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1.
Mar Drugs ; 22(4)2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38667778

RESUMO

Bacillus cereus, a common food-borne pathogen, forms biofilms and generates virulence factors through a quorum sensing (QS) mechanism. In this study, six compounds (dankasterone A, demethylincisterol A3, zinnimidine, cyclo-(L-Val-L-Pro), cyclo-(L-Ile-L-Pro), and cyclo-(L-Leu-L-Pro)) were isolated from the endophytic fungus Pithomyces sacchari of the Laurencia sp. in the South China Sea. Among them, demethylincisterol A3, a sterol derivative, exhibited strong QS inhibitory activity against B. cereus. The QS inhibitory activity of demethylincisterol A3 was evaluated through experiments. The minimum inhibitory concentration (MIC) of demethylincisterol A3 against B. cereus was 6.25 µg/mL. At sub-MIC concentrations, it significantly decreased biofilm formation, hindered mobility, and diminished the production of protease and hemolysin activity. Moreover, RT-qPCR results demonstrated that demethylincisterol A3 markedly inhibited the expression of QS-related genes (plcR and papR) in B. cereus. The exposure to demethylincisterol A3 resulted in the downregulation of genes (comER, tasA, rpoN, sinR, codY, nheA, hblD, and cytK) associated with biofilm formation, mobility, and virulence factors. Hence, demethylincisterol A3 is a potentially effective compound in the pipeline of innovative antimicrobial therapies.


Assuntos
Antibacterianos , Bacillus cereus , Biofilmes , Testes de Sensibilidade Microbiana , Percepção de Quorum , Percepção de Quorum/efeitos dos fármacos , Bacillus cereus/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Antibacterianos/farmacologia , Laurencia/microbiologia , Fatores de Virulência , China , Endófitos
2.
J Org Chem ; 89(8): 5498-5510, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38577943

RESUMO

Reactions allowing chemodivergence prove to be attractive strategies in synthetic organic chemistry. We herein described a highly practical, transition-metal-free, highly regioselective and chemodivergent cascade reaction controlled by fluorine sources, which involved a [3 + 2] cycloaddition or C-arylation process between aryne precursors and 3-aminomaleimides. These two pathways led to a wide scope of structurally diverse pyrrolo[3,4-b]indoles (19 examples) and 3-arylated maleimides (25 examples) in good-to-excellent yields. Furthermore, the reaction could be scaled up, and several synthetic transformations were accomplished for the preparation of functionalized molecules and might provide new opportunities for the discovery of N-heterocyclic drugs.

3.
J Org Chem ; 89(8): 5266-5276, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38592168

RESUMO

A transition metal-free concise and efficient protocol for the synthesis of thiocyanated aminomaleimides and benzo[e][1,4]thiazepine derivatives has been developed. The method involves an initial α-C-H thiocyanation of aminomaleimides with KSCN and TEMPO-mediated tandem S-CN bond cleavage/intramolecular cyclization substitution processes, which enables the formation of seven-membered S/N-heterocycles. This synthetic strategy provides a reliable method for the synthesis of biologically interesting benzo[e][1,4]thiazepine derivatives by using KSCN as sulfur sources as well as expands the application of enaminones thiocyanation reactions in heterocycles synthesis.

4.
BMC Anesthesiol ; 24(1): 124, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38561683

RESUMO

BACKGROUND: This study aimed to investigate the impact of intraoperative hypothermia on the recovery period of anesthesia in elderly patients undergoing abdominal surgery. METHODS: A prospective observational study was conducted based on inclusion and exclusion criteria. A total of 384 elderly patients undergoing abdominal surgery under general anesthesia were enrolled in a grade A tertiary hospital in Chengdu, Sichuan Province from October 2021 and October 2022. After anesthesia induction, inflatable warming blankets were routinely used for active heat preservation, and nasopharyngeal temperature was monitored to observe the occurrence of intraoperative hypothermia. Patients were divided into hypothermia group and nonhypothermia group according to whether hypothermia occurred during the operation. Anesthesia recovery time and the incidence of adverse events or unwanted events during anesthesia recovery between the two groups were compared. RESULTS: The numbers (percentage) of 384 patients who underwent abdominal surgery developed intraoperative hypothermia occurred in 240 (62.5%) patients, all of whom had mild hypothermia. There were statistically significant differences between mild hypothermia after active warming and nonhypothermia in the occurrence of shivering (χ2 = 5.197, P = 0.023) and anesthesia recovery time (Z = -2.269, P = 0.02) in elderly patients undergoing abdominal surgery during anesthesia recovery, and there were no statistically significant differences in hypoxemia, nausea or vomiting, hypertension, hypokalemia, hypocalcemia, analgesic drug use,postoperative wound infection or postoperative hospitalization days. CONCLUSIONS: The incidence of intraoperative mild hypothermia after active warming was high in elderly patients who underwent abdominal surgery. Mild hypothermia increased the incidence of shivering and prolonged anesthesia recovery time in elderly patients undergoing abdominal surgery.


Assuntos
Hipotermia , Humanos , Idoso , Hipotermia/epidemiologia , Hipotermia/etiologia , Temperatura Corporal , Anestesia Geral/efeitos adversos , Tremor por Sensação de Frio , Infecção da Ferida Cirúrgica/etiologia
5.
World J Gastrointest Surg ; 16(3): 717-730, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38577067

RESUMO

BACKGROUND: Due to the complexity and numerous comorbidities associated with Crohn's disease (CD), the incidence of postoperative complications is high, significantly impacting the recovery and prognosis of patients. Consequently, additional studies are required to precisely predict short-term major complications following intestinal resection (IR), aiding surgical decision-making and optimizing patient care. AIM: To construct novel models based on machine learning (ML) to predict short-term major postoperative complications in patients with CD following IR. METHODS: A retrospective analysis was performed on clinical data derived from a patient cohort that underwent IR for CD from January 2017 to December 2022. The study participants were randomly allocated to either a training cohort or a validation cohort. The logistic regression and random forest (RF) were applied to construct models in the training cohort, with model discrimination evaluated using the area under the curves (AUC). The validation cohort assessed the performance of the constructed models. RESULTS: Out of the 259 patients encompassed in the study, 5.0% encountered major postoperative complications (Clavien-Dindo ≥ III) within 30 d following IR for CD. The AUC for the logistic model was 0.916, significantly lower than the AUC of 0.965 for the RF model. The logistic model incorporated a preoperative CD activity index (CDAI) of ≥ 220, a diminished preoperative serum albumin level, conversion to laparotomy surgery, and an extended operation time. A nomogram for the logistic model was plotted. Except for the surgical approach, the other three variables ranked among the top four important variables in the novel ML model. CONCLUSION: Both the nomogram and RF exhibited good performance in predicting short-term major postoperative complications in patients with CD, with the RF model showing more superiority. A preoperative CDAI of ≥ 220, a diminished preoperative serum albumin level, and an extended operation time might be the most crucial variables. The findings of this study can assist clinicians in identifying patients at a higher risk for complications and offering personalized perioperative management to enhance patient outcomes.

6.
Eur J Surg Oncol ; 50(6): 108313, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38579659

RESUMO

OBJECTIVE: The study aimed to evaluate the accuracy of perineural invasion (PNI) diagnosis in cervical cancer, and to analyze the impact of PNI on the prognosis and postoperative adjuvant treatment decisions for cervical cancer. METHODS: A retrospective pathological review of PNI in cervical cancer was conducted from 2004 to 2016 in 15 hospitals. RESULTS: This study included a total of 1208 cases, comprising 273 cases with PNI and 935 cases without. The false positive rate and false negative rate of PNI diagnosis were 5.35% (50/935) and 33.33% (91/273), respectively. Adenocarcinoma, deep stromal invasion, lymphovascular space invasion (LVSI) (+), and margin involvement were independent risk factors for PNI. Both 5-year overall survival rate (OS) and 5-year disease-free survival rate (DFS) of PNI group were worse than non-PNI group. PNI was an independent risk factor for 5-year OS and 5-year DFS. In cases receiving standard postoperative adjuvant treatment, among those with two intermediate-risk factors, both 5-year OS and DFS were worse in the PNI group. Among cases with three intermediate-risk factors or at least one high-risk factor, there was no difference in 5-year OS between the two groups, but 5-year DFS was worse in the PNI group. CONCLUSION: The diagnosis of PNI in cervical cancer was not accurate. Adenocarcinoma, deep stromal invasion, LVSI, and margin involvement were independent risk factors for PNI. PNI was an independent risk factor for 5-year OS and DFS. PNI has the potential to serve as a new high-risk factor, thus providing guidance for postoperative adjuvant therapy.

7.
Int J Biol Macromol ; : 131721, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38649079

RESUMO

Interferon (IFN) alpha/beta receptor 1 (IFNAR1) is indispensable for antiviral responses and the immune regulation. Dysregulation of the IFNAR1-mediaetd signaling pathways leads to deleterious autoimmune diseases such as systemic lupus erythematosus (SLE). QX006N, a humanized therapeutic monoclonal antibody, specifically targets human IFNAR1 and is in the clinical trial phase for treating SLE, but the molecular mechanism underlying the QX006N-mediated recognition of IFNAR1 remains unclear. Here, we report the high neutralization activities of QX006N against IFNAR1-mediated signal transduction. Meanwhile, we determine the structures of the fragment antigen-binding domain (Fab) of QX006N (QX006N-Fab) and QX006N-Fab in complex with the subdomains 1-3 of IFNAR1 (IFNAR1-SD123) at 2.87 Šand 2.68 Šresolutions, respectively. In the structure of the QX006N-Fab/IFNAR1-SD123 complex, QX006N-Fab only recognizes the SD3 subdomain of IFNAR1 by the hydrophobic, hydrogen-bonding and electrostatic interactions. Compared with the structure of the IFN/IFNAR1/IFNAR2 complex, the binding of QX006N-Fab to IFNAR1-SD3 blocks its association with IFN due to steric hindrance, which inhibits the IFN/IFNAR1/IFNAR2 complex formation for signal transduction. The results of this study provide the structural evidence for the specific targeting of IFNAR1 by the therapeutic antibody QX006N and pave the way for the rational design of antibody drugs to combat IFNAR1-related autoimmune diseases.

8.
Int Immunopharmacol ; 132: 112015, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38608478

RESUMO

CXC chemokine receptor 6 (CXCR6), a seven-transmembrane domain G-protein-coupled receptor, plays a pivotal regulatory role in inflammation and tissue damage through its interaction with CXC chemokine ligand 16 (CXCL16). This axis is implicated in the pathogenesis of various fibrotic diseases and correlates with clinical parameters that indicate disease severity, activity, and prognosis in organ fibrosis, including afflictions of the liver, kidney, lung, cardiovascular system, skin, and intestines. Soluble CXCL16 (sCXCL16) serves as a chemokine, facilitating the migration and recruitment of CXCR6-expressing cells, while membrane-bound CXCL16 (mCXCL16) functions as a transmembrane protein with adhesion properties, facilitating intercellular interactions by binding to CXCR6. The CXCR6/CXCL16 axis is established to regulate the cycle of damage and repair during chronic inflammation, either through modulating immune cell-mediated intercellular communication or by independently influencing fibroblast homing, proliferation, and activation, with each pathway potentially culminating in the onset and progression of fibrotic diseases. However, clinically exploiting the targeting of the CXCR6/CXCL16 axis requires further elucidation of the intricate chemokine interactions within fibrosis pathogenesis. This review explores the biology of CXCR6/CXCL16, its multifaceted effects contributing to fibrosis in various organs, and the prospective clinical implications of these insights.

9.
Mol Biomed ; 5(1): 9, 2024 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-38461206

RESUMO

Sirolimus is a regularly applied immunosuppressant for patients undergoing liver transplantation (LT) for hepatocellular carcinoma (HCC). Sirolimus not only significantly inhibits HCC recurrence but also protects renal function. However, the improvement effect of sirolimus on nontumour-related death in patients is still unknown. The aim of our study was to investigate the therapeutic effect of sirolimus on nontumour-related deaths. In this study, we retrospectively enrolled 403 LT patients with HCC from January 1, 2015, to December 31, 2018. The median follow-up time was 47.1 months. The patients were divided into the sirolimus group (N = 184) and the sirolimus-free group (N = 219). There were no significant differences between the sirolimus group and the sirolimus-free group in survival (P = 0.054). In transplant patients who exceeded the Milan or Hangzhou criteria, the sirolimus group achieved higher survival than the sirolimus-free group (P = 0.005; P = 0.02). Moreover, multivariate analysis showed that sirolimus strongly reduced the hazard ratio (HR) for nontumour-related death in LT patients who exceeded the Milan (HR: 0.42; 95% CI: 0.18-1; P = 0.05) or Hangzhou criteria (HR: 0.26; 95% CI: 0.08-0.89; P = 0.032). HCC recurrence increased the risk of nontumour-related death. In conclusion, sirolimus-based immunosuppression can significantly reduce nontumour-related death in LT patients who exceed the criteria for transplantation. In addition, this finding will further promote the application of sirolimus after liver transplantation for hepatocellular carcinoma.

10.
J Integr Plant Biol ; 66(4): 731-748, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38482956

RESUMO

Soil salinity has a major impact on rice seed germination, severely limiting rice production. Herein, a rice germination defective mutant under salt stress (gdss) was identified by using chemical mutagenesis. The GDSS gene was detected via MutMap and shown to encode potassium transporter OsHAK9. Phenotypic analysis of complementation and mutant lines demonstrated that OsHAK9 was an essential regulator responsible for seed germination under salt stress. OsHAK9 is highly expressed in germinating seed embryos. Ion contents and non-invasive micro-test technology results showed that OsHAK9 restricted K+ efflux in salt-exposed germinating seeds for the balance of K+/Na+. Disruption of OsHAK9 significantly reduced gibberellin 4 (GA4) levels, and the germination defective phenotype of oshak9a was partly rescued by exogenous GA3 treatment under salt stress. RNA sequencing (RNA-seq) and real-time quantitative polymerase chain reaction analysis demonstrated that the disruption of OsHAK9 improved the GA-deactivated gene OsGA2ox7 expression in germinating seeds under salt stress, and the expression of OsGA2ox7 was significantly inhibited by salt stress. Null mutants of OsGA2ox7 created using clustered, regularly interspaced, short palindromic repeat (CRISPR)/CRISPR-associated nuclease 9 approach displayed a dramatically increased seed germination ability under salt stress. Overall, our results highlight that OsHAK9 regulates seed germination performance under salt stress involving preventing GA degradation by mediating OsGA2ox7, which provides a novel clue about the relationship between GA and OsHAKs in rice.


Assuntos
Giberelinas , Oryza , Giberelinas/farmacologia , Giberelinas/metabolismo , Germinação/fisiologia , Potássio/metabolismo , Oryza/metabolismo , Sementes/metabolismo , Estresse Salino , Proteínas de Membrana Transportadoras/metabolismo , Regulação da Expressão Gênica de Plantas
11.
Front Genet ; 15: 1360507, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38533207

RESUMO

Triple-negative breast cancer (TNBC) is a subtype of breast cancer with poor prognosis and limited treatment options. Although immune checkpoint inhibitors (ICIs) have been proven to improve outcomes in TNBC patients, the potential mechanisms and markers that determine the therapeutic response to ICIs remains uncertain. Revealing the relationship and interaction between cancer cells and tumor microenvironment (TME) could be helpful in predicting treatment efficacy and developing novel therapeutic agents. By analyzing single-cell RNA sequencing dataset, we comprehensively profiled cell types and subpopulations as well as identified their signatures in the TME of TNBC. We also proposed a method for quantitatively assessment of the TME immune profile and provided a framework for identifying cancer cell-intrinsic features associated with TME through integrated analysis. Using integrative analyses, RARRES1 was identified as a TME-associated gene, whose expression was positively correlated with prognosis and response to ICIs in TNBC. In conclusion, this study characterized the heterogeneity of cellular components in TME of TNBC patients, and brought new insights into the relationship between cancer cells and TME. In addition, RARRES1 was identified as a potential predictor of prognosis and response to ICIs in TNBC.

12.
PeerJ ; 12: e16816, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38313007

RESUMO

The reliability of neck circumference measurement as an assessment tool for older adults requiring long-term care remains unknown. This study aimed to evaluate the reliability of neck circumference measurement in older adults requiring long-term care, and the effect of edema on measurement error. Two physical therapists measured the neck circumference. Intraclass correlation coefficient (ICC) and Bland-Altman analyses were performed to examine the reliability of neck circumference measurement. Correlation analysis was used to evaluate the relationship between edema values (extracellular water/total body water) and neck circumference measurement difference. For inter-rater reliability of neck circumference measurement, the overall ICC (2,1) was 0.98. The upper and lower limits of the difference between examiners ranged from -0.9 to 1.2 cm. There was no association between edema values and neck circumference measurement error. Thus, measurement of the neck circumference in older adults requiring long-term care is a reliable assessment tool, with a low error rate, even in older adults with edema.


Assuntos
Assistência de Longa Duração , Pescoço , Humanos , Idoso , Variações Dependentes do Observador , Reprodutibilidade dos Testes , Edema/diagnóstico
13.
J Nutr Health Aging ; 28(2): 100017, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38388115

RESUMO

BACKGROUND: The association between dietary habits and metabolic syndrome (MetS) has not been well documented, due to the complexity and individualization of dietary culture in the Chinese population. OBJECTIVE: To construct a composite score from various bad dietary habits and to evaluate their comprehensive association with the prevalence of MetS and its components among Chinese men and women across various age groups. SETTING: Serial cross-sectional studies. METHODS: Twenty-three dietary habits were assessed through face-to-face interviews with 98,838 males and 83,099 females in health check-up programs from 2015 to 2021, among which eighteen bad dietary habits were observed to be associated independently with total MetS. The total score of bad dietary habits was composed of four categories via variable clustering analysis, including irregular dietary habits, unhealthy dietary flavors, unbalanced dietary structure, and high-fat diet. The 2016 Chinese guideline for the management of dyslipidemia in adults was used to define MetS. RESULTS: Men had a higher score of bad dietary habits than women (9.63 ± 3.11 vs. 8.37 ± 3.23), which decreased significantly with increasing age in both males and females (Pinteraction<0.01). The prevalence of total MetS increased significantly with the cumulative score of bad dietary habits in both males (highest quintile vs. lowest quintile: OR, 1.90; 95% confidence interval [CI], 1.80-2.00; Plinear<0.01) and females (OR, 2.23; 95% CI, 2.02-2.46; Plinear<0.01) after adjusted for age, education, smoking status, alcohol consumption, and physical activities. These linear trends were also observed for each MetS component (all Plinear<0.01). The role of irregular dietary habits and high-fat diet on MetS prevalence are much higher in males than in females, while unhealthy dietary flavors and unbalanced dietary structure had a greater influence on females. CONCLUSIONS: The accumulation of bad dietary habits contributes to the MetS developments. Thus, individualized lifestyle interventions are needed to correct bad dietary habits with regard to gender differences.


Assuntos
Dieta , Síndrome Metabólica , Feminino , Humanos , Masculino , Estudos Transversais , Dieta Hiperlipídica , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/etiologia , Prevalência , Fatores de Risco , População do Leste Asiático
16.
Bone Rep ; 20: 101732, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38226335

RESUMO

Purpose: Predictors of 'imminent' risk of second hip fracture are unknown. The aims of the study were to explore strength of hip areal bone mineral density (aBMD), and muscle area and density for predicting second hip fracture at different time intervals. Methods: Data of the Chinese Second Hip Fracture Evaluation were analyzed, a longitudinal study to evaluate the risk of second hip fracture (of the contralateral hip) by using CT images obtained immediately after first hip fracture. Muscle cross-sectional area and density were measured of the gluteus maximus (G.MaxM) and gluteus medius and minimus (G.Med/MinM) and aBMD of the proximal femur at the contralateral unfractured side. Patients were followed up for a median time of 4.5 years. Separate Cox models were used to predict second hip fracture risk at different time intervals after first event adjusted for age, sex, BMI and diabetes. Results: The mean age of subjects with imminent (within 1st or 2nd year) second hip fracture was 79.80 ± 5.16 and 81.56 ± 3.64 years. In the 1st year after the first hip fracture, femoral neck (FN) aBMD predicted second hip fracture (HR 5.88; 95 % CI, 1.32-26.09). In the remaining years of follow-up after 2nd year, muscle density predicted second hip fracture (G.MaxM HR 2.13; 95 % CI, 1.25-3.65,G.Med/MinM HR 2.10; 95 % CI, 1.32-3.34). Conclusions: Our results show that femoral neck aBMD is an important predictor for second hip fracture within the first year and therefore suggest supports the importance concept of early and rapid-acting bone-active drugs to increase hip BMD. In addition, the importance of muscle density predicting second hip fracture after the second year suggest post hip fracture rehabilitation and exercise programs could also be important to reduce muscle fatty infiltration.

17.
ACS Appl Mater Interfaces ; 16(4): 5050-5057, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38228493

RESUMO

Water-soluble quantum dots (QDs) are necessary to prepare patterned pixels or films for high-resolution displays with less environmental burden but are very limited by the trade-off between photoluminescence and stability of QDs. In this work, we proposed synthesizing water-soluble QDs with simultaneous excellent luminescence properties and high stability by coating the amphiphilic poly(maleic anhydride-alt-1-octadecene)-ethanol amine (PMAO-EA) polymer on the surface of silane-treated QDs. These coated QDs show a photoluminescence quantum yield (PLQY) as high as 94%, and they have good photoluminescence stability against light irradiation and thermal attacks, owing to the suppression of the nonradiative recombination by the polymer layer and the isolation of oxygen and water by the silica layer. The water-soluble QDs, mixed with ethylene glycol, enable inkjet printing of QD color conversion films (QD-CCFs) with an average diameter of 68 µm for each pixel and a high PLQY of 91%. The QD-CCFs are demonstrated to fabricate red-emitting mini-LEDs by combining with blue mini-LED chips, which have an external quantum efficiency as high as 25.86% and a luminance of 2.44 × 107 cd/m2. We believe that the proposed strategy is applicable to other water-soluble QDs and paves an avenue for inkjet printing environmentally friendly QD-CCFs for mini/micro-LED displays.

18.
Appl Opt ; 63(3): 816-822, 2024 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-38294396

RESUMO

To make the driving force of a zoom cam cylinder stable and easy to control, the correlation between the cam curves of the zoom group and the compensation group is established effectively by reasonably selecting and arranging the coordinate system. Two optimization methods of cam curve are proposed. First, the original data are processed directly by the function of the target cam curve, and then the dynamic parameter such as the pressure angle is verified again to obtain the expected cam curve. This optimization method is simple and convenient, and a variety of optimization results can be constructed. Second, a physical model of multiple cam curves and the driving force with only one variable is constructed. The step search optimization method is used to process the original data point by point, and the best cam curve matching the model is obtained. Through dynamic simulation, it is determined that the cam curves designed by this optimization method can drive the zoom group and compensation group to complete the whole continuous zoom movement with a stable torque.

19.
Adv Mater ; 36(1): e2308762, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37849029

RESUMO

Both cisplatin-based chemotherapy and immune checkpoint blockers (ICBs)-based immunotherapy are the first-line treatments for patients with advanced bladder cancer. Cancer cells can develop resistance to cisplatin through extensive DNA repair, while a low response rate to ICBs is mostly due to the presence of an immunosuppressive microenvironment and low PD-L1 expression. Herein, a glutathione (GSH)-responsive nanoparticle (NP2) loaded with cisplatin prodrug (Pt (IV)) and WEE1 inhibitor (MK1775) is designed. NP2 can be triggered by GSH in cancer cells, and the released MK1775 can inhibit the activity of WEE1 protein, which ultimately increases DNA damage by cisplatin. Genome-wide RNA sequencing first reveals that NP2 can inhibit DNA repair machinery by interfering with the cell cycle and significantly activate the stimulator of interferon genes pathway. Tumor growth is significantly inhibited by NP2 in vivo. As innate and adaptive immune responses are stimulated, the immunosuppressive microenvironment is modified, and the "immune cold tumor" is transformed into an "immune hot tumor". In addition, NP2 can upregulate PD-L1 expression in tumor cells, thereby increasing the response rate of PD-L1 monoclonal antibody (αPD-L1) and eliciting long-term immune responses in both primary and metastatic tumors.


Assuntos
Pró-Fármacos , Neoplasias da Bexiga Urinária , Humanos , Cisplatino/farmacologia , Platina , Antígeno B7-H1/metabolismo , Pró-Fármacos/farmacologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Dano ao DNA , Imunoterapia , Microambiente Tumoral , Linhagem Celular Tumoral , Proteínas Tirosina Quinases , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo
20.
Telemed J E Health ; 30(1): 187-197, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37437119

RESUMO

Background: Internet medical services (IMS) have been rapidly promoted across China, especially since the outbreak of COVID-19. However, a nationwide study is still lacking. Objective: To unveil the whole picture of IMS across tertiary and secondary hospitals in China, and to evaluate potential influence of the hospital general characteristics, medical staff reserve, and patient visiting capacity on IMS provision. Methods: An online cross-sectional survey was conducted, and 1,995 tertiary and 2,824 secondary hospitals completed questionnaires from 31 administrative regions in China during July 1 and October 31, 2021. Those hospitals are defined having abilities of providing IMS if at least one following service are available: (1) online appointment of diagnoses and treatments; (2) online disease consultation; (3) electronic prescription; and (4) drug delivery. The logistic regression models are used to detect the possible roles on developing IMS. Results: A majority (68.9%) of tertiary hospitals and 53.0% secondary hospitals have provided IMS (p < 0.01). Tertiary hospital also had much higher proportions than secondary hospitals in online appointment of diagnoses and treatments (62.6% vs. 46.1%), online disease consultation (47.3% vs. 16.9%), electronic prescription (33.2% vs. 9.6%), and drug delivery (27.8% vs. 4.6%). In multivariate model, IMS hospitals may be associated significantly with having more licensed doctors (≥161 vs. <161: odds ratio [OR], 1.30; 1.13-1.50; p < 0.01), having more frequency of registration appointments (≥3,356 vs. <3,356: OR, 1.77; 1.54-2.03; p < 0.01), having higher frequency of patient follow-ups (≥1,160 vs. <1,160: OR, 1.36; 1.15-1.61; p < 0.01), having laboratory test appointments (Yes vs. No: OR, 1.25; 1.06-1.48; p = 0.01), and having treatment appointments (Yes vs. No: OR, 1.27; 1.11-1.46; p < 0.01) in the past 3 months. Conclusions: The coverage of IMS is appreciable in China, but the IMS market is still greatly extended and improved. The provision of IMS depends primarily on the scales of the hospitals, including medical staff reserve and patient visiting capacity.


Assuntos
COVID-19 , Humanos , Estudos Transversais , COVID-19/epidemiologia , Centros de Atenção Terciária , Encaminhamento e Consulta , Inquéritos e Questionários , China/epidemiologia , Internet
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