1.Research status of conjunctival lymphangiectasia
Fuli WANG ; Xuandi SU ; Yujin WANG ; Jie RAN ; Duosheng XIA
International Eye Science 2025;25(1):59-63
Conjunctival lymphangiectasia is a low-incidence ocular surface disease that is currently rarely reported in the relevant literature. It may be related to cosmetic eyelid surgery, tumor, radiation or chemotherapy and other factors and often causes a foreign body sensation, lacrimation, eye pain, visual fatigue and other discomfort. These symptoms of constant eye irritation affect the patient's quality of life. At present, anterior segment optical coherence tomography can be used for clinical diagnosis, and the novel monoclonal antibody D2-40, as a marker of lymphatic endothelial cell dilatation, has high specificity in pathological diagnosis. Previous studies have not fully defined the pathogenesis of the disease, and treatment methods vary. Conventional treatment has resulted in varying degrees of damage to the conjunctiva in patients. In recent years, anti-vascular endothelial growth factor drugs have been reported to be effective in treating the disease with few complications. This article reviews the pathogenesis, diagnosis and treatment of this rare disease in order to gain a better understanding of conjunctival lymphangiectasia and provide more support for clinical diagnosis and treatment.
2.Development of a predictive model and application for spontaneous passage of common bile duct stones based on automated machine learning
Jian CHEN ; Kaijian XIA ; Fuli GAO ; Luojie LIU ; Ganhong WANG ; Xiaodan XU
Journal of Clinical Hepatology 2025;41(3):518-527
ObjectiveTo develop a predictive model and application for spontaneous passage of common bile duct stones using automated machine learning algorithms given the complexity of treatment decision-making for patients with common bile duct stones, and to reduce unnecessary endoscopic retrograde cholangiopancreatography (ERCP) procedures. MethodsA retrospective analysis was performed for the data of 835 patients who were scheduled for ERCP after a confirmed diagnosis of common bile duct stones based on imaging techniques in Changshu First People’s Hospital (dataset 1) and Changshu Traditional Chinese Medicine Hospital (dataset 2). The dataset 1 was used for the training and internal validation of the machine learning model and the development of an application, and the dataset 2 was used for external testing. A total of 22 potential predictive variables were included for the establishment and internal validation of the LASSO regression model and various automated machine learning models. The area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and accuracy were used to assess the performance of models and identify the best model. Feature importance plots, force plots, and SHAP plots were used to interpret the model. The Python Dash library and the best model were used to develop a web application, and external testing was conducted using the dataset 2. The Kolmogorov-Smirnov test was used to examine whether the data were normally distributed, and the Mann-Whitney U test was used for comparison between two groups, while the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. ResultsAmong the 835 patients included in the study, 152 (18.20%) experienced spontaneous stone passage. The LASSO model achieved an AUC of 0.875 in the training set (n=588) and 0.864 in the validation set (n=171), and the top five predictive factors in terms of importance were solitary common bile duct stones, non-dilated common bile duct, diameter of common bile duct stones, a reduction in serum alkaline phosphatase (ALP), and a reduction in gamma-glutamyl transpeptidase (GGT). A total of 55 models were established using automated machine learning, among which the gradient boosting machine (GBM) model had the best performance, with an AUC of 0.891 (95% confidence interval: 0.859 — 0.927), outperforming the extreme randomized tree mode, the deep learning model, the generalized linear model, and the distributed random forest model. The GBM model had an accuracy of 0.855, a sensitivity of 0.846, and a specificity of 0.857 in the test set (n=76). The variable importance analysis showed that five factors had important influence on the prediction of spontaneous stone passage, i.e., were solitary common bile duct stones, non-dilated common bile duct, a stone diameter of <8 mm, a reduction in serum ALP, and a reduction in GGT. The SHAP analysis of the GBM model showed a significant increase in the probability of spontaneous stone passage in patients with solitary common bile duct stones, non-dilated common bile duct, a stone diameter of <8 mm, and a reduction in serum ALP or GGT. ConclusionThe GBM model and application developed using automated machine learning algorithms exhibit excellent predictive performance and user-friendliness in predicting spontaneous stone passage in patients with common bile duct stones. This application can help avoid unnecessary ERCP procedures, thereby reducing surgical risks and healthcare costs.
3.Research progress on the role of NF-κB signaling pathway in acute lung injury and TCM intervention
China Pharmacy 2025;36(10):1277-1282
Acute lung injury (ALI) is a common clinical inflammatory respiratory emergency with high morbidity and mortality, for which there is no effective and safe therapeutic drug. Nuclear factor-κB (NF-κB), as a classic inflammatory signaling pathway, can interact with upstream and downstream regulatory factors such as Toll-like receptor 4 (TLR4), mitogen- activated protein kinase (MAPK), nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3), high mobility group box-1 protein 1 (HMGB1), to jointly affect ALI. This review summarizes the latest research findings in recent years regarding the treatment of ALI through traditional Chinese medicine (TCM) interventions targeting NF-κB signaling pathways. It has been found that a variety of TCM monomers (danshensu methyl ester, salidroside total glycosides, berberine, Codonopsis pilosula polysaccharides, ursolic acid, chrysophanol, and polyphenols from longan seed kernels, etc.) and compound formulas (Resolving-dampness and defeating-toxins formula, Jinyin qingre oral liquid, Xuebijing injection, Combined treatment of lung and intestine, Huangqi baihe decoction, etc.) can modulate NF-κB signaling pathway, and can prevent and control ALI by inhibiting inflammation, improving oxidative stress, reducing apoptosis and modulating the intestinal flora in a multi-pathway manner.
4.Association between cancer-related fatigue and PD-1 inhibitors in patients with malignant melanoma and its influencing factors
GAO Wenhua ; YANG Fuli ; ZHANG Jinzhong
Chinese Journal of Cancer Biotherapy 2025;32(7):761-764
[摘 要] 目的:探讨程序性死亡蛋白1(PD-1)抑制剂与恶性黑色素瘤患者癌性疲劳(CRF)之间的关系及其影响因素。方法:选取2019年4月至2024年4月期间在济南市人民医院接受治疗的100例恶性黑色素瘤患者作为研究对象,使用中文版Piper疲劳量表评估这些患者在接受首次PD-1抑制剂治疗前后3个月内的疲劳状况。结果:使用PD-1抑制剂前后的患者疲劳评分存在显著差异(P < 0.001)。单变量分析发现,性别、吸烟史、肿瘤位置以及使用的PD-1抑制剂类型对于疲劳程度没有明显影响(均P > 0.05),而与年龄、疾病分期、贫血状态、白细胞减少症、继发性甲状腺机能减退(甲减)、继发性肾上腺皮质醇功能减退(AI)、继发性促肾上腺皮质激素降低(P < 0.05或P < 0.01或P < 0.001)相关联。进一步的多变量回归分析揭示,继发性甲减、继发性AI、贫血、白细胞减低是导致此类患者出现严重CRF的关键独立风险因素(均P < 0.05)。结论: PD-1抑制剂的不良反应继发性甲减、继发性AI、贫血、白细胞减低是恶性黑色素瘤患者CRF的独立风险因素。
5.Experience in Treating Digestive Dysfunction in Chronic Renal Failure from the Perspective of Dampness
Journal of Traditional Chinese Medicine 2025;66(16):1719-1722
It is believed that dampness is a key pathological factor contributing to digestive dysfunction in chronic renal failure. Damp pathogens tend to be entangled with or transformed into other pathogenic factors, obstructing the flow of qi, disturbing the functions of the zang-fu organs, and impairing the spleen and stomach's transportation and transformation functions, ultimately leading to disease onset. Based on this understanding, the treatment principle emphasizes dispelling dampness, regulating qi, and harmonizing the five zang organs. For the syndrome of spleen and kidney qi deficiency with dampness, the self-formulated Buyuan Fengzang Decoction (补元封藏煎) is used to tonify the kidney, secure essence, strengthen the spleen, and eliminate dampness. For the syndrome of turbid dampness obstructing the lung and stomach, the self-formulated Sulian Xiexin Decoction (苏连泻心汤) is applied to open with acrid, descend with bitter, dry dampness, and discharge turbidity. For the syndrome of dampness stagnating and transforming into heat, with concurrent spleen deficiency and liver qi stagnation, the self-formulated Chailian Wendan Decoction (柴连温胆汤) is employed to soothe the liver, strengthen the spleen, and disperse the accumulation. For the syndrome of damp obstruction with qi stagnation and constrained yang, the self-formulated Caozhi Erchen Decoction (草知二陈汤) is used to resolve dampness, relieve constraint, raise yang, and promote the defensive qi.
6.Mechanism of Shenshuai Xiezhuo Decoction in Intervention of Chronic Kidney Disease Combined with Atherosclerosis Based on Regulation of PI3K/Akt/mTOR Signaling Pathway by miRNA126
Gengxin LIU ; Gedi ZHANG ; Wenqi YUAN ; Fusheng LI ; Min GUO ; Fuli LUO ; Ziyou YAN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(9):48-55
ObjectiveExploring the role of microRNA126 (miRNA126) in chronic kidney disease combined with atherosclerosis (CKD AS) by regulating the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway and the mechanism of Shenshuai Xiezhuo decoction in the intervention of CKD AS rats with 5/6 nephrectomy combined with high-fat feeding. MethodA total of 60 SD rats were randomly divided into sham operation group, model group, losartan group, and low, medium, and high dose groups of Shenshuai Xiezhuo decoction. The CKD AS rat model was established by 5/6 nephrectomy combined with high-fat feeding for 10 weeks. The low, medium, and high dose groups (6.0, 12.0, 24.0 g·kg-1·d-1) of Shenshuai Xiezhuo decoction and the losartan group (20 mg·kg-1·d-1) were gavaged, and the corresponding intervention was carried out for eight weeks. Then, the rats were killed, and samples were collected for corresponding detection. Fully automated biochemical analyzers were used to detect kidney function and blood lipids in rats: blood creatinine (SCr), blood urea nitrogen (BUN), total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) levels. Hematoxylin-eosin (HE) and Masson staining of aortic tissue and pathological observation under a light microscope were carried out, and autophagosomes and autophagy lysosomes were observed by transmission electron microscopy. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to determine the mRNA levels of miRNA126, PI3K, Akt, and mTOR in rats, and Western blot was used to determine the protein expression levels of phosphorylated (p)-PI3K, PI3K, p-Akt, Akt, p -mTOR, mTOR, benzyl chloride 1 (Beclin-1), and microtubule-associated protein light chain 3Ⅱ/Ⅰ (LC3Ⅱ/LC3Ⅰ). ResultCompared with the sham operation group, the serum SCr, BUN, TC, TG, and LDL-C in the model group were significantly increased (P<0.01). Compared with the model group, the SCr, BUN, TC, TG, and LDL-C were decreased in the losartan group and low, medium, and high dose groups of Shenshuai Xiezhuo decoction (P<0.05). Compared with the sham operation group, thickening plaques, infiltration of mononuclear macrophages, a small number of foam cells, disordered arrangement of smooth muscle fibers in the tunica media, and increased collagen fibers were observed in the model group, and the lesions in the losartan group and Shenshuai Xiezhuo decoction groups were alleviated compared with those in the model group. Compared with the model group, the number of autophagosomes and autophagy lysosomes increased in the medium and high dose groups of Shenshuai Xiezhuo decoction. Compared with the sham operation group, the expression of miRNA126 in the aortic tissue of the model group was significantly decreased (P<0.01), and the mRNA expressions of PI3K, Akt, and mTOR were significantly increased (P<0.01). Compared with the model group, the expression of miRNA126 in the aortic tissue of rats in high, medium, and low dose groups of Shenshuai Xiezhuo decoction and losartan group was significantly increased (P<0.01), while the mRNA expressions of PI3K, Akt, and mTOR were significantly decreased (P<0.01). Compared with the sham operation group, the protein expressions of p-PI3K, PI3K, p-Akt, Akt, p-mTOR, and mTOR in the model group were significantly increased (P<0.01), while the protein levels of Beclin-1, LC3Ⅰ, and LC3Ⅱ were significantly decreased (P<0.01). Compared with the model group, the protein expressions of p-PI3K, PI3K, p-Akt, Akt, p-mTOR, and mTOR in the losartan group and low, medium, and high dose groups of Shenshuai Xiezhuo decoction were decreased (P<0.05), while the protein levels of Beclin-1 and LC3Ⅱ/LC3Ⅰ were increased (P<0.05). ConclusionThe expression of miRNA126 is decreased in the aortic tissue of CKD AS rats, and the PI3K/Akt/mTOR pathway is activated to inhibit autophagy flux. Shenshuai Xiezhuo decoction regulates the PI3K/Akt/mTOR signaling pathway through miRNA126, restores the autophagy of aortic endothelial cells, protects the damage of CKD vessels, reduces the formation of As plaques, and slows the development of cardiovascular complications.
7.Modified Fixation of Levonorgestrel-releasing Intrauterine System for the Treatment of Adenomyosis
Jinbo LI ; Xueyun LI ; Fuli WU ; Shuqin CHEN
Journal of Sun Yat-sen University(Medical Sciences) 2024;45(2):290-296
ObjectiveTo introduce a fixation technique with the modified levonorgestrel-releasing intrauterine system (LNG-IUS) and evaluate its efficacy in the treatment of adenomyosis patients with previous LNG-IUS expulsion. MethodsA retrospective analysis was done on 22 adenomyosis patients who underwent modified LNG-IUS fixation due to LNG-IUS expulsion at three hospitals from June 2022 to June 2023. The baseline clinical characteristics, operative and postoperative details were collected and analyzed. The Visual analogu scale (VAS) scores and pictorial blood loss assessment chart (PBAC) scores were measured and compared before, 3 and 6 months after the LNG-IUS fixation. ResultsThe mean operative time was (19.51±7.41) min and intraoperative bleeding was (6.71±5.30) mL. Of the patients, 13 were operated under local anaesthesia and the other 9 under intravenous anaesthesia. There were 4 operations performed by a resident doctor, 15 by an attending doctor and 3 by a senior doctor. No intraoperative or postoperative complication was found. The mean follow-up was 11.51 months and no patient had a recurrence of LNG-IUS expulsion during the follow-up period. The mean level of hemoglobin at 1 month after operation was significantly higher than that before (P<0.001). VAS scores and PBAC scores at 3 and 6 months postoperatively were all improved significantly than those preoperatively (P<0.001). ConclusionsEffectively preventing the recurrence of LNG-IUS expulsion, modified LNG-IUS fixation is a safe and efficient method for adenomyosis patients with previous LNG-IUS expulsion. Modified LNG-IUS fixation deserves the clinical application due to its easy operation and wide range of use on women.
8.Determination of the Related Substances in Papaverine Hydrochloride Active Pharmaceutical Ingredients by HPLC
Ying LI ; Zhibo ZHENG ; Peng PENG ; Fuli ZHANG ; Liya LIN ; Jiangyuan HU ; Jianfen SHAO
Chinese Journal of Modern Applied Pharmacy 2024;41(13):1797-1802
OBJECTIVE
To establish an HPLC method for determination of the related substances in papaverine hydrochloride.
METHODS
NanoChrom ChromCore 120 C8 column was used; the mobile phase A consisted of 3.4 g·L−1 potassium dihydrogen phosphate aqueous solution, adjust pH to 3.5 with phosphoric acid-acetonitrile(90∶10), the mobile phase B was methanol, with gradient elution at the flow rate of 0.8 mL·min−1; the detection wavelength was 238 nm; the column temperature was 50 ℃.
RESULTS
The minimum separation between the main component and each impurity was >1.5; Papaverine and its thirteen impurities showed a good linear relationship in the self-concentration range(r>0.999); and the average recoveries were 93.1%−101.2% with RSDs of 2.3%−8.1%.
CONCLUSION
The method is accurate, sensitive and reliable, which is suitable for the determination of related substances in papaverine hydrochloride.
9.Diagnosis and treatment of prostate mucosa adenocarcinoma under multidisciplinary diagnosis and treatment mode: 2 cases report and literature review
Peng WU ; Fuli WANG ; Jing ZHANG ; Jing REN ; Zhiyong QUAN ; Wanni XU ; Lichun WEI ; Weijun QIN
Journal of Modern Urology 2024;29(2):154-157
【Objective】 To explore the clinicopathological characteristics and comprehensive treatment strategies of prostate mucosa adenocarcinoma under multidisciplinary diagnosis and treatment (MDT) mode. 【Methods】 Data of two patients with typical prostate mucosa adenocarcinoma treated in our hospital during Sep.2020 and Apr.2023 were retrospectively analyzed. 【Results】 In case 1, the clinical manifestation was macroscopic hematuria; multiparametric magnetic resonance imaging (mpMRI) indicated solid prostatic nodules, clinical stage T4N1Mx; initial prostate specific antigen (PSA) was 1.2 ng/mL; 6868Ga-prostate specific membrane antigen PET/CT (68Ga-PSMA PET/CT) suggested abnormal uptake of nuclear lesions in the prostate (SUV4.2-5.3); biopsy results indicated invasive mucinous adenocarcinoma.After prostate and pelvic field radiotherapy + androgen deprivation therapy (ADT) + antihypertensive treatment, lesions were significantly reduced, and hematuria symptoms were relieved.In case 2, the clinical manifestation was dysuria; initial PSA was 91.78 ng/mL; mpMRI suggested invasion of prostate mass into the bladder and clinical stage of T4N1M1b; 68Ga-PSMA PET/CT indicated prostate and pelvic lymph nodes, and multiple bone lesions showed increased nuclide uptake; biopsy results indicated prostate adenocarcinoma with mucinous adenocarcinoma.Initial endocrine treatment was performed.After 3 months, PSA was reduced to 0.083 ng/mL, and imaging showed the tumor was significantly reduced.Robotic-assisted laparoscopic tumor prostatectomy with extended pelvic lymph node dissection was performed, and endocrine adjuvant therapy was continued after surgery. 【Conclusion】 Prostate mucosa adenocarcinoma has different clinicopathological characteristics and prognosis from conventional acinar adenocarcinoma, and the whole-process management under MDT mode is of great value in the diagnosis and treatment of this disease.
10.The protective effect and mechanism of Taraxasterol on Erastin induced ferroptosis in chondrocytes
Fuli ZHOU ; Hao WANG ; Rendi ZHU ; Yingjie ZHAO ; Yaru YANG ; Renpeng ZHOU ; Wei HU ; Chao LU
Acta Universitatis Medicinalis Anhui 2024;59(6):1053-1059
Objective To investigate the role of Taraxasterol(TAR)on ferroptosis in chondrocytes induced by Erastin.Methods The C28/I2 chondrocyte line was treated with Erastin to construct the ferroptosis model of chon-drocytes in vitro and the experiments were divided into Control,Erastin,TAR,and TAR+Erastin groups.Cell via-bility was detected by the CCK-8 assay.Cytotoxicity was detected by the lactate dehydrogenase(LDH)kit and the Calcein/PI cytokinesis kit.Flow cytometry was used to detect lipid reactive oxygen species(ROS).The intracellular glutathione(GSH)content was detected by GSH kit.Mitochondrial membrane potential was detected by JC-1 stai-ning and RH123 staining.ACSL4 and GPX4 protein expression and the key indicators of ferroptosis were detected by Western blot.Results TAR restored the decreased cell viability of C28/I2 chondrocytes induced by Erastin treatment as well as reduced Erastin-induced cytotoxicity(P<0.01).Compared with the control group,the level of intracellular lipid ROS increased(P<0.01)and the content of GSH decreased(P<0.01)after treatment with Erastin,while TAR could reduce the production of lipid ROS(P<0.01)and increase the content of GSH(P<0.01).TAR restored mitochondrial membrane potential in C28/I2 chondrocytes ferroptosis,decreased ACSL4 pro-tein expression(P<0.01)and increased GPX4 protein expression(P<0.01).In addition,TAR restored the re-duced cell viability caused by IL-1 β treatment.Conclusion TAR can inhibit Erastin induced ferroptosis in C28/I2 chondrocytes,which may be related to the regulation of ACSL4 and GPX4 protein expression.


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