Tetrandrine(TET),a natural bisbenzyl isoquinoline alkaloid extracted from Stephania tetrandra S.Moore,has diverse pharmacological effects.However,its effects on melanoma remain unclear.Cellular prolif-eration assays,multi-omics analyses,and xenograft models were used to determine the effect of TET on melanoma.The direct target of TET was identified using biotin-TET pull-down liquid chromatograph-mass spectrometry(LC-MS),cellular thermal shift assays,and isothermal titration calorimetry(ITC)analysis.Our findings revealed that TET treatment induced robust cellular autophagy depending on activating transcription factor 6(ATF6)-mediated endoplasmic reticulum(ER)stress.Simultaneously,it hindered autophagic flux by inducing cytoskeletal protein depolymerization in melanoma cells.TET treatment resulted in excessive accumulation of reactive oxygen species(ROS)and simultaneously triggered mitophagy.Sirtuin 5(SIRT5)was ultimately found to be a direct target of TET.Mechanistically,TET led to the degradation of SIRT5 via the ubiquitin(Ub)-26S proteasome system.SIRT5 knockdown induced ROS accumulation,whereas SIRT5 overexpression attenuated the TET-induced ROS accumula-tion and autophagy.Importantly,TET exhibited anti-cancer effects in xenograft models depending on SIRT5 expression.This study highlights the potential of TET as an antimelanoma agent that targets SIRT5.These findings provide a promising avenue for the use of TET in melanoma treatment and underscore its potential as a therapeutic candidate.

Objective To analyze the clinical characteristics of patients with acute esophageal injuries in order to improve clinicians'diagnosis and treatment of such diseases.Methods The general data and treatment methods of 61 patients with acute esophageal injury from January 2013 to March 2023 were retrospectively analyzed.Results Majority of the patients with esophageal and cardia mucosal tear syndrome were male(72.2%),age(52.04±17.96)years,triggering factor was gastroscopy in 29 patients(53.7%),and vomiting of blood and black stools was the main clinical manifestation(63.0%),the average length of hospital stay was(6.39±3.53)d and 13(24.1%)patients had anaemic complications,blood transfusion was given to 8 patients(14.8%),39 patients(72.2%)were discharged after conservative treatment with transfusion,and only 15 patients(27.8%)required endoscopic hemostasis.1 case of esophageal hematoma combined with esophageal cardia mucosal tear syndrome was an elderly male patient with a history of hypertension,cerebral infarction,and long term use of oral aspirin,complicated by severe anemia,who was given desiprofloxacin to stop the hemostasis endoscopically,the total length of hospital stay was 22 d.4 patients with esophageal hematoma were young and middle-aged males,2 patients had a predisposing factor of poor diet prior to the onset of the disease,2 patients presented with vomiting of blood,1 with chest pain and 1 with a foreign body sensation in the throat,2 patients were discharged with endoscopic intervention,and the remaining 2 patients were discharged after conservative treatment.2 patients with spontaneous esophageal rupture were young and middle-aged males,clinical manifestations were chest tightness or retrosternal discomfort,and one patient had esophageal rupture with left-sided liquid pneumothorax,esophageal rupture repair+pleural adhesion branding+open thoracic hemostasis+intrathoracic foreign body removal was performed,and an esophageal stent was placed endoscopically after the operation,and the patient was discharged from the hospital after 52 d,in another case,the patient's esophageal fistula was small,and a three-lumen nutrient tube was placed under gastroscopic guidance,the patient's esophagus recovered well after 7 d,and the patient was discharged from the hospital.Conclusion Acute esophageal injury is a clinical emergency,among them,esophageal hematoma and spontaneous esophageal rupture are relatively rare.Prompt endoscopic clot removal is a viable option for patients with ruptured esophageal hematomas who have failed conservative treatment,and patients with spontaneous esophageal rupture who have surgically placed esophageal stents have good mucosal recovery.Clinicians need to be vigilant for patients with esophageal injuries that are associated with anemia,or even require blood transfusion,should make a clear diagnosis at an early stage,with timely endoscopic or surgical intervention to avoid progression of the disease.

Objective:To analyze circRNAs specifically differentially expressed in esophageal squamous cell carcinoma (ESCC) based on high-throughput sequencing data.Methods:Six patients with pathologically confirmed ESCC in Tangdu Hospital of Air Force Medical University from March 2018 to March 2019 were selected as the research subjects, among which 3 were stage Ⅰ ESCC and 3 were stage Ⅲ ESCC. High-throughput sequencing technology was used to analyze the difference in the expression of circRNA in cancer tissues and adjacent tissues of patients. GO enrichment analysis, KEGG enrichment analysis and Venn analysis were performed on differentially expressed genes. The circRNA-miRNA-mRNA network was constructed using Cytoscape software. The most significantly differentially expressed genes in cancer tissues were verified in cells and tissues, and the relationships between circRNAs and clinical pathological indicators of patients were analyzed.Results:A total of 553 differentially expressed circRNAs were screened in paracancerous tissues and cancer tissues of 3 stage Ⅰ ESCC patients, of which 413 were up-regulated and 140 were down-regulated in cancer tissues; A total of 425 differentially expressed circRNAs were screened in paracancerous tissues and cancer tissues of 3 stage Ⅲ ESCC patients, of which 276 were up-regulated and 149 were down-regulated in cancer tissues. GO enrichment analysis showed that the host genes of differential circRNAs in patients with stage Ⅰ ESCC were mainly enriched in cell cycle-related biological processes such as mitotic G 2/M transition. The host genes of differential circRNAs in patients with stage Ⅲ ESCC were mainly enriched in biological processes related to cell division and tumor development, such as mitotic spindle checkpoint and cell matrix adhesion. KEGG enrichment analysis showed that the differential circRNAs in cancer tissues of stage Ⅰ and stage Ⅲ ESCC patients were mainly enriched in cancer-related biological pathways such as cell adhesion. The results of Venn analysis showed that in stage Ⅰ ESCC patients and stage Ⅲ ESCC patients, 2 and 8 circRNAs that were only specifically expressed in paracancerous tissues and had significant differences were screened out respectively, and were only specifically expressed in cancer tissues with significant differences were 11 and 14 respectively. The circRNA-miRNA-mRNA network showed that the cancer tissue-related circRNA-miRNA-mRNA network in stage Ⅰ ESCC patients consisted of 7 circRNA nodes, 10 miRNA nodes and 28 mRNA nodes, and the cancer tissue-related circRNA-miRNA-mRNA network in stage Ⅲ ESCC patients consisted of 7 circRNA nodes, 9 miRNA nodes and 49 mRNA nodes. The most significantly differentially expressed hsa-circ-0060927 and hsa-circ-0109301 in cancer tissues of patients with stage Ⅰ ESCC and stage Ⅲ ESCC were selected for cytological and histological verification. The results showed that the relative expression levels of hsa-circ-0060927 in ESCC cell lines TE1, TE13, KYSE30, KYSE170, and human normal esophageal epithelial cell line HEEC were 7.82±1.96, 12.69±2.68, 12.78±2.74, 7.53±1.75, and 2.43±0.17, respectively, with a statistically significant difference ( F=4.68, P=0.004). The relative expression levels of hsa-circ-0060927 in ESCC cell lines TE1, TE13, KYSE30, and KYSE170 were higher than that in human normal esophageal epithelial cell line HEEC, with statistically significant differences ( P=0.009; P=0.003; P=0.003; P=0.007). The relative expression levels of hsa-circ-0109301 in ESCC cell lines TE1, TE13, KYSE30, KYSE170, and human normal esophageal epithelial cell line HEEC were 5.16±1.32, 6.28±1.57, 4.89±1.13, 8.92±2.12, and 22.56±4.13, respectively, with a statistically significant difference ( F=4.31, P=0.022). The relative expression levels of hsa-circ-0109301 in ESCC cell lines TE1, TE13, KYSE30, and KYSE170 were lower than that in human normal esophageal epithelial cell line HEEC, with statistically significant differences ( P=0.027; P=0.015; P=0.024; P=0.008). The expression level of hsa-circ-0060927 in cancer tissues of 13 early ESCC patients was 12.89±2.67, significantly higher than 5.73±1.18 in paracancerous tissue, and there was a statistically significant difference ( t=15.02, P<0.001) ; the expression level of hsa-circ-0109301 in cancer tissues of 19 patients with advanced ESCC was 7.78±2.17, significantly lower than 16.32±3.15 in paracancerous tissue, and there was a statistically significant difference ( t=9.73, P<0.001). The expression of hsa-circ-0109301 was related to the degree of tumor differentiation in advanced ESCC patients ( P=0.023) . Conclusion:One circRNA (hsa-circ-0060927 and hsa-circ-0109301) with the most significanty differential expression is selected in early and advanced ESCC patients respectively, in which hsa-circ-0060927 is highly expressed in ESCC cancer tissues and hsa-circ-0109301 is lowly expressed in ESCC cancer tissues, and the expression of hsa-circ-0109301 is correlated with the degree of tumor differentiation.

Objective:To explore the effect of mind mapping teaching of gastroenterology in the standardized training for general practitioners, and provide new ideas for general practice education.Methods:A total of 65 physicians who were enrolled in the standardized training of general practice from January to December 2017 were collected as the control group, and the traditional teaching method was adopted; another 58 physicians from January to December 2018 were selected as the experimental group, and the mind mapping was adopted based on the traditional teaching method. The learning effect (theoretical and operational results) and the satisfaction questionnaire of trainees and teachers were used as evaluation indicators. SPSS 21.0 was used for t test and chi-square test. Results:The theory exam and clinical skills examination results of experimental group (80.80±5.30, 82.66±5.90) were significantly higher than those of the control group (71.60±5.20, 75.72±4.57), and the difference was statistically significant ( P<0.05). Compared with the control group, the experimental group had better understanding of knowledge points of this discipline, clinical thinking ability, higher learning interest, teamwork ability, innovation ability and teacher satisfaction, with statistical significance ( P<0.05). Conclusion:The mind mapping has more advantages than traditional teaching methods in the standardized training for general practitioners, which can be further extended.

Non-coding RNAs (ncRNAs) is a kind of RNA without protein coding function. A large number of studies in recent years have shown that the occurrence and development of colorectal cancer (CRC) are closely related to the aberrant expression of ncRNAs. ncRNAs can be used as non-invasive biomarkers for early diagnosis of CRC. We review the research progress of ncRNAs in early diagnosis of CRC, and summarize the potential clinical value of ncRNAs detection, which can provide a theoretical basis for improving the early diagnosis rate of CRC.

OBJECTIVE: To investigate the value of positive lymph node ratio (LNR) in predicting the prognosis of patients with esophageal cancer. METHODS: We retrieved the data of a total of 862 patients with esophageal cancer with complete clinical pathology data archived in SEER database in 2010 to 2015. The best cutoff point of LNR was selected using X-tile software. Univariate and multivariate COX proportional hazard models were used to assess the value of LNR in predicting the prognosis of patients after propensity score matching (PSM). RESULTS: The best cut-off point of LNR determined using X-tile 3.6.1 software was 0.16. The patients with LNR < 0.16 and those with LNR≥0.16 showed significant differences in the number of positive lymph nodes, pathological type, T stage and M stage. After 1:1 propensity score matching, the two groups showed no significant difference in the clinical data or pathological parameters. Matched univariate and multivariate COX regression analyses showed that LNR, primary tumor site and M staging were all independent risk factors affecting the prognosis of patients, and among them LNR had the most significant predictive value (LNR < 0.16 LNR≥0.16: HR=1.827, 95% : 1.140-2.929; =0.000). The median survival time of patients with LNR < 0.16 was 31 months (95%: 22.556-39.444 months), as compared with 16 months (95%: 12.989-19.011) in patient with LNR≥0.16 (Log Rank χ=27.392, < 0.0001). LNR had a better accuracy than N stage for assessing the patients' prognosis with an area under the ROC curve of 0.617 (95%: 0.567-0.666), as compared with 0.515 (95%: 0.463-0.565) of N stage (=3.008, =0.0026). CONCLUSIONS LNR≥0.16 is an independent risk factor affecting the prognosis of patients with esophageal cancer and has better prognostic value than N stage.
Esophageal Neoplasms ; Humans ; Lymph Node Excision ; Lymph Node Ratio ; Lymph Nodes ; Lymphatic Metastasis ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Risk Factors

OBJECTIVE: To analyze the differences in reflux patterns in 24-hour esophageal pH-impedance monitoring in patients with non-erosive reflux disease (NERD), reflux hypersensitivity (RH) and functional heartburn (FH) and explore the possible mechanism of symptoms in patients with heartburn and negative endoscopic findings. METHODS: Seventy-nine patients with heartburn as the main symptoms but negative endoscopic findings, including 35 with NERD, 16 with RH and 28 with FH, were enrolled in this study.All the patients underwent 24-h esophageal pH-impedance monitoring and esophagogastroscopy, and the results were compared among the 3 groups. RESULTS: Acid reflux episode was significantly increased and weakly alkaline reflux episode was significantly decreased in NERD group in comparison with RH group and FH group ( CONCLUSIONS Patients with NERD, RH and FH had different reflux patterns.Acid reflux is predominant in the NERD, while weakly alkaline reflux is significantly increased RH and FH.In patients with normal esophageal acid exposure but without symptoms or without recorded symptoms during esophageal pH-impedance monitoring, analysis of the total reflux episode, mixed reflux episode, proximal acid reflux episode and percentage can help in the differential diagnosis between RH and FH.
Electric Impedance ; Esophageal pH Monitoring ; Gastroesophageal Reflux/diagnosis* ; Heartburn/etiology* ; Humans ; Hydrogen-Ion Concentration

Objective:To compare the clinical characteristics of patients with non-erosive gastroesophageal reflux disease (NERD), reflux hypersensitivity (RH) and functional heartburn (FH), in order to help the differential diagnosis and treatment of the three diseases.Methods:From October 2016 to February 2019, 64 patients with persistent heartburn who had negative endoscopy in the Department of Gastroenterology, the Second Affiliated Hospital of Xi′an Jiaotong University and with negative results of endoscopy examination were consecutively selected, which included 26 NERD patients (NERD group), 12 RH patients (RH group) and 26 FH patients (FH group). The gender, age, body mass index (BMI), presence of hiatus hernia, proton pump inhibitor (PPI) treatment effect, the score and incidence of gastroesophageal symptoms within one month before visit, and the incidence of overlapping functional dyspepsia (FD), postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS) of the three groups were compared. One-way analysis of variance, least-significant difference, Kruskal-Wallis H test, Mann-Whitney U test and chi-square test were used for statistical analysis. Results:There were no statistically significant differences in gender, age or incidence of esophageal hiatal hernia between NERD group, RH group and FH group (all P>0.05). BMI of NERD group was higher than that of FH group ((23.74±3.10) kg/m 2 vs. (21.26±2.75) kg/m 2), and the difference was statistically significant ( t=3.066, P=0.003). The effective rate of PPI treatment in NERD group was higher than those of RH group and FH group (19, 4, and 11 cases, respectively), the differences were statistically significant ( χ2=5.428 and 5.042, P=0.020 and 0.025). The score and incidence of burning sensation in upper abdomen of NERD group were both lower than those of FH group (0, 0 to 0 vs. 0, 0 to 5; 7.7%, 2/26 vs. 38.5%, 10/26), and the differences were statistically significant ( Z=-2.756, P=0.006; χ2=6.933, P=0.008). There were no statistically significant differences in the score of heartburn symptoms, or the scores and incidence of chest pain, reflux, globular sensation of hysteria, burning sensation of throat, cough, epigastric pain, early satiety or post meal fullness, belching, nausea or vomiting between NERD group, RH group and FH group (all P>0.05). There were no statistically significant differences in the incidence of overlapping FD or overlapping PDS between the NERD group, RH group and FH group (both P>0.05), but the incidence of overlapping EPS of FH group was higher than that of NERD group (46.2%, 12/26 vs. 11.5%, 3/26), and the difference was statistically significant ( χ2=7.589, P=0.013). Conclusions:There are certain differences in the clinical characteristics of patients with NERD, RH or FH, mainly reffected in the PPI treatment effects and whether overlapping EPS. The higher incidence of FH overlapping EPS further strengthens the hypothesis that functional gastrointestinal disorders have a common pathophysiological mechanism.

Objective To investigate the effectiveness and safety of oral olive oil combined with polyethylene glycol electrolyte ( PEG ) on bowel preparation before colonoscopy for chronic constipation patients. Methods A randomized, single-blind, prospective study was conducted on 180 patients with chronic constipation, who underwent colonoscopy at Tangdu Hospital of the Fourth Military Medical University from November 2017 to May 2018. Patients were randomly divided into three groups. Patients in group A took 60 mL olive oil and a piece of crystal sugar at 7:30 pm the day before colonoscopy, followed by 1500 mL PEG at 8:00 pm before the test, and 1500 mL PEG at 5:00 am the day of colonoscopy. Patients in group B took 60 mL olive oil and a piece of crystal sugar after administration of PEG at 8:00 pm the day before colonoscopy, followed by 1500 mL PEG at 5:00 am the day of colonoscopy. The group C was given 1500 mL PEG at 8:00 pm the day before colonoscopy, and another 1500 mL PEG at 5:00 am the day of colonoscopy. We recorded the time of first defecation after taking medication, the number of defecation before sleep, the total number of defecation, the score of Boston bowel preparation scale ( BBPS) of the right, middle and left colon, and the adverse reactions, and compared the data among the three groups. The measurement data was compared using the analysis of variance. After the difference was found, the LSD-t test was used to compare between the two groups. The enumeration data was compared using the Pearsonχ2 test. Results One patient in the group B terminated colonoscopy due to unable to continue cooperation during the examination. Group B and C both excluded one patient because of a large mass found in the descending colon of patients. Finally, there were 60 cases in the group A, 58 in the group B, and 59 in the group C. There was no statistical difference between the three groups in the general resource ( P>0. 05) . The time of first defecation after taking medication for the group A, B and C was (2. 25±2. 32) h, (2. 43±2. 39) h and (3. 36±2. 79) h respectively, with statistical difference (F=3. 36, P=0. 037). The time of first defecation was longer in the group C than that of the group A and B ( P = 0. 016 and P = 0. 046, respectively). The number of defecation before sleep for the group A, B and C was 3. 47±2. 09, 3. 24±1. 76 and 2. 49±1. 58 respectively, with statistical difference (F=4. 65, P=0. 011). The number of defecation before sleep was lesser in the group C than that of the group A and B ( P=0. 004, P=0. 027, respectively) . The total number of defecation for the group A, B and C was 7. 20 ± 2. 67, 6. 81 ± 2. 31 and 5. 64 ± 2. 22 respectively. The difference among the three groups was statistically significant ( F=6. 68, P=0. 002) . For the group A and B, the total number of defecation was both more than that of the group C ( P=0. 001, P=0. 010) . There were no statistical differences among the three groups in the BBPS score of the left and middle colon and the total BBPS score ( all P>0. 05) . The BBPS score of the right colon for the group A, B and C was 2. 03 ± 0. 82, 1. 95 ± 0. 87 and 1. 53 ± 0. 80 respectively, with statistical difference ( F=6. 38, P=0. 002) , and was lower in the group C than that of the group A and B ( P= 0. 001, P= 0. 006, respectively) . Adverse reactions after taking medication including nausea, vomiting, abdominal pain, and bloating were respectively reported in 7, 3, 0 and 3 cases in the group A, 5, 3, 0 and 6 in the group B, and 4, 2, 1 and 4 in the group C, and there was no statistical difference among the three groups (χ2=4. 35, P=0. 824) . Conclusion Administration of olive oil compared with PEG can improve the cleanness of right colon for chronic constipation patients, shorten the time of first defecation after taking medication, and increase the number of defecation before sleep and the total number of defecation during bowel preparation. Taking olive oil before or after PEG at the night before colonoscopy has no significantly effect on bowel preparation and adverse reactions.

To develop a clinical diagnosis technique for bluetongue virus infection, we established serotype-specific methods to detect serotype 4 of bluetongue virus (BTV-4). Two monoclonal antibodies (mAbs) against VP2 protein of BTV-4, named 4A-1G7 and 4B-1B6, were used as competitive antibodies in the competitive enzyme-linked immunosorbent assays (C-ELISA). We detected 50 negative serum samples from sheep, goats and cattle by C-ELISA. The cut-off values of 4A-1G7 and 4B-1B6 mAbs were 49% and 40%, respectively. The results of the sensitivity, specificity and repeatability by detecting standard positive serum, were consistent with the general standard of Office International Des Epizooties. Furthermore, serum samples of BTV-4, BTV-18 and BTV-20 infection could be screened out through the combined C-ELISAs by 4A-1G7 and 4B-1B6 mAbs. Thus, this technique may diagnose BTV-4, BTV-18 and BTV-20 infections.