1.Analysis of the correlation between metabolic syndrome and recurrent acute pancreatitis
Chinese Journal of Digestion 2024;44(1):38-43
Objective:To investigate the correlation between metabolic syndrome (MS)and recurrent acute pancreatitis (RAP).Methods:From June 1, 2012 to June 1, 2023, 463 patients with RAP (recurrent group) who visited the First Affiliated Hospital of Chongqing Medical University were retrospectively collected. The clinical data of 463 patients without RAP (non-recurrent group) during the same period were randomly selected. The patients in the recurrence group were treated at the First Affiliated Hospital of Chongqing Medical University for both initial acute pancreatitis and RAP. The differences in the proportion of patients combined with MS and its components (obesity (body mass index ≥25 kg/m 2), fasting blood triglyceride (TG) ≥1.7 mmol/L, hypertension, hyperglycemia, fasting blood high-density lipoprotein cholesterol (HDL-C) <1.04 mmol/L) between the two groups were analyzed by Chi-square test. Binary logistic regression analysis was used to identify the risk factors of acute pancreatitis recurrence. Results:Among the 463 patients in the recurrent group, there were 221 patients (47.7%) with MS, 276 patients (59.6%) with obesity, 223 patients (48.2%) with hypertension, 185 patients (40.0%) with hyperglycemia, and 365 patients (78.8%) with fasting blood TG ≥1.7 mmol/L. Among the 463 patients in the non-recurrence group, there were 95 patients (20.5%) with MS, 245 patients (52.9%) with obesity, 115 patients (24.8%) with hypertension, 92 patients (19.9%) with hyperglycemia, and 301 patients (65.0%) with fasting blood TG ≥ 1.7 mmol/L. The percentages of MS, obesity, hypertension, hyperglycemia, and fasting blood TG ≥1.7 mmol/L of the recurrent group were all higher than those of the non-recurrent group, and the differences were statistically significant ( χ2=76.27, 4.22, 54.35, 44.55, 21.90; P<0.001, =0.040, <0.001, <0.001, <0.001). There was no statistically significant difference in the percentage of patients with fasting blood HDL-C <1.04 mmol/L between the recurrent group and the non-recurrent group (68.5%, 317/463 vs. 65.4%, 303/463, P>0.05). The results of binary logistic regression analysis showed that combined with MS ( OR=3.538, 95% confidence interval (95% CI) 2.647 to 4.728), hypertension ( OR=2.700, 95% CI 2.025 to 3.602), hyperglycemia ( OR=2.228, 95% CI 1.633 to 3.039), and fasting blood TG ≥1.7 mmol/L ( OR=1.757, 95% CI 1.276 to 2.421) all significantly increased the risk of acute pancreatitis recurrence ( P<0.001, <0.001, <0.001, =0.001). Obesity was not an independent risk factor for RAP ( OR=0.967, 95% CI 0.727 to 1.286, P=0.816). Conclusion:The combination of MS, hypertension, hyperglycemia, and fasting blood TG ≥1.7 mmol/L are independent risk factors for RAP.
2.Trans-nasal biliary drainage tube water-injection ultrasound: a new method for detecting residual stones after endoscopic extraction of bile duct stones
Xiaodong WU ; Shaoshan TANG ; Shuodong WU
Chinese Journal of Digestion 2024;44(1):44-49
Objective:To observe the ability of abdominal ultrasonography (hereinafter referred to as water-injection ultrasonography) after injection of 0.9% sodium chloride solution via endoscopic nasobiliary drainage tube in the detection of residual stones in bile duct after stone extraction by endoscopic retrograde cholangiopancreatography (ERCP).Methods:From January 2015 to June 2023, at the Second Department of General Surgery, Shengjing Hospital, China Medical University, 342 patients, who were diagnosed with choledochal stones and received stone extraction by ERCP and at the same time placed endoscopic nasobiliary drainage tube, were enrolled.After stone extraction by ERCP, all the patients underwent cholangiography, conventional abdominal ultrasound, and water-injection ultrasonography. The patients with stones removed by the secondary ERCP were positive. The ability to detect residual stones in bile duct by cholangiography, conventional abdominal ultrasound and water-injection ultrasonography were compared. Chi-square test was performed for statistical analysis.Results:The results of cholangiography showed that 35 patients were suspected with residual stones in bile duct, among them 28 were confirmed to be true-positive, the sensitivity was 50.9% and specificity was 97.6%; the results of conventional abdominal ultrasound showed that 15 patients were suspected with residual stones in bile duct, among them 13 were confirmed to be true positive with a sensitivity of 23.6% and a specificity of 99.3%; and the results of water-injection ultrasonography showed that 56 patients were suspected with residual stones in bile duct, among them 50 were confirmed as true positive, with a sensitivity of 90.9% and a specificity of 97.9%. The number of true-positive patients detected by water-injection ultrasonography was greater than those determined by cholangiography and conventional abdominal ultrasonography, and the sensitivity was higher than that of cholangiography and conventional abdominal ultrasonography, and the differences were statistically significant ( χ2=21.33, 50.85, 38.77 and 92.53, all P<0.001). There was no statistically significant difference in the specificity among water-injection ultrasonography, cholangiography and conventional abdominal ultrasonography (both P>0.05). Conclusion:Water-injection ultrasonography can effectively improve the detection rate of residual stones in bile duct after ERCP.
3.An excerpt from 2023 International Liver Cancer Association ( ILCA) white paper on hepatocellular carcinoma risk stratification and surveillance
Chinese Journal of Digestion 2024;44(4):217-222
Major research efforts in liver cancer have been devoted to increasing the efficacy and effectiveness of surveillance for hepatocellular carcinoma (HCC). As with other cancers, surveillance programmes aim to detect tumors at an early stage, facilitate curative-intent treatment, and reduce cancer-related mortality. HCC surveillance is supported by a large randomized controlled trial in patients with chronic hepatitis B virus infection and several cohort studies in cirrhosis; however, effectiveness in clinical practice is limited by several barriers, including inadequate risk stratification, underuse of surveillance, and suboptimal accuracy of screening tests. There are several proposed strategies to address these limitations, including risk stratification algorithms and biomarkers to better identity at-risk individuals, interventions to increase surveillance, and emerging imaging- and blood-based surveillance tests with improved sensitivity and specificity for early HCC detection. Beyond clinical validation, data are needed to establish clinical utility, i. e. increased early tumor detection and reduced HCC-related mortality. If successful, these data could facilitate a precision screening paradigm in which surveillance strategies are tailored to individual HCC risk to maximise overall surveillance value. However, practical and logistical considerations must be considered when designing and implementing these validation efforts.To address these issues, the International Liver Cancer Association (ILCA) adjourned a single topic workshop on HCC risk stratification and surveillance in June 2022. Herein, we present a white paper on these topics, including the status of the field, ongoing research efforts, and barriers to the translation of emerging strategies.
4.A survey on the knowledge of Helicobacter pylori infection diagnosis and treatment among medical staff from general hospitals in Hainan Province
Hui ZHOU ; Guoning CHEN ; Yang GUO ; Yan TAN ; Cheng LAN ; Donghan WU ; Zhanliang MA ; Peng CHENG ; Cuiyi MO ; Ming WANG ; Peiyuan LI ; Ya LIN ; Yongqiang YANG ; Junling HAN ; Zhai CHEN ; Changling LIN ; Zhaona WU ; Shengxiong CHEN ; Zhengyi CHEN ; Xiaoxi HUANG
Chinese Journal of Digestion 2024;44(4):223-233
Objective:To investigate the knowledge of Sixth Chinese national consensus report on the management of Helicobacter pylori infection ( treatment excluded) (hereinafter referred to as sixth national consensus) and 2022 Chinese national clinical practice guideline on Helicobacter pylori eradication treatment (hereinafter referred to as the guideline)among medical staff from general hospitals in Hainan. Methods:From February 20 to May 7, 2023, a questionnaire survey on the diagnosis and treatment of Helicobacter pylori ( H. pylori) infection was conducted among 1 463 medical staff from 15 general hospitals in Hainan Province. The questionnaire was drawn up according to the sixth national consensus and the guideline, covering knowledge of 6 sections, induding H. pylori related diseases, detection of H. pylori, eradication, prevention and influence factors of eradication of H. pylori, etc. Chi-square test was used for statistical analysis. Results:A total of 1 463 valid questionnaires were collected with the effective responsive rate of 100.00%.The 1 463 subjects included 225 gastroenterologists and 1 238 other medical staff(including 503 physicians from other departments, 264 surgeons and 471 medical technologists and pharmacists). About 78.67%(177/225)of gastroenterologists agreed that the overall infection rate of H. pylori in China was more than 20%, the awareness rate was higher than that of other medical staff (physicians from other departments 65.41%(329/503), surgeons 61.74%(163/264), medical technologists and pharmacists 60.30%(284/471); the following datas were sorted by this position), and the difference was statistically significant ( χ2=30.97, P<0.001). About 51.11%(115/225) of gastroenterologists considered that H. pylori serological antibody test could not be used as a diagnostic method for current infection, the awareness rate was higher than that of other medical staff(22.07%(111/503), 14.02%(37/264), 12.31%(58/471)), and the difference was statistically significant( χ2 =152.66, P<0.001). Proton pump inhibitor and potassium-competitive acid blocker should be discontinued for 2 weeks, and antibiotics and bismuth should be discontinued for 4 weeks before urea breath test, and the awareness rates of gastroenterologists were higher than those of other medical staff (38.67%(87/225) vs. 23.26%(117/503), 19.70%(52/264), 18.47%(87/471); 60.89%(137/225) vs. 26.64%(134/503), 25.76%(68/264), 23.78%(112/471)), and the differences were statistically significant ( χ2 =133.70 and 165.51, both P<0.001). For refractory H. pylori infection, 98.67%(222/225)of gastroenterologists agreed with the individualized diagnosis and treatment of H. pylori infection should be guided by bacterial culture, antibiotic susceptibility test or drug resistance gene test, and the awareness rate was higher than that of other medical staff (91.85%(462/503), 93.56%(247/264), 93.21%(439/471)), and the difference was statistically significant( χ2=20.55, P=0.002). About 70.67% (159/225) of gastroenterologists recommended a bismuth containing quadruple regimen, 80.44% (181/225) supported a 10 to 14 day H. pylori eradication course, and the awareness rates were higher than other medical staff (46.92%(236/503), 33.33%(88/264), 32.91%(155/471); 67.20%(338/503), 59.09%(156/264), 53.93%(254/471)), and the differences were statistically significant ( χ2=111.25 and 59.99, both P<0.001). The understanding rates of the sixth national consensus and the guideline in gastroenterologists was 85.33% (192/225), which was higher than that of other medical staff (64.21%(323/503), 66.67%(176/264), 57.96%(273/471)), and the difference was statistically significant ( χ2=85.47, P<0.001). Conclusions:Gastroenterologists from general hospitals in Hainan Province have a better understanding of the sixth national consensus and the guideline than other medical staff. However, there is still a lack of deep understanding of the sixth national consensus and the guideline, and it is necessary to further strengthen the learning and application of the sixth national consensus and the guideline.
5.Cefuroxime-containing regimen in the treatment of Helicobacter pylori infection in patients with penicillin allergy: a single-center prospective cohort study
Yiling NI ; Qiufen YANG ; Yanjun CHEN ; Bingxin CHEN ; Weichang CHEN ; Huang FENG
Chinese Journal of Digestion 2024;44(4):234-237
Objective:To compare the eradication rate and incidence of adverse reactions between cefuroxime-containing and amoxicillin-containing bismuth quadruple regimen in the treatment of Helicobacter pylori ( H. pylori), and to evaluate the efficacy and safety of cefuroxime in the H. pylori infection patients with positive penicillin skin test results. Methods:From December 2020 to December 2021, a total of 498 patients who received initial H. pylori eradication treatment at the H. pylori Specialized Outpatient Clinic of the First Affiliated Hospital of Soochow University were selected to participate in this prospective cohort study. According to the history of penicillin allergy or positive penicillin skin test results, the patients were divided into amoxicillin group and cefuroxime group. A total of 394 patients were included in the amoxicillin group, and the treatment regimen was esomeprazole 20 mg, bismuth 220 mg, amoxicillin 1 g and clarithromycin 500 mg orally twice a day. A total of 104 patients were included in the cefuroxime group, and the treatment regimen was esomeprazole 20 mg, bismuth 220 mg, cefuroxime 500 mg and clarithromycin 500 mg orally twice a day. The treatment period was 14 days. 13C-urea breath test was conducted during 4 to 8 weeks after the treatment. The eradication rates of the 2 groups were compared by intention-to-treat (ITT) analysis and per-protocol (PP) analysis. The incidence of adverse reactions was compared between the 2 groups. Chi-square test was used for statistical analysis. Results:The results of ITT analysis and PP analysis indicated that the eradication rates of amoxicillin group were 84.3% (332/394, 95% confidence interval (95% CI) 80.6% to 87.6%) and 90.5% (332/367, 95% CI 87.2% to 93.3%), respectively, and the eradication rates of cefuroxime group were 62.5% (65/104, 95% CI 52.7% to 71.7%) and 69.1% (65/94, 95% CI 58.8% to 78.7%), respectively. The eradication rates of amoxicillin group in ITT and PP analysis were both higher than those of cefuroxime group, and the differences were statistically significant ( χ2=24.11 and 28.44, both P<0.001). The incidence of adverse reactions of amoxicillin group and cefuroxime group was 10.9% (43/394) and 14.4% (15/104), respectively, and there was no significant difference ( P>0.05). Conclusion:Cefuroxime and clarithromycin containing bismuth quadruplex regimen failed to achieve a satisfactory eradication rate in patients with H. pylori infection and penicillin allergy.
6.A survey of gastroenterologists′ knowledge and practice of the consensus and guideline of Helicobacter pylori infection (version 2022)
Yingying HAN ; Jiyan LI ; Yani ZHOU ; Jialun GUAN ; Mei LIU ; Jiazhi LIAO ; Peiyuan LI
Chinese Journal of Digestion 2024;44(4):238-244
Objective:To investigate the knowledge and practice of the Sixth Chinese national consensus report on the management of Helicobacter pylori ( H. pylori) infection (treament excluded) (referred to as sixth national consensus)and 2022 Chinese national clinical practice guideline on H. pylori eradication treatment (referred to as guideline) among gastroenterologists in China, so as to provide out relevant training in the future. Methods:A questionnaire was designed according to sixth national consensus and guideline, including knowledge and practice of sixth national consensus and guideline, and the detection, indications of eradication, the relationship between infection and gastrointestinal microbiota, and eradication of H. pylori. From November 1 to 30 in 2023, the questionnaire-based survey was conducted among 1 506 gastroenterologists from secondary and tertiary hospitals of 24 provinces, autonomous regions and municipalities in China with convenience sampling method using the "Questionnaire Star" online questionnaire platform and the questionnaire link was sent by WeChat. Descriptive methods were used for statistical analysis. Results:A total of 1 442 valid questionnaires were collected. The awareness rate of sixth national consensus and guideline of gastroenterologists was 83.7% (1 207/1 442), and 47.2% (680/1 442) had read the relevant content in detail. Urea breath test (97.4%, 1 404/1 442) was the most commonly used method for diagnosing current H. pylori infection, however, more than half of the physicians chose serological test (53.3%, 769/1 442) for the diagnosis of current infection. The common indications of H. pylori eradication could be identified by 84.3%(1 215/1 442) of gastroenterologists. The most well-known eradication regimen was bismuth quadruple regimen (98.5%, 1 421/1 442), while some physicians still believed that the standard triple regimen (31.8%, 459/1 442) and sequential regimen (21.9%, 316/1 442) were recommended by the guideline. A further 20.2% (291/1 442) frequently prescribed a triple regimen combined with gastric mucosal protectants and the awareness rate of high-dose dual regimen was 59.1% (852/1 442). Amoxicillin + clarithromycin (65.4%, 943/1 442) and amoxicillin+ furazolidone (20.1%, 290/1 442) were commonly used antibiotic combinations in bismuth quadruple therapy. Potassium-competitive acid blockers and double-dose proton pump inhibitors were commonly used in bismuth quadruple therapy by 45.4% (655/1 442) and 46.0% (664/1 442) of physicians, respectively. For patients with multiple failed eradications, furazolidone was the most commonly used antibiotic for re-eradication(71.7%, 1 034/1 442). Conclusion:The knowledge and practice of gastroenterologists on H. pylori infection in China deviates from the new consensus and guideline, and more publicity and training should be carried out in future to improve the ability of gastroenterologists to standardise the diagnosis and treatment of H. pylori infection.
7.A comparative study on flat-tipped injection needle and conical catheter in the treatment of hydrodynamic releasing of fecal calculus incarceration in the colonic diverticulum (with video)
Yanjuan LIN ; Yaokui HUANG ; Xiaozhong WANG
Chinese Journal of Digestion 2024;44(4):245-249
Objective:To explore the validity and safety of flat-tipped injection needle and conical catheter these 2 instruments in the hydrodynamic releasing treatment of fecal calculus incarceration in the colonic diverticulum.Methods:From 1 May 2022 to 31 July 2023, 77 patients with fecal calculus incarceration in colonic diverticulum detected by colonscopy at the Endoscope Center of Shantou Central Hospital were prospectively selected. According to the random number table method, 77 patients were randomly divided into the flat-tipped injection needle group (39 cases, 51 fecal stone embedded) and the conical catheter group (38 cases, 49 fecal stone embedded). The successful rate of fecal stone releasing, operation time and complications of 2 groups were observed. Independent samples t test and chi-square test were used for statistical analysis. Results:The successful rate of fecalith releasing of flat-tipped injection needle group was higher than that of the conical catheter group (100.0%, 51/51 vs. 83.7%, 41/49), and the difference was statistically significant ( χ2=9.05, P=0.002). There was no significant difference in the operation time of successful cases between the flat-tipped injection needle group and the conical catheter group ((5.7±1.2) s vs. (5.9±0.8) s, P>0.05). There were no cases of intraoperative or postoperative bleeding or perforation in the process of fecal stone releasing in both groups. Missed submucosal injection occurred in 4 cases of the flat-tipped injection needle group and occurred in three cases of the conical catheter group, and there was no significant difference in the incidence of complications between the 2 groups ( P>0.05). Conclusion:Both instruments are effective and safe in the hydrodynamic releasing treatment of fecal calculus incarceration in the colonic diverticulum, and the success rate of flat-tipped injection needle is higher than that of conical catheter.
8.A study on the characteristics of high-resolution anorectal manometry in patients with functional anorectal pain
Hongyan ZHENG ; Fan LIU ; Mengyang SUN ; Jin LIU ; Chengjing FENG ; Min NI
Chinese Journal of Digestion 2024;44(4):250-256
Objective:To explore the characteristics of anorectal motility and sensation in patients with functional anorectal pain (FAP) by high-resolution anorectal manometry (HR-ARM) .Methods:The clinical data of 81 FAP patients (FAP group) who underwent HR-ARM in Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine from January 1, 2020 to January 31, 2022 were retrospectively collected, and 80 healthy volunteers were recruited as healthy control group during the same period. The HR-ARM characteristics were compared between FAP group and the healthy control group, between the patients with different genders in the FAP group, the patients with different subtypes (proctalgia fugax, levator syndrome, and non-specific FAP) in the FAP group, which included anal resting pressure, anal squeeze pressure, rectal pressure during simulated defecation, anal residual pressure during simulated defecation, paradoxical contractions, initial sensation threshold, defecation threshold, defecation urgency threshold, and tolerance threshold. Visual analogue scale (VAS) was used to assess the pain level of the patients in the FAP group, and Spearman correlation analysis was used to analyze the correlation between VAS and HR-ARM characteristics. Independent sample t-test, least significant difference test, Tamhane′s T2 test, and Mann-Whitney U test were used for statistical analysis. Results:The anal resting pressure, anal squeeze pressure, anal residual pressure during simulated defecation, defecation urgency threshold, and tolerance threshold of the FAP group were all lower than those of the healthy control group ((59.56±24.71) mmHg (1 mmHg=0.133 kPa) vs. (81.94±15.87) mmHg, (119.04±46.94) mmHg vs.(154.62±37.95) mmHg, 59.00(40.75, 80.95) mmHg vs. 83.10(61.78, 94.30) mmHg, 70.00(55.00, 90.00) mL vs. 85.00(60.00, 110.00) mL, 105.00(87.50, 150.00) mL vs. 140.00(100.00, 180.00) mL), and the differences were all statistically significant ( t=-6.83 and -5.29, Z=-4.12, -3.12 and -2.82; all P<0.01).The rectal pressure during simulated defecation of male patients in the FAP group was higher than that of males in the healthy control group, and the defecation urgency threshold was lower than that of males in the healthy control group (42.40(29.60, 57.95) mmHg vs. 31.10(25.85, 36.80) mmHg, 80.00(62.50, 107.50) mL vs. 92.00(81.00, 140.00) mL), and the differences were statistically significant ( Z=-1.99 and -2.53, both P<0.05). The anal resting pressure, anal squeeze pressure, anal residual pressure during simulated defecation, defecation urgency threshold, and tolerance threshold of female patients in FAP group were all lower than those of female in the healthy control group ((55.67±21.61) mmHg vs. (87.04±15.54) mmHg, (102.70±37.09) mmHg vs. (155.98±31.44) mmHg, 52.55(40.53, 67.48) mmHg vs. 83.10(61.10, 94.50) mmHg, 60.00(52.50, 81.50) mL vs. 80.00(60.00, 100.00) mL, 101.00(80.00, 128.75) mL vs. 120.00(94.00, 155.00) mL), and the differences were statistically significant ( t=-8.77 and -8.16, Z=-4.57, -2.24 and -2.14; all P<0.05). The anal resting pressure, anal squeeze pressure, anal residual pressure during simulated defecation, incidence rate of paradoxical contractions, defecation urgency threshold, and tolerance threshold of female patients in FAP group were all lower than those of male patients in FAP group ((55.67±21.61) mmHg vs. (68.28±29.16) mmHg, (102.70±37.09) mmHg vs. (155.62±46.66) mmHg, 52.55(40.53, 67.48) mmHg vs. 79.00(59.55, 99.25) mmHg, 28.6%(16/56) vs. 68.0%(17/25), 44.00(35.00, 60.00) mL vs. 60.00(45.00, 70.00) mL, 60.00(52.50, 81.50) mL vs. 80.00(62.50, 107.50) mL), and the differences were statistically significant( t=2.17 and 5.47, Z=-2.96, χ2=11.10, Z=-2.93 and -2.34; all P<0.05). The anal squeeze pressure of patients with proctalgia fugax subtype was higher than that of patients with levator syndrome subtype ((140.19±56.51) mmHg vs. (80.56±30.79) mmHg), and the tolerance threshold was lower than that of patients with non-specific FAP subtype ((87.86±17.80) mL vs. (125.14±48.31) mL), and the differences were statistically significant ( t=2.35 and 2.02, both P<0.05). The results of Spearman correlation analysis showed that VAS was negatively correlated with anal resting pressure, anal squeeze pressure, and defecation urgency threshold in the patients of the FAP group ( r= -0.28, -0.23, and -0.24; all P< 0.05). Conclusion:The presence of anorectal dismotility and sensory dysfunction in FAP may be related to pelvic floor muscle abnormalities, muscle coordination disorders during defecation, and rectal hypersensitivity.
9.The predictive value of systemic immune-inflammatory response index combined with tumor burden score in the prognosis of patients after radical resection for intrahepatic cholangiocarcinoma
Hao YUAN ; Haofeng ZHANG ; Qingshan LI ; Guan HUANG ; Zhenwei YANG ; Pengyu CHEN ; Zuochao QI ; Chenxi XIE ; Bo MENG ; Haibo YU
Chinese Journal of Digestion 2024;44(4):257-265
Objective:To explore the prognostic value of systemic immune-inflammatory index(SII)combined with tumor burden score (TBS) (hereinafter referred to as STS) in patients with intrahepatic cholangiocarcinoma (ICC) after radical resection, and to construct a nomogram model.Methods:The clinical data (including the degree of tumor differentiation, vascular cancer thrombus, and lymph node metastasis, etc.) of 258 ICC patients who received radical resection at People′s Hospital of Zhengzhou University (170 cases, training set) and Cancer Hospital of Zhengzhou University (88 cases, validation set) from January 1, 2016 to January 31, 2020 were retrospectively analyzed and graded by SII, TBS and STS. Multivariate Cox regression analysis were used to identify independent factors affecting the prognosis of patients with ICC. Kaplan-Meier survival curve and receiver operating characteristic curve (ROC) were drawn to evaluate the predictive efficiency of SII, TBS and STS in the overall survival of patients with ICC after radical resection. The nomogram prediction model was constructed and evaluate the performance of nomogram model using consistency index (C-index) and calibration curve.Results:Among 170 ICC patients in the training set, there were 106 cases of SII grade 1 and 64 cases of SII grade 2; 137 cases of TBS grade 1 and 33 cases of TBS grade 2; and 98 cases of STS grade 1, 47 cases of STS grade 2, and 25 cases of STS grade 3. Among 88 ICC patients in the validation set, there were 33 cases of SII grade 1 and 55 cases of SII grade 2; 66 cases of TBS grade 1 and 22 cases of TBS grade 2; and 30 case of STS grade 1, 39 cases of TBS grade 2, and 19 cases of TBS grade 3.The multivariate Cox regression analysis showed that tumor differentiation degree (highly differentiated vs. moderately differentiated HR=0.157, 95% confidence interval(95% CI) 0.045 to 0.546, highly differentiated vs. poorly differentiated HR=0.452, 95% CI 0.273 to 0.750), STS (grade 3 vs. grade 2 HR=1.966, 95% CI 1.148 to 3.469; grade 3 vs. grade 1 HR=1.405, 95% CI 0.890 to 2.216), vascular cancer thrombus ( HR=2.006, 95% CI 1.313 to 3.066), nerve invasion ( HR=1.865, 95% CI 1.221 to 2.850), and lymph node metastasis ( HR=1.802, 95% CI 1.121 to 2.896) were independent influencing factors of overall survival in ICC patients after radical resection (all P<0.05). The Kaplan-Meier survival curve showed that SII, TBS, and STS were independent influencing factors of overall survival in ICC patients (all P<0.05). The results of ROC analysis showed that the areas under the curve of SII, TBS and STS in predicting overall survival of ICC patients after radical resection were 0.566 (95% CI 0.479 to 0.652), 0.585 (95% CI 0.499 to 0.672), and 0.657 (95% CI 0.522 to 0.692), respectively. Tumor differentiation, vascular tumor thrombus, nerve invassion, lymph node metastasis, and STS were included to constract the nomogram model. The C-indexes of the training set and validation set based on the nomogram model were 0.792 (95% CI 0.699 to 0.825) and 0.776 (95% CI 0.716 to 0.833), respectively. The calibration curves of the survival rate of the training set and the validation set were close to the reference lines, and the nomogram model had better predictive ability in both the training set and the validation set. Conclusions:Preoperative STS grading is an effective and practical predictor of overall survival in ICC patients after radical section. Compared with SII and TBS alone, it has better predictive value for the prognosis of patients with ICC.
10.A study on the NORAD-induced autophagy promotes oxaliplatin resistance in adenocarcinoma of the esophagogastric junction
Shoumiao LI ; Zhiqiang LIU ; Heng CAO ; Zhiyong NIE ; Hui LI ; Baozhong LI
Chinese Journal of Digestion 2024;44(4):266-273
Objective:To investigate the effects and molecular mechanism of non-coding RNA-activated DNA damage(NORAD)induced autophagy on oxaliplatin resistance in adenocarcinoma of esophagogastric junction (AEG).Methods:Four pairs of surgical samples of AEG and para-carcinoma normal tissues from patients with advance AEG treated in Anyang Tumor Hospital from January to June 2023 were collected. The expression of NORAD in AEG and para-carcinoma tissues was analyzed by long non-coding RNA microarray chip. The primary tumor cell line of AEG (PDC) was derived from fresh AEG tissues. Oxaliplatin-resistant cell lines of PDC and AEG cell line OE19 (PDC-R and OE19-R) were established. NORAD expression knockdown PDC-R and OE19 cell lines (shNORAD PDC-R and shNORAD OE19-R) were prepared by transfection. The target of NORAD, the correlation and interaction between microRNA-433-3p (miR-433-3p) and NORAD were predicted using Starbase v3.0 and DIANA-lncBase v3.0. PDC, PDC-R, OE19 and OE19-R cells were co-transfected with miR-144-3p and wild-type NORAD (NORAD-WT) or mutant NORAD (NORAD-Mut) plasmid, respectively. Dual-luciferase reporter assay was used to verify the correlation between NORAD and miR-433-3p. The expression levels of NORAD and miR-433-3p in normal gastric mucosal cell line GES-1 and AEG cell lines PDC, PDC-R, shNORAD PDC-R, OE19, OE19-R and shNORAD OE19-R were detected by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). The expression of p62 protein and microtubule-associated protein 1 light chain 3B-Ⅱ (LC3B-Ⅱ) was determined by Western blotting. The half inhibitory concentration (IC 50) of PDC, PDC-R, shNORAD PDC-R, OE19, OE19-R and shNORAD OE19-R cells was measured by cell counting kit-8 (CCK-8) assay. Independent sample t-test was used for statistical analysis. Results:The results of microarray analysis showed that NORAD was significantly up-regulated in AEG compared with that in para-carcinoma tissues (fold change≥2.0, P<0.05). Bioinformatics studies found that miR-433-3p was the potential target of NORAD. The results of dual-luciferase reporter assay indicated that the relative luciferase activity of the NORAD-WT group was lower than that of NORAD-Mut group in PDC and PDC-R cells (0.441±0.104 vs. 0.928±0.204, 0.449±0.112 vs. 0.947±0.201), and the differences were statistically significant ( t=-14.74 and -14.94, both P<0.001). The results of dual-luciferase reporter assay of OE19 and OE19-R cell lines were the same as those of PDC cell lines. The results of qRT-PCR showed that the expression of NORAD in GES-1 cells (1.016±0.213) was lower than that of PDC cells (2.194±0.322) and PDC-R cells (4.040±0.336), and the differences were statistically significant ( t=-14.94 and -37.21, both P<0.001). Furthermore, the expression level of NORAD in PDC was also found to be lower than that in PDC-R cells, and the difference was statistically significant ( t=-19.43, P<0.001). Additionally, shNORAD PDC-R cells exhibited lower expression level of NORAD (0.290±0.165) compared with PDC-R cells, and the difference was statistically significant ( t=-49.05, P<0.001). The expression level of miR-433-3p in GES-1 cells (1.017±0.248) was higher than that in PDC cells (0.470±0.156) and PDC-R cells (0.203±0.045), and the differences were statistically significant ( t=9.15 and 15.85, both P<0.001). Moreover, the expression level of miR-433-3p was found to be higher in PDC cells compared with PDC-R cells, and the difference was statistically significant ( t=8.11, P<0.001). Additionally, the expression level of miR-433-3p in shNORAD PDC-R cells (0.699±0.256) was also higher than that in PDC-R cells ( t=9.37, P<0.001). The results of Western blotting showed that the expression of LC3B-Ⅱ in PDC-R was higher than that in PDC cells (0.426±0.060 vs. 0.212±0.041), the expression of LC3B-Ⅱ in shNORAD PDC-R cells (0.155±0.029) was lower than that in PDC cells, and the differences were statistically significant ( t=8.70 and -79.45, both P<0.001). However the expression of p62 protein in each cell line showed an opposite trend, with a lower relative expression in PDC-R than PDC (0.205±0.031 vs. 0.311±0.400), and the expression in shNORAD PDC-R (0.504±0.084) was higher than that in PDC, and the differences were statistically significant ( t=-31.19 and 62.80, both P<0.001). The expression patterns of NORAD, miR-433-3p, LC3B-Ⅱ and p62 proteins in OE19, OE19-R and shNORAD OE19-R cells were similar to those in PDC. The results of CCK-8 assessment of target cell viability showed that the IC 50 values of PDC, PDC-R and shNORAD PDC-R cell lines were 14.28, 22.27 and 2.51 μg/mL, respectively; and the IC 50 values of OE19, OE19-R and shNORAD PDC-R cell lines were 3.95, 8.12 and 1.89 μg/mL, respectively. Conclusions:NORAD is highly expressed in AEG tissues and cells. NORAD is overexpressed in oxaliplatin-resistant cell lines and increase the autophagy activity of cells. After NORAD is knockdown, autophagy activity is inhibited and the sensitivity of AEG cells to oxaliplatin is significantly enhanced.

Result Analysis
Print
Save
E-mail