1.Bioinformatics-based construction of a cervical cancer prognosis-associated competing endogenous RNA network
Jingqin REN ; Changhui ZHOU ; Chengqing LIU ; Nazila SAITINIYAZI ; Nan YANG ; Rong LI
Journal of China Medical University 2024;53(5):385-391
Objective To comprehensively analyze the circulatory RNA-long non-coding RNA-microRNA-messenger RNA(circRNA-lncRNA-miRNA-mRNA)network in cervical cancer and construct a prognostic model.Methods Differential and key genes were ana-lyzed using bioinformatics based on data from The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)databases.Prognostic mRNA models were constructed based on TCGA database using univariate,Least Absolute Shrinkage and Selection Operator(LASSO),and multivariate Cox regression analyses and validated using the GEO database.The R package and Cystoscape software were used to construct a nomogram model and competing endogenous(ceRNA)network of circRNA-lncRNA-miRNA-mRNA in cervical cancer.Results A prognostic model including five mRNAs was constructed using univariate,LASSO,and multivariate Cox regression analyses,which had area under the receiver operating characteristic curve AUC values of 0.71,0.71,and 0.70 at 1,2,and 3 years,respec-tively,indicating its sensitivity and specificity in cervical cancer prognosis.Predictive results were validated using the GSE44001 dataset.The C-index of the nomogram model for this prognostic model was 0.707.In this study,a ceRNA network comprising 39 circRNAs,27 lncRNAs,12 miRNAs,and five mRNAs was constructed.Conclusion The network constructed in this study can help comprehensively elucidate the mechanism of ceRNAs in cervical cancer,and the construction of prognostic and Nomogram models can predict patient prog-nosis.
2.Mechanism of Notch signaling pathway regulated by YAP in NASH liver fibrosis mice and the intervention effect of Cigu Xiaozhi prescription
Li WANG ; Xingsheng WANG ; Xiuping ZHAO ; Aidi WANG ; Hongmei QU ; Yanhua MA
Journal of China Medical University 2024;53(5):392-400
Objective To investigate the regulatory mechanism of Notch signaling pathway by YAP in non-alcoholic steatohep-atitis(NASH)liver fibrosis,and assess the intervention effect of Cigu Xiaozhi prescription in detoxification and phlegm treatment.Methods C57BL/6J mice were randomly divided into different groups,including a normal group,NASH liver fibrosis model group,verteporfin(VP)intervention group,VP+Chinese medicine(Cigu Xiaozhi prescription)low-dose group,VP+Chinese medicine high-dose group,and dimethyl sulfoxide control group.The methionine/choline-deficient diet combined with low-dose CCl4 was used to construct the NASH liver fibrosis model.The degree of liver fibrosis was evaluated using hematoxylin and eosin(HE)and Masson staining.Four protein factors associated with liver fibrosis were detected using enzyme-linked immunosorbent assay,and hydroxyproline levels in the mouse liver was determined using the alkaline water method.The localization of α-SMA,ColⅠ,YAP,and Notch1 proteins in the liver was determined using immunohistochemistry.Additionally,the mRNA and protein expression levels of the Notch signaling pathway molecules,namely Notch1/2,J agged1,and DLL4,were assessed using real-time quantitative PCR and Western blotting analyses,respectively.Results The HE and Masson staining results revealed that the liver cells of NASH liver fibrosis mice were swollen and the cytoplasm was transparent.Additionally,evident fibrosis was observed in the hepatic lobule,portal area,and sinus;it was accompanied by heightened levels of inflam-matory cell infiltration,a large number of fat droplets,and instances of local hepatocyte necrosis,dissolution,and cirrhosis.The four factors associated with liver fibrosis showed a substantial increase(P<0.01).α-SMA,ColⅠ,YAP,and Notch1 were localized in the cytoplasm of hepatocytes.YAP,Notch1/2,and Jagged1 were highly expressed in the liver(P<0.01)but were downregulated after intervention with VP and VP+high and low doses of Cigu Xiaozhi prescription(P<0.05).Meanwhile,DLL4 factor was upregulated in the VP+high-dose of Cigu Xiaozhi prescription group(P<0.05).Conclusion YAP may inhibit activation of the Notch pathway by downregulating Notch1/2 and Jagged1 and upregulating DLL4,thereby interfering with the occurrence of liver fibrosis in NASH.Treatment with Cigu Xiaozhi pre-scription may inhibit Notch signaling pathway activation by downregulating YAP,Notch1/2,and Jagged1 and upregulating DLL4 through its multi-components and multi-targets properties,ultimately slow the progression of liver fibrosis in NASH.
3.Changes in the protein expression profiles of glomeruli during the treatment of lupus nephritis with hydroxychloroquine sulfate
Yanqiu LI ; Haichao WANG ; Xiaojie ZHENG ; Xiaodan LIU ; Xue LIU ; Shuyan TIAN ; Li YAO
Journal of China Medical University 2024;53(5):401-404,413
Objective To screen the differentially expressed proteins in glomeruli during the treatment of lupus nephritis(LN)with hydroxychloroquine sulfate(HCQ).Methods Sixty female NZB/WF1 mice were used.At the age of 28 weeks,40 mice with proteinuria of 3+to 4+were divided into HCQ and control groups.After feeding for 36 weeks,the glomerular proteins were extracted by magnetic beads and analyzed by two-dimensional fluorescence difference gel electrophoresis(2D-DIGE)and matrix-assisted laser desorption/ioniza-tion time-of-flight mass spectrometry(MALDI-TOF-MS).The expression of the candidate proteins in the glomeruli of the LN mice was exa-mined by immunohistochemistry.Results A total of 31 differentially expressed proteins were identified between the two groups,including 24 upregulated and seven downregulated proteins.Conclusion The expression of proteins like RI and ENOA in the glomeruli of LN mice was significantly different during HCQ treatment.These proteins may be involved in the pathogenesis of LN and are therefore potential targets of HCQ in the treatment of LN.
4.Transcription factor MYB activates CTSF to affect gastric cancer cell proliferation and stemness through glutamine metabolism
Journal of China Medical University 2024;53(5):405-413
Objective To investigate how the transcription factor MYB activates cathepsin F(CTSF)and affects gastric cancer cell proliferation and stemness through glutamine metabolism and to explore the underlying mechanisms.Methods We used the TCGA and KnockTF databases to analyze CTSFexpression in gastric cancer tissues and predict MYB as the transcription factor of CTSFand analyze MYB expression in gastric cancer,respectively.We performed dual-luciferase and ChIP assays to verify this binding relationship.We assessed CTSFand MYB expression using real-time PCR.We investigated cell proliferation using CCK-8 and colony formation assays.The cell spheroidal ability was detected using a sphere formation assay.We examined stem cell surface marker(OCT4,NANOG,and SOX2)and glutamine transporter(SLC1A5)expression using Western blotting.We used corresponding kits to measure the glutamine,glu-tamic acid,and α-ketoglutaric acid content as well as the NADPH/NADP+ratio,GSH/GSSG ratio,and aspartic and oxaloacetic acid levels.Results We detected low CTSFexpression levels in gastric cancer tissues and cells.CTSFoverexpression could inhibit gastric cancer cell stemness and proliferation.CTSFknockdown significantly increased the glutamine,glutamate acid,andα-ketoglutaric acid contents,NADPH/NADP+and GSH/GSSG ratios,and aspartic and oxaloacetic acid levels,and promoted cell proliferation and stemness.MYB was highly expressed in gastric cancer tissues and cells.Our bioinformatic prediction combined with ChIP and dual-luciferase experiments confirmed MYB as a transcription factor for CTSF.Conclusion The results of our study indicated that the transcription factor MYB acti-vated CTSFto promote gastric cancer cell proliferation and stemness through glutamine metabolism.
5.Rhizoma corydalis downregulates PD-L1 by targeting CXCL17 to activate AMPK signaling pathway and inhibits EBV-induced immune escape in gastric cancer
Chao HAN ; Xiaoyun HU ; Chang LIU ; Yangyang YU
Journal of China Medical University 2024;53(5):414-420
Objective To explore the effect of Rhizoma corydalis on the immune escape of Epstein-Barr virus(EBV)positive gastric cancer cells and its mechanism of targeting CXCL17 to affect immune escape of EBV-positive gastric cancer cells.Methods GEO2R online analysis software was used to screen differentially expressed genes in EBV-positive gastric cancer tissues.EBV-negative AGS gastric cancer cells and EBV-positive SUN-719 gastric cancer cells were used for the experiments.RT-qPCR and Western blotting were used to detect the expression of CXCL17in EBV-negative and EBV-positive gastric cancer cells.Transfection of CXCL17 siRNA into EBV-positive gastric cancer cells,detection of PD-L1 expression through Western blotting,coculture of EBV-positive gastric cancer cells with T cells,detection of cell viability using the CCK-8 assay,and detection of cell apoptosis rate through flow cytometry were conducted.EBV-positive gastric cancer cells were treated with different concentrations of a Rhizoma corydalis extract(2,4,and 8 μg/mL).The expression of CXCL17and PD-L1 was detected through Western blotting,and EBV-positive gastric cancer cells were cocultured with T cells.Cell viability was determined using CCK-8,and cell apoptosis rate through flow cytometry.The CXCL17overexpression plasmid was transfected into EBV-positive gastric cancer cells treated with Rhizoma corydalis extract(8μg/mL).The expression of PD-L1 and p-AMPK was detected through Western blotting,and EBV-positive gastric cancer cells were cocultured with T cells.Cell viability was determined using CCK-8,and cell apoptosis rate with flow cytometry.Results CXCL17 expression was upregulated in EBV-positive gastric cancer tissues and cells(P<0.05).Silencing of CXCL17reduced the expression of PD-L1 in EBV-positive gastric cancer cells,inhibited the proliferation of EBV-positive gastric cancer cells cocultured with T cells,and promoted cell apoptosis(P<0.05).Rhizoma corydalis treat-ment reduced the expression of CXCL17 and PD-L1 in EBV-positive gastric cancer cells,inhibited the proliferation of EBV-positive gas-tric cancer cells cocultured with T cells,and promoted apoptosis(P<0.05).Overexpression of CXCL17reversed the inhibitory effect of the Rhizoma corydalis treatment on PD-L1 expression and cell proliferation in EBV-positive gastric cancer cells,as well as the promoting effect of cell apoptosis(P<0.05).Overexpression of CXCL17also reduced the expression of p-AMPK in EBV-positive gastric cancer cells treated with Rhizoma corydalis(P<0.05).Conclusion CXCL17 expression is upregulated in EBV-positive gastric cancer cells,and Rhizoma corydalis inhibits immune escape in gastric cancer cells by downregulating CXCL17 expression in EBV-positive gastric cancer cells,which may be related to the activation of the AMPK signaling pathway.
6.Sedative effect of ciprofol combined with oxycodone on elderly patients undergoing endoscopic gastric mucosal dissection
Xiaodong ZHANG ; Peng DUAN ; Yingjie SUN ; Qi NA
Journal of China Medical University 2024;53(5):421-426
Objective To investigate the safety and efficacy of ciprofol combined with oxycodone in elderly patients who underwent endoscopic gastric mucosal dissection.Methods A total of 204 elderly patients in the outpatient department of the Northern Theater General Hospital who were to undergo endoscopic gastric mucosal dissection from March 2022 to December 2022 were selected as study participants.They were aged 60-75 years,with a body mass index of 18-30 kg/m2,and ASA grade Ⅱ or Ⅲ,regardless of sex.They were randomly divided into propofol(group P),ciprofol(group C),and ciprofol+oxycodone(group CO)groups,with 68 patients in each group.During anesthesia induction,group P was given propofol(1-1.5 mg/kg);group C,ciprofol(0.2-0.5 mg/kg);and group CO,oxyco-done hydrochloride(0.1-0.2 mg/kg)and ciprofol(0.2-0.5 mg/kg).The injection time of the three groups was>30 s.During anesthesia maintenance,ciprofol[1-1.5 mg/(kg·h)]was continuously injected intravenously in groups C and CO,and propofol[2-5 mg/(kg·h)]was continuously injected intravenously in group P.The modified observer's assessment of alertness/sedation score was evaluated at 3 min after anesthesia induction.If the score was≤1,endoscopy was started.The mean arterial pressure(MAP),heart rate(HR),and blood oxygen saturation(SpO2)at times T0(before drug injection),T1(when eyelash reflex disappeared),T2(when endoscopy began),and T3(when endoscope was withdrawn);visual analogue scale(VAS)scores at 30 min and 1 h after resuscitation;and induction time,recovery time,intravenous pain,respiratory depression,and other adverse reactions were recorded in the three groups.Results There were no significant differences in MAP,HR,and SpO2 at T0 and T3 among the three groups(all P>0.05).At T1 and T2,compared with those in group P,MAP,HR,and SpO2 in groups C and CO were significantly increased(all P<0.05).MAP,HR,and SpO2 in the CO group were slightly lower than those in the C group;however,the differences were not statistically significant(all P>0.05).Compared with that in group P,the incidence of respiratory depression and injection pain in groups C and CO was significantly reduced(P<0.05),but there was no statistically significant difference between groups C and CO(P>0.05).The VAS score at 30 min and 1 h after awakening and inci-dence of body movement in the CO group were lower than those in the P and C groups(all P<0.05);however,there was no statistically significant difference between the P and C groups(all P>0.05).Conclusion Ciprofol combined with oxycodone had definite sedative and analgesic effects in elderly patients undergoing endoscopic gastric mucosal dissection.Compared with the use of propofol or ciprofol alone,with combination therapy,the respiratory cycle is more stable,patients have fewer adverse reactions,and it is worthy of clinical application.
7.Relationship between serum uric acid levels in normotensive pregnant women at full-term of pregnancy and birth weight of newborns
Yue FAN ; Jun WANG ; Xiaoming WANG
Journal of China Medical University 2024;53(5):427-433,438
Objective To investigate the relationship between serum uric acid levels of full-term pregnant women with normal blood pressure and the birth weight of their newborns.Methods A total of 1200 pregnant women in the obstetrics ward of Shengjing Hospital of China Medical University were randomly selected by stratification for the study from January 2012 to December 2022.These women had full-term delive-ries and a normal blood pressure.According to the weight of neonates at delivery,they were divided into groups as follows:appropriate for gestational age(AGA,n=600),large for gestational age(LGA,n=300),and small for gestational age(SGA,n=300).Clinical data of the patients was collected for a retrospective study.Nonparametric tests were used to compare the differences in each group,and logistic regression was used to analyze the factors influencing neonatal birth weight.Results The maternal serum uric acid values in the LGA and SGA groups were 336(269-388)μmol/L and 377(297-431)μmol/L,respectively-much higher than that of the AGA group[288(243-350)μmol/L,P<0.001].Multivariate logistic regression analysis showed that the risk of occurrence for LGA(for every 10 μmol/L increase in the blood uric acid level of pregnant women,the adjusted OR=1.040,95%CI:1.020-1.060)and SGA(for every 10 μmol/L increase,the adjusted OR=1.072,95%CI:1.049-1.095)increased with the level of uric acid in the patients.The birth weight percentile of neonates in the LGA group was positively correlated with uric acid levels(r=0.108,P<0.05),while in the SGA group it was negatively correlated with uric acid levels(r=-0.224,P<0.01).Restrictive cubic spline regression analysis showed that the rela-tionship between maternal uric acid levels and newborn birth weight was similar to a"U"shape.When newborn birth weight was around 3000 g,maternal uric acid level was the lowest.Conclusion Serum uric acid level of full-term pregnant women with normal blood pres-sure is an independent risk factor for neonatal birth weight.Serum uric acid level of full-term pregnant women with normal blood pressure is closely associated to neonatal birth weight,and shows a positive correlation in the LGA group and negative correlation in the SGA group.
8.Clinical characteristics and prognosis of deep cervical abscesses
Journal of China Medical University 2024;53(5):434-438
Objective To analyze the clinical characteristics and prognostic factors of deep cervical abscesses.Methods The medical records of 166 patients with deep cervical abscesses who underwent emergency surgical treatment in the Department of Otolaryngology of our hospital between October 2014 and August 2023 were retrospectively analyzed.The age-adjusted Charlson comorbidity index(aCCI)was calculated based on the data obtained.The patients were divided into good and poor prognosis groups,and multivariate logistic regres-sion was used to analyze the impact of various indicators on the prognosis of the two groups of patients.Results Statistically significant differences in sex,age,mediastinal infection,sepsis,diabetes,hypertension,C-reactive protein(CRP)and procalcitonin(PCT)levels,and the aCCI scores were observed between the two groups(P<0.05).Thus,these factors have a significant impact on the prognosis of patients with deep cervical abscesses.Multivariate regression analysis showed that mediastinal infection,hypertension,and the aCCI score were independent predictors of poor prognosis in patients with deep cervical abscesses(P<0.05).Conclusion Mediastinal infection,hypertension,and the aCCI score are independent risk factors for poor prognosis in patients with deep neck abscesses and can be used to preliminarily evaluate the prognosis of patients with deep cervical abscesses.
9.Effect of tanshinone ⅡA on angiotensin Ⅱ-induced proliferation and migration of vascular smooth muscle cells
Liting LIU ; Zhiqian XIONG ; Yan JIANG ; Chaojiang SU ; Shuai ZHANG ; Zongyang LIU
Journal of China Medical University 2024;53(5):439-445
Objective To determine whether Tanshinone ⅡA(Tan ⅡA)has an effect on angiotensin Ⅱ(Ang Ⅱ)-induced prolifera-tion and migration of vascular smooth muscle cells(VSMCs),phenotypic switching,or autophagy.Methods In this study,murine aortic smooth muscle cell lines were treated with Ang Ⅱ to establish a model of cell proliferation.Different concentrations of Tan ⅡA were added and effects on cell proliferation and migration were determined by cell counting using a CCK-8 assay and a cell scratch assay,respectively.Alpha-smooth muscle actin(α-SMA),a marker of contractile VSMCs,was detected by Western blotting.Expression levels of osteopontin(OPN)and the autophagy-related proteins(p62,Beclin-1,LC3A/B)were assayed to determine the effect of Tan ⅡA on VSMC phenotypic transformation and autophagy.Cells were treated with the autophagy inhibitor 3-methyladenine(3-MA),combined with Tan ⅡA,and then cell proliferation,migration and expression levels of phenotypic markers and autophagy-related proteins were assessed.Results After Ang Ⅱ treatment,the proliferation and migratory capacity of VSMCs was significantly enhanced,and phenotypic transformation was sig-nificantly inhibited by Ang Ⅱ.Western blotting revealed that Ang Ⅱ reduced the expression of α-SMA,increased the expression of OPN,p62,Beclin-1,and LC3A/B,and that these effects increased with higher Tan ⅡA concentrations.After the addition of 3-MA to the treated cells,the proliferation and migration of VSMCs induced by Ang Ⅱ was inhibited,the expression of α-SMA was increased,and the expres-sion of OPN,p62,Beclin-1,and LC3A/B was decreased,which was consistent with the effect of Tan ⅡA.Conclusion Tan ⅡA may have inhibitory effects on phenotypic transformation,proliferation,migration,and autophagy of Ang Ⅱ-treated VSMC,suggesting that the inhi-bition of the proliferation and migration may be regulated by autophagy.
10.Application of egg yolk oil combined with Qingrejiedu decoction for external washing to promote wound healing after perianal abscess surgery
Shixiong WU ; Lihui WEN ; Manjun LIU ; Lei ZHANG ; Bo LIU ; Xutao QI
Journal of China Medical University 2024;53(5):446-450,457
Objective To explore the promoting effect of egg yolk oil combined with heat-clearing and detoxi-fying traditional Chinese medicine external washing on postoperative wound healing in patients with perianal abscesses based on growth factors in the wound granu-lation tissue.Methods Eighty patients with perianal abscesses admitted to our hospital from January 2023 to May 2023 were randomly divided into a control group and an observation group,with 40 patients in each group.Three days after surgery,the control group received routine treatment,such as external washing with heat-clearing and detoxifying Chinese herbal medicine and dressing changes with vase-line gauze.The observation group received additional treatment with egg yolk oil,and both groups were treated continuously for 7 days.The clinical efficacy,improvement in clinical symptoms,and wound recovery at different time points;serum inflammatory cytokines;and expression levels of wound granulation tissue-related factors were compared between the two groups.Results The total effective rate was higher in the observation group than the control group(95%vs.75%,P<0.05).The time of pruritus disappearance,decaying flesh,emer-gence of new epithelium,and healing were shorter in the observation group than in the control group(P<0.05).The pain degree,wound secretion,granulation morphology and surrounding tissue edema score of the observation group were significantly decreased at 7 and 10 days after surgery compared with the control group(P<0.05).Serum levels of interleukin(IL)-1β,IL-8,and tumor necrosis factor-α were lower in the observation group than the control group at 7 and 10 days after surgery(P<0.05).The levels of basic fibroblast growth factor,vascular endothelial cell growth factor,and transforming growth factor-βin wound granulation tissue were higher in the observation group than the control group at 7 and 10 days after surgery(P<0.05).Conclusion The external application of egg yolk oil combined with heat-clearing and detoxifying Chinese herbs can significantly improve the clinical symptoms of patients with perianal abscesses and promote wound healing,with significant therapeutic effects.This may be related to the inhibition of inflammatory cytokine expression and the promotion of wound granulation tissue growth factor expression.

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