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Potato (Solanum tuberosum L.) is cultivated worldwide for its underground tubers, which provide an important part of human nutrition and serve as a model system for belowground storage organ formation. Similar to flowering, stolon-expressed FLOWERING LOCUS T-like (FT-like) protein SELF-PRUNING 6A (StSP6A) plays an instrumental role in tuberization by binding to the bZIP transcription factors StABI5-like 1 (StABL1) and StFD-like 1 (StFDL1), causing transcriptional reprogramming at the stolon subapical apices. However, the molecular mechanism regulating the widely conserved FT-bZIP interactions remains largely unexplored. Here, we identified a TCP transcription factor StAST1 (StABL1 and StSP6A-associated TCP protein 1) binding to both StSP6A and StABL1. StAST1 is specifically expressed in the vascular tissue of leaves and developing stolons. Silencing of StAST1 leads to accelerated tuberization and a shortened life cycle. Molecular dissection reveals that the interaction of StAST1 with StSP6A and StABL1 attenuates the formation of the alternative tuberigen activation complex (aTAC). We also observed StAST1 directly activates the expression of potato GA 20-oxidase gene (StGA20ox1) to regulate GA responses. These results demonstrate StAST1 functions as a tuberization repressor by regulating plant hormone levels; our findings also suggest a mechanism by which the widely conserved FT-FD genetic module is fine-tuned.
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Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas , Tubérculos de la Planta , Solanum tuberosum , Factores de Transcripción , Solanum tuberosum/genética , Solanum tuberosum/metabolismo , Solanum tuberosum/fisiología , Solanum tuberosum/crecimiento & desarrollo , Tubérculos de la Planta/genética , Tubérculos de la Planta/crecimiento & desarrollo , Tubérculos de la Planta/metabolismo , Tubérculos de la Planta/fisiología , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Factores de Transcripción/metabolismo , Factores de Transcripción/genéticaRESUMEN
Prostate cancer (PCa), a prevalent malignancy among elderly males, exhibits a notable rate of advancement, even when subjected to conventional androgen deprivation therapy or chemotherapy. An effective progression prediction model would prove invaluable in identifying patients with a higher progression risk. Using bioinformatics strategies, we integrated diverse data sets of PCa to construct a novel risk model predicated on gene expression and progression-free survival (PFS). The accuracy of the model was assessed through validation using an independent data set. Eight genes were discerned as independent prognostic factors and included in the prediction model. Patients assigned to the high-risk cohort demonstrated a diminished PFS, and the areas under the curve of our model in the validation set for 1-year, 3-year, and 5-year PFS were 0.9325, 0.9041 and 0.9070, respectively. Additionally, through the application of single-cell RNA sequencing to two castration-related prostate cancer (CRPC) samples and two hormone-related prostate cancer (HSPC) samples, we discovered that luminal cells within CRPC exhibited an elevated risk score. Subsequent molecular biology experiments corroborated our findings, illustrating heightened SYK expression levels within tumour tissues and its contribution to cancer cell migration. We found that the knockdown of SYK could inhibit migration in PCa cells. Our progression-related risk model demonstrated the potential prognostic value of SYK and indicated its potential as a target for future diagnosis and treatment strategies in PCa management.
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Biología Computacional , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica , Neoplasias de la Próstata , Masculino , Humanos , Biología Computacional/métodos , Pronóstico , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/diagnóstico , Perfilación de la Expresión Génica , Biomarcadores de Tumor/genética , Factores de Riesgo , Línea Celular TumoralRESUMEN
Immune protection associated with consuming colostrum-based peptides is effective against bacterial and viral insults. The goal for this study was to document acute changes to immune surveillance and cytokine levels after consuming a single dose of a nutraceutical blend in the absence of an immune challenge. A double-blind, randomized, placebo-controlled, cross-over pilot study involved healthy participants attending two clinic visits. Blood draws were performed pre-consumption and at 1, 2, and 24 h after consuming a blend of bovine colostrum- and hen's egg-based low-molecular-weight peptides (CELMPs) versus a placebo. Immunophenotyping was performed by flow cytometry, and serum cytokines were measured by multiplex cytokine arrays. Consumption of CELMPs triggered increased immune surveillance after 1 h, involving monocytes (p < 0.1), natural killer (NK) cells (p < 0.1), and natural killer T (NKT) cells (p < 0.05). The number of NKT cells expressing the CD25 immunoregulatory marker increased at 1 and 2 h (p < 0.1). Increased serum levels of monocyte chemoattractant protein-1 (MCP-1) was observed at 2 and 24 h (24 h: p < 0.05). Selective reduction in pro-inflammatory cytokines was seen at 1, 2, and 24 h, where the 2-h reduction was highly significant for IL-6, IFN-γ, and IL-13. The rapid, transient increase in immune surveillance, in conjunction with the reduced levels of inflammatory markers, suggests that the CELMP blend of natural peptides provides immune benefits of use in preventive medicine. Further studies are warranted in chronic inflammatory conditions.
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OBJECTIVE: To explore the bidirectional relationship of late-onset epilepsy (LOE) with dementia and Alzheimer's disease (AD). METHODS: Using the common electronic databases, including PubMed, Cochrane Library databases and EMBASE, we systematically reviewed published cohort studies that assessed the risk of LOE in individuals comorbid with dementia or AD, and those with dementia or AD comorbid with LOE that had been published up to 31 March 2023. The data extraction process was carried out independently by two authors. The summary adjusted relative ratio (aRR) was calculated by employing Rev Man 5.3 for the inclusion of studies. To investigate the origins of heterogeneity, we conducted both subgroup and sensitivity analyses. In the presence of heterogeneity, a random-effects model was employed. To evaluate potential publication bias, we utilized the funnel plot and conducted Begg's and Egger's tests. RESULTS: We included 20 eligible studies in the final analysis after a rigorous screening process. Pooled results indicated that LOE was association with an increased risk of all-cause dementia (aRR: 1.34, 95% confidence interval [CI]: 1.13-1.59) and AD (aRR: 2.49, 95% CI: 1.16-5.32). In addition, the pooled effect size for LOE associated with baseline AD and all-cause dementia were 3.51 (95% CI: 3.47-3.56) and 2.53 (95% CI: 2.39-2.67), respectively. Both sensitivity and subgroup analyses showed that these positive correlations persisted. According to the results of the Egger's and Begg's tests, as well as visual inspection of funnel plots, none of the studies appeared to be biased by publication. CONCLUSION: The findings suggested that LOE is a potential risk factor for dementia and AD, and vice versa, dementia and AD are both potential risk indicators for LOE. Since there is substantial heterogeneity among the cohorts analyzed and more cohort studies should be conducted to confirm the correlations found in the current study.
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Demencia , Epilepsia , Humanos , Demencia/epidemiología , Demencia/etiología , Demencia/complicaciones , Epilepsia/epidemiología , Epilepsia/complicaciones , Estudios de Cohortes , Enfermedad de Alzheimer/epidemiología , Enfermedad de Alzheimer/complicaciones , Edad de Inicio , ComorbilidadRESUMEN
The detection of ascorbic acid (AA), dopamine (DA), and uric acid (UA) is crucial for understanding and managing various illnesses. In this research, Pt@g-C3N4 nanoparticles were synthesized via hydrothermal method and combined with N-doped carbon nanotubes (N-CNTs). The Pt@g-C3N4/N-CNTs-modified glassy carbon (GC) electrode was fabricated as an electrochemical sensor for the determination of AA, DA, and UA. The linear response range of AA, DA, and UA in the optimal condition was 100-3,000 µM, 1-100 µM, and 2-215 µM boasting a low detection limit (S/N = 3) of 29.44 µM (AA), 0.21 µM (UA), and 2.99 µM (DA), respectively. Additionally, the recoveries of AA, DA, and UA in serum sample were 100.4%-106.7%. These results corroborate the feasibility of the proposed method for the simultaneous, sensitive, and reliable detection of AA, DA, and UA. Our Pt@g-C3N4/N-CNTs/GC electrode can provide a potential strategy for disease diagnosis and health monitoring in clinical settings.
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Momelotinib-approved for treatment of myelofibrosis in adults with anemia-and its major active metabolite, M21, were assessed as drug-drug interaction (DDI) victims with a strong cytochrome P450 (CYP) 3A4 inhibitor (multiple-dose ritonavir), an organic anion transporting polypeptide (OATP) 1B1/1B3 inhibitor (single-dose rifampin), and a strong CYP3A4 inducer (multiple-dose rifampin). Momelotinib DDI perpetrator potential (multiple-dose) was evaluated with CYP3A4 and breast cancer resistance protein (BCRP) substrates (midazolam and rosuvastatin, respectively). DDI was assessed from changes in maximum plasma concentration (Cmax), area under the concentration-time curve (AUC), time to reach Cmax, and half-life. The increase in momelotinib (23% Cmax, 14% AUC) or M21 (30% Cmax, 24% AUC) exposure with ritonavir coadministration was not clinically relevant. A moderate increase in momelotinib (40% Cmax, 57% AUC) and minimal change in M21 was observed with single-dose rifampin. A moderate decrease in momelotinib (29% Cmax, 46% AUC) and increase in M21 (31% Cmax, 15% AUC) were observed with multiple-dose rifampin compared with single-dose rifampin. Due to potentially counteracting effects of OATP1B1/1B3 inhibition and CYP3A4 induction, multiple-dose rifampin did not significantly change momelotinib pharmacokinetics compared with momelotinib alone (Cmax no change, 15% AUC decrease). Momelotinib did not alter the pharmacokinetics of midazolam (8% Cmax, 16% AUC decreases) or 1'-hydroxymidazolam (14% Cmax, 16% AUC decreases) but increased rosuvastatin Cmax by 220% and AUC by 170%. Safety findings were mild in this short-term study in healthy volunteers. This analysis suggests that momelotinib interactions with OATP1B1/1B3 inhibitors and BCRP substrates may warrant monitoring for adverse reactions or dose adjustments.
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Benzamidas , Citocromo P-450 CYP3A , Pirimidinas , Ritonavir , Adulto , Humanos , Citocromo P-450 CYP3A/metabolismo , Rifampin/farmacología , Midazolam/farmacocinética , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2 , Rosuvastatina Cálcica/farmacocinética , Proteínas de Neoplasias/metabolismo , Interacciones Farmacológicas , Proteínas de Transporte de Membrana/metabolismoRESUMEN
Skin graft rejection is a significant challenge in skin allografts for skin defects, particularly in extensive burn injury patients when autografts are insufficient. Enhancing the survival duration of allogeneic skin grafts can improve the success rate of subsequent autologous skin grafting, thereby promoting the therapeutic efficacy for wound healing. Rapamycin (Rapa), a potent immunosuppressant with favorable efficacy in organ transplantation, is limited by its systemic administration-associated toxicity and side effects. Therefore, addressing the short survival time of allogeneic skin grafts and minimizing the toxicity related to systemic application of immunosuppressive agents is an urgent requirement. Here, we present a topical formulation based on bioadhesive poly (lactic acid)-hyperbranched polyglycerol nanoparticles (BNPs) with surface-modified encapsulation of Rapamycin (Rapa/BNPs), applied for local immunosuppression in a murine model of allogeneic skin grafts. Our Rapa/BNPs significantly prolong nanoparticle retention, reduce infiltration of T lymphocytes and macrophages, decrease the level of pro-inflammatory cytokines and ultimately extend skin allograft survival with little systemic toxicity compared to free Rapa or Rapamycin-loaded non-bioadhesive nanoparticles (Rapa/NNPs) administration. In conclusion, Rapa/BNPs effectively deliver local immunosuppression and demonstrate potential for enhancing skin allograft survival while minimizing localized inflammation, thus potentially increasing patient survival rates for various types of skin defects.
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Nanopartículas , Sirolimus , Humanos , Ratones , Animales , Inmunosupresores , Nanopartículas/uso terapéutico , Aloinjertos , Administración CutáneaRESUMEN
Hypoxia is a pervasive feature of solid tumors, which significantly limits the therapeutic effect of photodynamic therapy (PDT) and further influences the immunotherapy efficiency in breast cancer. However, the transient alleviation of tumor hypoxia fails to address the underlying issue of increased oxygen consumption, resulting from the rapid proliferation of tumor cells. At present, studies have found that the reduction of the oxygen consumption rate (OCR) by cytochrome C oxidase (COX) inhibition that induced oxidative phosphorylation (OXHPOS) suppression was able to solve the proposed problem. Herein, we developed a specific mitochondrial-targeting nanotrapper (I@MSN-Im-PEG), which exhibited good copper chelating ability to inhibit COX for reducing the OCR. The results proved that the nanotrapper significantly alleviated the hypoxic tumor microenvironment by copper chelation in mitochondria and enhanced the PDT effect in vitro and in vivo. Meanwhile, the nanotrapper improved photoimmunotherapy through both enhancing PDT-induced immunogenetic cell death (ICD) effects and reversing Treg-mediated immune suppression on 4T1 tumor-bearing mice. The mitochondrial-targeting nanotrapper provided a novel and efficacious strategy to enhance the PDT effect and amplify photoimmunotherapy in breast cancer.
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Nanopartículas , Neoplasias , Fotoquimioterapia , Animales , Ratones , Fotoquimioterapia/métodos , Cobre/farmacología , Hipoxia Tumoral , Línea Celular Tumoral , Neoplasias/tratamiento farmacológico , Hipoxia/tratamiento farmacológico , Inmunoterapia , Mitocondrias/metabolismo , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Fármacos Fotosensibilizantes/metabolismo , Microambiente TumoralRESUMEN
Hypertrophic scar development is a complication associated with wound healing, impacting local appearance and function. The type I/III collagen ratio affects the extent of hypertrophic scarring; a reduced ratio can ameliorate this. In this study, recombinant human collagen type III was developed. Liquid chromatography-tandem mass spectrometry was used to determine its amino acid sequence and confirm its high level of homology with natural human type III collagen. Recombinant human collagen type III displayed no cytotoxicity and did not confer skin irritation and sensitization. Immunofluorescence and western blot analyses of histidine following incubation with fibroblasts suggested cell entry of recombinant human collagen type III. Furthermore, recombinant human collagen type III promoted the synthesis of the natural type III collagen in fibroblasts, resulting in a more obvious increase of type III collagen content in fibroblasts than that of type I collagen, and then decreased the ratio of type I/III collagen. The results of 5-ethynyl-2'-deoxyuridine staining assay suggested enhanced fibroblast proliferation. Following local injection of recombinant human collagen type III, rabbit ear scarring was significantly reduced after 60 days. Vancouver Scar Scale evaluation showed that all index scores were significantly reduced. Western blotting and Picro-Sirius red staining showed that the natural type III collagen increase in scar tissue was greater than that of type I collagen, decreasing the type I/III ratio. In summary, recombinant human collagen type III can be taken up by fibroblasts and promote natural collagen synthesis-especially that of type III-thereby reducing the type I/III ratio and improving hypertrophic scarring.
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Intraperitoneal co-delivery of chemotherapeutic drugs (CDs) and immune checkpoint inhibitors (ICIs) brings hope to improve treatment outcomes in patients with peritoneal metastasis from ovarian cancer (OC). However, current intraperitoneal drug delivery systems face issues such as rapid drug clearance from lymphatic drainage, heterogeneous drug distribution, and uncontrolled release of therapeutic agents into the peritoneal cavity. Herein, we developed an injectable nanohydrogel by combining carboxymethyl chitosan (CMCS) with bioadhesive nanoparticles (BNPs) based on polylactic acid-hyperbranched polyglycerol. This system enables the codelivery of CD and ICI into the intraperitoneal space to extend drug retention. The nanohydrogel is formed by cross-linking of aldehyde groups on BNPs with amine groups on CMCS via reversible Schiff base bonds, with CD and ICI loaded separately into BNPs and CMCS network. BNP/CMCS nanohydrogel maintained the activity of the biomolecules and released drugs in a sustained manner over a 7 day period. The adhesive property, through the formation of Schiff bases with peritoneal tissues, confers BNPs with an extended residence time in the peritoneal cavity after being released from the nanohydrogel. In a mouse model, BNP/CMCS nanohydrogel loaded with paclitaxel (PTX) and anti-PD-1 antibodies (αPD-1) significantly suppressed peritoneal metastasis of OC compared to all other tested groups. In addition, no systemic toxicity of nanohydrogel-loaded PTX and αPD-1 was observed during the treatment, which supports potential translational applications of this delivery system.
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Quitosano , Sistemas de Liberación de Medicamentos , Hidrogeles , Inhibidores de Puntos de Control Inmunológico , Nanocompuestos , Neoplasias Ováricas , Neoplasias Peritoneales , Animales , Hidrogeles/química , Neoplasias Peritoneales/tratamiento farmacológico , Neoplasias Peritoneales/secundario , Neoplasias Peritoneales/patología , Ratones , Quitosano/química , Quitosano/análogos & derivados , Femenino , Inhibidores de Puntos de Control Inmunológico/farmacología , Inhibidores de Puntos de Control Inmunológico/química , Inhibidores de Puntos de Control Inmunológico/administración & dosificación , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/patología , Nanocompuestos/química , Humanos , Antineoplásicos/química , Antineoplásicos/farmacología , Antineoplásicos/administración & dosificación , Ratones Endogámicos BALB C , Glicerol/química , Glicerol/análogos & derivados , Línea Celular Tumoral , Polímeros/química , PoliésteresRESUMEN
BACKGROUND:It has been shown that long non-coding RNA(lncRNA)plays an important role in the development and progression of cardiac diseases,and whether it is involved in daisy leaf gentianone antagonizing adriamycin-induced cardiac injury in mice has not been reported. OBJECTIVE:To screen differentially expressed lncRNAs in myocardial tissue of mice with adriamycin-induced myocardial injury antagonized with daisy leaf gentianone and conduct a bioinformatics analysis. METHODS:Forty-eight C57 mice were randomly divided into normal group,model group,daisy leaf gentianone group and positive drug group,with 12 mice in each group.The mice in the model group,daisy leaf gentianone group and positive drug group were injected with adriamycin intraperitoneally once every other day for 8 times in total.The daisy leaf gentianone group and positive drug group were given daisy leaf gentianone suspension and captopril solution by gavage based on adriamycin injection once a day for 21 continuous days.After medication,mice in each group underwent electrocardiogram examination and the myocardial tissue was taken for pathomorphological observation.At the same time,high-throughput sequencing analysis of mouse myocardial tissue was carried out,differentially expressed lncRNAs were screened,and target genes were predicted for differentially expressed lncRNAs.Gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes signaling pathway analyses of target genes were performed. RESULTS AND CONCLUSION:The ST segment of the electrocardiogram of mice in the model group was significantly elevated.Compared with the model group,the degree of ST-segment elevation on the electrocardiogram was reduced in the daisy leaf gentianone group.Results from hematoxylin-eosin,Masson,and Sirius red staining indicated that in the model group,the myocardial cytoplasm was unevenly colored with varying shades of color,the integrity and continuity of myocardial fibers were poor,and a large number of collagen fibers were deposited.After treatment with gentianone daisy leaves,the abnormalities in myocardial tissue of mice were improved.The results of high-throughput sequencing analysis showed that compared with the model group,a total of 270 lncRNAs were identified in the myocardial tissue of mice in the daisy leaf gentianone group,including 165 up-regulated and 105 down-regulated lncRNAs.Combining the experimental results with related literature,three lncRNAs(NONMMUT149833.1,NONMMUT003237.2,and ENSMUST00000219015)and four related mRNAs(Alas2,Igf2,Acta1,and Cilp)were finally identified.The results of target gene prediction,gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes signaling pathway analyses showed that differentially expressed lncRNAs in myocardial tissue of mice with myocardial injury could regulate the expression of their target protein-coding genes through cis-and/or trans-regulation,and participate in regulating molecular functions and biological processes.To conclude,daisy leaf gentianone significantly improves cardiac function and partial lncRNA expression in mice with adriamycin-induced myocardial injury.
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Objective To investigate the protective effect and mechanism of oleanolic acid(OA)on kidneys in rats with type 2 diabetes mellitus(T2DM).Methods A total of 35 Sprague-Dawley(SD)rats were enrolled in this study.25 SD rats were randomly selected to establish T2DM model,after modeling,20 rats remained and divided into T2DM group(n=6),low-dose oleanolic acid group(LOA,n=6)and high-dose oleanolic acid group(HOA,n=8).And ten rats were selected as normal control group(NC,n=10).The biochemical indicators,24 h urine volume and 24 h urinary microalbumin(UAlb)were compared among the four groups.Renal lipid deposition was evaluated by Oil red O staining.The protein expressions of Adenosine 5'-monophosphate-activated protein kinase(AMPK),p-AMPK and peroxisome proliferator-activated receptor γ coactivator-1 α(PGC-1 α)were detected by Western blot.Results Compared with the NC group,the levels of 24 h urine volume,fasting blood glucose(FPG),serum total cholesterol(TC),triglyceride(TG),low density lipoprotein cholesterol(LDL-C),serum creatinine(Scr),serum uric acid(SUA)and 24 hUAlb were increased(P<0.05),while the body weight,high density lipoprotein cholesterol(HDL-C),p-AMPK and PGC-1α were decrease in the T2DM group(P<0.05).Compared with the T2DM group,the expressions of HDL-C,p-AMPK and PGC-1α were increased(P<0.05),while the levels of 24 h urine volume,FPG,TG,TC and LDL-C,Scr,SUA and 24 hUAlb were decreased in the LOA and HOA groups(P<0.05).Compared with LOA group,the expressions of HDL-C,p-AMPK and PGC-1α were increased(P<0.05),while the levels of 24 h urine volume,FPG,TG,TC,LDL-C,Scr,SUA and 24 h UAlb were decreased in the HOA group(P<0.05).Compared with the NC group,a large number of red-stained lipid droplets were deposited in the renal tubular epithelial cells in the T2DM group.Compared with the T2DM group,the lipid droplet deposition was reduced in the LOA and HOA groups,and the improvement was more significant in the HOA group.Conclusion OA can alleviate renal injury in T2DM rats,which may be linked to activation of AMPK/PGC-1α pathway.
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Objective To protect the economic benefits of the hospital by improving the medical record quality,quality control ability,and standardising the filling of the medical insurance settlement list.Methods Re-quality control of previous malignant tumour cases,with the help of the intelligent health insurance case collaboration system,compare the changes in case entry and benchmark costs after the revision of errors,analyse the results caused by different errors,and summarise the correct experience.Results Erroneous disease diagnoses can lead to losses or suspected fraud in health insurance billing,affecting the economic operation of healthcare organisations.Conclusion The improvement of the quality of the medical insurance settlement list not only needs to improve the quality of case writing,coding level,but also needs to read the connotation of the policy through extensive study.
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Objective To investigate whether E.coli infection increases surgical site infection and postoperative fever in comparison with other pathogens.Methods A retrospective cohort study was conducted on 506 patients who underwent urethral segment resection and end anastomosis for the bulb or posterior urethral stenosis in our department during 2011 and 2019.According to occurrence of postoperative surgical site infection(SSI)or postoperative fever(POF),they were divided into SSI group(n=19)and non-SSI group(n=487),as well as POF group(n=61)and non-POF group(n=445 patients)respectively.Multivariate logistic regression analysis and LASSO algorithm were used to screen the potential risk factors.According to the results of positive preoperative urine culture in 302 patients,they were subsequently divided into E.coli infection group(n=80)and other pathogen infection group(n=222),and after reducing potential bias with propensity score matching,finally 48 patients were assigned into E.coli infection group,and 192 into other pathogen infection groups.The differences in occurrences of SSI and POF were compared between the above 2 groups of patients.Results Multivariate logistic regression analysis and LASSO algorithm revealed that positive preoperative urine culture was an independent risk factor for predicting SSI(P=0.012)and POF(P<0.01).Among the 302 patients with positive results in preoperative urine culture,E.coli infections was in the first rank,accounting for 26.5%.After propensity score matched treatment,the incidence of SSI in the E.coli group and other pathogen groups was 29.2%and 2.1%,respectively(P<0.01).The incidence of POF was also higher in the E.coli infection group than the other pathogen infection group(27.1%vs 13.5%,P=0.02).Conclusion Preoperative E.coli infection may increase the risk of SSI and POF after urethroplasty when compared with other pathogen infections.
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Objective To analyze the budget impact of a price increase for carotid endarterectomy(CEA)on the total expenditure of health insurance expenditure in China.Methods We set 2021 as the base year,and 2022-2026 as the study years.A budget impact analysis model was developed to calculate the expenditure of health insurance funds over the next 5 years following a 30%price increase for carotid endarterectomy.Data on the target population,treatment costs,and market share changes both nationwide and in four sample cities were used.The data was collected in May to Jul 2022.Results The price increase for carotid endarterectomy will reduce total health insurance fund expenditures nationwide by 143.176 2 million yuan over five years.Total health insurance fund expenditures in the sample cities will also decrease to varying degrees.The higher the price increase for the surgical procedure,the greater the decrease in total expenditure of the health insurance fund.The market share of the surgical procedure has the greatest impact on the total expenditure of the health insurance fund.Conclusion Increasing the price of carotid endarterectomy may lead to increase in its market share and decline in the health insurance fund expenditures in future five years.
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【Objective】 To explore the diagnostic value of platelet long non-coding RNA (lncRNA) as a biomarker for early screening of lung adenocarcinoma (LUAD). 【Methods】 The GSE183635 and GSE89843 datasets, which contained the platelet transcriptome of LUAD and healthy controls, were used for differential analysis, and the intersection of the differentially expressed lncRNA(DElncRNA) of the two datasets was taken. The expression levels of DElncRNA in LUAD tissues and normal control tissues were analyzed using GEPIA2. The expression levels of LINC01088 in platelets of 51 healthy controls and 54 LUAD patients were detected by quantitative Real-time PCR (qRT-PCR), and the diagnostic ability of each index was evaluated by ROC curve. 【Results】 8 DElncRNAs and 1 265 DElncRNAs were obtained from GSE183635 and GSE89843 datasets, respectively. The key DElncRNA LINC01088 was selected after intersection. GEPIA2 analysis showed that the expression level of LINC01088 in LUAD tissues was lower than that in normal lung tissues (P<0.05). Platelet LINC01088 was significantly downregulated in patients with LUAD and early-stage LUAD than in healthy controls(P<0.001). The area under the curve (AUC) of platelet LINC01088 in the diagnosis of LUAD was 0.755, the sensitivity was 81.1%, and the specificity was 67.9%. The AUC for early LUAD diagnosis was 0.727, the sensitivity was 80.0%, and the specificity was 67.9%. The AUC of the combined diagnostic model composed of platelet LINC01088 and carcinoembryonic antigen (CEA) for LUAD diagnosis was 0.807, the sensitivity was 89.2%, and the specificity was 71.4%. The AUC for early LUAD was 0.770, the sensitivity was 86.7%, and the specificity was 71.4%. The combined diagnostic model of platelet LINC01088 and CEA was superior to CEA in the diagnosis of LUAD and early LUAD (Z=-2.288, -2.34, both P<0.05). 【Conclusion】 LINC01088 is down-regulated in platelets of LUAD patients. Platelet LINC01088 may be a biomarker for early screening and diagnosis of LUAD.
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Objective To compare the value of standard coronal MRI and multi-planar reconstruction(MPR)images for evaluation of anterolateral ligament(ALL).Methods Data of 130 patients who underwent knee joint MR examination were retrospectively analyzed,including standard coronal MRI and MPR images.ALL were identified on standard coronal MRI and MPR images and classified as fully visible,partially visible or invisible.The visibility of bilateral ALL on both standard coronal MRI and MPR images were compared,while Kappa test was used to evaluate the consistency on both kinds of images.Results Among 130 cases,on standard coronal MRI and MPR images,the left ALL was fully visible in 83 and 93 cases,partially visible in 21 and 12 cases but invisible cases in 26 and 25 cases,respectively,while the right side ALL was fully visible in 66 and 80 cases,partially visible cases in 29 and 15 cases but invisible cases each in 35 cases,respectively.Significant difference of visibility of bilateral ALL were found between standard coronal MRI and MPR images(both P<0.05),both with excellent consistency(both Kappa>0.80).Conclusion MPR could display bilateral ALL better than standard coronal MRI.If the scanning conditions for MPR could not be met,standard coronal MRI might be used to evaluate ALL rather accurately.
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Objective To understand the current status and trends of research on the TCM treatment for stable phase of chronic obstructive pulmonary disease(COPD);To provide references for relevant research.Methods Literature about TCM treatment for stable phase of COPD was retrieved from China National Knowledge Infrastructure,Wanfang Data,VIP Information Chinese Journal Service Platform,and SinoMed from the establishment of the databases to Sep 1,2022.NoteExpress 3.4 was used to sort out the basic data of papers.Excel 2016 was employed to count first authors,syndrome type,prescription and draw a run chart of publication,determine the number of journals in the core area according to Bradford law.Core authors statistically were analyzed according to Price law.Author collaboration network and keyword co-occurrence analysis were conducted using VOSviewer 1.6.18.CiteSpace 5.3.R4 was exploited to construct institutional collaboration network and study burst terms,and knowledge map was drawn.Results A total of 3 360 articles were included,involving 445 journals,with 2 691 first authors.The overall number of publications in this field showed an increasing trend,with clinical research being the main research type.There were 21 journals in the core region and the most frequently published journal was New Chinese Medicine.There were 125 core authors,with Li Zhuying and Li Jiansheng posting the most articles.Author collaboration network analysis showed 10 major research teams and the largest of which was Li Jiansheng's team.There were 1 451 institutions,mainly were universities and affiliated hospitals.There were 62 types of syndromes in the stable phase of COPD,the most common of which was the syndrome of qi deficiency of lung and spleen.There were 541 kinds of prescriptions in total,and the most commonly used was Bufei Decoction.Keyword co-occurrence analysis showed 8 subjects,and the high-frequency keywords included lung function,clinical efficacy,quality of life,clinical observation and TCM treatment.22 burst terms were obtained,with Budesonide Fumotro,six-word songs,Yupingfeng Powder and inflammatory factors highly concerned at present.Conclusion The research fever of TCM treatment for COPD in stable period shows an increasing trend,and clinical research accounts for the largest proportion,but the general quality is not high,and basic research is relatively lacking.The research focuses on the inhibition of airway inflammation and immune regulation,and lung function and quality of life are the most commonly used evaluation indicators.
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Objective:The quality of domestic diagnostic accuracy research was evaluated to explore the quality level of domestic diagnostic accuracy research based on Standards for Reporting of Diagnostic Accuracy 2015 (STARD2015).Methods:The Chinese core journals of CNKI and Wanfang Database were searched, and research literature on diagnostic accuracy published from 2017 to 2022 were collected. The main search terms are diagnostic test, sensitivity, specificity, receiver operating characteristic (ROC) curve, etc. The literature was selected according to the inclusion criteria, and the quality of the included literature was evaluated independently by two reviewers, and the conformity rate of the STARD2015 report and the STARD2015 article was calculated. The report quality of the literature was divided into three levels (low, medium and high) according to the conformity rate of the STARD2015 report. The proportion of literature at each level and the proportion of literature at medium and high level in each year were counted. According to quality analysis on the contents of the included articles, articles were divided into standardized reports and unstandardized reports. Intragroup correlation coefficient ( ICC) was used to analyze the consistency of two reviewers. The trend Chi-square test was used to analyze the trend of the proportion of medium and high level literature in each year. One-way analysis of variance was used to compare the coincidence rates evaluated by STARD2015 for each year. Results:A total of 6 771 studies on diagnostic accuracy published from 2017 to 2022 were included. The compliance rate sccording to STARD2015 was 39.56%±4.90%, and the reported compliance rate ranged from 17.65% to 64.71% (the number of reported items ranged from 6 to 22), and 93.53% (6 333/6 771) literatures were in the middle level. Compliance rate of STARD2015 reports varied significantly among different years ( F=25.023, P<0.01), and the compliance rate of 2021 was significantly higher than that of other years ( P<0.01). The proportion of medium and high level literatures according to STARD2015 showed an increasing trend ( χ 2=14.099, P<0.01). The reporting situation of each item varied significantly, and the conformity rate of items raned from 0 to 100%. According to report item, non-standard report rate was 10.34% (569/5 503) for item 6, 4.15% (277/6 677) for item 8, 21.84% (1 447/6 626) for item 20, 66.67% (24/36) for item 22, and 26.03% (877/3 369) for item 26. Conclusions:The overall report quality of published domestic literature on diagnostic accuracy from 2017 to 2022 is at a medium level according to STARD2015, and the reports conformity rate of each item vary significantly, indicating significant knowledge gap on STARD2015 among domestic researchers. The promotion of STARD2015 needs to be strengthened.
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Methamphetamine (METH) is a powerful stimulant drug that can cause addiction and serious health problems. It is one of the most widely abused drugs in the world. However, the mechanisms of how METH affects the brain and leads to addiction are still unclear, and there are no effective treatments for METH addiction in clinical practice. Therefore, it is important to explore the new addiction mechanisms and treatment strategies of METH. METH addiction is a complex and chronic brain disorder that involves multiple brain regions and neurotransmitter systems. Neurotransmitters are chemical messengers that transmit signals between neurons (nerve cells) in the brain. Some of the main neurotransmitters involved in METH addiction are dopamine (DA), glutamate (Glu), norepinephrine (NE), and serotonin (SNRIS). These neurotransmitters regulate various aspects of brain function, such as reward, reinforcement, motivation, cognition, emotion, and behavior. When a person takes METH, it causes a surge of these neurotransmitters in the brain, especially in the prefrontal cortex (mPFC), ventral tegmental area (VTA), and nucleus accumbens (NAc). These brain regions form a circuit called the mesocorticolimbic system, which is responsible for mediating the rewarding and reinforcing effects of drugs and natural stimuli. The increased levels of neurotransmitters in this circuit make the person feel euphoric, alert, confident, and energetic. However, repeated or chronic use of METH can also cause negative effects, such as anxiety, paranoia, psychosis, depression, and cognitive impairment. The effects of METH on the brain are not only due to the changes in neurotransmitter levels, but also to the changes in gene expression. Gene expression is the process by which genes are turned on or off to produce proteins that perform various functions in the cells. Gene expression can be influenced by environmental factors, such as drugs, stress, diet, etc. One way that environmental factors can affect gene expression is through epigenetic mechanisms. Epigenetics is a branch of genetics that studies the heritable changes in gene expression that are not caused by changes in DNA sequence. Epigenetic mechanisms include histone modifications, DNA methylation, and non-coding RNA regulation. These mechanisms can modulate the chromatin structure and accessibility, thereby affecting the transcriptional activity of genes. Chromatin is a complex of DNA and proteins that forms the chromosomes in the nucleus of the cell. The chromatin structure can be altered by adding or removing chemical groups to histones (proteins that wrap around DNA) or DNA itself. These chemical groups can either activate or repress gene expression by changing the affinity of transcription factors (proteins that bind to DNA and initiate transcription) or other regulatory molecules. Non-coding RNAs are RNA molecules that do not code for proteins but can regulate gene expression by interacting with DNA, RNA, or proteins. Epigenetic mechanisms provide a link between environmental stimuli and gene expression, and play an important role in various physiological and pathological processes, including drug addiction. Recent studies have shown that epigenetic mechanisms are involved in the regulation of neurotransmitter systems and neural plasticity in response to METH exposure. Neural plasticity is the ability of neurons to change their structure and function in response to experience or injury. Neural plasticity is essential for learning, memory, adaptation, and recovery. The expression of some genes related to METH addiction is altered by epigenetic modifications, such as histone acetylation, methylation, ubiquitination, and non-coding RNA regulation. These epigenetic changes may affect the synaptic function and morphology, neuronal connectivity, and circuitry formation in the brain regions implicated in METH addiction. Moreover, some epigenetic modifications may persist for a long time after METH withdrawal, suggesting that they may contribute to the development and maintenance of METH addiction. In this article, we review the current literature on the epigenetic mechanisms of METH addiction. We will first introduce METH and its pharmacological effects, and then discuss the epigenetic regulation of neurotransmitter systems and neural plasticity by METH. We will focus on the changes of histone, DNA, and RNA during METH addiction, and the possible causes and consequences of their relationship with METH addiction. We will also provide some perspectives on the potential applications of epigenetic interventions for METH addiction treatment.