1.Risk factors for rebleeding after endoscopic therapy for esophageal and gastric varices in liver cirrhosis patients and construction of a nomogram model
Huijuan SHAO ; Shini HAN ; Aiping ZHANG ; Yuling ZHANG ; Ting LI ; Ya HAN ; Jiucong ZHANG ; Wenshan DOU ; Xiuxia WANG ; Hongwei DU
Journal of Clinical Hepatology 2026;42(8):1845-1856
ObjectiveTo investigate the risk factors for rebleeding after endoscopic therapy for esophageal and gastric varices in liver cirrhosis patients, to construct a clinical predictive model, and to provide a reference for predicting rebleeding in the early stage, reducing the incidence rate of rebleeding, and improving the clinical outcome of patients. MethodsA retrospective analysis was performed for the clinical data of 194 liver cirrhosis patients with gastroesophageal variceal bleeding who received initial endoscopic therapy at Department of Gastroenterology, The Second People’s Hospital of Lanzhou, from January 1, 2021 to May 31, 2025. According to whether rebleeding occurred within 1 year after endoscopic therapy, the patients were divided into rebleeding group and non-rebleeding group. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. The patients enrolled were randomly divided into a training set and a validation set at a ratio of 7∶3. In the training set, the Lasso regression analysis was used to obtain optimal predictive variables, and the factors that might affect prognosis were included in the univariate and multivariate Logistic regression analyses to identify independent predictive factors for rebleeding after endoscopic therapy for esophageal and gastric varices in liver cirrhosis patients, which were used to construct a nomogram model. In both the training set and the validation set, the receiver operating characteristic (ROC) curve and the calibration curve were used to assess the discriminatory ability and calibration of the model, and decision curve analysis and the clinical impact curve were used to assess the clinical practicability of the model. ResultsAmong the 194 liver cirrhosis patients with esophageal and gastric varices, 116 (59.79%) experienced rebleeding within 1 year after endoscopic therapy, with 76 patients in the training set and 40 patients in the validation set. In the training set, the Lasso regression analysis and the univariate and multivariate Logistic regression analyses showed that etiology of liver cirrhosis (odds ratio [OR]=3.540, 95% confidence interval [CI]: 1.520 — 7.150, P<0.001), Child-Pugh class (OR=3.560, 95%CI: 1.380 — 9.500, P=0.019), severity of esophageal and gastric varices (OR=8.190, 95%CI: 3.568 — 17.850, P=0.026), and main portal vein diameter (OR=2.954, 95%CI: 1.349 — 15.030, P=0.044) were independent predictive factors for rebleeding of esophageal and gastric varices in liver cirrhosis patients. A nomogram model was constructed based on the above independent predictive factors. The ROC curve analysis showed that this model had an area under the ROC curve of 0.845 (95%CI: 0.778 — 0.912) in the training set and 0.801 (95%CI: 0.798 — 0.868) in the validation set. The model had an index of concordance of 0.832 in the training set and 0.820 in the validation set, suggesting that the model had a good discriminatory ability. The Hosmer-Lemeshow test showed P values of 0.320 and 0.550 in the training set and validation set, respectively, the calibration curve indicated that the predicted probabilities of the nomogram model were in good concordance with the actual observed probabilities, suggesting that the model had good calibration. The decision curve analysis and the clinical impact curve showed that the model had good clinical utility. ConclusionThe nomogram model based on etiology of liver cirrhosis, Child-Pugh class, severity of esophageal and gastric varices, and main portal vein diameter has a certain clinical value in predicting the risk of rebleeding from esophageal and gastric varices in liver cirrhosis.
2.Effect of Acupuncture Combined with Bloodletting and Cupping on the Expression of Coagulation-Complement-Mast Cell Activation Axis-Related Factors in Patients with Chronic Spontaneous Urticaria:Randomize-controlled Study
Yuzhu DU ; Yuqiang XUE ; Xiang LIU ; Yu SHI ; Hongkun LI ; Wenshan LIU ; Zan TIAN ; Yutong HU ; Yanjun WANG
Journal of Traditional Chinese Medicine 2025;66(2):150-156
ObjectiveTo observe the clinical efficacy of acupuncture combined with bloodletting and cupping in the treatment of chronic spontaneous urticaria(CSU) and to explore its potential mechanisms of action. MethodsSeventy CSU patients were randomly divided into loratadine group and acupuncture + bloodletting group, with 35 patients in each group. The loratadine group received oral loratadine tablets, 10 mg once daily in the evening. The acupuncture + bloodletting group received acupuncture at Zhongwan (CV 12), Guanyuan (CV 4), Tianshu (ST 25), Zusanli (ST 36), Sanyinjiao (SP 6), Xuehai (SP 10), Quchi (LI 11), Hegu (LI 4), Taichong (LR 3), Baihui (GV 20), and Shenting (GV 24), once daily,along with bloodletting and cupping at Dazhui (GV 14) and Geshu (BL 17), every other day. Both groups were treated for 4 weeks. The 7-day urticaria activity score(UAS7) was assessed before and after the treatment, and levels of serum immunoglobulin E (IgE), interleukin-4 (IL-4), interleukin-5 (IL-5), eosinophil cationic protein (ECP), plasma tissue factor (TF), activated factor Ⅶ (FⅦa), prothrombin fragment 1+2 (F1+2), D-dimer (D-D) and complement component 5a (C5a) were detected. ResultsA total of 65 patients were included in the final analysis, 32 in the loratadine group and 33 in the acupuncture + bloodletting group. Before treatment, there was no significant difference in UAS7 score, serum IgE, IL-4, IL-5, ECP levels, or plasma TF, FⅦa, F1+2, D-D, C5a levels between groups (P> 0.05). After treatment, both groups showed significant reductions in UAS7 score, serum IgE, IL-4, IL-5, and plasma TF, FⅦa, F1+2, D-D, and C5a levels compared to those before treatment (P<0.01). However, after treatment, there was no significant difference in UAS7 score and serum ECP, IgE, IL-4, IL-5 levels between groups (P>0.05). The acupuncture + bloodletting group showed lower plasma TF, FⅦa, F1+2, D-D and C5a levels compared to the loratadine group (P<0.05 or P<0.01). ConclusionAcupuncture combined with bloodletting and cupping can effectively improve the skin symptoms of CSU patients and reduce the levels of inflammatory factors. The potential mechanism of action may involve the regulation of the coagulation-complement-mast cell activation axis, thereby inhibiting mast cell degranulation.
3.Electroacupuncture inhibiting AGE-RAGE mediated proinflammatory signaling pathway to reduce neuroinflammation in postherpetic neuralgia rats
Yuzhu DU ; Hongkun LI ; Wenshan LIU ; Xiang LIU ; Yanjun WANG
International Journal of Traditional Chinese Medicine 2025;47(11):1538-1544
Objective:To investigate the effects of electroacupuncture on neuroinflammation in rats with postherpetic neuralgia (PHN) by regulating advanced glycation end products (AGE) and its receptor (RAGE) signaling pathway.Methods:Ten healthy male SD rats were randomly selected as the control group, and the remaining 30 SD rats were used to induce PHN model by resin toxin (RTX). Thirty SD rats were randomly divided into model group, positive drug group and electroacupuncture group, with 10 rats in each group. Intervention was conducted on the 7th day of modeling. The electroacupuncture group intervened with "Yanglingquan"(GB34) and "Huantiao"(GB30); the positive drug group was intragastrically administered with pregabalin suspension 27 mg/kg, once a day for 1 week; the control group and model group were not treated. The paw retraction threshold (PWMT) and paw retraction latency (PWTL) were measured before modeling and on the 7th, 14th, 21st and 28th days after modeling; histopathological changes of spinal cord were observed by HE staining; the levels of TNF-α, IL-1β and IL-6 in spinal cord tissue were detected by ELISA; the expressions of AGE-RAGE signaling pathway related proteins in spinal cord was detected by Western blot.Results:Compared with the model group, the degree of atrophy and inflammatory infiltration of spinal cord neurons in the positive drug group and electroacupuncture group were reduced. The PWMT value in the positive drug group increased ( P<0.05), and the PWTL value decreased ( P<0.05); compared with the model group, the levels of TNF-α, IL-1β and IL-6 in the spinal cord tissue of the electroacupuncture group and the positive drug group decreased ( P<0.05), and the expressions of AGE, RAGE, p-ERK1/2/ERK1/2, JNK, p-NF-κB/NF-κB and AP-1 decreased ( P<0.05); compared with the positive drug group, the levels of TNF-α, IL-1β and IL-6 in the spinal cord tissue of the electroacupuncture group decreased ( P<0.05), and the protein expressions of AGE, RAGE, p-ERK1/2/ERK1/2, JNK, p-NF-κB/NF-κB and AP-1 decreased ( P<0.05). Conclusion:Electroacupuncture can improve neuroinflammation in PHN rats, the mechanism of which may be related to the regulation of AGE-RAGE mediated pro-inflammatory signaling pathway.
4.Identification and optimization of peptide inhibitors to block VISTA/PSGL-1 interaction for cancer immunotherapy.
Xiaoshuang NIU ; Menghan WU ; Guodong LI ; Xiuman ZHOU ; Wenpeng CAO ; Wenjie ZHAI ; Aijun WU ; Xiaowen ZHOU ; Shengzhe JIN ; Guanyu CHEN ; Yanying LI ; Jiangfeng DU ; Yahong WU ; Lu QIU ; Wenshan ZHAO ; Yanfeng GAO
Acta Pharmaceutica Sinica B 2023;13(11):4511-4522
Developing new therapeutic agents for cancer immunotherapy is highly demanding due to the low response ratio of PD-1/PD-L1 blockade in cancer patients. Here, we discovered that the novel immune checkpoint VISTA is highly expressed on a variety of tumor-infiltrating immune cells, especially myeloid derived suppressor cells (MDSCs) and CD8+ T cells. Then, peptide C1 with binding affinity to VISTA was developed by phage displayed bio-panning technique, and its mutant peptide VS3 was obtained by molecular docking based mutation. Peptide VS3 could bind VISTA with high affinity and block its interaction with ligand PSGL-1 under acidic condition, and elicit anti-tumor activity in vivo. The peptide DVS3-Pal was further designed by d-amino acid substitution and fatty acid modification, which exhibited strong proteolytic stability and significant anti-tumor activity through enhancing CD8+ T cell function and decreasing MDSCs infiltration. This is the first study to develop peptides to block VISTA/PSGL-1 interaction, which could act as promising candidates for cancer immunotherapy.
5.Comparison and Cluster Analysis of Anthraquinone in Commercially Available Yiqing Granule
Wenshan DU ; Xigang LIU ; Cuizhe LIU
China Pharmacy 2016;27(15):2090-2094
OBJECTIVE:To establish a method for the contents determination and cluster analysis of free and combined anthra-quinone of aloe emodin,rhein,emodin,rhubarb phenol and physcion in commercially available Yiqing granule from different man-ufacturers. METHODS:HPLC was performed on the column of Eclipse plus C18 with mobile phase of methanol-0.1%Phosphoricac-id solution (gradient elution) at a flow rate of 0.8 ml/min,the detection wavelength was 254 nm,the column temperature was 25 ℃,and the injection volume was 20 μl. RESULTS:The linear range was 0.001 6-0.128 0 μg for aloe emodin(r=0.999 9), 0.003 4-0.273 6 μg for rhein(r=0.999 9),0.003 7-0.299 2 μg for emodin(r=0.999 9),0.006 7-0.536 0 μg for rhubarb phenol (r=0.999 9)and 0.001 7-0.134 4 μg(r=0.999 9)for physcion;RSDs of precision,stability and reproducibility tests were lower than 3%;recoveries were 97.77%-101.47%(RSD=1.30%,n=6),98.09%-100.26%(RSD=0.76%,n=6),96.42%-100.38%(RSD=1.58%,n=6),96.63%-102.50%(RSD=2.17%,n=6) and 97.10%-103.70%(RSD=2.47%,n=6),respectively;the content range of total anthraquinone was 0.042-0.218 mg/g, 0.029-0.448 mg/g, 0.022-0.167 mg/g, 0.032-0.284 mg/g and 0.006-0.060 mg/g,combined anthraquinone was 0.010-0.111 mg/g,0.013-0.092 mg/g,0.011-0.097 mg/g,0.030-0.246 mg/g and 0.001-0.034 mg/g,and free anthraquinone was 0.022 3-0.143 mg/g,0.015-0.356 mg/g,0.008-0.071 mg/g,0.006-0.075 mg/g and 0.003-0.032 mg/g. Cluster analysis showed there were 4 batches belonged to Category 1,2 batches belonged to Category 2 and 4 batches belonged to Category 3 for the total anthraquinone in 5 components;4 bathes belonged to Category 1,2 batches belonged to Category 2 and 4 batches belonged to Category 3 for the combined anthraquinone;and 6 bathes belonged to Category 1 and 4 batches belonged to Category 2 for the free anthraquinone. CONCLUSIONS:The method is simple and accurate,and can provide reference for improving the quality and diarrhea efficacy control of Yiqing granule;there were great differences in Rheum palma-tum and combined anthraquinone from different manufacturers.

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