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1.
Zhongguo Yi Liao Qi Xie Za Zhi ; 48(3): 306-311, 2024 May 30.
Article in Chinese | MEDLINE | ID: mdl-38863098

ABSTRACT

The study provides an overview of the development status of sleep disorder monitoring devices. Currently, polysomnography (PSG) is the gold standard for diagnosing sleep disorders, necessitating multiple leads and requiring overnight monitoring in a sleep laboratory, which can be cumbersome for patients. Nevertheless, the performance of PSG has been enhanced through research on sleep disorder monitoring and sleep staging optimization. An alternative device is the home sleep apnea testing (HSAT), which enables patients to monitor their sleep at home. However, HSAT does not attain the same level of accuracy in sleep staging as PSG, rendering it inappropriate for screening individuals with asymptomatic or mild obstructive sleep apnea-hypopnea syndrome (OSAHS). The study suggests that establishing a Chinese sleep staging database and developing home sleep disorder monitoring devices that can serve as alternatives to PSG will represent a future development direction.


Subject(s)
Polysomnography , Sleep Apnea, Obstructive , Humans , Monitoring, Physiologic , Monitoring, Ambulatory/instrumentation , Sleep Stages
2.
Food Res Int ; 187: 114428, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38763678

ABSTRACT

In this study, blackberry polysaccharide-selenium nanoparticles (BBP-24-3Se) were first prepared via Na2SeO3/Vc redox reaction, followed by coating with red blood cell membrane (RBC) to form core-shell structure polysaccharide-selenium nanoparticles (RBC@BBP-24-3Se). The particle size of BBP-24-3Se (167.1 nm) was increased to 239.8 nm (RBC@BBP-24-3Se) with an obvious core-shell structure after coating with RBC. FT-IR and XPS results indicated that the interaction between BBP-24-3 and SeNPs formed a new C-O···Se bond with valence state of Se0. Bioassays indicated that RBC coating markedly enhanced both the biocompatibility and bioabsorbability of RBC@BBP-24-3Se, and the absorption rate of RBC@BBP-24-3Se in HepG2 cells was 4.99 times higher than that of BBP-24-3Se at a concentration of 10 µg/mL. Compared with BBP-24-3Se, RBC@BBP-24-3Se possessed significantly heightened protective efficacy against oxidative damage and better regulation of glucose/lipid metabolism disorder induced by palmitic acid in HepG2 cells. Mechanistic studies demonstrated that RBC@BBP-24-3Se could effectively improve PI3K/AKT signaling pathway to promote glucose metabolism, inhibit the expression of lipid synthesis genes and up-regulate the expression of lipid-decomposing genes through AMPK signaling pathway to improve lipid metabolism. These results provided a theoretical basis for developing a new type of selenium supplement for the treatment of insulin resistance.


Subject(s)
Glucose , Lipid Metabolism , Nanoparticles , Polysaccharides , Rubus , Selenium , Humans , Selenium/chemistry , Hep G2 Cells , Polysaccharides/pharmacology , Polysaccharides/chemistry , Lipid Metabolism/drug effects , Glucose/metabolism , Nanoparticles/chemistry , Rubus/chemistry , Particle Size , Oxidative Stress/drug effects , Antioxidants/pharmacology , Signal Transduction/drug effects
3.
J Cardiothorac Surg ; 19(1): 141, 2024 Mar 19.
Article in English | MEDLINE | ID: mdl-38504347

ABSTRACT

BACKGROUND: Non-small cell lung cancer (NSCLC) is the leading cause of morality among all malignant tumors. Smoking is one of the most important causes of NSCLC, which contributes not only to the initiation of NSCLC but also to its progression. The identification of specific biomarkers associated with smoking will promote diagnosis and treatment. METHODS: Data mining was used to identify the smoking associated gene SERPINB12. CCK8 assays, colony formation assays, a mouse xenograft model and transwell assays were performed to measure the biological functions of SERPINB12 in NSCLC. GSEA, luciferase reporter assays and immunofluorescence were conducted to explore the potential molecular mechanisms of SERPINB12 in NSCLC. RESULTS: In this study, by data mining the TCGA database, we found that SERPINB12 was greatly upregulated in NSCLC patients with cigarette consumption behavior, while the expression level was positively correlated with disease grade and poor prognosis. SERPINB12 is a kind of serpin peptidase inhibitor, but its function in malignant tumors remains largely unknown. Functionally, knockdown of SERPINB12 observably inhibited the proliferation and metastasis of NSCLC cells in vitro and in vivo. Moreover, downregulation of SERPINB12 attenuated Wnt signaling by inhibiting the nuclear translocation of ß-catenin, which explained the molecular mechanism underlying tumor progression. CONCLUSIONS: In conclusion, SERPINB12 functions as a tumorigenesis factor, which could be a promising biomarker for NSCLC patients with smoking behavior, as well as a therapeutic target.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Serpins , Humans , Animals , Mice , Carcinoma, Non-Small-Cell Lung/pathology , Lung Neoplasms/pathology , Wnt Signaling Pathway/genetics , Up-Regulation , Cell Line, Tumor , Smoking/adverse effects , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic , Cell Movement , Serpins/genetics
4.
Pharmacol Res ; 201: 107100, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38341055

ABSTRACT

The development of natural products for potential new drugs faces obstacles such as unknown mechanisms, poor solubility, and limited bioavailability, which limit the broadened applicability of natural products. Therefore, there is a need for advanced pharmaceutical formulations of active compounds or natural products. In recent years, novel nano-drug delivery systems (NDDS) for natural products, including nanosuspensions, nanoliposomes, micelle, microemulsions/self-microemulsions, nanocapsules, and solid lipid nanoparticles, have been developed to improve solubility, bioavailability, and tissue distribution as well as for prolonged retention and enhanced permeation. Here, we updated the NDDS delivery systems used for natural products with the potential enhancement in therapeutic efficiency observed with nano-delivery systems.


Subject(s)
Biological Products , Drug Delivery Systems , Nanoparticle Drug Delivery System , Biological Availability
5.
Transplant Proc ; 56(3): 469-478, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38365513

ABSTRACT

BACKGROUND: The lack of donor organs is a major barrier to the advancement of organ transplantation. This study aimed to understand the current status of knowledge, attitudes, and willingness to donate organs among intensive care unit (ICU) health care workers and analyzed the influencing factors to provide a scientific basis for improving the situation of a serious imbalance between the ratio of organ supply and demand. METHODS: From November 2021 to March 2022, 160 ICU health care workers from 3 level 3A hospitals in Huzhou City, Zhejiang Province, China were chosen as subjects by the cluster sampling method. A cross-sectional study of the participants was carried out using a general information questionnaire, Organ Donation Knowledge Scale, Organ Donation Attitude Scale, and Organ Donation Willingness Scale. The determinants of ICU health care workers' knowledge, attitudes, and willingness toward organ donation were examined using multiple linear regression analysis. RESULTS: A total of 150 ICU health care workers completed the survey within the prescribed time, and the recovery rate of this questionnaire was 93.75%. The score on the Organ Donation Knowledge Scale was 7 (5, 7) points, and the full score was 10 points. The score on the Organ Donation Attitude Scale was (3.87 ± 0.93), and the full score was 7. The Organ Donation Willingness Scale score was 2 (2, 3) out of 5. The results of the multiple linear regression analysis revealed that several factors significantly influenced the score of organ donation knowledge. These factors were identified as the professional title and persuasive experience related to organ donation. Additionally, the score of organ donation attitude was found to be influenced primarily by the persuasive experience of organ donation. Furthermore, the score of organ donation willingness was influenced by 3 main factors: marital status, professional title, and persuasive experience in the context of organ donation. CONCLUSIONS: Although the level of ICU health care workers' knowledge and attitudes toward organ donation was above the median level, they still needed to be improved. The current status of ICU health care workers' desire to donate organs is not optimistic; thus, relevant departments should take specific actions to improve the situation.


Subject(s)
Attitude of Health Personnel , Health Knowledge, Attitudes, Practice , Health Personnel , Intensive Care Units , Tissue and Organ Procurement , Humans , Cross-Sectional Studies , Male , Female , Adult , Surveys and Questionnaires , Middle Aged , Health Personnel/psychology , China
6.
Expert Rev Clin Pharmacol ; 17(1): 57-72, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38108086

ABSTRACT

INTRODUCTION: Quetiapine exhibits notable pharmacokinetic and pharmacodynamic (PK/PD) variability, the origins of which are poorly understood. This systematic review summarizes published population PK/PD studies and identifies significant covariates accounting for this variability to inform precision dosing. METHODS: We systematically searched the PubMed, Web of Science, and Embase databases and compared study characteristics, model parameters, and covariate effects. Visual predictive distributions were used to compare different models. Forest plots and Monte Carlo simulations were used to assess the influence of covariates. RESULTS: Six population PK and three population PK/PD studies were included. The median apparent clearance in adults was 87.7 L/h. Strong and moderate cytochrome P450 3A4 inducers increased the apparent clearance approximately fourfold, while strong cytochrome P450 3A4 inhibitors reduced it by 93%. The half-maximum effect concentrations were 82.8 ng/mL for the Brief Psychiatric Rating Scale and 583 ng/mL for dopamine D2 receptor occupancy. Both treatment duration and quetiapine exposure were associated with weight gain. CONCLUSIONS: Concurrent administration of potent or moderate CYP3A4 inducers and inhibitors need to be avoided in quetiapine-treated patients. When co-medication is required, it is recommended to adjust the dosage based on therapeutic drug monitoring. Additional research is warranted to delineate the dose-exposure-response relationships of quetiapine and active metabolite norquetiapine in pediatrics, geriatrics, hepatically-impaired patients, and women using contraceptives or are pregnant or menopausal. PROSPERO REGISTRATION: CRD42023446654.


Subject(s)
Cytochrome P-450 Enzyme System , Models, Biological , Adult , Humans , Female , Child , Quetiapine Fumarate/pharmacology
7.
Front Public Health ; 11: 1282461, 2023.
Article in English | MEDLINE | ID: mdl-38026350

ABSTRACT

Aims: This research sought to assess the perceived levels of participation and autonomy in senior patients who had received total hip arthroplasty (THA) or total knee arthroplasty (TKA) in Hangzhou, China. Furthermore, the study aimed to identify the factors linked to these outcomes. Study design: This investigation will utilize a cross-sectional study design to assess perceived participation and autonomy among older adults total hip arthroplasty (THA) and total knee arthroplasty (TKA) patients. The research was conducted in Hangzhou, China, at a tertiary hospital. Methods: Convenient sampling was utilized to select 139 patients who underwent THA or TKA between March 2022 and March 2023 and met the inclusion criteria at a tertiary hospital in Hangzhou. The Impact on Participation and Autonomy Questionnaire, Hip/Knee Injury and Osteoarthritis Outcome Score (HOOS/KOOS), 5-Item Geriatric Depression Scale, Multidimensional Scale of Perceived Social Support, and Elders Health Empowerment Scale were used to assess perceived participation, hip/knee-related symptoms and functional restrictions, depression symptoms, social support, and health empowerment. Results: The mean score for perceived participation and autonomy was 22.554 (SD: 13.042). The mean scores for participation in indoor autonomy, outdoor autonomy, family roles, and social relations were 0.654 (SD: 0.608), 1.324 (SD: 0.792), 1.053 (SD: 0.657), and 0.664 (SD: 0.542), respectively. Negative correlations were observed between perceived participation/autonomy scores and HOOS/KOOS, social support, and health empowerment scores. Conversely, a positive correlation was found between perceived participation/autonomy scores and depression scores. The detrimental effect of HOOS/KOOS, social support, and health empowerment scores on perceived participation and autonomy was notable, while the impact of depressive symptoms was comparatively minor. Conclusion: Older Chinese patients, at first six months post THA/TKA surgery, reported higher levels of perceived participation compared to individuals with other conditions, such as stroke patients. Functional limitations resulting from hip/knee-related symptoms, as well as social support and health empowerment, emerged as significant influencing factors for perceived participation and autonomy. This research enhances our comprehension of the elements influencing perceived participation among older adults individuals who have undergone THA/TKA procedures.


Subject(s)
Arthroplasty, Replacement, Hip , Arthroplasty, Replacement, Knee , Humans , Aged , Cross-Sectional Studies , China
9.
Front Pharmacol ; 14: 1189058, 2023.
Article in English | MEDLINE | ID: mdl-37711169

ABSTRACT

Objective: This study aims to compare the effectiveness and safety of perampanel and oxcarbazepine as monotherapy in children with focal epilepsy (FE). Methods: This is an ambispective, single-center, non-inferiority study comparing the effectiveness and safety of perampanel (PER) monotherapy and oxcarbazepine (OXC) monotherapy in children with newly diagnosed FE. The primary endpoint was a six-month seizure freedom rate. The secondary endpoints included retention, responder, and seizure freedom rates at 3, 6, and 12 months, respectively. Adverse events (AEs) were also recorded for both groups. Results: One hundred and thirty children and adolescents aged from 4 to 18years newly diagnosed with FE between May 2020 and November 2022 in Wuhan Children's Hospital were included. There were 71 patients in the PER group and 59 patients in the OXC group. In the per protocol set (PPS), 50 (78.1%) in the PER group and 43 (78.2%) in the OXC group completed six months of treatment without seizures. The lower 95% CI (66.0%-87.5%) limit of PER was higher than the non-inferiority margin of 62.4% (80% of the 6-month seizure freedom rate in the OXC group); PER was non-inferior to OXC. The 3-month and 12-month seizure freedom rates were 77.1% and 82.9% for the PER group, respectively, while they were 80.4% and 75.8% for the OXC group. There were no serious adverse events in both groups. Conclusion: PER showed comparable effectiveness and safety compared with OXC in children with newly diagnosed focal epilepsy, which might be an effective and safe treatment for children and adolescents with newly diagnosed FE. Clinical Trial Registration: Identifier ChiCTR2300074696.

10.
Front Med (Lausanne) ; 10: 1190125, 2023.
Article in English | MEDLINE | ID: mdl-37593406

ABSTRACT

Objective: This study aims to explore the efficiency and effectiveness of a body area network-based smart bracelet for trauma care prior to hospitalization. Methods: To test the efficacy of the bracelet, an observational cohort study was conducted on the clinical data of 140 trauma patients pre-admission to the hospital. This study was divided into an experimental group receiving smart bracelets and a control group receiving conventional treatment. Both groups were randomized using a random number table. The primary variables of this study were as follows: time to first administration of life-saving intervention, time to first administration of blood transfusion, time to first administration of hemostatic drugs, and mortality rates within 24 h and 28 days post-admission to the hospital. The secondary outcomes included the amount of time before trauma team activation and the overall length of patient stay in the emergency room. Results: The measurement results for both the emergency smart bracelet as well as traditional equipment showed high levels of consistency and accuracy. In terms of pre-hospital emergency life-saving intervention, there was no significant statistical difference in the mortality rates between both groups within 224 h post-admission to the hospital or after 28-days of treatment in the emergency department. Furthermore, the treatment efficiency for the group of patients wearing smart bracelets was significantly better than that of the control group with regard to both the primary and secondary outcomes of this study. These results indicate that this smart bracelet has the potential to improve the efficiency and effectiveness of trauma care and treatment. Conclusion: A body area network-based smart bracelet combined with remote 5G technology can assist the administration of emergency care to trauma patients prior to hospital admission, shorten the timeframe in which life-saving interventions are initiated, and allow for a quick trauma team response as well as increased efficiency upon administration of emergency care.

11.
Biomed Pharmacother ; 165: 115198, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37536033

ABSTRACT

Systemic lupus erythematosus (SLE) is an autoimmune disease in which the immune system attacks its own tissues and organs. However, the causes of SLE remain unknown. Dyslipidemia is a common symptom observed in SLE patients and animal models and is closely correlated to disease activity. Lipid metabolic reprogramming has been considered as a hallmark of the dysfunction of T cells in patients with SLE, therefore, manipulating lipid metabolism provides a potential therapeutic target for treating SLE. A better understanding of the underlying mechanisms for the metabolic events of immune cells under pathological conditions is crucial for tuning immunometabolism to manage autoimmune diseases such as SLE. In this review, we aim to summarize the cross-link between lipid metabolism and the function of T cells as well as the underlying mechanisms, and provide light on the novel therapeutic strategies of active compounds from herbals for the treatment of SLE by targeting lipid metabolism in immune cells.


Subject(s)
Lupus Erythematosus, Systemic , T-Lymphocytes , Animals , T-Lymphocytes/metabolism , Lipid Metabolism , Lupus Erythematosus, Systemic/metabolism
12.
NeuroRehabilitation ; 53(1): 83-90, 2023.
Article in English | MEDLINE | ID: mdl-37424483

ABSTRACT

BACKGROUND: Neurogenic bowel dysfunction (NBD) is a common complication in stroke patients. OBJECTIVE: To investigate the effect of rectal balloon ice water stimulation on the rehabilitation of patients with NBD after a cerebral stroke. METHODS: Forty stroke patients with NBD were selected between March and August 2022 and randomly divided into a study group (n = 20) and a control group (n = 20). Based on routine rehabilitation training, rectal balloon ice water stimulation or finger rectal stimulation were performed on the study or control group, respectively. After two weeks, the changes in the NBD, self-rating depression scale (SDS) and self-rating anxiety scale (SAS) scores were compared between the two groups. RESULTS: Before the intervention, there were no significant differences in age, sex ratio, and NBD, SDS and SAS scores between the two groups (p > 0.05). The NBD, SDS and SAS scores of both groups were significantly decreased following intervention (p < 0.05). After 2 weeks of intervention, the NBD score of the study group was significantly lower than that of the control group (5.50±1.28 vs 6.45±1.05; p = 0.014). The SDS score of the study group was lower than that of the control group, and the difference was statistically significant (32.30±2.81 vs 44.05±2.19; p = 0.014). The study group also had significantly lower SAS scores than the control group (p = 0.024). In addition, the incidence of dizziness, headaches, nausea, vomiting and abdominal pain and distension in the study group was significantly lower than in the control group (p < 0.05). CONCLUSION: Rectal balloon ice water stimulation can significantly improve stroke patients with NBD's intestinal function and psychological status.


Subject(s)
Neurogenic Bowel , Stroke Rehabilitation , Stroke , Humans , Headache/complications , Neurogenic Bowel/etiology , Stroke/complications , Stroke Rehabilitation/adverse effects
13.
Acta Pharmacol Sin ; 44(12): 2504-2524, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37482570

ABSTRACT

Sinomenine (SIN) is an isoquinoline alkaloid isolated from Sinomenii Caulis, a traditional Chinese medicine used to treat rheumatoid arthritis (RA). Clinical trials have shown that SIN has comparable efficacy to methotrexate in treating patients with RA but with fewer adverse effects. In this study, we explored the anti-inflammatory effects and therapeutic targets of SIN in LPS-induced RAW264.7 cells and in collagen-induced arthritis (CIA) mice. LPS-induced RAW264.7 cells were pretreated with SIN (160, 320, 640 µM); and CIA mice were administered SIN (25, 50 and 100 mg·kg-1·d-1, i.p.) for 30 days. We first conducted a solvent-induced protein precipitation (SIP) assay in LPS-stimulated RAW264.7 cells and found positive evidence for the direct binding of SIN to guanylate-binding protein 5 (GBP5), which was supported by molecular simulation docking, proteomics, and binding affinity assays (KD = 3.486 µM). More importantly, SIN treatment markedly decreased the expression levels of proteins involved in the GBP5/P2X7R-NLRP3 pathways in both LPS-induced RAW264.7 cells and the paw tissue of CIA mice. Moreover, the levels of IL-1ß, IL-18, IL-6, and TNF-α in both the supernatant of inflammatory cells and the serum of CIA mice were significantly reduced. This study illustrates a novel anti-inflammatory mechanism of SIN; SIN suppresses the activity of NLRP3-related pathways by competitively binding GBP5 and downregulating P2X7R protein expression, which ultimately contributes to the reduction of IL-1ß and IL-18 production. The binding specificity of SIN to GBP5 and its inhibitory effect on GBP5 activity suggest that SIN has great potential as a specific GBP5 antagonist.


Subject(s)
Arthritis, Experimental , Arthritis, Rheumatoid , Humans , Mice , Animals , Arthritis, Experimental/chemically induced , Arthritis, Experimental/drug therapy , Interleukin-18/adverse effects , Receptors, Purinergic P2X7/therapeutic use , NLR Family, Pyrin Domain-Containing 3 Protein , Lipopolysaccharides/pharmacology , Signal Transduction , Arthritis, Rheumatoid/drug therapy , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , GTP-Binding Proteins
14.
J Cell Mol Med ; 28(5): e17856, 2023 Jul 17.
Article in English | MEDLINE | ID: mdl-37461162

ABSTRACT

The highly expressed oncogenic factor Krüppel-like factor 5 (KLF5) promotes various cancerous processes, such as cell growth, survival, anti-apoptosis, migration and metastasis, particularly in lung cancer. Nevertheless, the modifications to KLF5 after translation are poorly understood. Protein arginine methyltransferase 5 (PRMT5) is considered as an oncogene known to be involved in different types of carcinomas, including lung cancer. Here, we show that the expression levels of PRMT5 and KLF5 are highly expressed lung cancer. Moreover, PRMT5 interacts with KLF5 and facilitates the dimethylation of KLF5 at Arginine 41 in a manner that depends on methyltransferase activity. Downregulation or pharmaceutical suppression of PRMT5 reduces the expression of KLF5 and its downstream targets both in vitro and in vivo. Mechanistically, the dimethylation of KLF5 by PRMT5 promotes the maintenance and proliferation of lung cancer cells at least partially by stabilising KLF5 via regulation of the Akt/GSK3ß signalling axis. In summary, PRMT5 methylates KLF5 to prevent its degradation, thereby promoting the maintenance and proliferation of lung cancer cells. These results suggest that targeting PRMT5/KLF5 axis may offer a potential therapeutic strategy for lung cancer.

16.
Apoptosis ; 28(7-8): 1090-1112, 2023 08.
Article in English | MEDLINE | ID: mdl-37079192

ABSTRACT

Pancreatic cancer (PC) is a highly malignant digestive tract tumor, with a dismal 5-year survival rate. Recently, cuproptosis was found to be copper-dependent cell death. This work aims to establish a cuproptosis-related lncRNA signature which could predict the prognosis of PC patients and help clinical decision-making. Firstly, cuproptosis-related lncRNAs were identified in the TCGA-PAAD database. Next, a cuproptosis-related lncRNA signature based on five lncRNAs was established. Besides, the ICGC cohort and our samples from 30 PC patients served as external validation groups to verify the predictive power of the risk signature. Then, the expression of CASC8 was verified in PC samples, scRNA-seq dataset CRA001160, and PC cell lines. The correlation between CASC8 and cuproptosis-related genes was validated by Real-Time PCR. Additionally, the roles of CASC8 in PC progression and immune microenvironment characterization were explored by loss-of-function assay. As showed in the results, the prognosis of patients with higher risk scores was prominently worse than that with lower risk scores. Real-Time PCR and single cell analysis suggested that CASC8 was highly expressed in pancreatic cancer and related to cuproptosis. Additionally, gene inhibition of CASC8 impacted the proliferation, apoptosis and migration of PC cells. Furthermore, CASC8 was demonstrated to impact the expression of CD274 and several chemokines, and serve as a key indicator in tumor immune microenvironment characterization. In conclusion, the cuproptosis-related lncRNA signature could provide valuable indications for the prognosis of PC patients, and CASC8 was a candidate biomarker for not only predicting the progression of PC patients but also their antitumor immune responses.


Subject(s)
Pancreatic Neoplasms , RNA, Long Noncoding , Humans , RNA, Long Noncoding/genetics , Apoptosis/genetics , Pancreatic Neoplasms/genetics , Cell Death , Tumor Microenvironment/genetics , Pancreatic Neoplasms
17.
Br J Clin Pharmacol ; 89(7): 2066-2075, 2023 Jul.
Article in English | MEDLINE | ID: mdl-35332559

ABSTRACT

AIMS: Edoxaban is a non-vitamin K antagonist oral anticoagulant (NOAC) widely used for the long-term prevention of stroke in patients with non-valvular atrial fibrillation (NVAF). Adherence to NOAC therapy has been unsatisfactory and decreases over time. Remedial strategies are currently used to address the non-adherence events. Current recommendations, however, are generic and not well supported by evidence. The aim of this study was to explore appropriate remedial dosing regimens for non-adherent edoxaban-treated NVAF patients through Monte Carlo simulation. METHODS: Six regimens were compared with the current recommendations of the European Heart Rhythm Association (EHRA) guide based on total deviation time. Both edoxaban plasma concentration and intrinsic Factor Xa activity were considered. Monte Carlo simulations were performed using RxODE based on a published population pharmacokinetic/pharmacodynamic (PK/PD) model. RESULTS: The proposed remedial strategies were different than the EHRA recommendations and were related to the delay time. However, it was found that the missed dose can be administered immediately if the delay time is within 11 h. When the delay is between 12 and 19 h, a half dose followed by a regular dosing schedule is recommended. When the delay time exceeds 19 h, a full dose followed by a half dose is preferred. CONCLUSION: PK/PD modelling and simulation are effective in developing and evaluating the remedial strategies of edoxaban, which can help maximise its therapeutic effect.


Subject(s)
Atrial Fibrillation , Stroke , Humans , Atrial Fibrillation/complications , Atrial Fibrillation/drug therapy , Atrial Fibrillation/chemically induced , Anticoagulants/adverse effects , Stroke/etiology , Stroke/prevention & control , Stroke/drug therapy , Pyridines , Factor Xa Inhibitors , Administration, Oral
18.
Cell Oncol (Dordr) ; 46(1): 17-48, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36367669

ABSTRACT

Pancreatic ductal adenocarcinoma (PDAC), the most common type of pancreatic cancer, is characterized by poor treatment response and low survival time. The current clinical treatment for advanced PDAC is still not effective. In recent years, the research and application of immunotherapy have developed rapidly and achieved substantial results in many malignant tumors. However, the translational application in PDAC is still far from satisfactory and needs to be developed urgently. To carry out the study of immunotherapy, it is necessary to fully decipher the immune characteristics of PDAC. This review summarizes the recent progress of the tumor microenvironment (TME) of PDAC and highlights its link with immunotherapy. We describe the molecular cues and corresponding intervention methods, collate several promising targets and progress worthy of further study, and put forward the importance of integrated immunotherapy to provide ideas for future research of TME and immunotherapy of PDAC.


Subject(s)
Carcinoma, Pancreatic Ductal , Pancreatic Neoplasms , Humans , Tumor Microenvironment , Pancreatic Neoplasms/pathology , Immunotherapy/methods , Carcinoma, Pancreatic Ductal/pathology , Immunosuppression Therapy , Pancreatic Neoplasms
19.
Zhonghua Nan Ke Xue ; 29(5): 426-429, 2023 May.
Article in Chinese | MEDLINE | ID: mdl-38602759

ABSTRACT

OBJECTIVE: To analyze the causes of skin necrosis after penis lengthening surgery and corresponding treatment measures, and observe the clinical effect of free skin graft repair in the treatment of penile skin defects. METHODS: We retrospectively analyzed the clinical data on 12 cases of extensive penile skin necrosis and defect after penis lengthening surgery performed in our department from January 2017 to January 2022. The patients underwent free skin graft repair with medium- or full-thickness skin grafts from the thigh after wound preparation. RESULTS: The skin grafts survived well in all the 12 patients and the incisions healed in the first stage without any complications. At 6 months after surgery, skin sensation was mostly recovered in the area of penis skin grafting, no obvious skin ulceration or edema was observed, and the appearance of the penis was satisfactory. The IIEF-5 scores, Erectile Hardness Scale (EHS) scores, and the results of penile hardness tests of the patients all indicated normal erectile function. CONCLUSION: Free skin graft repair with autologous medium- or full-thickness skin grafts is a safe and effective surgical option for extensive penile skin necrosis after penis lengthening surgery.


Subject(s)
Penis , Skin , Humans , Male , Necrosis , Pelvis , Penis/surgery , Retrospective Studies
20.
Respir Res ; 23(1): 328, 2022 Dec 03.
Article in English | MEDLINE | ID: mdl-36463140

ABSTRACT

BACKGROUND: Bronchiectasis is a highly heterogeneous chronic airway disease with marked geographic and ethnic variations. Most influential cohort studies to date have been performed in Europe and USA, which serve as the examples for developing a cohort study in China where there is a high burden of bronchiectasis. The Establishment of China Bronchiectasis Registry and Research Collaboration (BE-China) is designed to: (1) describe the clinical characteristics and natural history of bronchiectasis in China and identify the differences of bronchiectasis between the western countries and China; (2) identify the risk factors associated with disease progression in Chinese population; (3) elucidate the phenotype and endotype of bronchiectasis by integrating the genome, microbiome, proteome, and transcriptome with detailed clinical data; (4) facilitate large randomized controlled trials in China. METHODS: The BE-China is an ongoing prospective, longitudinal, multi-center, observational cohort study aiming to recruit a minimum of 10,000 patients, which was initiated in January 2020 in China. Comprehensive data, including medical history, aetiological testing, lung function, microbiological profiles, radiological scores, comorbidities, mental status, and quality of life (QoL), will be collected at baseline. Patients will be followed up annually for up to 10 years to record longitudinal data on outcomes, treatment patterns and QoL. Biospecimens, if possible, will be collected and stored at - 80 °C for further research. Up to October 2021, the BE-China has enrolled 3758 patients, and collected 666 blood samples and 196 sputum samples from 91 medical centers. The study protocol has been approved by the Shanghai Pulmonary Hospital ethics committee, and all collaborating centers have received approvals from their local ethics committee. All patients will be required to provide written informed consent to their participation. CONCLUSIONS: Findings of the BE-China will be crucial to reveal the clinical characteristics and natural history of bronchiectasis and facilitate evidence-based clinical practice in China. Trial registration Registration Number in ClinicalTrials.gov: NCT03643653.


Subject(s)
Bronchiectasis , Humans , Bronchiectasis/diagnosis , Bronchiectasis/epidemiology , China/epidemiology , Cohort Studies , Multicenter Studies as Topic , Observational Studies as Topic , Prospective Studies , Quality of Life , Registries
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