Lycium barbarum glycopeptide(wolfberry extract)slows N-methyl-N-nitrosourea-induced degradation of photoreceptors

Photoreceptor cell degeneration leads to blindness, for which there is currently no effective treatment. Our previous studies have shown that Lycium barbarum(L. barbarum) polysaccharide(LBP) protects degenerated photoreceptors in rd1, a transgenic mouse model of retinitis pigmentosa. L. barbarum glycopeptide(Lb GP) is an immunoreactive glycoprotein extracted from LBP. In this study, we investigated the potential protective effect of Lb GP on a chemically induced photoreceptor-degenerative mouse model. Wild-type mice received the following: oral administration of Lb GP as a protective pre-treatment on days 1–7;intraperitoneal administration of 40 mg/kg N-methylN-nitrosourea to induce photoreceptor injury on day 7;and continuation of orally administered Lb GP on days 8–14. Treatment with Lb GP increased photoreceptor survival and improved the structure of photoreceptors, retinal photoresponse, and visual behaviors of mice with photoreceptor degeneration. Lb GP was also found to partially inhibit the activation of microglia in N-methyl-N-nitrosourea-injured retinas and significantly decreased the expression of two pro-inflammatory cytokines. In conclusion, Lb GP effectively slowed the rate of photoreceptor degeneration in N-methyl-N-nitrosourea-injured mice, possibly through an anti-inflammatory mechanism, and has potential as a candidate drug for the clinical treatment of photoreceptor degeneration.

Effectiveness of fecal DNA syndecan-2 methylation testing for detection of colorectal cancer in a high-risk Chinese population

BACKGROUND Colorectal cancer(CRC)is among the most prevalent and life-threatening malignancies worldwide.Syndecan-2 methylation(mSDC2)testing has emerged as a widely used biomarker for early detection of CRC in stool and serum samples.Cancer(CRC)is among the most prevalent and life-threatening malignancies worldwide.mSDC2 testing has emerged as a widely used biomarker for early detection of CRC in stool and serum samples.AIM To validate the effectiveness of fecal DNA mSDC2 testing in the detection of CRC among a high-risk Chinese population to provide evidence-based data for the development of diagnostic and/or screening guidelines for CRC in China.METHODS A high-risk Chinese cohort consisting of 1130 individuals aged 40-79 years was selected for evaluation via fecal mSDC2 testing.Sensitivity and specificity for CRC,advanced adenoma(AA)and advanced colorectal neoplasia(ACN)were determined.High-risk factors for the incidence of colorectal lesions were determined and a logistic regression model was constructed to reflect the efficacy of the test.RESULTS A total of 1035 high-risk individuals were included in this study according to established criteria.Among them,16 suffered from CRC(1.55%),65 from AA(6.28%)and 189 from non-AAs(18.26%);150 patients were diagnosed with polyps(14.49%).Diagnoses were established based upon colonoscopic and pathological examinations.Sensitivities of the mSDC2 test for CRC and AA were 87.50%and 40.00%,respectively;specificities were 95.61%for other groups.Positive predictive values of the mSDC2 test for CRC,AA and ACN were 16.09%,29.89%and 45.98%,respectively;the negative predictive value for CRC was 99.79%.After adjusting for other high-risk covariates,mSDC2 test positivity was found to be a significant risk factor for the occurrence of ACN(P<0.001).CONCLUSION Our findings confirmed that offering fecal mSDC2 testing and colonoscopy in combination for CRC screening is effective for earlier detection of malignant colorectal lesions in a high-risk Chinese population.

Identifying the core competencies of backup nurses in the acute care hospital through a modified Delphi process

Background:The backup nurses are created to meet emergencies in the case of inadequate nursing staff and emergency circumstances,and there are no clear definitions of the core competencies for training and evaluation of backup nurses in the acute care hospitals in China.Methods:This study used a modified Delphi process where an initial list of potential competencies is established following a framework of training need analysis(TNA),literature review,and focus groups.This process generated as a list of 47 core competencies,which is presented to an expert panel(n=20)for consideration in two rounds.Results:As determined by the survey,a combination of 26 core competencies in three specified categories is identified:professional practice ability,critical thinking ability,and interpersonal skills.A total of 154.99 h is required to complete all 26 core competencies,and each item has a corresponding evaluation method.Conclusions:The core competencies provide a scientific basis for the hospital nursing managers to train and evaluate backup nurses,and it may ensure consistency in standards across the country.

Real-world effectiveness and safety of goserelin 10.8-mg depot in Chinese patients with localized or locally advanced prostate cancer

Objective:Real-word data on long-acting luteinizing hormone-releasing hormone(LHRH)agonists in Chinese patients with prostate cancer are limited.This study aimed to determine the real-world effectiveness and safety of the LHRH agonist,goserelin,particularly the long-acting 10.8-mg depot formulation,and the follow-up patterns among Chinese prostate cancer patients.Methods:This was a multicenter,prospective,observational study in hormone treatment-na?ve patients with localized or locally advanced prostate cancer who were prescribed goserelin 10.8-mg depot every 12 weeks or 3.6-mg depot every 4 weeks with or without an anti-androgen.The patients had follow-up evaluations for 26 weeks.The primary outcome was the effectiveness of goserelin in reducing serum testosterone and prostate-specific antigen(PSA)levels.The secondary outcomes included testosterone and PSA levels,attainment of chemical castration(serum testosterone<50 ng/d L),and goserelin safety.The exploratory outcome was the monitoring pattern for serum testosterone and PSA.All analyses were descriptive.Results:Between September 2017 and December 2019,a total of 294 eligible patients received≥1 dose of goserelin;287 patients(97.6%)were treated with goserelin 10.8-mg depot.At week 24±2,the changes from baseline[standard deviation(95%confidence interval)]in serum testosterone(n=99)and PSA(n=131)were-401.0 ng/d L[308.4 ng/d L(-462.5,-339.5 ng/d L)]and-35.4 ng/m L[104.4 ng/m L(-53.5,-17.4 ng/m L)],respectively.Of 112 evaluable patients,100(90.2%)achieved a serum testosterone level<50 ng/d L.Treatment-emergent adverse events(TEAEs)and severe TEAEs occurred in 37.1%and 10.2%of patients,respectively.The mean testing frequency(standard deviation)was 1.6(1.5)for testosterone and 2.2(1.6)for PSA.Conclusions:Goserelin 10.8-mg depot effectively achieved and maintained castration and was well-tolerated in Chinese patients with localized and locally advanced prostate cancer.

Characterization of inflammatory factor-induced changes in mesenchymal stem cell exosomes and sequencing analysis of exosomal microRNAs

BACKGROUND Treatments utilizing stems cells often require stem cells to be exposed to inflammatory environments,but the effects of such environments are unknown.AIM To examine the effects of inflammatory cytokines on the morphology and quantity of mesenchymal stem cell exosomes(MSCs-exo)as well as the differential expression of microRNAs(miRNAs)in the exosomes.METHODS MSCs were isolated from human umbilical tissue by enzymatic digestion.Exosomes were then collected after a 48-h incubation period in a serum-free medium with one of the following the inflammatory cytokines:None(control),vascular cell adhesion molecule-1(VCAM-1),tumor necrosis factor(TNF)α,and interleukin(IL)6.The morphology and quantity of each group of MSC exosomes were observed and measured.The miRNAs in MSCs-exo were sequenced.We compared the sequenced data with the miRBase and other non-coding databases in order to detect differentially expressed miRNAs and explore their target genes and regulatory mechanisms.In vitro tube formation assays and Western blot were performed in endothelial cells which were used to assess the angiogenic potential of MSCs-exo after inflammatory cytokine stimulation.RESULTS MSCs-exo were numerous,small,and regularly shaped in the VCAM-1 group.TNFαstimulated MSCs to secrete larger and irregular exosomes.IL6 led to a reduced quantity of MSCs-exo.Compared to the control group,the TNFαand IL6 groups had more downregulated differentially expressed miRNAs,particularly angiogenesis-related miRNAs.The angiogenic potential of MSCs-exo declined after IL6 stimulation.CONCLUSION TNFαand IL6 may influence the expression of miRNAs that down-regulate the PI3K-AKT,MAPK,and VEGF signaling pathways;particularly,IL6 significantly down-regulates the PI3K-AKT signaling pathway.Overall,inflammatory cytokines may lead to changes in exosomal miRNAs that abnormally impact cellular components,molecular function,and biological processes.

Lutein delays photoreceptor degeneration in a mouse model of retinitis pigmentosa

Retinitis pigmentosa is a retinal disease characterized by photoreceptor degeneration.There is currently no effective treatment for retinitis pigmentosa.Although a mixture of lutein and other antioxidant agents has shown promising effects in protecting the retina from degeneration,the role of lutein alone remains unclear.In this study,we administered intragastric lutein to Pde6brd10 model mice,which display degeneration of retinal photoreceptors,on postnatal days 17(P17)to P25,when rod apoptosis reaches peak.Lutein at the optimal protective dose of 200 mg/kg promoted the survival of photoreceptors compared with vehicle control.Lutein increased rhodopsin expression in rod cells and opsin expression in cone cells,in line with an increased survival rate of photoreceptors.Functionally,lutein improved visual behavior,visual acuity,and retinal electroretinogram responses in Pde6brd10 mice.Mechanistically,lutein reduced the expression of glial fibrillary acidic protein in Müller glial cells.The results of this study confirm the ability of lutein to postpone photoreceptor degeneration by reducing reactive gliosis of Müller cells in the retina and exerting anti-inflammatory effects.This study was approved by the Laboratory Animal Ethics Committee of Jinan University(approval No.LACUC-20181217-02)on December 17,2018.

Diagnostic Value of the Post-Processing Technique of Multi-Slice Spiral CT in Orbital Cyst Diseases

Purpose:To analyze the features of CT imaging of orbital cystic disease. Methods:.A total of 30 patients were pathologically confirmed with orbital cystic disease between January 2007 and March 2012. Prior to operation, the participants underwent CT scans with image processing by maximum intensity projection (MIP) and volume rendering (VR). Preoperative CT diagnostic outcomes were compared with postoperative pathological findings. Results:.The patients presented with round,.oval and dumbbell shaped masses. Fourteen cases of dermoid cyst and 8 cases of epidermoid cyst showed heterogeneous density. Among the dermoid cyst patients, 6 cases had demixing phenomenon, 3 cases had lipid drift and 5 cases showed mild or moderate intensity enhancement in the cyst wall. No intensity enhancement was observed in the epidermoid cyst patients. Five cases had high intensity due to hemorrhage and 3 patients presented with adjacent sclerotin arc compression;.5 cases of myxoid cyst had homogenous density and no intensity enhancement was found when iohexol was injected..Three patients with atheromatous cyst had heterogeneous density,.with CT value ranging from -36Hu to 191Hu. Floss was noted centrally in 1 case and mild to moderate intensity enhancement was observed in the cyst wall with iohexol injection. Conclusion:.Multi-slice CT is useful in the diagnosis of orbital cystic disease. Multi-slice CT combined with image processing can be helpful in displaying the location and size of masses, and revealing the relationship between masses and surrounding boney tissue, providing an objective basis for surgical planning when combined with 3D-CT imaging.

Narciclasine induces colon carcinoma cell apoptosis by inhibiting the IL-17A/Act1/TRAF6/NF-kB signaling pathway

IL-17 A is a promoter of colorectal cancer initiation and progression.Narciclasine is a polyhydroxy alkaloid compound isolated from Narcissus plants,which has potent anti-inflammatory and antitumor actions.The effects of narciclasine on colorectal tumors were evaluated,with a focus on IL-17 A.Narciclasine reduced the growth of HCT-116 and SW-480 colon cancer cells in vitro and in vivo in murine xenografts.The results of flow cytometry on JC-1 and Annexin V/PI revealed that narciclasine significantly reduced the mitochondrial membrane potential and induced apoptosis,findings confirmed by western blotting results of reduced Bcl2 and enhanced Bax expression,as well as accumulation of cleaved Caspase-3,Caspase-8,Caspase-9,and cytoplasmic Cytochrome-c.After narciclasine incubation,IL-17 A,Act1,and TRAF6 were down-regulated,while p-P65(Ser536)accumulated in the cytoplasm,a finding confirmed by laser scanning confocal microscopy.IL17A substitution could partly reverse these narciclasine effects while they were elevated by IL17A silencing.Moreover,IL-17 A,Act1,and TRAF6 were significantly expressed to greater extents in human colorectal cancer compared to normal adjacent tissue specimens and were closely linked with a poor prognosis.This study provided evidence that narciclasine may be a useful therapeutic drug for colorectal cancer treatment through its actions in down-regulating the L-17A/Act1/TRAF6/NF-kB anti-apoptotic signaling pathway.

A colorimetric assay for cholesterol based on the encapsulation of multienzyme in leaf-shape crossed ZIF-L

The serum cholesterol level is an important indicator of healthy and there is a great necessity for frequent cholesterol monitoring to some cardiovascular-related diseases, which puts forward higher requirements for point-of-care testing(POCT) of cholesterol. In this work, a cascade catalytic system of cholesterol is developed by encapsulation of cholesterol oxidase(Ch Ox) and Pd Cu Au nanoparticles into zeolitic imidazolate framework-L(Ch Ox/PCA@ZIF-L). Results indicate that ZIF-L carrier can significantly increase the catalytic activity of single or multiple enzymes, due to its high loading capacity and efficient molecular transport. Under the optimal conditions, the absorbance of reaction system performs linear relationships with the concentration of cholesterol in two intervals from 0.0005 mmol/L to 1.0000 mmol/L, with a limit of detection of 0.2176 μmol/L. The proposed colorimetric strategy based on Ch Ox/PCA@ZIF-L performs a good agreement with the results provided by chemiluminescence method for the serum cholesterol detection. Interestingly, a simple paper-based sensing system is constructed through a pre-reaction-transfer operation, which gets rid of the complex pre-processing requirements of traditional operations on filter paper. The presented strategy allows for the sensitive, convenient, costless assay of serum cholesterol,and paves a new way to design the POCT device for daily monitoring of healthy.

Genomic divergences between the two polyphagous Spodoptera relatives provide cues for successful invasion of the fall armyworm

The fall armyworm Spodoptera frugiperda recently invaded China,ravaging crops in many provinces.Deciphering the possible genetic basics for its successful invasion is critical for innovative and specific control for this gluttonous pest.Here we generated comparative genomic analyses between S.frugiperda and its native relative,S.litura,which differs in host preference,locomotivity and production behavior.We demonstrated that S.frugiperda genes are enriched in taste sensory perception and nervous system,obv iously difTerent from those of S.litura.Potential host adaptation genes showed generally an elevated ratio of non-synonymous substitution rate to synonymous substitution rate,suggesting a faster evolution during the divergence of the two species.Focusing on these sets of genes,we identified 23 genes being under positive selection in S.frugiperda.Among them are two notable genes involved in sensory perception,gustatory receptor(GR)and an acetaldehyde oxidase,which are important for host detection in invasion and expansion processes.Another two genes are mitochondrial adenosine triphosphate synthase^subunit and ferritin heavy chain,which may be associated with the enhanced locomotivity and resistance,which fascinated long-distance migration needed for invasion and rapid expansion.Another interesting gene is chorion protein,in which positive selection sites in S.frugiperda were found and a replacement in one site is predicted to affect the protein function,which might be associated with competent reproductivity in S.frugiperda to ensure genetic resources for expansion.

Orthogonal Enzymatic Reactions to Control Supramolecular Hydrogelations

Enzyme-responsive hydrogels have great potential in applications of controlled drug release, tissue engineering, etc. In this study, we reported on a supramolecular hydrogel that showed responses to two enzymes, phosphatase which was used to form the hydrogels and esterase which could trigger gelsol phase transitions. The gelation process and visco-elasticity property of the resulting gel, morphology of the nanostructures in hydrogel, and peptide conformation in the self-assembled nanostructure were characterized by theology, transmission electron microscope （TEM）, and circular dichroism （CD）, respectively. Potential application of the enzyme-responsive hydrogel in drug release was also demonstrated in this study. Though only one potential application of drug release was proved in this study, the responsive hydrogel system in this study might have potentials for the applications in fields of cell culture, controlled-drug release, etc.

Development of a Handheld Nano-centrifugal Device for Visual Virus Detection

Gold nanoparticles(AuNPs)colorimetric assays based on distance-dependent optical characteristics have been widely employed for bioanalysis.However,this assay is not effective for visually detecting low-concentration targets due to the faint color change.Here,we developed a handheld nano-centrifugal device which could separate the crosslinked and non-crosslinked AuNPs.Results showed that the handheld nano-centrifugal device could easily reach more than 6000 r/min within 10 s simply by stretching and tightening the coiled rope in an appropriate rhythm.Further,combined with the CRISPR/Cas12a nucleic acids recognition system,a field-deployable colorimetric platform termed handheld nano-centrifugal device assisted CRISPR/Cas12a(Hand-CRISPR)has been validated.Moreover,clinical diagnostics applications for Epstein-Barr virus(EBV)and severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)detection with high sensitivity and accuracy(100%consistency with reverse transcription quantitative real-time polymerase chain reaction(RT-qPCR)test results)have been demonstrated.Overall,the Hand-CRISPR platform showed great promise in point-of-care-test(POCT)application,expected to become a powerful supplement to the standard nucleic acid testing method in remote or poverty-stricken areas.

Research Progress of Biological Risk Factors for Suicide with Major Depressive Disorder

This study is designed to investigate the biological risk factors of Suicide with Major Depressive Disorder(SMDD),mainly including population biological factors,severity of depressive disorder,blood lipids,neurobiochemical and neuroendocrine changes,molecular genetics and imaging and other aspects,and elaborate the problems like diagnosis difference,non-biological factors and sampling representativeness in line with the dilemma of research methodology.This study aims to understand the latest research trend of SMDD so as to provide the basis for further discuss and study its etiology and generation mechanism.

The association of N-terminal pro-B-type natriuretic peptide level with short-term mortality in elderly patients with sepsis

Background Sepsis is a dysregulated host response to an infection with high prevalence and mortality in elderly population. The predictive value of N-terminal pro-B-type natriuretic peptide(NT-pro BNP) in elderly septic patients is yet unknown. Method Elderly patients(≥60 years old) with sepsis, that admitted to the Guangzhou Panyu Central Hospital from January 2019 to December 2021 were consecutively recruited. All patients were followed up for 28 days since admission and the event of death was recorded. The Cox regression analysis and receiver operation characteristic(ROC) analysis were performed to study the association between NT-pro BNP and mortality. Results A total of 490 patients were included, and divided into: survival group(n=304, 62.0%)and death group(n=186, 38.0%). The multivariate Cox regression analysis showed that higher lg(NT-pro BNP)(HR=1.60, 95% CI 1.24-2.06, P<0.001, Table 2), liver disease(HR=5.22, 95% CI 2.26-12.03, P<0.001, Table 2),higher serum lactic acid(HR=1.09, 95% CI 1.05-1.14, P<0.001, Table 2) were independently associated with28-day mortality in sepsis. ROC analysis for NT-pro BNP in predicting 28-day mortality demonstrated an AUC of0.663(95%CI 0.614-0.712), with NT-pro BNP=7233 pg/ml as the optimal cut-off value. The sensitivity was 50.5%and the specificity was 73.7%. Conclusion NT-pro BNP could be a feasible predictor for mortality in elderly patients with sepsis.