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1.
Biopreserv Biobank ; 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38452333

RESUMO

Objective: Amniotic fluid (AF) plays a crucial role in diagnosing and predicting perinatal diseases, specifically preeclampsia (PE). Adequate preservation of AF samples is essential for advancing the development of PE-related biomarkers and understanding the disease's mechanisms. Materials and Methods: This study presents a method for preserving proteins in AF on a solid medium, specifically a nitrocellulose membrane, which is referred to as an AF membrane. Samples were collected from normotensive subjects and PE patients and treated with direct freezing and the AF membrane methods, respectively. Protein quality was assessed through sodium dodecyl sulfate-page and capillary electrophoresis. Liquid chromatography tandem mass spectrometry (LC-MS/MS) with data-independent acquisition was employed for proteomic analysis. Bioinformatics analysis identified differentially expressed proteins and pathways distinguishing normotensive subjects from PE patients. Results: Comparison of the AF membrane method to the direct freezing method showed no significant impact on the protein content in the AF. The preservation methods employed did not result in evident protein differences or degradation in the AF obtained from both normotensive subjects and PE patients. Analysis based on Gene Ontology and HALLMARK gene sets revealed the upregulation of pathways associated with angiotensin, reactive oxygen species, and coagulation in PE patients. Furthermore, several biomarkers previously reported to be increased in PE serum, namely ENG, ERN1, FLT1, GDF15, HSPA5, LGALS3, PAPPA, PTX3, and SERPINE1, were significantly elevated in the AF. Conclusion: The AF membrane method proved to be highly effective, reliable, and durable for preserving proteins in AF samples. Preserving AF samples in a solid state holds significant value in discovering novel protein biomarkers and investigating the underlying mechanisms of PE.

2.
Bioorg Med Chem Lett ; 104: 129725, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38555073

RESUMO

Natural product structures have long provided valuable pharmacophores and even candidates for drug discovery. Tanshinone scaffold showed moderately inhibitory activity in NLRP3 inflammasome/IL-1ß pathway. Herein, we designed a series of derivatives on different regions of Tanshinone IIA (TNA) scaffold. The biological evaluation identified compound T10, a scaffold hybrid of TNA and salicylic acid, as a potent NLRP3 inflammasome inhibitor. Mechanistically, T10 inhibits the production of ROS and prevents NLRP3 inflammasome-dependent IL-1ß production. In addition, treatment with T10 significantly attenuated inflammatory response in DSS-induced peritonitis. Our work describes a potential tanshinone-based derivative, which needs to be further structurally optimized as NLRP3 inflammasome inhibitors for treating inflammatory disorders.


Assuntos
Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Inflamassomos/metabolismo , Abietanos/farmacologia , Interleucina-1beta/metabolismo
3.
Postgrad Med J ; 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38507221

RESUMO

BACKGROUND: Mechanical ventilation, as an important respiratory support, plays an important role in general anesthesia and it is the cornerstone of intraoperative management of surgical patients. Different from spontaneous respiration, intraoperative mechanical ventilation can lead to postoperative lung injury, and its impact on surgical mortality cannot be ignored. Postoperative lung injury increases hospital stay and is related to preoperative conditions, anesthesia time, and intraoperative ventilation settings. METHOD: Through reading literature and research reports, the relationship between perioperative input parameters and output parameters related to mechanical ventilation and ventilator-related complications was reviewed, providing reference for the subsequent setting of input parameters of mechanical ventilation and new ventilation strategies. RESULTS: The parameters of inspiratory pressure rise time and inspiratory time can change the gas distribution, gas flow rate and airway pressure into the lungs, but there are few clinical studies on them. It can be used as a prospective intervention to study the effect of specific protective ventilation strategies on pulmonary complications after perioperative anesthesia. CONCLUSION: There are many factors affecting lung function after perioperative mechanical ventilation. Due to the difference of human body, the ventilation parameters suitable for each patient are different, and the deviation of each ventilation parameter can lead to postoperative pulmonary complications. Inspiratory pressure rise time and inspiratory time will be used as the new ventilation strategy.

4.
Eur J Pharmacol ; 965: 176331, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38220140

RESUMO

Inflammatory bowel disease (IBD) is a condition characterized by inflammation in the gastrointestinal tract. Reducing intestinal inflammation is a promising approach for treating IBD. The nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome, a critical component of the innate immune system, is implicated in the pathogenesis of IBD. Therefore, inhibiting NLRP3 inflammasome activation is a potential therapeutic strategy for IBD. In this study, we investigated the effects of the interleukin-5 (IL-5) receptor antagonist YM-90709 on dextran sulfate sodium-induced experimental colitis in mice. We found that YM-90709 reduced the expressions of IL-1ß and caspase-1 p20 in the colon and ameliorated colitis. Furthermore, we identified YM-90709 as an effective agent for inhibiting NLRP3 inflammasome activation. Knockdown of IL-5 receptor or using an inhibitor of STAT5, a key transcription factor downstream of the IL-5/IL-5 receptor signal pathway, also reduced NLRP3 inflammasome-dependent IL-1ß release and ASC speck formation. Our study is the first to demonstrate that the NLRP3 inflammasome may be a downstream signal of IL-5/IL-5 receptor and that YM-90709 protects against IBD by inhibiting IL-5 receptor. These findings suggest a new strategy for regulating intestinal inflammation and managing IBD.


Assuntos
Colite , Doenças Inflamatórias Intestinais , Animais , Camundongos , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Sulfato de Dextrana/toxicidade , Receptores de Interleucina-5 , Interleucina-5/efeitos adversos , Colite/induzido quimicamente , Colite/tratamento farmacológico , Inflamação , Caspase 1/metabolismo , Interleucina-1beta/metabolismo , Camundongos Endogâmicos C57BL
5.
Acta Pharmaceutica Sinica ; (12): 188-197, 2024.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1005428

RESUMO

The correct pairing of disulfide bonds maintains the correct folding mode and high-level structure formation of peptides and protein drugs, which is crucial for the quality control of products. In order to ensure that the disulfide bonds are correctly paired, disulfide bond analysis is an essential part of peptides and protein drug characterization. Mass spectrometry can be used to analyze disulfide bonds. However, insulin and its analogues have two pairs of disulfide bonds without restriction enzyme cutting site. Conventional collision-induced dissociation (CID) and high-energy induced cleavage (HCD) cannot accurately locate the complex disulfide bond. In our study, three methods were used to localize the complex disulfide, including enzyme digestion combined with key peptide fragment in source decay (ISD) fragmentation method, enzyme digestion combined with partial reduction alkylation method, intact protein source ISD and electron transfer dissociation (ETD) cleavage method, The applicability of insulin aspart, insulin lispro and insulin glargine were also investigated. This study provides a new way for the quality control of disulfide bonding mode of insulin and its analogues, and also provides a reference for the disulfide bond localization of peptides or proteins containing this complex disulfide bond.

6.
Nat Prod Res ; : 1-7, 2023 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-37794774

RESUMO

A new tetrahydroimidazopyridine named butyl (5R,6R,7S,8S)-5,6,7,8-tetrahydro-6,7,8-trihydroxy-5-(hydroxymethyl)imidazo[1,2-a]pyridine-2-carboxylate(1), together with eight known compounds (2-9), were isolated from the fermentation broth of a marine-derived fungus Paraconiothyrium sp. YK-03. Their chemical structures were elucidated by extensive analysis of one-dimensional and two-dimensional NMR spectroscopy, HR-ESIMS and optical rotation. Among these compounds, compound 1 represented a rare tetrahydroimidazopyridine, and compounds 2-7 were isolated from the Paraconiothyrium species for the first time. A plausible biosynthetic pathway for compound 1 was proposed.

7.
Front Microbiol ; 14: 1276928, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37849925

RESUMO

Cyclodepsipeptides are a large family of peptide-related natural products consisting of hydroxy and amino acids linked by amide and ester bonds. A number of cyclodepsipeptides have been isolated and characterized from fungi and bacteria. Most of them showed antitumor, antifungal, antiviral, antimalarial, and antitrypanosomal properties. Herein, this review summarizes the recent literatures (2010-2022) on the progress of cyclodepsipeptides from fungi and bacteria except for those of marine origin, in order to enrich our knowledge about their structural features and biological sources.

8.
Cardiol Rev ; 31(6): 293-298, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37796966

RESUMO

Lipid-lowering therapy with statins is well recognized as an effective therapy in reducing adverse cardiovascular events. However, the relationship between statin therapy and progression of coronary artery calcification (CAC) is unclear. A few of studies suggested that statins fail to slow and even accelerate progression of CAC; meanwhile, some researchers demonstrate opposite results. With the purpose of seeking out the effect of statin therapy on CAC, we summarized the existing evidence on statins and undertook meta-analyses of clinical trials assessing the effect of statin therapy on CAC. Fourteen trials were identified suitable for inclusion in the analysis of the effect of statin treatment on CAC, of which 11 were randomized controlled trails, 1 was case-control study, 1 was cross-sectional study, and 1 was observational study. In the meta-analysis of CAC progression, statin therapy seemed to accelerate the progression of CAC. Meanwhile, the analysis revealed a significant correlation between statin treatment and lower risk of cardiovascular events. In conclusion, meta-analyses of the available trials have shown a significant reduction of risk of cardiovascular events. In contrast, statins accelerated CAC. This suggests that statin-mediated atheroma calcification may enhance plaque stability and reduce the risk of plaque rupture.


Assuntos
Doença da Artéria Coronariana , Inibidores de Hidroximetilglutaril-CoA Redutases , Placa Aterosclerótica , Calcificação Vascular , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Estudos de Casos e Controles , Estudos Transversais , Calcificação Vascular/prevenção & controle , Calcificação Vascular/induzido quimicamente , Calcificação Vascular/tratamento farmacológico , Doença da Artéria Coronariana/prevenção & controle , Doença da Artéria Coronariana/tratamento farmacológico , Fatores de Risco , Estudos Observacionais como Assunto
10.
Zhongguo Zhong Yao Za Zhi ; 48(11): 2981-2988, 2023 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-37381958

RESUMO

Paris rugosa(Melanthiaceae) only grows in Yunnan province of China at present, and its chemical constituents have not been systematically studied. In this study, nine compounds, including one new compound pariposide G(1) and eight known compounds of cerin(2), stigmast-4-en-3-one(3), ß-ecdysone(4), ophiopogonin C'(5), methyl protogracillin(6), gracillin(7), parissaponin H(8), and parisyunnanoside G(9), were isolated and identified from the ethanol extract of P. rugosa rhizomes by column chromatography methods and semi-preparative high-performance liquid chromatography(HPLC). Compounds 1-9 were isolated from this plant for the first time. The antibacterial and antifungal activities of all the compounds were evaluated. The results showed that ophiopogonin C' had strong inhibitory effects on Candida albicans [MIC_(90)=(4.68±0.01) µmol·L~(-1)] and the fluconazole-resistant strain of C. albicans [MIC_(90)=(4.66±0.02) µmol·L~(-1)].


Assuntos
Liliaceae , Melanthiaceae , Antibacterianos , Candida albicans , China , Rizoma
11.
Fitoterapia ; 168: 105553, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37257697

RESUMO

Three undescribed lignan glycosides, echiunines E-G (1-3), as well as eight known compounds (4-11) were isolated from Fritillaria verticillata Willd. Among them, compounds 1-3 were a series of lignan glycosides reported for the first time from genus Fritillaria. Their structures were elucidated by analyses of extensive spectroscopic data and comparison of the NMR data with those reported previously, the absolute configuration of compounds were further confirmed by calculated ECD method. The NO release inhibitory effects of compounds were evaluated in LPS-activated RAW264.7 macrophages. Compounds 7-8 showed inhibitory acitivities in a dose-dependent manner.


Assuntos
Fritillaria , Lignanas , Lignanas/farmacologia , Lignanas/química , Estrutura Molecular , Glicosídeos/farmacologia , Glicosídeos/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química
12.
Phytochemistry ; 211: 113691, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37100221

RESUMO

Three undescribed santalane-type sesquiterpenoids (parasantalenoic acids A-C) and two undescribed epimeric isobenzofuranones (paraphthalides A and B) were isolated from cultures of the marine mud-associated fungus Paraconiothyrium sporulosum YK-03. Their structures were elucidated by analysis of the extensive spectroscopic and crystal X-ray diffraction data, combined with ECD calculations and comparison. Santalane-type sesquiterpenoids have been firstly found in the Paraconiothyrium species. Parasantalenoic acids A-C represent three rare polyhydroxylated santalane-type sesquiterpenoid carboxylic acids, and parasantalenoic acid A represents the first example of 2-chlorinated santalane-type sesquiterpenoid. A plausible biosynthetic pathway for parasantalenoic acids A-C was proposed. Additionally, the anti-neuroinflammatory activities of parasantalenoic acids A-C were investigated by evaluating their inhibitory effects on nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated BV-2 microglia cells. Among them, parasantalenoic acid C showed significant anti-neuroinflammatory activity with an inhibition of 86.45 ± 2.45% at 10 µM.


Assuntos
Ascomicetos , Sesquiterpenos , Sesquiterpenos/química , Ascomicetos/química , Análise Espectral , Estrutura Molecular
13.
Magn Reson Chem ; 61(7): 443-447, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36960574

RESUMO

A new amide tricholomine C was isolated from the dried fruiting bodies of Tricholoma bakamatsutake. Its structure was identified by a combination of nuclear magnetic resonance spectroscopic analysis and electronic circular dichroism (ECD) calculations. The ethyl alcohol crude extract and tricholomines A-C from T. bakamatsutake were evaluated for neuroprotective activities. Of these substances, the crude extract showed weak neurite outgrowth-promoting activity in rat pheochromocytoma (PC12) cells, as well as weak inhibitory activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE).


Assuntos
Acetilcolinesterase , Butirilcolinesterase , Ratos , Animais , Butirilcolinesterase/análise , Acetilcolinesterase/análise , Amidas/farmacologia , Amidas/análise , Carpóforos/química , Misturas Complexas/análise
14.
Phytochemistry ; 207: 113581, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36592859

RESUMO

Four undescribed and two known cucurbitane-type triterpenoids, including two heterodimers, elaeocarpudubins A and B, were isolated from the branches of Elaeocarpus dubius (Elaeocarpaceae). The chemical structures of these undescribed isolates were determined by analyses of 1D and 2D NMR and MS data, electronic circular dichroism (ECD) calculations, and chemical transformation. Biogenetically, elaeocarpudubins A and B might be derived from cucurbitacin F through Michael addition with vitamin C and (-)-catechin, respectively. These six isolates were evaluated for their cytotoxic activities against human leukemia HL-60, human lung adenocarcinoma A549, human hepatoma SMMC-7721, human breast cancer MCF-7, human colon cancer SW480, and paclitaxel-resistant A549 (A549/Taxol) cell lines, for their antioxidant properties using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay, and for their differentiation effects on nerve growth factor (NGF)-mediated neurite outgrowth in rat pheochromocytoma PC12 cells. Cucurbitacins F (IC50 of 4.98-38.11 µM) and D (IC50 of 0.03-4.40 µM) showed growth-inhibitory activities against these six cancer cell lines. Elaeocarpudubin B (IC50 of 61.04 µM) and elaeocarpudoside B (IC50 of 6.93 µM) showed antioxidant activities. Elaeocarpudubin B and elaeocarpudoside B also showed neurite outgrowth-promoting activities in PC12 cells at a concentration of 10 µM.


Assuntos
Elaeocarpaceae , Triterpenos , Ratos , Animais , Humanos , Antioxidantes/farmacologia , Estrutura Molecular , Triterpenos/química , Células PC12 , Esqueleto , Elaeocarpaceae/química
15.
Front Med (Lausanne) ; 10: 1269221, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38173939

RESUMO

Objective: Previous studies have proposed that genetic polymorphisms of CYP2D6*10, ADRB1, NPPA, CYP3A5*3, ACE, CYP2C9*3, and AGTR1 are involved in antihypertensive pharmacogenomics. The purpose of this study is to develop an amplification analysis using double allele-specific (AS) binding primers for accurate measurement of antihypertensive pharmacogenomics. Methods: To establish a quadruplex quantitative PCR (qPCR) analysis for genotyping of CYP2D6*10, ADRB1 (1165 G>C), NPPA (2238 T>C) and CYP3A5*3, and a triplex qPCR analysis for genotyping of ACE (I/D), CYP2C9*3 and AGTR1 (1166 A>C), mismatch AS F-primers were screened by detection of plasmid/gDNA, and were validated by agreement analysis/reproducibility evaluation, in which the ΔCq (differences in threshold cycles between the wild-type F-primer-based amplification assay and the mutant-type F-primer-based amplification assay) was employed to determine genotypes. Results: Seven pairs of primers were successfully selected through three rounds of F-primers screening. Except for ADRB1, the robustness assessment showed the amplification efficiency ranging from 0.9 to 1.1. In agreement analysis, two specimens in the training set (n = 203) were defined by the triplex analysis rather than NGS as heterozygotes for ACE, which was evidenced by gel electrophoresis. Reproducibility evaluation demonstrated that the coefficient of variation (CV) was <5%. Conclusion: Multiplex amplification analysis using screened AS binding primers is a simple, reliable, and accurate tool to guide drug delivery in antihypertensive personalized treatment.

16.
Cancer Research and Clinic ; (6): 185-192, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-996210

RESUMO

Objective:To investigate the value of SHOX2 and RASSF1A gene promoter region methylation detection for screening and diagnosis of early-stage lung adenocarcinoma.Methods:The mRNA sequencing data of 471 lung adenocarcinoma patients and corresponding methylation data of 413 cases were downloaded from The Cancer Genome Atlas (TCGA) database, the methylation levels of SHOX2 and RASSF1A gene promoter regions were calculated, and the difference in methy lation level between normal lung tissues and tumor tissues was analyzed. The clinical data of 54 patients with early-stage lung adenocarcinoma and 31 patients with benign lung tumors who underwent surgery at Drum Tower Hospital Affiliated to Nanjing University Medical School from January 2018 to January 2019 were retrospectively analyzed. The methylation status of SHOX2 and RASSF1A in tumor tissues and normal lung tissues (>5 cm from the edge of the tumor foci) (called clinical samples) was detect, and a positive methylation in the promoter region of either gene was considered as a combination of two genes methylation positivity. Using pathological diagnosis as the gold standard, the efficacy of gene methylation positivity in diagnosing early-stage lung adenocarcinoma was analyzed by receiver operating characteristic (ROC) curve. Patients with >80% of tumor cells in paraffin samples were screened, and mRNA high-throughput sequencing was performed in their tumor tissues and normal lung tissues. The relationship between positive methylation of the two genes and clinicopathological features was analyzed, and the correlation between the promoter region methylation level of the two genes and mRNA expression levels in clinical samples and TCGA database samples was analyzed by Spearman method. Gene set variance analysis (GSVA) method was used to analyze the differences in Kyoto Encyclopedia of Genes and Genomes enrichment pathways between two-gene methylation-positive clinical lung adenocarcinoma samples and corresponding methylation-negative lung adenocarcinoma.Results:In TCGA database, the SHOX2 promoter region methylation island contained 6 sequenced methylation sites, of which sites cg04532033 and cg01557547 methylation levels were higher in lung adenocarcinoma tissues than in normal lung tissues (both P < 0.05); the RASSF1A gene promoter region methylation island contained 11 sequenced methylation sites, and the methylation levels of 6 of these sites in lung adenocarcinoma tissues were higher than those in normal lung tissues (all P < 0.05). Compared with normal lung tissues, the methylation level of SHOX2 promoter region was higher in stage Ⅰ and Ⅱ lung adenocarcinoma tissues (both P < 0.05); the methylation level of RASSF1A promoter region was higher in all stages of lung adenocarcinoma ( P < 0.001). Among 54 patients with early-stage lung adenocarcinoma, 28 were positive for SHOX2 promoter region methylation in tumor tissues, 21 were positive for RASSF1A promoter region methylation, and 40 were positive for combined methylation of both genes; 31 benign lung nodules were negative for SHOX2 and RASSF1A methylation. ROC curve analysis showed that the sensitivity of positive SHOX2 promoter region methylation for diagnosing early-stage lung adenocarcinoma was higher than that of RASSF1A promoter region methylation positivity (51.8% vs. 38.9%), and the area under the curve (AUC) for diagnosis by two-gene methylation positivity was larger than that for diagnosis by SHOX2 or RASSF1A gene methylation positivity alone (0.870 vs. 0.759 and 0.694). The circulating thresholds (Ct) of SHOX2 and RASSF1A methylation tested by real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) in stage Ⅰ and Ⅱ lung adenocarcinoma were lower than those in normal lung tissues (all P < 0.05); patients with two-gene methylation positivity were characterized by older age, longer tumor longest diameter and more advanced pathological stage compared with patients with two-gene methylation negativity (all P < 0.05). In clinical stage Ⅰ-Ⅱ lung adenocarcinoma samples, the Ct of SHOX2 and RASSF1A promoter region methylation tested by qRT-PCR was negatively correlated with their mRNA relative expression levels ( r=-0.43, P = 0.003; r = -0.48, P = 0.001); in TCGA database stage Ⅰ-Ⅱ lung adenocarcinoma samples, the level of SHOX2 promoter region methylation was negatively correlated with its mRNA relative expression level ( r = -0.23, P < 0.001), and the level of RASSF1A promoter region methylation was also negatively correlated with its mRNA relative expression level, but without statistical difference ( r = -0.05, P = 0.310). In two-gene promoter methylation-positive lung adenocarcinoma samples, the pathways related to folate metabolism and DNA stability were upregulated, and the pathways related to vasoconstriction and cell growth and differentiation were downregulated. Conclusions:The combined detection of SHOX2 and RASSF1A promoter region methylation can be used as an indicator for screening and diagnosis of early-stage lung adenocarcinoma. Abnormal promoter region methylation of the two genes may affect multiple tumor-related pathways and promote the occurrence and progression of early-stage lung adenocarcinoma.

17.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-996043

RESUMO

Objective:To analyze the experiences and practice in the reform of public hospital salary system in Sichuan province, summarize the typical modes of such reform in the province, and provide references for further reform.Methods:As of October 29, 2021, the research group received 77 sets of typical experience materials submitted by the health commissions and public hospitals in Sichuan province on enforcing the reform of the public hospital salary system. The analysis framework was based on the five main elements proposed in the Guidance to Deepening the Reform of the Salary System of Public Hospitals for the purpose of furthering the reform. These five elements refer to " reasonably determining the level of salary in public hospitals" " fully implementing the autonomy of internal distribution in public hospitals " " establishing and improving the incentive and restraint mechanism for the remuneration of public hospital leaders" " improving the assessment and evaluation mechanism oriented to public welfare" and " funding sources ". A quantitative analysis was made on the typical experience materials using the social network analysis method, while a qualitative analysis was made on the typical experience materials using the content analysis method. Results:The results of social network analysis showed that the network density was 0.272; the highest point centrality was " fully implement the autonomy of internal distribution in public hospitals" (0.935), and the highest intermediary centrality was " improving the assessment and evaluation mechanism oriented to public welfare" (0.870), while the closeness to centrality of " establishing and improving the incentive and constraint mechanism for the salary of public hospital leaders" (0.434) and " funding sources" (0.421) were relatively low. The results of content analysis showed that the ones with higher frequency among all the typical experience materials were " fully implementing the autonomy of internal distribution of hospitals" (72 times) and " improving the assessment and evaluation mechanism oriented to public welfare" (67 times), while the ones with lower frequency were " establishing and improving the salary incentive and constraint mechanism for public hospital leaders" (17 times) and " funding sources" (14 times). In terms of unity and synergy, the typical models of public hospital salary system reform in the province could be categorized as the fine standard mode, the fair value mode, the autonomous synergy mode and the circular symbiosis mode.Conclusions:Deepening the reform of the salary system of public hospitals should unify the standards and improve the fair and refined assessment and evaluation mechanism; explore various forms of distribution and build an internal autonomous and synergistic incentive mechanism; pay attention to the weak remuneration incentive mechanism for hospital leaders and the problem of a relatively single source of funding.

18.
Acta Physiologica Sinica ; (6): 153-159, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-980992

RESUMO

This study was aimed to investigate the effect of hypoxia on lipopolysaccharide (LPS)-induced CXC-chemokine ligand-10 (CXCL10) expression and the underlying mechanism. C57BL/6J mice were randomly divided into control, hypoxia, LPS, and hypoxia combined with LPS groups. The LPS group was intraperitoneally injected with 0.5 mg/kg LPS, and the hypoxia group was placed in a hypobaric hypoxia chamber (simulated altitude of 6 000 m). The serum and hippocampal tissue samples were collected after 6 h of the treatment. The levels of CXCL10 in the serum and hippocampal tissue of mice were detected by ELISA. The microglia cell line BV2 and primary microglia were stimulated with hypoxia (1% O2) and/or LPS (100 ng/mL) for 6 h. The mRNA expression level of CXCL10 and its content in culture supernatant were detected by real-time quantitative PCR and ELISA, respectively. The phosphorylation levels of nuclear factor κB (NF-κB) signaling pathway-related proteins, p65 and IκBα, were detected by Western blot. Moreover, after NF-κB signaling pathway being blocked with a small molecular compound, PDTC, CXCL10 mRNA expression level was detected in the BV2 cells. The results showed that in the LPS-induced mouse inflammatory model, hypoxia treatment could promote LPS-induced up-regulation of CXCL10 in both serum and hippocampus. Compared with the cells treated with LPS alone, the expression of CXCL10 mRNA and the content of CXCL10 in the culture supernatant of BV2 cells treated with hypoxia combined with LPS were significantly increased. The CXCL10 mRNA level of primary microglial cells treated with hypoxia combined with LPS was significantly up-regulated. Compared with the cells treated with hypoxia or LPS alone, the phosphorylation levels of p65 and IκBα in the BV2 cells treated with hypoxia combined with LPS were significantly increased. PDTC blocked the induction of CXCL10 gene expression by LPS in the BV2 cells. These results suggest that hypoxia promotes LPS-induced expression of CXCL10 in both animal and cell models, and NF-κB signaling pathway plays an important role in this process.


Assuntos
Animais , Camundongos , Quimiocinas CXC/farmacologia , Hipóxia , Ligantes , Lipopolissacarídeos/farmacologia , Camundongos Endogâmicos C57BL , Microglia/metabolismo , NF-kappa B/metabolismo , Inibidor de NF-kappaB alfa/farmacologia , RNA Mensageiro/metabolismo
19.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-978414

RESUMO

ObjectiveTo describe the neuropsychological development screening of 0‒2 years in Tongzhou from 2017 to 2021 so as to understand the status and trend of developmental delay (DD). MethodsAnnual report data of 21 community health service centers in Tongzhou District from 2017 to 2021 were clustered, Chi square test was used to analyze the differences in positive rate and DD rate of children aged 0‒2 years with different ages and household registration, and Chi square trend test was used to analyze the linear trend of each age group and household registration. The Gesell test results in 762 children with developmental delay were analyzed, and Chi square test was used to compare the age distribution differences in gross motor, fine motor, language and personal-social behaviors. ResultsThe DD rate of children aged 0‒2 years in 2017‒2021 was 0.43%. A decreasing trend of DD rate in the 0‒ age group was observed (χ2=14.135, P<0.001), while an increasing trend of DD rate in the 1‒ and <3 age groups was observed (χ2=5.375, P=0.020; χ2=5.558, P=0.018). The DD rate of children aged 0‒2 years with Beijing household registration was higher (χ2=12.504, P<0.001). The DD rate of gross motor was the highest in the 0‒ age group (64.60%), the DD rate of language was the highest in the <3 age group (85.97%), and a statistically significant difference of gross motor and language was separately found in the three age groups (χ2=183.061, P<0.001; χ2=78.450, P<0.001). ConclusionAge and Beijing household registration are the influencing factors of DD for children aged 0‒2, and 0‒ years and <3 years are the critical periods for guidance and intervention to promote the development of gross motor and language abilities.

20.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-989065

RESUMO

Group B streptococcus(GBS), also known as streptococcus agalactis, is a Gram-positive conditionally causative coccus that can colonize healthy humans.GBS is a common pathogen of bacterial meningitis in infants under 3 months of age.GBS serotype Ⅲ and sequence type 17(ST 17)are the most common and virulent, and there is a significant correlation between serotype Ⅲ and ST 17, and erythromycin resistance is high.Penicillin or ampicillin is the first-line drug in China.Children with GBS meningitis are at high risk of poor prognosis.Intrapartum antibiotic prophylaxis(IAP)may be given in the presence of specific risk factors for GBS invasion in newborns. IAP reduced the incidence of early-onset GBS, but did not significantly reduce early-onset mortality and late-onset morbidity.

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