1.Dual activation of GCGR/GLP1R signaling ameliorates intestinal fibrosis via metabolic regulation of histone H3K9 lactylation in epithelial cells.
Han LIU ; Yujie HONG ; Hui CHEN ; Xianggui WANG ; Jiale DONG ; Xiaoqian LI ; Zihan SHI ; Qian ZHAO ; Longyuan ZHOU ; JiaXin WANG ; Qiuling ZENG ; Qinglin TANG ; Qi LIU ; Florian RIEDER ; Baili CHEN ; Minhu CHEN ; Rui WANG ; Yao ZHANG ; Ren MAO ; Xianxing JIANG
Acta Pharmaceutica Sinica B 2025;15(1):278-295
Intestinal fibrosis is a significant clinical challenge in inflammatory bowel diseases, but no effective anti-fibrotic therapy is currently available. Glucagon receptor (GCGR) and glucagon-like peptide 1 receptor (GLP1R) are both peptide hormone receptors involved in energy metabolism of epithelial cells. However, their role in intestinal fibrosis and the underlying mechanisms remain largely unexplored. Herein GCGR and GLP1R were found to be reduced in the stenotic ileum of patients with Crohn's disease as well as in the fibrotic colon of mice with chronic colitis. The downregulation of GCGR and GLP1R led to the accumulation of the metabolic byproduct lactate, resulting in histone H3K9 lactylation and exacerbated intestinal fibrosis through epithelial-to-mesenchymal transition (EMT). Dual activating GCGR and GLP1R by peptide 1907B reduced the H3K9 lactylation in epithelial cells and ameliorated intestinal fibrosis in vivo. We uncovered the role of GCGR/GLP1R in regulating EMT involved in intestinal fibrosis via histone lactylation. Simultaneously activating GCGR/GLP1R with the novel dual agonist peptide 1907B holds promise as a treatment strategy for alleviating intestinal fibrosis.
2.Quantitative evaluation of left ventricular myocardial work in patients with systemic scleroderma using pressure-strain loop
Sen MAO ; Yuping JIANG ; Youdong HAN ; Kaihua LIU ; Yue YIN ; Xuyu HE ; Luping ZHAO
Chinese Journal of Rheumatology 2025;29(2):133-138
Objective:To evaluate left ventricular systolic function in patients with systemic scleroderma (SSc) with normal left ventricular ejection fraction using pressure-strain loop (PSL) .Methods:To collect 30 patients with SSc who were treated in the Rheumatology and Immunology Department of Jining Medical University from January 2022 to March 2024 as the observation group, 30 healthy volunteers were selected as the control group after 1:1 matching with the observation group according to the age ±3 years old and the same gender. Clinical and ultrasound data were collected, PSL was used to evaluate and compare the differences between the two groups in left ventricular longitudinal strain (GLS), global work index (GWI), global useful work (GCW), global useless work (GWW) and global work efficiency (GWE), and the statistically significant variables were analyzed by multivariate logistic regression to analyze the independent predictors of early left ventricular function impairment in patients with SSc,and constructed receiver operating characteristic (ROC) curve to analyze the predictive value of GLS, GWI, GCW, GWW and GWE in early left ventricular function impairment in SSc patients.Results:Compared with the control group, the observation group GLS,GWI, GCW and GWE decreased( P<0.05), while the GWW increased( P<0.05). Multivariate logistic regression analysis showed that GLS[ OR(95% CI)=0.51(0.26, 1.02), P=0.055]、GWI[ OR(95% CI)=1.00(0.99, 1.01), P=0.969)、GCW[ OR(95% CI)=1.00(0.99, 1.02), P=0.771]、GWW[ OR(95% CI)=0.90(0.81, 1.01), P=0.075]and GWE[ OR(95% CI)=0.02(0.00, 0.55), P=0.022], in which GWE had the highest significance in predicting left ventricular myocardial work in SSc patients. ROC curve showed that compared with GLS, GWI, GCW and GWW, the area under GWE curve (0.953) was the largest, and the sensitivity of GWE≤94% to predict myocardial damage in SSc patients was 80.0%, and the specificity was 93.3%. The results of the repeatability test showed that the reproducibility of the intra-observer and inter-observer measurements was good. Conclusion:The PSL provides a new method for the quantitative assessment of early left ventricular systolic function impairment in patients with SSc, and GWE can be used as a sensitive index to predict early left ventricular systolic function impairment in patients with SSc.
3.Clinical efficacy and safety of laparoscopic abdominoperineal resection with pelvicperitoneum colsure for low rectal cancer:a meta-analysis
Fei GAO ; Bin HAN ; Hao-yong ZHAO ; Yong-han ZHANG ; Mao-sen GUO ; Hao WANG ; Shang-jie GUO
Chinese Journal of Current Advances in General Surgery 2025;28(4):271-278
Objective:To investigatetheclinicalefficacy and satetyoflaparoscopic abdominoperineal resection with pelvicperitoneum colsure for low rectal cancer.Methods:A comprehesive search was conducted across multiple da-tabases,including the Cochrane Library、PubMed、Embase、CBM、VIP、CNKI、and WanFang Data,focusing on studies re-lated to pelvic peritoneum colsure(PPC)-oriented laparoscopic abdominoperineal resection from database inception to July,2024.Then,meta-analysis was performed using RevMan 5.3 software.Results:A total of 12 studies involving 999 patients were included.The results showed that there was no significant difference in intraoperative blood loss.The laparoscopic pelvicperitoneum colsure takes a longer time,with a statistically significant difference(WMD=12.37,95%CI=2.27~22.46,P=0.02),but the postoperative exhaust time and hospitalization time are shorter,with a statistically significant difference(WMD=0.40,95%CI=0.07~0.72,P=0.02;WMD=-2.36,95%CI=-3.33~-1.38,P<0.00001).In terms of postoperative complications,the overall complication rate was higher in the group that did not undergo pelvic-peritoneum colsure,with a statistically significant difference(OR=0.12,95%CI=0.08~0.18,P<0.00001).The incidence of postoperative intestinal obstruction,perineal incisional hernia,pelvic effusion infection,and radiation enteritis was higher,and the differences were statistically significant(OR=0.24,95%CI=0.13~0.45,P<0.00001,OR=0.23,95%CI=0.11~0.49,P=0.0001,OR=0.27,95%CI=0.14~0.51,P<0.0001,OR=0.24,95%CI:0.07~0.81,P=0.03).Conclusion:In lapa-roscopic abdominoperineal resection,closing the pelvicperitoneum has lower postoperative complications,shorter post-operative exhaust time and hospitalization time,and longer operation time,which has better clinical efficacy and safety.
4.Risk prediction of demoralization syndrome in patients with oral cancer.
Liyan MAO ; Xixi YANG ; Xiaoqin BI ; Min LIU ; Chongyang ZHAO ; Zuozhen WEN
West China Journal of Stomatology 2025;43(3):395-405
OBJECTIVES:
This study aimed to construct a risk prediction model for the occurrence of the demora-lization syndrome in patients with oral cancer and provide a scientific basis for the prevention of this syndrome in patients with oral cancer and the development of personalized care programs.
METHODS:
A total of 486 patients with oral cancer in West China Hospital of Stomatology of Sichuan University and Sun Yat-sen Memorial Hospital of Sun Yat-sen University from 2024 March to July were selected by convenience sampling. We integrated clinical data and evidence from previous studies to identify the key variables affecting the demoralization syndrome in patients with oral cancer. The 486 patients were divided into a training set and a validation set in an 8∶2 ratio. A clinical risk prediction model was established based on the individual data of 365 patients in the development cohort. Through least absolute shrinkage and selection operator (LASSO) regression, a moderate to severe risk prediction model of demoralization syndrome in oral cancer was constructed, and a clinical machine-learning nomogram was constructed. Bootstrap resampling was used for internal validation. The data of 121 patients in the validation cohort were externally validated.
RESULTS:
The incidence of the demoralization syndrome in patients with oral cancer was 405 cases (83.3%), of which 279 cases (57.4%) were mild, 176 cases (36.2%) were moderate, and 31 cases (6.4%) were severe. The core model, including patient education level, disease understanding, and MDASI-HN score, was used to predict the risk of outcome. Internal validation of the model yielded C statistic of 0.783 6 (95% CI: 0.78-0.87), beta of 0.843 4, and calibration intercept of -0.040 6. Through external validation, the validation set C statistic was 0.80 (95%CI: 0.71-0.87), beta was 0.80, and calibration intercept was -0.08.
CONCLUSIONS
Our risk prediction mo-del of the demoralization syndrome in patients with oral cancer performed robustly in validation cohorts of different nur-sing environments. The model has good correction and good discrimination and can be used as an evaluation and prediction item at admission.
Humans
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Mouth Neoplasms/complications*
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Male
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Female
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Nomograms
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Middle Aged
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Syndrome
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Aged
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Adult
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Risk Factors
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Risk Assessment
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Machine Learning
6.Predictive value of dose surface histogram for acute radiation proctitis induced by image guided radiotherapy for cervical cancer
Qing-xiao LIU ; Yue-xiang ZHU ; Wei WEI ; Long TIAN ; Song-lin YANG ; Zheng WANG ; Yu-sen ZHAO ; Su-li WANG ; Mao-ye CHANG
Chinese Medical Equipment Journal 2025;46(3):48-53
Objective To explore the predictive value of dose surface histogram(DSH)in image guided radiotherapy(IGRT)for radiotherapy-induced acute radiation proctitis(ARP)in cervical cancer(CCA).Methods Totally 380 patients with CCA IGRT admitted to some hospital from May 2019 to May 2023 were selected prospectively and randomly divided into a control group(n=1 80)and an experimental group(n=200).The patients in the 2 groups were followed up and the incidence rates of ARP were counted,and rectal dose distribution was evaluated using dose volume histogram(DVH)in the control group and DSH in the experimental group.The predictive values of DVH and DSH for ARP were evaluated and compared using ROC curves.Statistical analysis was performed using SPSS 21.0 software.Results The two groups did not have statistically significant difference in the incidence rate of ARP(P>0.05),while there were significant differences in the evaluation indicators of the rectal dose distribution(P<0.05).V40,V50,S40 and S50 proved to have low predictive values for grade Ⅰ-Ⅳ ARP with AUC 0.700(P<0.05);V60 and S60 had moderate predictive values for grade Ⅰ-Ⅳ ARP with AUC greater than 0.700 and less than or equal to 0.900(P<0.05);V70,V78,S70 and S7s showed high predictive values for grade Ⅰ-Ⅳ ARP with AUC higher than 0.900(P<0.05).Delong's test results indicated that DVH and DSH had no significant differences in AUC when used to predict gradeⅠ-Ⅳ ARP(allP>0.05).Conclusion DSH is essentially the same as DVH when used for the prediction of grade Ⅰ-Ⅳ ARP due to CCA IGRT,and thus can be used for the supplementation and optimization of radiotherapy planning systems.[Chinese Medical Equipment Journal,2025,46(3):48-53]
7.Predictive value of dose surface histogram for acute radiation proctitis induced by image guided radiotherapy for cervical cancer
Qing-xiao LIU ; Yue-xiang ZHU ; Wei WEI ; Long TIAN ; Song-lin YANG ; Zheng WANG ; Yu-sen ZHAO ; Su-li WANG ; Mao-ye CHANG
Chinese Medical Equipment Journal 2025;46(3):48-53
Objective To explore the predictive value of dose surface histogram(DSH)in image guided radiotherapy(IGRT)for radiotherapy-induced acute radiation proctitis(ARP)in cervical cancer(CCA).Methods Totally 380 patients with CCA IGRT admitted to some hospital from May 2019 to May 2023 were selected prospectively and randomly divided into a control group(n=1 80)and an experimental group(n=200).The patients in the 2 groups were followed up and the incidence rates of ARP were counted,and rectal dose distribution was evaluated using dose volume histogram(DVH)in the control group and DSH in the experimental group.The predictive values of DVH and DSH for ARP were evaluated and compared using ROC curves.Statistical analysis was performed using SPSS 21.0 software.Results The two groups did not have statistically significant difference in the incidence rate of ARP(P>0.05),while there were significant differences in the evaluation indicators of the rectal dose distribution(P<0.05).V40,V50,S40 and S50 proved to have low predictive values for grade Ⅰ-Ⅳ ARP with AUC 0.700(P<0.05);V60 and S60 had moderate predictive values for grade Ⅰ-Ⅳ ARP with AUC greater than 0.700 and less than or equal to 0.900(P<0.05);V70,V78,S70 and S7s showed high predictive values for grade Ⅰ-Ⅳ ARP with AUC higher than 0.900(P<0.05).Delong's test results indicated that DVH and DSH had no significant differences in AUC when used to predict gradeⅠ-Ⅳ ARP(allP>0.05).Conclusion DSH is essentially the same as DVH when used for the prediction of grade Ⅰ-Ⅳ ARP due to CCA IGRT,and thus can be used for the supplementation and optimization of radiotherapy planning systems.[Chinese Medical Equipment Journal,2025,46(3):48-53]
8.Clinical efficacy and safety of laparoscopic abdominoperineal resection with pelvicperitoneum colsure for low rectal cancer:a meta-analysis
Fei GAO ; Bin HAN ; Hao-yong ZHAO ; Yong-han ZHANG ; Mao-sen GUO ; Hao WANG ; Shang-jie GUO
Chinese Journal of Current Advances in General Surgery 2025;28(4):271-278
Objective:To investigatetheclinicalefficacy and satetyoflaparoscopic abdominoperineal resection with pelvicperitoneum colsure for low rectal cancer.Methods:A comprehesive search was conducted across multiple da-tabases,including the Cochrane Library、PubMed、Embase、CBM、VIP、CNKI、and WanFang Data,focusing on studies re-lated to pelvic peritoneum colsure(PPC)-oriented laparoscopic abdominoperineal resection from database inception to July,2024.Then,meta-analysis was performed using RevMan 5.3 software.Results:A total of 12 studies involving 999 patients were included.The results showed that there was no significant difference in intraoperative blood loss.The laparoscopic pelvicperitoneum colsure takes a longer time,with a statistically significant difference(WMD=12.37,95%CI=2.27~22.46,P=0.02),but the postoperative exhaust time and hospitalization time are shorter,with a statistically significant difference(WMD=0.40,95%CI=0.07~0.72,P=0.02;WMD=-2.36,95%CI=-3.33~-1.38,P<0.00001).In terms of postoperative complications,the overall complication rate was higher in the group that did not undergo pelvic-peritoneum colsure,with a statistically significant difference(OR=0.12,95%CI=0.08~0.18,P<0.00001).The incidence of postoperative intestinal obstruction,perineal incisional hernia,pelvic effusion infection,and radiation enteritis was higher,and the differences were statistically significant(OR=0.24,95%CI=0.13~0.45,P<0.00001,OR=0.23,95%CI=0.11~0.49,P=0.0001,OR=0.27,95%CI=0.14~0.51,P<0.0001,OR=0.24,95%CI:0.07~0.81,P=0.03).Conclusion:In lapa-roscopic abdominoperineal resection,closing the pelvicperitoneum has lower postoperative complications,shorter post-operative exhaust time and hospitalization time,and longer operation time,which has better clinical efficacy and safety.
9.Quantitative evaluation of left ventricular myocardial work in patients with systemic scleroderma using pressure-strain loop
Sen MAO ; Yuping JIANG ; Youdong HAN ; Kaihua LIU ; Yue YIN ; Xuyu HE ; Luping ZHAO
Chinese Journal of Rheumatology 2025;29(2):133-138
Objective:To evaluate left ventricular systolic function in patients with systemic scleroderma (SSc) with normal left ventricular ejection fraction using pressure-strain loop (PSL) .Methods:To collect 30 patients with SSc who were treated in the Rheumatology and Immunology Department of Jining Medical University from January 2022 to March 2024 as the observation group, 30 healthy volunteers were selected as the control group after 1:1 matching with the observation group according to the age ±3 years old and the same gender. Clinical and ultrasound data were collected, PSL was used to evaluate and compare the differences between the two groups in left ventricular longitudinal strain (GLS), global work index (GWI), global useful work (GCW), global useless work (GWW) and global work efficiency (GWE), and the statistically significant variables were analyzed by multivariate logistic regression to analyze the independent predictors of early left ventricular function impairment in patients with SSc,and constructed receiver operating characteristic (ROC) curve to analyze the predictive value of GLS, GWI, GCW, GWW and GWE in early left ventricular function impairment in SSc patients.Results:Compared with the control group, the observation group GLS,GWI, GCW and GWE decreased( P<0.05), while the GWW increased( P<0.05). Multivariate logistic regression analysis showed that GLS[ OR(95% CI)=0.51(0.26, 1.02), P=0.055]、GWI[ OR(95% CI)=1.00(0.99, 1.01), P=0.969)、GCW[ OR(95% CI)=1.00(0.99, 1.02), P=0.771]、GWW[ OR(95% CI)=0.90(0.81, 1.01), P=0.075]and GWE[ OR(95% CI)=0.02(0.00, 0.55), P=0.022], in which GWE had the highest significance in predicting left ventricular myocardial work in SSc patients. ROC curve showed that compared with GLS, GWI, GCW and GWW, the area under GWE curve (0.953) was the largest, and the sensitivity of GWE≤94% to predict myocardial damage in SSc patients was 80.0%, and the specificity was 93.3%. The results of the repeatability test showed that the reproducibility of the intra-observer and inter-observer measurements was good. Conclusion:The PSL provides a new method for the quantitative assessment of early left ventricular systolic function impairment in patients with SSc, and GWE can be used as a sensitive index to predict early left ventricular systolic function impairment in patients with SSc.
10.A nomogram model for differentiating gastric schwannoma from gastric stromal tumor based on CT imaging features
Luping ZHAO ; Haoran LU ; Yuhong WANG ; Jingjing XU ; Zhanguo SUN ; Yueqin CHEN ; Zecan WENG ; Sen MAO
Chinese Journal of Postgraduates of Medicine 2024;47(7):624-630
Objective:To construct a nomogram model for differentiating gastric schwannoma (GS) from gastric stromal tumor (GST) (diameters 2 to 5 cm) based on CT imaging features before surgery.Methods:The clinical and imaging data of 49 patients with GS and 240 patients with GST in the Affiliated Hospital of Jining Medical University from July 2009 to April 2023 and Guangdong Provincial People′s Hospital from June 2017 to September 2022 were analyzed retrospectively. The independent factors for differentiating GS from GST were obtained by multivariate Logistic regression analysis. The nomogram model was constructed by R4.3.1 software. The efficacy of the nomogram model for differentiating GS from GST was evaluated by the receiver operating characteristics (ROC) curve, and calibration curve and decision curve analysis were used to evaluate the predictive efficacy and clinical application value of the nomogram model.Results:There were no statistical differences in the clinical symptom rate, calcification rate, ulcer rate, tumor vessel rate, ratio of long diameter to short diameter and CT value difference during the arterial and nonenhanced phases (CTV A-N) between GS patients and GST patients ( P>0.05). The proportion of female, incidence of lesions located in central or lower part of stomach, extraluminal or mixed growth rate, tumor-associated lymph node rate, strong enhancement rate, CT value difference during the portal and nonenhanced phases (CTV P-N), CT value difference during the delayed and nonenhanced phases (CTV D-N), CT value difference during the portal and arterial phases (CTV P-A) and CT value difference during the delayed and portal phases (CTV D-P) in GS patients were significantly higher than those in GST patients: 75.51% (37/49) vs. 58.33% (140/240), 85.71% (42/49) vs. 54.17% (130/240), 75.51% (37/49) vs. 45.00% (108/240), 44.90% (22/49) vs. 5.42% (13/240), 51.02% (25/49) vs. 27.08% (65/240), 32.0 (26.0, 43.5) HU vs. 29.0 (22.0, 37.7) HU, (44.59 ± 13.46) HU vs. (32.94 ± 12.47) HU, 20.0 (11.5, 25.0) HU vs. 10.0 (5.0, 17.0) HU and 9.0 (6.0, 12.0) HU vs. 4.0 (-2.7, 7.0) HU, the age, irregular shape rate, cystic degeneration rate and heterogeneous enhancement rate were significantly lower than those in GST patients: (58.12 ± 12.59) years old vs. (62.05 ± 11.22) years old, 16.33% (8/49) vs. 38.33% (92/240), 18.37% (9/49) vs. 51.25% (123/240) and 34.69% (17/49) vs. 56.25% (135/240), and there were statistical differences ( P<0.05 or<0.01). Multivariate Logistic regression analysis result showed that location, cystic degeneration, tumor-associated lymph node, CTV P-A and CTV D-P were the independent factors for differentiating GS from GST ( OR= 3.599, 0.201, 19.031, 1.124 and 1.160; 95% CI 1.184 to 10.938, 0.070 to 0.578, 6.159 to 58.809, 1.066 to 1.185 and 1.094 to 1.231; P<0.05 or<0.01). The nomogram model for differentiating GS from GST was constructed based on location, cystic degeneration, tumor-associated lymph node, CTV P-A and CTV D-P. The area under curve of the nomogram model for differentiating GS from GST was 0.924 (95% CI 0.887 to 0.951). The calibration curve analysis result showed that there was a good agreement between the predicted GS curve and the actual GS curve (the mean absolute error was 0.033). The result of the Hosmer-Lemeshow goodness-of-fit test indicated that the calibration of the nomogram model was appropriate ( χ2 = 2.52, P = 0.961). The clinical decision curve analysis result showed that when the threshold for the nomogram model for differentiating the two tumors was>0.03, the nomogram yielded more net benefits than the "all patients treated as GS" or "all patients treated as GST" scenarios. Conclusions:The nomogram model based on CT imaging features can be used to differentiate GS from GST before surgery.

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