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35 result(s) for "Guo, Jiwu"
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From centripetal to centrifugal: pathological regression patterns after neoadjuvant or conversion therapy as markers of nodal risk and a framework for future research on individualized lymphadenectomy in gastric cancer
To analyze the relationship between tumor regression patterns and ypN positivity and explore their implications for postoperative nodal-risk stratification after neoadjuvant or conversion therapy in advanced gastric cancer, while generating hypotheses for future individualized lymphadenectomy research. Tumor regression patterns were classified as centripetal, diffuse/mixed, or centrifugal. Clinical and pathological characteristics were compared using the Kruskal-Wallis and χ² tests. Using ypN positivity as the outcome, a multivariable logistic regression model was constructed. Sensitivity analyses were performed in the subgroup with ≥16 retrieved lymph nodes, after additional adjustment for ypT and Becker tumor regression grade (TRG), and in the non-pCR subgroup. Internal validation was performed using a 7:3 stratified random split and 10-fold cross-validation. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC), 95% confidence intervals, calibration, and the Brier score. We additionally compared a baseline clinicopathological model with a combined model incorporating regression pattern to assess incremental predictive value. Among 195 patients, 74 (38.0%) exhibited centripetal regression, 43 (22.1%) had diffuse/mixed regression, and 78 (40.0%) demonstrated centrifugal regression. Centripetal regression was characterized by low PRI, higher LRI and CER, and a very low ypN positivity rate (5.4%), whereas centrifugal regression showed the opposite pattern and the highest ypN positivity rate (75.6%); diffuse/mixed regression showed intermediate features (all p < 0.001). Multivariable analysis identified diffuse/mixed and centrifugal regression as the strongest independent predictors of ypN positivity. The apparent full-cohort model demonstrated an AUC of 0.875 (95% CI 0.826-0.922) with good calibration and a Brier score of 0.137. These associations remained robust after additional adjustment for ypT and Becker TRG and in the non-pCR subgroup. Internal validation showed acceptable performance, with a validation AUC of 0.826 in the 7:3 split-sample analysis and a pooled AUC of 0.822 in 10-fold cross-validation. Addition of regression pattern to the baseline clinicopathological model improved discrimination and reduced prediction error. Pathological regression patterns provide effective stratification of residual lymph node metastasis after neoadjuvant or conversion therapy. Centripetal regression indicates a very low residual nodal-risk phenotype, whereas centrifugal regression is associated with a heavier nodal burden. At present, regression patterns may be most appropriately used for postoperative risk assessment and multidisciplinary stratification. Their potential role in individualized lymphadenectomy should be viewed as a future translational direction requiring validated preoperative or intraoperative surrogate markers and prospective confirmation.
Immune checkpoint inhibitor therapy for gastric cancer: current status, therapeutic challenges, and future prospects
Gastric cancer is among the most prevalent malignant tumors of the digestive system worldwide. In recent years, immune checkpoint inhibitors (ICIs) have achieved substantial advances in the treatment of gastric cancer. By blocking the PD-1/PD-L1 and CTLA-4 signaling pathways, ICIs enhance antitumor immune responses and offer novel therapeutic options for patients. However, their clinical application continues to face significant challenges, including therapeutic resistance, immune-related adverse events, the lack of reliable biomarkers, and an immunosuppressive tumor microenvironment. This narrative review summarizes recent advances in ICIs-based therapies for gastric cancer, provides an in-depth analysis of existing clinical challenges, and highlights key future research directions, including biomarker discovery, development of predictive models, optimization of combination regimens, targeting of resistance mechanisms, modulation of the tumor-associated microbiota, and improved toxicity management. Moving forward, efforts should focus on advancing immunotherapy toward individualized and precision-based approaches to maximize both efficacy and safety, thereby enabling further optimization and breakthroughs in gastric cancer immunotherapy.
Random-forest algorithm based biomarkers in predicting prognosis in the patients with hepatocellular carcinoma
Background Hepatocellular carcinoma (HCC) one of the most common digestive system tumors, threatens the tens of thousands of people with high morbidity and mortality world widely. The purpose of our study was to investigate the related genes of HCC and discover their potential abilities to predict the prognosis of the patients. Methods We obtained RNA sequencing data of HCC from The Cancer Genome Atlas (TCGA) database and performed analysis on protein coding genes. Differentially expressed genes (DEGs) were selected. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were conducted to discover biological functions of DEGs. Protein and protein interaction (PPI) was performed to investigate hub genes. In addition, a method of supervised machine learning, recursive feature elimination (RFE) based on random forest (RF) classifier, was used to screen for significant biomarkers. And the basic experiment was conducted by lab, we constructe a clinical patients’ database, and obtained the data and results of immunohistochemistry. Results We identified five biomarkers with significantly high expression to predict survival risk of the HCC patients. These prognostic biomarkers included SPC25, NUF2, MCM2, BLM and AURKA. We also defined a risk score model with these biomarkers to identify the patients who is in high risk. In our single-center experiment, 95 pairs of clinical samples were used to explore the expression levels of NUF2 and BLM in HCC. Immunohistochemical staining results showed that NUF2 and BLM were significantly up-regulated in immunohistochemical staining. High expression levels of NUF2 and BLM indicated poor prognosis. Conclusion Our investigation provided novel prognostic biomarkers and model in HCC and aimed to improve the understanding of HCC. In the results obtained, we also conducted a part of experiments to verify the theory described earlier, The experimental results did verify our theory.
Pathologic response and safety of preoperative treatment regimens in gastric cancer undergoing D2 gastrectomy: a real-world cohort study
To compare pathological response and safety among three preoperative treatment regimens-chemotherapy alone, chemotherapy plus immunotherapy, and chemotherapy plus immunotherapy and targeted therapy-in gastric cancer undergoing D2 gastrectomy, and to assess biomarker associations with response. We retrospectively included 195 patients who received preoperative systemic therapy followed by D2 gastrectomy: chemotherapy alone (n = 47), chemotherapy plus immunotherapy (n = 100), or chemotherapy plus immunotherapy and targeted therapy (n = 48). Preoperative therapy was considered neoadjuvant for cM0 disease and conversion therapy for selected baseline cM1 disease. The primary endpoint was MPR (including pCR). pCR was also reported separately as a subset of MPR; secondary endpoints were preoperative treatment-related adverse events, surgical and pathological outcomes, and disease-free and overall survival (DFS, OS). Logistic regression was used to identify factors associated with MPR; DFS and OS were evaluated with Kaplan-Meier and Cox models. Overall pCR and MPR rates were 20.5% and 40.0%. MPR rates were 27.7%, 37.0%, and 58.3% in the chemotherapy, chemotherapy+immunotherapy, and triple-regimen groups. The triple regimen improved MPR versus chemotherapy in unadjusted analysis, but regimen type was not an independent predictor after adjustment. Lauren intestinal subtype and PD-L1 CPS ≥5 were strongly associated with higher MPR, and in PD-L1-low tumors the triple regimen was associated with higher MPR. Rates of grade ≥3 adverse events and postoperative complications were similar across groups. DFS and OS did not differ significantly; higher cN stage and older age were associated with worse outcomes. Preoperative treatment regimens containing immunotherapy, particularly the triple combination, improved pathological response without increasing preoperative risk. Tumor biology-especially Lauren subtype and PD-L1 expression-had a greater impact on response than regimen intensity, supporting biomarker-guided strategies.
Spontaneous subcapsular hepatic hematoma with hepatic rupture and hemorrhage in the postpartum period: a case report and literature review
Subcapsular hepatic hematoma with hepatic rupture in the postpartum period is a rare but potentially fatal condition, most commonly associated with hypertensive disorders of pregnancy and HELLP syndrome. In women without typical risk factors, non-specific symptoms may delay diagnosis. We report a previously healthy term primiparous woman who developed sudden, persistent right upper abdominal pain with nausea 3 h after vaginal delivery. On admission, she had right upper abdominal tenderness, tachycardia, and relative hypotension. Laboratory tests showed anemia, markedly elevated transaminases, and mild coagulation abnormalities. Contrast-enhanced CT demonstrated a large right-lobe subcapsular hepatic hematoma (14.8 × 12.4 cm) with hepatic parenchymal laceration and contrast extravasation, indicating active bleeding, together with perihepatic and abdominopelvic fluid. Emergency angiography confirmed multifocal bleeding from hepatic arterial branches with a hepatic artery–portal vein shunt, and superselective transcatheter arterial embolization achieved hemostasis. Because CT and pelvic angiography raised concern for a possible concurrent occult uterine arterial bleeding source, adjunct bilateral uterine artery embolization was performed in the same session. Recovery was uneventful, with progressive clinical and laboratory improvement. At 5-month follow-up, imaging showed marked hematoma resolution without rebleeding or related complications. This case highlights that persistent postpartum upper abdominal pain warrants early imaging evaluation even in the absence of typical HDP/HELLP-related risk factors. In selected patients with imaging evidence of active bleeding who remain suitable for urgent angiographic intervention, transcatheter arterial embolization may provide an effective minimally invasive hemostatic option.
Gastrointestinal stromal tumor with secondary thrombocytosis: a case report of a high-risk patient
Gastrointestinal stromal tumor (GIST) with secondary thrombocytosis is a rare clinical case, exhibiting specificity in clinical diagnosis and treatment. We report a case of GIST with secondary thrombocythemia to raise clinicians’ attention to this disease. On October 11, 2024, a 58-year-old male patient was admitted to the hospital due to “intermittent right lower abdominal pain with increased bowel movements for more than 1 month.” The patient had no prior history of tumors, chronic inflammatory diseases, hematologic disorders or family history of genetic disorders. MRI-enhanced scans of the small intestine highly indicated a lymphoma of intestinal origin. Small bowel endoscopy and pathological biopsy revealed mild chronic inflammation of the intestinal mucosa, with intact villous architecture, no plasmacytosis, granulomas, or vasculitis, and no indication of GIST. Laboratory tests showed platelet count of 909 × 10 9 /L, white blood cell count of 11.86 × 10 9 /L, neutrophil ratio of 75.10%, lymphocyte ratio of 15.30% and hemoglobin 101 g/L. Bone marrow biopsy microscopically showed a normal number of megakaryocytes without abnormal aggregation and no myelofibrosis, suggesting there was no obvious hematologic malignancy and the thrombocytosis may have been secondary. The patient underwent partial resection of the small intestine and resection of mesenteric lesions on October 18, 2024. The intraoperative frozen section suggested a stromal tumor. The postoperative pathological biopsy suggested a GIST and genetic testing showed a mutation in the c-KIT gene (Exon 13). Postoperatively, the patient was treated with oral imatinib mesylate (400 mg/d) as adjunctive therapy. Three months after surgery, imaging showed no recurrence, platelet decreased and returned to normal levels.
Epidemiology, Quality and Reporting Characteristics of Systematic Reviews of Traditional Chinese Medicine Interventions Published in Chinese Journals
Systematic reviews (SRs) of TCM have become increasingly popular in China and have been published in large numbers. This review provides the first examination of epidemiological characteristics of these SRs as well as compliance with the PRISMA and AMSTAR guidelines. To examine epidemiological and reporting characteristics as well as methodological quality of SRs of TCM published in Chinese journals. Four Chinese databases were searched (CBM, CSJD, CJFD and Wanfang Database) for SRs of TCM, from inception through Dec 2009. Data were extracted into Excel spreadsheets. The PRISMA and AMSTAR checklists were used to assess reporting characteristics and methodological quality, respectively. A total of 369 SRs were identified, most (97.6%) of which used the terms systematic review or meta-analysis in the title. None of the reviews had been updated. Half (49.8%) were written by clinicians and nearly half (47.7%) were reported in specialty journals. The impact factors of 45.8% of the journals published in were zero. The most commonly treated conditions were diseases of the circulatory and digestive disease. Funding sources were not reported for any reviews. Most (68.8%) reported information about quality assessment, while less than half (43.6%) reported assessing for publication bias. Statistical mistakes appeared in one-third (29.3%) of reviews and most (91.9%) did not report on conflict of interest. While many SRs of TCM interventions have been published in Chinese journals, the quality of these reviews is troubling. As a potential key source of information for clinicians and researchers, not only were many of these reviews incomplete, some contained mistakes or were misleading. Focusing on improving the quality of SRs of TCM, rather than continuing to publish them in great quantity, is urgently needed in order to increase the value of these studies.
Knockdown of Nedd8-conjugating enzyme UBE2M suppresses the proliferation and induces the apoptosis of intrahepatic cholangiocarcinoma cells
As an important regulator of neddylation, neural precursor cell expressed developmentally downregulated 8 (Nedd8)-conjugating enzyme E2M (UBE2M) mediates cullin neddylation. Upregulation of the neddylation pathway is associated with tumor progression in intrahepatic cholangiocarcinoma (ICC). The present study was designed to assess the effects of Nedd8-conjugating enzyme UBE2M knockdown on intrahepatic cholangiocarcinoma cells, and to determine the potential underlying mechanisms. UBE2M and associated protein expression levels were determined via immunohistochemistry and western blotting. ICC cells were transfected with short hairpin RNA to knockdown UBE2M expression. Cell Counting Kit-8 and colony formation assays, and xenograft experiments were used to examine cell viability and colony survival in vitro, and tumor formation in vivo. Survival was evaluated using Kaplan-Meier analysis and log-rank tests. Patients with ICC presenting high expression of UBE2M exhibited worse accumulative recurrence and overall survival compared with patients with low expression. Knockdown of UBE2M expression led to a decrease in the viability and clonogenic survival of QBC939 and HUCCT1 cells, and suppressed tumor formation in vivo. UBE2M silencing caused accumulation of cullin-RING ligase substrates (chromatin-licensing and DNA replication factor 1 and origin recognition complex subunit 1), inducing DNA damage responses and apoptosis. The present findings suggested that UBE2M serves an important role in ICC progression and may present as a novel target for the treatment of ICC.
Interactional role of microRNAs and bHLH-PAS proteins in cancer (Review)
MicroRNAs (miRNAs) are recognized as an emerging class of master regulators that regulate human gene expression at the post-transcriptional level and are involved in many normal and pathological cellular processes. Mammalian basic HLH (helix-loop-helix)-PER-ARNT-SIM (bHLH-PAS) proteins are heterodimeric transcriptional regulators that sense and respond to environmental signals (such as chemical pollutants) or to physiological signals (for instance hypoxia). In the normal state, bHLH-PAS proteins are responsible for multiple critical aspects of physiology to ensure the cell accurate homeostasis, but dysregulation of these proteins has been shown to contribute to carcinogenic events such as tumor initiation, promotion, and progression. Increasing epidemiological and experimental studies have shown that bHLH-PAS proteins regulate a panel of miRNAs, whereas some miRNAs also target bHLH-PAS proteins. The interaction between miRNAs and certain bHLH-PAS proteins [hypoxia-inducible factor (HIF) and aryl hydrocarbon receptor (AHR)] is relevant to many vital events associated with tumorigenesis. This review will summarize recent findings on the interesting and complicated underlying mechanisms that miRNAs interact with HIFs or AHR in tumors, hopefully to benefit the discovery of novel drug-interfering targets for cancer therapy.