1.Mechanism of Qiju Dihuang Wan in Treatment of Diabetic Retinopathy Based on NLRP3/Caspase-1/GSDMD Signaling Pathway
Ge ZHANG ; Chunlin ZHAO ; Li PAN ; Ying ZHANG ; Zehai CHEN ; Siya ZHANG ; Yiming FANG ; Wei SHI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(20):11-21
ObjectiveTo investigate the protective effect of Qiju Dihuang Wan on diabetic retinopathy (DR) and its regulatory mechanism on the NOD-like receptor protein 3/Cysteinyl aspartate-specific proteinase-1/Gasdermin D (NLRP3/Caspase-1/GSDMD) signaling pathway. MethodsHuman retinal microvascular endothelial cells (HRMEC) were divided into the blank group, model group, and Qiju Dihuang Wan low- and high-dose groups. Except for the blank group, all groups were induced with 40 mmol·L-1 high glucose, and the treatment groups were supplemented with 6% and 12% Qiju Dihuang Wan-containing serum, respectively, based on the induction. After 24 h of culture, the levels of interleukin (IL)-1β and IL-18 were measured by enzyme-linked immunosorbent assay (ELISA), pyroptosis-related protein expression was detected by immunofluorescence and Western blot, and the mRNA levels of NLRP3/Caspase-1/GSDMD signaling pathway-related molecules were determined by real-time polymerase chain reaction (Real-time PCR). The mice were randomly divided into the blank group, model group, Qiju Dihuang Wan low-, medium-, and high-dose groups (11, 22, 44 g·kg-1·d-1), and calcium dobesilate group (0.13 g·kg-1·d-1). Except for the blank group, all groups were intraperitoneally injected with streptozotocin to establish the DR model. After successful modeling, the treatment groups received corresponding doses of Qiju Dihuang Wan crude drug or calcium dobesilate suspension by gavage once daily, while the blank group and model group received an equal volume of normal saline, for 8 consecutive weeks. Fundus changes were examined by optical coherence tomography, optical coherence tomography angiography, and fundus fluorescein angiography. Retinal pathological morphology was observed by hematoxylin-eosin staining. Real-time PCR was used to detect the mRNA levels of NLRP3, Caspase‑1, GSDMD, IL‑1β, and IL‑18 in retinal tissue, and Western blot was used to detect the protein expression of NLRP3, ASC, cleaved Caspase‑1, and GSDMD‑N. ResultsCell experiments showed that compared with the blank group, the model group showed significantly decreased HRMEC viability (P<0.01), and significantly increased levels of IL-1β, IL-18, as well as increased protein expression of NLRP3, cleaved Caspase-1, and GSDMD-N (P<0.01). Compared with the model group, the above indicators were significantly reduced in the high-dose Qiju Dihuang Wan groups (P<0.05, P<0.01). Animal experiments showed that compared with the blank group, the model group had elevated blood glucose (P<0.01), decreased retinal thickness and vascular density (P<0.01), up‑regulated mRNA expression of NLRP3, Caspase‑1, GSDMD, IL‑1β and IL‑18 in retinal tissue (P<0.01), and up‑regulated protein expression of NLRP3, ASC, cleaved Caspase‑1 and GSDMD‑N (P<0.01). Compared with the model group, the Qiju Dihuang Wan medium- and high‑dose groups showed decreased blood glucose (P<0.01), increased retinal thickness and vascular density (P<0.01), alleviated retinal pathological damage, and down‑regulated mRNA expression of NLRP3, Caspase‑1, GSDMD, IL‑1β, IL‑18, as well as protein expression of NLRP3, ASC, cleaved Caspase‑1, and GSDMD‑N (P<0.05, P<0.01). ConclusionQiju Dihuang Wan may exert protective effects against diabetic retinopathy by inhibiting the activation of the NLRP3/Caspase-1/GSDMD signaling pathway and alleviating high glucose-induced retinal pyroptosis.
2.Mechanism of Qiju Dihuang Wan in Treatment of Diabetic Retinopathy Based on NLRP3/Caspase-1/GSDMD Signaling Pathway
Ge ZHANG ; Chunlin ZHAO ; Li PAN ; Ying ZHANG ; Zehai CHEN ; Siya ZHANG ; Yiming FANG ; Wei SHI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(20):11-21
ObjectiveTo investigate the protective effect of Qiju Dihuang Wan on diabetic retinopathy (DR) and its regulatory mechanism on the NOD-like receptor protein 3/Cysteinyl aspartate-specific proteinase-1/Gasdermin D (NLRP3/Caspase-1/GSDMD) signaling pathway. MethodsHuman retinal microvascular endothelial cells (HRMEC) were divided into the blank group, model group, and Qiju Dihuang Wan low- and high-dose groups. Except for the blank group, all groups were induced with 40 mmol·L-1 high glucose, and the treatment groups were supplemented with 6% and 12% Qiju Dihuang Wan-containing serum, respectively, based on the induction. After 24 h of culture, the levels of interleukin (IL)-1β and IL-18 were measured by enzyme-linked immunosorbent assay (ELISA), pyroptosis-related protein expression was detected by immunofluorescence and Western blot, and the mRNA levels of NLRP3/Caspase-1/GSDMD signaling pathway-related molecules were determined by real-time polymerase chain reaction (Real-time PCR). The mice were randomly divided into the blank group, model group, Qiju Dihuang Wan low-, medium-, and high-dose groups (11, 22, 44 g·kg-1·d-1), and calcium dobesilate group (0.13 g·kg-1·d-1). Except for the blank group, all groups were intraperitoneally injected with streptozotocin to establish the DR model. After successful modeling, the treatment groups received corresponding doses of Qiju Dihuang Wan crude drug or calcium dobesilate suspension by gavage once daily, while the blank group and model group received an equal volume of normal saline, for 8 consecutive weeks. Fundus changes were examined by optical coherence tomography, optical coherence tomography angiography, and fundus fluorescein angiography. Retinal pathological morphology was observed by hematoxylin-eosin staining. Real-time PCR was used to detect the mRNA levels of NLRP3, Caspase‑1, GSDMD, IL‑1β, and IL‑18 in retinal tissue, and Western blot was used to detect the protein expression of NLRP3, ASC, cleaved Caspase‑1, and GSDMD‑N. ResultsCell experiments showed that compared with the blank group, the model group showed significantly decreased HRMEC viability (P<0.01), and significantly increased levels of IL-1β, IL-18, as well as increased protein expression of NLRP3, cleaved Caspase-1, and GSDMD-N (P<0.01). Compared with the model group, the above indicators were significantly reduced in the high-dose Qiju Dihuang Wan groups (P<0.05, P<0.01). Animal experiments showed that compared with the blank group, the model group had elevated blood glucose (P<0.01), decreased retinal thickness and vascular density (P<0.01), up‑regulated mRNA expression of NLRP3, Caspase‑1, GSDMD, IL‑1β and IL‑18 in retinal tissue (P<0.01), and up‑regulated protein expression of NLRP3, ASC, cleaved Caspase‑1 and GSDMD‑N (P<0.01). Compared with the model group, the Qiju Dihuang Wan medium- and high‑dose groups showed decreased blood glucose (P<0.01), increased retinal thickness and vascular density (P<0.01), alleviated retinal pathological damage, and down‑regulated mRNA expression of NLRP3, Caspase‑1, GSDMD, IL‑1β, IL‑18, as well as protein expression of NLRP3, ASC, cleaved Caspase‑1, and GSDMD‑N (P<0.05, P<0.01). ConclusionQiju Dihuang Wan may exert protective effects against diabetic retinopathy by inhibiting the activation of the NLRP3/Caspase-1/GSDMD signaling pathway and alleviating high glucose-induced retinal pyroptosis.
3.Characteristics of gut mycobiome in gout patients and their clinical correlation
Yusong GE ; Chunlin ZHANG ; Yinxuan DU ; Xiaoqin GUO ; Yuanyuan LEI ; Zhanjie HOU ; Lei RAN ; Jing XU ; Shiming YANG
Journal of Army Medical University 2025;47(8):858-869
Objective To compare the gut fungal composition between gout patients and healthy individuals through high-throughput sequencing of ribosomal DNA internal transcribed spacer 1(ITS1).Methods Gout patients and healthy volunteers who visited our hospital from January 2023 to December 2024 were enrolled in this study.Then based on established medical guidelines,the gout patients were categorized into 3 groups:Group H(asymptomatic hyperuricemia,n=14),Group G(acute gouty arthritis,n=14),and Group I(intercritical period of gouty arthritis,n=15),and the healthy individuals were assigned into Group N(n=9).Fecal samples were collected from all the participants to undergo ITS1 sequencing analysis.The differences in diversity and composition of gut mycobiome,and FunGuild-derived fungal functions and nutritional status were compared among the 4 groups,and the correlation between the gut mycobiome and clinical indicators was analyzed.Results There were no significant differences in baseline features such as gender,age,glomerular filtration rate(GFR),and levels of serum creatinine(SCr)and serum urea among Group N and other gout groups,but obvious differences were observed in body mass index(BMI),erythrocyte sedimentation rate,and levels of C-reactive protein(CRP),serum uric acid(SUA),and IL-1β and IL-6(P<0.05).In terms of gut fungal diversity,ITS1 analysis showed there were no statistical differences in α-diversity or the principal coordinate analysis(PCoA)of β-diversity among the groups.However,as gout progressed,significant changes were observed in β-diversity indices,indicating a shift in the gut fungal community composition with disease advancement(P<0.05).The phyla Ascomycota,Basidiomycota,and Mucoromycotina were the dominant fungal phyla in all groups.Compared with the other 3 gout groups,the abundance of Pichia was significantly increased in Group N(P<0.05),that of Saccharomyces was in Group H(P<0.05),and that of Starmerella was in Group G(P<0.05).Correlation analysis between the gut mycobiome and clinical indices indicated that the relative abundance of Starmerella was significantly positively correlated with IL-1β(P<0.01)and IL-6(P<0.05).The relative abundance of Pichia was significantly positively correlated with IL-1β and IL-6 levels(P<0.05),and negatively correlated with serum urea level(P<0.05),and the relative abundance of Saccharomyces was negatively correlated with IL-1β and IL-6 levels(P<0.05).Conclusion There exist significant alterations in both the diversity and composition of gut fungi among patients with gout at various stages.Notably,the fluctuations in the relative abundance of Starmerella,Pichia and Saccharomyces appear to correlate with key clinical indicators.
4.Value of multimodal ultrasound combined with immune-inflammatory indicators in predicting axillary lymph node metastasis in patients with breast cancer
Junhui LI ; Shu GE ; Jue WANG ; Qing ZHANG ; Chunlin YANG
Journal of Clinical Medicine in Practice 2025;29(15):1-5
Objective To investigate the value of multimodal ultrasound combined with immune-inflammatory indicators in predicting axillary lymph node(ALN)metastasis in patients with breast cancer.Methods The clinical data of 106 breast cancer patients treated in the Ultrasound Depart-ment of Nantong Cancer Hospital from January 2023 to June 2024 were analyzed,and the patients were divided into ALN metastasis group and non-metastasis group based on postoperative pathological re-sults.Univariate and multivariate Logistic regression models were used to analyze the immune-inflam-matory indicators and ultrasound parameters in both groups.The receiver operating characteristic(ROC)curve was plotted to evaluate the predictive value of each indicator.Results Univariate anal-ysis showed significant differences between the ALN metastasis group and the non-metastasis group in terms of the neutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio(PLR),aspect ratio,maximum tumor diameter,and Adler blood flow grade(P<0.05).NLR,PLR,maximum tumor di-ameter,and Adler blood flow grade were independent influencing factors for predicting ALN metastasis in breast cancer(P<0.05).The area under the curve(AUC)for predicting ALN metastasis using multimodal ultrasound combined with immune-inflammatory indicators was 0.877,with a diagnostic sensitivity of 84.7%and a specificity of 76.6%.The predictive efficacy of the combined multi-indicators was significantly higher than that of individual indicators(P<0.05).Conclusion Multimodal ultrasound combined with immune-inflammatory indicators is associated with ALN metastasis in breast cancer patients and can provide a reference basis for clinical diagnosis,subsequent treatment,and prognosis evaluation.
5.Comprehensive analysis of the clinical and pathological features and prognoses of children with immunoglobulin A vasculitis nephritis with immunoglobulin M deposits in glomeruli
Pao YU ; Pei ZHANG ; Bi ZHOU ; Zheng GE ; Zhiqiang ZHANG ; Chunlin GAO ; Zhengkun XIA
Kidney Research and Clinical Practice 2025;44(5):814-824
The clinical significance of immunoglobulin M (IgM) deposition in the glomeruli of children with immunoglobulin A vasculitis (IgAV) nephritis remains unclear. This study aimed to analyze the clinical and pathological characteristics and prognoses of this population. Methods: Patients were divided into three groups according to histopathological IgM deposition intensity: grade A (204 cases); grade B (101 cases); and grade C + D (54 cases). The clinicopathological characteristics and follow-up information of the three groups of patients were collected and compared. Results: This study included 359 children with IgAV nephritis and found that 44.9% of them had IgM deposition in the kidney glomerulus. Children with IgM deposition and IgAV nephritis have relatively severe clinicopathological features. A total of 39 children (10.9%) had entered the end-stage kidney disease stage. Kaplan-Meier analysis showed that cumulative renal survival was significantly lower in children with higher glomerular IgM deposition (log-rank test chi-square = 55.341, p < 0.001). Multivariable Cox regression analysis found that IgM deposition (grade C + D: hazard ratio [HR], 2.04; 95% confidence interval [CI], 1.67–3.93; p = 0.04; grade B: HR, 2.59; 95% CI, 1.08–4.23; p = 0.03) and S1 (HR, 1.76; 95% CI, 0.42–2.98; p = 0.03) were independent risk factors for poor prognoses in children with IgAV nephritis. The receiver operating characteristic curve indicated that IgM deposition presented significant predictive capability. Conclusion: There are differences in the clinicopathological features of IgAV nephritis with different degrees of mesangial IgM deposition. IgM deposition and S1 are independent risk factors for poor prognoses of IgAV nephritis in children.
6.Improving the positional adaptability: structure-based design of biphenyl-substituted diaryltriazines as novel non-nucleoside HIV-1 reverse transcriptase inhibitors.
Kaijun JIN ; Minjie LIU ; Chunlin ZHUANG ; Erik DE CLERCQ ; Christophe PANNECOUQUE ; Ge MENG ; Fener CHEN
Acta Pharmaceutica Sinica B 2020;10(2):344-357
In order to improve the positional adaptability of our previously reported naphthyl diaryltriazines (NP-DATAs), synthesis of a series of novel biphenyl-substituted diaryltriazines (BP-DATAs) with a flexible side chain attached at the C-6 position is presented. These compounds exhibited excellent potency against wild-type (WT) HIV-1 with EC values ranging from 2.6 to 39 nmol/L and most of them showed low nanomolar anti-viral potency against a panel of HIV-1 mutant strains. Compounds and had the best activity against WT, single and double HIV-1 mutants and reverse transcriptase (RT) enzyme comparable to two reference drugs (EFV and ETR) and our lead compound NP-DATA (). Molecular modeling disclosed that the side chain at the C-6 position of DATAs occupied the entrance channel of the HIV-1 reverse transcriptase non-nucleoside binding pocket (NNIBP) attributing to the improved activity. The preliminary structure-activity relationship and PK profiles were also discussed.
7.Clinical analysis of abdominal bronchogenic cyst in seven cases
Zhongyi WU ; Yuanhong XU ; Jin LONG ; Zhe LIU ; Kejian GUO ; Shaowei SONG ; Chunlin GE
Chinese Journal of General Surgery 2017;32(3):220-223
Objective To explore the diagnosis and treatment of bronchogenic cyst in the abdomen.Methods Clinical data of 7 cases with abdominal bronchogenic cyst in the First Affiliated Hospital of China Medical University from October 2001 to February 2016 were retrospectively analyzed.Results Of the 7 patients,5 were male and 2 were female aging from 36 to 50 years with a median age of 37 years.Two cases were complaining for upper abdominal pain,5 cases were asymptomatic.Ultrasonography revealed hypoechoic or anechoic mass.Color doppler flow imaging showed no blood flow.Contrast-enhanced CT scans showed no obvious enhancement in 6 out of 7 cases,all patients underwent cystectomy successfully.Cysts were of unilocular in 6 cases and multilocular in one.Bronchogenic cysts were diagnosed by pathology in all 7 cases.Six patients were followed up from 1 month to 6 years with no recurrence.Conclusions Abdominal bronchogenic cyst is benign and postoperative prognosis is very good.
8.Advances in the mechanism of action of L1CAM in pancreatic cancer invasion and me-tastasis
Chinese Journal of Clinical Oncology 2017;44(7):349-353
Pancreatic cancer has the highest mortality among malignant cancers. Known asthe king of cancer,it lacks early symp-toms, diagnostic methods and oncologic markers. Early lymph node metastasis could be found in this disease. Moreover, advanced panereatic cancer is incurable by surgery. Due to the limited efficacy of surgery, as well as radiotherapy and chemotherapy tolerance, therapeutic methods for pancreatic cancer are being explored. L1 cell adhesion molecule (L1CAM) is a member of the cell adhesion molecule inmunoglobulin (Ig) super family that is usually expressed in normal developing nervous tissues. L1CAM is highly expressed in pancreatic cancer cells, binds withα5-integrin to activate downstream factors that mediate tumor metastasis and invasion via the TGF-β1/JUK/slug signaling pathway, induces epithelium-mesenchymal transition, and resists chemotherapy drugs. However, L1CAM forms abnormal vessels that increase the invasiveness of pancreatic cancer cells. This abnormal L1CAM expression in pancreatic can-cer cells is a new therapeutic target in pancreatic cancer treatment. Therefore, future studies on L1CAM could promote the develop-ment of pancreatic cancer therapy and provide new treatment methods.
9.Clinical features of pancreatic cystic neoplasms and its therapeutic strategy
Journal of Clinical Hepatology 2016;32(5):860-863
The detection rate of pancreatic cystic neoplasms obviously increases with the development of imaging technology. However, it is still difficult to make the differential diagnosis between different types of pancreatic cystic neoplasms. For pancreatic cystic neoplasms, the physical condition of the patient, tumor size, location, patient preference, and other potential factors should be considered to develop an individualized treatment. The incidence rate of complications is high, although the operative mortality of pancreatic cystic neoplasms is very low. Therefore, it is necessary to strictly make the treatment decision for pancreatic cystic neoplasms.
10.The value of pancreatic CT perfusion on biological behavior assessment in pancreatic cancer
Fanbin MENG ; Kejian GUO ; Chunlin GE ; Shaowei SONG
China Oncology 2015;(5):387-391
Background and purpose:The prognosis of pancreatic cancer is poor. This study aimed to evaluate the value of pancreatic CT perfusion on biological behavior assessment in pancreatic cancer. Methods:This study collected 78 cases of pancreatic cancer which diagnosed by the method of pancreatic CT perfusion, and detected the differences of the values of blood lfow (BF), blood volume (BV), permeability (per), peak value (PE) and time to peak (TTP) between normal pancreatic tissues and tumor tissues. Combined with clinical and pathological data. Besides, this study evaluated the relationship between perfusion parameters of tumor tissues and tumor size, lymph node metastasis, distant metastasis, preoperative serum CA199 level, Ki-67, p53, CEA, CA199, CD34 expression of tumor tissues. Results:The values of BF, BV, per and PE in pancreatic tumor tissue were signiifcantly lower than those in normal pancreatic tissue. The BF values of cases with high levels of serum CA199 and with CA199 positively expressed tissues were signiifcantly higher than those with negative expression. The PE values of cases with positive tissue expression of Ki-67 were significantly higher than those with negative expression. The TTP values of cases with positive tissue expression of CEA were signiifcantly lower than those with negative expression. The per values of well differentiated cases was signiifcantly higher than those of moderately/poorly differentiated cases. Conclusion:CT perfusion may have its value on assessment of tumor biological behavior in pancreatic cancer.

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