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1.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 36(5): 508-513, 2024 May.
Article in Chinese | MEDLINE | ID: mdl-38845498

ABSTRACT

OBJECTIVE: To systematically evaluate the effect of different durations of prone ventilation on the efficacy of patients with acute respiratory distress syndrome (ARDS). METHODS: A computer search was conducted in databases including PubMed, Cochrane Library, Embase, CNKI, Wanfang Database, VIP Database, and China Biomedical Literature Database for studies on prone ventilation for the treatment of adult patients with ARDS published from the establishment of the database to September 2023. Studies were categorized into ≤ 24 hours group and > 24 hours group based on the duration of prone ventilation. Outcome indicators included mortality, the length of intensive care unit (ICU) stay, incidence of pressure ulcers, and operation of tracheotomy. Two researchers independently screened the literature, extracted information, and evaluated the risk of bias of the included literature. The quality of the included literature was assessed using the NOS scale, and the effect of different durations of prone ventilation on the efficacy of ARDS was analyzed by Meta-analysis. RESULTS: A total of 517 patients from 4 papers were finally included, including 249 patients with prone ventilation duration ≤ 24 hours and 268 patients with prone ventilation duration > 24 hours. All 4 studies were cohort studies, and the overall inclusion of literature assessed for methodological quality indicated high study quality and low risk of bias. Meta-analysis showed that there were no significantly differences in mortality [relative risk (RR) = 1.02, 95% confidence interval (95%CI) was 0.79 to 1.31, P = 0.88], the length of ICU stay [mean difference (MD) = -2.68, 95%CI was -5.30 to - 0.05, P = 0.05] between the prone ventilation duration ≤ 24 hours group and prone ventilation duration > 24 hours group. Compared with the prone ventilation duration ≤24 hours group, the incidence of pressure ulcers (RR = 0.76, 95%CI was 0.59 to 0.98, P = 0.04) and the operation of tracheotomy (RR = 0.71, 95%CI was 0.53 to 0.94, P = 0.02) were significantly increased in the prone ventilation duration > 24 hours group. CONCLUSIONS: The duration of prone ventilation had no significant effect on the mortality and the length of ICU stay in ARDS patients, but prone ventilation for > 24 hours increased the incidence of pressure ulcers and the operation of tracheotomy, which still needs to be further verified by a large number of studies due to the small number of included studies.


Subject(s)
Intensive Care Units , Length of Stay , Respiration, Artificial , Respiratory Distress Syndrome , Humans , Respiratory Distress Syndrome/therapy , Respiration, Artificial/methods , Prone Position , Time Factors
2.
Carbohydr Polym ; 338: 122183, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-38763721

ABSTRACT

Phosphorus is a critical factor in the control of eutrophication. We developed a three-dimensional porous, bimetallic-modified adsorbent La-Ca-CS/ATP to remove excess phosphate from water. Langmuir model showed that the theoretical adsorption capacity of La-Ca-CS/ATP was up to 123 mg P/g. The amount of La and Ca leached by La-Ca-CS/ATP was small, and the adsorption of 36.08 mg P/g was maintained during the five cycles of La-Ca-CS/ATP. The La-Ca-CS/ATP adsorption mechanism mainly involved surface precipitation, ligand exchange, electrostatic attraction, and inner-sphere complexation. Molecular dynamics demonstrated that La and Ca had complementary effects on binding sites and energy barriers within the range of 0.5-0.7 nm and 1.2-2 nm, enhancing the adsorption effect of La-Ca-CS/ATP. The life cycle assessment results showed that adding calcium could help reduce the environmental impact of lanthanum and chitosan. The production of La-Ca-CS/ATP adsorbed 73.88 P mg/g and emitted 24.73 kg CO2 eq, which was less than other adsorbents.

3.
Heliyon ; 10(9): e29910, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38707344

ABSTRACT

Aim: To compare the survival outcomes between male and female patients with intrahepatic cholangiocarcinoma who underwent liver resection. Methods: Data from 976 consecutive intrahepatic cholangiocarcinoma patients undergoing liver resection between January 2005 and May 2013 at the Eastern Hepatobiliary Surgery Hospital were prospectively collected and retrospectively reviewed. Patient clinicopathological characteristics, overall survival, and cumulative recurrence rates were compared between male and female patients using propensity score matching. Results: Propensity score matching generated 313 matched pairs of patients. Among the entire cohort, the 1-, 3-, and 5-year overall survival and recurrence rates of the male and female patients were 60.2 %, 37.3 %, and 27.7 % vs. 65.8 %, 40.4 %, and 31.0 % (P = 0.380) and 50.6 %, 67.4 %, and 74.2 % vs. 44.4 %, 63.5 %, and 69.6 % (P = 0.123), respectively. In the matched cohort, the 1-, 3-, and 5-year overall survival and recurrence rates of the male and female patients were 60.6 %, 35.9 % and 22.4 % vs. 66.4 %, 40.6 % and 31.1 % (P = 0.041) and 51.5 %, 69.3 % and 83.9 % vs. 44.3 %, 63.6 %, and 69.9 % (P = 0.041), respectively. After adjustment for other confounding variables by multivariate Cox regression analysis, male sex was independently associated with worse overall survival (hazard ratio = 1.322, 95 % confidence interval: 1.079-1.621, P = 0.007) and tumor recurrence (hazard ratio = 1.337, 95 % confidence interval: 1.088-1.645, P = 0.006). A subgroup analysis of patients younger than 55 years old after propensity score matching showed that male patients had significantly worse overall survival and higher recurrence rates than female patients after surgery, while no significant difference in long-term overall survival and recurrence was observed between male and female patients older than 55 years old after propensity score matching. Conclusion: Male sex was an independent risk factor for overall survival and tumor recurrence in patients after liver resection for intrahepatic cholangiocarcinoma.

4.
HPB (Oxford) ; 2024 Apr 27.
Article in English | MEDLINE | ID: mdl-38724439

ABSTRACT

BACKGROUND: We sought to elucidate the impact of postoperative complications on patient outcomes relative to differences in alpha-fetoprotein-tumor burden score (ATS) among patients with hepatocellular carcinoma (HCC). METHODS: Patients who underwent resection of HCC between 2000 and 2020 were identified from an international database. Moderate/severe complications were defined using the optimal cut-off value of the comprehensive complication index (CCI) based on the log-rank test. RESULTS: A total of 1124 patients was included. CCI cut-off value of 16.6 was identified as the optimal prognostic threshold. Patients who experienced moderate/severe complications were more likely to have worse recurrence free survival [RFS] versus individuals who had no/mild complications (2-year RFS; no/mild complication: 55.9% vs. moderate/severe complication: 38.1% p < 0.001). Of note, low and medium ATS patients who experienced moderate/severe complications had a higher risk of recurrence (2-year RFS; no/mild complication: postoperative complications 70.0% vs. moderate/severe complication: 51.1%, p = 0.006; medium: no/mild complication: 50.8% vs moderate/severe complication: 56.7%, p = 0.01); however, postoperative complications were not associated with worse outcomes among patients with high ATS (no/mild complication: 39.1% vs. moderate/severe complication: 29.2%, p = 0.20). CONCLUSION: These data serve to emphasize how reduction in postoperative complications may be crucial to improve prognosis, particularly among patients with favorable HCC characteristics.

5.
HPB (Oxford) ; 2024 May 16.
Article in English | MEDLINE | ID: mdl-38796346

ABSTRACT

OBJECTIVE: We sought to develop Artificial Intelligence (AI) based models to predict non-transplantable recurrence (NTR) of hepatocellular carcinoma (HCC) following hepatic resection (HR). METHODS: HCC patients who underwent HR between 2000-2020 were identified from a multi-institutional database. NTR was defined as recurrence beyond Milan Criteria. Different machine learning (ML) and deep learning (DL) techniques were used to develop and validate two prediction models for NTR, one using only preoperative factors and a second using both preoperative and postoperative factors. RESULTS: Overall, 1763 HCC patients were included. Among 877 patients with recurrence, 364 (41.5%) patients developed NTR. An ensemble AI model demonstrated the highest area under ROC curves (AUC) of 0.751 (95% CI: 0.719-0.782) and 0.717 (95% CI:0.653-0.782) in the training and testing cohorts, respectively which improved to 0.858 (95% CI: 0.835-0.884) and 0.764 (95% CI: 0.704-0.826), respectively after incorporation of postoperative pathologic factors. Radiologic tumor burden score and pathological microvascular invasion were the most important preoperative and postoperative factors, respectively to predict NTR. Patients predicted to develop NTR had overall 1- and 5-year survival of 75.6% and 28.2%, versus 93.4% and 55.9%, respectively, among patients predicted to not develop NTR (p < 0.0001). CONCLUSION: The AI preoperative model may help inform decision of HR versus LT for HCC, while the combined AI model can frame individualized postoperative care (https://altaf-pawlik-hcc-ntr-calculator.streamlit.app/).

6.
Res Sq ; 2024 May 07.
Article in English | MEDLINE | ID: mdl-38766088

ABSTRACT

Activated T cells undergo a metabolic shift to aerobic glycolysis to support the energetic demands of proliferation, differentiation, and cytolytic function. Transmembrane glucose flux is facilitated by glucose transporters (GLUT) that play a vital role in T cell metabolic reprogramming and anti-tumour function. GLUT isoforms are regulated at the level of expression and subcellular distribution. GLUTs also display preferential selectivity for carbohydrate macronutrients including glucose, galactose, and fructose. GLUT5, which selectively transports fructose over glucose, has never been explored as a genetic engineering strategy to enhance CAR-T cells in fructose-rich tumour environments. Fructose levels are significantly elevated in the bone marrow and the plasma of acute myeloid leukaemia (AML) patients. Here, we demonstrate that the expression of wild-type GLUT5 restores T cell metabolic fitness in glucose-free, high fructose conditions. We find that fructose supports maximal glycolytic capacity and ATP replenishment rates in GLUT5-expressing T cells. Using steady state tracer technology, we show that 13C6 fructose supports glycolytic reprogramming and TCA anaplerosis in CAR-T cells undergoing log phase expansion. In cytotoxicity assays, GLUT5 rescues T cell cytolytic function in glucose-free medium. The fructose/GLUT5 metabolic axis also supports maximal migratory velocity, which provides mechanistic insight into why GLUT5-expressing CAR-Ts have superior effector function as they undergo "hit-and-run" serial killing. These findings translate to superior anti-tumour function in a xenograft model of AML. In fact, we found that GLUT5 enhances CAR-T cell anti-tumour function in vivo without any need for fructose intervention. Accordingly, we hypothesize that GLUT5 is sufficient to enhance CAR-T resilience by increasing the cells' competitiveness for glucose at physiologic metabolite levels. Our findings have immediate translational relevance by providing the first evidence that GLUT5 confers a competitive edge in a fructose-enriched milieu, and is a novel approach to overcome glucose depletion in hostile tumour microenvironments (TMEs).

7.
Article in English | MEDLINE | ID: mdl-38816990

ABSTRACT

OBJECTIVE: Metabolic dysfunction-associated steatotic liver disease (MASLD) is becoming an escalating health problem in pediatric populations. This study aimed to investigate the role of N-acetyltransferase 10 (NAT10) in maternal high-fat diet (HFD)-induced MASLD in offspring at early life. METHODS: We generated male hepatocyte-specific NAT10 knockout (Nat10HKO) mice and mated them with female Nat10fl/fl mice under chow or HFD feeding. Body weight, liver histopathology, and expression of lipid metabolism-associated genes (Srebp1c, Fasn, Pparα, Cd36, Fatp2, Mttp, and Apob) were assessed in male offspring at weaning. Lipid uptake assays were performed both in vivo and in vitro. The mRNA stability assessment and RNA immunoprecipitation were performed to determine NAT10-regulated target genes. RESULTS: NAT10 deletion in hepatocytes of male offspring alleviated perinatal lipid accumulation induced by maternal HFD, decreasing expression levels of Srebp1c, Fasn, Cd36, Fatp2, Mttp, and Apob while enhancing Pparα expression. Furthermore, Nat10HKO male mice exhibited reduced lipid uptake. In vitro, NAT10 promoted lipid uptake by enhancing the mRNA stability of CD36 and FATP2. RNA immunoprecipitation assays exhibited direct interactions between NAT10 and CD36/FATP2 mRNA. CONCLUSIONS: NAT10 deletion in offspring hepatocytes ameliorates maternal HFD-induced hepatic steatosis through decreasing mRNA stability of CD36 and FATP2, highlighting NAT10 as a potential therapeutic target for pediatric MASLD.

8.
Anal Chem ; 2024 May 31.
Article in English | MEDLINE | ID: mdl-38820243

ABSTRACT

Pathological cardiac hypertrophy is a complex process that often leads to heart failure. Label-free proteomics has emerged as an important platform to reveal protein variations and to elucidate the mechanisms of cardiac hypertrophy. Endomyocardial biopsy is a minimally invasive technique for sampling cardiac tissue, but it yields only limited amounts of an ethically permissible specimen. After regular pathological examination, the remaining trace samples pose significant challenges for effective protein extraction and mass spectrometry analysis. Herein, we developed trace cardiac tissue proteomics based on the anchor-nanoparticles (TCPA) method. We identified an average of 6666 protein groups using ∼50 µg of myocardial interventricular septum samples by TCPA. We then applied TCPA to acquire proteomics from patients' cardiac samples both diagnosed as hypertrophic hearts and myocarditis controls and identified significant alterations in pathways such as regulation of actin cytoskeleton, oxidative phosphorylation, and cGMP-PKG signaling pathway. Moreover, we found multiple lipid metabolic pathways to be dysregulated in transthyretin cardiac amyloidosis compared to other types of cardiac hypertrophy. TCPA offers a new technique for studying pathological cardiac hypertrophy and can serve as a platform toolbox for proteomic research in other cardiac diseases.

9.
Surgery ; 176(1): 137-147, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38734502

ABSTRACT

BACKGROUND: Despite the Barcelona Clinic Liver Cancer system discouraging hepatectomy for intermediate/advanced hepatocellular carcinoma, the procedure is still performed worldwide, particularly in Asia. This study aimed to develop and validate nomograms for predicting survival and recurrence for these patients. METHODS: We analyzed patients who underwent curative-intent hepatectomy for intermediate/advanced hepatocellular carcinoma between 2010 and 2020 across 3 Chinese hospitals. The Eastern Hepatobiliary Surgery Hospital cohort was used as the training cohort for the nomogram construction, and the Jilin First Hospital and Fujian Mengchao Hepatobiliary Hospital cohorts served as the external validation cohorts. Independent preoperative predictors for survival and recurrence were identified through univariable and multivariable Cox regression analyses. Predictive accuracy was measured using the concordance index and calibration curves. The predictive performance between nomograms and conventional hepatocellular carcinoma staging systems was compared. RESULTS: A total of 1,328 patients met the inclusion criteria. The nomograms for predicting survival and recurrence were developed using 10 and 6 independent variables, respectively. Nomograms' concordance indices in the training cohort were 0.777 (95% confidence interval 0.759-0.800) and 0.719 (95% confidence interval 0.697-0.742) for survival and recurrence, outperforming 4 conventional staging systems (P < .001). Nomograms accurately stratified risk into low, intermediate, and high subgroups. These results were validated well by 2 external validation cohorts. CONCLUSION: We developed and validated nomograms predicting survival and recurrence for patients with intermediate/advanced hepatocellular carcinoma, contradicting Barcelona Clinic Liver Cancer surgical guidelines. These nomograms may facilitate clinicians to formulate personalized surgical decisions, estimate long-term prognosis, and strategize neoadjuvant/adjuvant anti-recurrence therapy.


Subject(s)
Carcinoma, Hepatocellular , Hepatectomy , Liver Neoplasms , Neoplasm Recurrence, Local , Neoplasm Staging , Nomograms , Humans , Liver Neoplasms/surgery , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Carcinoma, Hepatocellular/surgery , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Male , Female , Middle Aged , Neoplasm Recurrence, Local/epidemiology , Retrospective Studies , Aged , Adult
10.
J Diabetes Investig ; 2024 Apr 27.
Article in English | MEDLINE | ID: mdl-38676417

ABSTRACT

We present an in-depth analysis of dyslipidemia management strategies for patients with diabetes mellitus in Taiwan. It critically examines the disparity between established guideline recommendations and actual clinical practices, particularly in the context of evolving policies affecting statin prescriptions. The focus is on synthesizing the most recent findings concerning lipid management in patients with diabetes mellitus, with a special emphasis on establishing consensus regarding low-density lipoprotein cholesterol treatment targets. The article culminates in providing comprehensive, evidence-based recommendations tailored to the unique needs of those living with diabetes mellitus in Taiwan. It underscores the criticality of personalized care approaches, which incorporate multifaceted factors, and the integration of novel therapeutic options to enhance cardiovascular health outcomes.

11.
Anal Chim Acta ; 1304: 342541, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38637051

ABSTRACT

BACKGROUND: Digital polymerase chain reaction (digital PCR) is an important quantitative nucleic acid analysis method in both life science research and clinical diagnostics. One important hypothesis is that by physically constraining a single nucleic acid molecule in a small volume, the relative concentration can be increased therefore further improving the analysis performance, and this is commonly defined as the confinement effect in digital PCR. However, experimental investigation of this confinement effect can be challenging since it requires a microfluidic device that can generate partitions of different volumes and an instrument that can monitor the kinetics of amplification. (96). RESULTS: Here, we developed a real-time digital PCR system with a multivolume droplet array SlipChip (Muda-SlipChip) that can generate droplet of 125 nL, 25 nL, 5 nL, and 1 nL by a simple "load-slip" operation. In the digital region, by reducing the volume, the relative concentration is increased, the amplification kinetic can be accelerated, and the time to reach the fluorescence threshold, or Cq value, can be reduced. When the copy number per well is much higher than one, the relative concentration is independent of the partition volume, thus the amplification kinetics are similar in different volume partitions. This system is not limited to studying the kinetics of digital nucleic acid amplification, it can also extend the dynamic range of the digital nucleic acid analysis by additional three orders of magnitude by combining a digital and an analog quantification algorithm. (140). SIGNIFICANCE: In this study, we experimentally investigated for the first time the confinement effect in the community of digital PCR via a new real-time digital PCR system with a multivolume droplet array SlipChip (Muda-SlipChip). And a wider dynamic range of quantification methods compared to conventional digital PCR was validated by this system. This system provides emerging opportunities for life science research and clinical diagnostics. (63).


Subject(s)
Nucleic Acid Amplification Techniques , Nucleic Acids , Real-Time Polymerase Chain Reaction , Nucleic Acid Amplification Techniques/methods , Lab-On-A-Chip Devices , Algorithms
12.
J Gastrointest Surg ; 28(4): 417-424, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38583891

ABSTRACT

BACKGROUND: We sought to investigate whether minimally invasive hepatectomy (MIH) was superior to open hepatectomy (OH) in terms of achieving textbook outcome in liver surgery (TOLS) after resection of hepatocellular carcinoma (HCC). METHODS: Patients who underwent resection of HCC between 2000 and 2020 were identified from an international database. TOLS was defined by the absence of intraoperative grade ≥2 events, R1 resection margin, posthepatectomy liver failure, bile leakage, major complications, in-hospital mortality, and readmission. RESULTS: A total of 1039 patients who underwent HCC resection were included in the analysis. Although most patients underwent OH (n = 724 [69.7%]), 30.3% (n = 315) underwent MIH. Patients who underwent MIH had a lower tumor burden score (3.6 [IQR, 2.6-5.2] for MIH vs 6.1 [IQR, 3.9-10.1] for OH) and were more likely to undergo minor hepatectomy (84.1% [MIH] vs 53.6% [OH]) than patients who had an OH (both P < .001). After propensity score matching to control for baseline differences between the 2 cohorts, the incidence of TOLS was comparable among patients who had undergone MIH (56.6%) versus OH (64.8%) (P = .06). However, MIH was associated with a shorter length of hospital stay (6.0 days [IQR, 4.0-8.0] for MIH vs 9.0 days [IQR, 6.0-12.0] for OH). Among patients who had MIH, the odds ratio of achieving TOLS remained stable up to a tumor burden score of 4; after which the chance of TOLS with MIH markedly decreased. CONCLUSION: Patients with HCC who underwent resection with MIH versus OH had a comparable likelihood of TOLS, although MIH was associated with a short length of stay.


Subject(s)
Carcinoma, Hepatocellular , Laparoscopy , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/pathology , Hepatectomy , Retrospective Studies , Propensity Score , Length of Stay , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Postoperative Complications/surgery , Treatment Outcome
13.
Immunotherapy ; 2024 Apr 05.
Article in English | MEDLINE | ID: mdl-38578121

ABSTRACT

Aim: The study aimed to assess the value of pretreatment peripheral blood neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), pan-immune-inflammation value (PIV) and systemic immune-inflammation index (SII) for predicting immunotherapy prognosis and efficacy in advanced gastric cancer (GC). Methods: A total of 84 advanced GC patients received immunotherapy were retrospectively collected. The optimal cut-off values were determined by receiver operating characteristic curves. The univariate and multivariate analysis investigated the effects of NLR, PLR, PIV and SII on patients prognosis. Results: NLR, PLR, PIV and SII had predictive value of efficacy. NLR ≥3.65 was an independent risk factor for worse outcomes. Conclusion: NLR, PLR, PIV and SII have predictive value of efficacy and NLR ≥3.65 suggests a poor prognosis following immunotherapy in advanced GC.


Immunotherapy can make gastric cancer patients live longer. However, not all patients live longer. We need simple, inexpensive and effective indicators to find patients who can live longer with immunotherapy. Routine blood test is common in our daily lives. Previous studies reported that some indicators in routine blood test can predict the prognosis and efficacy of surgery in gastric cancer patients. But it is not clear in immunotherapy for advanced gastric cancer patients. In our trial, we found that some indicators in routine blood test can help predict the effect of immunotherapy in patients with advanced gastric cancer and screen which patients will live longer with immunotherapy.

14.
Biomicrofluidics ; 18(2): 021504, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38571909

ABSTRACT

Microfluidics or lab-on-a-chip technology has shown great potential for the separation of target particles/cells from heterogeneous solutions. Among current separation methods, vortex sorting of particles/cells in microcavities is a highly effective method for trapping and isolating rare target cells, such as circulating tumor cells, from flowing samples. By utilizing fluid forces and inertial particle effects, this passive method offers advantages such as label-free operation, high throughput, and high concentration. This paper reviews the fundamental research on the mechanisms of focusing, trapping, and holding of particles in this method, designs of novel microcavities, as well as its applications. We also summarize the challenges and prospects of this technique with the hope to promote its applications in medical and biological research.

15.
J Gene Med ; 26(5): e3689, 2024 May.
Article in English | MEDLINE | ID: mdl-38676365

ABSTRACT

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is a highly aggressive malignancy characterized by a poor prognosis and closely linked to tumor stemness. However, the key molecules that regulate ICC stemness remain elusive. Although Y-box binding protein 1 (YBX1) negatively affects prognosis in various cancers by enhancing stemness and chemoresistance, its effect on stemness and cisplatin sensitivity in ICC remains unclear. METHODS: Three bulk and single-cell RNA-seq datasets were analyzed to investigate YBX1 expression in ICC and its association with stemness. Clinical samples and colony/sphere formation assays validated the role of YBX1 in stemness and sensitivity to cisplatin. AZD5363 and KYA1979K explored the interaction of YBX1 with the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB/AKT) and WNT/ß-catenin pathways. RESULTS: YBX1 was significantly upregulated in ICC, correlated with worse overall survival and shorter postoperative recurrence time, and was higher in chemotherapy-non-responsive ICC tissues. The YBX1-high group exhibited significantly elevated stemness scores, and genes linked to YBX1 upregulation were enriched in multiple stemness-related pathways. Moreover, YBX1 expression is significantly correlated with several stemness-related genes (SOX9, OCT4, CD133, CD44 and EPCAM). Additionally, YBX1 overexpression significantly enhanced the colony- and spheroid-forming abilities of ICC cells, accelerated tumor growth in vivo and reduced their sensitivity to cisplatin. Conversely, the downregulation of YBX1 exerted the opposite effect. The transcriptomic analysis highlighted the link between YBX1 and the PI3K/AKT and WNT/ß-catenin pathways. Further, AZD5363 and KYA1979K were used to clarify that YBX1 promoted ICC stemness through the regulation of the AKT/ß-catenin axis. CONCLUSIONS: YBX1 is upregulated in ICC and promotes stemness and cisplatin insensitivity via the AKT/ß-catenin axis. Our study describes a novel potential therapeutic target for improving ICC prognosis.


Subject(s)
Cholangiocarcinoma , Cisplatin , Drug Resistance, Neoplasm , Gene Expression Regulation, Neoplastic , Y-Box-Binding Protein 1 , beta Catenin , Animals , Female , Humans , Male , Mice , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , beta Catenin/metabolism , beta Catenin/genetics , Bile Duct Neoplasms/genetics , Bile Duct Neoplasms/metabolism , Bile Duct Neoplasms/pathology , Bile Duct Neoplasms/drug therapy , Cell Line, Tumor , Cell Proliferation , Cholangiocarcinoma/genetics , Cholangiocarcinoma/metabolism , Cholangiocarcinoma/drug therapy , Cholangiocarcinoma/pathology , Cholangiocarcinoma/mortality , Cisplatin/pharmacology , Cisplatin/therapeutic use , Drug Resistance, Neoplasm/genetics , Neoplastic Stem Cells/metabolism , Prognosis , Proto-Oncogene Proteins c-akt/metabolism , Wnt Signaling Pathway , Xenograft Model Antitumor Assays , Y-Box-Binding Protein 1/metabolism , Y-Box-Binding Protein 1/genetics
16.
Int J Biol Macromol ; 267(Pt 1): 131471, 2024 May.
Article in English | MEDLINE | ID: mdl-38599419

ABSTRACT

The conversion of glucose into fructose can transform cellulose into high-value chemicals. This study introduces an innovative synthesis method for creating an MgO-based ordered mesoporous carbon (MgO@OMC) catalyst, aimed at the efficient isomerization of glucose into fructose. Throughout the synthesis process, lignin serves as the exclusive carbon precursor, while Mg2+ functions as both a crosslinking agent and a metallic active center. This enables a one-step synthesis of MgO@OMC via a solvent-induced evaporation self-assembly (EISA) method. The synthesized MgO@OMCs exhibit an impeccable 2D hexagonal ordered mesoporous structure, in addition to a substantial specific surface area (378.2 m2/g) and small MgO nanoparticles (1.52 nm). Furthermore, this catalyst was shown active, selective, and reusable in the isomerization of glucose to fructose. It yields 41 % fructose with a selectivity of up to 89.3 % at a significant glucose loading of 7 wt% in aqueous solution over MgO0.5@OMC-600. This performance closely rivals the current maximum glucose isomerization yield achieved with solid base catalysts. Additionally, the catalyst retains a fructose selectivity above 60 % even after 4 cycles, a feature attributable to its extended ordered mesoporous structure and the spatial confinement effect of the OMCs, bestowing it with high catalytic efficiency.


Subject(s)
Carbon , Fructose , Glucose , Lignin , Magnesium Oxide , Fructose/chemistry , Lignin/chemistry , Glucose/chemistry , Carbon/chemistry , Porosity , Magnesium Oxide/chemistry , Catalysis , Isomerism
17.
J Gastrointest Surg ; 28(2): 132-140, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38445934

ABSTRACT

BACKGROUND: This study aimed to develop a tool based on preoperative factors to predict the risk of perioperative complications based on the Comprehensive Complication Index (CCI) and long-term survival outcomes after liver resection for primary liver cancer. METHODS: Patients with hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (ICC) undergoing curative-intent hepatectomy between 1990 and 2020 were identified using a multi-institutional international database. RESULTS: Among 1411 patients who underwent curative-intent hepatic resection (HCC: 997, 70.7%; ICC: 414, 29.3%), median patient age was 66.0 years (IQR, 57.0-73.0), and most patients were male (n = 1001, 70.9%). In the postoperative setting, 699 patients (49.5%) experienced a complication; moreover, 112 patients (7.9%) had major complications. Although most patients had a favorable risk complication-overall survival (CompOS) profile (CCI score > 40 risk of <30% and median survival of >5 years: n = 778, 55.1%), 553 patients (39.2%) had an intermediate-risk profile, and 80 patients (5.7%) had a very unfavorable risk profile (CCI score > 40 risk of ≥30% and/or median survival of ≤1.5 years). The areas under the curve of the test and validation cohorts were 0.73 and 0.76, respectively. CONCLUSION: The CompOS risk model accurately stratified patients relative to short- and long-term risks, identifying a subset of patients at a high risk of major complications and poor overall survival.


Subject(s)
Bile Duct Neoplasms , Carcinoma, Hepatocellular , Cholangiocarcinoma , Liver Neoplasms , Humans , Male , Middle Aged , Aged , Female , Carcinoma, Hepatocellular/surgery , Liver Neoplasms/surgery , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Cholangiocarcinoma/surgery , Bile Duct Neoplasms/surgery , Bile Ducts, Intrahepatic
19.
Sensors (Basel) ; 24(6)2024 Mar 10.
Article in English | MEDLINE | ID: mdl-38544046

ABSTRACT

In the blood sample management pipeline environment, we have innovatively improved the traditional A-star algorithm to enhance the efficiency of mobile robots. This study employs a grid environmental modeling approach to accurately simulate medical testing laboratories. On the grid map, we utilize an 8-neighbor search method for path planning to accommodate the complex structure within the laboratory. By introducing an improved evaluation function and a bidirectional search strategy, we have successfully reduced the number of search nodes and significantly improved path search efficiency. Additionally, we eliminate redundant nodes in the path, smooth the path using cubic uniform B-spline curves, remove unnecessary inflection points, and further optimize the motion trajectory of the robot. The experimental results of the path planning simulation under different scenarios and specifications show that the improved A-star algorithm has higher search efficiency and traverses fewer nodes compared to the traditional A-star algorithm and the bidirectional A-star algorithm. Overall, the simulation experiments verify the feasibility of the improved A-star algorithm, which can better meet the needs of actual mobile robots in real medical testing laboratories.

20.
Ann Surg Oncol ; 2024 Mar 23.
Article in English | MEDLINE | ID: mdl-38520582

ABSTRACT

INTRODUCTION: Although up to 50-70% of patients with intrahepatic cholangiocarcinoma (ICC) recur following resection, data to predict post-recurrence survival (PRS) and guide treatment of recurrence are limited. METHODS: Patients who underwent resection of ICC between 2000 and 2020 were identified from an international, multi-institutional database. Data on primary disease as well as laboratory and radiologic data on recurrent disease were collected. Factors associated with PRS were examined and a novel scoring system to predict PRS (PRS score) was developed and internally validated. RESULTS: Among 986 individuals who underwent resection for ICC, 588 (59.6%) patients developed recurrence at a median follow up of 20.3 months. Among patients who experienced a recurrence, 97 (16.5%) underwent re-resection/ablation for recurrent ICC; 88 (15.0%) and 403 (68.5%) patients received intra-arterial treatment or systemic chemotherapy/supportive therapy, respectively. Patient American Society of Anesthesiologists (ASA) class > 2 (1 point), primary tumor N1/Nx status (1 point), primary R1 resection margin (1 point), primary tumor G3/G4 grade (1 point), carbohydrate antigen (CA) 19-9 > 37 UI/mL (2 points) at recurrence and carcinoembryonic antigen (CEA) > 5 ng/mL (2 points) at recurrence, as well as recurrent bilateral disease (1 point) and early recurrence (1 point) were included in the PRS score. The PRS score successfully stratified patients relative to PRS and demonstrated strong discriminatory ability (C-index 0.70, 95% confidence interval 0.68-0.72). While a PRS score of 0-3 was associated with a 3-year PRS of 62.5% following resection/ablation for recurrent ICC, a PRS score > 3 was associated with a low 3-year PRS of 35.5% (p = 0.03). CONCLUSIONS: The PRS score demonstrated strong discriminatory ability to predict PRS among patients who had developed recurrence following initial resection of ICC. The PRS score may be a useful tool to guide treatment among patients with recurrent ICC.

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