Diabetic retinopathy, a prevalent and vision-threatening microvascular complication of diabetes mellitus, is the leading cause of blindness among middle-aged and elderly individuals. Natural diterpenoids isolated from Siegesbeckia pubescens demonstrate potent anti-inflammatory properties. This study aimed to identify novel bioactive diterpenoids from S. pubescens and investigate their effects on oxidative stress and inflammatory responses in diabetic retinopathy, both in vitro and in vivo. Three new ent-pimarane-type diterpenoids (1-3) and six known compounds (4-9) were isolated from the aerial parts of S. pubescens. Their structures were elucidated through spectroscopic data interpretation, and absolute configurations were determined by comparing calculated and experimental electronic circular dichroism (ECD) spectra. Among these compounds, 14β,16-epoxy-ent-3β,15α,19-trihydroxypimar-7-ene (5) exhibited the most potent protective effect against high glucose and interleukin-1β (IL-1β)-stimulated human retinal endothelial cells. Mechanistically, compound 5 promoted endothelial cell survival while ameliorating oxidative stress and inflammatory response in diabetic retinopathy, both in vivo and in vitro. These findings not only suggest that diterpenoids such as compound 5 are important anti-inflammatory constituents in S. pubescens, but also indicate that compound 5 may serve as a lead compound for preventing or treating vascular complications associated with diabetic retinopathy.
Diabetic Retinopathy/metabolism* ; Humans ; Oxidative Stress/drug effects* ; Animals ; Diterpenes, Kaurane/administration & dosage* ; Asteraceae/chemistry* ; Male ; Endothelial Cells/drug effects* ; Abietanes/administration & dosage* ; Molecular Structure ; Mice ; Anti-Inflammatory Agents/chemistry* ; Plant Extracts/chemistry* ; Mice, Inbred C57BL

The guidelines for curriculum ideological and political of nursing ethics explored the ideological and political elements of Chinese nursing,and proposed the curriculum's ideological and political goals.The development framework and basic ideas of guidelines were formed from the aspects of the integration path of curriculum ideological and political,and professional teaching,searching for the entry point of curriculum ideological and political,reforming the teaching methodology,enriching the form of teaching,and constructing the case base of curriculum ideological and political.It promoted the deep integration of nursing professional knowledge transmission and ideological value guidance,created a distinctive education system of curriculum ideological and political for nursing ethics,and provided a reference for the curriculum ideological and political construction of national nursing ethics.

Humans ; Aminoquinolines/therapeutic use* ; Carcinoma, Non-Small-Cell Lung/genetics* ; Lung Neoplasms/genetics* ; Mutation/genetics* ; Standard of Care

BACKGROUND: Previous research demonstrated that a homozygous mutation of g.136372044G>A (S12N) in caspase recruitment domain family member 9 ( CARD9 ) is critical for producing Aspergillus fumigatus -induced ( Af -induced) T helper 2 (T H 2)-mediated responses in allergic bronchopulmonary aspergillosis (ABPA). However, it remains unclear whether the CARD9S12N mutation, especially the heterozygous occurrence, predisposes the host to ABPA. METHODS: A total of 61 ABPA patients and 264 controls (including 156 healthy controls and 108 asthma patients) were recruited for sequencing the CARD9 locus to clarify whether patients with this heterozygous single-nucleotide polymorphisms are predisposed to the development of ABPA. A series of in vivo and in vitro experiments, such as quantitative real-time polymerase chain reaction, flow cytometry, and RNA isolation and quantification, were used to illuminate the involved mechanism of the disease. RESULTS: The presence of the p.S12N mutation was associated with a significant risk of ABPA in ABPA patients when compared with healthy controls and asthma patients, regardless of Aspergillus sensitivity. Relative to healthy controls without relevant allergies, the mutation of p.S12N was associated with a significant risk of ABPA (OR: 2.69 and 4.17 for GA and AA genotypes, P = 0.003 and 0.029, respectively). Compared with patients with asthma, ABPA patients had a significantly higher heterozygous mutation (GA genotype), indicating that p.S12N might be a significant ABPA-susceptibility locus ( aspergillus sensitized asthma: OR: 3.02, P = 0.009; aspergillus unsensitized asthma: OR: 2.94, P = 0.005). The mutant allele was preferentially expressed in ABPA patients with heterozygous CARD9S12N , which contributes to its functional alterations to facilitate Af -induced T H 2-mediated ABPA development. In terms of mechanism, Card9 wild-type ( Card9WT ) expression levels decreased significantly due to Af -induced decay of its messenger RNA compared to the heterozygous Card9S12N . In addition, ABPA patients with heterozygous CARD9S12N had increased Af -induced interleukin-5 production. CONCLUSION Our study provides the genetic evidence showing that the heterozygous mutation of CARD9S12N , followed by allele expression imbalance of CARD9S12N , facilitates the development of ABPA.
Humans ; Aspergillosis, Allergic Bronchopulmonary/complications* ; Aspergillus fumigatus/genetics* ; Asthma/genetics* ; Aspergillus ; Mutation/genetics* ; CARD Signaling Adaptor Proteins/genetics*

Objective:Cushing′s disease(CD) is caused by the pituitary adrenocorticotroph hormone(ACTH) secreting adenomas, leading to increased serum cortisol levels and various abnormal metabolic processes. Untreated CD is linked to high mortality, thus it is critical to elucidate its pathogenesis. This study aims to explore the pathogenesis of pituitary ACTH adenomas using whole-genome sequencing analysis.Methods:Fresh tumor tissues and peripheral blood samples were collected in 9 confirmed cases of pituitary ACTH adenomas who underwent surgery. Whole genome sequencing was then performed, followed by analysis and verification of single nucleotide mutations, copy number variation(CNV) and chromosome structure variations.Results:Somatic USP8 mutations(p.Ser718del, p. Ser718Pro, p. Pro720Arg, p. Pro720Gln) were found in 5 patients, with a rate of 55.6%; CNV of USP8 was detected in 1 patient; TP53(p.Cys135Tyr), NF1(p.Val1049Glufs*11) and KMT2C(c.3323+ 1G>A) mutations were identified in 1 patient harboring wild-type USP8. CNV analysis showed a loss of heterozygosity in multiple chromosomes in a wild-type USP8 patient. Structural variations were found in 2 with unknown significance. No germline gene mutations were detected in this study.Conclusion:Somatic USP8 mutations, increased copy number of USP8, variations of tumor-related genes such as TP53 and extensive somatic CNV all contribute to pathogenesis of CD. Chromosomal structure variations may suggest high-risk pituitary ACTH adenomas, and call for frequent follow-up and aggressive treatment.

Esophageal squamous cell carcinoma(ESCC)is a major histological subtype of esopha-geal cancer with a poor prognosis.Although several serum metabolomic investigations have been reported,ESCC tumor-associated metabolic alterations and predictive biomarkers in sera have not been defined.Here,we enrolled 34 treatment-naive patients with ESCC and collected their pre-and post-esophagectomy sera together with the sera from 34 healthy volunteers for a metabo-lomic survey.Our comprehensive analysis identified ESCC tumor-associated metabolic alterations as represented by a panel of 12 serum metabolites.Notably,postoperative abrosia and parenteral nutrition substantially perturbed the serum metabolome.Furthermore,we performed an examina-tion using sera from carcinogen-induced mice at the dysplasia and ESCC stages and identified three ESCC tumor-associated metabolites conserved between mice and humans.Notably,among these metabolites,the level of pipecolic acid was observed to be progressively increased in mouse sera from dysplasia to cancerization,and it could be used to accurately discriminate between mice at the dysplasia stage and healthy control mice.Furthermore,this metabolite is essential for ESCC cells to restrain oxidative stress-induced DNA damage and cell proliferation arrest.Together,this study revealed a panel of 12 ESCC tumor-associated serum metabolites with potential for monitor-ing therapeutic efficacy and disease relapse,presented evidence for refining parenteral nutrition composition,and highlighted serum pipecolic acid as an attractive biomarker for predicting ESCC tumorigenesis.

We developed a high-efficiency microfluidic chip for extracting exosomes from human plasma. We collected peripheral blood from normal human, designed and fabricated a microfluidic chip based on nanoporous membrane and agarose gel electrophoresis to isolate exosomes. The extracted exosomes were characterized by transmission electron microscopy, nanosight and Western blotting, the morphology, concentration and particle size of exosomes were identified and analyzed. Meanwhile, we used ultracentrifugation and microfluidic chip to isolate exosomes separately. The particle size and concentration of the exosomes extracted by two methods were compared and analyzed, and their respective extraction efficiency was discussed. Finally, the expression level of miRNA-21 in exosomes was analyzed by RT-PCR. The microfluidic chip isolated (in 1 hour) high-purity exosomes with size ranging from 30-200 nm directly from human plasma, allowing downstream exosomal miRNA analysis. By comparing with ultracentrifugation, the isolation yield of microfluidic chip was 3.80 times higher than ultracentrifugation when the volume of plasma sample less than 100 μL. The optimized parameters for exosome isolation by gel electrophoresis microfluidic chip were: voltage: 100 V; concentration of agarose gel: 1.0%; flow rate of injection pump: 0.1 mL/h. The gel electrophoresis microfluidic chips could rapidly and efficiently isolate the exosomes, showing great potential in the research of exosomes and cancer biomarkers.
Exosomes ; Humans ; MicroRNAs/genetics* ; Microfluidics ; Plasma ; Ultracentrifugation

Objective: To analyze the characteristics and influencing factors of the newly diagnosed cases locally infected with HIV through sexual contact in Jinhua,so as to provide reference for AIDS prevention and control. Methods: An epidemiological survey was conducted among the HIV/AIDS cases diagnosed in 2017 in Jinhua to collect the information about demographic characteristics,local infection and sexual behaviors. The logistic regression model was used to analyze the related factors for local HIV infection. Results: A total of 438 HIV/AIDS cases infected through sexual contact were recruited,with 272（62.10%）cases infected in Jinhua. The proportion of local infection was 86.67%,79.47%,63.04%,69.09%,77.46% and 77.97%,respectively,among those people aged 60 years or over,permanent residents in Jinhua,employees / students,farmers,those who had lived in Jinhua for more than five years,and those who had a HIV testing in one year. The Results of the multivariate logistic regression analysis showed that heterosexual transmission cases who were permanent residents in Jinhua（OR=3.437,95%CI：1.250-9.451）,who had lived in Jinhua for more than five years（OR=3.609,95%CI：1.403-9.284）,who had commercial heterosexual behaviors in Jinhua（OR=5.463,95%CI：2.529-11.803）were more likely to be infected with HIV in Jinhua;homosexual transmission cases who were permanent residents in Jinhua（OR=4.812,95%CI：1.744-13.275）and who had non-commercial,temporary homosexual behaviors in Jinhua（OR=10.641,95%CI：4.369-25.916）were more likely to be infected with HIV in Jinhua. Conclusion Among the HIV/AIDS cases diagnosed in 2017 infected through sexual contact in Jinhua,having permanent residence,long-term residence,commercial heterosexual behaviors and non-commercial,temporary homosexual behaviors were risk factors for local infection.

Objective: To explore the new ideas and methods for training nurses, and improve the training effect of specialist nurses through the Internet + micro-course platform training model. Methods: Sixty-four nurses who participated in the training of specialist nurses in Department of Cardiology for 2017-2018 years were divided into two groups with 32 cases each according to the year. The control group received the traditional training mode, the experimental group applied the Internet + micro curriculum platform training mode, and after the training, two groups of students were investigated for nursing operation examination, theoretical examination, critical thinking scale, and feedback surveys were conducted to analyze the Internet + micro course platform training. Results: Before training, the theoretical examination, the operation examination, critical thinking scale were (85.78 ± 2.59), (85.66 ± 2.60), (347.50 ± 6.61) points in the experimental group and (86.75 ± 2.63), (86.38 ± 2.59), (348.81 ± 5.28) points in the control group, the difference was not statistically significant (P > 0.05). After training, the theoretical examination, the operation examination, critical thinking scale were (94.25 ± 1.75), (95.68 ± 2.02), (407.81 ± 5.45) points in the experimental group and (90.34 ± 1.40), (94.25 ± 1.75), (380.40 ± 11.20) points in the control group, the difference was statistically significant (t=-9.572, -2.960, 12.445, all P <0.05). Conclusions The training mode of the Internet + micro course platform is superior to the traditional training mode, which can improve the critical thinking ability of the specialist nurses in Department of Cardiology, and is conductive to the training of clinical nurses′ ability of clinical strain.

To summarize key points of nursing care of 25 patients with secondary hyperparathyroidism underwent parathyroid autotransplantation with forearm (tPTX+AT).The integrated mode was adopted during the perioperative period,focusing on the following key points:perioperative management of environment,nursing of vascular access,intro-operative management of sample,nursing management during anesthesia and recovery,management of drawing blood,treatment and nursing care of postoperative hypocalcemia,prevention and nursing care of infection and hemorrhage,wound care in the forearm and monitoring of graft.Compared with the preoperative period,levels of intact parathyroid hormone(iPTH),calcium and phosphorus were significantly decreased during the postoperative period (P＜0.01);symptoms were significantly improved after surgery included bone and joint pain,muscular weakness,and insomnia.