1.Prognostic analysis of genes related to pyroptosis in prostate cancer cells and the regulatory role of NLRP1
Xiaolu MA ; Jiaqin CHEN ; Junlong FENG ; Qi ZHAO ; Bin WANG
Journal of Modern Urology 2025;30(1):73-81
[Objective] To analyze the prognostic value of prostate cancer (PCa) pyroptosis-related genes (PRGs) using gene expression databases and to explore the regulatory mechanism of nucleotidebinding oligomerization domain-like receptor containing pyrin domain 1 (NLRP1) in the pyroptosis of PCa cells. [Methods] Fragments per kilobase of exon model per million reads mapped (FPKM) data and clinical information from PCa and adjacent tissues from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were obtained. Differentially expressed PRGs between PCa and adjacent tissues, classified subtypes and plotted survival curves were analyzed. Univariate Cox regression analysis, least absolute shrinkage and selection operator (LASSO) regression analysis were conducted to screen prognosis-related PRGs, risk scores were calculated, and a prognostic risk model was constructed and validated. Patients were divided into high and low risk groups based on the median risk scores from the training and validation sets, and gene ontology (GO) enrichment and kyoto encyclopedia of genes and genomes (KEGG) analysis were conducted on differentially expressed PRGs. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression level of NLRP1 in PCa cell lines, and pyroptosis was induced in DU145 and LNCaP cells while morphological changes were observed. Western blot (WB) was performed to detect the expression of pyroptosis-related molecules. [Results] A total of 6 prognostic-related PRGs were obtained, including CHMP4C, CYCS, GPX4, GSDMB, NLRP1, and PLCG1. The risk score was positively correlated with the risk of recurrence but negatively correlated with the progression-free survival (P<0.001). The area under the receiver operating characteristic curves (AUCs) for the training set at 1, 3, and 5 years were 0.769 (95%CI: 0.652-0.878), 0.804 (95%CI: 0.736-0.882), and 0.772 (95%CI: 0.631-0.905), respectively, while those for the validation set were 0.731 (95%CI: 0.647-0.826), 0.753 (95%CI: 0.674-0.818), and 0.763 (95%CI: 0.626-0.849), respectively. Differences in expression levels of the 6 PRGs were observed between the high and low risk groups in both the training and validation sets (P<0.05). Cox regression analysis showed that T stage, prostate specific antigen (PSA), Gleason grade, and risk score were independent predictors of PCa prognosis (P<0.05). Differences in risk scores were observed among patients of different ages, T stages, and Gleason grades (P<0.05). NLRP1 was found to be lowly expressed in PCa cell lines and was involved in the regulation of pyroptosis in DU145 and LNCaP cells. [Conclusion] The prognostic risk model constructed based on PRGs has a certain predictability for the prognosis of PCa patients, and NLRP1 may be involved in the regulation of pyroptosis in PCa cells.
2.Functionalized self-assembled micelles enhance effect of tranexamic acid in treatment of cutaneous hyperpigmentation
Junlong QI ; Junyi LIU ; Yuzhou HE ; Wei QIANG ; Shiying ZHANG ; Qiao LIU ; Hongda ZHU
Chinese Journal of Tissue Engineering Research 2025;29(28):6061-6069
BACKGROUND:Topical administration of tranexamic acid can be used for anti-skin pigmentation,but its large polarity makes it difficult to break through the cuticle barrier and cell membrane when administered topically,and the subcutaneous accumulation concentration is not easy to reach the effective therapeutic concentration.OBJECTIVE:To design functionalized self-assembled micelles to enhance the anti-pigmentation effect of tranexamic acid.METHODS:The plant polyphenol derivative epigallocatechin gallate palmitate and metformin were used as carrier materials.The self-assembled micelles with synergistic anti-pigging activity and enhanced drug permeability were prepared by hydrogen bonding and electrostatic interaction.The nanoscale properties and stability of self-assembled drug-loaded micelles were tested,and their transdermal permeability was evaluated,and their biocompatibility and cellular effects were investigated.RESULTS AND CONCLUSION:(1)Functional self-assembled drug-carrying micelles with average particle size of(176.27±5.23)nm,polydispersity coefficient of 0.23±0.02,and the Zeta potential of(-25.67±0.98)mV had good stability.The mass concentrations of tranexamic acid and metformin in the self-assembled drug-carrying micelles were(20.03±0.12)and(6.67±0.08)mg/mL,respectively.The drug loadings of tranexamic acid and metformin in the self-assembled drug-carrying micelles were(19.97±0.12)%and(6.65±0.08)%,respectively.(2)In vitro transdermal results showed that the self-assembled drug-carrying micelles had higher penetration and intradermal retention per unit skin area,and could penetrate and diffuse to deeper parts of the skin.(3)MTT assay results demonstrated that undrug-loaded self-assembled micelles containing tranexamic acid 50-250 μg/mL had no toxic effects on mouse fibroblasts and mouse skin melanoma cells.The self-assembled drug-carrying micelles containing tranexamic acid 500 μg/mL had a slight toxic effect on mouse skin melanoma cells.The self-assembled drug-carrying micelles containing 50-500 μg/mL of tranexamic acid did not cause hemolysis and had good biological safety.(4)In vitro cell culture results showed that self-assembled drug-carrying micelles containing 500 μg/mL tranexamic acid could significantly inhibit the tyrosinase activity and melanin release of mouse skin melanoma cells,and the inhibitory effect was stronger than that of tranexamic acid solution or metformin solution alone.These results indicated that functionalized self-assembled micelles could synergize with tranexamic acid to inhibit tyrosinase activity,reduce melanin synthesis,and enhance the anti-skin pigmentation effect of tranexamic acid.
3.Functionalized self-assembled micelles enhance effect of tranexamic acid in treatment of cutaneous hyperpigmentation
Junlong QI ; Junyi LIU ; Yuzhou HE ; Wei QIANG ; Shiying ZHANG ; Qiao LIU ; Hongda ZHU
Chinese Journal of Tissue Engineering Research 2025;29(28):6061-6069
BACKGROUND:Topical administration of tranexamic acid can be used for anti-skin pigmentation,but its large polarity makes it difficult to break through the cuticle barrier and cell membrane when administered topically,and the subcutaneous accumulation concentration is not easy to reach the effective therapeutic concentration.OBJECTIVE:To design functionalized self-assembled micelles to enhance the anti-pigmentation effect of tranexamic acid.METHODS:The plant polyphenol derivative epigallocatechin gallate palmitate and metformin were used as carrier materials.The self-assembled micelles with synergistic anti-pigging activity and enhanced drug permeability were prepared by hydrogen bonding and electrostatic interaction.The nanoscale properties and stability of self-assembled drug-loaded micelles were tested,and their transdermal permeability was evaluated,and their biocompatibility and cellular effects were investigated.RESULTS AND CONCLUSION:(1)Functional self-assembled drug-carrying micelles with average particle size of(176.27±5.23)nm,polydispersity coefficient of 0.23±0.02,and the Zeta potential of(-25.67±0.98)mV had good stability.The mass concentrations of tranexamic acid and metformin in the self-assembled drug-carrying micelles were(20.03±0.12)and(6.67±0.08)mg/mL,respectively.The drug loadings of tranexamic acid and metformin in the self-assembled drug-carrying micelles were(19.97±0.12)%and(6.65±0.08)%,respectively.(2)In vitro transdermal results showed that the self-assembled drug-carrying micelles had higher penetration and intradermal retention per unit skin area,and could penetrate and diffuse to deeper parts of the skin.(3)MTT assay results demonstrated that undrug-loaded self-assembled micelles containing tranexamic acid 50-250 μg/mL had no toxic effects on mouse fibroblasts and mouse skin melanoma cells.The self-assembled drug-carrying micelles containing tranexamic acid 500 μg/mL had a slight toxic effect on mouse skin melanoma cells.The self-assembled drug-carrying micelles containing 50-500 μg/mL of tranexamic acid did not cause hemolysis and had good biological safety.(4)In vitro cell culture results showed that self-assembled drug-carrying micelles containing 500 μg/mL tranexamic acid could significantly inhibit the tyrosinase activity and melanin release of mouse skin melanoma cells,and the inhibitory effect was stronger than that of tranexamic acid solution or metformin solution alone.These results indicated that functionalized self-assembled micelles could synergize with tranexamic acid to inhibit tyrosinase activity,reduce melanin synthesis,and enhance the anti-skin pigmentation effect of tranexamic acid.
4.Effect of preoperative anemia on perioperative red blood cell transfusion and prognosis in children with septal defect
Yu QI ; Li ZHANG ; Junlong YANG ; Yajuan WU ; Ting YUAN
Chinese Journal of Blood Transfusion 2023;36(5):380-383
【Objective】 To analyze the impact of preoperative anemia on perioperative red blood cell transfusion and prognosis of children undergoing septal defect repair. 【Methods】 The medical records of 208 patients under 18 years old with septal defect, i. e. ventricular septal, atrial septal, ventricular septal with atrial septal defect, in a hospital from December 2018 to March 2022 were collected. They were divided into anemic group (n=52) and non-anemic group (n=156) according to whether they were anemic before operation. The basic information, as well as preoperative, intraoperative and postoperative blood transfusion, postoperative ICU stay, postoperative infection rate and average length of stay were compared between the two groups. 【Results】 The incidence of preoperative anemia in the children with septal defect was 25.0% (52/208). The age, preoperative body weight(kg) and hemoglobin (g/L) of anemic group and non-anemic group was 0.67(0.33, 2) vs 2(1, 3), 6.5(5, 10) vs10.5(8, 14) and 102(91.5, 107) vs 127(121, 134) respectively, all P<0.05. Preoperative, intraoperative and postoperative blood transfusion rates in the anemic and non-anemic groups were 11.54% (6/52) vs 0% (0/156), 92.31% (48/52) vs 72.44% (113/156), 51.92% (27/52) vs 25.0% (39/156), all P<0.05. Postoperative ICU stay (d) and mean length of stay(d) of anemia group and non-anemia group was 3 (2, 6) vs 2 (2, 3) and 19(13, 25) vs14(11, 18) respectively, P<0.05. 【Conclusion】 Preoperative anemia is an important factor affecting perioperative red blood cell transfusion in children with septal defect repair, and also an important reason for prolonging postoperative ICU stay and hospital stay.
5.Tenofovir vs. entecavir on recurrence of hepatitis B virus-related hepatocellular carcinoma beyond Milan criteria after hepatectomy.
Junyi SHEN ; Weili QI ; Junlong DAI ; Shusheng LENG ; Kangyi JIANG ; Yu ZHANG ; Shun RAN ; Chuan LI ; Tianfu WEN
Chinese Medical Journal 2021;135(3):301-308
BACKGROUND:
Hepatectomy for hepatocellular carcinoma (HCC) beyond the Milan criteria is shown to be beneficial. However, a high rate of post-operative HCC recurrence hinders the long-term survival of the patients. This study aimed to investigate and compare the impacts of tenofovir (TDF) and entecavir (ETV) on the recurrence of hepatitis B viral (HBV)-related HCC beyond the Milan criteria.
METHODS:
Data pertaining to 1532 patients who underwent hepatectomy and received antiviral therapy between January 2014 and January 2019 were collected from five centers. Recurrence-free survival (RFS) analysis was performed using the Kaplan-Meier method. Cox proportional hazards regression analysis was performed to determine prognostic factors for HCC recurrence.
RESULTS:
The analysis incorporates 595 HBV-related HCC patients. The overall 5-year RFS was 21.3%. Among them, 533 and 62 patients received ETV and TDF treatment, respectively. The 1-, 3-, and 5-year RFS rates were 46.3%, 27.4%, and 19.6%, respectively, in the ETV group compared with 65.1%, 41.8%, and 37.2%, respectively, in the TDF group (P < 0.001). Multivariate analysis showed that TDF treatment (hazard ratio [HR]: 0.604, P = 0.005), cirrhosis (HR: 1.557, P = 0.004), tumor size (HR: 1.037, P = 0.008), microvascular invasion (MVI) (HR: 1.403, P = 0.002), portal vein tumor thrombus (PVTT) (HR: 1.358, P = 0.012), capsular invasion (HR: 1.228, P = 0.040), and creatinine levels (CREA) (HR: 0.993, P = 0.031) were statistically significant prognostic factors associated with RFS.
CONCLUSIONS
Patients with HCC beyond the Milan criteria exhibited a high rate of HCC recurrence after hepatectomy. Compared to the ETV therapy, TDF administration significantly lowered the risk of HCC recurrence.
Antiviral Agents/therapeutic use*
;
Carcinoma, Hepatocellular/surgery*
;
Guanine/analogs & derivatives*
;
Hepatectomy
;
Hepatitis B virus
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Hepatitis B, Chronic/drug therapy*
;
Humans
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Liver Neoplasms/surgery*
;
Retrospective Studies
;
Tenofovir/therapeutic use*
6.Clinical characteristics and risk factors of delayed intracranial hemorrhage after ventriculoperitoneal shunt in traffic hydrocephalus
Xiaolong QI ; Folin LAN ; Zhiqin LIN ; Dongbin GUO ; Junlong HUANG ; Tianqing LIU ; Jing LU
Chinese Journal of Neuromedicine 2020;19(1):48-53
Objective To analyze the clinical features and risk factors of delayed intracranial hemorrhage (DICH) after ventriculoperitoneal shunt (VPS) in patients with communicating hydrocephalus.Methods One hundred and seventy-six patients with ventriculoperitoneal shunt due to communicating hydrocephalus secondary to craniocerebral trauma,hypertensive intracerebral hemorrhage,brain tumor or intracranial aneurysm rupture hemorrhage,admitted to our hospital from January 2012 to August 2018,were selected in our study;these patients were divided into DICH group and non-DICH group according to whether or not DICH occurred.The clinical features,including incidence,time and location of DICH,were analyzed.The differences of age,gender,length of stay,concomitant diseases,previous operation history,incidences of subdural effusion and puncture canal edema after ventriculoperitoneal shunt,and history of down-regulating shunt valve within 2 weeks between the two groups were compared by univariate analysis.The independent risk factors for DICH were further assessed using multivariable Logistic regression.Results Among 176 patients,23 (13.07%) had DICH;2-11 d after surgery,DICH appeared,manifesting as subdural,ventriculoventricular end canal and/or hemorrhage in one or more areas of the ventricle.There were significant differences in incidence of subdural effusion and history of down-regulating shunt valve within 2 weeks between the two groups (P<0.05).Multivariate Logistic regression analysis showed that subdural effusion after surgery and down-regulation of shunt valve pressure within 2 weeks after ventriculoperitoneal shunt were independent risk factors for DICH (OR=4.516,95%CI:1.555-13.110,P=0.006;OR=5.352,95%CI:1.987-14.414,P=0.001).Conclusion High incidence of DICH mighty be noted within two weeks of ventriculoperitoneal shunt;subdural effusion and pressure reduction of shunt valve within 2 weeks are independent risk factors for DICH,which needs close monitoring and clinical intervention.
7.Glucose transporter-1 promotes migration of osteosarcoma MG63 cells via the Wnt/β-catenin pathway
HAO Junlong ; WANG Yapeng ; YANG Kai ; QI Jin ; WANG Xun ; WANG Jing
Chinese Journal of Cancer Biotherapy 2018;25(5):469-474
[Abstract] Objective: To explore the mechanism of glucose transport protein-1(Glut-1) promoting the migration of osteosarcoma MG63 cells through Wnt/β-catenin pathway. Methods: RNA interference recombinant adenovirus targeting Glut-1 gene (Ad-Glut-siRNA) and control recombinant adenovirus (Ad-GFP) were constructed and transfected into MG63 cells to silence Glut-1 gene expression. The cell migration ability of Blank group, Ad-AFP group, Ad-Glut-siRNA group and AZD2858 (inhibitor of GSK-3) group were detected by Transwell chamber migration assay. Immunofluorescence assay was used to detect the expression of E-cadherin and vimentin in each group and the nuclear translocation of β-catenin. The expression of MMP-2 and MMP-9 in each group and FZD7, β-catenin, Dsh protein in Blank group, Ad-AFP group, Ad-Glut-siRNA group were detected by Western blotting assay. Results: The migration ability of MG63 cells was significantly decreased (P<0.05) after Glut-1 gene silencing, which was restored afterAZD2858 treatment (P <0.05). Compared with Blank group and Ad-GFP group, the E-cadherin level in MG63 cells in Ad-Glut-siRNA group was significantly increased (P<0.05), while the expressions of vimentin, MMP-2, MMP-9, FZD7, β-catenin and Dsh protein were significantly reduced (all P<0.05). Compared with Ad-Glut-siRNA group, E-cadherin expression of AZD2858 group was significantly reduced, while the expressions of vimentin, MMP-2, MMP-9 were significantly up-regulated (P<0.05). Conclusion: The high expression of Glut-1 gene is closely related to the invasion and metastasis of MG63 cells. The possible mechanism is that the high expression of Glut-1 leads to the activation of Wnt/β-catenin pathway, which leads to the decrease of EMT-related protein E-cadherin, and the increase of vimentin and MMP-2, MMP-9, and further promotes the migration of MG63 cells.
8.Rationale and clinical application of simplified modified radical thyroidectomy for differentiated thyroid Carcinoma
Yang ZHANG ; Zhaoqing CUI ; Shanping SUN ; Yubo REN ; Junlong XU ; Yumin YAO ; Qi CHEN ; Wei ZHANG ; Rui LI ; Zhong GUAN ; De JIAO ; Wenlei LI ; Changxin ZHOU
Journal of Endocrine Surgery 2011;05(2):103-105
Objective To explore rationale and clinical application of simplified modified radical thyroideetomy for differentiated thyroid carcinoma.Methods From Jan.2007 to Jun.2010,349 cases of differentiated thyroid carcinoma received simplified operative procedure based on standard modified radical thyroidectomy.The simplified procedure took a low small collar incision(about 10-12 cm).In separating upper and lower skin flaps,subcutaneous tissues covering posterior triangle of neck and posterior edge of sternoeleidomastoid muscle were spared to protect sensory nerves.Subtotal thyroidectomy Was performed to resect the affected lobe,isthmus,and the majority of opposite lobe without considering the size of primary tumor or whether metastasis to the neck lymph nodes happened.Soft tissues of the mainly metastatic areas(Ⅱ a、Ⅲ、Ⅳ、Ⅴb)were cleared.The accessory nerve was not exposed routinely to avoid stimulation.Lymph nodes metastasis in different areas was recorded respectively.Complications in different operative modes were compared.Results Compared with standard modified radical thyroidectomy,the simplified mode had shorter scar-and no limit of neck mobility.Because of muscles and nerves pemervation,movement dysfunction and abnormal sensation of neck and shoulder decreased obviously.The operation duration was shortened.Cervical lymph node status Was evaluated,which provided basis for prognosis judgment and comprehensive treatment.Conclusions The simplified modified radical procedure has the benefit of decreased trauma while maintains the similar recurrence rate compared to modified radical thyroidectomy.It improvs the life quality of patients.This procedure fits the principle of functional radical neck dissection better.
9.Exploration on thinking approach and methodology of syndrome standardization.
Lei GUO ; Qi-Ming ZHANG ; Yong-Yan WANG ; Junlong ZHANG ; Zhibin ZHANG
Chinese Journal of Integrated Traditional and Western Medicine 2006;26(3):258-261
The researching thinking approach of "descending the dimension with the lowering rank, ascending the rank with the raising of nsion of dimension", which could exclude the intervention of non-crucial fact ors and reveal the complexity of syndrome as well, provides a feasible approach for syndrome standardization. A study was conducted by analyzing some syndromes and their correlated factors selected from the "Ancient Good-sized Medical Records Database" through unconditional logistic multivariate stepwise regression by SAS 6.12 universal statistical software to sieve the variable, and the mathematical mode of regression equation was obtained eventually, expressed as logit (p) = alpha + beta1X1 + beta2X2 + ... + betamXm. With that, the research of syndrome standardization was proceeded on the syndromes with diagnostic significance to provide references for standardization of syndrome differentiation. I
Diagnosis, Differential
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Humans
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Logistic Models
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Medicine, Chinese Traditional
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methods
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standards
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Reference Standards
;
Research Design
10.Expressions and significance of survivin and Ki-67 in breast cancer tissues after neoadjuvant chemotherapy
Qi CHEN ; Yumin YAO ; Ying ZHANG ; Junlong XU
Chinese Journal of General Surgery 1994;0(05):-
Objective To explore the expressions of survivin and Ki-67 in breast cancer tissues after neo-adjuvant chemotherapy and their clinical significance.Methods The expressions of survivin and Ki-67 in 60 cases of breast cancer with neo-adjuvant chemotherapy(NACT) with CTF regimen and 60 cases without NACT were detected by SABC immunohistochemical technique.ResultsThe positive rates of survivin(36.7%)and Ki-67(38.3%) in neo-adjuvant chemotherapy group were significantly lower than those in control group(71.7%,61.7%)(P0.05).ConclusionsThe therapeutic effect of neo-adjuvant chemotherapy with CTF regimen can increase the remission rate of breast cancer.Neo-adjuvant chemotherapy could inhibit the expression of survivin protein,and thus further inhibit proliferation of tumor cell.

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