1.Expression of AU-rich element RNA-binding factor 1 in hepatocellular carcinoma and its value in prognostic evaluation
Yuan DUAN ; Ting ZHANG ; Jing ZHANG ; Guiwen GUAN ; Jingzhou WANG ; Xiangmei CHEN
Journal of Clinical Hepatology 2024;40(9):1833-1839
Objective To investigate the effect of AU-rich element RNA-binding factor 1(AUF1)on the proliferation,apoptosis,and migration abilities of hepatocellular carcinoma(HCC)cells and possible mechanisms,and to clarify the role and molecular mechanism of AUF1 in the progression of HCC.Methods The UALCAN and TCGA-HCC databases were used to analyze the expression of AUF1 in pan-cancer and investigate the association of the expression level of AUF1 with the clinicopathological features and prognosis of HCC patients.CCK-8 assay,cell apoptosis assay,and Transwell chamber assay were used to investigate the function of AUF1 at the cellular level,and RNA-seq assay was used to investigate transcriptome changes in HCC cells after AUF1 knockdown.The t-test was used for comparison of continuous data between two groups;the Kaplan-Meier method was used to plot survival curves,and the log-rank test was used for comparison of survival rates.Results There were abnormal mRNA and protein expression levels of AUF1 in various tumor tissues compared with normal tissue(P<0.05).The mRNA expression level of AUF1 was positively correlated with the degree of HCC malignancy and the poor prognosis of early-stage HCC(P<0.05).Compared with the control group,the overexpression of exogenous AUF1 in HCC cells promoted the proliferation of HCC cells and inhibited the apoptosis and migration of HCC cells,while AUF1 knockdown inhibited HCC cell proliferation and promoted the apoptosis and migration of HCC cells.The RNA-seq analysis showed that AUF1 knockdown mainly affected the Wnt/β-catenin pathway and downregulated the protein expression level of β-catenin.Conclusion The abnormal expression of AUF1 is associated with the prognosis of early-stage HCC,and AUF1 may exert an oncogenic effect by activating the Wnt signaling pathway.
2.Effect of cyclin D1 on HBV transcription and replication
Siwen PENG ; Guiwen GUAN ; Ting ZHANG ; Fengmin LU ; Jia LIU ; Xiangmei CHEN
Journal of Clinical Hepatology 2023;39(2):316-324
Objective To investigate the effect of cyclin D1 (with CCND1 as the gene name) on HBV replication and its potential mechanism. Methods With reference to GSE84044 dataset, the Spearman's rank correlation analysis was used to investigate the correlation between the expression levels of genes in liver tissue and serum HBV DNA load in patients with HBV-related liver fibrosis. Cyclin D1 and cyclin D1 T286A mutant were transiently expressed in the HBV cell replication model, and time-resolved immunofluorescence and quantitative real-time PCR were used to measure the levels of HBsAg/HBeAg and HBV DNA in cell culture supernatant; Western blot was used to measure the level of HBV core protein in cells; reverse-transcription quantitative real-time PCR was used to measure the level of HBV RNA in cells; dual-luciferase reporter assay was used to observe the effect of cyclin D1 on the activity of HBV basic core promoter (BCP). GSE83148 dataset was used to investigate the correlation between CCND1 and HBV-related regulatory factors. The independent samples t -test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups. Results The analysis of GSE84044 data showed that 7 cell cycle genes were significantly negatively correlated with HBV DNA load in liver tissue of the patients with HBV-related liver fibrosis (all r < -0.3, all P < 0.05), which included the CCND1 gene ( r =-0.474, P < 0.001). Exogenous expression of cyclin D1 and cyclin D1 T286A mutant reduced the levels of HBsAg, HBeAg, and HBV DNA in culture supernatant of the HBV replication cell model, as well as the levels of HBV core protein and HBV RNA in cells. Exogenous expression of cyclin D1 significantly inhibited the transcriptional activity of HBV BCP. The expression level of CCND1 in liver tissue of chronic hepatitis B patients was significantly positively correlated with the expression of APOBEC3G ( r =0.575, P < 0.001), SMC5 ( r =0.341, P < 0.001), and FOXM1 ( r =0.333, P < 0.001) which inhibited HBV replication, while it was significantly negatively correlated with the expression of the HBV entry receptor NTCP ( r =-0.511, P < 0.001) and HNF1α as the transcription factor for positive regulation of HBV replication ( r =-0.430, P < 0.001). Overexpression of cyclin D1 in HepG2 cells reduced the transcriptional levels of HNF1α and NTCP. Conclusion Cyclin D1 inhibits HBV transcription and replication possibly by downregulating the expression of HNF1α and NTCP.
3.Effects of ginkgo biloba extract on oxidative stress and the balance of excitation/inhibition of pyramidal neurons in the medial prefrontal cortex of depressive model mice
Chuanan ZHU ; Xianhua ZHANG ; Jindong CHEN ; Yuping XIA ; Zhiyuan HUANG ; Zengming MA ; Bin XIE ; Yanying XIE ; Yibin XIE ; Guiwen LI
Chinese Journal of Behavioral Medicine and Brain Science 2023;32(3):210-217
Objective:To investigate the effect of ginkgo biloba extract (GBE) on oxidative stress in medial prefrontal cortex and excitatory/inhibitory balance of pyramidal neurons in chronic unpredictable mild stress (CUMS)-induced depressive model mice.Methods:Totally 48 SPF grade 7-week-old male C57BL/6J mice were divided into 4 groups according to random number table method: control+ saline group (CTRL+ Veh), control+ GBE group (CTRL+ GBE), model+ saline group (CUMS+ Veh), model+ GBE group (CUMS+ GBE), with 12 mice in each group.Mice in CUMS+ Veh group and CUMS+ GBE group were established by CUMS method, and mice in CTRL+ GBE group and CUMS+ GBE group were intraperitoneally injected with GBE (70 mg/kg) once a day, and mice in CTRL+ Veh group and CUMS+ Veh group were injected intraperitoneally with 0.9% sodium chloride solution.Then, the sucrose preference test, forced swimming test (FST) and tail suspension test (TST) were performed to evaluate the depressive-like behavior of mice, and open field test (OFT) was performed to evaluate the autonomous locomotion and exploration ability and anxiety-like behavior.The content of malondialdehyde (MDA) and activity of superoxide dismutase (SOD) in mPFC were determined by ELISA.Spontaneous excitatory postsynaptic currents (sEPSC) and spontaneous inhibitory postsynaptic currents (sIPSC) were detected by whole-cell recording.SPSS 23.0 was used for data analysis and two-factor analysis of variance(whether to get GBE, whether to mold, show as GBE×CUMS) was used for statistical analysis.Results:(1) Behavioral results: the the time spent in center and total distance of OFT and sugar preference rate of the four groups of mice were compared, and the interaction of GBE×CUMS was significant( F=24.90, 4.82, 3.91, all P<0.05). The results of simple effect analysis showed that the time spent in center ((47.15±3.58) s), the total distance((19.33±0.86) m) and the sugar preference rate((59.11±8.79)%) of the mice in CUMS+ Veh group were lower than those in the CTRL+ Veh group((61.55±2.49) s, (23.24±1.21) m, (84.02±7.45) %) (all P<0.01), and the above indexes in CUMS+ GBE group ((56.51±3.53) s, (20.75±1.31) m, (70.80±11.79)%) were higher than those in CUMS+ Veh group (all P<0.05). In the immobility time of FST and TST of mice in the 4 groups, the interaction of GBE×CUMS were significant( F=85.53, 83.39, both P<0.01). The immobility time of FST and TST in CUMS+ Veh group were higher than those in CTRL+ Veh group (both P<0.01 ), and the above indexes in CUMS+ GBE group were lower than CUMS+ Veh group(both P<0.05). (2)The results of ELISA showed that the interaction of GBE×CUMS of SOD level of mice in the 4 groups was not significant ( F=3.52, P=0.07), but the main effects of GBE factor and CUMS factor were both significant ( F=4.69, 46.93, both P<0.05). The interaction of GBE×CUMS of MDA level was significant( F=16.61, P<0.01). The level of SOD in the CUMS+ Veh group was lower than that in the CTRL+ Veh group ( P<0.01), and the level of SOD in the CUMS+ GBE group was higher than that in the CUMS+ Veh group ( P<0.05). The level of MDA in the CUMS+ Veh group was higher than that of the CTRL+ Veh group ( P<0.01), and the level of MDA in CUMS+ GBE group was lower than that of the CUMS+ Veh group ( P<0.01). (3) The results of whole-cell recording showed that the interaction of GBE×CUMS of frequency and quantification of sEPSC in the four groups were significant ( F=5.45, 6.94, both P<0.05). The sEPSC frequency and quantification in the CUMS+ Veh group were lower than those in the CTRL+ Veh group (both P<0.01), and the sEPSC frequency and quantification in CUMS+ GBE group were higher than those of CUMS+ Veh group (both P<0.05). The interaction of GBE×CUMS of frequency and quantification of sIPSC in the four groups were significant ( F=7.78, 8.96, both P<0.01). The sIPSC frequency and quantification of the CUMS+ Veh group were higher than those of CTRL+ Veh group (both P<0.01), and the above indexes of CUMS+ GBE group were lower than those of CUMS+ Veh group (both P<0.01). As for the sEPSC/sIPSC ratio, GBE×CUMS interaction was significant ( F=5.45, P=0.02). The sEPSC/sIPSC ratio of CUMS+ Veh group (0.09±0.01) was lower than that of CTRL+ Veh group (0.28±0.04) ( P<0.01), and the sEPSC/sIPSC ratio of CUMS+ GBE group (0.14±0.03) was higher than that of CUMS+ Veh group ( P<0.05). Conclusion:Ginkgo biloba extract can improve the depression-like behavior of mice induced by CUMS, reduce the oxidative stress of mPFC and improve the excitation/inhibition balance of pyramidal neurons in depressive model mice.
4.Advances of hydrogel in early protection of exposed intra-abdominal organs after open abdomen
Canwen CHEN ; Kang CHEN ; Ze LI ; Yungang JIANG ; Guiwen QU ; Ye LIU ; Sicheng LI ; Jinjian HUANG ; Xiuwen WU ; Jian'an REN
Chinese Journal of Gastrointestinal Surgery 2023;26(9):898-902
The protection of open abdomen (OA) wound is a significant subject in the field of trauma surgery. The key technical challenge in the early stage of OA wound management involves promoting granulation tissue filling between intestinal segments, reducing intestinal wall abrasion, and preventing the development of enteroatmospheric fistulas (EAF). Hydrogels, characterized by their high water content and exceptional biocompatibility, serve as extracellular matrix-mimicking materials, and are extensively employed in various medical and healthcare applications. In this review, we discuss the application of hydrogel developed by natural biomaterials in OA wounds protection, taking into consideration the unique pathophysiological characteristics of the OA wounds. This review aims to provide valuable insights for the development of hydrogel materials for early-stage OA wound protection in future research.
5.Comparisons of the efficacy of drug injections for the treatment of keloid: a network meta-analysis
Hongfan DING ; Xiao XU ; Shiyi LI ; Yichen WANG ; Qian WU ; Ruiqi BAI ; Guiwen ZHOU ; Qiang FU ; Yue LIU ; Minliang CHEN
Chinese Journal of Plastic Surgery 2023;39(12):1311-1323
Objective:To conduct a network meta-analysis comparing the efficacy and safety of various drug injections for treating keloids.Methods:The search terms of "triamcinolone acetonide, 5-fluorouracil, verapamil, botulinum toxin, platelet rich plasma, keloid, scar, drug injection" were retrieved in PubMed, Embase, Web of Science, CNKI and Wanfang database to obtain the publicly published randomized controlled trials comparing single or combined drug injection for treating keloid from January 2010 to February 2023. The outcome index was the effective proportion of treatment, incidence proportion of adverse reactions, and recurrence proportion. NoteExpress, RevMan 5.4, and Stata 16.0 statistical software were utilized to perform a network meta-analysis of eligible studies that met the inclusion and exclusion criteria.Results:A total of 1 679 patients were enrolled in 21 studies that evaluated nine treatment modalities: triamcinolone (TAC), 5-fluorouracil (5-FU), botulinum toxin type A (BTA), platelet-rich plasma (PRP), Verapamil, BTA+ 5-FU, TAC+ 5-FU, TAC+ BTA, and TAC+ PRP. The network diagram revealed that there were 36 pairwise comparisons among the 9 treatment measures, with direct comparisons in 13 of them. The funnel plot demonstrated a symmetrical distribution of effect size points, and both Beggs test and Eggers test yielded P values greater than 0.05, indicating a low likelihood of publication bias. Nine treatment measures formed five closed loops with good consistency. The result of the network meta-analysis indicated that BTA+ 5-FU was more effective than TAC, 5-FU, or PRP alone; TAC+ 5-FU was more effective than TAC, 5-FU, or PRP alone; TAC+ BTA was more effective than TAC, 5-FU, BTA, or PRP alone; Verapamil was more effective than 5-FU and BTA was more effective than 5-FU. All result were found to be statistically significant ( P<0.05). A surface under the cumulative ranking area (SUCRA) map was generated, displaying the efficacy ranking and corresponding SUCRA values for each treatment: BTA+ 5-FU (85.6%)>TAC+ 5-FU (84.8%)>BTA+ TAC (76.7%)>Verapamil (48.9%)>BTA (45.0%)>TAC+ PRP (43.8%)>PRP (32.1%)>TAC (24.7%)>5-FU(8.3%). In terms of recurrence rate, the incidence of recurrence was higher with 5-FU compared to BTA or TAC+ 5-FU, and the incidence of recurrence was higher with TAC compared to TAC+ 5-FU; these differences were statistically significant ( P<0.05). A SUCRA map was generated with the ranking and SUCRA value for each treatment as follows: 5-FU (80.4%)>TAC (73.5%)>Verapamil (65.7%)>TAC+ BTA (52.5%)>PRP (34.8%)>BTA+ 5-FU (33.7%)>TAC+ 5-FU (30.2%)>BTA (29.3%). The qualitative analysis revealed a significantly lower incidence of systemic and local adverse reactions following combined drug injection compared to single drug injection. Conclusion:In the treatment of keloids using drug injection, combination therapy utilizing multiple drugs has demonstrated superior efficacy, lower recurrence rates, and fewer adverse reactions in comparison to single-drug therapy. Notably, the utilization of BAT, 5-FU, and TAC in combination may yield the most favorable outcomes.
6.Comparisons of the efficacy of drug injections for the treatment of keloid: a network meta-analysis
Hongfan DING ; Xiao XU ; Shiyi LI ; Yichen WANG ; Qian WU ; Ruiqi BAI ; Guiwen ZHOU ; Qiang FU ; Yue LIU ; Minliang CHEN
Chinese Journal of Plastic Surgery 2023;39(12):1311-1323
Objective:To conduct a network meta-analysis comparing the efficacy and safety of various drug injections for treating keloids.Methods:The search terms of "triamcinolone acetonide, 5-fluorouracil, verapamil, botulinum toxin, platelet rich plasma, keloid, scar, drug injection" were retrieved in PubMed, Embase, Web of Science, CNKI and Wanfang database to obtain the publicly published randomized controlled trials comparing single or combined drug injection for treating keloid from January 2010 to February 2023. The outcome index was the effective proportion of treatment, incidence proportion of adverse reactions, and recurrence proportion. NoteExpress, RevMan 5.4, and Stata 16.0 statistical software were utilized to perform a network meta-analysis of eligible studies that met the inclusion and exclusion criteria.Results:A total of 1 679 patients were enrolled in 21 studies that evaluated nine treatment modalities: triamcinolone (TAC), 5-fluorouracil (5-FU), botulinum toxin type A (BTA), platelet-rich plasma (PRP), Verapamil, BTA+ 5-FU, TAC+ 5-FU, TAC+ BTA, and TAC+ PRP. The network diagram revealed that there were 36 pairwise comparisons among the 9 treatment measures, with direct comparisons in 13 of them. The funnel plot demonstrated a symmetrical distribution of effect size points, and both Beggs test and Eggers test yielded P values greater than 0.05, indicating a low likelihood of publication bias. Nine treatment measures formed five closed loops with good consistency. The result of the network meta-analysis indicated that BTA+ 5-FU was more effective than TAC, 5-FU, or PRP alone; TAC+ 5-FU was more effective than TAC, 5-FU, or PRP alone; TAC+ BTA was more effective than TAC, 5-FU, BTA, or PRP alone; Verapamil was more effective than 5-FU and BTA was more effective than 5-FU. All result were found to be statistically significant ( P<0.05). A surface under the cumulative ranking area (SUCRA) map was generated, displaying the efficacy ranking and corresponding SUCRA values for each treatment: BTA+ 5-FU (85.6%)>TAC+ 5-FU (84.8%)>BTA+ TAC (76.7%)>Verapamil (48.9%)>BTA (45.0%)>TAC+ PRP (43.8%)>PRP (32.1%)>TAC (24.7%)>5-FU(8.3%). In terms of recurrence rate, the incidence of recurrence was higher with 5-FU compared to BTA or TAC+ 5-FU, and the incidence of recurrence was higher with TAC compared to TAC+ 5-FU; these differences were statistically significant ( P<0.05). A SUCRA map was generated with the ranking and SUCRA value for each treatment as follows: 5-FU (80.4%)>TAC (73.5%)>Verapamil (65.7%)>TAC+ BTA (52.5%)>PRP (34.8%)>BTA+ 5-FU (33.7%)>TAC+ 5-FU (30.2%)>BTA (29.3%). The qualitative analysis revealed a significantly lower incidence of systemic and local adverse reactions following combined drug injection compared to single drug injection. Conclusion:In the treatment of keloids using drug injection, combination therapy utilizing multiple drugs has demonstrated superior efficacy, lower recurrence rates, and fewer adverse reactions in comparison to single-drug therapy. Notably, the utilization of BAT, 5-FU, and TAC in combination may yield the most favorable outcomes.
7.Advances of hydrogel in early protection of exposed intra-abdominal organs after open abdomen
Canwen CHEN ; Kang CHEN ; Ze LI ; Yungang JIANG ; Guiwen QU ; Ye LIU ; Sicheng LI ; Jinjian HUANG ; Xiuwen WU ; Jian'an REN
Chinese Journal of Gastrointestinal Surgery 2023;26(9):898-902
The protection of open abdomen (OA) wound is a significant subject in the field of trauma surgery. The key technical challenge in the early stage of OA wound management involves promoting granulation tissue filling between intestinal segments, reducing intestinal wall abrasion, and preventing the development of enteroatmospheric fistulas (EAF). Hydrogels, characterized by their high water content and exceptional biocompatibility, serve as extracellular matrix-mimicking materials, and are extensively employed in various medical and healthcare applications. In this review, we discuss the application of hydrogel developed by natural biomaterials in OA wounds protection, taking into consideration the unique pathophysiological characteristics of the OA wounds. This review aims to provide valuable insights for the development of hydrogel materials for early-stage OA wound protection in future research.
8.Vascular complications caused by hyaluronic acid injection: a clinical analysis
Kang CHEN ; Guiwen ZHOU ; Xiao XU ; Qiang FU ; Yi YANG ; Minliang CHEN
Chinese Journal of Medical Aesthetics and Cosmetology 2022;28(3):218-222
Objective:To analyze the epidemiological characteristics of vascular complications induced by hyaluronic acid facial injection.Methods:Patients with vascular complication induced by facial hyaluronic acid facial injection were collected in the Fourth Medical Center of the General Hospital of the Chinese People's Liberation Army from January 1, 2016 to October 1, 2021, including 5 males and 37 females. The age ranged from 16 to 70 (34±10) years. The clinical data, injection site, clinical symptoms and previous facial surgery history of the patients were analyzed and investigated.Results:Vascular complications occurred in 12 cases (28.6%). Nasolabial fold in 8 (19.0%) cases; Glabella in 6 (14.3%) cases; frontal part in 6 (14.3%) cases. There were 27 patients (64.3%) with a history of facial surgery. Furthermore, history of facial surgery had no effect on the clinical manifestations of vascular complications ( P>0.05). Among the 18 patients with visual impairment, 12 patients reported that the symptoms of ptosis, bulbar conjunctival congestion, and eye movement dysfunction had diminished after thrombolytic treatment, while 4 patients showed recovery to some extent in visual acuity. Likewise, 24 patients with blood circulation disorders were healed after treatment, with residual pigmentation and a slight scar left. Conclusions:Women aged 30 to 39 years old are the main target population of cosmetic surgery, as well as the most common population of vascular complications. Particular care should be taken in the nose, nasolabial fold, glabella and forehead areas of the operation. Patients with previous surgical history should be adequately informed before surgery, and postoperative observation time should be appropriately prolonged.
9.Effect of AU-rich element RNA-binding factor 1 on the level of glypican 3 in hepatocellular carcinoma
Ting ZHANG ; Guiwen GUAN ; Jing ZHANG ; Fengmin LU ; Xiangmei CHEN
Journal of Clinical Hepatology 2021;37(5):1116-1120.
ObjectiveTo investigate the effect of AU-rich element RNA-binding factor 1 (AUF1) on glypican 3 (GPC3) in hepatocellular carcinoma (HCC) and its possible mechanism. MethodsTCGA-HCC gene expression data were downloaded from Broad Institute Genome Data Analysis Center, and finally 371 HCC tissue samples with different etiologies and 50 adjacent tissue samples were included; LCI-HCC gene expression data were downloaded from GSE14520, and 214 patients with hepatitis B-associated HCC who had follow-up data were enrolled. A total of 35 primary liver cancer samples and corresponding adjacent tissue samples were collected from HCC patients who underwent radical surgery in Henan Provincial Cancer Hospital from 2009 to 2013. Immunohistochemistry was used to measure the protein expression of GPC3 and AUF1 in HCC tissue; Western Blot and qRT-PCR were used to measure the expression of GPC3 after AUF1 knockdown or overexpression in hepatoma cell lines; RNA-binding protein immunoprecipitation and RNA turnover assay were used to investigate the potential mechanism of AUF1 in regulating the expression of GPC3. The t-test was used for comparison of quantitative data between two groups, and the chi-square test was used for comparison of rates between two groups; the Kaplan-Meier method was used for survival analysis after surgery, and the log-rank test was used for comparison of survival rates. ResultsIn TCGA and LCI databases, the expression of GPC3 in HCC tissue was significantly higher than that in adjacent tissue (P<0.05), and in TCGA database, the high expression of GPC3 was associated with the poor prognosis of HCC patients (P<0.05). Immunohistochemistry showed that both GPC3 and AUF1 proteins are highly expressed in HCC tissue, with a positive expression rate of 77.1% (27/35) and 74.3% (26/35), respectively. In vitro experiment showed that AUF1 knockdown significantly reduced the expression of GPC3 in HepG2 and Huh-7 cells (P<0.05), while AUF1 overexpression significantly increased the expression of GPC3 (P<0.05). AUF1 protein could bind to GPC3 mRNA, and AUF1 knockdown reduced the stability of GPC3 mRNA. ConclusionAUF1 is an important post-transcriptional regulator of the GPC3 gene, and the abnormal high expression of AUF1 and GPC3 may be involved in the development and progression of HCC.
10.Research advancement on the complications of neuroscopy surgery
Jiasheng JU ; Guiwen CHEN ; Jianliang CHEN
Journal of Chinese Physician 2021;23(2):318-320,f3
With the progress of imaging, optics and other science and technology, neuroendoscopy technology has been greatly developed, the application of more and more widely, but also become one of the techniques that neurosurgeons must be familiar with and master. With the further popularization of neuroendoscopy technology, related complications have also attracted wide attention. Endoscopic techniques are being used extensively used in the current times for the diagnosis and treatment of numerous intracranial pathologies. Although the incidence of complications related to neuroendoscopy is lower than that of traditional surgery, neuroendoscopy itself may bring complications such as hemorrhage, cerebrospinal fluid leakage, subdural hematoma and so on. This article reviews the complications related to neuroendoscopic surgery, in order to improve the understanding of complications and timely and correct treatment, so as to improve the curative effect of neuroendoscopic surgery.

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