal ; Drug Evaluation, Preclinical ; methods ; Drug Hypersensitivity ; Female ; Injections, Subcutaneous ; methods ; Male ; Rats ; Rats, Sprague-Dawley ; Skin ; drug effects

OBJECTIVETo develop animal models and methodologies for assay of pseudoallergy induced by injectable drugs.

METHODMouse anaphylactoid reaction model was developed by intravenous injection of test substance solutions containing Evans blue (EB). Scores of ear blue staining and quantitation of ear EB exudation were the parameters for the pseudoallergy reaction.

RESULTMouse anaphylactoid reaction was characterized as vascular hyperpermeability which was detectable in ears by quantitation of blue staining score and EB exudation. Compound 48/80 and histamine caused severe ear bluing and EB exudation by inducing obvious vascular hyperpermeability which indicated that they can induce mouse pseudoallergy. Intravenous injection of either normal saline or 5% glucose injection showed no ear bluing. The mouse pseudoallergy model was validated by intravenous injections of western drugs and Chinese medicine.

CONCLUSIONMice could be developed into pseudoallergy model for preclinical safety evaluation of injectable drugs. The pseudoallergy reaction in this model is of high clinic consistency, sensitivity, reproducibility, and maneuverability. The model is suitable for the evaluation for pseudoallergy induced by injectable products prepared from Chinese materia medica This model can also be used for safety assay and quality control in manufacturing process, spot checking of marketed products, screening of allergen as well as studying of pseudoallergy mechanism.

Animals ; Disease Models, Animal ; Drug Evaluation, Preclinical ; methods ; Drug Hypersensitivity ; Injections, Intravenous ; Mice ; Mice, Inbred ICR

Lung cancer ranks the top of malignancies that cause cancer-related deaths worldwide.The leaves of Morus alba L are traditional Chinese medicine widely applied in respiratory diseases.Our previous work has demonstrated the anti-lung cancer effect of secondary metabolites of mulberry leaf,but their mechanism of action has still not fully elucidated.We synthesized Moracin N(MAN)-Probe conjugated with alkyne to label lung cancer cells and identified protein targets by chemical proteomic analysis.MAN and its probe exerted similar growth-inhibitory effect on human lung cancer cells.Chemical proteomic results showed that MAN targeted the programmed death ligand 1(PD-L1)checkpoint pathway and T cell receptor(TCR)signaling pathway,indicating its immune-regulatory function.Cell-free surface plasmon resonance(SPR)results showed the direct interaction of MAN with PD-L1 protein.Molecular docking analysis demonstrated that MAN bound to E158 residue of PD-L1 protein.MAN downregulated the expression levels of PD-L1 in a time-and dose-dependent manner and disrupted the PD-L1/programmed death 1(PD-1)binding,including other secondary metabolites of mulberry leaves Guangsangon E(GSE)and Chalcomoracin(CMR).Human peripheral blood mononuclear cells(PBMCs)co-cultured with MAN-treated A549 cells,resulting in the increase of CD8+GZMB+T cells and the decrease of CD8+PD-1+T cells.It suggested that MAN exerts anti-cancer effect through blocking the PD-L1/PD-1 signaling.In vivo,MAN combined with anti-PD-1 antibody significantly inhibited lung cancer development and metastasis,indicating their synergistic effect.Taken together,secondary metabolites of mulberry leaves target the PD-L1/PD-1 signaling,enhance T cell-mediated immunity and inhibit the tumorigenesis of lung cancer.Their modulatory effect on tumor microenvironment makes them able to enhance the therapeutic efficacy of immune checkpoint inhibitors in lung cancer.

Background and purpose:Colorectal cancer(CRC)is one of the major malignant tumors threatening human health worldwide,with long-term high incidence and mortality rate.Potassium channel modulatory factor 1(KCMF1)is a member of the E3 ubiquitin ligase family.It binds to target proteins through the RING domain and participates in the regulation of a variety of biological processes in vivo.However,the function of KCMF1 in CRC remains unclear.This study aimed to investigate the expression level of E3 ubiquitin ligase KCMF1 in colorectal tumor,and to explore the effects of KCMF1 on the proliferation of CRC cells and its underlying molecular mechanism.Methods:The The Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)databases were used to analyze the expression level of KCMF1 in CRC tissues and adjacent tissues and the association between the KCMF1 expression and the prognosis of CRC patients.Furthermore,immunohistochemical staining was performed to detect the protein level of KCMF1 in 90 paired human CRC tissues and adjacent non-tumor tissues.Lentiviral shRNA delivery system was employed to specifically target the KCMF1 gene(shKCMF1)in HCT116 and HCT15 CRC cell lines.The effects of KCMF1 knockdown on cell proliferation,apoptosis and cell cycle distribution were assessed by methyl thiazoyl terazolium(MTT)assay,colony formation assay,Western blot and flow cytometry.Changes in the transcriptional profile in HCT116 cells upon KCMF1 knockdown were identified by RNA sequencing(RNA-Seq),and the affected signaling pathways were evaluated by bioinformatics analysis.Real-time fluorescence quantitative polymerase chain reaction(RTFQ-PCR),Western blot,luciferase reporter assay and cell immunofluorescence assay were utilized to validate the alteration of the affected signaling pathway.Results:The TCGA and GTEx databases and IHC results showed that the mRNA and protein expression levels of KCMF1 in CRC tissues were significantly upregulated compared with adjacent tissues(P＜0.01).KCMF1 expression level was negatively correlated with the survival time of patients with CRC(P＜0.01),and was positively associated with CRC clinical stage(P＜0.05).Compared with control cells,KCMF1 knockdown significantly inhibited the proliferation of HCT116 and HCT15 cells(P＜0.001),induced cell apoptosis(P＜0.001),and led to cell cycle arrest in G1 phase(P＜0.01).RNA-Seq analysis showed that KCMF1 was involved in the regulation of several signaling pathways,including nuclear factor-κB(NF-κB)signaling pathway.KCMF1 knockdown reduced the transcription levels of the target genes of NF-κB signaling pathway,including BCL-XL,XIAP and CIAP(P＜0.05),and suppressed the expression of phosphorylated p65 and nuclear translocation of p65(P＜0.01).Meanwhile,the activity of NF-κB reporter was reduced in tumor cells upon KCMF1 knockdown(P＜0.01).Conclusion:The expression of KCMF1 is significantly upregulated in human CRC tissues and positively associated with advanced clinical stage and poor prognosis.KCMF1 may promote the proliferation of CRC cells by activating the NF-κB signaling pathway.KCMF1 may be a potential new therapeutic target for CRC.

Parkin, an E3 ubiquitin ligase, plays a role in maintaining mitochondrial homeostasis through targeting damaged mitochondria for mitophagy. Accumulating evidence suggests that the acetylation modification of the key mitophagy machinery influences mitophagy level, but the underlying mechanism is poorly understood. Here, our study demonstrated that inhibition of histone deacetylase (HDAC) by treatment of HDACis activates mitophagy through mediating Parkin acetylation, leading to inhibition of cervical cancer cell proliferation. Bioinformatics analysis shows that Parkin expression is inversely correlated with HDAC2 expression in human cervical cancer, indicating the low acetylation level of Parkin. Using mass spectrometry, Parkin is identified to interact with two upstream molecules, acetylase acetyl-CoA acetyltransferase 1 (ACAT1) and deacetylase HDAC2. Under treatment of suberoylanilide hydroxamic acid (SAHA), Parkin is acetylated at lysine residues 129, 220 and 349, located in different domains of Parkin protein. In in vitro experiments, combined mutation of Parkin largely attenuate the interaction of Parkin with PTEN induced putative kinase 1 (PINK1) and the function of Parkin in mitophagy induction and tumor suppression. In tumor xenografts, the expression of mutant Parkin impairs the tumor suppressive effect of Parkin and decreases the anticancer activity of SAHA. Our results reveal an acetylation-dependent regulatory mechanism governing Parkin in mitophagy and cervical carcinogenesis, which offers a new mitophagy modulation strategy for cancer therapy.