Objective To analyze the clinical efficacy of microwave ablation in the colorectal cancer with simultaneously multiple liver metastases that was initially evaluated as potentially resectable.Methods The patients with potentially resectable colorectal cancer with simultaneous multiple liver metastases treated in the De-partment of General Surgery of the First Affiliated Hospital of Hebei North University,the Center of Minimally Invasive Therapy in Oncology of Traditional Chinese and Western Medicine in Dongzhimen Hospital of Beijing U-niversity of Chinese Medicine,and the Second Department of General Surgery in the Fourth Hospital of Hebei Medical University from October 1,2018 to October 1,2020 were selected in this study.The general data,pathological features,treatment methods,and clinical efficacy of the patients were collected.According to the treatment methods,the patients were assigned into a surgical resection group(conversion therapy + laparoscopic primary resection +hepatectomy)and a microwave ablation group(conversion therapy +laparoscopic primary re-section +microwave ablation).The surgical indicators(operation duration,time to first postoperative anal ex-haust,hospital stay,etc.)and postoperative complications(anastomotic stenosis,anastomotic hemorrhage,incision infection,etc.)were compared between the two groups.The survival period was followed up,including the overall survival period and disease-free survival period,and the survival curves were drawn to analyze the clinical efficacy of the two treatment regimens.Results A total of 198 patients with potentially resectable color-ectal cancer with simultaneous multiple liver metastases were included in this study.Sixty-six patients were cured by neoadjuvant chemotherapy(FOLFOX or FOLFIRI),including 30 patients in the surgical resection group and 36 patients in the microwave ablation group(with 57 tumors ablated).After the first ablation,54(94.74%)tumors achieved complete ablation,and all of them reached no evidence of disease status after re-ablation.The microwave ablation group had shorter operation duration,less intraoperative blood loss,shorter time to first post-operative anal exhaust,shorter time of taking a liquid diet,shorter hospital stay,and lower hospitalization cost than the surgical resection group(all P<0.001).In addition,the microwave ablation group had lower visual analogue scale score(P<0.001)than the surgical resection group.The incidences of complications such as inci-sion infection(P =0.740),anastomotic fistula(P =1.000),and anastomotic stenosis(P =1.000),the over-all survival period(P =0.191),and the disease-free survival period(P =0.934)showed no significant differ-ences between the two groups.Conclusions For patients with colorectal cancer with simultaneous multiple liver metastases initially assessed as potentially resectable,laparoscopic primary resection +surgical resection/microwave ablation after conversion therapy was safe,effective,and had similar survival outcomes.Microwave ablation outper-formed surgical resection in postoperative recovery,economy,and tolerability,being worthy of clinical promotion.

Objective To analyze the sensitivity of ARHGAP8 in predicting the efficacy of neoadjuvant chemotherapy in the patients with locally advanced mid-low colorectal cancer and provide accurate evidence for the treatment of advanced colorectal cancer.Methods The differentially expressed gene ARHGAP8 was screened out by bioinformatics analysis.Cancer tissue and rectal tissue of 68 patients with primary rectal cancer were select-ed.The rectal cancer tissue samples and the rectal tissue samples were collected for clinical validation of ARH-GAP8 expression by quantitative real-time PCR,Western blotting,and immunohistochemistry.The clinical and pathological features such as gender,age,tumor stage,differentiation degree,and pathological type of the pa-tients were collected for functional validation.Forty-four patients with locally advanced mid-low rectal cancer who received neoadjuvant chemotherapy were selected for immunohistochemical examination of ARHGAP8 expres-sion.The expression level of ARHGAP8 was compared between before and after chemotherapy and among different efficacy groups.Results The bioinformatics analysis revealed differences in the expression level of ARHGAP8 between the cancer tissue and rectal tissue(P＜0.001).The expression level of ARHGAP8 was correlated with tumor stage(P=0.024),lymph node metastasis(P=0.007),and age(P=0.005).Quantitative real-time PCR results showed that the mRNA level of ARHGAP8 in the cancer tissue was higher than that in the rectal tis-sue(P＜0.001).Western blotting and immunohistochemistry results demonstrated that the protein level of ARH-GAP8 in the cancer tissue was higher than that in the rectal tissue(P=0.011).The expression of ARHGAP8 was correlated with tumor size(P=0.010)and pathological stage(P=0.005),while it showed no significant association with tumor differentiation degree,lymph node metastasis,liver metastasis,Ki-67,or microsatellite instability expression level.The 44 patients receiving neoadjuvant chemotherapy included 13,8,8,and 15 pa-tients of tumor regression grades 0,1,2,and 3,respectively.Among them,65.91％(29/44)patients showed responses to the treatment.After neoadjuvant chemotherapy,the expression of ARHGAP8 in the cancer tissue was down-regulated in the patients who responded to the chemotherapy(P＜0.001).The response rate in the patients with low protein level of ARHGAP8 was 92.86％,which was higher than that(53.33％)in the patients with high pro-tein level of ARHGAP8(P=0.033).Conclusions ARHGAP8 is highly expressed in the rectal cancer tissue.The pa-tients with locally advanced mid-low rectal cancer and low ARHGAP8 expression are more sensitive to neoadjuvant chemotherapy with the XELOX protocol.ARHGAP8 can serve as a potential biomarker for the occurrence and develop-ment of rectal cancer and an important index for evaluating the efficacy of neoadjuvant chemotherapy with the XELOX protocol in the patients with locally advanced mid-low rectal cancer.

Objective To report the diagnosis and treatment process of a case of cryptogenic multifocal ulcerous stenosing enteritis(CMUSE)to enhance the understanding of gastrointestinal hemorrhage caused by multiple ulcers in small intestine and provide reference for clinical diagnosis and treatment.Methods A case of early CMUSE admitted to Tianjin Union Medical Center in September 2021 was analyzed based on clinical characteristics,laboratory examinations,imaging examinations,endoscopy examinations,pathological tissues,treatment methods and follow-up results,and the statistical analysis of related literature was conducted.CMUSE was compared with Crohn's disease(CD),non-steroidal anti-inflammatory drug(NSAID)associated enteritis and intestinal tuberculosis,and the treatment principles and clinical experience of CMUSE were summarized.Results The patient,a 54-year-old male,was diagnosed in September 2021 due to"dark red bloody stool for 5 days".Enteroscopy revealed multiple patchy ulcers in the jejunoileum with local white fur,swelling at the edges,partially healed,and circumferential stenosis in some of the intestinal lumen.Histopathological examination showed acute and chronic inflammation of jejunum and ileum mucosa with ulcers and granulation tissue as well as abundant neutrophil infiltrations.The patient was diagnosed with CMUSE after ruling out other small intestine diseases.Treatment with methylprednisolone for 28 days led to significant improvements in imaging and laboratory indicators.A follow-up enteroscopy 2 years later showed no abnormalities,and as of September 2023,there has been no recurrence.Conclusions CMUSE is a rare disease of unknown etiology.CMUSE should be considered in the case of gastrointestinal hemorrhage due to multiple ulcers of small intestine and chronic small intestinal obstruction caused by fibrous stenosis at the ulcer site.Capsule endoscopy and enteroscopy can support the diagnosis,but capsule endoscopy may be entrapped in the stenosis segment,which can lead to intestinal obstruction.Glucocorticoid hormone therapy should be used as soon as possible after diagnosis,and satisfactory results can be achieved.

The matrix metalloproteinases family (MMPs) are proteins related to tumor formation and metastasis that have attracted the attention of scholars in recent years. Tumor cells can secrete MMPs during malignant transformation, and the expression of MMPs in different malignant tumors is diverse, and different members of MMPs do not have exactly the same biological properties. Matrix metalloproteinase-19 (MMP-19) is a new member of MMPs whose secretion increases rapidly during the malignant transformation of cells and is released into the extracellular space to participate in biological processes such as proliferation, adhesion, invasion, migration, and angiogenesis of tumor cells. In this paper, the progress of research on the biological properties of MMP-19 in tumors was reviewed to provide a theoretical basis for exploring the development of tumors, especially for studying the invasion and metastasis of tumor cells.

Metabolic reprogramming is a hallmark of cancer, including lung cancer. However, the exact underlying mechanism and therapeutic potential are largely unknown. Here we report that protein arginine methyltransferase 6 (PRMT6) is highly expressed in lung cancer and is required for cell metabolism, tumorigenicity, and cisplatin response of lung cancer. PRMT6 regulated the oxidative pentose phosphate pathway (PPP) flux and glycolysis pathway in human lung cancer by increasing the activity of 6-phospho-gluconate dehydrogenase (6PGD) and α-enolase (ENO1). Furthermore, PRMT6 methylated R324 of 6PGD to enhancing its activity; while methylation at R9 and R372 of ENO1 promotes formation of active ENO1 dimers and 2-phosphoglycerate (2-PG) binding to ENO1, respectively. Lastly, targeting PRMT6 blocked the oxidative PPP flux, glycolysis pathway, and tumor growth, as well as enhanced the anti-tumor effects of cisplatin in lung cancer. Together, this study demonstrates that PRMT6 acts as a post-translational modification (PTM) regulator of glucose metabolism, which leads to the pathogenesis of lung cancer. It was proven that the PRMT6-6PGD/ENO1 regulatory axis is an important determinant of carcinogenesis and may become a promising cancer therapeutic strategy.

Tubeimoside-1 (TBMS1) is a triterpene saponins active components with large content in Cucurbitaceae plant Fritillaria, which is water-soluble and stable. It has a broad inhibitory effect on lung cancer, colorectal cancer, breast cancer, gastric cancer and other tumors. The mechanism is mainly related to the inhibition of tumor cell growth, induction of tumor cell apoptosis, inhibition of tumor cell invasion and metastasis, induction of cell autophagy, and inhibition of tumor angiogenesis.

Bone regeneration remains a great clinical challenge. Low intensity near-infrared (NIR) light showed strong potential to promote tissue regeneration, offering a promising strategy for bone defect regeneration. However, the effect and underlying mechanism of NIR on bone regeneration remain unclear. We demonstrated that bone regeneration in the rat skull defect model was significantly accelerated with low-intensity NIR stimulation. In vitro studies showed that NIR stimulation could promote the osteoblast differentiation in bone mesenchymal stem cells (BMSCs) and MC3T3-E1 cells, which was associated with increased ubiquitination of the core circadian clock protein Cryptochrome 1 (CRY1) in the nucleus. We found that the reduction of CRY1 induced by NIR light activated the bone morphogenetic protein (BMP) signaling pathways, promoting SMAD1/5/9 phosphorylation and increasing the expression levels of Runx2 and Osterix. NIR light treatment may act through sodium voltage-gated channel Scn4a, which may be a potential responder of NIR light to accelerate bone regeneration. Together, these findings suggest that low-intensity NIR light may promote in situ bone regeneration in a CRY1-dependent manner, providing a novel, efficient and non-invasive strategy to promote bone regeneration for clinical bone defects.
Animals ; Rats ; Bone Morphogenetic Protein 2/metabolism* ; Bone Regeneration ; Cell Differentiation ; Circadian Clocks ; Cryptochromes/metabolism* ; Osteoblasts/metabolism* ; Osteogenesis ; Transcription Factors/metabolism*

Objective:To discuss the effect of sarcopenia (Sa) on the prognosis of transjugular intrahepatic portosystemic shunt (TIPS) in patients with portal hypertension (PHT).Methods:Totally 131 PHT patients treated with TIPS were retrospectively collected from August 2013 to December 2017 in the First Affiliated Hospital of USTC, and were divided into the Sa group [maximum transverse diameter of the psoas major muscle/height (TPMT/H) ≤16.8 mm/m, n=60] and the control group (TPMT/H>16.8 mm/m, n=71). The patients were followed up with a median time of 42 months. The Kaplan-Meier method was used to calculate the incidence of hepatic encephalopathy, recurrence rate of PHT-related complications and survival rate of PHT patients after TIPS, and the differences were compared by Log-rank test. Results:The incidences of hepatic encephalopathy within 6 months after TIPS and severe hepatic encephalopathy requiring hospitalization in the Sa group [36.7% (95%CI 24.5%-48.8%) and 15.0% (95%CI 6.0%-24.0%)] were higher than those of the control group [15.7% (95%CI 7.3%-24.1%) and 2.8% (95%CI 0-6.7%)], with statistically significant differences (χ2=7.843, 16.442, P=0.005, 0.001). The 5-year overall recurrence rate of PHT-related complications of the Sa group after TIPS [15.8% (95%CI 6.4%-25.2%)] was higher than that of the control group [5.7% (95%CI 0.2%-11.2%)], with a statistically significant difference (χ2=4.431, P =0.035. The 1, 3 and 5-year survival rates in the Sa group were 88.3% (95%CI 80.3%-96.3%), 86.7% (95%CI 78.1%-95.3%) and 77.8% (95%CI 65.1%-90.5%) respectively, which were all lower than those of the control group [97.2% (95%CI 93.3%-100%), 95.8% (95%CI 91.1%-100.0%) and 93.7% (95%CI 87.6%-99.87%) respectively], and the difference was statistically significant (χ2=5.055, P=0.025). Conclusion:Sa has a higher incidence in PHT patients, which can increase the incidence of hepatic encephalopathy and recurrence rate of PHT-related complications, and can decrease the survival rate in PHT patients after TIPS. Hence, the Sa is an indicator of the poor prognosis in PHT patients with TIPS.

Objective: To investigate the inhibitory effect of Triptolide on vasculogenesis of human cervical microvascular endothelial cells, and to explore the mechanism. Methods: Human cervical microvascular endothelial cells (HCerMECs) were used as research subject, and treated with different concentrations of Triptolide (0, 5, 10, 20 and 40 ng/ml) i n v i t r o . The effect of Triptolide on cell proliferation was determined by CCK-8, the cell migration ability was detected by Transwell assay while the expression of vascular endothelial growth factor (VEGF) was examined by western blotting. Results: Triptolide inhibited the proliferation and migration of HCerMECs in a dose-dependent manner ( P <0.05). In addition, Triptolide could inhibit the expression of VEGF in HCerMECs in a concentration-dependent manner. Conclusions: Triptolide could inhibit the proliferation and migration activity of HCerMECs which is related with the suppression of VEGF expression.

Objective: To investigate the effects of Wilms’tumor 1-associating protein (WTAP) on proliferation, migration and invasion of human lung adenocarcinoma A549 cells. Methods: Human lung adenocarcinoma cell line A549 and HEK293T cells were chosen for this study. Two sets of shWTAP interference sequences were designed to construct lentiviral vector plasmid. Human lung adenocarcinomaA549 cells were infected after packaging lentivirus in HEK293T cells, and the control group was transfected with 277 empty vector plasmid. The mRNAand protein expression levels of WTAPinA549 cells were detected by qPCR and WB. Changes in proliferation, migration and invasion of A549 cells were detected by BrdU assay, cell scratch healing assay and Transwell assay, respectively. Results: Two plasmids, shWTAP-1 and shWTAP-2, were successfully constructed. Compared with the control group, the mRNA and protein expression levels of WTAP were significantly down-regulated inA549 cells with WTAP knockdown (both P<0.05), and the proliferation, migration and invasion ability of cells were significantly decreased (all P<0.05). Conclusion: Knockdown of WTAP significantly inhibited the proliferation, migration and invasion of human lung adenocarcinoma A549 cells. The expression of WTAP gene is associated with the occurrence and development of lung adenocarcinoma. WTAP may be a potential target for the diagnosis and treatment of lung adenocarcinoma.