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1.
Global Spine J ; : 21925682231174192, 2023 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-37129361

RESUMO

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVES: Postoperative ileus (POI) can negatively impact patient recovery and surgical outcomes after spine surgery. Emerging studies have focused on the risk factors for POI after spine surgery. This study aimed to review the available literature on risk factors associated with POI following elective spine surgery. METHODS: Electronic databases were searched to identify relevant studies. Meta-analysis was performed using random-effect model. Risk factors for POI were summarized using pooled odds ratio (OR) with 95% confidence intervals (CI). RESULTS: Twelve studies were included in the present review. Meta-analysis demonstrated males exhibited a higher risk of POI than females odds ratio (OR, 1.76; 95% CI, 1.54-2.01). Patients with anemia had a higher risk of POI than those without anemia (OR, 1.48; 95% CI, 1.04-2.11). Patients with liver disease (OR, 3.3; 95% CI, 1.2-9.08) had a higher risk of POI. The presence of perioperative fluid and electrolyte imbalances was a predictor of POI (OR, 3.24; 95% CI, 2.62-4.02). Spine surgery involving more than 3 levels had a higher risk of POI compared to that with 1-2 levels (OR, 1.82; 95% CI, 1.03-3.23). CONCLUSIONS: Male sex and the presence of anemia and liver disease were significant patient factors associated with POI. Perioperative fluid and electrolyte imbalance and multilevel spine surgery significantly increased the risk of POI. In addition, through this comprehensive review, we identified several perioperative risk factors associated with the development of POI after spine surgery.

2.
J Formos Med Assoc ; 2023 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-37142476

RESUMO

BACKGROUND: /Purpose: Reactivity at the Bacillus Calmette-Guérin (BCG) scar is a pathognomonic feature of Kawasaki disease (KD). However, its value in predicting KD outcomes has not been emphasized. This study explored the clinical significance of BCG scar redness with respect to coronary artery outcomes. METHODS: This retrospective study collected data on children with KD from 13 hospitals in Taiwan during 2019-2021. Children with KD were categorized into four groups based on the KD type and BCG scar reactivity. Risk factors of coronary artery abnormalities (CAA) were analyzed in all groups. RESULTS: BCG scar redness occurred in 49% of 388 children with KD. BCG scar redness was associated with younger age, early intravenous immunoglobulin (IVIG) treatment, hypoalbuminemia, and CAA at the first echocardiogram (p < 0.01). BCG scar redness (RR 0.56) and pyuria (RR 2.61) were independent predictors of any CAA within 1 month (p < 0.05). Moreover, pyuria (RR 5.85, p < 0.05) in children with complete KD plus BCG scar redness was associated with CAA at 2-3 months; first IVIG resistance (RR 15.2) and neutrophil levels ≥80% (RR 8.37) in children with complete KD plus BCG scar non-redness were associated with CAA at 2-3 months (p < 0.05). We failed to detect any significant risk factors of CAA at 2-3 months in children with incomplete KD. CONCLUSION: BCG scar reactivity contributes to diverse clinical features in KD. It can be effectively applied to determine the risk factors of any CAA within 1 month and CAA at 2-3 months.

3.
Int J Mol Sci ; 24(9)2023 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-37175754

RESUMO

Nicotinamide adenine dinucleotide (NAD+) is a critical cofactor essential for various cellular processes. Abnormalities in NAD+ metabolism have also been associated with a number of metabolic disorders. The regulation and interconnection of NAD+ metabolic pathways are not yet completely understood. By employing an NAD+ intermediate-specific genetic system established in the model organism S. cerevisiae, we show that histone deacetylases (HDACs) Hst1 and Rpd3 link the regulation of the de novo NAD+ metabolism-mediating BNA genes with certain aspects of the phosphate (Pi)-sensing PHO pathway. Our genetic and gene expression studies suggest that the Bas1-Pho2 and Pho2-Pho4 transcription activator complexes play a role in this co-regulation. Our results suggest a model in which competition for Pho2 usage between the BNA-activating Bas1-Pho2 complex and the PHO-activating Pho2-Pho4 complex helps balance de novo activity with PHO activity in response to NAD+ or phosphate depletion. Interestingly, both the Bas1-Pho2 and Pho2-Pho4 complexes appear to also regulate the expression of the salvage-mediating PNC1 gene negatively. These results suggest a mechanism for the inverse regulation between the NAD+ salvage pathways and the de novo pathway observed in our genetic models. Our findings help provide a molecular basis for the complex interplay of two different aspects of cellular metabolism.


Assuntos
Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Saccharomyces cerevisiae/metabolismo , NAD/metabolismo , Histona Desacetilases/genética , Histona Desacetilases/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Fosfatos/metabolismo , Sirtuína 2/genética , Sirtuína 2/metabolismo , Transativadores/metabolismo , Proteínas de Homeodomínio/metabolismo
4.
Surg Obes Relat Dis ; 2023 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-37211506

RESUMO

BACKGROUND: Bariatric surgery is associated with significant improvements in immunity in individuals with obesity, but the exact efficacy in reducing pneumonia and influenza infections is unclear. OBJECTIVE: To investigate the association between bariatric surgery and the risk of pneumonia and influenza infection. SETTING: Nondiabetic patients who underwent bariatric surgery and matched controls were identified from the National Health Insurance Research Database of Taiwan. METHODS: We identified 1648 nondiabetic patients who underwent bariatric surgery from the National Health Insurance Research Database of Taiwan in 2001-2009. These patients were matched by propensity score with 4881 nondiabetic patients with obesity who did not undergo bariatric surgery. We followed the surgical and control cohorts until death, any diagnosis of pneumonia or influenza, or December 31, 2012. The Cox proportional hazards regression model was used to calculate the relative risk of pneumonia and influenza infection in those who underwent bariatric surgery compared with those who did not. RESULTS: Overall, there was a .87-fold (95% CI, .78-.98) reduced risk of pneumonia and influenza infection in the surgical group versus the control group. Four years after bariatric surgery, a sustainable effect of the surgery was observed, and the risk of pneumonia and influenza infection was .83-fold reduced in the surgical group (95% CI, .73-.95). Individuals with obesity who underwent bariatric surgery had a reduced risk of pneumonia and influenza infection compared with matched control individuals. CONCLUSION: Individuals with obesity who underwent bariatric surgery had a reduced risk of pneumonia and influenza infection compared with matched control individuals.

5.
Artigo em Inglês | MEDLINE | ID: mdl-37213022

RESUMO

Lead (Pb) is a toxic metal that has been extensively used in various industrial processes, and it persists in the environment, posing a continuous risk of exposure to humans. This study investigated blood lead levels in participants aged 20 years and older, who resided in Dalinpu for more than two years between 2016 to 2018, at Kaohsiung Municipal Siaogang Hospital. Graphite furnace atomic absorption spectrometry was used to analyze the blood samples for lead levels, and the LDCT (Low-Dose computed tomography) scans were interpreted by experienced radiologists. The blood lead levels were divided into quartiles, with Q1 representing levels of ≤1.10 µg/dL, Q2 representing levels of >1.11 and ≤1.60 µg/dL, Q3 representing levels of >1.61 and ≤2.30 µg/dL, and Q4 representing levels of >2.31 µg/dL. Individuals with lung fibrotic changes had significantly higher (mean ± SD) blood lead levels (1.88±1.27vs. 1.72±1.53 µg/dl, p< 0.001) than those with non-lung fibrotic changes. In multivariate analysis, we found that the highest quartile (Q4: >2.31 µg/dL) lead levels (OR: 1.36, 95% CI: 1.01-1.82; p= 0.043) and the higher quartile (Q3: >1.61 and ≤2.30 µg/dL) (OR: 1.33, 95% CI: 1.01-1.75; p= 0.041) was significantly associated with lung fibrotic changes compared with the lowest quartile (Q1: ≤1.10 µg/dL) (Cox and Snell R2, 6.1 %; Nagelkerke R2, 8.5 %). The dose-response trend was significant (Ptrend= 0.030). Blood lead exposure was significantly associated lung fibrotic change. To prevent lung toxicity, it is recommended to maintain blood lead levels lower than the current reference value.

6.
Cells ; 12(9)2023 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-37174688

RESUMO

Immune checkpoint blockade (ICB) therapy can improve the survival of cancer patients with a high tumor mutation burden (TMB-H) or deficiency in DNA mismatch repair (dMMR) in their tumors. However, most cancer patients without TMB-H and dMMR do not benefit from ICB therapy. The inhibition of ATM can increase DNA damage and activate the interferon response, thus modulating the tumor immune microenvironment (TIME) and the efficacy of ICB therapy. In this study, we showed that ATM inhibition activated interferon signaling and induced interferon-stimulated genes (ISGs) in cisplatin-resistant and parent cancer cells. The ISGs induced by ATM inhibition were correlated with survival in cancer patients who received ICB therapy. In oral cancer, high expressions of ISG15, IFI27, and OASL were associated with low expressions of ATM, the activation of inflamed immune pathways, and increased tumor-infiltrating scores of CD8+ T, natural killer, and dendritic cells. The high expressions of ISG15, IFI27, and OASL were also correlated with complete remission in patients with cervical cancer treated with cisplatin. These results suggest that ATM inhibition can induce the interferon response and inflamed TIME, which may benefit ICB therapy.


Assuntos
Cisplatino , Neoplasias , Humanos , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Cisplatino/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/genética , Neoplasias/patologia , Interferons/metabolismo , Imunoterapia/métodos , Microambiente Tumoral , Ubiquitinas/metabolismo , Citocinas/metabolismo , Proteínas de Membrana/metabolismo , Proteínas Mutadas de Ataxia Telangiectasia/genética , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo
7.
Diagnostics (Basel) ; 13(8)2023 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-37189575

RESUMO

The present study aimed to develop an AI-based system for the detection and classification of polyps using colonoscopy images. A total of about 256,220 colonoscopy images from 5000 colorectal cancer patients were collected and processed. We used the CNN model for polyp detection and the EfficientNet-b0 model for polyp classification. Data were partitioned into training, validation and testing sets, with a 70%, 15% and 15% ratio, respectively. After the model was trained/validated/tested, to evaluate its performance rigorously, we conducted a further external validation using both prospective (n = 150) and retrospective (n = 385) approaches for data collection from 3 hospitals. The deep learning model performance with the testing set reached a state-of-the-art sensitivity and specificity of 0.9709 (95% CI: 0.9646-0.9757) and 0.9701 (95% CI: 0.9663-0.9749), respectively, for polyp detection. The polyp classification model attained an AUC of 0.9989 (95% CI: 0.9954-1.00). The external validation from 3 hospital results achieved 0.9516 (95% CI: 0.9295-0.9670) with the lesion-based sensitivity and a frame-based specificity of 0.9720 (95% CI: 0.9713-0.9726) for polyp detection. The model achieved an AUC of 0.9521 (95% CI: 0.9308-0.9734) for polyp classification. The high-performance, deep-learning-based system could be used in clinical practice to facilitate rapid, efficient and reliable decisions by physicians and endoscopists.

8.
Biomedicines ; 11(4)2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-37189688

RESUMO

Varicocele is a frequently encountered urological disorder, which has a prevalence rate of 8 to 15% among healthy men. However, the incidence is higher in male patients with primary or secondary infertility, with up to 35 to 80% of varicocele cases occurring in this population. The clinical manifestations of varicocele typically include the presence of an asymptomatic mass that feels like a "bag of worms", chronic scrotal pain, and infertility. Most patients with varicocele only undergo varicocelectomy after conservative treatments have failed. Unfortunately, some patients may still experience persistent scrotal pain due to a recurrence of varicocele, the development of hydrocele, neuralgia, referred pain, ureteral lesions, or nutcracker syndrome. Therefore, clinicians should consider these conditions as potential causes of postoperative scrotal pain, and take measures to address them. Several factors can assist in predicting surgical outcomes for patients with varicocele. Clinicians should consider these factors when deciding whether to perform surgery and what type of surgical intervention to use. By doing so, they can increase the likelihood of a successful surgical outcome and minimize the risk of complications such as postoperative scrotal pain.

9.
Int J Surg ; 2023 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-37204443

RESUMO

BACKGROUND: Postoperative nerve palsy is a major complication following resection of neck peripheral nerve sheath tumors (PNSTs). Accurate preoperative identification of the nerve origin (NO) can improve surgical outcomes and patient counseling. MATERIAL AND METHODS: This study was a retrospective cohort and quantitative analysis of the literature. We introduced a parameter, the carotid-jugular angle (CJA), to differentiate the NO. A literature review of neck PNST cases from 2010 to 2022 was conducted. The CJA was measured from eligible imaging data, and quantitative analysis was performed to evaluate the ability of the CJA to predict the NO. External validation was performed using a single-center cohort from 2008 to 2021. RESULTS: In total, 17 patients from our single-center cohort and 88 patients from the literature were analyzed. Among them, 53, 45, and 7 patients had sympathetic, vagus, and cervical nerve PNSTs, respectively. Vagus nerve tumors had the largest CJA, followed by sympathetic tumors, whereas cervical nerve tumors had the smallest CJA (P<0.001). Multivariate logistic regression identified a larger CJA as a predictor of vagus NO (P<0.001), and receiver operating characteristic (ROC) analysis showed an area under the curve (AUC) of 0.907 (0.831-0.951) for the CJA to predict vagus NO (P<0.001). External validation showed an AUC of 0.928 (0.727-0.988) (P<0.001). Compared with the AUC of the previously proposed qualitative method (AUC=0.764, 0.673-0.839), that of the CJA was greater (P=0.011). The cutoff value identified to predict vagus NO was ≥100°. ROC analysis showed an AUC of 0.909 (0.837-0.956) for the CJA to predict cervical NO (P<0.001), with a cutoff value <38.5°. CONCLUSIONS: A CJA ≥ 100° predicted a vagus NO and a CJA < 100° predicted a non-vagus NO. Moreover, a CJA < 38.5 was associated with an increased likelihood of cervical NO.

10.
Biomedicine (Taipei) ; 13(1): 13-21, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37168728

RESUMO

Background: The porcine mammary glands share morphological and physiological similarities with human ones, making primary porcine mammary cells (PMC) suitable for biomedical research and a potential cellular therapeutic for breast cancer xenogeneic cell immunotherapy. Primary cells isolated from tissues remain the physiological functions of origin tissues but their self-renewal ability is restricted and cells acquire senescence during in vitro expansion. To overcome these drawbacks, here we sought to establish an approach to efficiently increase PMC's in vitro growth. We studied the effects of the hepatocyte growth factor (HGF) to maintain the expansion capacity of porcine mammary cells and identify the possible mechanisms. Purpose: HGF could allow for the increase in vitro proliferation capacity of primary epithelial cells isolated from tissue samples. To effectively produce cells for biomedical research and xenogeneic cell therapy, we planned to study the effects of HGF and its potential mechanisms of action to stimulate cell growth for PMC expansion. Methods: After HGF treatment, the growth, cell cycle, senescence and the cell marker gene expression of PMCs were analyzed in standard 10% FBS and low serum 1% FBS containing medium. Results: HGF significantly enhanced the cell proliferation by shifting the cell cycle population from G1 phase into S phase to increase cell division, reduced the senescent cells and reprogrammed gene expression profiles. Conclusion: We demonstrated that HGF could maintain the expansion capacity of PMCs by increasing cell growth and anti-senescence capability, suggesting its potential application in optimizing the long-term culture of primary cells. Adding a specific growth factor such as HGF in culture allows enhanced expansion of heterogeneous cell populations from normal porcine mammary glandular tissues in vitro. We believe that this cell culture approach will efficiently provide cells for studying mammary cell function and supply cells for therapeutic uses.

11.
Br J Neurosurg ; : 1-7, 2023 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-37170634

RESUMO

OBJECTIVE: This study aimed at the evaluation and assessment of a simple method, the transverse process resection (TPR) technique, for freehand thoracic pedicle screw placement and the learning curve for trainee surgeons. METHODS: In the TPR technique, the tip of the thoracic transverse process (TP) is removed to create an entry point in the cancellous bone of the TP, and the thoracic pedicle is cannulated from the TP. We retrospectively evaluated the safety and radiographic results of the TPR technique and compared with that of conventional pedicle screws. The training performance of seven neurosurgical residents with TPR techniques were evaluated. RESULTS: Among 46 patients, a total of 322 thoracic screws were analyzed, including 178 screws placed using the TPR technique and 144 screws using the conventional straight-forward (SF) technique. TPR screws had greater medial angulations in all levels from T2 to T12 compared to SF screws (p < 0.001). The incidence of pedicle breach was lower in the TPR screws compared to SF screws (6.2% vs. 21.5%, p < 0.001), especially for screws placed by residents (6.7% vs. 29.6%, p < 0.001). Residents had improved performance following a cadaveric training course on the TPR technique (p = 0.001). CONCLUSION: This study demonstrated the safety of the TPR technique for thoracic pedicle screw placement and its short learning curve for trainee surgeons.

12.
Artigo em Inglês | MEDLINE | ID: mdl-37191196

RESUMO

OBJECTIVES: This study investigates the efficacy and adverse events of beta-3 agonists and antimuscarinic agents for managing overactive bladder syndrome in Sjogren syndrome. METHODS: Sjogren's syndrome patients with an Overactive Bladder Symptom Score (OABSS) >5 were enrolled and were randomly assigned to mirabegron 50 mg/day or solifenacin 5 mg/day. Patients were evaluated on the recruitment day and reassessed at Week 1, 2, 4, and 12. The study's primary endpoint was to have a significant change in OABSS at Week 12. The secondary endpoint was the adverse event and crossover rate. RESULTS: A total of 41 patients were included in the final analysis, with 24 in the mirabegron group and 17 in the solifenacin group. The study's primary outcome was a change of the OABSS at Week 12. We found that both mirabegron and solifenacin significantly reduce patients' OABSS after 12 weeks of treatment. The evolution of the OABSS was -3.08 for mirabegron and -3.71 for solifenacin (p = .56). Six out of 17 patients from the solifenacin group crossed over to the mirabegron arm due to severe dry mouth or constipation, while none from the mirabegron arm crossed over to the solifenacin group. Sjogren's syndrome-related pain was also improved in the mirabegron group (4.96-1.67, p = .008) compared to the solifenacin group (4.39-3.4, p = .49). CONCLUSIONS: Our study showed that mirabegron is equally effective as solifenacin in treating Sjogren's syndrome patients with overactive bladder. Mirabegron is superior to solifenacin in terms of treatment-related adverse events.

13.
Midwifery ; 123: 103726, 2023 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-37192569

RESUMO

OBJECTIVE: To determine and describe the needs of women undergoing termination of pregnancy for fetal anomaly (TOPFA) in China. STUDY DESIGN: Qualitative study with semi-structured interviews. Consolidated Criteria for Reporting Qualitative Studies checklist was used for reporting. SETTING: Three general hospitals and one special hospital in Changsha, Hunan, China. PARTICIPANTS: 12 women who had undergone TOPFA and 12 healthcare providers who had experienced in caring for these women. METHODS: This study was based on the cognitive-emotional-behavioral framework (CEBF) of women who had to undergo TOPFA. Twenty-four participants (12 women and 12 healthcare providers) were recruited from two hospitals in China. Semi-structured face-to-face interviews were conducted based on interview guides. ATLAS.ti software was used to encode and analyze data. Qualitative content analysis was also applied. FINDINGS: Four themes emerged: information, emotional, professional psychological, and social supports. Each theme was subdivided into four phases for a detailed description of the temporal order (denial, confirmation, decision-making, and recovery phases) within the framework. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Our study analyzes the four needs of women who underwent TOPFA and the specifics of each need at different phases based on the CEBF. The importance of offering professional psychological support, detailed information, timely emotional support, and comprehensive social support for these women is illustrated. This study contributes to the understanding of women's needs, hence providing a theoretical basis for the construction of supportive programs.

14.
Front Psychiatry ; 14: 1058721, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37215667

RESUMO

Sleep inertia (SI) is a time period during the transition from sleep to wakefulness wherein individuals perceive low vigilance with cognitive impairments; SI is generally identified by longer reaction times (RTs) in attention tasks immediately after awakening followed by a gradual RT reduction along with waking time. The sluggish recovery of vigilance in SI involves a dynamic process of brain functions, as evidenced in recent functional magnetic resonance imaging (fMRI) studies in within-network and between-network connectivity. However, these fMRI findings were generally based on the presumption of unchanged neurovascular coupling (NVC) before and after sleep, which remains an uncertain factor to be investigated. Therefore, we recruited 12 young participants to perform a psychomotor vigilance task (PVT) and a breath-hold task of cerebrovascular reactivity (CVR) before sleep and thrice after awakening (A1, A2, and A3, with 20 min intervals in between) using simultaneous electroencephalography (EEG)-fMRI recordings. If the NVC were to hold in SI, we hypothesized that time-varying consistencies could be found between the fMRI response and EEG beta power, but not in neuron-irrelevant CVR. Results showed that the reduced accuracy and increased RT in the PVT upon awakening was consistent with the temporal patterns of the PVT-induced fMRI responses (thalamus, insula, and primary motor cortex) and the EEG beta power (Pz and CP1). The neuron-irrelevant CVR did not show the same time-varying pattern among the brain regions associated with PVT. Our findings imply that the temporal dynamics of fMRI indices upon awakening are dominated by neural activities. This is the first study to explore the temporal consistencies of neurovascular components on awakening, and the discovery provides a neurophysiological basis for further neuroimaging studies regarding SI.

15.
Diagnostics (Basel) ; 13(9)2023 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-37174919

RESUMO

Enterovesical fistula (EVF) is a rare complication of Crohn's disease (CD), characterized by recurrent urinary tract infections, fecaluria, and pneumaturia. However, most diagnostic tools have low sensitivity for EVF. Management consists of conservative and surgical approaches. Conservative treatment is usually adopted first. However, the appropriate time to consider surgery remains controversial. Herein, we report on the case of a 34-year-old male who presented with diffuse abdominal pain with fullness for one day. Enteroscopy and biopsy confirmed the diagnosis of Crohn's disease. Contrast-enhanced computed tomography (CT) suggested a fistula between the ileum and urinary bladder; however, cystoscopy did not find an obvious tract. The patient initially received medical treatment, but the symptoms persisted with recurrent urinary tract infections and subsequent bilateral hydronephrosis. He then underwent successful fistulectomy, partial cystectomy, and two segmental resections of the small bowel with end-to-end primary sutures. No complications or symptomatic urinary tract infections were noted during 30 months of follow-up after surgery, suggesting no recurrence of EVF. Surgical intervention is warranted when medical treatment fails or complications occur. Clinical symptoms and laboratory data are often less informative for the diagnosis of EVF, and CT is the most helpful diagnostic modality. Our management strategy provides an option for such patients.

16.
Exp Cell Res ; 429(1): 113652, 2023 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-37209991

RESUMO

Damage associated molecular patterns (DAMPs), including calreticulin (CRT) exposure, high-mobility group box 1 protein (HMGB1) elevation, and ATP release, characterize immunogenic cell death (ICD) and may play a role in cancer immunotherapy. Triple negative breast cancer (TNBC) is an immunogenic subtype of breast cancer with higher lymphocyte infiltration. Here, we found that regorafenib, a multi-target angiokinase inhibitor previously known to suppress STAT3 signaling, induced DAMPs and cell death in TNBC cells. Regorafenib induced the expression of HMGB1 and CRT, and the release of ATP. Regorafenib-induced HMGB1 and CRT were attenuated following STAT3 overexpression. In a 4T1 syngeneic murine model, regorafenib treatment increased HMGB1 and CRT expression in xenografts, and effectively suppressed 4T1 tumor growth. Immunohistochemical staining revealed increased CD4+ and CD8+ tumor-infiltrating T cells in 4T1 xenografts following regorafenib treatment. Regorafenib treatment or programmed death-1 (PD-1) blockade using anti-PD-1 monoclonal antibody reduced lung metastasis of 4T1 cells in immunocompetent mice. While regorafenib increases the proportion of MHC II high expression on dendritic cells in mice with smaller tumors, the combination of regorafenib and PD-1 blockade did not show a synergistic effect on anti-tumor activity. These results suggest that regorafenib induces ICD and suppresses tumor progression in TNBC. It should be carefully evaluated when developing a combination therapy with an anti-PD-1 antibody and a STAT3 inhibitor.

17.
Front Med (Lausanne) ; 10: 1167445, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37228399

RESUMO

Background: Successful weaning from mechanical ventilation is important for patients admitted to intensive care units. However, models for predicting real-time weaning outcomes remain inadequate. Therefore, this study aimed to develop a machine-learning model for predicting successful extubation only using time-series ventilator-derived parameters with good accuracy. Methods: Patients with mechanical ventilation admitted to the Yuanlin Christian Hospital in Taiwan between August 2015 and November 2020 were retrospectively included. A dataset with ventilator-derived parameters was obtained before extubation. Recursive feature elimination was applied to select the most important features. Machine-learning models of logistic regression, random forest (RF), and support vector machine were adopted to predict extubation outcomes. In addition, the synthetic minority oversampling technique (SMOTE) was employed to address the data imbalance problem. The area under the receiver operating characteristic (AUC), F1 score, and accuracy, along with the 10-fold cross-validation, were used to evaluate prediction performance. Results: In this study, 233 patients were included, of whom 28 (12.0%) failed extubation. The six ventilatory variables per 180 s dataset had optimal feature importance. RF exhibited better performance than the others, with an AUC value of 0.976 (95% confidence interval [CI], 0.975-0.976), accuracy of 94.0% (95% CI, 93.8-94.3%), and an F1 score of 95.8% (95% CI, 95.7-96.0%). The difference in performance between the RF and the original and SMOTE datasets was small. Conclusion: The RF model demonstrated a good performance in predicting successful extubation in mechanically ventilated patients. This algorithm made a precise real-time extubation outcome prediction for patients at different time points.

18.
Environ Pollut ; : 121844, 2023 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-37230174

RESUMO

Arsenic exposure is associated with airway inflammation and decreased lung function tests. Whether arsenic exposure associated with lung interstitial changes remains unknown. We conducted this population-based study in southern Taiwan during 2016 and 2018. Our study recruited individuals aged over 20 years, residing in the vicinity of a petrochemical complex and with no history of cigarette smoking. In both the 2016 and 2018 cross-sectional studies, we conducted chest low-dose computed tomography (LDCT) scans, as well as urinary arsenic and blood biochemistry analyses. Lung interstitial changes included lung fibrotic changes that were defined as the presence of curvilinear or linear densities, fine lines, or plate opacity in specific lobes; additionally, other interstitial changes were defined as the presence of ground-glass opacity (GGO) or bronchiectasis on the LDCT images. In both cross-sectional studies conducted in 2016 and 2018, participants with lung fibrotic changes exhibited a statistically significant increase in the mean urinary arsenic concentrations compared to those without fibrotic changes (geometric mean = 100.1 vs. 82.8 µg/g creatinine, p < 0.001 for cross-sectional study 2016, and geometric mean = 105.6 vs. 71.0 µg/g creatinine, p < 0.001 for cross-sectional study 2018). After controlling for age, gender, body mass index, platelet counts, hypertension, aspartate aminotransferase, cholesterol, HbA1c, and educational levels, we observed a significant positive association between a unit increase in log urinary arsenic concentrations and the risk of lung fibrotic changes in both cross-sectional study 2016 (odds ratio [OR] = 1.40, 95% confidence interval [CI] = 1.04-1.90, p = 0.028) and cross-sectional study 2018 (OR = 3.03, 95% CI = 1.38-6.63, p = 0.006). Our study did not find a significant association between arsenic exposure and bronchiectasis or GGO. It is imperative for the government to take significant measures to reduce arsenic exposure levels among individuals living near petrochemical complexes.

19.
J Clin Nurs ; 2023 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-37154497

RESUMO

AIM: To understand the issues surrounding collaborative practice and collaboration experiences among general ward staff in the escalation of care for clinically deteriorating patients. DESIGN: A systematic synthesis without meta-analysis. REVIEW METHODS: Seven electronic databases (CINAHL, Cochrane, Embase, PsycINFO, PubMed, Scopus and ProQuest Theses and Dissertations) were searched from their inception to 30 April 2022. Two reviewers independently screened titles, abstracts and full text for eligibility. The critical appraisal skill programme, Joanna Briggs Institute checklist for analytical cross-sectional studies and mixed methods appraisal tool were used to appraise the quality of the included studies. Both quantitative and qualitative research data were extracted, analysed and then synthesised using the data-based convergent qualitative synthesis approach. This review adhered to the Synthesis without meta-analysis (SWiM) reporting guidelines. RESULTS: A total of 17 studies were included. Two themes and six sub-themes were generated: (1) intraprofessional factors-inadequate handover, workload and mutual support, raising and acting on concerns, and seeking help from seniors and (2) interprofessional factors-differences in communication styles, and hierarchical approach versus interpersonal relationships. CONCLUSIONS: This systematic review highlights the need to address the intra- and interprofessional issues surrounding collaborative practice in escalation of care among general ward staff. IMPLICATIONS FOR THE PROFESSION: Findings from this review will inform healthcare leaders and educators on the development of relevant strategies and multi-disciplinary training to foster effective teamwork among nurses and doctors, with the goal of improving the escalation of care for patients with clinical deterioration. NO PATIENT OR PUBLIC CONTRIBUTION: This systematic review did not directly involve patient or public contribution to the manuscript.

20.
PLoS One ; 18(5): e0286032, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37205704

RESUMO

Identifying essential targets in the genome-scale metabolic networks of cancer cells is a time-consuming process. The present study proposed a fuzzy hierarchical optimization framework for identifying essential genes, metabolites and reactions. On the basis of four objectives, the present study developed a framework for identifying essential targets that lead to cancer cell death and evaluating metabolic flux perturbations in normal cells that have been caused by cancer treatment. Through fuzzy set theory, a multiobjective optimization problem was converted into a trilevel maximizing decision-making (MDM) problem. We applied nested hybrid differential evolution to solve the trilevel MDM problem to identify essential targets in genome-scale metabolic models for five consensus molecular subtypes (CMSs) of colorectal cancer. We used various media to identify essential targets for each CMS and discovered that most targets affected all five CMSs and that some genes were CMS-specific. We obtained experimental data on the lethality of cancer cell lines from the DepMap database to validate the identified essential genes. The results reveal that most of the identified essential genes were compatible with the colorectal cancer cell lines obtained from DepMap and that these genes, with the exception of EBP, LSS, and SLC7A6, could generate a high level of cell death when knocked out. The identified essential genes were mostly involved in cholesterol biosynthesis, nucleotide metabolisms, and the glycerophospholipid biosynthetic pathway. The genes involved in the cholesterol biosynthetic pathway were also revealed to be determinable, if a cholesterol uptake reaction was not induced when the cells were in the culture medium. However, the genes involved in the cholesterol biosynthetic pathway became non-essential if such a reaction was induced. Furthermore, the essential gene CRLS1 was revealed as a medium-independent target for all CMSs.


Assuntos
Neoplasias Colorretais , Genes Essenciais , Humanos , Genes Essenciais/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Sistemas de Transporte de Aminoácidos Básicos/genética
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