1.Role of SHP2 in development of colitis-associated colon cancer and colorectal cancer and its potential as a therapeutic target
Hao ZHANG ; Qingfei DIAO ; Jianchun FAN ; Meng LI ; Juming JIA ; Chunbaixue YANG ; Xueliang WU
Chinese Journal of Comparative Medicine 2025;35(1):163-171
Colorectal cancer(CRC)is one of the most common malignant life-threatening tumors,with serious impacts on patient quality of life.Src homology 2 domain-containing protein tyrosine phosphatase(SHP2)has recently become a hot topic in the field of cancer research,and has demonstrated a close relationship with CRC.SHP2,encoded by the PTPN11 gene,is a non-receptor tyrosine kinase commonly present in various tissues and cells of the human body.Existing research shows that SHP2 plays a crucial role in regulating CRC and colitis-associated colon cancer(CAC),and the emergence of SHP2 allosteric inhibitors has identified SHP2 as a potential new therapeutic target for patients with CRC.Here we review the structure of SHP2 and its roles in CRC and CAC.
2.Research progress in haptoglobin in digestive system tumors
Chao HE ; Chunbaixue YANG ; Hao ZHANG ; Qingfei DIAO ; Juming JIA ; Jianchun FAN ; Xueliang WU
Chinese Journal of Comparative Medicine 2025;35(3):147-155
Digestive system tumors account for more than half of all malignant tumors in terms of incidence and mortality,and thus pose a serious threat to human health.Haptoglobin(Hp)is an acute-phase glycoprotein that is elevated in both plasma and tumor tissues in various clinical conditions,including different types of cancer,such as liver,gastric,colorectal,pancreatic,and gallbladder cancer.Numerous studies have indicated that Hp plays a significant role in the prognosis of cancer patients,highlighting its potential as a prognostic marker for gastrointestinal tumors,with important clinical applications.Despite its demonstrated crucial role in the development of various tumors,however,the specific mechanisms of Hp in gastrointestinal tumors remain controversial.This review considers the differential expression and clinical significance of Hp in the five major types of gastrointestinal tumors,to explore its role in different stages of cancer progression and prognosis.This review thus aims to provide reliable and accurate serum biomarkers for the screening,early diagnosis,treatment,and prognosis monitoring of gastrointestinal tumors,with important implications for predicting the survival and prognosis of cancer patients.
3.The prospect of interleukin -23p19 inhibitors in precision treatment of Crohn's disease: mechanisms and clinical evidence
Yujing SUN ; Xueliang SUN ; Zhaozheng ZHANG ; Hongyan ZHENG ; Xiao YANG ; Xingru CHEN ; Ke WEN
Chinese Journal of Inflammatory Bowel Diseases 2025;09(5):390-396
Interleukin- (IL) 23 drives pathogenic differentiation of Th17 cells via the JAK2-STAT3 signaling pathway, upregulates IL-17A/IL-22 expression, and disrupts intestinal barrier integrity, thereby playing a pivotal role in the pathogenesis of Crohn's disease (CD). IL-23p19 inhibitors—exemplified by risankizumab, mirikizumab, and guselkumab—precisely block this pathway. Key phase 3 trials have demonstrated their efficacy in CD, showing significant clinical benefits in patients refractory to conventional therapies or biologics, with no new safety signals identified. The ultimate treatment goal for CD is deep healing (mucosal-transmural-biochemical composite remission) as defined by STRIDE II. However, current evidence exhibits critical limitations: absence of head-to-head drug comparisons, insufficient data on biologic-experienced subpopulations, and heterogeneous follow-up durations leading to uncertainties in long-term safety. Future studies require standardized head-to-head trials with enhanced subgroup analyses to optimize precision therapeutics.
4.Research progress in haptoglobin in digestive system tumors
Chao HE ; Chunbaixue YANG ; Hao ZHANG ; Qingfei DIAO ; Juming JIA ; Jianchun FAN ; Xueliang WU
Chinese Journal of Comparative Medicine 2025;35(3):147-155
Digestive system tumors account for more than half of all malignant tumors in terms of incidence and mortality,and thus pose a serious threat to human health.Haptoglobin(Hp)is an acute-phase glycoprotein that is elevated in both plasma and tumor tissues in various clinical conditions,including different types of cancer,such as liver,gastric,colorectal,pancreatic,and gallbladder cancer.Numerous studies have indicated that Hp plays a significant role in the prognosis of cancer patients,highlighting its potential as a prognostic marker for gastrointestinal tumors,with important clinical applications.Despite its demonstrated crucial role in the development of various tumors,however,the specific mechanisms of Hp in gastrointestinal tumors remain controversial.This review considers the differential expression and clinical significance of Hp in the five major types of gastrointestinal tumors,to explore its role in different stages of cancer progression and prognosis.This review thus aims to provide reliable and accurate serum biomarkers for the screening,early diagnosis,treatment,and prognosis monitoring of gastrointestinal tumors,with important implications for predicting the survival and prognosis of cancer patients.
5.Analysis of risk factors and development of a nomogram model for early recurrence following curative resection of resectable pancreatic cancer
Chengyu HU ; Jianyu YANG ; Yannan XU ; Yifan YIN ; Minwei YANG ; Xueliang FU ; Dejun LIU ; Yanmiao HUO ; Wei LIU ; Junfeng ZHANG ; Yongwei SUN ; Rong HUA
Chinese Journal of Pancreatology 2025;25(2):104-111
Objective:To identify independent risk factors for early recurrence following curative resection of resectable pancreatic cancer and establish a nomogram prediction model.Methods:Clinical data from 405 patients with resectable pancreatic cancer treated at Renji Hospital, Shanghai Jiao Tong University School of Medicine from February 2010 to December 2020 were retrospectively reviewed. Patients were stratified into a training cohort (265 patients form February 2010 to December 2018) and a validation cohort (140 patients from January 2019 to December 2020) based on surgery dates. Optimal cutoff values for clinical variables were determined using X-tile software. Independent risk factors were identified through univariate and multivariate Cox proportional hazards regression analyses. Kaplan-Meier curves for recurrence-free survival (RFS) were generated across subgroups, and a nomogram was developed to predict early recurrence (within 1 year post-surgery). Time-dependent receiver operating characteristic (tROC) curves was drawn and area under the curve (AUC) metrics were utilized to evaluate predictive accuracy, while model reliability was assessed by calibration curves. Individualized risk scores derived from the nomogram were stratified into high- and low-risk groups using X-tile-derived cutoff values. Survival differences between groups were analyzed via log-rank tests. The clinical application value was judged by decision curve analysis (DCA) compared to TNM staging. Results:In the training cohort, 139 patients (52.45%) experienced early recurrence, with a median RFS of 11.1 months [interquartile range ( IQR): 6.0-26.0]. The validation cohort reported 70 early recurrences (50.00%) and a median RFS of 11.8 months ( IQR: 4.9-21.4). Univariate analysis revealed significant associations between early recurrence and tumor diameter, carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 125 (CA125), systemic immune-inflammation index (SⅡ), and prognostic nutritional index (PNI). Multivariate analysis identified tumor diameter ≥3.75 cm ( HR=1.718, 95% CI 1.223-2.412, P=0.002), CA19-9≥218 U/ml ( HR=1.567, 95% CI 1.107-2.220, P=0.011), CA125≥20.98 U/ml ( HR=2.501, 95% CI 1.768-3.539, P<0.001), SⅡ≥388.28 ( HR=1.708, 95% CI 1.096-2.662, P=0.018), and PNI<53.18 ( HR=0.596, 95% CI 0.404-0.879, P=0.009) as independent risk factors for early recurrence. The nomogram achieved AUC values of 0.771 and 0.708 in the training and validation cohorts, respectively. Calibration curves demonstrated strong agreement between predicted and observed survival probabilities. Kaplan-Meier analysis revealed significantly lower 1-year RFS rates in high-risk versus low-risk groups for both cohorts (training: HR=3.65, 95% CI 2.45-5.44, P<0.001; validation: HR=2.37, 95% CI 1.39-4.06, P=0.001). DCA indicated superior net benefit of the nomogram over TNM staging across threshold probabilities of 0.2-0.9. Conclusions:The proposed nomogram effectively integrates clinical and serological biomarkers to preoperatively assess early recurrence risk in resectable pancreatic cancer patients, offering enhanced precision for clinical decision-making.
6.Integrated imaging and clinical features of glottic squamous cell carcinoma of the larynx: pathological association and prognosis assessment.
Yuqiao ZHANG ; Wulin WEN ; Fengxia YANG ; Dongke MA ; Xueliang SHEN ; Ningyu FENG ; Xixi LI ; Zhiling ZENG ; Zhipeng MI ; Xiyuan YAN ; Ruixia MA
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2025;39(8):709-716
Objective:To explore the clinical, imaging, and pathological features of glottic squamous cell carcinoma of the larynx and their relationship with prognosis. Methods:A retrospective analysis was conducted on the clinical, imaging, and pathological data of 130 patients with glottic squamous cell carcinoma of the larynx who were treated at the First People's Hospital of Yinchuan and the General Hospital of Ningxia Medical University from January 2018 to March 2023. Imaging examinations (CT and MRI) were used to evaluate the lesion boundary clarity, density, enhancement nature, and enhancement degree. Postoperative pathological examination was used to determine the pathological nature, immunohistochemistry, etc. Statistical methods such as χ² test, Spearman correlation analysis, multivariate logistic regression analysis, and Kaplan-Meier method were used to analyze the data. Results:Among the 130 patients, 127 were male and 3 were female, with an average age of (61.92±9.595) years. There was a correlation between clinical, imaging, and pathological features. Multivariate analysis showed that heterogeneous MRI density (OR=12.414;P=0.019) and squamous cell carcinoma as a subtype were correlated. The initial symptom of non-hoarseness (HR=6.045;P=0.010) and unclear MRI boundary (HR=12.559; P=0.029) were independent risk factors for poor prognosis in patients with glottic squamous cell carcinoma of the larynx. Conclusion:There is a correlation between the clinical, imaging, and pathological features of patients with glottic squamous cell carcinoma of the larynx, and they can affect prognosis. The initial symptom of non-hoarseness and unclear MRI boundary of the tumor are independent risk factors for poor prognosis.
Humans
;
Laryngeal Neoplasms/diagnosis*
;
Prognosis
;
Male
;
Female
;
Retrospective Studies
;
Middle Aged
;
Carcinoma, Squamous Cell/diagnosis*
;
Magnetic Resonance Imaging
;
Glottis/pathology*
;
Tomography, X-Ray Computed
;
Aged
7.Pollen-food allergy syndrome: association between allergen cross-reactivity and symptom severity.
Yuqiao ZHANG ; Fengxia YANG ; Xiaohui YAN ; Xueliang SHEN ; Ningyu FENG ; Ting YAO ; Shurong LI ; Xiyuan YAN ; Ruixia MA
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2025;39(12):1156-1162
Objective:To investigate the clinical characteristics and major allergens of patients with pollen-food allergy syndrome(PFAS) and their correlation with the severity of symptoms, and to provide a basis for identifying high-risk patients, optimizing the allergen testing process and developing individualized dietary management strategies. Methods:The clinical data of 166 patients with PFAS admitted to our hospital from January 2021 to July 2023 were retrospectively analyzed. The clinical symptoms, pollen types and food allergy of the patients were analyzed by questionnaire survey and serum specific IgE detection. phi coefficient, Apriori algorithm modeling and multivariate logistic regression analysis were used to evaluate the association between allergen and symptom severity. Results:Artemisia pollen was the most common allergen in this area, with a positive rate of 96.39%. Peach and mango were the most common food allergens, which caused allergic reactions in 24.10% and 22.89% of patients, respectively. Oral mucosal symptoms were the main symptoms. Correlation analysis showed that there was a correlation between pollen allergens and allergenic food. Association rule analysis showed that when the patient was allergic to the combination of peanuts and trees, the probability of high severity of symptoms was 82.35%. Multivariate analysis showed that ragweed allergy was significantly positively correlated with the severity of PFAS symptoms. Conclusion:Artemisia pollen and related food allergens play an important role in the pathogenesis of PFAS. Association rule mining and network map analysis revealed direct associations between peanut and tree combination allergy and symptom severity, as well as potential links between other inhaled allergens and specific food allergies. Ragweed and peach allergy are independent risk factors for the aggravation of PFAS symptoms, which can be used as early warning indicators. These results help to improve the screening of high-risk patients and the construction of regional allergen databases.
Humans
;
Food Hypersensitivity/immunology*
;
Allergens/immunology*
;
Retrospective Studies
;
Pollen/immunology*
;
Cross Reactions
;
Immunoglobulin E/blood*
;
Rhinitis, Allergic, Seasonal/immunology*
;
Artemisia/immunology*
;
Male
;
Female
;
Adult
;
Prunus persica/immunology*
;
Arachis/immunology*
;
Middle Aged
;
Surveys and Questionnaires
;
Oral Allergy Syndrome
8.Effects of Netupitant and palonosetron hydrochloride capsules on the pharmacokinetics of albumin-bound paclitaxel in rats under different intestinal microenvironments
Yuanman QIN ; Wenhao CHU ; Jiaqi XU ; Yutong LI ; Bo LIANG ; Xueliang ZHANG ; Jian LIU
China Pharmacy 2025;36(16):1993-1999
OBJECTIVE To investigate the impact of Netupitant and palonosetron hydrochloride capsules (NEPA) on the pharmacokinetics of Paclitaxel for injection (albumin bound) (i. e. albumin-bound paclitaxel) under different intestinal microenvironment conditions. METHODS Male SD rats were divided into a normal group and a model group (n=16). Rats in the model group were intragastrically administered vancomycin solution to establish an intestinal disorder model. The next day after modeling, intestinal microbiota diversity was analyzed, and the mRNA expressions of cytochrome P450 3A1 (CYP3A1) and CYP2C11 in small intestine and liver tissues as well as those protein expressions in liver tissue were measured. Male SD rats were grouped as described above (n=16). The normal group was subdivided into the TP chemotherapy group (TP-1 group) and the TP chemotherapy+NEPA group (TP+NEPA-1 group); the model group was subdivided into the TP chemotherapy group (TP-2 group) and the TP chemotherapy+NEPA group (TP+NEPA-2 group) (n=8). Rats in the TP+NEPA-1 and TP+NEPA-2 groups received a single intragastric dose of NEPA suspension (25.8 mg/kg, calculated by netupitant). One hour later, all four groups received a single tail vein injection of albumin-bound paclitaxel and cisplatin. Blood samples were collected at different time points after the last administration. Using azithromycin as the internal standard, plasma paclitaxel concentrations were determined by liquid chromatography-tandem mass spectrometry. The main pharmacokinetic parameters were calculated using DAS 2.0 software and compared between groups. RESULTS Compared with the normal group, the model group showed significantly decreased Chao1 and Shannon indexes (P<0.05), significant alterations in microbiota composition and relative abundance, and significantly downregulated expressions of CYP3A1 mRNA in liver tissue and CYP2C11 mRNA in both small intestine and liver tissues (P<0.05). Compared with the TP-1 group, the AUC0-t, AUC0-∞, MRT0-t of paclitaxel in the TP-2 group, the cmax, AUC0-t, AUC0-∞ of paclitaxel in the TP+NEPA-1 group and TP+NEPA-2 group were significantly increased or prolonged; CL of paclitaxel in the TP-2 group, Vd and CL of paclitaxel in the TP+NEPA-1 group and the TP+NEPA-2 group were significantly decreased or shortened (P<0.05). Compared with the TP-2 group, cmax of paclitaxel in the TP+NEPA-2 group was significantly increased, and Vd and MRT0-t were significantly decreased or shortened (P<0.05). CONCLUSIONS Intestinal microbiota disorder affects the mRNA expressions of CYP3A1 and CYP2C11, leading to decreased clearance and increased systemic exposure of paclitaxel. Concomitant administration of NEPA under normal intestinal microbiota condition increases paclitaxel exposure. However, under conditions of intestinal microbiota disorder, concomitant administration of NEPA has a limited impact on paclitaxel systemic exposure.
9.The prospect of interleukin -23p19 inhibitors in precision treatment of Crohn's disease: mechanisms and clinical evidence
Yujing SUN ; Xueliang SUN ; Zhaozheng ZHANG ; Hongyan ZHENG ; Xiao YANG ; Xingru CHEN ; Ke WEN
Chinese Journal of Inflammatory Bowel Diseases 2025;09(5):390-396
Interleukin- (IL) 23 drives pathogenic differentiation of Th17 cells via the JAK2-STAT3 signaling pathway, upregulates IL-17A/IL-22 expression, and disrupts intestinal barrier integrity, thereby playing a pivotal role in the pathogenesis of Crohn's disease (CD). IL-23p19 inhibitors—exemplified by risankizumab, mirikizumab, and guselkumab—precisely block this pathway. Key phase 3 trials have demonstrated their efficacy in CD, showing significant clinical benefits in patients refractory to conventional therapies or biologics, with no new safety signals identified. The ultimate treatment goal for CD is deep healing (mucosal-transmural-biochemical composite remission) as defined by STRIDE II. However, current evidence exhibits critical limitations: absence of head-to-head drug comparisons, insufficient data on biologic-experienced subpopulations, and heterogeneous follow-up durations leading to uncertainties in long-term safety. Future studies require standardized head-to-head trials with enhanced subgroup analyses to optimize precision therapeutics.
10.Analysis of risk factors and development of a nomogram model for early recurrence following curative resection of resectable pancreatic cancer
Chengyu HU ; Jianyu YANG ; Yannan XU ; Yifan YIN ; Minwei YANG ; Xueliang FU ; Dejun LIU ; Yanmiao HUO ; Wei LIU ; Junfeng ZHANG ; Yongwei SUN ; Rong HUA
Chinese Journal of Pancreatology 2025;25(2):104-111
Objective:To identify independent risk factors for early recurrence following curative resection of resectable pancreatic cancer and establish a nomogram prediction model.Methods:Clinical data from 405 patients with resectable pancreatic cancer treated at Renji Hospital, Shanghai Jiao Tong University School of Medicine from February 2010 to December 2020 were retrospectively reviewed. Patients were stratified into a training cohort (265 patients form February 2010 to December 2018) and a validation cohort (140 patients from January 2019 to December 2020) based on surgery dates. Optimal cutoff values for clinical variables were determined using X-tile software. Independent risk factors were identified through univariate and multivariate Cox proportional hazards regression analyses. Kaplan-Meier curves for recurrence-free survival (RFS) were generated across subgroups, and a nomogram was developed to predict early recurrence (within 1 year post-surgery). Time-dependent receiver operating characteristic (tROC) curves was drawn and area under the curve (AUC) metrics were utilized to evaluate predictive accuracy, while model reliability was assessed by calibration curves. Individualized risk scores derived from the nomogram were stratified into high- and low-risk groups using X-tile-derived cutoff values. Survival differences between groups were analyzed via log-rank tests. The clinical application value was judged by decision curve analysis (DCA) compared to TNM staging. Results:In the training cohort, 139 patients (52.45%) experienced early recurrence, with a median RFS of 11.1 months [interquartile range ( IQR): 6.0-26.0]. The validation cohort reported 70 early recurrences (50.00%) and a median RFS of 11.8 months ( IQR: 4.9-21.4). Univariate analysis revealed significant associations between early recurrence and tumor diameter, carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 125 (CA125), systemic immune-inflammation index (SⅡ), and prognostic nutritional index (PNI). Multivariate analysis identified tumor diameter ≥3.75 cm ( HR=1.718, 95% CI 1.223-2.412, P=0.002), CA19-9≥218 U/ml ( HR=1.567, 95% CI 1.107-2.220, P=0.011), CA125≥20.98 U/ml ( HR=2.501, 95% CI 1.768-3.539, P<0.001), SⅡ≥388.28 ( HR=1.708, 95% CI 1.096-2.662, P=0.018), and PNI<53.18 ( HR=0.596, 95% CI 0.404-0.879, P=0.009) as independent risk factors for early recurrence. The nomogram achieved AUC values of 0.771 and 0.708 in the training and validation cohorts, respectively. Calibration curves demonstrated strong agreement between predicted and observed survival probabilities. Kaplan-Meier analysis revealed significantly lower 1-year RFS rates in high-risk versus low-risk groups for both cohorts (training: HR=3.65, 95% CI 2.45-5.44, P<0.001; validation: HR=2.37, 95% CI 1.39-4.06, P=0.001). DCA indicated superior net benefit of the nomogram over TNM staging across threshold probabilities of 0.2-0.9. Conclusions:The proposed nomogram effectively integrates clinical and serological biomarkers to preoperatively assess early recurrence risk in resectable pancreatic cancer patients, offering enhanced precision for clinical decision-making.

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