This study aimed to investigate the mechanism of resveratrol(RES) combined with irinotecan(IRI) in the treatment of colorectal cancer(CRC). The targets of RES, IRI, and CRC were obtained from databases, and the targets of RES combined with IRI in the treatment of CRC were acquired by Venn diagram. The protein functional cluster analysis, GO and KEGG enrichment analyses were performed. In addition, the protein-protein interaction(PPI) network was constructed. The core target genes were screened out and the target-signaling pathway network was set up. IGEMDOCK was used to dock the core target gene molecules. Besides, the relationship between the expression level of key target genes and the prognosis and immune infiltration of CRC was analyzed. Based on the in vitro cell experiment, the molecular mechanism of RES combined with IRI in the treatment of CRC was explored and analyzed. According to the results, 63 potential targets of RES combined with IRI were obtained for CRC treatment. Furthermore, cluster analysis revealed that protein functions included 23% transmembrane signal receptors, 22% protein modifying enzymes, and 14% metabolite converting enzymes. GO analysis indicated that BPs were mainly concentrated in protein autophosphorylation, CCs in receptor complex and plasma membrane, and MFs in transmembrane receptor protein tyrosine kinase activity. Moreover, KEGG signaling pathways were mainly enriched in central carbon metabolism in cancer. The key targets of RES combined with IRI in the treatment of CRC were PIK3CA, EGFR, and IGF1R, all of which were significantly positively correlated with the immune infiltration of CRC. As shown by the molecular docking results, PIK3CA had the most stable binding with RES and IRI. Compared with the results in the control group, the proliferation ability and EGFR protein expression of CRC cells in the RES-treated group, the IRI-treated group, and the RES+IRI treated group significantly decreased. Moreover, the cell proliferation ability and EGFR protein expression level of CRC cells in the RES+IRI treated group were remarkably lower than those in the IRI-treated group. In conclusion, PIK3CA, EGFR, and IGF1R are the key targets of RES combined with IRI in CRC treatment. In addition, RES can inhibit the proliferation of CRC cells and improve IRI chemoresistance by downregulating the EGFR signaling pathway.
Humans ; Irinotecan ; Colorectal Neoplasms/genetics* ; Resveratrol ; Molecular Docking Simulation ; ErbB Receptors/genetics*

In recent years, the clinical treatment of colorectal cancer(CRC) has made great progress, but chemoresistance is still one of the main reasons for reducing the survival rate of patients with colorectal cancer. Therefore, ameliorating chemotherapy resis-tance is an urgent problem to be solved. The purpose of this study was to investigate the regulatory role and related molecular mechanisms of hydroxysafflor yellow A(HSYA) in colorectal cancer cell proliferation, migration, and 5-fluorouracil(5-FU) chemoresistance. In this study, HCT116 and HT-29 cells were used as research subjects. Firstly, methyl thiazolyl tetrazolium(MTT) assay and colony formation assay were used to detect and analyze the effect of HSYA on the proliferation of CRC cells. Secondly, the effect of HSYA on the cell cycle in CRC cells was analyzed by cell cycle assay. Furthermore, the effect of HSYA on the migration of CRC cells was analyzed by wound-healing assay and Transwell assay. Based on the above, the influences of HSYA on 5-FU chemoresistance of CRC cells and related molecular mechanisms were explored and analyzed. The results showed that HSYA significantly inhibited the proliferation and migration of CRC cells, and arrested the cell cycle in G_0/G_1 phase. In addition, HSYA significantly ameliorated the chemoresistance of CRC cells to 5-FU. The results of acridine orange staining and Western blot showed that the autophagy activity of CRC cells in the HSYA and 5-FU combined treatment group was significantly higher than that in the 5-FU single drug treatment group. As compared with the 5-FU single drug treatment group, the phosphorylation levels of protein kinase B(Akt) and mammalian target of rapamycin(mTOR) in the HSYA and 5-FU combined treatment group were significantly reduced, indicating that the Akt/mTOR signaling pathway in the combined treatment group was down-regulated in CRC cells. In conclusion, HSYA may upregulate autophagy activity through the Akt/mTOR signaling pathway, thereby inhibiting the proliferation and migration of CRC cells and ameliorating the chemoresistance to 5-FU.
Humans ; Proto-Oncogene Proteins c-akt/metabolism* ; Drug Resistance, Neoplasm ; Cell Line, Tumor ; TOR Serine-Threonine Kinases/metabolism* ; Fluorouracil/pharmacology* ; Cell Proliferation ; Autophagy ; Colorectal Neoplasms/drug therapy*

OBJECTIVE: To explore the effect of general anesthesia combined with epidural anesthesia and patient-controlled epidural analgesia on the incidence of the post-operative cognitive dysfunction (POCD) in elderly patients.
 METHODS: A total of 100 elderly patients with gastric cancer, who underwent radical gastrectomy in Yan'an People's Hospital from March 2012 to March 2015, were randomly divided into 3 groups: a general anesthesia and patient-controlled intravenous analgesia (PCIA) (Group I, n=35), a general anesthesia combined with epidural anesthesia and PCIA (Group II, n=30), and a general anesthesia combined with epidural anesthesia and patient-controlled epidural analgesia (PCEA) (Group III, n=35). There was no significant difference in age, gender, body mass index (BMI), length of operation, American Society of Anesthesiologists (ASA) grade and Mini-Mental State Examination (MMSE) score (all P>0.05). The cognitive function was assessed at the 1st day before operation and at the 6 h, 12 h, 2 d and 6 d after operation by the Mini-Mental State Examination test (MMSE), and the incidence of POCD was compared among the 3 groups. The mean arterial pressure (MAP), blood glucose, cortisol and tumor necrosis factor α (TNF-α) content during the operation were considered. The dosage of sevoflurane (SEVO) in the operation process and the pain score at the 6, 12 and 24 h after operation were recorded.
 RESULTS: The incidence of POCD at 6 h was 45.71% in the Group I and 34.28% in the Group II, which were higher than that in the Group III (10.00%). The incidence of POCD at 12 h was 34.29% in the Group I and 28.57% in the Group II, which were higher than that in the Group III (3.33%). The incidence of POCD at the 2 d was 28.57% in the Group I and 17.14% in the Group II, which were higher than that in the Group III (0). The incidence of POCD at 6 d was 17.14% in the Group I and 2.85% in the Group II, which were higher than that in the Group III (0). The blood glucose, cortisol and TNF-α content were consistent with the incidence of POCD, with significant difference (all P<0.05). The amplitude of MAP in the Group II and the Group III was significantly less than that in the Group I, and the postoperative analgesia effect in the Group III was obviously better than that in the other two groups (both P<0.05).
 CONCLUSION The general anesthesia combined with epidural anesthesia and patient-controlled epidural analgesia can effectively maintain the stable hemodynamic status in the patients and display inhibitory effect on postoperative cognitive dysfunction.
Analgesia, Epidural ; Analgesia, Patient-Controlled ; Anesthesia, Epidural ; Anesthesia, General ; Cognition ; Cognition Disorders ; Cognitive Dysfunction ; Gastrectomy ; Humans ; Incidence ; Methyl Ethers ; Neuropsychological Tests ; Postoperative Complications ; Sevoflurane ; Stomach Neoplasms ; Tumor Necrosis Factor-alpha

Colorectal cancer (CRC) is one of the malignant tumors with the highest incidence and mortality in the world. The pathogenic mechanism of CRC has not been fully elucidated until now. Ubiquitination plays an important role in CRC development, and its effects mainly depend on E3 ubiquitin ligases, which could modify substrate proteins by ubiquitination, in turn altering their activity or mediating ubiquitin-proteasome degradation. Here research progress of the regulatory roles of RING (really interesting new gene) type and HECT(homologous to E6AP C-terminus) type E3 ubiquitin ligases in CRC cell proliferation, apoptosis, migration, invasion and chemotherapy sensitivity as well as targeted inhibitors of these E3 ligases are reviewed, providing new clues for the study of pathogenesis and targeted therapy of CRC.

AIM: To investigate the onset of age, gender, profession, marital characteristics, clinical symptoms, signs, image characteristics of fundus and laser scanning features of syphilitic chorioretinitis.METHODS: Retrospective case series study. A total of 114 patients(138 eyes), 24 of whom were double eyes diagnosed with syphilitic chorioretinitis from January 2006 to January 2023 were included in this study. All of the data were collected from eye examination including the best corrected visual acuity(BCVA), intraocular pressure(IOP), fundus photography, optical coherence tomography(OCT), fundus fluorescein angiography(FFA), indocyanine green angiography(ICGA), visual field, visual evoked response; and blood tests including rapid plasma reagin(RPR)test and treponema pallidum hemagglutination(TPPA)test, tuberculin test, tuberculosis spot test, human immunodeficiency virus, human leukocyte antigen-B27, rheumatism series examination.RESULTS: All patients tested positive for RPR and TPPA, while other laboratory tests were negative, confirming the diagnosis of syphilitic chorioretinopathy. The average age of onset was 44±13.1 years old, with 59 males(51.8%), 55 females(48.2%), 90 monocular cases(78.9%), and 24 binocular cases(21.1%), and there were no significant differences in gender, marriage, or occupation. The main clinical features were visual loss, hyperemia of the optic disc, grayish-yellow opacity of the central retina; FFA mainly showed early dot weak background fluorescence in the peripheral region of the macula, retinal blood vessel fluorescence leakage staining, retinal pigment epithelium(RPE)fluorescence accumulation and optic disc staining or strong fluorescence; ICGA and OCT were mainly manifested by squamous weak fluorescence of the posterior retina; and the manifestations of FFA and ICGA were symmetrical; OCT revealed hyperreflective dots and pinpoint projection of RPE.CONCLUSION: The median age of onset in patients with syphilitic chorioretinitis is 44 years old, and monocular onset is more common. The patient's gender, marriage, and occupation have no significant characteristics. The clinical manifestations mainly include decreased vision, gray white cells in the vitreous body, thickening of the posterior pole retina, and grayish yellow changes. Correctly identifying OCT, FFA, and ICGA features can reduce missed diagnosis and misdiagnosis, and make an early and correct diagnosis and treatment of patients.

This paper aims to study the effects of traditional Chinese medicine on multidrug resistant human gastric cancer cells in the cell proliferation, migration, invasion and apoptosis, and to study the apoptosis-inducing pathway. Different dilutions of extract were used to process human multidrug resistant gastric cancer SGC7901/ADR cells. Cell proliferation inhibition phenomenon was determined by MTT experiment. Nuclear morphological changes of apoptotic cells and apoptotic indexes were observed and determined by Hochest33528 staining followed with fluorescence microscope observing. Flow cytometry was used to detect cell apoptosis rate. Cell migration and invasion ability were observed and determined by Transwell method. Spectrophotometry was used to detect caspase-3 and caspase-9 enzyme activity. Western blotting was used to detect subcellular distribution of cytochrome c. The results showed that extract had obvious inhibition effect on proliferation of gastric cancer multidrug resistant SGC7901/ADR cells, which was time- and concentration-dependent. After processing multidrug resistant gastric cancer SGC7901/ADR cells with extract, the apoptotic index and apoptosis rate were significantly increased than those in the control group, which showed a time- and dose-dependent mode; but if a caspase inhibitor was added, apoptosis index was not obviously increased. Transwell method showed that migration and invasion ability of the extract-processed SGC7901/ADR cells dropped significantly. Spectrophotometry showed that in extract-processed SGC7901/ADR cells, caspase-3 and caspase-9 expression were increased, which had significant differences with the control group. Western blotting test showed that the distribution of cytochrome c decreased in mitochondria, while increased in the cytoplasm (i.e., cytochrome c escaped from mitochondria to the cytoplasm). In conclusion, extract could inhibit the proliferation, migration and invasion, and induce apoptosis in human gastric cancer multidrug resistant SGC7901/ADR cells; and cytochrome c, caspase-9 and caspase-3 might be involved in cell apoptosis induced by extract, suggesting endogenous or mitochondrial apoptotic pathway.

Objective To investigate the effects of PRPF19 knockdown on the proliferation, migration, and invasion of pancreatic cancer cells. Methods The expression of PRPF19 in pancreatic cancer and normal tissues was analyzed using the GEPIA database. The protein and mRNA expression levels of PRPF19 in pancreatic cancer cells were detected by Western blot and qRT-PCR. Small interfering RNA (siRNA) was used to silence the expression of PRPF19 in pancreatic cancer cells, and the knockdown efficiency was verified by Western blot and qRT-PCR. CCK-8, colony forming, and Transwell assay were used to detect the effects of knockdown of PRPF19 on the proliferation, colony forming, migration, and invasion of pancreatic cancer cells. Results GEPIA analysis showed that PRPF19 was highly expressed in pancreatic cancer tissues compared with normal pancreatic tissues. In comparison with normal pancreatic cells, PRPF19 was highly expressed in various pancreatic cancer cell lines such as MIA PaCa-2 and PANC-1 (P < 0.05). In comparison with the control group, PRPF19 knockdown significantly reduced the proliferation rate, colony forming, cell migration, and invasion of pancreatic cancer cells (P < 0.05). Conclusion PRPF19 knockdown inhibits the proliferation, migration, and invasion of pancreatic cancer cells. PRPF19 may play an important role as an oncogene of pancreatic cancer.

Objective To explore the molecular mechanism underlying miR-9500 regulating the migration and invasion of lung adenocarcinoma cells by targeting SMAD2. Methods The core target genes of miR-9500 were screened out by bioinformatics analysis, and their GO function analysis, KEGG signaling pathway enrichment, and survival analysis were performed. The targeted binding sites between miR-9500 and SMAD2 were predicted, and the direct targeting relationship between miR-9500 and SMAD2 was verified by dual-luciferase reporter assay. qRT-PCR and Western blot were used to assess the effect of miR-9500 on the mRNA and protein expression levels of SMAD2. Wound healing assay, Transwell assay, and Matrigel invasion assay were used to determine the effect of miR-9500 on the migration and invasion of lung adenocarcinoma cells. Results The core target genes of miR-9500 were mainly enriched in the cancer pathway, TGF-β signaling pathway, and focal adhesion. However, only the expression levels of VAMP2, SMAD2, and RXRA among the top 10 core target genes were significantly correlated with the overall survival of patients with lung adenocarcinoma. miR-9500 targeted SMAD2 and down-regulated the expression levels of SMAD2, and overexpression of miR-9500 significantly inhibited the migration and invasion of lung adenocarcinoma cells and markedly decreased the expression levels of MMP2 and MMP9. Conclusion miR-9500 can inhibit the migration and invasion of lung adenocarcinoma cells by targeting SMAD2, which may play an important role in the tumorigenesis and development of lung adenocarcinoma as a tumor suppressor.

OBJECTIVETo explore the clinical value of multi-slice spiral computed tomography portography (MSCTP) in assessing severity of liver cirrhosis and predicting episode risks of hepatic encephalopathy (HE).

METHODSEighty-six patients with liver cirrhosis who were hospitalized in the Department of Gastroenterology at the Affiliated Hospital of Yan'an University were included in the study.All patients underwent 64-slice MSCTP to grade the portal vein anatomy.The West Haven criteria were used for semi-quantitative assessment of each patient's mental state.The Child-Pugh grading system was used to assess the extent of cirrhosis.Comparison of measurement data between multiple groups was made by one-way ANOVA analysis, and comparison of such between two groups was made by the Mann-Whitney U test, Ranked data were compared with the rank-sum test, and count data were compared by the Chi-Square test.Correlation analysis was performed with Spearman's correlation test.

RESULTSComparison of the HE grade III group and the HE grade I group showed significant differences between the two in the diameters of left gastric vein, the splenic vein, the intrahepatic left portal vein and the intrahepatic right portal vein (P less than 0.05).Comparison of the Child-Pugh grade C group and the Child-Pugh grade A group showed significant differences between the two in diameters of the left gastric vein, the splenic vein, the intrahepatic left portal vein and the intrahepatic right portal vein (P less than 0.05).The diameters of the main portal vein were not significantly different between the ChildPugh grades and HE classifications (P more than 0.05).The results of MSCTP did show significant differences between different HE classifications in patients with liver cirrhosis and the rate of formation of portal vein thrombosis and fistulas of the hepatic artery-portal vein (P less than 0.05), .but no significant differences with the esophageal and gastric varices, varicose veins around the esophagus, and periumbilical varicose veins (P more than 0.05).HE classification was significantly correlated with formation of portal vein thrombosis and fistula of the hepatic artery-portal vein (r=0.687, P less than 0.05 and r=0.565, P less than 0.05, respectively).MSCTP grading (grade 1:n=35, grade 2:n=36, grade 3:n=15) was not correlated with the Child-Pugh grade (grade A:n=36, grade B:n=32, grade C:n=18) (Z=-0.135, P more than 0.05).Incidence of HE was significantly different among the different MSCTP grades (grade 1:0%(0), grade 2:33.3% (12/36), grade 3:66.7% (10/15); x2=26.468, P less than 0.05).The MSCTP grade was significantly correlated with the episode risks of HE (r=0.552, P less than 0.05).

CONCLUSIONMSCTP may be valuable for assessing severity of liver cirrhosis and for predicting episode risks of HE; however, future studies with larger sample numbers is required for validation of our findings.

Esophageal and Gastric Varices ; Hepatic Encephalopathy ; etiology ; Hepatic Veins ; Humans ; Liver Cirrhosis ; diagnostic imaging ; pathology ; Portal Vein ; Portography ; Risk Factors ; Tomography, Spiral Computed

OBJECTIVE: To screen the tumor markers of laryngeal carcinoma and to investigate their expression in preoperative and postoperative serum. METHOD: The distinct protein in serum was detected in 32 cases of laryngeal carcinoma and 38 healthy people by IMAC-Cu proteinchip array and surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS). The distinct proteins in serum were detected in 32 cases of laryngeal carcinoma preoperation and within 10 days 15 cases of laryngeal carcinoma postoperation with the same methods. The discriminatory profiling between preoperative and postoperative patients was analyzed by Biomarker Wizard software and Biomarker Pattern software. RESULT: The results showed that fifteen differentially expressed proteins in serum were screened by analysis of proteomic spectra of preoperative patients and normal subjects. Seventeen kinds of protein differentially expressed in serum were screened by analysis of proteomic spectra of preoperative and postoperative patients. Six kinds of protein (2958.52, 3796.89, 5148.86, 6115.57, 4052.18, and 7770.76) were obtained for making up patterns that was able to class the preoperative-team and postoperative-team. Corresponding correct ratio were 84.38% (27/32) and 73.33% (11/15). CONCLUSION The preliminary results suggest that classification system will provide a highly accurate and innovative approach for the early diagnosis of laryngeal carcinoma and judgement of prognosis. SELDI-TOF-MS technology is a useful tool for a high throughput screening of large-sized serum samples to discover potential biomarkers for laryngeal carcinoma.
Aged ; Biomarkers, Tumor ; blood ; Female ; Humans ; Laryngeal Neoplasms ; blood ; pathology ; Male ; Middle Aged ; Prognosis ; Protein Array Analysis ; methods ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; methods