الملخص
Liver failure is a common clinical syndrome of severe liver disease with rapid progression and high mortality. Therefore， early intervention in pre-liver failure or “golden window” is of great significance in improving the prognosis of patients. Hepatitis B virus-related acute-on-chronic liver failure and alcohol-related acute-on-chronic liver failure are the main topics of studies on pre-liver failure. This article discusses the pathogenesis of pre-liver failure and artificial liver support therapy， so as to guide the reasonable and affective applications of artificial liver technology in clinical practice， promote related studies， and thereby reduce the mortality rate of patients with liver failure.
الملخص
Objective To investigate the correlation between the concentration of air pollutants (PM10, SO2, NO2) and the number of outpatient and emergency visits for pediatric respiratory diseases in a general hospital in Shanghai. Methods Data including pediatric respiratory disease outpatient and emergency visits in a hospital in Pudong New Area of Shanghai from May 1, 2013 to March 20, 2022 were collected. Daily concentration of air pollutants including PM10, SO2 and NO2 and meteorological data in Pudong New Area during the same period were collected. A case-crossover study with distributed lag non-linear model was conducted to explore the correlation between air pollutants (PM10, SO2, NO2) and the number of outpatient and emergency visits for pediatric respiratory diseases. Results The concentrations of PM10, SO2 and NO2 were positively with the number of outpatient and emergency visits for pediatric respiratory diseases. The strongest cumulative effect was observed on six days lag (Lag0-5) for PM10. For a 10 μg/m3 increase of the concentrations of PM10, the corresponding increase of cumulative pediatric respiratory disease outpatients was 1.10% (95%CI:0.97%, 1.23%) in Lag0-5. The strongest cumulative effect was observed on eight days lag (Lag0-7) for SO2 and NO2. For a 10 μg /m3 increase of the concentrations of SO2 and NO2, the corresponding increase of cumulative pediatric respiratory disease outpatients was 5.64% (95%CI:5.16%, 6.13%) and 5.41% (95%CI:5.15%, 5.66%) in Lag 0-7, respectively. The association of PM10 and SO2 with the number of pediatric respiratory disease visits in males was significantly stronger than that in females. The impact of PM10 on the number of pediatric respiratory disease visits in children aged 0-6 was higher than that in children aged 7-14, while the impact of SO2 and NO2 on the number of pediatric respiratory disease visits in children aged 7-14 was higher than that in children aged 0-6. Conclusion The concentration of ambient PM10, SO2, and NO2 is positively correlated with outpatient and emergency visits for pediatric respiratory diseases, with obvious lag and cumulative effect. Boys and children aged 0-6 are more susceptible to the hazard of air pollution.
الملخص
Four pyrazines were isolated from the n-butanol fraction of Hypecoum erectum L. by using various chromatographic methods, including MCI gel, ODS, silica gel and semi-preparative HPLC. The structures of the isolated compounds were identified as hyperectpyrazin A (1), 1′S-(6-methylpyrazin-2-yl)-ethane-1′,2′-diol (2), 2-hydroxymethyl-6-methylpyrazin (3) and pyrazine-2-carboxylic acid (4) by spectroscopy methods (1D NMR, 2D NMR, UV, IR, MS, etc.). The absolute configuration of compound 2 was determined by using the Mo2(OAc)4 induced CD analysis for the first time. Compound 1 was a new compound, compounds 2-4 were isolated from H. erectum for the first time. Compounds 1-4 were evaluated for their inhibition against acetylcholinesterase and nitric oxide generation induced by lipopolysaccharide-RAW264.7 macrophage cells. At a concentration of 50 μmol·L-1, compounds 2 and 4 displayed inhibitory effects on acetylcholinesterase with the inhibition rates of 44.40% and 43.99%, respectively.
الملخص
The coronavirus disease 2019 (COVID-19) is an acute infectious disease caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which has led to serious worldwide economic burden. Due to the continuous emergence of variants, vaccines and monoclonal antibodies are only partial effective against infections caused by distinct strains of SARS-CoV-2. Therefore, it is still of great importance to call for the development of broad-spectrum and effective small molecule drugs to combat both current and future outbreaks triggered by SARS-CoV-2. Cathepsin L (CatL) cleaves the spike glycoprotein (S) of SARS-CoV-2, playing an indispensable role in enhancing virus entry into host cells. Therefore CatL is one of the ideal targets for the development of pan-coronavirus inhibitor-based drugs. In this study, a CatL enzyme inhibitor screening model was established based on fluorescein labeled substrate. Two CatL inhibitors IMB 6290 and IMB 8014 with low cytotoxicity were obtained through high-throughput screening, the half inhibition concentrations (IC50) of which were 11.53 ± 0.68 and 1.56 ± 1.10 μmol·L-1, respectively. SDS-PAGE and cell-cell fusion experiments confirmed that the compounds inhibited the hydrolysis of S protein by CatL in a concentration-dependent manner. Surface plasmon resonance (SPR) detection showed that both compounds exhibited moderate binding affinity with CatL. Molecular docking revealed the binding mode between the compound and the CatL active pocket. The pseudovirus experiment further confirmed the inhibitory effects of IMB 8014 on the S protein mediated entry process. In vitro pharmacokinetic evaluation indicated that the compounds had relatively good drug-likeness properties. Our research suggested that these two compounds have the potential to be further developed as antiviral drugs for COVID-19 treatment.
الملخص
Objective To investigate the association between the index finger and ring finger length ratio (2D ∶ 4D) and of four loci (rs6461992‚ rs6968828‚ rs7801581‚ rs17427875) polymorphism of homeobox (HOX) A11 gene among Ningxia college students. Methods Digit camera was used to collect frontal hand photos of 667 Han college students (348 males and 319 females) from Ningxia province; Image analysis software was used to mark the anatomical points and measure finger lengths of the index and ring fingers of both hands; multiplex PCR was used to detect each locus polymorphisms of HOXA11 gene; statistical software was used to compare and analyze the differences and associations of 2D ∶4D and gene polymorphisms between different genders. Results Among Ningxia Han college students‚ both left hand and right hand 2D ∶ 4D were significantly higher in females than those of in males (all P< 0. 05)‚ and there were no significant sex differences in right-left hand 2D ∶4D; the genotypes and allele frequencies of rs7801581 locus of HOXA11 gene differed significantly between genders (all P < 0. 05)‚ and none of the other locus polymorphisms showed any significant sex differences; only female left hand 2D ∶4D was significantly associated with rs6461992 locus genotype in the relationship between 2D ∶4D and HOXA11 polymorphisms (P<0. 05). Conclusion There were significant sex differences in 2D ∶ 4D among Han college students in Ningxia‚ and the rs6461992 locus polymorphism of HOXA11 gene may be associated with the formation of 2D ∶4D in females.
الملخص
Free fatty acids, as important energy metabolism substrates for the heart, play an important role in various cardiovascular diseases; ω-3 PUFA, as an important branch of free fatty acids, has been confirmed by more and more researches to be closely related to cardiovascular diseases. Heart failure, as a common cardiovascular problem, seriously affects people's quality of life. Studies have shown that ω-3 PUFA plays a significant role in the development of heart failure. In this paper, we try to review the metabolism, pathogenesis and therapeutic significance of ω-3 PUFA in heart failure.
الملخص
Positron emission tomography (PET) now plays an important role in the research and development (R&D) of central nervous system (CNS) drugs. PET could characterize the biodistribution, pharmacokinetics, and receptor binding of CNS drugs quantitatively. The present review summarized the quantitative methods of PET used in the pharmacokinetics and receptor occupancy analysis of CNS drugs. Moreover, the present review listed various applications of PET supporting R&D of CNS drugs, which could provide a new direction for the R&D of CNS drugs.
الملخص
Aim To investigate the regulatory effect of Cortaetin on pathological myocardial hypertrophy induced by isoprenaline (ISO) and the underlying mechanism. Methods ISO was used to stimulate neonatal rat cardiomyocytes for 24 h, and myocardial hypertrophy model was established at the cellular level. C57BL/6 mice were injected subcutaneously with ISO for one week to establish myocardial hypertrophy model at animal level. RT-qPCR was used to detect the changes of mRNA and Western blot was used to detect the changes of relative protein content. Immunofluorescence was used to measure the subcellular location of Cortaetin and the change of its expression. The overex-pression of Cortaetin by adenovirus infection and the knockdown of Cortaetin by transfection of small interfering RNA were studied. Results On the cellular and animal levels, ISO-induced myocardial hypertrophy models were successfully established, and it was observed that ISO caused the decrease of Cortaetin and N-cadherin protein levels. Overexpression of Cortaetin could reverse the decrease of N-cadherin protein level and myocardial hypertrophy caused by ISO. Knockdown of Cortaetin showed the opposite effect. Conclusion Cortaetin, in combination with N-cadherin, may play a role in combating myocardial hypertrophy by enhancing the connections between cardiomyocytes.
الملخص
Aim To investigate the effect of ellagic acid (EA) on cognitive function in APP/PS 1 double- transgenic mice, and to explore the regulatory mechanism of ellagic acid on the level of oxidative stress in the hippocampus of double-transgenic mice based on the phosphatidylinositol 3-kinase/protein kinase B/glycogen synthase kinase-3 (PI3K/AKT/GSK-3 β) signaling pathway. Methods Thirty-two SPF-grade 6-month-old APP/PS 1 double transgenic mice were randomly divided into four groups, namely, APP/PS 1 group, APP/PS1 + EA group, APP/PS1 + LY294002 group, APP/PS 1 + EA + LY294002 group, with eight mice in each group, and eight SPF-grade C57BL/6J wild type mice ( Wild type) were selected as the blank control group. The APP/PS 1 + EA group was given 50 mg · kg
الملخص
In the post-epidemic era, medical workers have more responsibilities and the medical environment is becoming increasingly complex, so more exquisite medical technology and higher-level professionalism are needed. In the post-epidemic era, medical students’ cognition of the value of life itself, their reflection on the ethical relationship between life individuals and their understanding of the ethical relationship between freedom and responsibility make it more significance to strengthen the cultivation of professional spirit. The ideological and political course is the key course to implement the fundamental task of cultivating people with virtue. Integrating the professional principle education of "Life is the highest", highlighting the philosophical thinking education and strengthening the great anti-epidemic spirit education in the ideological and political course is an effective way to cultivate the professionalism of medical students in the post-epidemic era.
الملخص
This paper took a hospital in Anhui province as an example, aimed at the problems existing in the protection of human subjects’ rights and interests in China, and put forward relevant suggestions from the ethical perspective. The suggestions included shaping the international vision, playing the core role of ethics committee, strengthening the construction of legal and regulatory protection mechanism, setting up the human research protection committee and actively promoting the construction of subject protection system. These measures will effectively promote the construction and improvement of the rights and interests protection system of human subjects in China.
الملخص
The intervention and prevention of perioperative hypothermia is not only reflected in the technical level, but also reveals the important role of humanistic care in the whole intervention work. If perioperative patients have hypothermia, it is likely to cause a series of complications such as postoperative shivering, which seriously threatens the life safety of patients. Prevention and intervention was based on a comprehensive understanding of the causes and hazards of hypothermia, especially the impact on the lives of the elderly. Effective supervision was implemented in the whole process of operation, such as dynamic monitoring of vital signs including body temperature, followed by room temperature regulation, body temperature protection and preoperative and postoperative psychological nursing. At this time, the sense of responsibility, good humanistic care of medical staff are of positive significance to effectively prevent and reduce the probability of perioperative hypothermia and accelerate the postoperative rehabilitation of patients.
الملخص
The life view of "human life is the most important" in Traditional Chinese Medicine (TCM) originates from the people-oriented theory of Chinese traditional culture, the benevolence thought of Confucianism, the rebirth thought of Taoism and the compassion thought of Buddhism. Taking the life view of "human life is the most important" as the starting point, it has formed medical ethics thoughts such as the social responsibility of saving the world, the medical practice purpose of treating all patients equally, the meticulous working attitude, the diligent and tireless learning attitude, and the exploration spirit of widely exploring the medical roots, which still has important educational significance. Therefore, the life view of "human life is the most important" should be integrated into the medical ethics education of medical students, and the medical ethics literacy of medical students should be improved through the following ways: strengthen the vocational ideal education of saving the dying and healing the wounded, and enhance the sense of social responsibility of medical students; consolidate the theme of life first classroom education and improve the professional identity of medical students; enrich and innovate the practice forms of protecting life, pay attention to the practicality of medical ethics education.
الملخص
One of the crux of the problem of doctor-patient relationship is the uneven division of rights and obligations between doctors and patients. Among them, it is significantly essential to emphasize the patient’s obligation as a weak point. The reasons cover many aspects. On the one hand, it is of great significance to standardize patient obligations: the definition of patients’ obligations is better health protection for patients; the emphasis on patients’ obligations is the moral support for doctors’ responsibilities; the fulfillment of patients’ obligations promotes the win-win interests of doctors and patients. On the other hand, the current situation of standardizing patients’ obligations is not optimistic: the provisions of patients’ obligations in existing laws and regulations are not ideal; the current ethical discussion on patient obligations also needs to be deepened. Therefore, in order to standardize patients’ obligations, build harmonious doctor-patient relationship and build a community of doctor-patient, this paper put forward specific suggestions from three aspects: improving laws and regulations, standardizing the management of medical institutions and enhancing patients’ literacy.
الملخص
Objective@#To investigate the prevalence of overweight/obesity and its associations with sleep duration among children and adolescents aged 6-17 in Gansu Province, so as to formulate tailored prevention and control strategies and intervention measures.@*Methods@#Using a multi stage stratified cluster random sampling method, a questionnaire survey and physical examination were conducted among 2 172 students aged 6-17 from 2 monitoring points in Gansu Province from May to July 2022. Using Chi square test to analyze the inter group differences in the detection rates of overweight and obesity and the composition of sleep duration, and using Logistic regression model to analyze the correlation between overweight and obesity and sleep duration.@*Results@#The prevalence of overweight and obesity were 10.45% and 6.86%, respectively. The average sleep duration was ( 8.28 ±1.66)h/d. The detection rate of overweight was high among high school students aged 16-17 and those with sleep duration<8 h/d ( χ 2=12.51, 19.32, 14.96), while the detection rate of obesity was high among male and non residential students ( χ 2= 5.89 , 9.59)( P ＜0.05). For both boys and girls, the rates of overweight and obesity among primary school students increased with the decrease in sleep duration ( χ 2=38.84, 9.80, 19.61, 41.60, P <0.05). The rates of obesity in boys were higher than girls across varying sleep durations among the general population (sleep duration <8 h/d: 6.07%, 11.11%, 8~<9 h/d: 5.76%, 6.09 %, 9~<10 h/d: 6.02%, 8.19 %, ≥10 h/d: 4.04%, 6.90%). Multivariate Logistic regression analysis showed that insufficient sleep duration among primary school students was positively associated with the risk of overweight and obesity, and adequate sleep duration among high school students was negatively associated with the risk of overweight and obesity (sleep duration 8~<9 h/d: OR primary school students = 1.89 , 9~< 10 h/d: OR primary school students =1.54, 8~<9 h/d: OR high school students =0.30, P <0.05).@*Conclusions@#Insufficient sleep is a risk factor for overweight and obesity among primary and secondary school students at monitoring sites in Gansu Province. Prevention strategies and interventions should be developed for different populations to ensure adequate sleep duration and reduce the risk of overweight and obesity among primary and secondary school students.
الملخص
Gorham-Stout disease (GSD) is a sporadic chronic disease characterized by progressive bone dissolution, absorption, and disappearance along with lymphatic vessel infiltration in bone-marrow cavities. Although the osteolytic mechanism of GSD has been widely studied, the cause of lymphatic hyperplasia in GSD is rarely investigated. In this study, by comparing the RNA expression profile of osteoclasts (OCs) with that of OC precursors (OCPs) by RNA sequencing, we identified a new factor, semaphorin 3A (Sema3A), which is an osteoprotective factor involved in the lymphatic expansion of GSD. Compared to OCPs, OCs enhanced the growth, migration, and tube formation of lymphatic endothelial cells (LECs), in which the expression of Sema3A is low compared to that in OCPs. In the presence of recombinant Sema3A, the growth, migration, and tube formation of LECs were inhibited, further confirming the inhibitory effect of Sema3A on LECs in vitro. Using an LEC-induced GSD mouse model, the effect of Sema3A was examined by injecting lentivirus-expressing Sema3A into the tibiae in vivo. We found that the overexpression of Sema3A in tibiae suppressed the expansion of LECs and alleviated bone loss, whereas the injection of lentivirus expressing Sema3A short hairpin RNA (shRNA) into the tibiae caused GSD-like phenotypes. Histological staining further demonstrated that OCs decreased and osteocalcin increased after Sema3A lentiviral treatment, compared with the control. Based on the above results, we propose that reduced Sema3A in OCs is one of the mechanisms contributing to the pathogeneses of GSD and that expressing Sema3A represents a new approach for the treatment of GSD.
الموضوعات
Animals , Mice , Endothelial Cells/metabolism , Lymphatic Vessels , Osteoclasts/pathology , Osteolysis, Essential/pathology , Semaphorin-3A/metabolismالملخص
OBJECTIVES@#To investigate the clinical characteristics and risk factors of delayed bleeding after intestinal polypectomy in children, and to provide a theoretical basis for clinical surgical intervention of intestinal polyps.@*METHODS@#A retrospective analysis was conducted on the clinical data of 2 456 children with intestinal polyps who underwent endoscopic high-frequency electrocoagulation loop resection in the Endoscopy Center of Children's Hospital Affiliated to Zhengzhou University from January 2014 to December 2021. According to the presence or absence of delayed bleeding after surgery, they were divided into bleeding group with 79 children and non-bleeding group with 2 377 children. A multivariate logistic regression analysis was used to investigate the risk factors for delayed bleeding. The receiver operating characteristic (ROC) curve was used to investigate the value of various indicators in predicting delayed bleeding.@*RESULTS@#Of all 2 456 children, 79 (3.22%) experienced delayed bleeding, among whom 5 children with severe delayed bleeding underwent emergency colonoscopy for hemostasis and 74 received conservative treatment, and successful hemostasis was achieved for all children. There were significant differences between the bleeding and non-bleeding groups in age, body mass index, constipation rate, location of lesion, time of endoscopic procedure, resection method (P<0.05). Children with a diameter of polyps of 6-10 mm and >20 mm were more likely to develop delayed bleeding after resection (P<0.05). The multivariate logistic regression analysis showed that endoscopic operation time, polyp diameter, and resection method were significantly associated with delayed bleeding (P<0.05). The ROC curve analysis showed that the endoscopic operation time, polyp diameter, and resection method had a good value in predicting delayed bleeding after intestinal polypectomy, with an area under the ROC curve of 0.706, 0.688, and 0.627, respectively.@*CONCLUSIONS@#Endoscopic high-frequency electrocoagulation loop resection has a lower incidence of delayed bleeding in children with intestinal polyps, and the endoscopic operation time, polyp diameter, and resection method are closely associated with the occurrence of postoperative delayed bleeding.
الموضوعات
Child , Humans , Retrospective Studies , Intestines , Hemorrhage , Intestinal Polyps/surgery , Risk Factorsالملخص
OBJECTIVE To prepare anemoside B4 （AB4） and programmed cell death ligand 1 （PDL1） siRNA （siP） co- delivered cRGD-modified targeting liposomes （AB4/siP-c-L）， and to study the cellular uptake in vitro. METHODS The cRGD- modified AB4-loaded targeted liposomes （AB4-c-L） were prepared by ethanol injection. AB4-c-L was mixed with 20 nmol/L siP in the same volume and AB4/siP-c-L was obtained through electrostatic adsorption. The particle size， Zeta potential， morphology， encapsulation efficiency and drug content， in vitro release behavior and serum stability of AB4/siP-c-L were investigated by laser scattering particle size tester， transmission electron microscopy， ultrafiltration centrifugation， dialysis and agar-gel electrophoresis block test. Cellular uptake of AB4/siP-c-L by Lewis lung cancer cells LLC and its intracellular localization were evaluated by flow cytometry and confocal laser scan technique. RESULTS The average particle size of AB4/siP-c-L was （187.4±3.1） nm， and the Zeta potential was （33.5±1.4） mV. AB4/siP-c-L was spheroidal in shape. The encapsulation efficiency and content of AB4 were （95.2±0.4） % and （1.0±0.2） mg/mL， respectively. AB4/siP-c-L could better package siP， and exhibited good serum stability， obvious pH sensitivity and sustained release property. The uptake rate of AB4/siP-c-L by LLC cells was significantly higher than that of free drug， and was able to accumulate in cytoplasm. CONCLUSIONS AB4/siP-c-L can effectively realize the co-loading of AB4 and gene drug siP， which has certain in vitro targeting to LLC cells.
الملخص
Objective To identify M1 macrophage-related genes in rejection after kidney transplantation and construct a risk prediction model for renal allograft survival. Methods GSE36059 and GSE21374 datasets after kidney transplantation were downloaded from Gene Expression Omnibus (GEO) database. GSE36059 dataset included the samples from the recipients with rejection and stable allografts. Using this dataset, weighted gene co-expression network analysis (WGCNA) and differential analysis were conducted to screen the M1 macrophage-related differentially expressed gene (M1-DEG). Then, GSE21374 dataset (including the follow-up data of graft loss) was divided into the training set and validation set according to a ratio of 7∶3. In the training set, a multivariate Cox's model was constructed using the variables screened by least absolute shrinkage and selection operator (LASSO), and the ability of this model to predict allograft survival was evaluated. CIBERSORT was employed to analyze the differences of infiltrated immune cells between the high-risk group and low-risk group, and the distribution of human leukocyte antigen (HLA)-related genes was analyzed between two groups. Gene set enrichment analysis (GSEA) was used to further clarify the biological process and pathway enrichment in the high-risk group. Finally, the database was employed to predict the microRNA (miRNA) interacting with the prognostic genes. Results In the GSE36059 dataset, 14 M1-DEG were screened. In the GSE21374 dataset, Toll-like receptor 8 (TLR8), Fc gamma receptor 1B (FCGR1B), BCL2 related protein A1 (BCL2A1), cathepsin S (CTSS), guanylate binding protein 2(GBP2) and caspase recruitment domain family member 16 (CARD16) were screened by LASSO-Cox regression analysis, and a multivariate Cox's model was constructed based on these 6 M1-DEG. The area under curve (AUC) of receiver operating characteristic of this model for predicting the 1- and 3-year graft survival was 0.918 and 0.877 in the training set, and 0.765 and 0.736 in the validation set, respectively. Immune cell infiltration analysis showed that the infiltration of rest and activated CD4+ memory T cells, γδT cells and M1 macrophages were increased in the high-risk group (all P < 0.05). The expression level of HLA I gene was up-regulated in the high-risk group. GSEA analysis suggested that immune response and graft rejection were enriched in the high-risk group. CTSS interacted with 8 miRNA, BCL2A1 and GBP2 interacted with 3 miRNA, and FCGR1B interacted with 1 miRNA. Conclusions The prognostic risk model based on 6 M1-DEG has high performance in predicting graft survival, which may provide evidence for early interventions for high-risk recipients.
الملخص
OBJECTIVE@#To assess the value of copy number variation sequencing (CNV-seq) for the diagnosis of children with intellectual disability (ID), developmental delay (DD), and autistic spectrum disorder (ASD).@*METHODS@#Forty patients with ID/DD/ASD referred to Nanshan Maternity and Child Health Care Hospital from September 2018 to January 2022 were enrolled. G-banded karyotyping analysis was carried out for the patients. Genomic DNA was extracted from peripheral blood samples and subjected to CNV-Seq analysis to detect chromosome copy number variations (CNVs) in such patients. ClinVar, DECIPHER, OMIM and other database were searched for data annotation.@*RESULTS@#Among the 40 patients (including 30 males and 10 females), 16, 15 and 6 were diagnosed with ID, DD and ASD, respectively. One patient had combined symptoms of ID and DD, whilst the remaining two had combined ID and ASD. Four patients were found with abnormal karyotypes, including 47,XY,+mar, 46,XY,inv(8)(p11.2q21.2), 46,XX,del(5)(p14) and 46,XX[76]/46,X,dup(X)(p21.1q12). Chromosome polymorphism was also found in two other patients. CNV-seq analysis has detected 32 CNVs in 20 patients (50.0%, 20/40). Pathogenic CNVs were found in 10 patients (25.0%), 15 CNVs of uncertain clinical significance were found in 12 patients (30.0%), and 7 likely benign CNVs were found in 4 patients (10.0%).@*CONCLUSION@#Chromosome CNVs play an important role in the pathogenesis of ID/DD/ASD. CNV-seq can detect chromosomal abnormalities including microdeletions and microduplications, which could provide a powerful tool for revealing the genetic etiology of ID/DD/ASD patients.