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1.
Bioengineering (Basel) ; 11(6)2024 May 29.
Article in English | MEDLINE | ID: mdl-38927787

ABSTRACT

BACKGROUND: Acute coronary syndrome (ACS) is a severe cardiovascular disease with globally rising incidence and mortality rates. Traditional risk assessment tools are widely used but are limited due to the complexity of the data. METHODS: This study introduces a gated Transformer model utilizing machine learning to analyze electronic health records (EHRs) for an enhanced prediction of major adverse cardiovascular events (MACEs) in ACS patients. The model's efficacy was evaluated using metrics such as area under the curve (AUC), precision-recall (PR), and F1-scores. Additionally, a patient management platform was developed to facilitate personalized treatment strategies. RESULTS: Incorporating a gating mechanism substantially improved the Transformer model's performance, especially in identifying true-positive cases. The TabTransformer+Gate model demonstrated an AUC of 0.836, a 14% increase in average precision (AP), and a 6.2% enhancement in accuracy, significantly outperforming other deep learning approaches. The patient management platform enabled healthcare professionals to effectively assess patient risks and tailor treatments, improving patient outcomes and quality of life. CONCLUSION: The integration of a gating mechanism within the Transformer model markedly increases the accuracy of MACE risk predictions in ACS patients, optimizes personalized treatment, and presents a novel approach for advancing clinical practice and research.

2.
Sci Rep ; 14(1): 13997, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38886202

ABSTRACT

Efficient seawater desalination is an effective way to solve the shortages of fresh water and energy but with limitations of the low fresh water production rate and high cost. Here, a hollow carbon fiber (HCF) wrapped by regular reduced graphene oxide (rGO) wave-like folds (rGO@HCF) is prepared on account of the differences in thermal shrinkage performance between graphene oxide (GO) and willow catkins fiber. Under one sun irradiation (1 kW m-2), the dry and wet surface temperature of the resulting evaporator reached up to 119.1 °C and 61.7 °C, respectively, and the water steam production rate reached 3.42 kg m-2 h-1. Also, for the outdoor experiment, the rGO@HCF exhibits good evaporator performance which reach up 27.8 kg m-2 day-1. Additionally, rGO@HCF also shows good seawater desalination performance and excellent durability for longtime work. DSC results indicate that the evaporation enthalpy of bulk water and adsorbed water decreased from 2503.92 to 1020.54 J g-1. The excellent evaporating performance is mainly attributed to the regular wave-like microstructure surface of the HCF, which can enhance the light absorption, reduced the vaporization enthalpy of the adsorption water. The findings not only introduce a novel approach for agricultural utilization, but also establish a crucial theoretical foundation for the design of regular wave-like microstructures.

3.
Chin Clin Oncol ; 13(3): 33, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38859601

ABSTRACT

BACKGROUND: Breast cancer (BRCA) represents a significant health challenge for women globally, with refractory cases showing resistance to current therapeutic strategies. The discovery of novel molecular markers and therapeutic targets is critical for improving outcomes in these patients. The primary aim of this study is to elucidate the role of tumor protein D52 (TPD52) as a novel molecular marker and potential therapeutic target to improve outcomes for BRCA patients. METHODS: Using bioinformatics methods, we screened and evaluated the expression, prognosis, and associated mechanisms of TPD52 in BRCA. Two hundred and thirty-eight BRCA cases and 19 control cases were collected from Shanghai First Maternity and Infant Hospital, and the protein expression of TPD52 was detected by immunohistochemistry, and the correlation between TPD52 and the prognosis of BRCA was analyzed. RESULTS: The expression of TPD52 in BRCA tissues was significantly higher than that in the control (P<0.001), displaying a strong association with key clinical variables, concurrently indicating an unfavorable prognostic implication. The survival analysis revealed high TPD52 expression was an independent adverse prognostic factor for overall (P=0.008) and disease-specific survival (P=0.005). Gene set enrichment analysis showed that TPD52 negatively correlated with estradiol, AMP-activated protein kinase, and other responses. Immune infiltration analysis showed that TPD52 was associated with immune cell infiltration, Th-1/Th-2 cell balance, and immune defense cells such as dendritic and plasmacytoid dendritic cells. It is further found that high TPD52 expression is associated with progression-free and disease-free survival from the analysis of immunohistochemical data of the patients at our hospital. CONCLUSIONS: In summary, TPD52 may serve as an independent prognostic biomarker for BRCA, which may represent a promising novel therapeutic target, particularly for the refractory estrogen receptor-positive (ER+)/progesterone receptor-positive (PR+)/human epidermal growth factor receptor 2-positive (HER2+) BRCA cases that have failed endocrine therapy and targeted treatment.


Subject(s)
Biomarkers, Tumor , Breast Neoplasms , Humans , Female , Breast Neoplasms/pathology , Prognosis , Biomarkers, Tumor/metabolism , Middle Aged , Neoplasm Proteins/metabolism , Receptors, Estrogen/metabolism , Receptor, ErbB-2/metabolism , Adult , Receptors, Progesterone/metabolism
4.
J Gastroenterol ; 59(7): 531-542, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38819499

ABSTRACT

BACKGROUND: Microbiota may be associated with esophageal squamous cell carcinoma (ESCC) development. However, it is not known the predictive value of microbial biomarkers combining epidemiological factors for the early detection of ESCC and precancerous lesions. METHODS: A total of 449 specimens (esophageal swabs and saliva) were collected from 349 participants with different esophageal statuses in China to explore and validate ESCC-associated microbial biomarkers from genes level to species level by 16S rRNA sequencing, metagenomic sequencing and real-time quantitative polymerase chain reaction. RESULTS: A bacterial biomarker panel including Actinomyces graevenitzii (A.g_1, A.g_2, A.g_3, A.g_4), Fusobacteria nucleatum (F.n_1, F.n_2, F.n_3), Haemophilus haemolyticus (H.h_1), Porphyromonas gingivalis (P.g_1, P.g_2, P.g_3) and Streptococcus australis (S.a_1) was explored by metagenomic sequencing to early detect the participants in Need group (low-grade intraepithelial neoplasia, high-grade intraepithelial neoplasia and ESCC) vs participants without these lesions as the Noneed group. Significant quantitative differences existed for each microbial target in which the detection efficiency rate was higher in saliva than esophageal swab. In saliva, the area under the curve (AUC) based on the microbial biomarkers (A.g_4 ∩ P.g_3 ∩ H.h_1 ∩ S.a_1 ∩ F.n_2) was 0.722 (95% CI 0.621-0.823) in the exploration cohort. Combining epidemiological factors (age, smoking, drinking, intake of high-temperature food and toothache), the AUC improved to 0.869 (95% CI 0.802-0.937) in the exploration cohort, which was validated with AUC of 0.757 (95% CI 0.663-0.852) in the validation cohort. CONCLUSIONS: It is feasible to combine microbial biomarkers in saliva and epidemiological factors to early detect ESCC and precancerous lesions in China.


Subject(s)
Early Detection of Cancer , Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Precancerous Conditions , Humans , Esophageal Neoplasms/diagnosis , Esophageal Neoplasms/epidemiology , Esophageal Neoplasms/microbiology , Male , Female , Middle Aged , Precancerous Conditions/diagnosis , Precancerous Conditions/microbiology , China/epidemiology , Esophageal Squamous Cell Carcinoma/diagnosis , Esophageal Squamous Cell Carcinoma/epidemiology , Esophageal Squamous Cell Carcinoma/microbiology , Early Detection of Cancer/methods , Aged , Saliva/microbiology , RNA, Ribosomal, 16S/genetics , Microbiota , Biomarkers, Tumor , Adult , Metagenomics/methods , Predictive Value of Tests
5.
Heliyon ; 10(7): e29109, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38601625

ABSTRACT

PHD finger protein 10 (PHF10) plays an important role in the tumorigenesis of gastric cancer (GC). However, clinical significance and underlying molecular mechanisms about PHF10 is unclear. In the article, it suggested that PHF10 involved in tumor progression and metastasis based on the analysis of datasets and 190 cases of tumor tissues in GC. And PHF10 provided the diagnostic value with areas under the receiver operating characteristics curve of 0.71 ± 0.069. Then we established GC cell lines MKN28 with PHF10 overexpression and SGC7901 with PHF10 knockdown. CCK8 assay and tumor xenograft experiment showed that upregulation of PHF10 could promote MKN28 cell proliferation, while PHF10 knockdown would inhibit the proliferation of SGC7901 in vitro and vivo. Nevertheless, PHF10 could upregulate CD44 mRNA expression by acting on its promoter at the level of transcription. This effect could be associated with BRG, BAF155 and SNF5, which were conserved subunits of switch/sucrose non-fermentable (SWI/SNF) complex. In conclusion, PHF10 targeting CD44 plays an essential part during the modulation of proliferation of GC cell and may offer a new therapeutic direction for GC.

6.
Eur J Med Chem ; 271: 116428, 2024 May 05.
Article in English | MEDLINE | ID: mdl-38653068

ABSTRACT

Recent evidence suggests that histone deacetylases (HDACs) are important regulators of autosomal dominant polycystic kidney disease (ADPKD). In the present study, a series of benzothiazole-bearing compounds were designed and synthesized as potential HDAC inhibitors. Given the multiple participation of HDACs in ADPKD cyst progression, we embarked on a targeted screen using HeLa nuclear extracts to identify potent pan-HDAC inhibitors. Compound 26 emerged as the most efficacious candidate. Subsequent pharmacological characterization showed that compound 26 effectively inhibits several HDACs, notably HDAC1, HDAC2, and HDAC6 (IC50 < 150 nM), displaying a particularly high sensitivity towards HDAC6 (IC50 = 11 nM). The selected compound significantly prevented cyst formation and expansion in an in vitro cyst model and was efficacious in reducing cyst growth in both an embryonic kidney cyst model and an in vivo ADPKD mouse model. Our results provided compelling evidence that compound 26 represents a new HDAC inhibitor for the treatment of ADPKD.


Subject(s)
Benzothiazoles , Histone Deacetylase Inhibitors , Polycystic Kidney, Autosomal Dominant , Histone Deacetylase Inhibitors/pharmacology , Histone Deacetylase Inhibitors/chemistry , Histone Deacetylase Inhibitors/chemical synthesis , Polycystic Kidney, Autosomal Dominant/drug therapy , Polycystic Kidney, Autosomal Dominant/pathology , Humans , Animals , Mice , Benzothiazoles/pharmacology , Benzothiazoles/chemistry , Benzothiazoles/chemical synthesis , Structure-Activity Relationship , Molecular Structure , Dose-Response Relationship, Drug , HeLa Cells , Histone Deacetylases/metabolism
7.
Nat Commun ; 15(1): 2548, 2024 Mar 21.
Article in English | MEDLINE | ID: mdl-38514631

ABSTRACT

The importance of P-stereogenic heterocycles has been widely recognized with their extensive use as privileged chiral ligands and bioactive compounds. The catalytic asymmetric synthesis of P-stereogenic phosphindane derivatives, however, remains a challenging task. Herein, we report a catalytic kinetic resolution of phosphindole oxides via rhodium-catalyzed diastereo- and enantioselective conjugate addition to access enantiopure P-stereogenic phosphindane and phosphindole derivatives. This kinetic resolution method features high efficiency (s factor up to >1057), excellent stereoselectivities (all >20:1 dr, up to >99% ee), and a broad substrate scope. The obtained chiral phosphindane oxides exhibit promising therapeutic efficacy in autosomal dominant polycystic kidney disease (ADPKD), and compound 3az is found to significantly inhibit renal cyst growth both in vitro and in vivo, thus ushering in a promising scaffold for ADPKD drug discovery. This study will not only advance efforts towards the asymmetric synthesis of challenging P-stereogenic heterocycles, but also surely inspire further development of P-stereogenic entities for bioactive small-molecule discovery.


Subject(s)
Polycystic Kidney, Autosomal Dominant , Humans , Catalysis , Drug Discovery , Kinetics , Oxides/pharmacology
8.
Chin Med J (Engl) ; 137(8): 980-989, 2024 Apr 20.
Article in English | MEDLINE | ID: mdl-38445358

ABSTRACT

BACKGROUND: Somatic copy number variations (SCNVs) in the CDKN2A gene are among the most frequent events in the dysplasia-carcinoma sequence of esophageal squamous cell carcinoma. However, whether CDKN2A SCNVs are useful biomarkers for the risk stratification and management of patients with esophageal squamous cell dysplasia (ESCdys) is unknown. This study aimed to investigate the characteristics and prognostic value of CDKN2A SCNVs in patients with mild or moderate (m/M) ESCdys. METHODS: This study conducted a prospective multicenter study of 205 patients with a baseline diagnosis of m/M ESCdys in five high-risk regions of China (Ci County, Hebei Province; Yanting, Sichuan Province; Linzhou, Henan Province; Yangzhong, Jiangsu Province; and Feicheng, Shandong Province) from 2005 to 2019. Genomic DNA was extracted from paraffin biopsy samples and paired peripheral white blood cells from patients, and a quantitative polymerase chain reaction assay, P16-Light, was used to detect CDKN2A copy number. The cumulative regression and progression rates of ESCdys were evaluated using competing risk models. RESULTS: A total of 205 patients with baseline m/M ESCdys were enrolled. The proportion of ESCdys regression was significantly lower in the CDKN2A deletion cohort than in the diploid and amplification cohorts (18.8% [13/69] vs. 35.0% [28/80] vs. 51.8% [29/56], P  <0.001). In the univariable competing risk analysis, the cumulative regression rate was statistically significantly lower ( P = 0.008), while the cumulative progression rate was higher ( P = 0.017) in ESCdys patients with CDKN2A deletion than in those without CDKN2A deletion. CDKN2A deletion was also an independent predictor of prognosis in ESCdys ( P = 0.004) in the multivariable analysis. CONCLUSION: The results indicated that CDKN2A SCNVs are associated with the prognosis of ESCdys and may serve as potential biomarkers for risk stratification.


Subject(s)
Cyclin-Dependent Kinase Inhibitor p16 , DNA Copy Number Variations , Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Humans , DNA Copy Number Variations/genetics , Female , Male , Middle Aged , Esophageal Neoplasms/genetics , Esophageal Neoplasms/pathology , Cyclin-Dependent Kinase Inhibitor p16/genetics , Esophageal Squamous Cell Carcinoma/genetics , Esophageal Squamous Cell Carcinoma/pathology , Prospective Studies , Prognosis , Aged , Adult
9.
BMC Musculoskelet Disord ; 25(1): 100, 2024 Jan 29.
Article in English | MEDLINE | ID: mdl-38287282

ABSTRACT

BACKGROUND: A understanding of morphological characteristics are important to femoral neck fractures (FNFs) resulting in high rates of complications in the young and middle-aged adults and the detailed data is lack in the literature. We aimed to report on the detailed morphological characteristics and the relationship between them in young and middle-aged adults with femoral neck fractures (FNFs). METHODS: The postoperative CT images of one hundred and fifty-two adults with FNFs were retrospectively reviewed. After image standardization, morphological characteristics including fracture orientation, cortex comminution, and intraosseous bone defects were measured and analyzed. Additionally, the distribution and correlation of these morphological features were analyzed using Pauwels classification, the right angle of the neck axis (VNA) classification, and the anteromedial oblique angle (AMA). RESULTS: Pauwels III fractures accounted for approximately half (55.2%) of the FNFs analyzed. Pauwels II and III could be detected in all four VNA types, and the distribution of the Pauwels types in VNA classification showed significant differences (χ2 = 106.363, p < 0.001). The VNA (9.0° ± 12.1) showed positive correlation with the neck-shaft angle (139.5° ± 6.3) and modified Pauwels angle (49.8° ± 10.6) (r = 0.441, r = 0.855, all p < 0.001). Cortical comminutions were commonly observed in the posterior (86.7%) and the inferior (80.7%). AMAs within the cases without posterior and inferior cortex comminutions were significantly larger than those with comminution (t = 2.594, 2.1196; p = 0.01, 0.036), but no difference could be detected after the AMA being divided into three groups (< 85°, 85°-95°, > 95°). The MPA, VNA and AMA of the group with an intraosseous defect were significantly different compared with those without (t = 2.847, 2.314, 2.268; p = 0.005, 0.022,0.025). The incidence of intraosseous defects within the groups with coronal and axial cortex comminutions were significantly higher than those within the groups without comminutions (χ2 = 34.87, 25.303; p < 0.001). CONCLUSIONS: The present study highlights the morphological diversity and complexity within FNFs in young and middle-aged adults, which allows for more accurate simulation of FNF patterns in the future biomechanical studies.


Subject(s)
Femoral Neck Fractures , Fenofibrate , Adult , Middle Aged , Humans , Retrospective Studies , Fracture Fixation, Internal/methods , Femoral Neck Fractures/diagnostic imaging , Femoral Neck Fractures/epidemiology , Femoral Neck Fractures/surgery , Computer Simulation
10.
Biochem Biophys Res Commun ; 697: 149547, 2024 Feb 19.
Article in English | MEDLINE | ID: mdl-38245926

ABSTRACT

A new series of thiophenpiperazine amide derivatives as potent dual ligands for the µ-opioid (MOR) and sigma-1 (σ1R) receptors are reported. Compound 23 exhibited good affinity to σ1R (Ki = 44.7 ± 7.05 nM) and high selectivity to σ2R. Furthermore, Compound 23 exerted MOR agonism and σ1R antagonism and potent analgesic activity in animal moldes (the abdominal constriction test (ED50 = 3.83 mg/kg) and carrageenan-induced inflammatory hyperalgesia model (ED50 = 5.23 mg/kg)). We obtained new dual ligands that might serve as starting points for preparing targeted tools. Furthermore, 23 may be a useful chemical probe for understanding more fully analgesic effects associated with MOR agonism and σ1R antagonism.


Subject(s)
Amides , Receptors, sigma , Animals , Amides/pharmacology , Amides/therapeutic use , Pain/chemically induced , Pain/drug therapy , Analgesics/pharmacology , Analgesics/therapeutic use , Analgesics/chemistry , Hyperalgesia/chemically induced , Hyperalgesia/drug therapy , Ligands , Receptors, Opioid, mu
11.
Expert Rev Mol Diagn ; 23(12): 1251-1261, 2023.
Article in English | MEDLINE | ID: mdl-37905778

ABSTRACT

INTRODUCTION: This study aimed to update the association between Helicobacter pylori (H. pylori) infection and gastric cancer (GC). METHODS: We searched PubMed, Embase, and Cochrane Library from 1990 to December 2021 to identify prospective studies. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were summarized to validate the relationship between H. pylori infection and GC. RESULTS: Including 27 studies, findings indicated a strong link between H. pylori and non-cardia gastric cancer (NCGC) in both Europe/North America (OR=5.37, 95%CI:4.39-6.57) and Asia (OR = 2.50, 95%CI:1.89-3.32), and a positive association with cardia gastric cancer (CGC) in Asia (OR = 1.74, 95%CI:1.38-2.19), but an inverse association in European/American populations (OR = 0.64, 95%CI: 0.51 to 0.79). Furthermore, the strength of association was greater in studies that detected H. pylori by immunoblotting versus ELISA, and also in studies testing for H. pylori detection further back in time prior to cancer diagnosis (Ptrend<0.05). Approximately 79% of NCGC in Asia and 87% in Europe/North America, along with 62% of CGC in Asia, could be attributable to H. pylori infection. CONCLUSIONS: The meta-analysis supports the significant attributable risk of H. pylori infection for GC and underscores the potential impact of targeting H. pylori in GC prevention programs. PROSPERO REGISTRATION: CRD42021274120.


Subject(s)
Helicobacter Infections , Helicobacter pylori , Stomach Neoplasms , Humans , Stomach Neoplasms/diagnosis , Stomach Neoplasms/epidemiology , Stomach Neoplasms/etiology , Cardia , Prospective Studies , Helicobacter Infections/complications , Risk Factors
12.
Adv Sci (Weinh) ; 10(34): e2303091, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37863665

ABSTRACT

Erlotinib, an EGFR tyrosine kinase inhibitor, is used for treating patients with cancer exhibiting EGFR overexpression or mutation. However, the response rate of erlotinib is low among patients with gastric cancer (GC). The findings of this study illustrated that the overexpression of bromodomain PHD finger transcription factor (BPTF) is partially responsible for erlotinib resistance in GC, and the combination of the BPTF inhibitor AU-1 with erlotinib synergistically inhibited tumor growth both in vivo and in vitro. AU-1 inhibited the epigenetic function of BPTF and decreased the transcriptional activity of c-MYC on PLCG1 by attenuating chromosome accessibility of the PLCG1 promoter region, thus decreasing the expression of p-PLCG1 and p-Erk and eventually improving the sensitivity of GC cells to erlotinib. In patient-derived xenograft (PDX) models, AU-1 monotherapy exhibited remarkable tumor-inhibiting activity and is synergistic anti-tumor effects when combined with erlotinib. Altogether, the findings illustrate that BPTF affects the responsiveness of GC to erlotinib by epigenetically regulating the c-MYC/PLCG1/pErk axis, and the combination of BPTF inhibitors and erlotinib is a viable therapeutic approach for GC.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Stomach Neoplasms , Humans , Erlotinib Hydrochloride/pharmacology , Erlotinib Hydrochloride/therapeutic use , Carcinoma, Non-Small-Cell Lung/genetics , Lung Neoplasms/genetics , ErbB Receptors/genetics , Stomach Neoplasms/drug therapy , Stomach Neoplasms/genetics , Drug Resistance, Neoplasm/genetics , Cell Line, Tumor , Phospholipase C gamma/pharmacology
14.
Neurosurgery ; 93(1): 224-232, 2023 07 01.
Article in English | MEDLINE | ID: mdl-36862952

ABSTRACT

BACKGROUND: To date, few data are available on the cognitive function of patients with vestibular schwannoma (VS) before treatment. OBJECTIVE: To provide a cognitive profile of patients with VS. METHODS: This cross-sectional observational study recruited 75 patients with an untreated VS and 60 age-, sex-, and education-matched healthy control subjects. A set of neuropsychological tests were administered to each participant. RESULTS: Compared with the matched controls, patients with VS exhibited impaired general cognitive function, memory, psychomotor speed, visuospatial ability, attention and processing speed, and executive function. The subgroup analyses displayed that patients with severe-to-profound unilateral hearing loss were more cognitively impaired than patients with no-to-moderate unilateral hearing loss. In addition, patients with right-sided VS scored worse than those with left-sided VS on tests of memory, attention and processing speed, and executive function. No differences were observed in cognitive performance between patients with or without brainstem compression and those with or without tinnitus. We also found that worse hearing and longer hearing loss duration were associated with poorer cognitive performance in patients with VS. CONCLUSION: The findings of this study provide evidence for cognitive impairment in patients with untreated VS. It can thus be said that including cognitive assessment in the routine clinical management of patients with VS may facilitate more appropriate clinical decision-making and improve patients' quality of life.


Subject(s)
Hearing Loss, Unilateral , Neuroma, Acoustic , Humans , Neuroma, Acoustic/complications , Cross-Sectional Studies , Quality of Life , Cognition , Neuropsychological Tests
15.
Anal Methods ; 15(5): 553-561, 2023 02 02.
Article in English | MEDLINE | ID: mdl-36606412

ABSTRACT

Quantification of metabolites present within exhaled breath is a major challenge for on-line breath analysis. It is also important for gauging the analytical performance, accuracy, reproducibility, reliability, and stability of the measuring technology. Short-chain fatty acids (SCFAs) are of high interest for nutrition and health. Their quantification enables a deep mechanistic understanding of a wide range of biological processes and metabolic pathways, while their high volatility makes them an attractive target for breath analysis. This article reports, for the first time, the development and testing of a modular, dynamic vapor generator for the qualitative and quantitative analysis of volatile SCFAs in the gaseous phase using a secondary electrospray ionization (SESI) source coupled to a high-resolution mass spectrometer. Representative compounds tested included acetic acid, propionic acid, butyric acid, pentanoic acid and hexanoic acid. Gas-phase experiments were performed both in dry and humid (95% relative humidity) conditions from ppt to low ppb concentrations. The results obtained exhibited excellent linearity within the examined concentration range, low limits of detection and quantification down to the lower ppt area. Mixture effects were also investigated and are presented.


Subject(s)
Fatty Acids, Volatile , Spectrometry, Mass, Electrospray Ionization , Spectrometry, Mass, Electrospray Ionization/methods , Reproducibility of Results , Fatty Acids, Volatile/analysis , Fatty Acids, Volatile/metabolism , Butyric Acid , Gases
16.
Neurosurgery ; 92(2): 421-430, 2023 02 01.
Article in English | MEDLINE | ID: mdl-36637276

ABSTRACT

BACKGROUND: MR vascular wall imaging (VWI) may have prognostic value in patients with unruptured intracranial aneurysms (UIAs). OBJECTIVE: To evaluate the value of VWI as a predictor of surgical outcome in patients with UIAs. METHODS: This prospective cohort study evaluated surgical outcomes in consecutive patients with UIAs who underwent surgical clipping at a single center. All participants underwent high-resolution VWI and were followed for at least 6 months. The primary clinical outcome was modified Rankin scale (mRS) score 6 months after surgery. RESULTS: The number of patients in the no wall enhancement, uniform wall enhancement (UWE), and focal wall enhancement (FWE) groups was 37, 145, and 154, respectively. Incidence of postoperative complications was 15.5% in the FWE group, 12.4% in the UWE group, and 5.4% in the no wall enhancement group. The proportion of patients with mRS score >2 at the 6-month follow-up was significantly higher in the FWE group than in the UWE group (14.3% vs 6.9%; P = .0389). In the multivariate analysis, FWE (odds ratio, 2.573; 95% CI 1.001-6.612) and positive proximal artery remodeling (odds ratio, 10.56; 95% CI 2.237-49.83) were independent predictors of mRS score >2 at the 6-month follow-up. CONCLUSION: Preoperative VWI can improve the surgeon's understanding of aneurysm pathological structure. Type of aneurysmal wall enhancement on VWI is associated with clinical outcome and incidence of salvage anastomosis and surgical complications.


Subject(s)
Intracranial Aneurysm , Humans , Intracranial Aneurysm/diagnostic imaging , Intracranial Aneurysm/surgery , Intracranial Aneurysm/pathology , Prospective Studies , Magnetic Resonance Imaging/methods , Prognosis , Treatment Outcome
17.
Transl Oncol ; 27: 101577, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36332599

ABSTRACT

BACKGROUND: Adjuvant chemotherapy (ACT) with 5-FU alone or 5-FU plus platinum after curative surgery improves the prognosis of pStage II-III gastric cancer (GC). However, only a subset of patients benefits from adjuvant platinum. To avoid the side effects of platinum, it is significant to accurately screen the patients who would benefit maximally with this treatment. The present study aimed to assess the value of DKK1 in predicting the benefit of adjuvant platinum chemotherapy in patients with pStage II -III GC. METHODS: Platinum sensitivity-related genes were screened by bioinformatics. DKK1 expression in 380 GC specimens was detected by immunohistochemistry (IHC) staining, and the correlation with adjuvant platinum-specific benefits were analyzed. RESULTS: DKK1 was screened as the most significant platinum sensitivity-related gene. In patients with DKK1high GC, the estimated absolute 5-year overall survival (OS) benefits from adjuvant platinum for pStage II-III, II, IIIA, IIIB, and IIIC were 25.5%, 17.3%, 36.4%, 29.2% and 31.1%, respectively, and the estimated absolute 5-year disease-free survival (DFS) benefits in the corresponding stages were 27.4%, 17.5%, 36.7%, 29.7% and 31.5%, respectively. These benefits were significantly higher than those in the same TNM stage without adjusting for DKK1 status. The performance of DKK1 was independent of the TNM stage and other clinicopathological variables. Similar results were obtained in the TCGA and ACRG cohorts. Furthermore, nomograms were constructed to predict the survival benefits in DKK1 subgroups. CONCLUSIONS: The stratification strategy based on DKK1 status is more precise than the TNM staging system for the selection of pStage II-III GC patients suitable for platinum-containing ACT.

18.
J Cancer ; 13(14): 3566-3574, 2022.
Article in English | MEDLINE | ID: mdl-36484007

ABSTRACT

Background: Gastric cancer (GC) is characterized by tissue invasion and metastasis, which lead to an aggressive and highly lethal disease. However, the underlying molecular mechanism remains largely unclear. Although multiple miRNAs are known to regulate crucial cellular events during cancer metastasis, their individual roles are still not fully described. Methods: miR-29c overexpressed cell lines were constructed. The wound healing, migration and invasion assays were performed to investigate the effect of miR-29c on metastasis of GC. HUVECs proliferation and tube formation assays were used to test the ability of angiogenesis of miR-29c. The target gene VEGFA was predicted by bioinformatic algorithms and validated by luciferase activity assay. Peritoneal spreading and pulmonary metastasis mice models were applied in vivo. Results: In the current study, we report the results that introduction of exogenous miR-29c inhibits GC cell migration, invasion and angiogenesis. Epithelial-mesenchymal transition (EMT) and cancer stem cells (CSCs) properties are participated in the miR-29c mediated cell metastasis. Furthermore, by performing tumor metastasis PCR array and luciferase reporter assay, we find that the expression of VEGFA is regulated by miR-29c through direct targeting of its 3'-UTR. In addition, we show that the VEGFA/VEGFR2/ERK pathway is involved in this process. Conclusion: These data taken together reveal the crucial functions of miR-29c-VEGFA/VEGFR2/ERK signaling axis in the metastasis progression of GC via regulating EMT and CSCs properties, which make them potential targets for clinical intervention in GC.

19.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 34(11): 1206-1208, 2022 Nov.
Article in Chinese | MEDLINE | ID: mdl-36567567

ABSTRACT

In the emergency department, open endotracheal suctioning for mechanically ventilated patients with endotracheal intubation will lead to the spread of respiratory droplets and aerosols, polluting the surrounding environment and medical staff. The traditional heat-and-moisture exchanger has the effect of warming and humidifying, and can block pathogenic microorganisms, but it does not have the function of inserting a sputum suction tube. When the heat-and-moisture exchanger is pulled out for sputum suction, it is easy to cause sputum splash, which pollutes the surrounding environment and medical personnel. The addition of closed sputum suction devices will increase the economic burden on patients. Thus, the medical staff of emergency department of the First People's Hospital of Tongxiang City of Zhejiang Province designed a new type of heat-and-moisture exchanger with anti-splash sputum suctioning function and obtained the National Utility Model Patent of China (ZL 2021 2 0017615.0). The new heat-and-moisture exchanger is mainly composed of a receiving cavity, a connecting tube, a sputum suction tube intubation tube, a sealing valve, etc. The disposable sputum suction tube can be used to insert sputum suction, and at the same time, it can prevent the secretion from splashing to ensure sealing. The patent combines the humidification and pathogen blocking functions of the heat-and-moisture exchanger with the anti-splash sputum suctioning function, which is suitable for use in the emergency and critical care medicine departments and has clinically practical value.


Subject(s)
Hot Temperature , Sputum , Humans , Suction , Trachea , Intubation, Intratracheal , Respiration, Artificial
20.
JMIR Med Inform ; 10(12): e42664, 2022 Dec 19.
Article in English | MEDLINE | ID: mdl-36534448

ABSTRACT

BACKGROUND: Diabetes needs to be under control through management and intervention. Management of diabetes through mobile health is a practical approach; however, most diabetes mobile health management systems do not meet expectations, which may be because of the lack of standardized management processes in the systems and the lack of intervention implementation recommendations in the management knowledge base. OBJECTIVE: In this study, we aimed to construct a diabetes management care pathway suitable for the actual situation in China to express the diabetes management care pathway using ontology and develop a diabetes closed-loop system based on the construction results of the diabetes management pathway and apply it practically. METHODS: This study proposes a diabetes management care pathway model in which the management process of diabetes is divided into 9 management tasks, and the Diabetes Care Pathway Ontology (DCPO) is constructed to represent the knowledge contained in this pathway model. A telehealth system, which can support the comprehensive management of patients with diabetes while providing active intervention by physicians, was designed and developed based on the DCPO. A retrospective study was performed based on the data records extracted from the system to analyze the usability and treatment effects of the DCPO. RESULTS: The diabetes management pathway ontology constructed in this study contains 119 newly added classes, 28 object properties, 58 data properties, 81 individuals, 426 axioms, and 192 Semantic Web Rule Language rules. The developed mobile medical system was applied to 272 patients with diabetes. Within 3 months, the average fasting blood glucose of the patients decreased by 1.34 mmol/L (P=.003), and the average 2-hour postprandial blood glucose decreased by 2.63 mmol/L (P=.003); the average systolic and diastolic blood pressures decreased by 11.84 mmHg (P=.02) and 8.8 mmHg (P=.02), respectively. In patients who received physician interventions owing to abnormal attention or low-compliance warnings, the average fasting blood glucose decreased by 2.45 mmol/L (P=.003), and the average 2-hour postprandial blood glucose decreased by 2.89 mmol/L (P=.003) in all patients with diabetes; the average systolic and diastolic blood pressure decreased by 20.06 mmHg (P=.02) and 17.37 mmHg (P=.02), respectively, in patients with both hypertension and diabetes during the 3-month management period. CONCLUSIONS: This study helps guide the timing and content of interactive interventions between physicians and patients and regulates physicians' medical service behavior. Different management plans are formulated for physicians and patients according to different characteristics to comprehensively manage various cardiovascular risk factors. The application of the DCPO in the diabetes management system can provide effective and adequate management support for patients with diabetes and those with both diabetes and hypertension.

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