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1.
BMC Complement Med Ther ; 24(1): 348, 2024 Oct 02.
Article in English | MEDLINE | ID: mdl-39358730

ABSTRACT

BACKGROUND: Advanced cancer patients commonly suffer from a fatigue-sleep disturbance symptom cluster. Baduanjin is considered a promising mind-body exercise for relieving the fatigue-sleep disturbance symptom cluster. However, few studies have investigated a tailored Baduanjin for advanced cancer patients. The proposed study will create an optimized Baduanjin exercise program to adapt to advanced cancer patients and evaluate the effect of a Simple Sitting Baduanjin (SSBDJ) mind-body exercise on the fatigue-sleep disturbance symptom cluster among advanced cancer patients. METHODS: The study will be a prospective, assessor-blinded, two-arm, randomized controlled trial, involving a 12-week intervention and 4-week follow-up. A total of 108 advanced cancer patients experiencing the fatigue-sleep disturbance symptom cluster will be recruited from two tertiary general hospitals in China. Participants will be randomized to an experimental group (n = 54) or a control group (n = 54). The experimental group will receive a 12-week SSBDJ intervention plus the usual care, and the control group will receive only the usual care. Outcomes including fatigue-sleep disturbance symptom cluster, fatigue, sleep disturbance, and quality of life will be measured before the intervention, at the 4th, 8th, and 12th weeks of the intervention, and 4 weeks after the intervention. The intention-to-treat principle and a generalized estimating equation will be used to analyze data. DISCUSSION: This study may produce a new Baduanjin exercise prescription that is user-friendly, simple to execute, more targeted, and adaptable. If proven effective, this approach may be integrated into routine cancer care to manage the fatigue-sleep disturbance symptom cluster and improve QOL in advanced cancer patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-2,300,072,331. Registered on 9 June 2023.


Subject(s)
Fatigue , Neoplasms , Sleep Wake Disorders , Adult , Female , Humans , Male , Middle Aged , China , Exercise Therapy/methods , Fatigue/therapy , Fatigue/etiology , Mind-Body Therapies/methods , Neoplasms/complications , Prospective Studies , Quality of Life , Randomized Controlled Trials as Topic , Sleep Wake Disorders/therapy , Sleep Wake Disorders/etiology
3.
Nat Chem ; 2024 Sep 04.
Article in English | MEDLINE | ID: mdl-39232136

ABSTRACT

Developing highly effective catalysts for ammonia (NH3) synthesis is a challenging task. Even the current, prevalent iron-derived catalysts used for industrial NH3 synthesis require harsh reaction conditions and involve massive energy consumption. Here we show that anchoring buckminsterfullerene (C60) onto non-iron transition metals yields cluster-matrix co-catalysts that are highly efficient for NH3 synthesis. Such co-catalysts feature separate catalytic active sites for hydrogen and nitrogen. The 'electron buffer' behaviour of C60 balances the electron density at catalytic transition metal sites and enables the synergistic activation of nitrogen on transition metals in addition to the activation and migration of hydrogen on C60 sites. As demonstrated in long-term, continuous runs, the C60-promoting transition metal co-catalysts exhibit higher NH3 synthesis rates than catalysts without C60. With the involvement of C60, the rate-determining step in the cluster-matrix co-catalysis is found to be the hydrogenation of *NH2. C60 incorporation exemplifies a practical approach for solving hydrogen poisoning on a wide variety of oxide-supported Ru catalysts.

4.
Dalton Trans ; 2024 Sep 26.
Article in English | MEDLINE | ID: mdl-39324845

ABSTRACT

Herein, we synthesized new manganese(I) complexes coordinated with the tetradentate ligand PNNP. The complexes show higher activity and excellent substituent tolerance in contrast to their manganese counterparts and are applicable in the hydrogenation of a wide range of aromatic, aliphatic and heterocyclic ketones to their corresponding alcohols.

5.
Int J Comput Assist Radiol Surg ; 19(10): 2011-2021, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39112914

ABSTRACT

PURPOSE: We introduce a novel approach for bronchoscopic navigation that leverages neural radiance fields (NeRF) to passively locate the endoscope solely from bronchoscopic images. This approach aims to overcome the limitations and challenges of current bronchoscopic navigation tools that rely on external infrastructures or require active adjustment of the bronchoscope. METHODS: To address the challenges, we leverage NeRF for bronchoscopic navigation, enabling passive endoscope localization from bronchoscopic images. We develop a two-stage pipeline: offline training using preoperative data and online passive pose estimation during surgery. To enhance performance, we employ Anderson acceleration and incorporate semantic appearance transfer to deal with the sim-to-real gap between training and inference stages. RESULTS: We assessed the viability of our approach by conducting tests on virtual bronchscopic images and a physical phantom against the SLAM-based methods. The average rotation error in our virtual dataset is about 3.18 ∘ and the translation error is around 4.95 mm. On the physical phantom test, the average rotation and translation error are approximately 5.14 ∘ and 13.12 mm. CONCLUSION: Our NeRF-based bronchoscopic navigation method eliminates reliance on external infrastructures and active adjustments, offering promising advancements in bronchoscopic navigation. Experimental validation on simulation and real-world phantom models demonstrates its efficacy in addressing challenges like low texture and challenging lighting conditions.


Subject(s)
Bronchoscopy , Phantoms, Imaging , Bronchoscopy/methods , Humans , Surgery, Computer-Assisted/methods , Neural Networks, Computer
6.
iScience ; 27(8): 110420, 2024 Aug 16.
Article in English | MEDLINE | ID: mdl-39104413

ABSTRACT

C3N4 is widely applied in the synthesis of single-atom catalysts. However, understanding on the active site and the reaction mechanism is not fully in consensus. Especially, bare studies have considered the coordination environment of the single-atomic dopant and the effect of nitrogen vacancy on C3N4. In this study, we found that the presence of nitrogen vacancies promotes the activation of water and reduces the activation energy barrier for hydrogen generation. The results show that a synergistic effect between single-atom Pt and nitrogen vacancies enables the catalyst to achieve a superior hydrogen production rate of 3,890 µmol/g/h, which is 16.8 times higher than that of pristine C3N4. Moreover, the catalyst is also applicable for photocatalytic hydrogen production from seawater without significantly decreased hydrogen production rate. This study paves the way for the rational design and optimization of next-generation photocatalysts for sustainable energy applications, particularly in solar-driven hydrogen production.

7.
Sci Rep ; 14(1): 19103, 2024 08 17.
Article in English | MEDLINE | ID: mdl-39154083

ABSTRACT

Peritoneal recurrence (PR) in gastric cancer after curative resection has poor prognosis. Therefore, we aimed to construct a nomogram to predict PR, and establish PR score for risk stratification to guide adjuvant chemotherapy. A total of 315 patients with gastric cancer after radical surgery were included, and randomly stratified into training group (n = 221) and validation group (n = 94). Univariate and multivariate analyses were used to determine predictive factors of PR. The nomogram was constructed to predict the risk of PR. We utilized the time-dependent area under the receiver operating characteristic (ROC) curves (AUCs), calibration curves, and decision curve analysis (DCA) to evaluate the performance of the nomogram. Multivariate analysis showed that tumor site, N stage, preoperative CEA, and postoperative CA199 were independent predictors of PR. A nomogram was constructed to predict PR based on these factors. The AUC value was 0.755 in the training group and 0.715 in the validation group. The calibration curves showed good agreement between prediction and observation in the training and validation groups. The decision curve analysis displayed a good net benefit of the nomogram. The novel PR score was developed and patients were stratified into the low-, medium-, and high -risk groups. For the high-risk group, postoperative adjuvant chemotherapy significantly improved patients' overall survival (OS) and disease-free survival (DFS). The establishment of nomogram facilitates the prediction of PR after radical gastrectomy, and a novel PR score may help guide adjuvant chemotherapy for gastric cancer.


Subject(s)
Neoplasm Recurrence, Local , Nomograms , Peritoneal Neoplasms , Stomach Neoplasms , Humans , Stomach Neoplasms/surgery , Stomach Neoplasms/pathology , Stomach Neoplasms/mortality , Male , Female , Middle Aged , Peritoneal Neoplasms/surgery , Peritoneal Neoplasms/secondary , Peritoneal Neoplasms/mortality , Aged , Risk Assessment/methods , ROC Curve , Prognosis , Gastrectomy , Chemotherapy, Adjuvant , Adult , Risk Factors
8.
PLoS One ; 19(7): e0306981, 2024.
Article in English | MEDLINE | ID: mdl-38990912

ABSTRACT

OBJECTIVES: This study aimed to examine the mediating role of readiness for hospital discharge (RHD) and stoma self-efficacy (SSE) in the relationship between quality of discharge teaching (QDT) and health-related quality of life (HRQOL) in colorectal cancer patients with temporary enterostomy, and the gender difference of mediating effect. BACKGROUND: It is not clear how RHD, QDT, SSE and HRQOL interact in colorectal cancer patients with temporary enterostomy. METHODS: This was a prospective follow-up survey. 221 colorectal cancer patients with temporary enterostomy were conveniently recruited from a general hospital in Southeast China. The Quality of Discharge Teaching Scale, Readiness for Hospital Discharge Scale, Stoma Self-Efficacy Scale, and Stoma Quality of Life Scale were used to collect data. Pearson's correlation and structural equation models were used to analyze the data. SPSS 26.0 and Amos 28.0 software were used for analysis the collected data. RESULTS: Regarding the relationship of QDT and HRQOL, only QDT-T had a direct effect among colorectal cancer patients with stomas (b = 0.233, P<0.001, percentile 95% CI = [0.145, 0.314]). However, both QDT-T and QDT-R can predict HRQOL indirectly through three paths: (1) the mediating role of SSE (b = 0.050, P = 0.009, percentile 95% CI = [0.013, 0.098]; b = 0.077, P = 0.008, percentile 95% CI = [0.021, 0.164]), (2) the mediating role of RHD (b = 0.044, P = 0.004, percentile 95% CI = [0.014, 0.085]; b = 0.044, P = 0.005, percentile 95% CI = [0.010, 0.102]), and (3) the chain mediating role of SSE and RHD (b = 0.030, P = 0.003, percentile 95% CI = [0.011, 0.059]; b = 0.047, P = 0.003, percentile 95% CI = [0.015, 0.103]). The similar chain mediating effect in male stoma patients was also found (b = 0.041, P = 0.002, percentile 95% CI = [0.016, 0.080]; b = 0.046, P = 0.004, percentile 95% CI = [0.011, 0.114]). CONCLUSIONS: Stoma self-efficacy and readiness for hospital discharge played important intermediary roles in the relationship between quality of discharge teaching and health-related quality of life in colorectal cancer patients with stomas. Health care providers can design SSE-enhancing and RHD-enhancing discharge planning for colorectal cancer patients with temporary enterostomies.


Subject(s)
Colorectal Neoplasms , Enterostomy , Patient Discharge , Quality of Life , Self Efficacy , Humans , Colorectal Neoplasms/surgery , Colorectal Neoplasms/psychology , Male , Female , Middle Aged , Prospective Studies , Aged , Adult , Surgical Stomas , Follow-Up Studies , China , Surveys and Questionnaires
9.
J Am Chem Soc ; 146(31): 21612-21622, 2024 Aug 07.
Article in English | MEDLINE | ID: mdl-39046371

ABSTRACT

Thermoset polymers have become integral to our daily lives due to their exceptional durability, making them feasible for a myriad of applications; however, this ubiquity also raises serious environmental concerns. Covalent adaptable networks (CANs) with dynamic covalent linkages that impart efficient reprocessability and recyclability to thermosets have garnered increasing attention. While various dynamic exchange reactions have been explored in CANs, many rely on the stimuli of active nucleophilic groups and/or catalysts, introducing performance instability and escalating the initial investment. Herein, we propose a new direct and catalyst-free C═C/C═N metathesis reaction between α-cyanocinnamate and aldimine as a novel dynamic covalent motif for constructing recyclable thermosets. This chemistry offers mild reaction conditions (room temperature and catalyst-free), ensuring high yields and simple isolation procedures. By incorporating dynamic C═C/C═N linkages into covalently cross-linked polymer networks, we obtained dynamic thermosets that exhibit both malleability and reconfigurability. The resulting tunable dynamic properties, coupled with the high thermal stability and recyclability of the C═C/C═N linkage-based networks, enrich the toolbox of dynamic covalent chemistry.

10.
BMC Health Serv Res ; 24(1): 780, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38977998

ABSTRACT

BACKGROUND: Although prior research has estimated the overarching cost burden of heart failure (HF), a thorough analysis examining medical expense differences and trends, specifically among commercially insured patients with heart failure, is still lacking. Thus, the study aims to examine historical trends and differences in medical costs for commercially insured heart failure patients in the United States from 2006 to 2021. METHODS: A population-based, cross-sectional analysis of medical and pharmacy claims data (IQVIA PharMetrics® Plus for Academic) from 2006 to 2021 was conducted. The cohort included adult patients (age > = 18) who were enrolled in commercial insurance plans and had healthcare encounters with a primary diagnosis of HF. The primary outcome measures were the average total annual payment per patient and per cost categories encompassing hospitalization, surgery, emergency department (ED) visits, outpatient care, post-discharge care, and medications. The sub-group measures included systolic, diastolic, and systolic combined with diastolic, age, gender, comorbidity, regions, states, insurance payment, and self-payment. RESULTS: The study included 422,289 commercially insured heart failure (HF) patients in the U.S. evaluated from 2006 to 2021. The average total annual cost per patient decreased overall from $9,636.99 to $8,201.89, with an average annual percentage change (AAPC) of -1.11% (95% CI: -2% to -0.26%). Hospitalization and medication costs decreased with an AAPC of -1.99% (95% CI: -3.25% to -0.8%) and - 3.1% (95% CI: -6.86-0.69%). On the other hand, post-discharge, outpatient, ED visit, and surgery costs increased by an AAPC of 0.84% (95% CI: 0.12-1.49%), 4.31% (95% CI: 1.03-7.63%), 7.21% (95% CI: 6.44-8.12%), and 9.36% (95% CI: 8.61-10.19%). CONCLUSIONS: The study's findings reveal a rising trend in average total annual payments per patient from 2006 to 2015, followed by a subsequent decrease from 2016 to 2021. This decrease was attributed to the decline in average patient costs within the Medicare Cost insurance category after 2016, coinciding with the implementation of the Medicare Access and CHIP Reauthorization Act (MACRA) of 2015. Additionally, expenses related to surgical procedures, emergency department (ED) visits, and outpatient care have shown substantial growth over time. Moreover, significant differences across various variables have been identified.


Subject(s)
Heart Failure , Insurance, Health , Humans , Heart Failure/therapy , Heart Failure/economics , United States , Male , Female , Cross-Sectional Studies , Middle Aged , Aged , Adult , Insurance, Health/economics , Insurance, Health/statistics & numerical data , Health Care Costs/statistics & numerical data , Health Care Costs/trends , Insurance Claim Review , Hospitalization/economics , Health Expenditures/statistics & numerical data , Health Expenditures/trends
11.
Front Pharmacol ; 15: 1396713, 2024.
Article in English | MEDLINE | ID: mdl-38863982

ABSTRACT

Background: As a class of analgesics, opioids are frequently used to treat both acute and chronic moderate to severe pain. Patients frequently receive opioid painkillers after orthopedic accidents or surgeries. Evidence suggests that opioid drug users have a 55.1% higher risk of fracture and poor bone repair than non-users of opioid drugs. The key pathogenic alterations in the incidence and progression of poor bone repair are over apoptosis and aging of osteoblasts due to the stress caused by oxidation. Dexmedetomidine (Dex) has been proven to protect against a variety of degenerative illnesses by reducing oxidative stress. However, nothing is known about how it affects bone repair. Methods: PI3K/Akt/Nrf2 pathway was detected by immunofluorescence and Western blot. SOD, CAT, JC-1, dihydroethidium and mitosox were used in the Oxidative Stress. Micro-CT, H&E and Masson's staining, immunohistochemically were performed to evaluate the therapeutic effects of DEX on calvarial defects in the morphine-induced rat model. Results: We found that morphine-induced an imbalance in the metabolism and catabolism of primary rat Osteoblasts. However, these conditions could be inhibited by DEX treatment. In the meantime, DEX induced the expression of Nrf2-regulated antioxidant enzymes such as NQO1, HO-1, GCLm, GCLc, and TrxR1. DEX-mediated Nrf2 activation is linked to the PI3K/Akt signaling system. Furthermore, it has been established that intravenous DEX enhanced the growth of bone healing in a model of a surgically produced rat cranial lesion. Conclusion: This is the first description of the unique DEX mechanism acting as a Nrf2 activator against morphine-mediated oxidative harm, raising the possibility that the substance may be used to prevent bone defects.

12.
Environ Res ; 257: 119291, 2024 Sep 15.
Article in English | MEDLINE | ID: mdl-38823607

ABSTRACT

The presence of butylparaben (BP), a prevalent pharmaceutical and personal care product, in surface waters has raised concerns regarding its impact on aquatic ecosystems. Despite its frequent detection, the toxicity of BP to the cyanobacterium Microcystis aeruginosa remains poorly understood. This study investigates the influence of BP on the growth and physiological responses of M. aeruginosa. Results indicate that low concentrations of BP (below 2.5 mg/L) have negligible effects on M. aeruginosa growth, whereas higher concentrations (5 mg/L and 10 mg/L) lead to significant growth inhibition. This inhibition is attributed to the severe disruption of photosynthesis, evidenced by decreased Fv/Fm values and chlorophyll a content. BP exposure also triggers the production of reactive oxygen species (ROS), resulting in elevated activity of antioxidant enzymes. Excessive ROS generation stimulates the production of microcystin-LR (MC-LR). Furthermore, lipid peroxidation and cell membrane damage indicate that high BP concentrations cause cell membrane rupture, facilitating the release of MC-LR into the environment. Transcriptome analysis reveals that BP disrupts energy metabolic processes, particularly affecting genes associated with photosynthesis, carbon fixation, electron transport, glycolysis, and the tricarboxylic acid cycle. These findings underscore the profound physiological impact of BP on M. aeruginosa and highlight its role in stimulating the production and release of MC-LR, thereby amplifying environmental risks in aquatic systems.


Subject(s)
Microcystis , Microcystis/drug effects , Microcystis/growth & development , Microcystis/metabolism , Microcystins/biosynthesis , Biomass , Cell Membrane/drug effects , Cell Membrane/metabolism , Marine Toxins/biosynthesis , Parabens/pharmacology , Antioxidants/metabolism
13.
Sci Total Environ ; 946: 174203, 2024 Oct 10.
Article in English | MEDLINE | ID: mdl-38909793

ABSTRACT

Inorganic nitrates were considered to be a potential source of atmospheric NO2-/HONO during the daytime. To better evaluate the contribution of nitrate photochemistry on NO2-/HONO formation, the photolysis of nitrates in the real atmospheric environment needs to be further explored. Here, the NO2- generation by the photolysis of inorganic nitrates in the presence of total water-soluble organic carbon (WSOC) was quantified. The physicochemical properties of WSOC were measured to understand the underlying mechanism for the photolysis of inorganic nitrates with WSOC. WSOC enhanced or suppressed the photochemical conversion of nitrates to NO2-, with the quantum yield of NO2- (ΦNO2-) varying from (0.07 ± 0.02)% to (3.11 ± 0.04)% that depended on the light absorption properties of WSOC. Reactive oxygen species (ROS) generated from WSOC, including O2-/HO2 and OH, played a dual role in the NO2- formation. Light-absorbing substances in WSOC, such as N-containing and carbonyl aromatics, produced O2-/HO2 that enhanced the secondary conversion of NO2 to NO2-. On the other hand, OH deriving from the WSOC photochemistry inhibited the nitrate photodegradation and the NO2- formation. HONO source strength by the aqueous photolysis of nitrates with WSOC was estimated to be lower than 100 ppt h-1, which may partly contribute to the atmospheric HONO source in some cases.

15.
BMC Palliat Care ; 23(1): 136, 2024 May 29.
Article in English | MEDLINE | ID: mdl-38811953

ABSTRACT

BACKGROUND: An accurate perception of death risk is a prerequisite for advanced cancer patients to make informed end-of-life care decisions. However, there is to date no suitable scale to measure death risk perception. This study was to develop and psychometrically test the death risk perception scale (DRPS) for advanced cancer patients. METHODS: Process of instrument development and psychometric evaluation were used. First, qualitative research, a literature review, brainstorming, a Delphi study, and cognitive interviews were conducted to construct a pretest scale of death risk perception. Second, a scale-based survey was administered to 479 advanced cancer patients. Item, exploratory factor, and confirmatory factor analyses were employed to optimize the scale. The Cronbach's alpha was calculated as a reliability analysis. The validity analysis included construct, convergent, discriminant, and content validity values. RESULTS: A three-dimension, 12-item scale was developed, including deliberative, affective, and experiential risk perception. The confirmatory factor analysis supported the three-factor model with satisfactory convergent and discriminant validity levels. The Cronbach's alpha coefficient for internal consistency was 0.807 and scale-level content validity index was 0.98. CONCLUSIONS: The 12-item DRPS is a reliable and valid instrument for assessing the level of death risk perception in advanced cancer patients. More studies are needed to examine its structure and robustness prior to use.


Subject(s)
Attitude to Death , Neoplasms , Perception , Psychometrics , Humans , Psychometrics/instrumentation , Psychometrics/methods , Neoplasms/psychology , Neoplasms/mortality , Male , Female , Middle Aged , Surveys and Questionnaires , Reproducibility of Results , Aged , Adult , Qualitative Research , Risk Assessment/methods , Risk Assessment/standards , Delphi Technique , Factor Analysis, Statistical , Aged, 80 and over
16.
Cancer Lett ; 593: 216956, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38735381

ABSTRACT

Anti-CDK4/6 therapy has been employed for the treatment for head and neck squamous cell carcinoma (HNSCC) with CDK4/6 hyperactivation, but the response rate is relatively low. In this study, we first showed that CDK4 and CDK6 was over-expressed and conferred poor prognosis in HNSCC. Moreover, in RB-positive HNSCC, STAT3 signaling was activated induced by CDK4/6 inhibition and STAT3 promotes RB deficiency by upregulation of MYC. Thirdly, the combination of Stattic and CDK4/6 inhibitor results in striking anti-tumor effect in vitro and in Cal27 derived animal models. Additionally, phospho-STAT3 level negatively correlates with RB expression and predicts poor prognosis in patients with HNSCC. Taken together, our findings suggest an unrecognized function of STAT3 confers to CDK4/6 inhibitors resistance and presenting a promising combination strategy for patients with HNSCC.


Subject(s)
Cyclin-Dependent Kinase 4 , Cyclin-Dependent Kinase 6 , Head and Neck Neoplasms , Protein Kinase Inhibitors , STAT3 Transcription Factor , Squamous Cell Carcinoma of Head and Neck , Xenograft Model Antitumor Assays , Humans , Cyclin-Dependent Kinase 4/antagonists & inhibitors , Cyclin-Dependent Kinase 6/antagonists & inhibitors , STAT3 Transcription Factor/metabolism , Animals , Head and Neck Neoplasms/drug therapy , Head and Neck Neoplasms/pathology , Head and Neck Neoplasms/metabolism , Head and Neck Neoplasms/genetics , Squamous Cell Carcinoma of Head and Neck/drug therapy , Squamous Cell Carcinoma of Head and Neck/metabolism , Squamous Cell Carcinoma of Head and Neck/genetics , Cell Line, Tumor , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/therapeutic use , Signal Transduction/drug effects , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/genetics , Female , Male , Mice, Nude , Mice , Retinoblastoma Protein/metabolism , Cell Proliferation/drug effects , Drug Synergism , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Drug Resistance, Neoplasm/drug effects , Phosphorylation
17.
Cell Rep Med ; 5(5): 101519, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38692271

ABSTRACT

Osteosarcoma (OS) is the most common malignant bone tumor with a poor prognosis. Here, we show that the nuclear receptor RORγ may serve as a potential therapeutic target in OS. OS exhibits a hyperactivated oxidative phosphorylation (OXPHOS) program, which fuels the carbon source to promote tumor progression. We found that RORγ is overexpressed in OS tumors and is linked to hyperactivated OXPHOS. RORγ induces the expression of PGC-1ß and physically interacts with it to activate the OXPHOS program by upregulating the expression of respiratory chain component genes. Inhibition of RORγ strongly inhibits OXPHOS activation, downregulates mitochondrial functions, and increases ROS production, which results in OS cell apoptosis and ferroptosis. RORγ inverse agonists strongly suppressed OS tumor growth and progression and sensitized OS tumors to chemotherapy. Taken together, our results indicate that RORγ is a critical regulator of the OXPHOS program in OS and provides an effective therapeutic strategy for this deadly disease.


Subject(s)
Bone Neoplasms , Mitochondria , Nuclear Receptor Subfamily 1, Group F, Member 3 , Osteosarcoma , Oxidative Phosphorylation , Osteosarcoma/metabolism , Osteosarcoma/pathology , Osteosarcoma/genetics , Humans , Oxidative Phosphorylation/drug effects , Mitochondria/metabolism , Mitochondria/pathology , Nuclear Receptor Subfamily 1, Group F, Member 3/metabolism , Nuclear Receptor Subfamily 1, Group F, Member 3/genetics , Cell Line, Tumor , Animals , Bone Neoplasms/metabolism , Bone Neoplasms/pathology , Bone Neoplasms/genetics , Bone Neoplasms/drug therapy , Mice , Reactive Oxygen Species/metabolism , Apoptosis/drug effects , Gene Expression Regulation, Neoplastic , Ferroptosis/genetics , Ferroptosis/drug effects , Mice, Nude , Male , Cell Proliferation , RNA-Binding Proteins
18.
Commun Med (Lond) ; 4(1): 99, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38783011

ABSTRACT

BACKGROUND: Alzheimer's disease (AD) is the most common neurodegenerative disease. Studying the effects of drug treatments on multiple health outcomes related to AD could be beneficial in demonstrating which drugs reduce the disease burden and increase survival. METHODS: We conducted a comprehensive causal inference study implementing doubly robust estimators and using one of the largest high-quality medical databases, the Oracle Electronic Health Records (EHR) Real-World Data. Our work was focused on the estimation of the effects of the two common Alzheimer's disease drugs, Donepezil and Memantine, and their combined use on the five-year survival since initial diagnosis of AD patients. Also, we formally tested for the presence of interaction between these drugs. RESULTS: Here, we show that the combined use of Donepezil and Memantine significantly elevates the probability of five-year survival. In particular, their combined use increases the probability of five-year survival by 0.050 (0.021, 0.078) (6.4%), 0.049 (0.012, 0.085), (6.3%), 0.065 (0.035, 0.095) (8.3%) compared to no drug treatment, the Memantine monotherapy, and the Donepezil monotherapy respectively. We also identify a significant beneficial additive drug-drug interaction effect between Donepezil and Memantine of 0.064 (0.030, 0.098). CONCLUSIONS: Based on our findings, adopting combined treatment of Memantine and Donepezil could extend the lives of approximately 303,000 people with AD living in the USA to be beyond five-years from diagnosis. If these patients instead have no drug treatment, Memantine monotherapy or Donepezil monotherapy they would be expected to die within five years.


Alzheimer's disease is the most common type of dementia, affecting millions of people worldwide. In this study, we investigated the effects of two drugs commonly prescribed to people with Alzheimer's disease called Donepezil and Memantine to see whether they had an impact on when people died. We found that the combined use of Donepezil and Memantine significantly increased the probability of a person surviving five years compared to no drug treatment or treatment with Donepezil or Memantine alone. Our results suggest that the lives of many Alzheimer's patients in the USA who are currently on no drug treatment or just Donepezil or Memantine could be extended if they were treated with both drugs simultaneously.

19.
Front Public Health ; 12: 1349753, 2024.
Article in English | MEDLINE | ID: mdl-38699425

ABSTRACT

Background: An increase in Heatstroke cases occurred in southwest China in 2022 due to factors like global warming, abnormal temperature rise, insufficient power supply, and other contributing factors. This resulted in a notable rise in Heatstroke patients experiencing varying degrees of organ dysfunction. This descriptive study aims to analyze the epidemiology and clinical outcomes of Heatstroke patients in the ICU, providing support for standardized diagnosis and treatment, ultimately enhancing the prognosis of Heatstroke. Methods: A retrospective, multicenter, descriptive analysis was conducted on Heatstroke patients admitted to ICUs across 83 hospitals in southwest China. Electronic medical records were utilized for data collection, encompassing various aspects such as epidemiological factors, onset symptoms, complications, laboratory data, concurrent infections, treatments, and patient outcomes. Results: The dataset primarily comprised classic heatstroke, with 477 males (55% of total). The patient population had a median age of 72 years (range: 63-80 years). The most common initial symptoms were fever, mental or behavioral abnormalities, and fainting. ICU treatment involved respiratory support, antibiotics, sedatives, and other interventions. Among the 700 ICU admissions, 213 patients had no infection, while 487 were diagnosed with infection, predominantly lower respiratory tract infection. Patients presenting with neurological symptoms initially (n = 715) exhibited higher ICU mortality risk compared to those without neurological symptoms (n = 104), with an odds ratio of 2.382 (95% CI 1.665, 4.870) (p = 0.017). Conclusion: In 2022, the majority of Heatstroke patients in southwest China experienced classical Heatstroke, with many acquiring infections upon admission to the ICU. Moreover, Heatstroke can result in diverse complications.


Subject(s)
Heat Stroke , Intensive Care Units , Humans , Heat Stroke/epidemiology , Heat Stroke/mortality , Male , China/epidemiology , Female , Retrospective Studies , Aged , Middle Aged , Aged, 80 and over , Intensive Care Units/statistics & numerical data , Risk Factors
20.
Int J Nurs Stud ; 155: 104769, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38676992

ABSTRACT

BACKGROUND: Nursing care of colorectal cancer patients with stomas presents unique challenges, particularly during the transition from hospital to home. Early discharge programs can assist patients during this critical period. However, the effects of delivering a nurse-led discharge planning program remain under-studied. OBJECTIVE: Evaluate the effects of a nurse-led discharge planning on the quality of discharge education, stoma self-efficacy, readiness for hospital discharge, stoma quality of life, incidence of stoma complications, unplanned readmission rate, and length of stays. DESIGN: Assessor-blind parallel-arm randomized controlled trial with a repeated-measures design. SETTING(S): Participants were recruited from inpatients in the colorectal surgery unit of a university-affiliated hospital in Fujian, China. PARTICIPANTS: A total of 160 patients with colorectal cancer who received enterostomy surgery and were scheduled to be discharged to their homes. METHOD: Participants were randomly allocated to the experimental and control groups. The former received nurse-led discharge planning in addition to the usual discharge education, while the control group received only the usual discharge education. The program included an assessment, health education, stoma care, stoma support, discharge review, discharge medication and checklist integration, discharge referral, and post-hospital follow-up. Baseline data were collected prior to the intervention (T0). Data on the quality of discharge teaching, readiness for hospital discharge, stoma self-efficacy, and stoma quality of life were measured on the day of discharge from the hospital (T1). Patients' stoma self-efficacy and quality of life were repeat-measured 30 (T2) and 90 days post-discharge (T3). Data on stoma complications (T1, T2, T3), length of stays (T1), and unplanned readmission (T2, T3) were collected from medical records. RESULTS: Participants in the intervention group showed significant improvement in the quality of discharge teaching, readiness for hospital discharge, stoma self-efficacy, stoma quality of life, complications, and unplanned readmission, compared to the control group (p < 0.001). However, no statistically significant differences were observed in length of stays (p > 0.05). CONCLUSIONS: The program was effective for improving quality of discharge teaching, readiness for hospital discharge, stoma self-efficacy, and stoma quality of life, as well as for reducing complications and unplanned readmission among stoma patients. Integration of discharge planning into the usual process of care is recommended for clinical practice to facilitate a successful transition from hospital to home. REGISTRATION: This study was registered at the Chinese clinical trial registry (ChiCTR2200058756) on April 16, 2022, and participant recruitment was initiated in May 2022.


Subject(s)
Colorectal Neoplasms , Patient Discharge , Humans , Colorectal Neoplasms/nursing , Colorectal Neoplasms/surgery , Female , Male , Middle Aged , Aged , Surgical Stomas , China , Quality of Life
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