Yaning Wei’s research while affiliated with First Affiliated Hospital of China Medical University and other places

Background Mucinous adenocarcinoma is a rare type of colorectal cancer (CRC) associated with poor prognosis, particularly when it includes signet ring cell components. Furthermore, its rate of microsatellite instability-high (MSI-H) is significantly higher compared to non-mucinous adenocarcinoma. Immunotherapy has emerged as the standard treatment for MSI-H metastatic CRC (mCRC). In the KEYNOTE-177 trial, for individuals with advanced CRC exhibiting MSI-H or mismatch repair deficiency (dMMR), treatment with pembrolizumab as a single agent demonstrated a superior outcome compared to standard systemic chemotherapy. The study revealed a notably higher objective response rate (43.8% versus 33.1%) and an extended progression-free survival duration (16.5 versus 8.2 months). These findings imply that pembrolizumab may be regarded as a front-line treatment option for patients with advanced CRC who have MSI-H/dMMR status. Case Description The patient with double primary CRC, both of which were identified as MSI-H through next generation sequencing (NGS). Following a regimen of immunotherapy-based combination therapy, the rectal lesion achieved a complete clinical response (cCR), while the colon lesion displayed continued progression, indicating primary resistance to treatment. Conclusions Specific histological subtypes of CRC, such as mucinous adenocarcinoma, might adversely affect the efficacy of immunotherapy, resulting in primary treatment resistance. Consequently, in the case of this particular cancer subtype, local surgical resection may be a more appropriate treatment strategy.

Primary colorectal squamous cell carcinoma (CSCC) is a rare pathological subtype. Currently, clinical data with regards to its prognosis and treatment is limited, and there is no optimal treatment method. The case presented involves a proficient mismatch repair (pMMR) and microsatellite-stable (MSS) Colorectal cancer (CRC) patient with squamous cell carcinoma (SCC) located transversely in the colon. Based on the imaging assessment, the tumor infiltration depth is classified as T4. After receiving 4 cycles of neoadjuvant treatment with oxaliplatin and capecitabine (XELOX), the patients were evaluated for partial response (PR) in 2 cycles and stable disease (SD) in 4 cycles. The patient underwent a right hemicolectomy and received postoperative paclitaxel/cisplatin (TC) adjuvant chemotherapy. After 23 months, a systemic examination revealed abdominal metastasis. A needle biopsy was conducted on the detected abdominal metastases, with the resulting pathology indicating the presence of metastatic SCC. The individual exhibited expression of programmed cell death ligand 1 (PD-L1) and a mutation in the TP53 gene. Considering the patient’s disease recurrence based on medical history, a treatment plan was formulated. This involved Sintilimab plus Cetuximab and the combination of leucovorin, fluorouracil, and irinotecan (FOLFIRI) regimen. The patient received four cycles of treatment with an efficacy evaluation of SD- and seven cycles of treatment with an efficacy evaluation of SD+, which resulted in a progression-free survival (PFS) duration of 7 months. This case study presents the conventional XELOX chemotherapy protocol, which has shown limited effectiveness, and highlights the favorable results achieved by implementing the TC adjuvant chemotherapy regimen in individuals diagnosed with primary colonic SCC. Furthermore, combining immune checkpoint blockade (ICB) with other therapies for patients with advanced disease is anticipated to provide an extended duration of survival.

Introduction: Evidence has shown that some microRNAs (miRNAs) play a role in tumorigenesis of hepatocellular carcinoma (HCC). Herein, we aimed to evaluate the diagnostic and prognostic values of serum exosomal miR-370-3p and miR-196a-5p in patients with HCC. Material and methods: Serum exosomes in 90 HCC patients were extracted and identified. Serum exosomal miR-370-3p and miR-196a-5p expression in HCC patients were detected. The diagnostic value of miR-370-3p and miR-196a-5p, relationship between miR-370-3p and miR-196a-5p expression and clinicopathological features and prognosis of patients with HCC were analyzed. Relationship between miR-370-3p and miR-196a-5p expression and liver function indices such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL) in HCC patients were analyzed. The effects of miR-370-3p and miR-196a-5p on Huh7 HCC cells' proliferation, invasion and migration were determined. Results: Lower expression of miR-370-3p and higher expression of miR-196a-5p were found in serum exosomes of HCC patients. Serum exosomal miR-370-3p and miR-196a-5p were associated with tumor size, tumor grade and TNM stage as well as prognosis and liver function indices of HCC patients. Overexpressed miR-370-3p or silenced miR-196a-5p suppressed proliferation, invasion and migration of Huh7 HCC cells. Conclusions: We suggest that miR-370-3p/miR-196a-5p in serum exosomes of HCC patients could be potential biomarkers for the diagnosis and prognosis of HCC.

Breast cancer treatment with poly(ADP‑ribose)polymerase (PARP) inhibitors is currently limited to cells defective in the homologous recombination repair (HRR) pathway. The chemical inhibition of many HRR deficiency genes may sensitize cancer cells to PARP inhibitors. In the present study, Rad51, a central player in the HRR pathway, was selected to explore additional low variation and highly representative markers for PARP inhibitor activity. A CRISPR/Cas9‑based saturated mutation approach for the Rad51 WALKER domain was used to evaluate the sensitivity of the PARP inhibitor olaparib. Five amino acid mutation sites were identified in olaparib‑resistant cells. Two Rad51 haplotypes were assembled from the mutations, and may represent useful pharmacogenomic markers of PARP inhibitor sensitivity.

Medicine and food homology (MFH) materials are rich in polysaccharides, proteins, fats, vitamins, and other components. Hence, they have good medical and nutritional values. Polysaccharides are identified as one of the pivotal bioactive constituents of MFH materials. Accumulating evidence has revealed that MFH polysaccharides (MFHPs) have a variety of biological activities, such as antioxidant, immunomodulatory, anti-tumor, hepatoprotective, anti-aging, anti-inflammatory, and radioprotective activities. Consequently, the research progress and future prospects of MFHPs must be systematically reviewed to promote their better understanding. This paper reviewed the extraction and purification methods, structure, biological activities, and potential molecular mechanisms of MFHPs. This review may provide some valuable insights for further research regarding MFHPs.

Ultrasound assisted aqueous two-phase extraction of polysaccharides from Lilium lancifolium Thunb was modeled by response surface methodology (RSM) and artificial neural network (ANN), and optimized using genetic algorithm coupled with ANN (GA-ANN). Statistical analysis showed that the models obtained by RSM and ANN could accurately predict the Lilium lancifolium Thunb polysaccharides (LLPs) yield. However, ANN prediction was more accurate than RSM. The optimum extraction parameters to achieve the highest LLPs yield (15.17 ± 0.21)% was obtained at the ultrasound power of 250 W, extraction temperature of 63 °C, liquid-to-solid ratio of 21 mL/g, and extraction time of 32 min. Subsequently, the crude LLPs were further purified via DEAE-52 and Sephadex G-100 chromatography to obtain a homogenous fraction (LLPs-2-SG, 421.41 kDa) that contained mannose, glucose, and galactose in a molar ratio of 10.52:23.06:7.19. The structure of LLPs-2-SG was characterized with UV–vis, FT–IR, AFM, and SEM. The findings provide a critical method for the extraction, separation and purification of polysaccharides from natural resources.

MicroRNA-365 (miR-365) has been revealed to be a vital regulator in tumorigenesis of multiple cancers, while there is a large gap in the knowledge about miR-365 expression and gastric cancer (GC). This research focused on the effects of miR-365 and paired box 6 (PAX6) on GC development. Levels of miR-365 and PAX6 in GC tissues and cell lines were determined, followed by the screening of the AGS and NCI-N87 cells. Gain- or loss-of-function assays were used to analyze the effect of miR-365, PAX6 on AGS and NCI-N87 cell behaviors. The effects of altered miR-365 and PAX6 on animal models were observed. Moreover, to assess the interaction between miR-365 and PAX6, we implemented the bioinformatic method and dual luciferase reporter gene assay. MiR-365 was decreased while PAX6 was increased in GC tissues and cell lines. There existed a negative association between miR-365 and PAX6. The promoted miR-365 could repress oncogenicity in vivo and malignant transformation in vitro of GC. PAX6 was the target gene of miR-365. Overexpression of PAX6 reversed the inhibitory effect of up-regulated miR-365 on malignant behavior of gastric cancer cells. Our research displays that the amplification of miR-365 could suppress the malignant behaviors of GC cells via inhibiting PAX6, which may be helpful for GC treatment.

Purpose: To investigate the effect of apatinib combined with chemotherapy on quality of life (QOL) and related complications in patients with advanced gastric cancer (AGC). Methods: Clinical data for 102 AGC patients treated in The Affiliated Hospital of Hebei University (January 2018 - December 2019) were retrospectively analyzed. The subjects were randomly and equally split into chemotherapy group and combination group. Both groups of patients were treated with 180 mg/m2 of paclitacel, and patients in the combination group were additionally given 500 mg of apatinib daily, for a treatment time to disease remission in both groups. Clinical efficacy, QOL, complications as well as serum SIL-2R, VEGF and TNF-α levels in the two groups were compared to analyze the effect of apatinib combined with chemotherapy on AGC patients. Results: Disease control rate (DCR) and overall response rate (ORR) of gastric cancer patients in the combination group were notably higher than those in the chemotherapy group (p < 0.05). After treatment, the serum SIL-2R, VEGF and TNF-α levels in the two groups decreased significantly, of which the levels in the combination group were clearly lower (p < 0.05). No notable difference in the incidence of complications was observed between the two groups (p > 0.05). After treatment, the QOL scores of both groups increased significantly, of which QOL score in the combination group was notably higher (p < 0.05). Conclusion: Apatinib combined with chemotherapy effectively enhances the clinical efficacy of AGC patients, controls the overexpression of serum SIL-2R, VEGF and TNF-α, and improves the QOL of patients without increasing adverse reactions. Therefore, the combination therapy is safe and effective.

Background Immune cell infiltration plays a critical role in regulating peptic ulcer disease (PUD) and gastrointestinal cancer (GC). However, regulators of the cell signaling hubs remain unclear. Aim This study characterizes genes that are differentially expressed in PUD and GC tissue samples. Bioinformatics is used to define the immune-associated hub genes associated with the malignant transfer process of PUD to GC. Methods Total expression data from PUD and early-stage GC tissue samples were obtained from GEO and TCGA. Differentially expressed genes were assessed and immunological enrichment analysis was performed. Protein–protein interaction (PPI) and Cytoscape analysis were used together to identify the hub genes. CIBERSORT and COX analysis were used to analyze the differentially infiltrated immune cell landscapes and determine HR scores of the hub genes. Results Expression data identified 437 DEGs as common to both GC and PUD tissue. Of these, 49 immune-related DEGs were grouped by function, and seven hub genes were identified by PPI analysis. The NRP2 and SEMA3D genes were then selected for survival analysis. SEMA3D had a higher hazard ratio than NRP2 and was defined as the hub for PUD carcinogenesis. Conclusion SEMA3D was characterized as the hub gene for PUD carcinogenesis.

Objective: We investigated whether miR-183 played a role in regulating mTOR expression and influencing autophagy of GC cells. Methods: Tumor tissues and paracancerous tissues were collected from GC patients to detect the expressions of miR-183, mTOR, autophagy-related proteins Beclin-1. SGC-7901 cells were cultured in vitro and divided into 5 groups: MiR-NC group, MiR-183 mimic group, si-NC group, small interfering RNA transfected (si)-mTOR group, miR-183 mimic + si-mTOR group, to compare the expression of mTOR, apoptosis rate and clonality in all groups, and detect the expressions of Beclin-1 under starvation condition. Results: The expressions of miR-183, Beclin-1 in GC tissues were significantly decreased, and the expression of mTOR was significantly increased compared with those in paracancerous tissues. There was a targeted-regulating relationship between miR-183 and mTOR. Compared with GES-1 cells, miR-183 expression was decreased and mTOR expression was increased in SGC-7901 cells, and under starvation condition, the expressions of Beclin-1 were decreased. After transfected with miR-183 mimic and/or si-mTOR, the expression of mTOR in SGC-7901 cells was decreased significantly, the cell clonality was significantly reduced, apoptosis was increased significantly, and cell autophagy activity induced by starvation was significantly enhanced. Conclusion: miR-183 can influence the proliferation, apoptosis and autophagy of GC cells through targeted inhibition of mTOR expression.