1.Sesquiterpene ZH-13 from Aquilariae Lignum Resinatum Improves Neuroinflammation by Regulating JNK Phosphorylation
Ziyu YIN ; Yun GAO ; Junjiao WANG ; Weigang XUE ; Xueping PANG ; Huiting LIU ; Yunfang ZHAO ; Huixia HUO ; Jun LI ; Jiao ZHENG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):139-145
ObjectiveTo study the pharmacological substances and mechanisms through which sesquiterpene ZH-13 from Aquilariae Lignum Resinatum improves neuroinflammation. MethodsBV-2 microglial cells were stimulated with lipopolysaccharide (LPS) to induce neuroinflammation. The cells were divided into the normal group, the model group, and the ZH-13 low- and high-dose treatment groups (10, 20 μmol·L-1). The model group was treated with 1 μmol·L-1 LPS. Cell viability was assessed using the cell proliferation and activity assay (CCK-8 kit). Nitric oxide (NO) release in the cell supernatant was measured using a nitric oxide kit (Griess method). The mRNA expression levels of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS), and interleukin-6 (IL-6) were detected by real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). The phosphorylation of mitogen-activated protein kinase (MAPK) pathway proteins was assessed by Western blot. ResultsCompared with the model group, ZH-13 dose-dependently reduced NO release from BV-2 cells under LPS stimulation (P<0.05, P<0.01). In the 20 μmol·L-1 ZH-13 treatment group, the mRNA expression levels of IL-1β, TNF-α, iNOS, and IL-6 were significantly reduced compared to the model group (P<0.05, P<0.01). In both the low- and high-dose ZH-13 groups, the expression of the inflammatory factor TNF-α and the phosphorylation of c-Jun N-terminal kinase (JNK) in the upstream MAPK pathway were significantly reduced (P<0.05). After stimulation with the JNK agonist anisomycin (Ani), both low- and high-dose ZH-13 treatment groups showed reduced phosphorylation of JNK proteins compared to the Ani-treated group (P<0.01). ConclusionThe sesquiterpene compound ZH-13 from Aquilariae Lignum Resinatum significantly ameliorates LPS-induced neuroinflammatory responses in BV-2 cells by inhibiting excessive JNK phosphorylation and reducing TNF-α expression. These findings elucidate the pharmacological substances and mechanisms underlying the sedative and calming effects of Aquilariae Lignum Resinatum.
2.Efficacy and safety of whole-brain low-dose radiotherapy combined with ICI and intrathecal chemotherapy for leptomeningeal metastases from lung cancer
Xiang LISHA ; Zhang XUANWEI ; Yu MIN ; Xiu WEIGANG ; Zou BINGWEN ; Xu YONG ; Liu YONGMEI ; Zhou LIN ; Xue JIANXIN ; Lu YOU
Chinese Journal of Clinical Oncology 2024;51(18):943-949
Objective:To explore the efficacy and safety of whole-brain low-dose radiotherapy(LDRT)combined with PD-1 inhibitor sin-tilimab and intrathecal pemetrexed(IP)for the treatment of refractory non-small cell lung cancer(NSCLC)with leptomeningeal metastases(LM).Methods:Retrospective analysies were was performed on eight NSCLC patients with LM at the West China Hospital of Sichuan Uni-versity from December 2022 to May 2024.Among the eight patients,there were four were males and four were females,with a median age of 49 years(rangeing,between 34 to 58 years).All patients were treated with whole-brain LDRT combined with immune checkpoint inhibit-or(ICI)and intrathecal chemotherapy regimens,and the therapeutic efficacy was evaluated according to the Response Assessment in Neuro-Oncology(RANO)criteria and the Karnofsky physical status(KPS)score.Adverse reactions were assessed according to the Common Criteria for the Evaluation of Adverse Events(CTCAE version 5.0).Survival analysis was performed using the Kaplan-Meier method.The classification proportion of cerebrospinal fluid subsets before and after treatment was analyzed using by single-cell sequencing,and the differential ana-lysis of gene expression in parallel cells was performed.Results:The best clinical treatment effects in eight patients were were evaluated us-ing the RANO criteria:five patients(62.5%)were evaluated as improved and three(37.5%)as stable.The median KPS score of the eight pa-tients was 30(20-50)before treatment,which was significantly improved to 60(40-90)after treatment(P=0.000 9).The remission rate of neurological symptoms was 100%(8/8)in eight patients.The median neurological progression-free survival(NPFS)was 12 months.The res-ults of single-cell sequencing in CSF of patientss(P1)showed that the proportion of T cells in the patient samples after whole-brain LDRT treatment was significantly higher than that before treatment(6.08%vs.68.87%),and the proportion of tumor cells was significantly lower(12.92%vs.0.6%).The differential analysis of gene expression showed that CCL5 and CXCL13 were significantly upregulated in T cells of CSF after WB-LDRT treatment.Conclusions:The combination of whole-brain LDRT with ICI and IP in the treatment of NSCLC with LM can signific-antly alleviate neurological symptoms,improve quality of life and prolong the NPFS of patients,which is a safe and effective treatment.
3.Adverse drug reactions associated with thalidomide treatment for oral mucosal diseases: a report of 44 cases
Xiaojuan XUE ; Jing HUANG ; Bin FENG ; Weigang WANG ; Jiao YUE ; Yanfei MA ; Yao LIN
Chinese Journal of Primary Medicine and Pharmacy 2024;31(10):1457-1462
Objective:To analyze the categories, characteristics, and clinical symptoms of adverse reactions associated with thalidomide treatment for oral mucosal diseases, providing a reference for the safe use of this medication in patients.Methods:A cross-sectional study was conducted to retrospectively analyze the adverse reactions to thalidomide treatment in 44 patients with oral mucosal diseases who received treatment at the Third Affiliated Hospital of Air Force Medical University from January 2019 to December 2023. The correlation between the age and sex of patients experiencing adverse reactions, the timing of these reactions in relation to sex, the organs and their appendages affected by the adverse reactions, and the outcomes of these reactions were statistically analyzed.Results:The incidence of adverse reactions associated with thalidomide treatment at the hospital was 0.21% (44/21 329), with a higher prevalence among female patients. Multiple organs were affected in 50.00% (22/44) of the cases, though the reactions were relatively concentrated, primarily involving the skin and its appendages, the central and peripheral nervous systems, and the gastrointestinal system. The main manifestations included rash and dizziness.Conclusion:In the treatment of oral mucosal diseases with thalidomide, it is essential to monitor adverse drug reactions, particularly those affecting the nervous system. Special attention should be given to the potential teratogenicity of thalidomide in individuals of childbearing age. In addition, it is vital to consistently investigate strategies to ensure the safety of patients using medication at home.
4.Gemcitabine Inhibits the Progression of Pancreatic Cancer by Restraining the WTAP/MYC Chain in an m6A-Dependent Manner
Pei CAO ; Weigang ZHANG ; Junyi QIU ; Zuxiong TANG ; Xiaofeng XUE ; Tingting FENG
Cancer Research and Treatment 2024;56(1):259-271
Purpose:
Pancreatic cancer (PC) is a common malignant tumor of the digestive system, and its 5-year survival rate is only 4%. N6-methyladenosine (m6A) RNA methylation is the most common post-transcriptional modification and dynamically regulates cancer development, while its role in PC treatment remains unclear.
Materials and Methods:
We treated PC cells with gemcitabine and quantified the overall m6A level with m6A methylation quantification. Real-time quantitative reverse transcription polymerase chain reaction and Western blot analyses were used to detect expression changes of m6A regulators. We verified the m6A modification on the target genes through m6A-immunoprecipitation (IP), and further in vivo experiments and immunofluorescence (IF) assays were applied to verify regulation of gemcitabine on Wilms’ tumor 1–associated protein (WTAP) and MYC.
Results:
Gemcitabine inhibited the proliferation and migration of PC cells and reduced the overall level of m6A modification. Additionally, the expression of the “writer” WTAP was significantly downregulated after gemcitabine treatment. We knocked down WTAP in cells and found target gene MYC expression was significantly downregulated, m6A-IP also confirmed the m6A modification on MYC. Our experiments showed that m6A-MYC may be recognized by the “reader” IGF2BP1. In vivo experiments revealed gemcitabine inhibited the tumorigenic ability of PC cells. IF analysis also showed that gemcitabine inhibited the expression of WTAP and MYC, which displayed a significant trend of co-expression.
Conclusion
Our study confirmed that gemcitabine interferes with WTAP protein expression in PC, reduces m6A modification on MYC and RNA stability, thereby inhibiting the downstream pathway of MYC, and inhibits the progression of PC.
5.The diagnosis and risk factors for postoperative acute pancreatitis following pancreaticoduodenectomy
Daobin WANG ; Ding SUN ; Weigang ZHANG ; Zuxiong TANG ; Junyi QIU ; Lei QIN ; Haixin QIAN ; Xiaofeng XUE
Chinese Journal of General Surgery 2022;37(7):487-491
Objective:To study factors associated with postoperative acute pancreatitis (POAP) in patients following pancreaticoduodenectomy.Methods:This retrospective analysis included 60 patients who underwent pancreaticoduodenectomy at the First Affiliated Hospital of Soochow University from Jan 2020 to Aug 2021. Enhanced computed tomography was used to identify POAP during postoperative period of 4 to 9 days. Univariate analysis and multivariate analysis were used to find out the risk factors of POAP.Results:Of the 60 patients, 13 cases (21.7%) developed POAP. The incidence of clinically related pancreatic fistula with abdominal abscess (76.9% vs.19.1%, χ2=15.71, P<0.000 1), postoperative hospital stay (26 d vs. 18 d, U=141.5, P=0.002 5) and the severity of complications (Clavien-Dindo grade≥Ⅲ: 53.8% vs. 21.3%, χ2=5.32, P=0.02) were significantly higher in the POAP group. But there was no significant deviation between the two groups when it comes to the severe post pancreatectomy delayed hemorrhage (7.7% vs. 0, χ2=3.68, P=0.06) and the delayed gastric emptying (30.8% vs. 21.3%, χ2=0.51, P=0.47). In the univariate analysis, patients with higher body mass index ( P=0.000 3), smaller main pancreatic duct diameter ( P<0.000 1) and softer texture of the pancreas ( P=0.009) were more likely to develop POAP after pancreaticoduodenectomy. In the multivariate analysis, the pancreatic duct diameter≤2 mm ( OR=0.005,95% CI 0.000 06-0.44, P=0.020), the softer texture of pancreas ( OR=0.005, 95% CI 0.000 04-0.47, P=0.023) were risk factors for POAP. Conclusions:Patients with postoperative acute pancreatitis increased the incidence of pancreatic fistula complicating abdominal abscess.Small caliber pancreatic tube, soft texture of pancreas were risk factors of POAP.
6.Long non-coding RNA XLOC009038 promotes proliferation, migration and invasion of esophageal squamous cell carcinoma
Xin DING ; Yong ZHENG ; Jing LI ; Xue ZHENG ; Juanjuan TONG ; Danping YANG ; Weigang CHEN
The Journal of Practical Medicine 2019;35(3):369-374
Objective To observe the effects of long-chain non-coding RNA XLOC009038 on the proliferation, apoptosis, migration and invasion of esophageal squamous cell carcinoma EC 109 and EC9706 cells and explore its mechanism. Methods XLOC009038 interfering plasmid was constructed and transfected into EC 109 and EC9706 cells to down-regulate the expression of XLOC009038 gene. MTT colorimetry and clonogenic assay were used to observe the changes of cell proliferation and cloning ability before and after gene down-regulation.Flow cytometry was used to detect apoptosis. Transwell was used to measure the changes of cell migration and invasion ability before and after transfection. Western blot was used to detect the expression of procaspase 3 protein in cells before and after transfection. Results The expression of XLOC009038 gene in the two cells was significantly lower than that in the control group (P < 0.001). After down-regulation of XLOC009038 gene expression, the cloning and proliferation ability of EC 109 and EC9706 cells decreased significantly (P< 0.05). Compared with the control group, the migration and invasion ability of EC 109 and EC9706 cells decreased significantly (P < 0.001).Flow cytometry showed that the apoptosis rate of EC 109 and EC9706 cells increased after down-regulation of XLOC009038 (P <0.001). The expression of procaspase 3 increased in the experimental group after interfering with XLOC009038 (P = 0.013; P < 0.001). Conclusions Over-expression of XLOC009038 might be closely related to occurrence and development of the esophageal cancer. Over-expression of XLOC009038 can enhance the proliferation, apoptosis, migration and invasion of esophageal cancer cells in vitro through the procaspase3 pathway.
7.Differences of gut microbiota between type 2 diabetes and non-diabetic population
Shixuan LIU ; Yong XUE ; Tao YUAN ; Yong FU ; Naishi LI ; Yingyue DONG ; Baoli ZHU ; Weigang ZHAO
Chinese Journal of Clinical Nutrition 2019;27(6):342-348
Objective To explore the difference of gut microbiota between type 2 diabetes mellitus (T2DM) and non-diabetic population in Beijing. Methods 83 T2DM patients were selected as T2DM group and 64 non-diabetic subjects were selected as control group. Fecal samples were collected from all the subjects. The intestinal flora was detected by metagenome sequencing technology. Results 11 bacterialphyla were detec-ted in the two groups, there were significant differences in species diversity of Actinobacteria (P=0. 013), Firmicutes (P=0. 005), Fusobacteria (P=0. 001), Proteobacteria (P<0. 001) between the two groups. Actinobacteria, Fusobacteria and Proteobacteria were all enriched in the T2DM group, Firmicutes were enriched in the control group. 152 bacterial genera were detected in the two groups with 31 bacterial genera ofsignificant differences. In T2DM group, the levels of Roseburia, Eubacterium and Faecalibacterium decreased, while the levels of Bifidobacterium, Lactobacillus and Escherichia increased. Conclusion There are significant differ-ences in the composition of gut microbiota between T2DM patients and non-diabetic population. Regulation of gut microbiota in T2DM patients may be helpful to improve the condition of T2DM.
8. Ultrasonography-guided wire-localization and nano-carbon staining for detection of sentinel lymph node in breast cancer
Xuye ZHAO ; Weigang WANG ; Yaling LI ; Shuai LIANG ; Nan ZHAO ; Ailing LIU ; Xiangyang GUO ; Huijuan XU ; Xia LI ; Yanfeng XI ; Xinzheng LI ; Gaiqin XUE
Cancer Research and Clinic 2018;30(8):536-540
Objective:
To evaluate the usage of ultrasound guided wire-localization, nano-carbon staining and the combination of the above two methods in detecting sentinel lymph node (SLN) in breast cancer.
Methods:
A total of 159 cases of breast cancer from May 2015 to December 2017 in Shanxi Provincial Cancer Hospital were selected, and they were treated with ultrasound guided wire-localization, nano-carbon staining and combination of the two methods separately to detect SLN before the operation. After the operation, SLN and axillary lymph node in each group were marked and made pathological diagnosis.
Results:
There were 69 cases with pathological diagnosis of SLN metastasis and 90 cases without abnormal representation. With the patient as the unit, the sensitivity of ultrasound guided wire-localization was 100.0% (69/69), the sensitivity of nano-carbon staining was 98.6% (68/69), and the sensitivity of combination of the two methods was 97.1% (67/69). The specificity of ultrasound guided wire-localization was 3.3% (3/90), the specificity of nano-carbon staining was 2.2% (2/90), and the specificity of combination of the two methods was 5.6% (5/90). With the count of SLN as the unit, the combination of the two methods had the highest diagnostic efficiency in detecting SLN, and the difference was statistical significant (
9.Expression and signification of microRNA-31 in the plasma of esophageal squamous cell carcinoma of Xinjiang Kazak and Han nationality patients
Guijun SHI ; Xue KANG ; Yong ZHENG ; Yanzhi HAN ; Ning ZHANG ; Cuihua QI ; Weigang CHEN
The Journal of Practical Medicine 2016;32(1):61-64
Objective To analyze the correlation between miR-31 and ESCC in expression of miR-31 in the plasma of ESCC in Xinjiang Kazak and Han nationality patients. Methods The plasma samples were collected respectively from patients with ESCC in 20 cases and healthy subjects in 20 cases. The relatively expression of miR-31 was detected by real-time Q-PCR. Results The expression of miR-31 with ESCC were higher than those of the normal control group, which related to the degree of tumor differentiation in Kazak ESCC patients (P < 0.01); the levels of miR-31 relative expression in Kazak were higher than that of Han (P = 0.008, P = 0.027). Conclusion miR-31 may be involved in the occurrence of ESCC in Han and Kazak nationality. miR-31 might be another risk factor in high incidence of ESCC in Kazak than Han nationality.
10.Practice and insights on standardized residency training at PUMCH
Shuyang ZHANG ; Hui PAN ; Huadan XUE ; Huijuan ZHU ; Weigang FANG ; Yupei ZHAO
Chinese Journal of Hospital Administration 2015;31(12):914-916
A profile of the standardized residency training at PUMCH in nine decades depicted the rigorous attitude, strict requirements, tight methodology, enhanced basic theories, basic knowledge and basic skills training, which constitute the characteristic standardized residency training system of the hospital.

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