A phase IV study to evaluate the safety of fruquintinib in Chinese patients in real-world clinical practice.

INTRODUCTION: Fruquintinib is approved in China for patients with metastatic colorectal cancer (CRC) who progressed after 2 lines of chemotherapy. This postmarketing study was conducted to evaluate the safety of fruquintinib in the Chinese population, including previously treated patients with advanced CRC and other solid tumors. METHODS: Patients in the first cycle of fruquintinib or expected to start fruquintinib within a week were enrolled. Fruquintinib was administrated according to the label or per physicians' discretion. Patient characteristics and safety information were collected at baseline, 1 month, and 6 months after consent (or 30 days after the last dose). RESULTS: Overall, 3005 patients enrolled between April 24, 2019 and September 27, 2022. All enrolled patients received at least one dose of fruquintinib. Most patients had metastases at baseline. The median age was 60 years. More than half (64.0%) of the patients started fruquintinib at 5 mg, and the median treatment exposure was 2.7 months. Nearly one-third (32.5%) of patients with CRC received fruquintinib with concomitant antineoplastic agents. Treatment-emergent adverse events (TEAEs) leading to dose modification were reported in 626 (20.8%) patients, and 469 (15.6%) patients experienced TEAEs leading to treatment discontinuation. The most common grade ≥ 3 TEAEs were hypertension (6.6%), palmar-plantar erythrodysesthesia syndrome (2.2%), and platelet count decreased (1.0%). Combination therapy did not lead to excessive toxicities. CONCLUSIONS: The safety profile of fruquintinib in the real world was generally consistent with that in clinical studies, and the incidence of TEAEs was numerically lower than known VEGF/VEGFR inhibitor-related AEs. Fruquintinib exhibited manageable safety and tolerability in Chinese patients in the real-world setting.

Integrating cfDNA liquid biopsy and organoid-based drug screening reveals PI3K signaling as a promising therapeutic target in colorectal cancer.

BACKGROUND: The current precision medicine relies on biomarkers, which are mainly obtained through next-generation sequencing (NGS). However, this model failed to find effective drugs for most cancer patients. This study tried to combine liquid biopsy with functional drug tests using organoid models to find potential drugs for cancer patients. METHODS: Colorectal cancer (CRC) patients were prospectively enrolled and blood samples were collected from patients before the start of treatment. Targeted deep sequencing of cfDNA samples was performed using a 14-gene panel. Gastrointestinal (GI) cancer organoids were established and PI3K and mTOR inhibitors were evaluated on organoid models. RESULTS: A total of 195 mutations were detected across 58 cfDNA samples. The most frequently mutated genes were KRAS, TP53, PIK3CA, and BRAF, all of which exhibited higher mutation rates than tissue biopsy. Although 81% of variants had an allele frequency of less than 1%, certain mutations in KRAS, TP53, and SMAD4 had high allele frequencies exceeding 10%. Notably, among the seven patients with high allele frequency mutations, six had metastatic tumors, indicating that a high allele frequency of ctDNA could potentially serve as a biomarker of later-stage cancer. A high rate of PIK3CA mutation (31 out of 67, or 46.3%) was discovered in CRC patients, suggesting possible tumor progression mechanisms and targeted therapy opportunities. To evaluate the value of anti PI3K strategy in GI cancer, different lines of GI cancer organoids were established. The organoids recapitulated the morphologies of the original tumors. Organoids were generally insensitive to PI3K inhibitors. However, CRC-3 and GC-4 showed response to mTOR inhibitor Everolimus, and GC-3 was sensitive to PI3Kδ inhibitor Idelalisib. The CRC organoid with a PIK3CA mutation showed greater sensitivity to the PI3K inhibitor Alpelisib than wildtype organoids, suggesting potential treatment options for the corresponding patients. CONCLUSION: Liquid biopsy holds significant promise for improving precision treatment and tumor prognosis in colorectal cancer patients. The combination of biomarker-based drug prediction with organoid-based functional drug sensitivity assay may lead to more effective cancer treatment.

Predictive value of the neutrophil percentage-to-albumin ratio for coronary atherosclerosis severity in patients with CKD.

BACKGROUND: The neutrophil percentage-to-albumin ratio (NPAR), which is defined as the percentage of neutrophils divided by the concentration of albumin, is a cost-effective and readily available biomarker of inflammation. This study aimed to evaluate the association between the NPAR and the severity of coronary atherosclerosis in patients with chronic kidney disease (CKD). METHODS: A total of 280 CKD patients who underwent coronary angiography were retrospectively enrolled in this study. The severity of coronary atherosclerosis was evaluated using the Gensini score (GS). Patients were divided into low-, medium- and high-NPAR groups according to the tertiles of the NPAR values. Logistic regression analysis was conducted to analyze the relationship between the NPAR and the GS. The cutoff points for the sensitivity and specificity of the NPAR in predicting the GS were estimated via receiver operating characteristic (ROC) analysis. RESULTS: There was a higher prevalence of coronary artery disease (CAD) among CKD patients with higher NPARs (P =0.041). More patients in the high-NPAR group had complex CAD (triple-vessel disease and/or left main coronary artery stenosis) and chronic total occlusion lesions, and more of these patients required revascularization therapy (P<0.05). Multivariate logistic regression analysis revealed a significant positive correlation between the NPAR and the severity of coronary stenosis (adjusted OR 2.68, 95% CI 1.25-5.76, p=0.012), particularly among female and older (age ≥65) patients. The ROC analysis indicated that the optimal cutoff value for the NPAR in predicting severe coronary artery stenosis (GS>60) in CKD patients was 1.91 (sensitivity 0.495, specificity 0.749), with an area under the curve (AUC) of 0.650 (95% CI 0.581-0.719, P<0.001). A subgroup analysis according to sex revealed that the NPAR exhibited stronger predictive value in female patients (AUC 0.730, 95% CI 0.643-0.817) than in male patients (AUC 0.565, 95% CI 0.460-0.670) (P<0.001), and the optimal cutoff value for the NPAR in female patients was 1.80 (sensitivity 0.667, specificity 0.705). CONCLUSIONS: Our study demonstrated that the NPAR is independently associated with the severity of coronary atherosclerosis in CKD patients, especially in female and elderly patients (≥65 years old). Moreover, the NPAR can effectively predict the severity of coronary atherosclerosis, exhibiting greater predictive value in females than in males.

The Relationship and Clinical Significance of Hepc-20, LpPLA2, PTX3, and Acute Myocardial Infarction in Patients with Varying Degrees of Coronary Artery Disease.

Objective: This study aimed to investigate the association between hepcidin-20 (Hepc-20), lipoprotein-associated phospholipase A2 (LpPLA2), pentraxin 3 (PTX3), acute myocardial infarction (AMI) occurrence, the severity of coronary artery lesions, and their predictive effectiveness. Methods: A total of 100 patients diagnosed and treated for AMI at our hospital between January 2021 and January 2022 were included in the AMI group. Based on the severity of coronary artery lesions determined by the Gensini score, patients were divided into the mild group and the moderate-to-severe group. Additionally, 100 healthy individuals were selected as control samples and included in the normal group. Serum levels of Hepc-20, LpPLA2, and PTX3 were compared, and receiver operating characteristic curves (ROC curves) were constructed to analyze the predictive efficacy of these biomarkers for AMI occurrence and the degree of coronary artery disease. Results: Compared to the normal group, the AMI group exhibited significantly increased serum levels of Hepc-20, LpPLA2, and PTX3 (P < .05). The sensitivity and specificity of serum Hepc-20, LpPLA2, and PTX3 in predicting AMI occurrence and the severity of coronary artery lesions were >60.00%, and the Area Under Curve (AUC) was >0.70. Moreover, compared to the mild group, the moderate-to-severe group showed significantly higher serum levels of Hepc-20, LpPLA2, and PTX3 (P < .05). Hepc-20, LpPLA2, and PTX3 demonstrated positive correlations with the severity of coronary artery lesions (P < .05). Conclusions: The levels of Hepc-20, LpPLA2, and PTX3 are elevated abnormally in AMI patients and positively associated with the degree of coronary artery disease. Hepc-20, LpPLA2, and PTX3 have the potential to serve as sensitive and accurate predictors of AMI occurrence and the severity of coronary artery disease, thereby warranting their clinical application.

m6A modification-mediated lncRNA TP53TG1 inhibits gastric cancer progression by regulating CIP2A stability.

Long noncoding RNAs (lncRNAs) are associated with various types of cancer. However, the precise roles of many lncRNAs in tumor progression remain unclear. In this study, we found that the expression of the lncRNA TP53TG1 was downregulated in gastric cancer (GC) and it functioned as a tumor suppressor. In addition, low TP53TG1 expression was significantly associated with poor survival in patients with GC. TP53TG1 inhibited the proliferation, metastasis, and cell cycle progression of GC cells, while it promoted their apoptosis. m6A modification sites are highly abundant on TP53TG1, and demethylase ALKBH5 reduces TP53TG1 stability and downregulates its expression. TP53TG1 interacts with cancerous inhibitor of protein phosphatase 2A (CIP2A) and triggers its ubiquitination-mediated degradation, resulting in the inhibition of the PI3K/AKT pathway. These results suggest that TP53TG1 plays an important role in inhibiting the progression of GC and provides a crucial target for GC treatment.

Metabolic syndrome and its component traits present gender-specific association with liver cancer risk: a prospective cohort study.

BACKGROUND & AIMS: Little is known on the gender-specific effect and potential role of non-linear associations between metabolic syndrome (MetS) components and liver cancer risk. We evaluated these associations based on the UK Biobank cohort. METHODS: We included 474,929 individuals without previous cancer based on the UK Biobank cohort. Gender-specific hazard ratios (HRs) and 95% confidence interval (CIs) were calculated by Cox proportional hazards regression, adjusting for potential confounders. Non-linear associations for individual MetS components were assessed by the restricted cubic spline method. RESULTS: Over a median follow-up of 6.6 years, we observed 276 cases of liver cancer (175 men, 101 women). MetS [HR 1.48, 95% CI 1.27-1.72] and central obesity [HR 1.65, 95% CI 1.18-2.31] were associated with higher risk of liver cancer in men but not in women. Participants with hyperglycaemia has higher risk of liver cancer. High waist circumference and blood glucose were dose-dependently associated with increased liver cancer risk in both genders. For high density lipoprotein (HDL) cholesterol (both genders) and blood pressure (women), U-shaped associations were observed. Low HDL cholesterol (< 1.35 mmol/L) in men and high HDL cholesterol in women (> 1.52 mmol/L) were associated with increased liver cancer risk. CONCLUSIONS: MetS components showed gender-specific linear or U- shaped associations with the risk of liver cancer. Our study might provide evidence for individualized management of MetS for preventing liver cancer.

CT-based radiomics scores predict response to neoadjuvant chemotherapy and survival in patients with gastric cancer.

BACKGROUND: Neoadjuvant chemotherapy is a promising treatment option for potential resectable gastric cancer, but patients' responses vary. We aimed to develop and validate a radiomics score (rad_score) to predict treatment response to neoadjuvant chemotherapy and to investigate its efficacy in survival stratification. METHODS: A total of 106 patients with neoadjuvant chemotherapy before gastrectomy were included (training cohort: n = 74; validation cohort: n = 32). Radiomics features were extracted from the pre-treatment portal venous-phase CT. After feature reduction, a rad_score was established by Randomised Tree algorithm. A rad_clinical_score was constructed by integrating the rad_score with clinical variables, so was a clinical score by clinical variables only. The three scores were validated regarding their discrimination and clinical usefulness. The patients were stratified into two groups according to the score thresholds (updated with post-operative clinical variables), and their survivals were compared. RESULTS: In the validation cohort, the rad_score demonstrated a good predicting performance in treatment response to the neoadjuvant chemotherapy (AUC [95% CI] =0.82 [0.67, 0.98]), which was better than the clinical score (based on pre-operative clinical variables) without significant difference (0.62 [0.42, 0.83], P = 0.09). The rad_clinical_score could not further improve the performance of the rad_score (0.70 [0.51, 0.88], P = 0.16). Based on the thresholds of these scores, the high-score groups all achieved better survivals than the low-score groups in the whole cohort (all P < 0.001). CONCLUSION: The rad_score that we developed was effective in predicting treatment response to neoadjuvant chemotherapy and in stratifying patients with gastric cancer into different survival groups. Our proposed strategy is useful for individualised treatment planning.

Inhibition of SLC1A5 sensitizes colorectal cancer to cetuximab.

Cetuximab resistance is a key barrier in treating metastatic colorectal cancer (mCRC). Targeting of metabolic resources import could resensitize drug-resistant cancer cells to anticancer treatments. Here we showed that the expression of the glutamine transporter solute carrier 1 family member 5 (SLC1A5) in clinical CRC samples of patients resisted to cetuximab was significantly higher than in those of patients responded to cetuximab. Inhibition of SLC1A5 by shRNA-mediated gene silencing or pharmacological inhibitor significantly suppressed the growth of CRC. Moreover, inhibition of SLC1A5 significantly enhanced the inhibitory efficacy of cetuximab on CRC proliferation both in vitro and in vivo. Mechanistically, SLC1A5 inhibition facilitated EGFR degradation through the ubiquitin-proteasome pathway, and decreased the expression of nuclear EGFR, both of which might have contribution to the improved response to cetuximab. This study provides the metabolic molecule SLC1A5 as a potential therapeutic target to increase the efficacy of cetuximab on CRC.

Long Non-Coding RNA RP11-789C1.1 Suppresses Epithelial to Mesenchymal Transition in Gastric Cancer Through the RP11-789C1.1/MiR-5003/E-Cadherin Axis.

BACKGROUND/AIMS: Gastric cancer (GC) is a common malignancy with a global incidence that ranks fourth among all tumor types. Epithelial-to-mesenchymal transition (EMT) is a tumor biological process with a role in GC cell metastasis. Long non-coding RNAs (lncRNAs) and microRNAs possess important regulatory functions at the cellular level and in diverse pathophysiological processes. This study was conducted to investigate whether lncRNA RP11-789C1.1 regulates EMT in GC by mediating the miR-5003/E-cadherin pathway. METHODS: RP11-789C1.1 and miR-5003 expression was detected in GC specimens and cell lines by quantitative real-time PCR. Western blotting and immunohistochemistry were performed to detect EMT markers in GC. Cell Counting Kit 8 assays were carried out to explore cell proliferation. Wound healing and Transwell assays were conducted to determine the migration and invasion of GC cells. To clarify the correlation between RP11-789C1.1, miR-5003, and E-cadherin, dual-luciferase reporter assays were applied. RESULTS: LncRNA RP11-789C1.1 was significantly down-regulated in GC patients and cell lines, along with the concomitant up-regulation of miR-5003. Silencing RP11-789C1.1 and over-expressing miR-5003 significantly promoted the tumor behavior of GC cells. Dual-luciferase reporter assays confirmed that miR-5003 was the target of both RP11-789C1.1 and E-cadherin. Furthermore, at both the mRNA and protein level, silencing RP11-789C1.1 remarkably reduced the expression of E-cadherin and promoted EMT, which were reversed by knocking down miR-5003. CONCLUSIONS: LncRNA RP11-789C1.1 inhibited EMT in GC through the RP11-789C1.1/miR-5003/E-cadherin axis, which could be a promising therapeutic target for GC.

The efficiency of electronic list-based multidisciplinary team meetings in management of gastrointestinal malignancy: a single-center experience in Southern China.

BACKGROUND: The multidisciplinary team (MDT) discussion has earned increasing popularity for the delivery of cancer care. However, MDT meeting (MDTM) is time and resource intensive, and some efforts to optimize discussion processes are required. This study aims to investigate the efficiency of electronic list-based MDTM in treatment of gastrointestinal (GI) malignancy. METHODS: Between January 2015 and December 2016, patients with GI cancers were retrospectively reviewed. Patients permitting an MDTM with our novel technique (eMDT group) were compared with those undergoing a traditional discussion (cMDT group). The efficiency of MDT working, including time cost per meeting or case and overall number of reviewed cases, was checked, with accuracy of clinical staging and other outcomes explored meanwhile. RESULTS: Three thousand six hundred seventy-four patients were included, with 2156 (58.7%) and 1518 (41.3%) cases for eMDT and cMDT groups, respectively. Comparisons in age (P = 0.529), gender (P = 0.844), cancer type (P = 0.218), treatment plan (P = 0.737), and pathological stage (P = 0.098) were not significant between groups. However, the average time cost in both each meeting (149.4 vs. 205.1 min; P < 0.001) and each case (3.1 vs. 6.2 min; P < 0.001) was markedly reduced. Besides, this novel technique was associated with improved accuracy of clinical staging (P = 0.070) and reduced hospital stay (P < 0.001) compared with the traditional approach, with similar incidence of complications observed (P = 0.243). CONCLUSIONS: The MDT working based on an intelligent checklist could save considerable time while not affecting treatment of GI malignancies. The improved efficiency also earns an increased capacity of hospital admission and in-patient care.

Hispidulin mediates apoptosis in human renal cell carcinoma by inducing ceramide accumulation.

Hispidulin, a polyphenolic flavonoid extracted from the traditional Chinese medicinal plant S involucrata, exhibits anti-tumor effects in a wide array of human cancer cells, mainly through growth inhibition, apoptosis induction and cell cycle arrest. However, its precise anticancer mechanisms remain unclear. In this study, we investigated the molecular mechanisms that contribute to hispidulin-induced apoptosis of human clear-cell renal cell carcinoma (ccRCC) lines Caki-2 and ACHN. Hispidulin (10, 20 µmol/L) decreased the viability of ccRCC cells in dose- and time-dependent manners without affecting that of normal tubular epithelial cells. Moreover, hispidulin treatment dose-dependently increased the levels of cleaved caspase-8 and caspase-9, but the inhibitors of caspase-8 and caspase-9 only partly abrogated hispidulin-induced apoptosis, suggesting that hispidulin triggered apoptosis via both extrinsic and intrinsic pathways. Moreover, hispidulin treatment significantly inhibited the activity of sphingosine kinase 1 (SphK1) and consequently promoted ceramide accumulation, thus leading to apoptosis of the cancer cells, whereas pretreatment with K6PC-5, an activator of SphK1, or overexpression of SphK1 significantly attenuated the anti-proliferative and pro-apoptotic effects of hispidulin. In addition, hispidulin treatment dose-dependently activated ROS/JNK signaling and led to cell apoptosis. We further demonstrated in Caki-2 xenograft nude mice that injection of hispidulin (20, 40 mg·kg-1·d-1, ip) dose-dependently suppressed tumor growth accompanied by decreased SphK1 activity and increased ceramide accumulation in tumor tissues. Our findings reveal a new explanation for the anti-tumor mechanisms of hispidulin, and suggest that SphK1 and ceramide may serve as potential therapeutic targets for the treatment of ccRCC.

Hispidulin inhibits proliferation and enhances chemosensitivity of gallbladder cancer cells by targeting HIF-1α.

Gallbladder cancer (GBC) is an aggressive malignancy of the bile duct, which is associated with a low (5-year) survival and poor prognosis. The transcription factor HIF-1α is implicated in the angiogenesis, cell survival, epithelial mesenchymal transition (EMT) and invasiveness of GBC. In this study, we have investigated the role of HIF-1α in the pathobilogy of GBC and effect of hispidulin on the molecular events controlled by this transcription factor. We observed that hispidulin caused induction of apoptosis, blockade of growth and cell cycle progression in GBC cells. Our results have demonstrated for the first time that hispidulin-exerted anti-tumor effect involved the suppression of HIF-1α signaling. Hispidulin was found to repress the expression of HIF-1α protein dose-dependently without affecting the HIF-1α mRNA expression. In addition, the inhibition of HIF-1α protein synthesis was revealed to be mediated through the activation of AMPK signaling. Hispidulin also sensitized the tumor cells to Gemcitabine and 5-Fluoroucil by down-regulating HIF-1α/P-gp signaling. Given the low cost and exceedingly safe profile, hispidulin appears to be a promising and novel chemosensitizer for GBC treatment.

The relationship between neutrophil counts on admission and angiographic no-reflow after primary percutaneous coronary intervention in patients with ST-segment elevation myocardial infarction.

BACKGROUND: The no-reflow phenomenon during primary percutaneous coronary intervention in patients with ST-segment elevation myocardial infarction (STEMI) can lead to poor outcomes. Increased neutrophil counts have been associated with an increased risk of adverse clinical events after acute myocardial infarction (AMI). The aim of this study was to assess the relation between admission neutrophil counts and angiographic no-reflow after PPCI. METHODS: A total of 217 patients with acute STEMI who underwent PPCI, were enrolled. The patients were divided into two groups: no-reflow and normal-reflow. The neutrophil counts and other laboratory parameters were measured on admission before PPCI. RESULTS: There were 41 patients (18.9%) in the no-reflow group and 176 patients in the normal-reflow group. Patients with no-reflow were older (68.0 ± 11.7 years vs 60.7 ± 13.2 years, P = 0.019) and had significantly higher admission neutrophil counts (9.02 ± 3.97 × 109/L vs 7.57 ± 2.82 × 109/L, P = 0.007). Also, high-sensitivity C-reactive protein (hsCRP), white blood counts, monocyte counts were significantly higher while haemoglobin values were significantly lower in the no-reflow group. In multivariate analysis, neutrophil counts remained a strong independent predictor of angiographic no-reflow (odds ratio 1,200, 95% confidence interval 1.073-1.342, P = 0.001) together with age (odds ratio 1.041, 95% confidence interval 1.012-1.071, P = 0.005). CONCLUSIONS: Neutrophil counts on admission and age were independent clinical predictors of no-reflow following primary PCI in patients with STEMI. Our findings suggest that admission neutrophil counts may be available for early risk stratification of no-reflow after primary PCI and might allow the improvement of strategies to prevent this phenomenon.

Endoscopic resection versus surgery for early gastric cancer: a systematic review and meta-analysis.

OBJECTIVES: Endoscopic resection (ER) is becoming an increasingly used treatment option for early gastric cancer (EGC); however, data comparing the long-term outcomes of ER and surgery are limited. Accordingly, we here aimed to perform a meta-analysis to clarify the long-term outcomes and safety of ER and surgery for EGC. METHODS: Literature on the direct comparison of ER and surgery for EGC was retrieved from the Medline, PubMed and Scopus databases. We selected the eligible studies, extracted data, and assessed the quality scores according to the guidelines. The overall survival (OS), recurrence-free survival (RFS), and adverse event rates were investigated, and the pooled hazard ratio (HR), odds ratio (OR), and 95% confidence interval (CI) were estimated. RESULTS: Nine retrospective studies were identified, including 973 and 1190 participants undergoing ER and surgery, respectively. There were no significant differences regarding the OS (HR: 0.995, 95% CI: 0.836-1.185; P = 0.959) and adverse event rates (OR: 0.50, 95% CI: 0.20-1.28, P = 0.148) between ER and gastrectomy. However, patients undergoing ER had significantly shorter RFS (HR: 7.226, 95% CI: 1.718-30.400, P = 0.007) than those undergoing gastrectomy. CONCLUSIONS: Despite the limitations of this review, including the retrospective nature of all included studies, our results suggest that ER might be a feasible and safe treatment strategy compared to that of gastrectomy for EGC; however, careful endoscopic surveillance is needed for ensuring favorable outcomes. These findings should be confirmed in further large-scale, prospective, randomized, controlled trials from different countries.

SOX2 Promotes the Epithelial to Mesenchymal Transition of Esophageal Squamous Cells by Modulating Slug Expression through the Activation of STAT3/HIF-α Signaling.

UNLABELLED: The transcription factor sex determining region (Y SRY)-box 2 (SOX2) is known to play a crucial role in the maintenance of self renewal or pluripotency of undifferentiated embryonic and neuronal stem cells. An elevated expression of SOX2 has been correlated with poor prognosis of esophageal squamous cell carcinoma (ESCC). We sought to investigate the mechanism(s) by which SOX2 modulates the ESCC metastasis. The SOX2 coding DNA sequence was inserted into pCMV vector and stably transfected in ESCC cells (Eca-109). The effect of SOX2 over expression was evaluated on cell migration, invasion and epithelial to mesenchymal transition (EMT). We also measured the expression of Slug to explore if this transcription factor is involved in SOX2-mediated regulation of cell migration/invasion and EMT. In addition, we determined the role of STAT3/HIF-1α to further probe the mechanism of SOX2-mediated metastasis via Slug. Our results demonstrated that SOX2 over expressing Eca-109 cells showed an enhanced cell migration/invasion. Moreover, these cells exhibited the EMT characteristics, that is, a significantly suppressed expression of the epithelial cells marker with a concomitant enhancement of those of the mesenchymal markers. An increased expression of Slug in SOX2 over expressing cells suggested the involvement of this transcription factor in SOX2-regulated metastasis. Whereas the expressions of STAT3/HIF-1α were found to be up-regulated in SOX2 expressing cells, blockade of these transcription factors resulted in the inhibition of Slug expression at both protein and mRNA levels. CONCLUSION: These results suggest that SOX2 promoted the metastasis of ESCC, at least in part, by modulating Slug expression through the activation of STAT3/HIF-1α signaling.

Unusual calcifying fibrous tumor in the fallopian tube: review and discussion of the differential diagnosis.

Calcifying fibrous tumor (CFT) is a rare benign soft tissue tumor of unknown etiology and extremely rare in female reproductive system. We present a case of unusual CFT in the ampulla of fallopian tube occurring in a middle-aged female patient with multiple uterine leiomyomas. A hysterectomy was performed on a 48-year-old woman for uterine leiomyomas. At surgery, a solitary, well-defined nodule, measuring 1.0 cm in diameter, was incidentally observed on the wall of ampulla of right fallopian tube. The lesion of fallopian tube was resected totally. Histologically, this lesion was unencapsulated and composed of hyalinized collagenous fibrous tissue with psammomatous calcification and focal lymphoplasmacytic infiltrate. Sparsely fibroblast-like spindle cells were scattered in the dense hyalinized background with bland nuclei. By immunohistochemistry, vimentin was diffusely positive in most cells, and a focal reactivity for CD34 was also observed in spindle cells. However, they were negative for cytokeratin (AE1/AE3), S-100 protein, CD117, DOG1, SMA, desmin, and ALK. The Ki-67 labeling index of the lesion was <1%. A diagnosis of primary CFT of fallopian tube was made. To our knowledge, this is the first report of CFT occurring in female reproductive tract. Awareness of CFT and its distinctive features is important to avoid a diagnostic pitfall caused by histologic similarities to other spindle cell or calcifying lesions in unusual locations. Although marginal excision is usually adequate for most of CFT, long-term follow-up is suggested as delayed recurrence might occur infrequently.

[Analysis of clinicopathological features of 1879 cases of gastric cancer in Southern China: a single center experience].

OBJECTIVE: To investigate the clinicopathological features of gastric cancer in Southern China, and provide a base of research and therapy for gastric cancer. METHODS: A total of 1 879 cases of gastric cancer with radical gastrectomy from Southern China were collected from August 1994 to July 2012. Analyze and summarize the characters of gender, age, tumor location, WHO histopathologic type and grade, pTNM stage and family history, retrospectively. RESULTS: Among all cases, male to female ratio was 2.08: 1, while female was more than male before 40 years (χ(2) = 77.831, P = 0.000). Cases aged over 60 years had a highest incidence of gastric cancer (46.0%), with predilection of sinus (45.7%), body (26.3%) and cardia (20.1%). The common WHO histopathologic types were tubular or papillary adenocarcinoma (81.5%) and signet ring cell carcinoma (11.0%). Most patients were at III or IV stage on pTNM staging (40.5% and 26.5%). CONCLUSIONS: Gastric cancer in Southern China has a predilection on male, while female is more than male before 40 years. Gastric sinus and adenocarcinoma is most common. Most patients are diagnosed at advanced stages.

Impact of serum iron levels on in-hospital mortality and clinical outcomes in patients with ST segment elevation myocardial infarction undergoing emergency percutaneous coronary intervention: a retrospective analysis.

BACKGROUND: Despite advances in percutaneous coronary intervention (PCI) for ST segment elevation myocardial infarction (STEMI), in-hospital mortality remains a concern, highlighting the need for the identification of additional risk factors such as serum iron levels. OBJECTIVE: This study aims to assess the relationship between serum iron levels and in-hospital mortality among patients with STEMI undergoing emergency PCI. METHODS: A total of 685 patients diagnosed with STEMI, treated with emergency PCI between January 2020 and June 2023, were included in this retrospective observational study. Participants were categorized based on serum iron levels into a low serum iron group (Fe <7.8 µmol/L) and a control group (Fe ≥7.8 µmol/L). Clinical and biochemical variables were compared between the groups. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors for in-hospital mortality. RESULTS: The low serum iron group demonstrated significantly higher in-hospital mortality rates (9.3 vs. 1.0%, P  < 0.05) compared with the control group. Multivariate logistic regression revealed that a left ventricular ejection fraction less than 40% upon admission [odds ratio (OR), 8.01; 95% confidence interval (CI), 1.230-52.173; P  = 0.029], the occurrence of no-reflow during PCI (OR, 7.13; 95% CI, 1.311-38.784; P  = 0.023), and serum iron levels below 7.8 µmol/L (OR, 11.32; 95% CI, 2.345-54.640; P  = 0.003) were independent risk factors for in-hospital mortality. CONCLUSION: Low serum iron levels are associated with increased in-hospital mortality in patients with STEMI undergoing emergency PCI. Serum iron levels may serve as an independent prognostic marker and could inform risk stratification and therapeutic targeting in this patient population.