Objective To investigate the effect of glycine N-methyl transferase (GNMT)on intrauterine adhesion (IUA)fibrosis and its related mechanism.Methods In vivo experiment:A total of 36 healthy female SD rats (SPF grade,6～8 weeks old and weighing from 180～220 g)were subjected in this study.IUA model of SD rats and IUA model of GNMT overexpressed rats were established.RT-qPCR and immunofluorescence assay were applied to detect GNMT expression level in normal uterus and model group.RT-qPCR and Western blotting were used to detect the mRNA and protein levels of fibrosis-related molecules and the activation of TGF-β1/Smad3 signaling pathway in each group.The number of endometrial glands in each group was observed by HE staining.Masson staining was used to analyze the severity of endometrial fibrosis in each group.In vitro experiment:transformed human endometrial stromal cells (THESCs)fibrotic phenotype model was constructed using TGF-β1,and THESCs stably transfected with GNMT overexpression lentvirus were treated with TGF-β1.RT-qPCR and Western blotting were used to detect the mRNA and protein expression of fibrosis-related molecules.The expression of TGF-β1/Smad3 signaling pathway was detected by Western blotting.TGF-β1/Smad3 signaling pathway was activated by TGF-β1/Smad signaling pathway activator (SRI-011381),and the expression of TGF-β1/Smad3 signaling pathway and key molecular proteins of fibrosis phenotype was measured with Western blotting.Results In vivo experiment,the mRNA and protein expression levels of GNMT were significantly decreased in the IUA rats than the control rats (P<0.05).Overexpression of GNMT decreased the mRNA and protein levels of fibrosis related molecules,Collagen Ⅰ,Collagen Ⅲ and FN in the IUA rats (P<0.05),and decreased the phosphorylation levels of TGF-β1 and its downstream Smad3 protein (P<0.05).HE and Masson staining showed that overexpression of GNMT could increase the number of endometrial glands and reduce the severity of fibrosis in the IUA rats (P<0.05).In vitro experiments:overexpression of GNMT decreased the mRNA and protein levels of Collagen Ⅰ,Collagen Ⅲ and FN associated with fibrotic phenotype of THESCs (P<0.05),and reduced the phosphorylation level of Smad3 protein,downstream of TGF-β1 (P<0.05).After activation of TGF-β1/Smad3 signaling pathway,the protein levels of TGF-β1/Smad3 signaling pathway and downstream fibrosis phenotype molecules,Collagen Ⅲ and FN,were significantly decreased in the LV-GNMT+SRI-011381 group.Conclusion Overexpression of GNMT can inhibit endometrial fibrosis by regulating TGF-β1/Smad3 signaling pathway,thus achieving therapeutic effect on IUA.

Objective:To understand the current clinical practice status of evidence on blood glucose management in ICU patients with insulin intravenous infusion, analyze barriers and formulate action strategies, so as to provide reference for the translation of evidence into clinical practice.Methods:Based on the clinical evidence application model of the Joanna Briggs Institute (JBI) Evidence-Based Health Care Center, clinical nursing problems were identified, literature search, evaluating and summarizing evidence were carried out, and review indicators and methods were developed. From July to August 2023, convenience sampling was used to select 42 nurses and 80 patients with insulin intravenous infusion from the comprehensive ICU of Wuxi Second People's Hospital as participants for baseline review. Barriers were analyzed and change strategies were developed based on baseline review results.Results:A total of 16 pieces of evidence were introduced regarding blood glucose management in ICU patients with insulin intravenous infusion. Nineteen review indicators were formulated, of which 13 had a compliance rate of less than 60%. Analysis identified 18 barriers and 13 facilitators. Sixteen change strategies were developed based on barriers and facilitators.Conclusions:There is still a significant gap between the evidence of ICU insulin intravenous infusion blood glucose management and clinical practice. Evidence-based practice programs should be constructed based on intervention strategies to effectively promote the application of evidence in clinical practice.

Objective To retrieve,evaluate and summarize the best evidence on the management of ocular complications in intensive care patients ventilated in prone position,and to provide references for clinical practice.Methods Evidence on management of ocular complications in intensive care patients ventilated in prone position was systemically retrieved in the guideline websites,professional association websites and databases,such as the BMJ Best Practice,UpToDate,Cochrane Library,Joanna Briggs Institute,PubMed,Web of Science,Science Direct,Embase,CNKI,Wanfang and other databases,including guidelines,clinical decisions,evidence summaries,expert consensuses,group standards,systematic reviews and scoping reviews,published from January 2013 to June 2023.The guidelines were individually evaluated by 4 researchers,and the remaining literature was individually evaluated by 2 researchers.The literature that met the criteria was extracted and graded.Results A total of 15 articles were involved,including 6 guidelines,2 clinical decisions,2 evidence summaries,3 systematic reviews,1 scoping review and 1 group standard.Finally,6 evidence topics and 16 pieces of best evidence were formed,including organization and training,risk identification,eye assessment,eye protection,position management and regular observation.Conclusion This study summarized the best evidence on the management of ocular complications in intensive care patients ventilated in prone position.In the application,the best evidence should be selected according to the clinical situation,so as to reduce the incidence of ocular complications and improve the quality of life of patients.

Objective: To investigate of e-cigarette use among middle school students in Hainan Province, so as to provide insights into tobacco control among adolescents. Methods: Students were randomly sampled using a multistage stratified cluster random sampling method from three junior high schools, two high schools and one vocational high school in Hainan Province from July to October, 2021. Participants' basic features, use of e-cigarettes, e-cigarette advertising exposure were collected using the Questionnaire on Tobacco and Alcohol Prevalence among Chinese Adolescents in 2021 prepared by Chinese Center for Disease Control and Prevention. Following data weighting, students' use of e-cigarettes and exposure to e-cigarette advertisements were descriptively analyzed, and factors affecting current use of e-cigarettes were identified using a multivariable logistic regression model. Results: A total of 8 561 questionnaires were allocated, and 8 538 valid questionnaires were recovered, with an effective recovery rate of 99.73%. The respondents included 4 470 boys (52.35%) and 4 068 girls (47.65%), and there 4 367 junior high school students (51.15%), 3 482 high school students (40.78%), and 689 vocational high school students (8.07%). The rate of e-cigarette use was 25.01% and the rate of current e-cigarette use was 4.68%. There were 2 728 respondents with exposure to e-cigarette advertising during the past 30 days, and the number of weighted individuals were 210 932 (32.60%). The route of e-cigarette advertising exposure mainly included point-of-sale (21.59%), stores (13.61%), and shopping websites (9.01%). Multivariable logistic regression analysis identified region (OR=0.610, 95%CI: 0.482-0.772), males (OR=1.332, 95%CI: 1.062-1.669), high school students (OR=0.376, 95%CI: 0.259-0.545), companion smoking (OR=6.645, 95%CI: 4.935-8.948) and advertising exposure (OR=3.229, 95%CI: 2.581-4.040) as factors affecting current use of e-cigarettes. Conclusions The use of e-cigarettes among middle school students is higher in Hainan Province than the national level, and exposure to e-cigarette advertisements may facilitate use of e-cigarettes. It is necessary to strengthen the supervision of e-cigarettes, strictly restrict e-cigarettes advertisements and promotions.

Enzyme-driven micro/nanomotors consuming in situ chemical fuels have attracted lots of attention for biomedical applications. However, motor systems composed by organism-derived organics that maximize the therapeutic efficacy of enzymatic products remain challenging. Herein, swimming proteomotors based on biocompatible urease and human serum albumin are constructed for enhanced antitumor therapy via active motion and ammonia amplification. By decomposing urea into carbon dioxide and ammonia, the designed proteomotors are endowed with self-propulsive capability, which leads to improved internalization and enhanced penetration in vitro. As a glutamine synthetase inhibitor, the loaded l-methionine sulfoximine further prevents the conversion of toxic ammonia into non-toxic glutamine in both tumor and stromal cells, resulting in local ammonia amplification. After intravesical instillation, the proteomotors achieve longer bladder retention and thus significantly inhibit the growth of orthotopic bladder tumor in vivo without adverse effects. We envision that the as-developed swimming proteomotors with amplification of the product toxicity may be a potential platform for active cancer treatment.

AIM: To observe the effects of single-dose of fentanyl on sedation and agitation during recovery after pediatric adenotonsillectomy day surgery during anesthesia induction. METHODS: A total of 157 children undergoing elective adenotonsillectomy, with ASA physical status I or II, aged 3-10 years were selected during January and March in 2022 in the Second Affiliated Hospital of Wenzhou Medical University. The children were divided into two groups according to random number table method: remifentanil combined with fentanyl group (group RF, n = 78) and remifentanil group (group R, n = 79). Children in group RF received a single-dose injection of 1 μg/kg of fentanyl and 2.5 μg/kg of remifentanil during induction, children in group R received an equal volume of normal saline and 2.5 μg/kg of remifentanil injection. Children in both groups were intubated after propofol induction and anesthetized with combination of sevoflurane-remifentanil. The incidence and severity of emergence agitation (EA), Ramsay sedation score and FLACC pain score in post-anesthesia care unit (PACU), extubation time, recovery time, PACU stay time, discharge time were recorded. RESULTS: Compared with group R, the incidence of EA was significantly lower (38.0% vs. 18.0%, P = 0.005), the maximum PAED score during recovery was significantly lower (7.7 ±3.3 vs. 8.9 ± 3.4, P = 0.027), and the Ramsay sedation score was significantly higher at 15 min after admission of PACU (4.4 ± 1.1 vs. 3.8 ± 1.4, P = 0.01), as well as discharge of PACU (2.0 ± 0.3 vs. 1.8 ±0.4, P = 0.03) in RF group . There was no significant difference in extubation time, recovery time, PACU stay time, discharge time, pain score (discharge of PACU and 2 h after operation) between two groups (P > 0.05). CONCLUSION: A single-dose injection of fentanyl (1 μg/kg) during anesthesia induction can increase the degree of sedation and reduce the incidence of EA in PACU after pediatric daytime adenotonsillectomy.

Age-associated changes in immune cells have been linked to an increased risk for infection. However, a global and detailed characterization of the changes that human circulating immune cells undergo with age is lacking. Here, we combined scRNA-seq, mass cytometry and scATAC-seq to compare immune cell types in peripheral blood collected from young and old subjects and patients with COVID-19. We found that the immune cell landscape was reprogrammed with age and was characterized by T cell polarization from naive and memory cells to effector, cytotoxic, exhausted and regulatory cells, along with increased late natural killer cells, age-associated B cells, inflammatory monocytes and age-associated dendritic cells. In addition, the expression of genes, which were implicated in coronavirus susceptibility, was upregulated in a cell subtype-specific manner with age. Notably, COVID-19 promoted age-induced immune cell polarization and gene expression related to inflammation and cellular senescence. Therefore, these findings suggest that a dysregulated immune system and increased gene expression associated with SARS-CoV-2 susceptibility may at least partially account for COVID-19 vulnerability in the elderly.
Adult ; Aged ; Aged, 80 and over ; Aging ; genetics ; immunology ; Betacoronavirus ; CD4-Positive T-Lymphocytes ; metabolism ; Cell Lineage ; Chromatin Assembly and Disassembly ; Coronavirus Infections ; immunology ; Cytokine Release Syndrome ; etiology ; immunology ; Cytokines ; biosynthesis ; genetics ; Disease Susceptibility ; Flow Cytometry ; methods ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; Gene Rearrangement ; Humans ; Immune System ; cytology ; growth & development ; immunology ; Immunocompetence ; genetics ; Inflammation ; genetics ; immunology ; Mass Spectrometry ; methods ; Middle Aged ; Pandemics ; Pneumonia, Viral ; immunology ; Sequence Analysis, RNA ; Single-Cell Analysis ; Transcriptome ; Young Adult

ABSTRACT OBJECTIVE：To establish a method for simultaneous determination of 8 components in the lyophilized product of Chaihu shugan san decoction. METHODS：UPLC method was adopted to determine the contents of albiflorin，paeoniflorin，ferulic acid，naringin，hesperidin，benzoyl paeoniflorin，glycyrrhizic acid and α-cyperone in 6 batches of lyophilized product of Chaihu shugan san decoction. The determination was performed on Phenomenex column with mobile phase consisted of 0.1％ formic acid water-acetonitrile at the flow rate of 1 mL/min，the sample volume was 10 μL. The detection wavelength was set at 250 nm，and column temperature was 30 ℃. RESULTS：The linear range of albiflorin，paeoniflorin，ferulic acid，naringin，hesperidin，benzoyl paeoniflorin，glycyrrhizic acid and α-cyperone were 3.606-8.414，23.988-55.972，1.218-2.842，35.964-83.916，12.009-28.021， 1.194-2.786，3.609-8.421，5.294-12.352 μg/mL，respectively（r＝0.999 5-0.999 9）. The limits of quantitation were 0.206，0.178， 0.256，0.168，0.196，0.242，0.268，0.157 μg/mL，respectively. RSDs of precision，stability（12 h）and repeatability tests were all lower than 2％（n＝5 or 6）；the recoveries were 97.93％，98.18％，96.57％，97.61％，98.51％，97.45％，98.14％，96.91％（all RSD＜2％ ）. The average contents of albiflorin， paeoniflorin， ferulic acid， naringin， hesperidin， benzoyl guanosine， and glycyrrhizic acid in 6 batches of samples were 59.258，429.237，23.173，625.847，200.424，15.048，67.620 μg/g，respectively. α-cyperone was not detected because of its volatility. CONCLUSIONS：The method is simple，stable，reliable and accurate. It could provide reference for quality control of the lyophilized product of Chaihu shugan san decoction

Objective:To study the influence of the choice of main diagnosis on diagnosis-related groups(DRG) grouping and weight change, by taking cerebral infarction as the entry point.Methods:From January 1, 2019 to March 31, 2019, 331 patients in three DRG groups(BR25, BR23, BR21) with cerebral infarction were selected. The original group was used as the control group; the main diagnosis was exchanged with the first other diagnosis, then DRG group was used as the experimental group. The difference of the number of cases and weight between the two groups was analyzed.Results:41.4%(137/331) of the patients in the experimental group were enrolled in BZ11 with other neurological disorders associated with important comorbidities and comorbidities, and 82.5%(273/331) patients′ weight increased after diagnostic conversion.Conclusions:Choosing other diagnosis as the main diagnosis may change the weight of the disease and affect the corresponding disease benefit. In order to prevent downcoding, DRG grouping should be detailed, and DRG payment should consider how to reflect the value of difficult cases; for upcoding behavior, medical insurance center and relevant medical institutions should check the correctness of coding, and monitor in place.

Objective To investigate the colonization of Gram-negative bacilli carrying mcr-1 gene in intestinal tracts of inpatients and people having physical examination for further elucidating the molecular and epidemiological features of mcr-1 gene. Methods A total of 1263 and 750 fecal specimens were col-lected from inpatients in the First Affiliated Hospital of Guangzhou Medical University and people having physical examination in the Kingmed Physical Examination Centre, respectively. Drug-resistant bacteria were isolated using Maconkey agar supplemented with colistin. PCR was performed to detect the bacteria carrying mcr-1 gene. Multilocus sequence typing ( MLST) and enterobacterial repetitive intergenic consensus-PCR ( ERIC-PCR) were used for homology analysis. The transferability of mcr-1 gene was verified by plasmid transfer assays. Plasmids of mcr-1-carrying strains were typed by PCR-based replicon typing techniques. Twelve virulence-related genes were also detected by PCR. Results Ninety-two colistin-resistant strains were isolated from the 1263 samples from inpatients(7. 3％, 92/1263) and two of them were positive for mcr-1 gene ( one strain also carried the blaNDM-5 gene) . Thirty-six colistin-resistant strains were isolated from the 750 samples of physical examination group (4. 8％, 36/750) and one of them carried the mcr-1 gene. MLST analysis showed that three mcr-1-carrying Escherichia coli strains ( minimum inhibitory concentration of colistin:8 μg/ml) belonged to three different sequence types. Moreover, they exhibited different banding patterns in ERIC-PCR analysis. All of the mcr-1-carrying isolates could transfer mcr-1 gene to the recipient strains successfully. Six types of incompatibility plasmids were detected in the mcr-1-carrying isolates ( IncFⅡ, IncX2, IncHI2, IncFIB, IncX4 and IncX1). Virulence-related genes fimH, iutA and fyuA were detec-ted in all mcr-1-carrying Escherichia coli strains. Conclusions Colistin-resistant strains and mcr-1 gene are prevalent in inpatients and people having physical examination, which brings potential risk for the control of clinical infections.