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1.
Front Immunol ; 15: 1409461, 2024.
Article in English | MEDLINE | ID: mdl-38979425

ABSTRACT

Primary immune thrombocytopenia (ITP) is an acquired autoimmune disorder characterized by the destruction of platelets. Although it was long believed that the critical role of autoantibodies in platelet destruction, primarily through the Fc-dependent platelet clearance pathway, recent findings indicate that the significance of the Fc-independent platelet clearance pathway mediated by hepatocytes, thus shedding light on a previously obscure aspect of ITP pathogenesis. Within this context, the desialylation of platelets has emerged as a pivotal biochemical marker. Consequently, targeting platelet desialylation emerges as a novel therapeutic strategy in the pathogenesis of ITP. Notably, prevailing research has largely focused on antiplatelet antibodies and the glycosylation-associated mechanisms of platelet clearance, while comprehensive analysis of platelet desialylation remains scant. In response, we retrospectively discuss the historical progression, inducing factors, generation process, and molecular regulatory mechanisms underlying platelet desialylation in ITP pathogenesis. By systematically evaluating the most recent research findings, we contribute to a comprehensive understanding of the intricate processes involved. Moreover, our manuscript delves into the potential application of desialylation regulatory strategies in ITP therapy, heralding novel therapeutic avenues. In conclusion, this manuscript not only fills a critical void in existing literature but also paves the way for future research by establishing a systematic theoretical framework. By inspiring new research ideas and offering insights into the development of new therapeutic strategies and targeted drugs, our study is poised to significantly advance the clinical management of ITP.


Subject(s)
Biomarkers , Blood Platelets , Purpura, Thrombocytopenic, Idiopathic , Humans , Purpura, Thrombocytopenic, Idiopathic/blood , Purpura, Thrombocytopenic, Idiopathic/immunology , Purpura, Thrombocytopenic, Idiopathic/therapy , Blood Platelets/metabolism , Blood Platelets/immunology , Animals , Autoantibodies/blood , Autoantibodies/immunology , Glycosylation
2.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 38(7): 830-835, 2024 Jul 15.
Article in Chinese | MEDLINE | ID: mdl-39013820

ABSTRACT

Objective: To investigate the effectiveness of the reverse traction device in the preoperative treatment of high-energy tibial plateau fractures. Methods: A retrospective study was conducted to analyze the clinical data of 33 patients with high-energy tibial plateau fractures who met the selection criteria between December 2020 and December 2023. All patients were treated by open reduction and internal fixation. According to the preoperative traction method, they were divided into the observation group (16 cases, treated with a reverse traction device on the day of admission) and the control group (17 cases, treated with heel traction on the day of admission). There was no significant difference in baseline data such as gender, age, body mass index, affected side, cause of injury, fracture Schatzker classification between the two groups ( P>0.05). Preoperative waiting time, preoperative related complications (nail channel loosening, nail channel oozing, nail channel infection, soft tissue necrosis, soft tissue infection, deep vein thrombosis of the lower extremity, etc.), operation time, and total hospitalization time were recorded and compared between the two groups. On the 4th day after traction, visual analogue scale (VAS) score was used to evaluate the pain relief of the patients, the swelling value of the affected limb was measured, and the Immobilization Comfort Questionnaire (ICQ) score was used to evaluate the perioperative hospital comfort of the patients. Results: Both groups of patients completed the operation successfully, and the operation time, total hospitalization time, and preoperative waiting time of the observation group were significantly less than those of the control group ( P<0.05). There was no preoperative related complications in the observation group; in the control group, 3 patients had nail channel loosening and oozing, and 2 cases had the deep vein thrombosis of the lower extremity; the difference in the incidence of complication between the two groups was significant ( P<0.05). On the 4th day after traction, the ICQ score, VAS score, and limb swelling value of the observation group were significantly better than those of the control group ( P<0.05). X-ray films showed that the tibial plateau fracture separation and lower limb alignment recovered after calcaneal traction in the control group, but not as obvious as in the observation group. The fracture gap in the observation group significantly reduced, the tibial plateau alignment was good, and the lateral angulation deformity was corrected. Conclusion: The use of reverse traction treatment in patients with high-energy tibial plateau fractures on admission can accelerate the swelling around the soft tissues to subside, reduce patients' pain, shorten the preoperative waiting time, improve the patients' preoperative quality of life, and contribute to the shortening of the operation time, with a good effectiveness.


Subject(s)
Fracture Fixation, Internal , Tibial Fractures , Traction , Humans , Traction/methods , Tibial Fractures/surgery , Fracture Fixation, Internal/methods , Fracture Fixation, Internal/instrumentation , Female , Male , Bone Plates , Treatment Outcome , Operative Time , Postoperative Complications , Tibial Plateau Fractures
3.
JCO Precis Oncol ; 8: e2400111, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38976830

ABSTRACT

PURPOSE: Simultaneous profiling of cell-free DNA (cfDNA) methylation and fragmentation features to improve the performance of cfDNA-based cancer detection is technically challenging. We developed a method to comprehensively analyze multimodal cfDNA genomic features for more sensitive esophageal squamous cell carcinoma (ESCC) detection. MATERIALS AND METHODS: Enzymatic conversion-mediated whole-methylome sequencing was applied to plasma cfDNA samples extracted from 168 patients with ESCC and 251 noncancer controls. ESCC characteristic cfDNA methylation, fragmentation, and copy number signatures were analyzed both across the genome and at accessible cis-regulatory DNA elements. To distinguish ESCC from noncancer samples, a first-layer classifier was developed for each feature type, the prediction results of which were incorporated to construct the second-layer ensemble model. RESULTS: ESCC plasma genome displayed global hypomethylation, altered fragmentation size, and chromosomal copy number alteration. Methylation and fragmentation changes at cancer tissue-specific accessible cis-regulatory DNA elements were also observed in ESCC plasma. By integrating multimodal genomic features for ESCC detection, the ensemble model showed improved performance over individual modalities. In the training cohort with a specificity of 99.2%, the detection sensitivity was 81.0% for all stages and 70.0% for stage 0-II. Consistent performance was observed in the test cohort with a specificity of 98.4%, an all-stage sensitivity of 79.8%, and a stage 0-II sensitivity of 69.0%. The performance of the classifier was associated with the disease stage, irrespective of clinical covariates. CONCLUSION: This study comprehensively profiles the epigenomic landscape of ESCC plasma and provides a novel noninvasive and sensitive ESCC detection approach with genome-scale multimodal analysis.


Subject(s)
Cell-Free Nucleic Acids , DNA Methylation , Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Humans , Esophageal Neoplasms/genetics , Esophageal Neoplasms/blood , Esophageal Neoplasms/diagnosis , Male , Female , Middle Aged , Cell-Free Nucleic Acids/blood , Cell-Free Nucleic Acids/genetics , Esophageal Squamous Cell Carcinoma/genetics , Aged , Epigenome
4.
Int J Surg ; 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38905505

ABSTRACT

BACKGROUND: Video-assisted thoracoscopic (VATS) lobectomy can affect patients' pulmonary function and quality of life significantly. No optimal protocol combining patient-reported outcome-based symptom management and post-discharge rehabilitation programme has yet been established. This study aimed to assess the efficacy of a novel smartphone app designed for home-based symptom management and rehabilitation. METHODS: The app was developed based on three modules: a symptom reporting system with alerts, aerobic and respiratory training exercises, and educational material. Four core symptoms were selected based on a questionnaire survey of 201 patients and three rounds of Delphi voting by 30 experts. We screened 265 patients and randomly assigned 136 equally to the app group and usual care group. The primary outcome was pulmonary function recovery at 30 days postoperatively. Secondary outcomes included symptom burden and interference with daily living (both rated using the MD Anderson Symptom Inventory for Lung Cancer), aerobic exercise intensity, emergency department visits, app-related safety, and satisfaction with the app. FINDINGS: Of the 136 participants, 56.6% were women and their mean age was 61 years. The pulmonary function recovery ratio 1 month after surgery in the app group was significantly higher than that in the usual care group (79.32% vs. 75.73%; P=0.040). The app group also recorded significantly lower symptom burden and interference with daily living scores and higher aerobic exercise intensity after surgery than the usual care group. Thirty-two alerts were triggered in the app group. The highest pulmonary function recovery ratio and aerobic exercise intensity were recorded in those patients who triggered alerts in both groups. INTERPRETATION: Using a smartphone app is an effective approach to accelerate home-based rehabilitation after VATS lobectomy. The symptom alert mechanism of this app could optimise recovery outcomes, possibly driven by patients' increased self-awareness.

5.
Sci Total Environ ; 945: 173894, 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-38880136

ABSTRACT

Metropolization has emerged as a prominent feature of 21st-century urbanization. To gain a comprehensive understanding of global urbanization patterns and pathways, as well as to interpret their consequences and implications, we aimed to provide a comparative characterization on urban transformation in metropolitan areas of developed and developing countries. Here, we quantified and compared the urban growth rates, growth modes, urban landscape metrics, and the co-evolution of urban land and population in 21 representative metropolitan areas across the United States, Europe, and China from 1985 to 2020, using remotely sensed impervious-surface dynamic dataset and patch-based analyses. The results showed that each metropolitan area has experienced substantial urban expansion with different scales and growth rates. Developing China possessed a relatively lower urbanization level but urbanized faster compared to the developed counterparts. Spatially, with infilling expansion increasing and even dominating, American and European metropolitan areas developed into more compact central urban cores, demonstrating the coalesced trajectories. Chinese metropolitan areas showed point-axis urban development mainly via edge-expansion in concentric rings. Furthermore, the horizontal co-evolution of urban area and population generally showed stable economies of scale in the United States and Europe whereas transitioned from diseconomy to economy of scale in China, evidencing that the century-long urbanization journey traversed by developed countries can be completed by emerging-developing ones within several decades. Temporally, the urban expansion greatly outpaced population growth in all metropolitan areas except London, signifying that urban land use efficiency is still a grand challenge in the Metropolitan Century. Effective metropolitan governance should be tailored to spatial configuration for efficient urban land use and intercity coordinated development towards a sustainable urban future, particularly for developing countries with emerging metropolization.

6.
Eur J Cardiothorac Surg ; 66(1)2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38913856

ABSTRACT

OBJECTIVES: The evaluation of Fontan-associated liver disease is often challenging. Diffusion-weighted magnetic resonance imaging can detect hepatic fibrosis from capillary perfusion and diffusion abnormalities from extracellular matrix accumulation. This study investigated its role in the evaluation of liver disease in Fontan patients and explored possible diagnostic methods for early detection of advanced liver fibrosis. METHODS: Stable adult Fontan patients who could safely be examined with magnetic resonance imaging were enrolled, and blood biomarkers, transient elastography were also examined. RESULTS: Forty-six patients received diffusion-weighted imaging; and 58.7% were diagnosed with advanced liver fibrosis (severe liver fibrosis, 37.0%, and cirrhosis 21.7%). Two parameters of hepatic dysfunction, platelet counts (Spearman's ρ: -0.456, P = 0.001) and cholesterol levels (Spearman's ρ: -0.383, P = 0.009), decreased with increasing severity of fibrosis. Using transient elastography, a cut-off value of 14.2 kPa predicted the presence of advanced liver fibrosis, but with a low positive predictive value. When we included platelet count, cholesterol, post-Fontan years and transient elastography values as a composite, the capability of predicting advanced liver fibrosis was the most satisfactory (C statistic 0.817 ± 0.071, P < 0.001). A cut-off value of 5.0 revealed a sensitivity of 78% and a specificity of 82%. CONCLUSIONS: In Fontan patients, diffusion-weighted imaging was helpful in detecting liver fibrosis that was correlated with hepatic dysfunction. A simple score was proposed for long-term surveillance and early detection of advanced liver disease in adult Fontan patients. For adult Fontan patients with a calculated score > 5.0, we may consider timely diffusion-weight imaging and early management for liver complications.


Subject(s)
Diffusion Magnetic Resonance Imaging , Fontan Procedure , Liver Cirrhosis , Humans , Fontan Procedure/adverse effects , Liver Cirrhosis/diagnostic imaging , Liver Cirrhosis/surgery , Male , Diffusion Magnetic Resonance Imaging/methods , Female , Adult , Young Adult , Elasticity Imaging Techniques/methods , Adolescent , Liver/diagnostic imaging , Liver/pathology , Biomarkers/blood
7.
Drug Metab Dispos ; 52(8): 824-835, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-38906699

ABSTRACT

Asphyxiated neonates often undergo therapeutic hypothermia (TH) to reduce morbidity and mortality. Since both perinatal asphyxia (PA) and TH influence physiology, altered pharmacokinetics (PK) and pharmacodynamics (PD) are expected. Given that TH is the standard of care for PA with moderate to severe hypoxic-ischemic encephalopathy, disentangling the effect of PA versus TH on PK/PD is not possible in clinical settings. However, animal models can provide insights into this matter. The (neonatal) Göttingen Minipig, the recommended strain for nonclinical drug development, was selected as translational model. Four drugs-midazolam (MDZ), fentanyl (FNT), phenobarbital (PHB), and topiramate (TPM)-were intravenously administered under four conditions: control (C), therapeutic hypothermia (TH), hypoxia (H), and hypoxia plus TH (H+TH). Each group included six healthy male neonatal Göttingen Minipigs anesthetized for 24 hours. Blood samples were drawn at 0 (predose) and 0.5, 2, 2.5, 3, 4, 4.5, 6, 8, 12, and 24 hours post drug administration. Drug plasma concentrations were determined using validated bioanalytical assays. The PK parameters were estimated through compartmental and noncompartmental PK analysis. The study showed a statistically significant decrease in FNT clearance (CL; 66% decrease), with an approximately threefold longer half-life (t1/2) in the TH group. The H+TH group showed a 17% reduction in FNT CL, with a 62% longer t1/2 compared with the C group; however, it was not statistically significant. Although not statistically significant, trends toward lower CL and longer t1/2 were observed in the TH and H+TH groups for MDZ and PHB. Additionally, TPM demonstrated a 28% decrease in CL in the H group compared with controls. SIGNIFICANCE STATEMENT: The overarching goal of this study using the neonatal Göttingen Minipig model was to disentangle the effects of systemic hypoxia and TH on PK using four model drugs. Such insights can subsequently be used to inform and develop a physiologically based pharmacokinetic model, which is useful for drug exposure prediction in human neonates.


Subject(s)
Animals, Newborn , Asphyxia Neonatorum , Hypothermia, Induced , Midazolam , Swine, Miniature , Animals , Swine , Hypothermia, Induced/methods , Asphyxia Neonatorum/therapy , Asphyxia Neonatorum/drug therapy , Male , Midazolam/pharmacokinetics , Phenobarbital/pharmacokinetics , Fentanyl/pharmacokinetics , Disease Models, Animal , Infant, Newborn , Hypoxia-Ischemia, Brain/therapy , Hypoxia-Ischemia, Brain/metabolism , Humans
8.
Minerva Anestesiol ; 90(5): 439-451, 2024 05.
Article in English | MEDLINE | ID: mdl-38619185

ABSTRACT

INTRODUCTION: The medical application of music therapy (MT) has received widespread attention in recent years and some researchers have attempted to apply MT to the treatment of patients with anxiety and delirium in ICU. EVIDENCE ACQUISITION: Relevant randomized controlled trials (randomized controlled trials s) were searched in databases, such as Web of Science, PubMed, Embase, Cochrane Library, Medline, Scopus, and CINAHL. Researchers performed literature screening, data extraction, literature quality assessment, and heterogeneity analysis among RCTs. EVIDENCE SYNTHESIS: Fourteen studies met the inclusion criteria. In general, we included RCTs with low risk of bias, and the primary outcome indicators, including the Chinese version of the State-Trait Anxiety Inventory (C-STAI), Visual Analogue Scale for Anxiety Measurement (VAS-A), and Facial Anxiety Scale (FAS), with a recommended level of evidence of "strong". The pooled results indicated that MT was effective in alleviating the anxiety state of ICU patients (95% CI, SMD=-1.09 [-1.52, -0.67], P<0.05) and could reduce mental and physical fatigue in patients with anxious delirium in ICU (95% CI, WMD=-2.35 [-3.37, -1.33], P <0.05). There were significant differences in the therapeutic effects of MT with different intervention durations. Both 15-minute and 30-minute MT were effective in reducing anxiety levels in patients with anxiety disorders in the ICU (15min: 95%CI, SMD=-1.70[-2.15, -1.24], P<0.05; 30min: 95%CI, SMD=-0.73[-1.16, - 0.29], P<0.05). However, when the duration of MT exceeded 45 min, the overtreatment of MT instead interfered with patient rest and failed to produce a positive therapeutic effect (95% CI, SMD=-1.04 [-3.06, 0.97], P=0.31). In addition, a meta-analysis of physiological outcomes found that MT was effective in maintaining the stabilization of heart rate (HR), respiratory rate (RR), and systolic blood pressure (SBP) in ICU patients with anxiety (P<0.05), but did not affect patients' oxygen saturation, mean arterial pressure and diastolic blood pressure (P>0.05). No adverse events occurred during MT treatment in the reports of included 14 studies. CONCLUSIONS: MT can safely and effectively reduce the anxiety level of patients with anxiety and delirium in ICU and relieve their psychological and physical fatigue. And MT was able to maintain the stability of HR, RR, and SBP in ICU patients.


Subject(s)
Anxiety , Delirium , Intensive Care Units , Music Therapy , Randomized Controlled Trials as Topic , Humans , Music Therapy/methods , Delirium/therapy , Anxiety/therapy , Treatment Outcome , Critical Care/methods
9.
Zhongguo Yi Liao Qi Xie Za Zhi ; 48(2): 138-143, 2024 Mar 30.
Article in Chinese | MEDLINE | ID: mdl-38605611

ABSTRACT

Adrenal vein sampling is required for the staging diagnosis of primary aldosteronism, and the frames in which the adrenal veins are presented are called key frames. Currently, the selection of key frames relies on the doctor's visual judgement which is time-consuming and laborious. This study proposes a key frame recognition algorithm based on deep learning. Firstly, wavelet denoising and multi-scale vessel-enhanced filtering are used to preserve the morphological features of the adrenal veins. Furthermore, by incorporating the self-attention mechanism, an improved recognition model called ResNet50-SA is obtained. Compared with commonly used transfer learning, the new model achieves 97.11% in accuracy, precision, recall, F1, and AUC, which is superior to other models and can help clinicians quickly identify key frames in adrenal veins.


Subject(s)
Deep Learning , X-Rays , Radiography
10.
Elife ; 132024 Apr 04.
Article in English | MEDLINE | ID: mdl-38573820

ABSTRACT

Thrombocytopenia caused by long-term radiotherapy and chemotherapy exists in cancer treatment. Previous research demonstrates that 5-Hydroxtrayptamine (5-HT) and its receptors induce the formation of megakaryocytes (MKs) and platelets. However, the relationships between 5-HT1A receptor (5-HTR1A) and MKs is unclear so far. We screened and investigated the mechanism of vilazodone as a 5-HTR1A partial agonist in promoting MK differentiation and evaluated its therapeutic effect in thrombocytopenia. We employed a drug screening model based on machine learning (ML) to screen the megakaryocytopoiesis activity of Vilazodone (VLZ). The effects of VLZ on megakaryocytopoiesis were verified in HEL and Meg-01 cells. Tg (itga2b: eGFP) zebrafish was performed to analyze the alterations in thrombopoiesis. Moreover, we established a thrombocytopenia mice model to investigate how VLZ administration accelerates platelet recovery and function. We carried out network pharmacology, Western blot, and immunofluorescence to demonstrate the potential targets and pathway of VLZ. VLZ has been predicted to have a potential biological action. Meanwhile, VLZ administration promotes MK differentiation and thrombopoiesis in cells and zebrafish models. Progressive experiments showed that VLZ has a potential therapeutic effect on radiation-induced thrombocytopenia in vivo. The network pharmacology and associated mechanism study indicated that SRC and MAPK signaling are both involved in the processes of megakaryopoiesis facilitated by VLZ. Furthermore, the expression of 5-HTR1A during megakaryocyte differentiation is closely related to the activation of SRC and MAPK. Our findings demonstrated that the expression of 5-HTR1A on MK, VLZ could bind to the 5-HTR1A receptor and further regulate the SRC/MAPK signaling pathway to facilitate megakaryocyte differentiation and platelet production, which provides new insights into the alternative therapeutic options for thrombocytopenia.


Subject(s)
Thrombocytopenia , Vilazodone Hydrochloride , Mice , Animals , Vilazodone Hydrochloride/adverse effects , Vilazodone Hydrochloride/metabolism , Zebrafish , Receptor, Serotonin, 5-HT1A/metabolism , Blood Platelets/metabolism , Thrombocytopenia/drug therapy , Thrombocytopenia/metabolism , Megakaryocytes/metabolism , Thrombopoiesis
11.
Eur J Pharmacol ; 971: 176548, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38570080

ABSTRACT

OBJECTIVES: Thrombocytopenia is a disease in which the number of platelets in the peripheral blood decreases. It can be caused by multiple genetic factors, and numerous challenges are associated with its treatment. In this study, the effects of alnustone on megakaryocytes and platelets were investigated, with the aim of developing a new therapeutic approach for thrombocytopenia. METHODS: Random forest algorithm was used to establish a drug screening model, and alnustone was identified as a natural active compound that could promote megakaryocyte differentiation. The effect of alnustone on megakaryocyte activity was determined using cell counting kit-8. The effect of alnustone on megakaryocyte differentiation was determined using flow cytometry, Giemsa staining, and phalloidin staining. A mouse model of thrombocytopenia was established by exposing mice to X-rays at 4 Gy and was used to test the bioactivity of alnustone in vivo. The effect of alnustone on platelet production was determined using zebrafish. Network pharmacology was used to predict targets and signaling pathways. Western blotting and immunofluorescence staining determined the expression levels of proteins. RESULTS: Alnustone promoted the differentiation and maturation of megakaryocytes in vitro and restored platelet production in thrombocytopenic mice and zebrafish. Network pharmacology and western blotting showed that alnustone promoted the expression of interleukin-17A and enhanced its interaction with its receptor, and thereby regulated downstream MEK/ERK signaling and promoted megakaryocyte differentiation. CONCLUSIONS: Alnustone can promote megakaryocyte differentiation and platelet production via the interleukin-17A/interleukin-17A receptor/Src/RAC1/MEK/ERK signaling pathway and thus provides a new therapeutic strategy for the treatment of thrombocytopenia.


Subject(s)
Megakaryocytes , Thrombocytopenia , Mice , Animals , Megakaryocytes/metabolism , Zebrafish/metabolism , Interleukin-17/metabolism , Blood Platelets , Thrombocytopenia/drug therapy , Thrombocytopenia/metabolism , Signal Transduction , Mitogen-Activated Protein Kinase Kinases/metabolism , Mitogen-Activated Protein Kinase Kinases/pharmacology
12.
Nat Commun ; 15(1): 3382, 2024 Apr 20.
Article in English | MEDLINE | ID: mdl-38643164

ABSTRACT

Cancer models play critical roles in basic cancer research and precision medicine. However, current in vitro cancer models are limited by their inability to mimic the three-dimensional architecture and heterogeneous tumor microenvironments (TME) of in vivo tumors. Here, we develop an innovative patient-specific lung cancer assembloid (LCA) model by using droplet microfluidic technology based on a microinjection strategy. This method enables precise manipulation of clinical microsamples and rapid generation of LCAs with good intra-batch consistency in size and cell composition by evenly encapsulating patient tumor-derived TME cells and lung cancer organoids inside microgels. LCAs recapitulate the inter- and intratumoral heterogeneity, TME cellular diversity, and genomic and transcriptomic landscape of their parental tumors. LCA model could reconstruct the functional heterogeneity of cancer-associated fibroblasts and reflect the influence of TME on drug responses compared to cancer organoids. Notably, LCAs accurately replicate the clinical outcomes of patients, suggesting the potential of the LCA model to predict personalized treatments. Collectively, our studies provide a valuable method for precisely fabricating cancer assembloids and a promising LCA model for cancer research and personalized medicine.


Subject(s)
Lung Neoplasms , Humans , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Tumor Microenvironment , Organoids/pathology , Precision Medicine/methods
14.
J Antimicrob Chemother ; 79(5): 1157-1163, 2024 05 02.
Article in English | MEDLINE | ID: mdl-38546761

ABSTRACT

BACKGROUND: Monitoring the trends of pre-treatment drug resistance (PDR) and resistance-associated mutations (RAMs) among antiretroviral-naïve people with HIV (PWH) is important for the implementation of HIV treatment and control programmes. We analysed the trends of HIV-1 PDR after the introduction of second-generation integrase strand-transfer inhibitors (INSTIs) in 2016 in Taiwan, when single-tablet regimens of non-nucleoside reverse-transcriptase inhibitor (NNRTI-) and INSTI-based antiretroviral therapy became the preferred treatments. MATERIALS AND METHODS: In this multicentre study, we included newly diagnosed, antiretroviral-naïve PWH who underwent tests for RAMs between 2016 and 2022. Pre-treatment genotypic resistance testing was performed, along with HIV-1 subtyping and determinations of plasma HIV RNA load and CD4 lymphocyte counts. RAMs were analysed using the Stanford University HIV Drug Resistance Database and only RAMs conferring at least low-level resistance were included. RESULTS: From 2016 to 2022, pre-treatment blood samples from 3001 newly diagnosed PWH, which constituted 24.3% of newly diagnosed PWH in Taiwan during the study period, were tested. Of the PWH with analysable gene sequences, the HIV-1 PDR prevalence to NNRTIs, nucleoside reverse-transcriptase inhibitors (NRTIs), first- and second-generation INSTIs and PIs was 10.0%, 2.1%, 2.5%, 0.6% and 0.4%, respectively. While the trends of PDR remained stable for NRTIs, INSTIs and PIs, there was a significantly increasing trend of PDR to NNRTIs from 6.0% in 2016% to 13.1% in 2022 (P = 0.001). CONCLUSIONS: After the introduction of second-generation INSTIs in Taiwan, the trends of HIV-1 PDR to NRTIs and INSTIs remained low. Furthermore, there was no significant decrease of the prevalence of PDR toward NNRTIs between 2016 and 2022.


Subject(s)
Drug Resistance, Viral , HIV Infections , HIV-1 , Viral Load , Humans , Taiwan/epidemiology , HIV-1/drug effects , HIV-1/genetics , HIV Infections/drug therapy , HIV Infections/virology , Male , Drug Resistance, Viral/genetics , Female , Adult , Middle Aged , Mutation , Genotype , HIV Integrase Inhibitors/therapeutic use , HIV Integrase Inhibitors/pharmacology , CD4 Lymphocyte Count , Anti-HIV Agents/therapeutic use , Anti-HIV Agents/pharmacology , Young Adult , Reverse Transcriptase Inhibitors/therapeutic use , Reverse Transcriptase Inhibitors/pharmacology , RNA, Viral/genetics
15.
Front Oncol ; 14: 1367200, 2024.
Article in English | MEDLINE | ID: mdl-38529383

ABSTRACT

Background: Controversy surrounds the efficacy of adjuvant chemotherapy (ACT) in the treatment of stage I lung adenocarcinoma (LUAD). The objective of this study was to examine the impact of the maximum standardized uptake value (SUVmax) as measured by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) on the efficacy of ACT in patients diagnosed with stage I LUAD. Methods: We scrutinized the medical records of 928 consecutive patients who underwent complete surgical resection for pathological stage I LUAD at our institution. The ideal cut-off value for primary tumor SUVmax in terms of disease-free survival (DFS) and overall survival (OS) was determined using the X-tile software. The Kaplan-Meier method and Cox regression analysis were used for survival analysis. Results: Based on the SUVmax algorithm, the ideal cutoff values were determined to be 4.9 for DFS and 5.0 for OS. We selected 5.0 as the threshold because OS is the more widely accepted predictive endpoint. In a multivariate Cox regression analysis, SUVmax ≥ 5.0, problematic IB stage, and sublobectomy were identified as independent risk factors for poor DFS and OS. It is noteworthy that patients who were administered ACT had significantly longer DFS and OS than what was observed in the subgroup of patients with pathological stage IB LUAD and SUVmax ≥ 5.0 (p < 0.035 and p ≤ 0.046, respectively). However, there was no observed survival advantage for patients in stages IA or IB who had an SUVmax < 5.0. Conclusion: The preoperative SUVmax of tumors served as an indicator of the impact of ACT in the context of completely resected pathological stage I LUAD. Notably, patients within the Stage IB category exhibiting elevated SUVmax levels emerged as a subgroup experiencing substantial benefits from postoperative ACT.

16.
Heliyon ; 10(3): e24545, 2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38322901

ABSTRACT

Aims and objective: To explain the components and elements of glucose management in critically ill adult patients from the healthcare providers' experiences. Background: Critically ill adults are highly susceptible to stress-induced hyperglycaemia due to glucose metabolic disorders. Healthcare workers play a key role in the glycaemic management of critically ill patients. However, there is a lack of qualitative studies on the content and elements of glycaemic management and healthcare workers' perceptions about glycaemic management in China. Design: Qualitative study that followed the Consolidated Criteria for Reporting Qualitative Research (COREQ) guidelines. Methods: Individual semi-structured interviews were conducted from January to April 2022. Fifteen physicians and nurses were recruited from ten hospitals in mainland China. Data were analysed using inductive thematic analysis. Results: Glucose management in critically ill adult patients from their experiences included two parts: the inner ring (practice behaviours) and the external space (methods and drivers). The practice behaviours of glucose management include five elements, while the methods and drivers of glucose management focus on three elements. The content covered under each element was identified. Conclusion: This study developed a glycaemic management model for critically ill adult patients, clarified its elements based on the perceptions of healthcare providers and elaborated on the methods and drivers covered under each element to provide a reference for physicians and nurses to develop a comprehensive glycaemic management guideline for critically ill adult patients. Relevance to clinical practice: Our study proposed a glucose management practice model for critically ill adult patients, and the elements and components included in this model can provide a reference for physicians and nurses when performing glucose management in critically ill patients.

17.
Heliyon ; 10(4): e25948, 2024 Feb 29.
Article in English | MEDLINE | ID: mdl-38384528

ABSTRACT

Social media marketing plays a relevant role in the brand promotion of enterprises owing to its advantages of rapid and diversified communication with consumers. The Chinese Internet enterprise Alipay launched Ant Forest as a mobile application with gamified social functions, bringing consumer-brand engagement. Ant Forest provides a variety of gamification functions (e.g. point, leaderboard, badge, task and teamwork) to encourage users to participate in environmental protection and public welfare activities. These gamification mechanisms, combined with the spread of social media, have realised the co-creation of user brand value. In the current study, 305 Gen Z users of Ant Forest were surveyed through an online questionnaire, and the data analysis was conducted using the partial least squares structural equation modelling (PLS-SEM) method. This study indicates that the four elements of entertainment, trendiness, customisation and word-of-mouth in social media marketing have statistically significant direct effects on the consumer-brand engagement in Ant Forest. In addition, gamification shows a significant positive moderating effect on the relationship between customisation and consumer-brand engagement and a significant negative moderating effect on the relationship between trendiness and consumer-brand engagement in Ant Forest. This study adds gamification to the conceptual system of social media marketing and provides suggestions for the development of gamified social media marketing applications.

18.
J Colloid Interface Sci ; 661: 237-248, 2024 May.
Article in English | MEDLINE | ID: mdl-38301462

ABSTRACT

Lithium ion capacitors (LICs) are a new generation of energy storage devices that combine the super energy storage capability of lithium ion batteries with the satisfactory power density of supercapacitors. The development of high-performance LICs still faces great challenges due to the unbalanced reaction kinetics at the anode and cathode. Therefore, it is an inevitable need to enhance the electron/ion transfer capability of the anode materials. In this paper, to obtain a superior-rate and high-capacity Ni3S2-based anode, highly conductive Ti3C2Tx MXene sheets were introduced to sever as the carrier of Ni3S2 nanoparticles and simultaneously an amorphous carbon layer which coats onto the surface of Ni3S2 nanoparticles was in-situ generated by the carbonization of dopamine reactant. The as-synthesized Ni3S2/Ti3C2Tx/C composite exhibits a high specific surface area (112.6 m2/g) because of the addition of Ti3C2Tx that can reduce the aggregation of Ni3S2 nanoparticles and the in-situ generated amorphous carbon layer that can suppress the growth of Ni3S2 nanoparticles. The Ni3S2/Ti3C2Tx/C anode possesses a remarkable reversible discharge specific capacity (626.0 mAh/g under 0.2 A/g current density), which increases to 1150.8 mAh/g after 400-cycle charge/discharge measurement at the same measurement condition indicating eminent cyclability, along with superior rate capability. To construct a superior-performance LIC device, a sterculiae lychnophorae derived porous carbon (SLPC) cathode with an average discharge specific capacity of 73.4 mAh/g@0.1A/g was prepared. The Ni3S2/Ti3C2Tx/C//SLPC LIC device with optimal cathode/anode mass ratio has a satisfactory energy density ranging from 32.8 to 119.1 Wh kg-1 at the corresponding power density of 8799.4 to 157.5 W kg-1, together with a prominent capacity retention (95.5 %@1 A/g after 10,000 cycles).

19.
Int J Infect Dis ; 140: 1-8, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38163618

ABSTRACT

OBJECTIVES: WHO has recommended same-day antiretroviral therapy (SDART) initiation since 2017; however, higher attrition rates were noted in developing countries. METHODS: We included newly diagnosed people with HIV (PWH) from 2018 to 2022 at 18 hospitals around Taiwan. SDART initiation was defined as starting ART on the same day of HIV diagnosis and rapid initiation as starting ART within 14 days of diagnosis. A composite unfavorable outcome was defined as death after 30 days of diagnosis, loss to follow-up (LTFU), or virologic failure or rebound at 12 months. RESULTS: At 12 months, PWH on SDART initiation and those on rapid ART initiation showed similar rates of engagement in care with plasma HIV-1 RNA <50 copies/mL (87.5% vs 87.7%) and composite unfavorable outcome (7.7% vs 7.7%). PWH aged >30 years were less likely to have LTFU (aHR 0.44, 95% CI 0.28-0.70). PWH aged >30 years (aHR 0.59, 95% CI 0.41-0.85) and gay, bisexual, and men who have sex with men (GBMSM) (aHR 0.50, 95% CI 0.32-0.79) were less likely to have composite unfavorable outcomes. CONCLUSIONS: SDART and rapid ART initiation resulted in comparable clinical outcomes and viral suppression rates. PWH aged >30 years and GBMSM were less likely to have unfavorable outcomes.


Subject(s)
Anti-HIV Agents , HIV Infections , Sexual and Gender Minorities , Male , Humans , Taiwan/epidemiology , Homosexuality, Male , CD4 Lymphocyte Count , HIV Infections/drug therapy , Anti-HIV Agents/therapeutic use
20.
Crit Care Nurse ; 44(1): 21-32, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38295867

ABSTRACT

BACKGROUND: Continuous insulin infusion is a method for maintaining blood glucose stability in critically ill patients with hyperglycemia. Many insulin infusion protocols have been applied in intensive care units. Understanding the content of these protocols can help clinical staff choose the most appropriate and convenient protocol and promote best practices in managing glucose levels in critically ill adult patients. OBJECTIVE: To examine the types of insulin infusion therapies performed for blood glucose management in critically ill patients. METHODS: For this scoping review, 3 Chinese-language and 8 English-language databases were searched for articles published from May 25, 2016, to October 25, 2022. RESULTS: Twenty-one articles met the inclusion criteria. Twenty-one insulin infusion protocols were examined. Most of the insulin infusion protocols were paper protocols. Fourteen glucose management indicators were included in the 21 protocols. The glucose target range for all 21 protocols ranged from 70 to 180 mg/dL (3.9-10.0 mmol/L). Nurses were primarily responsible for protocol implementation in most protocol development processes. The roles of nurses differed in nurse-led insulin infusion protocols and non-nurse-led insulin infusion protocols. DISCUSSION: This scoping review indicates an urgent need for more comprehensive glycemic control guidelines for patients receiving critical care. Because insulin infusion protocols are core aspects of blood glucose management guidelines, different population subgroups should also be considered. CONCLUSIONS: Nurse-led guidelines must be based on the best available evidence and should include other variables related to glucose management (eg, patient disease type, medication, and nutrition) in addition to insulin infusion.


Subject(s)
Blood Glucose , Hyperglycemia , Adult , Humans , Hypoglycemic Agents/therapeutic use , Critical Illness/therapy , Insulin/therapeutic use , Hyperglycemia/drug therapy , Review Literature as Topic
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