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1.
Oncogene ; 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-39014193

ABSTRACT

Circular RNAs (circRNAs) have emerged as key regulators of cancer occurrence and progression, as well as promising biomarkers for cancer diagnosis and prognosis. However, the potential mechanisms of circRNAs implicated in lymph node (LN) metastasis of gastric cancer remain unclear. Herein, we identify a novel N6-methyladenosine (m6A) modified circRNA, circPAK2, which is significantly upregulated in gastric cancer tissues and metastatic LN tissues. Functionally, circPAK2 enhances the migration, invasion, lymphangiogenesis, angiogenesis, epithelial-mesenchymal transition (EMT), and metastasis of gastric cancer in vitro and in vivo. Mechanistically, circPAK2 is exported by YTH domain-containing protein 1 (YTHDC1) from the nucleus to the cytoplasm in an m6A methylation-dependent manner. Moreover, increased cytoplasmic circPAK2 interacts with Insulin-Like Growth Factor 2 mRNA-Binding Proteins (IGF2BPs) and forms a circPAK2/IGF2BPs/VEGFA complex to stabilize VEGFA mRNA, which contributes to gastric cancer vasculature formation and aggressiveness. Clinically, high circPAK2 expression is positively associated with LN metastasis and poor prognosis in gastric cancer. This study highlights m6A-modified circPAK2 as a key regulator of LN metastasis of gastric cancer, thus supporting circPAK2 as a promising therapeutic target and prognostic biomarker for gastric cancer.

2.
Am J Cancer Res ; 14(5): 2272-2286, 2024.
Article in English | MEDLINE | ID: mdl-38859846

ABSTRACT

OBJECTIVE: To establish nomogram models for predicting the overall survival (OS) and cancer-specific survival (CSS) of gastric cancer liver metastasis (GCLM) patients. METHODS: Data from the Surveillance, Epidemiology, and End Results (SEER) database for 5,451 GCLM patients diagnosed between 2010 and 2015 were analyzed. The cohort was divided into a training set (3,815 cases) and an internal validation set (1,636 cases). External validation included 193 patients from the Fourth Hospital of Hebei Medical University and 171 patients from the People's Hospital of Shijiazhuang City, spanning 2016-2018. Multivariable Cox regression analysis identified eight independent prognostic factors for OS and CSS in GCLM patients, including age, histological type, grade, tumor size, surgery, chemotherapy, bone metastasis, and lung metastasis. Two nomogram models were developed based on these factors and evaluated using time-dependent receiver operating characteristic curve analysis, calibration curves, and decision curve analysis. RESULTS: Internal validation showed that the nomogram models outperformed the American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging system in predicting 1-year, 2-year, and 3-year OS and CSS in GCLM patients (1-year OS: 0.801 vs. 0.593, P < 0.001; 1-year CSS: 0.807 vs. 0.598, P < 0.001; 2-year OS: 0.803 vs. 0.630, P < 0.001; 2-year CSS: 0.802 vs. 0.633, P < 0.001; 3-year OS: 0.824 vs. 0.691, P < 0.001; 3-year CSS: 0.839 vs. 0.692, P < 0.001). CONCLUSION: This study developed and validated nomogram models using SEER database data to predict OS and CSS in GCLM patients. These models offer improved prognostic accuracy over traditional staging systems, aiding in clinical decision-making.

3.
J Exp Clin Cancer Res ; 43(1): 181, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38937855

ABSTRACT

BACKGROUND: This study aimed to develop a novel six-gene expression biomarker panel to enhance the early detection and risk stratification of peritoneal recurrence and micrometastasis in locally advanced gastric cancer (LAGC). METHODS: We used genome-wide transcriptome profiling and rigorous bioinformatics to identify a six-gene expression biomarker panel. This panel was validated across multiple clinical cohorts using both tissue and liquid biopsy samples to predict peritoneal recurrence and micrometastasis in patients with LAGC. RESULTS: Through genome-wide expression profiling, we identified six mRNAs and developed a risk prediction model using 196 samples from a surgical specimen training cohort. This model, incorporating a 6-mRNA panel with clinical features, demonstrated high predictive accuracy for peritoneal recurrence in gastric cancer patients, with an AUC of 0.966 (95% CI: 0.944-0.988). Transitioning from invasive surgical or endoscopic biopsy to noninvasive liquid biopsy, the model retained its predictive efficacy (AUC = 0.963; 95% CI: 0.926-1.000). Additionally, the 6-mRNA panel effectively differentiated patients with or without peritoneal metastasis in 95 peripheral blood specimens (AUC = 0.970; 95% CI: 0.936-1.000) and identified peritoneal micrometastases with a high efficiency (AUC = 0.941; 95% CI: 0.874-1.000). CONCLUSIONS: Our study provides a novel gene expression biomarker panel that significantly enhances early detection of peritoneal recurrence and micrometastasis in patients with LAGC. The RSA model's predictive capability offers a promising tool for tailored treatment strategies, underscoring the importance of integrating molecular biomarkers with clinical parameters in precision oncology.


Subject(s)
Biomarkers, Tumor , Gene Expression Profiling , Neoplasm Micrometastasis , Neoplasm Recurrence, Local , Peritoneal Neoplasms , Stomach Neoplasms , Humans , Stomach Neoplasms/genetics , Stomach Neoplasms/pathology , Liquid Biopsy/methods , Female , Neoplasm Micrometastasis/genetics , Male , Peritoneal Neoplasms/secondary , Peritoneal Neoplasms/genetics , Neoplasm Recurrence, Local/genetics , Neoplasm Recurrence, Local/pathology , Biomarkers, Tumor/genetics , Gene Expression Profiling/methods , Middle Aged , Transcriptome , Aged
4.
Abdom Radiol (NY) ; 2024 May 10.
Article in English | MEDLINE | ID: mdl-38727742

ABSTRACT

PURPOSE: Although microsatellite stability/Epithelial-mesenchymal transition (MSS/EMT) subtypes have been reported in multiple cancer prognosis studies, strong confounding factors between MSS/EMT (usually with Lauren's diffuse phenotype) and diffuse gastric cancer (GC) may obscure the independent prognostic value of diffuse GC. Additionally, recent studies suggest a strong correlation between mural stratification based on CT and diffuse GC. This study aims to investigate potential prognostic factors of MSS diffuse GC using mural stratification and to develop a risk assessment model. METHODS: This retrospective study included 131 patients with MSS diffuse GC who underwent radical surgery. Univariate and multivariate Cox proportional hazards regression analysis was used to identify model predictors and construct a nomogram for overall survival (OS) and recurrence-free survival (RFS) risks. The model's performance was evaluated using ROC, accuracy, and C-index. Internal validation of the model was conducted using the bootstrap resampling method. RESULTS: Among 131 cases, 60 cases (45.8%) exhibited grade 2 mural stratification, which correlated with a poorer tumor prognosis and a more invasive phenotype. Furthermore, a nomogram for predicting OS and RFS prognosis was established based on multivariate results (age, extranodal invasion, mural stratification, and/or P53). The nomogram demonstrated excellent performance, with an AUC of 0.859 (95% CI 0.794-0.924) for OS and 0.859 (95% CI 0.789-0.929) for RFS. Internal validation using 1000 bootstrap samples yielded AUC values of 0.845 and 0.846 for OS and RFS, respectively. CONCLUSION: Grade 2 mural stratification based on CT imaging revealed a more aggressive invasive phenotype, characterized by increased LN metastasis, higher rates of peritoneal metastasis, and a poorer short-term prognosis. Furthermore, the CT phenotype-based nomogram demonstrates favorable discrimination and calibration, enabling convenient individual short-term prognostic evaluation following resection of MSS diffuse GC.

5.
Am J Cancer Res ; 14(4): 1747-1767, 2024.
Article in English | MEDLINE | ID: mdl-38726268

ABSTRACT

To develop nomogram models for predicting the overall survival (OS) and cancer-specific survival (CSS) of early-onset gastric cancer (EOGC) patients. A total of 1077 EOGC patients from the Surveillance, Epidemiology, and End Results (SEER) database were included, and an additional 512 EOGC patients were recruited from the Fourth Hospital of Hebei Medical University, serving as an external test set. Univariate and multivariate Cox regression analyses were performed to identify independent prognostic factors. Based on these factors, two nomogram models were established, and web-based calculators were developed. These models were validated using receiver operating characteristics (ROC) curve analysis, calibration curves, and decision curve analysis (DCA). Multivariate analysis identified gender, histological type, stage, N stage, tumor size, surgery, primary site, and lung metastasis as independent prognostic factors for OS and CSS in EOGC patients. Calibration curves and DCA curves demonstrated that the two constructed nomogram models exhibited good performance. These nomogram models demonstrated superior performance compared to the 7th edition of the AJCC tumor-node-metastasis (TNM) classification (internal validation set: 1-year OS: 0.831 vs 0.793, P = 0.072; 1-year CSS: 0.842 vs 0.816, P = 0.190; 3-year OS: 0.892 vs 0.857, P = 0.039; 3-year CSS: 0.887 vs 0.848, P = 0.018; 5-year OS: 0.906 vs 0.880, P = 0.133; 5-year CSS: 0.900 vs 0.876, P = 0.109). In conclusion, this study developed two nomogram models: one for predicting OS and the other for CSS of EOGC patients, offering valuable assistance to clinicians.

6.
Mol Carcinog ; 63(7): 1378-1391, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38656643

ABSTRACT

Accumulating evidence suggests that lymphangiogenesis plays a crucial role in lymphatic metastasis, leading to tumor immune tolerance. However, the specific mechanism remains unclear. In this study, miR-431-5p was markedly downregulated in both gastric cancer (GC) tissues and plasma exosomes, and its expression were correlated negatively with LN metastasis and poor prognosis. Mechanistically, miR-431-5p weakens the TGF-ß1/SMAD2/3 signaling pathway by targeting ZEB1, thereby suppressing the secretion of VEGF-A and ANG2, which in turn hinders angiogenesis, lymphangiogenesis, and lymph node (LN) metastasis in GC. Experiments using a popliteal LN metastasis model in BALB/c nude mice demonstrated that miR-431-5p significantly reduced popliteal LN metastasis. Additionally, miR-431-5p enhances the efficacy of anti-PD1 treatment, particularly when combined with galunisertib, anti-PD1 treatment showing a synergistic effect in inhibiting GC progression in C57BL/6 mice. Collectively, these findings suggest that miR-431-5p may modulate the TGF-ß1/SMAD2/3 pathways by targeting ZEB1 to impede GC progression, angiogenesis, and lymphangiogenesis, making it a promising therapeutic target for GC management.


Subject(s)
Gene Expression Regulation, Neoplastic , Lymphangiogenesis , Lymphatic Metastasis , Mice, Inbred BALB C , MicroRNAs , Neovascularization, Pathologic , Signal Transduction , Smad2 Protein , Smad3 Protein , Stomach Neoplasms , Transforming Growth Factor beta1 , Zinc Finger E-box-Binding Homeobox 1 , Stomach Neoplasms/pathology , Stomach Neoplasms/genetics , Stomach Neoplasms/metabolism , Humans , Animals , MicroRNAs/genetics , Lymphangiogenesis/genetics , Mice , Neovascularization, Pathologic/genetics , Neovascularization, Pathologic/pathology , Neovascularization, Pathologic/metabolism , Transforming Growth Factor beta1/metabolism , Transforming Growth Factor beta1/genetics , Zinc Finger E-box-Binding Homeobox 1/genetics , Zinc Finger E-box-Binding Homeobox 1/metabolism , Smad3 Protein/metabolism , Smad3 Protein/genetics , Smad2 Protein/metabolism , Smad2 Protein/genetics , Mice, Nude , Male , Female , Cell Line, Tumor , Mice, Inbred C57BL , Prognosis , Middle Aged , Angiogenesis
7.
Eur J Clin Invest ; 54(8): e14201, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38533747

ABSTRACT

BACKGROUND: Robotic gastrectomy is increasingly utilized for gastric cancer, but high morbidity remains a concern. Myosteatosis or low skeletal muscle density reflecting fatty infiltration, associates with complications after other cancer surgeries but has not been evaluated for robotic gastrectomy. METHODS: This retrospective study analysed 381 patients undergoing robotic gastrectomy for gastric cancer from September 2019 to October 2022. Myosteatosis was quantified on preoperative computed tomography (CT) images at lumbar 3 (L3). Propensity score matching addressed potential confounding between myosteatosis and non-myosteatosis groups. Outcomes were postoperative complications, 30 days mortality, 30 days readmissions and survival. RESULTS: Myosteatosis was present in 33.6% of patients. Myosteatosis associated with increased overall (47.7% vs. 26.5%, p < 0.001) and severe complications (12.4% vs. 4.9%, p < 0.001). After matching, myosteatosis remained associated with increased overall complications, major complications, intensive care unit (ICU) transfer and readmission (all p < 0.05). Myosteatosis independently predicted overall [odds ratio (OR) = 2.86, 95% confidence interval (CI): 1.57-5.20, p = 0.001] and severe complications (OR = 4.81, 95% CI: 1.51-15.27, p = 0.008). Myosteatosis also associated with reduced overall (85.0% vs. 93.2%, p = 0.015) and disease-free survival (80.3% vs. 88.4%, p=0.029). On multivariate analysis, myosteatosis independently predicted poorer survival [hazard ratio (HR) = 2.83, 95% CI: 1.32-6.08, p=0.012] and disease-free survival (HR = 1.83, 95% CI: 1.01-3.30, p=0.032). CONCLUSION: Preoperative CT-defined myosteatosis independently predicts increased postoperative complications and reduced long-term survival after robotic gastrectomy for gastric cancer. Assessing myosteatosis on staging CT could optimize preoperative risk stratification.


Subject(s)
Gastrectomy , Postoperative Complications , Propensity Score , Robotic Surgical Procedures , Stomach Neoplasms , Tomography, X-Ray Computed , Humans , Stomach Neoplasms/surgery , Stomach Neoplasms/mortality , Gastrectomy/adverse effects , Male , Female , Postoperative Complications/epidemiology , Middle Aged , Aged , Retrospective Studies , Patient Readmission/statistics & numerical data , Sarcopenia/diagnostic imaging , Muscle, Skeletal/diagnostic imaging
8.
Nutrition ; 123: 112408, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38513525

ABSTRACT

BACKGROUND: Sarcopenia, defined as decreased muscle mass and function, correlates with postoperative morbidity and mortality in cancer surgery. However, sarcopenia's impact specifically following robotic gastrectomy for gastric cancer has not been clearly defined. This study aimed to determine the influence of sarcopenia on short- and long-term clinical outcomes after robotic gastrectomy for gastric cancer. METHODS: This retrospective study analyzed 381 gastric cancer patients undergoing robotic gastrectomy. Sarcopenia was diagnosed by preoperative computed tomography (CT) body composition analysis. Propensity score matching created 147 pairs of sarcopenia and nonsarcopenia patients for comparison. Outcomes included postoperative complications, survival, inflammatory markers, length of stay, intensive care unit (ICU) transfer, and readmissions. RESULTS: Sarcopenia patients exhibited significantly higher rates of overall (53.7% versus 21.1%, P < 0.001), serious (12.9% versus 4.1%, P = 0.007), and grade III-IV complications compared to nonsarcopenia pairs after matching. Sarcopenia independently predicted reduced 3-years overall (HR = 2.53, 95% CI: 1.19-5.40, P = 0.016) and disease-free survival (HR = 1.99, 95% CI: 1.09-3.66, P = 0.026). Sarcopenia patients also showed heightened postoperative leukocyte, neutrophil, platelet, platelet to lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and monocyte to lymphocyte ratio (MLR) levels alongside suppressed lymphocytes, monocytes, and neutrophil to lymphocyte ratio (NLR). CONCLUSION: Preoperative sarcopenia is correlated with increased postoperative complications and poorer long-term survival in gastric cancer patients undergoing robotic gastrectomy. Sarcopenia assessment can optimize preoperative risk stratification and perioperative management in this population.


Subject(s)
Gastrectomy , Postoperative Complications , Propensity Score , Robotic Surgical Procedures , Sarcopenia , Stomach Neoplasms , Humans , Sarcopenia/etiology , Stomach Neoplasms/surgery , Stomach Neoplasms/complications , Male , Female , Retrospective Studies , Gastrectomy/adverse effects , Gastrectomy/methods , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Robotic Surgical Procedures/methods , Robotic Surgical Procedures/adverse effects , Aged , Middle Aged , Prognosis , Preoperative Period , Length of Stay/statistics & numerical data
9.
Mol Psychiatry ; 2024 Mar 18.
Article in English | MEDLINE | ID: mdl-38499656

ABSTRACT

Autism spectrum disorder (ASD) is a major neurodevelopmental disorder affecting 1 in 36 children in the United States. While neurons have been the focus of understanding ASD, an altered neuro-immune response in the brain may be closely associated with ASD, and a neuro-immune interaction could play a role in the disease progression. As the resident immune cells of the brain, microglia regulate brain development and homeostasis via core functions including phagocytosis of synapses. While ASD has been traditionally considered a polygenic disorder, recent large-scale human genetic studies have identified SCN2A deficiency as a leading monogenic cause of ASD and intellectual disability. We generated a Scn2a-deficient mouse model, which displays major behavioral and neuronal phenotypes. However, the role of microglia in this disease model is unknown. Here, we reported that Scn2a-deficient mice have impaired learning and memory, accompanied by reduced synaptic transmission and lower spine density in neurons of the hippocampus. Microglia in Scn2a-deficient mice are partially activated, exerting excessive phagocytic pruning of post-synapses related to the complement C3 cascades during selective developmental stages. The ablation of microglia using PLX3397 partially restores synaptic transmission and spine density. To extend our findings from rodents to human cells, we established a microglia-incorporated human cerebral organoid model carrying an SCN2A protein-truncating mutation identified in children with ASD. We found that human microglia display increased elimination of post-synapse in cerebral organoids carrying the SCN2A mutation. Our study establishes a key role of microglia in multi-species autism-associated models of SCN2A deficiency from mouse to human cells.

10.
Cell Death Dis ; 15(1): 3, 2024 01 04.
Article in English | MEDLINE | ID: mdl-38177102

ABSTRACT

Current treatment strategies for cancer, especially advanced cancer, are limited and unsatisfactory. One of the most substantial advances in cancer therapy, in the last decades, was the discovery of a new layer of immunotherapy approach, immune checkpoint inhibitors (ICIs), which can specifically activate immune cells by targeting immune checkpoints. Immune checkpoints are a type of immunosuppressive molecules expressed on immune cells, which can regulate the degree of immune activation and avoid autoimmune responses. ICIs, such as anti-PD-1/PD-L1 drugs, has shown inspiring efficacy and broad applicability across various cancers. Unfortunately, not all cancer patients benefit remarkably from ICIs, and the overall response rates to ICIs remain relatively low for most cancer types. Moreover, the primary and acquired resistance to ICIs pose serious challenges to the clinical application of cancer immunotherapy. Thus, a deeper understanding of the molecular biological properties and regulatory mechanisms of immune checkpoints is urgently needed to improve clinical options for current therapies. Recently, circular RNAs (circRNAs) have attracted increasing attention, not only due to their involvement in various aspects of cancer hallmarks, but also for their impact on immune checkpoints in shaping the tumor immune microenvironment. In this review, we systematically summarize the current status of immune checkpoints in cancer and the existing regulatory roles of circRNAs on immune checkpoints. Meanwhile, we also aim to settle the issue in an evidence-oriented manner that circRNAs involved in cancer hallmarks regulate the effects and resistance of ICIs by targeting immune checkpoints.


Subject(s)
Neoplasms , RNA, Circular , Humans , RNA, Circular/genetics , Immune Checkpoint Inhibitors/pharmacology , Immune Checkpoint Inhibitors/therapeutic use , Neoplasms/drug therapy , Neoplasms/genetics , Neoplasms/pathology , Immunotherapy , Tumor Microenvironment/genetics
11.
Article in English | MEDLINE | ID: mdl-38073380

ABSTRACT

OBJECTIVE: Deep vein thrombosis (DVT) formation of lower extremities can lead to serious complications including pulmonary embolism (PE) and chronic post-thrombotic syndrome (PTS). We aimed to explore the relationship between the ratio of thrombotic density and the occurrence of PE and PTS in patients with DVT of the lower extremities. METHODS: A retrospective analysis was conducted in patients who performed computed tomography venography, dividing into DVT with PE group (54 patients) and DVT-alone group (34 patients), The clinical data were recorded. Univariate and multivariate logistic regression analysis were used to analysis variables associated with PE. The ability of thrombosis density ratio and Wells score to diagnose PE was evaluated by using the receiver operating characteristic curve (ROC) area under the curve (AUC). According to the treatment and follow-up results, subgroup analysis was performed, and the Villata score was used to determine the presence or absence of PTS and its severity. RESULTS: Compare with the DVT-alone group, more patients had dyspnea and chest pain in the DVT with PE group. DVT with PE group had lower the percentage of neutrophils, white blood cell count and platelet count, while had higher blood cell count, D-dimer, wells score, thrombus and thrombus density ratio. Multivariate logistic analysis showed that percentage of neutrophils (OR(95% CIs)=1.15 (1.01,1.31), P = 0.040), platelets (OR(95% CIs)=0.96 (0.93,0.99), P = 0.011), and thrombus density ratio (OR(95% CIs)=5.99 (1.96,18.35), P = 0.002) are independent predictors of PE. The Wells score and thrombosis density ratio were consistent in the diagnostic efficacy of PE. In the subgroup analysis, there was a relevance between the ratio of thrombosis density and the Villalta score. CONCLUSION: Percentage of neutrophils, platelets, and thrombus density ratio are independent predictors of PE. The thrombosis density of DVT patients may be an index to predict the risk of PE and PTS in DVT patients.

12.
bioRxiv ; 2023 Oct 31.
Article in English | MEDLINE | ID: mdl-37961213

ABSTRACT

Neuronal hyperexcitability is a hallmark of seizures. It has been recently shown in rodent models of seizures that microglia, the brain's resident immune cells, can respond to and modulate neuronal excitability. However, how human microglia interacts with human neurons to regulate hyperexcitability mediated by epilepsy-causing genetic mutation found in human patients remains unknown. The SCN2A genetic locus is responsible for encoding the voltage-gated sodium channel Nav1.2, recognized as one of the leading contributors to monogenic epilepsies. Previously, we demonstrated that the recurring Nav1.2-L1342P mutation identified in patients with epilepsy leads to hyperexcitability in a hiPSC-derived cortical neuron model from a male donor. While microglia play an important role in the brain, these cells originate from a different lineage (yolk sac) and thus are not naturally present in hiPSCs-derived neuronal culture. To study how microglia respond to diseased neurons and influence neuronal excitability, we established a co-culture model comprising hiPSC-derived neurons and microglia. We found that microglia display altered morphology with increased branch length and enhanced calcium signal when co-cultured with neurons carrying the Nav1.2-L1342P mutation. Moreover, the presence of microglia significantly lowers the action potential firing of neurons carrying the mutation. Interestingly, we further demonstrated that the current density of sodium channels in neurons carrying the epilepsy-associated mutation was reduced in the presence of microglia. Taken together, our work reveals a critical role of human iPSCs-derived microglia in sensing and dampening hyperexcitability mediated by an epilepsy-causing mutation present in human neurons, highlighting the importance of neuron-microglia interactions in human pathophysiology.

13.
Front Oncol ; 13: 1201928, 2023.
Article in English | MEDLINE | ID: mdl-37841441

ABSTRACT

Background: Currently, gastric cancer with positive lavage cytology without gross peritoneal dissemination (GC-CY1) is a special type of metastatic form with poor prognosis. Consensus guidelines on treatment strategies for patients with GC-CY1 have not been established. This study involves a single-arm, prospective, phase II clinical trial to examine the efficacy and safety of neoadjuvant intraperitoneal and systemic (NIPS) albumin-bound paclitaxel combined with Camrelizumab and S-1 in the treatment of GC-CY1 patients. Methods/design: This is a prospective single-center exploratory study, and the primary endpoints of the trial are R0 resection rate and conversion rate of abdominal free cancer cells (FCCs), with secondary endpoints of 3-year progression-free survival (PFS); 3-year overall survival (OS); objective remission rate (ORR); disease control rate (DCR); safety and TRG classification. Discussion: This study is the first to apply NIPS albumin-bound paclitaxel combined with Camrelizumab and S-1 to the conversion therapy of GC-CY1 patients. It is speculated that this combination of regimens will increase the negative conversion rate of FCCs by 20%, which will provide innovative insights into conversion treatment ideas for GC-CY1 patients to be managed in a more comprehensive and optimized manner. Clinical trial registration: http://clinicaltrials.gov/, identifier NCT05410847.

14.
Res Sq ; 2023 Sep 28.
Article in English | MEDLINE | ID: mdl-37841865

ABSTRACT

Autism spectrum disorder (ASD) is a major neurodevelopmental disorder affecting 1 in 36 children in the United States. While neurons have been the focus to understand ASD, an altered neuro-immune response in the brain may be closely associated with ASD, and a neuro-immune interaction could play a role in the disease progression. As the resident immune cells of the brain, microglia regulate brain development and homeostasis via core functions including phagocytosis of synapses. While ASD has been traditionally considered a polygenic disorder, recent large-scale human genetic studies have identified SCN2A deficiency as a leading monogenic cause of ASD and intellectual disability. We generated a Scn2a-deficient mouse model, which displays major behavioral and neuronal phenotypes. However, the role of microglia in this disease model is unknown. Here, we reported that Scn2a-deficient mice have impaired learning and memory, accompanied by reduced synaptic transmission and lower spine density in neurons of the hippocampus. Microglia in Scn2a-deficient mice are partially activated, exerting excessive phagocytic pruning of post-synapses related to the complement C3 cascades during selective developmental stages. The ablation of microglia using PLX3397 partially restores synaptic transmission and spine density. To extend our findings from rodents to human cells, we established a microglial-incorporated human cerebral organoid model carrying an SCN2A protein-truncating mutation identified in children with ASD. We found that human microglia display increased elimination of post-synapse in cerebral organoids carrying the SCN2A mutation. Our study establishes a key role of microglia in multi-species autism-associated models of SCN2A deficiency from mouse to human cells.

17.
Animals (Basel) ; 13(13)2023 Jul 07.
Article in English | MEDLINE | ID: mdl-37444031

ABSTRACT

We described a new species of genus Pareas from Baise City, Guangxi Zhuang Autonomous Region, China, based on morphological and molecular evidence. Pareas baiseensis sp. nov. is distinguished from its congeners by the combination of (1) Yellowish-brown body colouration; (2) Frontal subhexagonal to diamond-shaped with its lateral sides converging posteriorly; (3) The anterior pair of chin shields is longer than it is broad; (4) Loreal not in contact with the eye, prefrontal in contact with the eye, two or three suboculars; (5) Rows of 15-15-15 dorsal scales, five rows of mid-dorsal scales keeled at the middle of the body, one vertebral scale row enlarged; (6) 187-191 ventrals, 89-97 subcaudals, all divided, cloacal plate single; (7) Two postocular stripes, the nuchal area forming a dark black four-pointed fork collar with the middle tines shorter than the outside tines. The genetic divergence (uncorrected p-distance) between the new species and other representatives of Pareas ranged from 13.9% to 24.4% for Cytochrome b (Cyt b) and 12.1% to 25.5% for NADH dehydrogenase subunit 4 (ND4). Phylogenetic analyses of mitochondrial DNA gene data recovered the new species from being the sister taxon to (P. boulengeri + P. chinensis) from China.

18.
Zootaxa ; 5319(3): 389-402, 2023 Jul 26.
Article in English | MEDLINE | ID: mdl-37518224

ABSTRACT

We describe a new species of the genus Achalinus Peters, 1869 from Daming Mountain, Shanglin County, Nanning City, Guangxi Zhuang Autonomous Region, China, based on a single adult male specimen. It can be distinguished from all the other species in Achalinus by a combination of the following morphological characters: (1) a bright yellow collar around the neck, extending forward to the ventral of the head; (2) tail length comparatively long, TaL/Tol ratio 0.25; (3) DSR 23-23-23, moderately keeled; (4) VS 3+162; (5) SC 74, unpaired; (6) cloacal plate entire; (7) SPL 6, the fourth and fifth in contact with the eye; (8) IFL 6, the first three touching the first pair of chin shields; (9) a single loreal; (10) length of suture between internasal significantly longer than that between prefrontal, LSBI/LSBP ratio 1.34; (11) two pairs of chin shields; (12) longitudinal vertebral line absent. In addition, the uncorrected p-distances between the new species and other known congeners ranged from 6.3% to 25.4% for the cytochrome c oxidase subunit 1 (CO1). With the addition of the new species the total number of described Achalinus species is increased to 23 of which 17 are found in China.


Subject(s)
Lizards , Snakes , Male , Animals , China , Animal Distribution , Phylogeny
19.
Zootaxa ; 5319(1): 76-90, 2023 Jul 24.
Article in English | MEDLINE | ID: mdl-37518249

ABSTRACT

A new species of the genus Hebius Thompson, 1913 is described from Youjiang District, Baise City, Guangxi Zhuang Autonomous Region, China, based on a single adult female specimen. It can be distinguished from its congeners by the following combination of characters: (1) dorsal scale rows 19-17-17, feebly keeled except the outermost row; (2) tail length comparatively long, TAL/TL ratio 0.30 in females; (3) ventrals 160 (+ 3 preventrals); (4) subcaudals 112; (5) supralabials 9, the fourth to sixth in contact with the eye; (6) infralabials 10, the first 5 touching the first pair of chin shields; (7) preocular 1; (8) postoculars 2; (9) temporals 4, arranged in three rows (1+1+2); (10) maxillary teeth 30, the last 3 enlarged, without diastem; (11) postocular streak presence; (12) background color of dorsal brownish black, a conspicuous, uniform, continuous beige stripe extending from behind the eye to the end of the tail; (13) anterior venter creamish-yellow, gradually fades to the rear, with irregular black blotches in the middle and outer quarter of ventrals, the posterior part almost completely black. The discovery of the new species increases the number of species in the genus Hebius to 51.


Subject(s)
Colubridae , Lizards , Female , Animals , China , Animal Distribution , Tail , Animal Structures , Phylogeny
20.
Eur Radiol ; 33(12): 9275-9285, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37414883

ABSTRACT

OBJECTIVE: Accurate prediction of preoperative occult peritoneal metastasis (OPM) is critical to selecting appropriate therapeutic regimen for gastric cancer (GC). Considering the clinical practicability, we develop and validate a visible nomogram that integrates the CT images and clinicopathological parameters for the individual preoperative prediction of OPM in GC. METHODS: This retrospective study included 520 patients who underwent staged laparoscopic exploration or peritoneal lavage cytology (PLC) examination. Univariate and multivariate logistic regression results were used to screen model predictors and construct nomograms of OPM risk. The performance of the model was detected by using ROC, accuracy, and C-index. The bootstrap resampling method was considered internal validation of the model. The Delong test was used to evaluate the difference in AUC between the two models. RESULTS: Grade 2 mural stratification, tumor thickness, and the Lauren classification diffuse were significant predictors of OPM (p < 0.05). The nomogram of these three factors (compared with the original model) showed a higher predictive effect (p < 0.001). The area under the curve (AUC) of the model was 0.830 (95% CI 0.788-0.873), and the internally validated AUC of 1000 bootstrap samples was 0.826 (95% CI 0.756-0.870). The sensitivity, specificity, and accuracy were 76.0%, 78.8%, and 78.3%, respectively. CONCLUSIONS: CT phenotype-based nomogram demonstrates favorable discrimination and calibration, and it can be conveniently used for preoperative individual risk rating of OPM in GC. CLINICAL RELEVANCE STATEMENT: In this study, the preoperative OPM prediction model based on CT images (mural stratification, tumor thickness) combined with pathological parameters (the Lauren classification) showed excellent predictive ability in GC, and it is also suitable for clinicians to use rather than limited to professional radiologists. KEY POINTS: • Nomogram based on CT image analysis can effectively predict occult peritoneal metastasis in gastric cancer (training area under the curve (AUC) = 0.830 and bootstrap AUC = 0.826). • Nomogram model combined with CT features performed better than the original model (established using only clinicopathological parameters) in differentiating occult peritoneal metastasis of gastric cancer.


Subject(s)
Peritoneal Neoplasms , Stomach Neoplasms , Humans , Stomach Neoplasms/pathology , Retrospective Studies , Peritoneal Neoplasms/diagnosis , Cytology , Nomograms , Tomography, X-Ray Computed/methods
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