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2.
Asian J Surg ; 2024 Aug 07.
Article in English | MEDLINE | ID: mdl-39117545

ABSTRACT

BACKGROUND: Follicular thyroid carcinoma (FTC), the second most prevalent thyroid cancer after papillary thyroid cancer (PTC), tends to metastasize distantly, leading to poorer outcomes. Despite substantial research, a holistic bibliometric analysis of FTC literature is lacking. This study aims to fill this gap by employing bibliometric methods to track FTC research evolution. METHODS: English FTC publications were systematically gathered from the Web of Science. Bibliometric analysis, using R, VOSviewer, CiteSpace, and Excel, synthesized data and explored global research trends and topics. RESULTS: From 2000 to 2023, 9086 authors from 1953 institutions across 75 countries contributed to 1776 papers in 491 academic journals on FTC. The last two decades have witnessed a steady increase in publications related to FTC, with the United States leading in terms of publication volume. The United States dominated both in publications and citations, with the National Cancer Institute and Sheue-Yann Cheng as leading contributors. The journal 'Thyroid' featured the most publications, while the 'Journal of Clinical Endocrinology and Metabolism' ranked highest in citation frequency. Research focused on gene expression analysis and preoperative diagnostics, with recent trends shifting toward prognosis management and machine learning due to advances in medical technology and increased health awareness. CONCLUSION: This comprehensive bibliometric analysis has mapped the landscape of FTC research, highlighting key contributors, institutions, and thematic trends. Current discourse predominantly revolves around genetic analysis, prognostic determinants, and preoperative diagnostics in FTC. This foundational work guides future FTC research, providing insights into its evolution.

3.
Surg Endosc ; 2024 Aug 20.
Article in English | MEDLINE | ID: mdl-39164439

ABSTRACT

BACKGROUND: There are limited data on the effect of different sutures and surgical approaches on the quality of pancreaticojejunostomy in minimally invasive pancreaticoduodenectomy (MIPD). This study compares the incidence of clinically relevant postoperative pancreatic fistula (CR-POPF) between the use of barbed sutures (BSs) and conventional sutures (CSs). METHODS: A retrospective cohort study was conducted on 253 consecutive patients who had undergone MIPD from July 2016 to April 2023. Patients were excluded if conversion to open surgery or open anastomosis was necessary. 220 patients were enrolled and divided into BS (n = 148) and CS (n = 72) groups. After 1:1 propensity score matching (PSM), 67 cases remained in each group. Univariate and multivariate analyses identified factors associated with CR-POPF. Comparisons were also made between laparoscopic (LPD) and robotic (RPD) pancreaticoduodenectomy. RESULTS: After PSM, BSs were associated with significantly lower rates of CR-POPF (7.5 vs. 22.4%, P = 0.015) and severe complications (Clavien-Dindo ≥ III) (7.5vs. 19.4%, P = 0.043). No significant differences were found in operative time, length of postoperative hospital stay, or other major morbidities. Multivariate analyses revealed BMI ≥ 22 kg/m2 (OR = 5.048, 95% CI: 1.256-20.287, P = 0.023) and the use of BSs (OR = 0.196, 95% CI: 0.059-0.653, P = 0.008) as the independent predictors of CR-POPF. There were no significant differences in postoperative outcomes between the LPD and RPD groups, but RPD was associated with significantly shorter operative time (402.8 min vs. 429.4 min, P = 0.015). CONCLUSIONS: In conclusion, using BSs for PJ during MIPD is feasible and has the potential to reduce CR-POPF and severe complications.

4.
Infect Drug Resist ; 17: 2853-2862, 2024.
Article in English | MEDLINE | ID: mdl-39005851

ABSTRACT

Purpose: Voriconazole, a first-line therapeutic agent for chronic pulmonary aspergillosis, is metabolized by the cytochrome 450 enzymes, specifically CYP2C19 and CYP3A4. Rifampicin and rifapentine act as inducers of the cytochrome P450 enzyme. The current study explored the potential drug interactions arising from the co-administration of voriconazole with either rifampicin or rifapentine, as well as the duration of this effect on serum voriconazole levels after discontinuation of rifampicin or rifapentine. Patients and Methods: A retrospective study was conducted in tuberculosis patients with chronic pulmonary aspergillosis. These patients underwent a combination therapy involving voriconazole and rifampicin or rifapentine, or they were treated with voriconazole after discontinuation of rifampicin or rifapentine. The serum concentrations of voriconazole at steady-state were monitored. Data on demographic characteristics and the serum voriconazole levels were used for statistical analyses. Results: A total of 124 serum voriconazole concentrations from 109 patients were included in the study. The average serum concentration of voriconazole fell below the effective therapeutic range in patients treated with both voriconazole and rifampicin or rifapentine. Notably the co-administration of rifapentine led to a substantial (>70%) decrease in serum voriconazole levels in two patients. Moreover, this interfering effect persisted for at least 7 days following rifampicin discontinuation, while it endured for 5 days or more after discontinuation of rifapentine. Conclusion: Concomitant use of voriconazole and rifampicin or rifapentine should be avoided, and it is not recommended to initiate voriconazole therapy within 5 or 7 days after discontinuation of rifapentine or rifampicin. Therapeutic drug monitoring not only provides a basis for the adjustment of clinical dose, but also serves as a valuable tool for identifying drug interactions.

5.
J Cancer ; 15(14): 4636-4642, 2024.
Article in English | MEDLINE | ID: mdl-39006075

ABSTRACT

Objective: To investigate the outcomes of SIB-WBRT in patients with brain metastases and analyze the impact of some factors on prognosis. Materials and Methods: This single-arm retrospective study analyzed patients with brain metastases who were treated with SIB-WBRT at Peking Union Medical College Hospital from September 2015 to December 2021. The primary endpoint was intracranial progression free survival (iPFS). Secondary endpoints included overall survival (OS), intracranial new foci, and tumor control. The Kaplan-Meier method was then used to depict and estimate iPFS, OS, intracranial neoplasia, and tumor control. Finally, the Cox model was used to analyze the association between some relevant factors and outcomes. Results: A total of 107 patients were included and the median iPFS in these patients treated with SIB-WBRT was 13.4 (95% CI: 4.2-22.6) months, with 68.0% (95% CI: 57.4%-78.6%) and 50.8% (95% CI: 38.3%-63.3%) iPFS at 6- and 12-months. The median local control was 37.6 (95% CI: 28.3-46.8) months, with local control rates of 84.3% (95% CI: 80.6%-88.0%) and 73.3% (95% CI: 68.2%-78.4%) at 6- and 12-months. The median time to appearance of new intracranial foci was 17.4 (95% CI: 14.1-20.8) months, and the 6- and 12-month control rates were 74.5% (95% CI: 64.5%-84.5%) and 61.5% (95% CI: 49.0%-74.0%). The number of brain metastases in patients before treatment was significantly associated with iPFS (HR=0.4, 95% CI: 0.2-0.973, P=0.043). Conclusions: The iPFS, local control, and intracranial new foci of patients with brain metastases after treatment with SIB-WBRT were acceptable. In addition, the number of brain metastases in patients before treatment may be associated with iPFS.

6.
Eur Radiol ; 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39009880

ABSTRACT

OBJECTIVES: To explore the interrelationships between structural and functional changes as well as the potential neurotransmitter profile alterations in drug-naïve benign childhood epilepsy with central-temporal spikes (BECTS) patients. METHODS: Structural magnetic resonance imaging (sMRI) and resting-state functional MRI data from 20 drug-naïve BECTS patients and 33 healthy controls (HCs) were acquired. Parallel independent component analysis (P-ICA) was used to identify covarying components among gray matter volume (GMV) maps and fractional amplitude of low-frequency fluctuations (fALFF) maps. Furthermore, we explored the spatial correlations between GMV/fALFF changes derived from P-ICA and neurotransmitter maps in JuSpace toolbox. RESULTS: A significantly positive correlation (p < 0.001) was identified between one structural component (GMV_IC6) and one functional component (fALFF_IC4), which showed significant group differences between drug-naïve BECTS patients and HCs (GMV_IC6: p < 0.01; fALFF_IC4: p < 0.001). GMV_IC6 showed increased GMV in the frontal lobe, temporal lobe, thalamus, and precentral gyrus as well as fALFF_IC4 had enhanced fALFF in the cerebellum in drug-naïve BECTS patients compared to HCs. Moreover, significant correlations between GMV alterations in GMV_IC6 and the serotonin (5HT1a: p < 0.001; 5HT2a: p < 0.001), norepinephrine (NAT: p < 0.001) and glutamate systems (mGluR5: p < 0.001) as well as between fALFF alterations in fALFF_IC4 and the norepinephrine system (NAT: p < 0.001) were detected. CONCLUSION: The current findings suggest co-altered structural/functional components that reflect the correlation of language and motor networks as well as associated with the serotonergic, noradrenergic, and glutamatergic neurotransmitter systems. CLINICAL RELEVANCE STATEMENT: The relationship between anatomical brain structure and intrinsic neural activity was evaluated using a multimodal fusion analysis and neurotransmitters which might provide an important window into the multimodal neural and underlying molecular mechanisms of benign childhood epilepsy with central-temporal spikes. KEY POINTS: Structure-function relationships in drug-naïve benign childhood epilepsy with central-temporal spikes (BECTS) patients were explored. The interrelated structure-function components were found and correlated with the serotonin, norepinephrine, and glutamate systems. Co-altered structural/functional components reflect the correlation of language and motor networks and correlate with the specific neurotransmitter systems.

7.
Biomed Chromatogr ; : e5966, 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-39021259

ABSTRACT

The metabolites of sweroside were first investigated in vivo with ultra-performance liquid chromatography time-of-flight mass spectrometry (UPLC-TOF-MS) in combination with 2,4-dinitrophenylhydrazine derivatization. In addition, the mass detection sensitivity of the major metabolites, epinaucledal and naucledal, via UPLC-TOF-MS was significantly enhanced, and the epimer metabolites were distinctly discovered from plasma following gavage of sweroside in rats. The plasma concentration of epinaucledal and naucledal was quantified via UPLC-TOF-MS in negative mode using erythrocentaurin as the internal standard. The maximum mean plasma concentrations of naucledal and epinaucledal were 75.36 ± 20.10 and 43.52 ± 15.60 ng/ml within 2 h, respectively, following gavage of sweroside at 20 mg/kg. Moreover, the area under the concentration-time curve of naucledal was three times that of epinaucledal. The metabolic process of conversion of sweroside to epinaucledal and naucledal was deduced, and the pharmacological effects of epinaucledal and naucledal will clarify the clinical efficacy of sweroside.

8.
Ann Surg Oncol ; 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39008209

ABSTRACT

BACKGROUND: Evidence is limited for the treatment of pancreatic cancer among minimally invasive pancreatoduodenectomy. METHODS: This retrospective analysis evaluated patients who underwent robotic pancreaticoduodenectomy (RPD) or laparoscopic pancreaticoduodenectomy (LPD) from April 2016 to April 2023. Their baseline and perioperative data, including operative time, R0 resection rates, and severe complications rates, were analyzed, and the follow-up data, such as disease-free survival (DFS) and overall survival (OS), were collected. RESULTS: A total of 253 cases of LPD and RPD were performed, and 101 cases with pancreatic cancer were included, of which 54 were LPD and 47 were RPD. The conversion rate (4.3% vs. 29.6%, p = 0.001) and blood loss (400 vs. 575 mL, p < 0.05) were lower in the RPD group. No significant difference was observed between the two groups in terms of operative time, vessel resection rates, and TNM-stage diagnosis; however, R0 resection rates (80.9% vs. 70.4%) and lymph node harvest (24.2 vs. 21.9) had a higher tendency in the RPD group, and postoperative length of stay was shorter in the RPD cohort (11 vs. 13 days). Moreover, improved 1- to 3-years DFS (75.7%, 61.7%, and 36.0% vs. 59.0%, 35.6%, and 21.9%) and OS (94.7%, 84.7%, and 50.8% vs. 84.1%, 63.6%, and 45.5%) was found in the RPD group in comparison with the LPD group. CONCLUSIONS: RPD had advantages in surgical safety and oncological outcomes compared with LPD, but was similar to the latter in perioperative outcomes. Long-term outcomes require further study.

9.
Theranostics ; 14(10): 3827-3842, 2024.
Article in English | MEDLINE | ID: mdl-38994027

ABSTRACT

Rationale: In male mammals, many developmental-stage-specific RNA transcripts (both coding and noncoding) are preferentially or exclusively expressed in the testis, where they play important roles in spermatogenesis and male fertility. However, a reliable platform for efficiently depleting various types of RNA transcripts to study their biological functions during spermatogenesis in vivo has not been developed. Methods: We used an adeno-associated virus serotype nine (AAV9)-mediated CRISPR-CasRx system to knock down the expression of exogenous and endogenous RNA transcripts in the testis. Virus particles were injected into the seminiferous tubules via the efferent duct. Using an autophagy inhibitor, 3-methyladenine (3-MA), we optimized the AAV9 transduction efficiency in germ cells in vivo. Results: AAV9-mediated delivery of CRISPR-CasRx effectively and specifically induces RNA transcripts (both coding and noncoding) knockdown in the testis in vivo. In addition, we showed that the co-microinjection of AAV9 and 3-MA into the seminiferous tubules enabled long-term transgene expression in the testis. Finally, we found that a promoter of Sycp1 gene induced CRISPR-CasRx-mediated RNA transcript knockdown in a germ-cell-type-specific manner. Conclusion: Our results demonstrate the efficacy and versatility of the AAV9-mediated CRISPR-CasRx system as a flexible knockdown platform for studying gene function during spermatogenesis in vivo. This approach may advance the development of RNA-targeting therapies for conditions affecting reproductive health.


Subject(s)
CRISPR-Cas Systems , Dependovirus , Gene Knockdown Techniques , Spermatogenesis , Testis , Male , Animals , Dependovirus/genetics , CRISPR-Cas Systems/genetics , Mice , Testis/metabolism , Gene Knockdown Techniques/methods , Spermatogenesis/genetics , RNA/genetics , Genetic Vectors/genetics , Genetic Vectors/administration & dosage
10.
Cancer Commun (Lond) ; 44(8): 855-878, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38958445

ABSTRACT

BACKGROUND: Lymph node metastasis (LNM) is the primary mode of metastasis in gastric cancer (GC). However, the precise mechanisms underlying this process remain elusive. Tumor cells necessitate lipid metabolic reprogramming to facilitate metastasis, yet the role of lipoprotein lipase (LPL), a pivotal enzyme involved in exogenous lipid uptake, remains uncertain in tumor metastasis. Therefore, the aim of this study was to investigate the presence of lipid metabolic reprogramming during LNM of GC as well as the role of LPL in this process. METHODS: Intracellular lipid levels were quantified using oil red O staining, BODIPY 493/503 staining, and flow cytometry. Lipidomics analysis was employed to identify alterations in intracellular lipid composition following LPL knockdown. Protein expression levels were assessed through immunohistochemistry, Western blotting, and enzyme-linked immunosorbent assays. The mouse popliteal LNM model was utilized to investigate differences in LNM. Immunoprecipitation and mass spectrometry were employed to examine protein associations. In vitro phosphorylation assays and Phos-tag sodium dodecyl-sulfate polyacrylamide gel electrophoresis assays were conducted to detect angiopoietin-like protein 4 (ANGPTL4) phosphorylation. RESULTS: We identified that an elevated intracellular lipid level represents a crucial characteristic of node-positive (N+) GC and further demonstrated that a high-fat diet can expedite LNM. LPL was found to be significantly overexpressed in N+ GC tissues and shown to facilitate LNM by mediating dietary lipid uptake within GC cells. Leptin, an obesity-related hormone, intercepted the effect exerted by ANGPTL4/Furin on LPL cleavage. Circulating leptin binding to the leptin receptor could induce the activation of inositol-requiring enzyme-1 (IRE1) kinase, leading to the phosphorylation of ANGPTL4 at the serine 30 residue and subsequently reducing its binding affinity with LPL. Moreover, our research revealed that LPL disrupted lipid homeostasis by elevating intracellular levels of arachidonic acid, which then triggered the cyclooxygenase-2/prostaglandin E2 (PGE2) pathway, thereby promoting tumor lymphangiogenesis. CONCLUSIONS: Leptin-induced phosphorylation of ANGPTL4 facilitates LPL-mediated lipid uptake and consequently stimulates the production of PGE2, ultimately facilitating LNM in GC.


Subject(s)
Leptin , Lipoprotein Lipase , Lymphatic Metastasis , Stomach Neoplasms , Lipoprotein Lipase/metabolism , Stomach Neoplasms/metabolism , Stomach Neoplasms/pathology , Humans , Animals , Mice , Leptin/metabolism , Lipid Metabolism , Male , Cell Line, Tumor , Angiopoietin-Like Protein 4/metabolism , Female , Phosphorylation
11.
J Robot Surg ; 18(1): 298, 2024 Jul 28.
Article in English | MEDLINE | ID: mdl-39068626

ABSTRACT

With the development of robotic systems, robotic pancreatoduodenectomies (RPDs) have been increasingly performed. However, the number of cases required by surgeons with extensive laparoscopic pancreatoduodenectomy (LPD) experience to overcome the learning curve of RPD remains unclear. Therefore, we aimed to analyze and explore the impact of different phases of the learning curve of RPD on perioperative outcomes. Clinical data were prospectively collected and retrospectively analyzed for 100 consecutive patients who underwent RPD performed by a single surgeon. This surgeon had previous experience with LPD, having performed 127 LPDs with low morbidity. The learning curve for RPD was analyzed using the cumulative sum (CUSUM) method based on operation time, and perioperative outcomes were compared between the learning and proficiency phases. Between April 2020 and November 2022, one hundred patients (56 men, 44 women) were included in this study. Based on the CUSUM curve of operation time, the learning curve for RPD was divided into two phases: phase I was the learning phase (cases 1-33) and phase II was the proficiency phase (cases 34-100). The operation time during the proficiency phase was significantly shorter than that during the learning phase. In the learning phase of RPD, no significant increases were observed in estimated blood loss, conversion to laparotomy, severe complications, postoperative pancreatic hemorrhage, clinical pancreatic fistula, or other perioperative complications compared to the proficiency phases of either RPD or LPD. A surgeon with extensive prior experience in LPD can safely surmount the RPD learning curve without increasing morbidity in the learning phase. The proficiency was significantly improved after accumulating experience of 33 RPD cases.


Subject(s)
Laparoscopy , Learning Curve , Operative Time , Pancreaticoduodenectomy , Robotic Surgical Procedures , Humans , Pancreaticoduodenectomy/methods , Pancreaticoduodenectomy/education , Robotic Surgical Procedures/education , Robotic Surgical Procedures/methods , Male , Female , Laparoscopy/methods , Laparoscopy/education , Middle Aged , Retrospective Studies , Aged , Surgeons/education , Postoperative Complications/etiology , Postoperative Complications/epidemiology , Adult , Clinical Competence , Blood Loss, Surgical/statistics & numerical data
12.
J Mol Neurosci ; 74(3): 59, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38890235

ABSTRACT

Binge drinking causes a range of problems especially damage to the nervous system, and the specific neural mechanism of brain loss and behavioral abnormalities caused by which is still unclear. Extracellular regulated protein kinases (ERK) maintain neuronal survival, growth, and regulation of synaptic plasticity by phosphorylating specific transcription factors to regulate expression of brain-derived neurotrophic factor (BDNF). Dual-specific phosphatase 1 (DUSP1) and DUSP6 dephosphorylate tyrosine and serine/threonine residues in ERK1/2 to inactivate them. To investigate the molecular mechanism by which alcohol affects memory and emotion, a chronic intermittent alcohol exposure (CIAE) model was established. The results demonstrated that mice in the CIAE group developed short-term recognition memory impairment and anxiety-like behavior; meanwhile, the expression of DUSP1 and DUSP66 in the mPFC was increased, while the levels of p-ERK and BDNF were decreased. Micro-injection of DUSP1/6 inhibitor BCI into the medial prefrontal cortex (mPFC) restored the dendritic morphology by reversing the activity of ERK-BDNF and ultimately improved cognitive and emotional impairment caused by CIAE. These findings indicate that CIAE inhibits ERK-BDNF by increasing DUSP1/6 in the mPFC that may be associated with cognitive and emotional deficits. Consequently, DUSP1 and DUSP6 appear to be potential targets for the treatment of alcoholic brain disorders.


Subject(s)
Brain-Derived Neurotrophic Factor , Dual Specificity Phosphatase 1 , Ethanol , Mice, Inbred C57BL , Prefrontal Cortex , Animals , Brain-Derived Neurotrophic Factor/metabolism , Brain-Derived Neurotrophic Factor/genetics , Mice , Male , Dual Specificity Phosphatase 1/metabolism , Dual Specificity Phosphatase 1/genetics , Prefrontal Cortex/metabolism , Prefrontal Cortex/drug effects , Ethanol/toxicity , Ethanol/pharmacology , Dual Specificity Phosphatase 6/metabolism , Dual Specificity Phosphatase 6/genetics , Aminoacetonitrile/analogs & derivatives , Aminoacetonitrile/pharmacology , Aminoacetonitrile/therapeutic use , Anxiety/drug therapy , Anxiety/etiology , MAP Kinase Signaling System
13.
Bioorg Chem ; 150: 107588, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38936051

ABSTRACT

With the advent of mitochondrial targeting moiety such as triphenlyphosphonium cation (TPP+), targeting mitochondria in cancer cells has become a promising strategy for combating tumors. Herein, a series of novel 4-aryl-1,3-thiazole derivatives linked to TPP+ moiety were designed and synthesized. The cytotoxicity against a panel of four cancer cell lines was evaluated by CCK-8 assay. Most of these compounds exhibited moderate to good inhibitory activity over HeLa, PC-3 and HCT-15 cells while MCF-7 cells were less sensitive to most compounds. Among them, compound 12a exhibited a significant anti-proliferative activity against HeLa cells, and prompted for further investigation. Specifically, 12a decreased mitochondrial membrane potential and enhanced levels of reactive oxygen species (ROS). The flow cytometry analysis revealed that compound 12a could induce apoptosis and cell cycle arrest at G0/G1 phase in HeLa cells. In addition, mitochondrial bioenergetics assay revealed that 12a displayed mild mitochondrial uncoupling effect. Taken together, these findings suggest the therapeutic potential of compound 12a as an antitumor agent targeting mitochondria.


Subject(s)
Antineoplastic Agents , Apoptosis , Cell Proliferation , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Membrane Potential, Mitochondrial , Mitochondria , Reactive Oxygen Species , Thiazoles , Humans , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Proliferation/drug effects , Mitochondria/drug effects , Mitochondria/metabolism , Structure-Activity Relationship , Thiazoles/pharmacology , Thiazoles/chemistry , Thiazoles/chemical synthesis , Molecular Structure , Membrane Potential, Mitochondrial/drug effects , Apoptosis/drug effects , Reactive Oxygen Species/metabolism , Cell Line, Tumor , Organophosphorus Compounds/pharmacology , Organophosphorus Compounds/chemistry , Organophosphorus Compounds/chemical synthesis
14.
Front Med (Lausanne) ; 11: 1391545, 2024.
Article in English | MEDLINE | ID: mdl-38831987

ABSTRACT

Objective: The significance of interstitial cells of Cajal (ICC) in the gastrointestinal tract has garnered increasing attention. In recent years, approximately 80 articles on ICC have been published annually in various journals. However, no bibliometric study has specifically focused on the literature related to ICC. Therefore, we conducted a comprehensive bibliometric analysis of ICC to reveal dynamic scientific developments, assisting researchers in exploring hotspots and emerging trends while gaining a global perspective. Methods: We conducted a literature search in the Web of Science Core Collection (WoSCC) from January 1, 2013, to December 31, 2023, to identify relevant literature on ICC. We employed bibliometric software, namely VOSviewer and CiteSpace, to analyze various aspects including annual publication output, collaborations, research hotspots, current status, and development trends in this domain. Results: A total of 891 English papers were published in 359 journals by 928 institutions from 57 countries/regions. According to the keyword analysis of the literature, researchers mainly focused on "c-Kit," "expression," "smooth muscle," and "nitric oxide" related to ICC over the past 11 years. However, with "SIP syncytium," "ANO1," "enteric neurons," "gastrointestinal stromal tumors (GIST)," and "functional dyspepsia (FD)," there has been a growing interest in the relationship between ANO1, SIP syncytium, and ICC, as well as the role of ICC in the treatment of GIST and FD. Conclusion: Bibliometric analysis has revealed the current status of ICC research. The association between ANO1, SIP syncytium, enteric neurons and ICC, as well as the role of ICC in the treatment of GIST versus FD has become the focus of current research. However, further research and collaboration on a global scale are still needed. Our analysis is particularly valuable to researchers in gastroenterology, oncology, and cell biology, providing insights that can guide future research directions.

15.
Cancer Cell Int ; 24(1): 159, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38714991

ABSTRACT

BACKGROUND: Single nuclear polymorphisms (SNPs) have been published to be correlated with multiple diseases. Transcription Factor 21 (TCF21) is a critical transcription factor involved in various types of cancers. However, the association of TCF21 genetic polymorphisms with gastric cancer (GC) susceptibility and prognosis remains unclear. METHODS: A case-control study comprising 890 patients diagnosed with GC and an equal number of cancer-free controls was conducted. After rigorous statistical analysis, molecular experiments were carried out to elucidate the functional significance of the SNPs in the context of GC. RESULTS: TCF21 rs2327430 (OR = 0.78, P = 0.026) provides protection against GC, while rs4896011 (OR = 1.39, P = 0.005) exhibit significant associations with GC risk. Furthermore, patients with the (TC + CC) genotype of rs2327430 demonstrate a relatively favorable prognosis (OR = 0.47, P = 0.012). Mechanistically, chromatin immunoprecipitation assay and luciferase reporter assay revealed that the C allele of rs2327430 disrupts the binding of Transcription Factor AP-2 Alpha (TFAP2A) to the promoter region of TCF21, resulting in increased expression of TCF21 and inhibition of malignant behaviors in GC cells. CONCLUSION: Our findings highlight the significant role of TCF21 SNPs in both the risk and prognosis of GC and provide valuable insights into the underlying molecular mechanisms. Specifically, the disruptive effect of rs2327430 on TCF21 expression and its ability to modulate malignant cell behaviors suggest that rs2327430 may serve as a potential predictive marker for GC risk and prognosis.

16.
Thromb Haemost ; 2024 May 24.
Article in English | MEDLINE | ID: mdl-38788766

ABSTRACT

BACKGROUND: Thromboangiitis obliterans (TAO) is a vascular condition characterized by poor prognosis and an unclear etiology. This study employs Mendelian randomization (MR) to investigate the causal impact of circulating inflammatory proteins on TAO. METHODS: In this MR analysis, summary statistics from a genome-wide association study meta-analysis of 91 inflammation-related proteins were integrated with independently sourced TAO data from the FinnGen consortium's R10 release. Methods such as inverse variance weighting, MR-Egger regression, weighted median approaches, MR-PRESSO, and multivariable MR (MVMR) analysis were utilized. RESULTS: The analysis indicated an association between higher levels of C-C motif chemokine 4 and a reduced risk of TAO, with an odds ratio (OR) of 0.44 (95% confidence interval [CI]: 0.29-0.67; p = 1.4 × 10-4; adjusted p = 0.013). Similarly, glial cell line-derived neurotrophic factor exhibited a suggestively protective effect against TAO (OR: 0.43, 95% CI: 0.22-0.81; p = 0.010; adjusted p = 0.218). Conversely, higher levels of C-C motif chemokine 23 were suggestively linked to an increased risk of TAO (OR: 1.88, 95% CI: 1.21-2.93; p = 0.005; adjusted p = 0.218). The sensitivity analysis and MVMR revealed no evidence of heterogeneity or pleiotropy. CONCLUSION: This study identifies C-C motif chemokine 4 and glial cell line-derived neurotrophic factor as potential protective biomarkers for TAO, whereas C-C motif chemokine 23 emerges as a suggestive risk marker. These findings elucidate potential causal relationships and highlight the significance of these proteins in the pathogenesis and prospective therapeutic strategies for TAO.

17.
Adv Mater ; 36(31): e2402666, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38632497

ABSTRACT

Shaping room temperature phosphorescence (RTP) materials into 3D bodies is important for stereoscopic optoelectronic displays but remains challenging due to their poor processability and mechanical properties. Here, konjac glucomannan (KGM) is employed to anchor arylboronic acids with various π conjugations via a facile B─O covalent reaction to afford printable inks, using which full-color high-fidelity 3D RTP objects with high mechanical strength can be obtained via direct ink writing-based 3D printing and freeze-drying. The doubly rigid structure supplied by the synergy of hydrogen bonding and B─O covalent bonding can protect the triplet excitons; thus, the prepared 3D RTP object shows a striking lifetime of 2.14 s. The printed counterparts are successfully used for 3D anti-counterfeiting and can be recycled and reprinted nondestructively by dissolving in water. This success expands the scope of printable 3D luminescent materials, providing an eco-friendly platform for the additive manufacturing of sophisticated 3D RTP architectures.

18.
Cancer Lett ; 591: 216848, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38604312

ABSTRACT

FBXO43 is a member of the FBXO subfamily of F-box proteins, known to be a regulatory hub during meiosis. A body of data showed that FBXO43 is overexpressed in a number of human cancers. However, whether and how FBXO43 affects cell cycle progression and growth of cancer cells remain elusive. In this study, we provide first piece of evidence, showing a pivotal role of FBXO43 in cell cycle progression and growth of cancer cells. Specifically, FBXO43 acts as a positive cell cycle regulator with an oncogenic activity in variety types of human cancer, including non-small cell lung cancer, hepatocellular carcinoma and sarcoma. Mechanistically, FBXO43 interacts with phosphorylated SKP2 induced by AKT1, leading to reduced SKP2 auto-ubiquitylation and subsequent proteasome degradation. Taken together, our study demonstrates that FBXO43 promotes cell cycle progression by stabilizing SKP2, and FBXO43 could serve as a potential anti-cancer target.


Subject(s)
Cell Cycle , F-Box Proteins , Proto-Oncogene Proteins c-akt , S-Phase Kinase-Associated Proteins , Ubiquitination , Animals , Humans , Mice , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Non-Small-Cell Lung/genetics , Cell Line, Tumor , Cell Proliferation , F-Box Proteins/metabolism , F-Box Proteins/genetics , Gene Expression Regulation, Neoplastic , HEK293 Cells , Lung Neoplasms/pathology , Lung Neoplasms/metabolism , Lung Neoplasms/genetics , Neoplasms/pathology , Neoplasms/metabolism , Neoplasms/genetics , Phosphorylation , Proteasome Endopeptidase Complex/metabolism , Proteolysis , Proto-Oncogene Proteins c-akt/metabolism , S-Phase Kinase-Associated Proteins/metabolism , S-Phase Kinase-Associated Proteins/genetics
19.
Gland Surg ; 13(3): 314-324, 2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38601278

ABSTRACT

Background: The occurrence of cervical lymph node metastasis in T1 stage papillary thyroid carcinoma (PTC) is frequently observed. Notably, lateral lymph node metastasis (LLNM) emerges as a critical risk factor adversely affecting prognostic outcomes in PTC. The primary aim of this investigation was to delineate the risk factors associated with LLNM in the initial stages of PTC. Methods: This retrospective analysis encompassed 3,332 patients diagnosed with T1 stage PTC without evident LLNM at the time of diagnosis. These individuals underwent primary surgical intervention at West China Hospital, Sichuan University between June 2017 and February 2023. The cohort was divided into two groups: patients manifesting LLNM and those without metastasis at the time of surgery. Additionally, T1 stage PTC patients were subdivided into T1a and T1b categories. Factors influencing LLNM were scrutinized through both univariate and multivariate analyses. Results: The incidence of LLNM was observed in 6.2% of the cohort (206 out of 3,332 patients). Univariate analysis revealed significant correlations between LLNM and male gender (P<0.001), tumor localization in the upper lobe (P<0.001), maximal volume of the primary tumor (P<0.001), largest tumor diameter (P<0.001), multifocality (P<0.001), and bilaterality (P<0.001), with the exception of age (P=0.788) and duration of active surveillance (AS) (P=0.978). Multivariate logistic regression analysis identified male gender (P<0.001), upper lobe tumor location (P<0.001), maximal primary tumor volume (P<0.001), and multifocality (P<0.001) as independent predictors of LLNM. However, age categories (≤55, >55 years), maximum tumor diameter, bilaterality, and surveillance duration did not exhibit a significant impact. Comparative analyses between T1a and T1b subgroups showed congruent univariate results but revealed differences in multivariate outcomes. In the T1a subgroup, gender, tumor location, and multifocality (all P<0.05) were associated with elevated LLNM risk. Conversely, in the T1b subgroup, tumor location, dimensions, and multifocality (all P<0.05) were significant predictors of LLNM risk, whereas gender (P=0.097) exerted a marginal influence. Conclusions: The investigation highlights several key risk factors for LLNM in T1 stage PTC patients, including gender, upper lobe tumor location, larger tumor size, and multifocality. Conversely, prolonged AS and younger age did not significantly elevate LLNM risk, suggesting the viability of AS as a strategic option in selected cases.

20.
Dev Cell ; 59(13): 1707-1723.e8, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38657611

ABSTRACT

RNA-binding proteins (RBPs), as key regulators of mRNA fate, are abundantly expressed in the testis. However, RBPs associated with human male infertility remain largely unknown. Through bioinformatic analyses, we identified 62 such RBPs, including an evolutionarily conserved RBP, DEAD-box helicase 20 (DDX20). Male germ-cell-specific inactivation of Ddx20 at E15.5 caused T1-propsermatogonia (T1-ProSG) to fail to reenter cell cycle during the first week of testicular development in mice. Consequently, neither the foundational spermatogonial stem cell (SSC) pool nor progenitor spermatogonia were ever formed in the knockout testes. Mechanistically, DDX20 functions to control the translation of its target mRNAs, many of which encode cell-cycle-related regulators, by interacting with key components of the translational machinery in prospermatogonia. Our data demonstrate a previously unreported function of DDX20 as a translational regulator of critical cell-cycle-related genes, which is essential for cell-cycle reentry of T1-ProSG and formation of the SSC pool.


Subject(s)
Cell Cycle , DEAD-box RNA Helicases , Spermatogenesis , Spermatogonia , Testis , Animals , Male , Mice , Adult Germline Stem Cells/metabolism , Adult Germline Stem Cells/cytology , Cell Cycle/genetics , DEAD-box RNA Helicases/metabolism , DEAD-box RNA Helicases/genetics , Gene Expression Regulation, Developmental , Mice, Knockout , RNA-Binding Proteins/metabolism , RNA-Binding Proteins/genetics , Spermatogenesis/genetics , Spermatogenesis/physiology , Spermatogonia/metabolism , Spermatogonia/cytology , Testis/metabolism , Testis/cytology
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