1.Expression of Rh family C glycoprotein in esophageal squamous carcinoma and its clinical significance
Ziru ZHOU ; Mengfei SUN ; Huakun ZHANG ; Shuyan SUN ; Qi SUN ; Feng LI ; Yunzhao CHEN ; Jie YU ; Yuwen CAO ; Xiaobin CUI
Journal of Jilin University(Medicine Edition) 2025;51(4):1019-1027
Objective:To discuss the expression of Rh family C glycoprotein(RHCG)in the esophageal squamous cell carcinoma(ESCC)tissue and its effect on the malignant biological behavior of ESCC cells,and to clarify the value of RHCG as a diagnostic and prognostic marker for the ESCC patients.Methods:A total of 143 ESCC tissue samples and 105 adjacent normal tissue samples were collected.Using immunohistochemical staining method,141 ESCC samples were divided into two groups:RHCG low expression group(immunohistochemistry score≤6)and RHCG high expression group(immunohistochemistry score>6).Immunohistochemical method was used to detect the RHCG protein expression in 143 ESCC tissues and 105 normal tissues,and the relationship between the clinicopathological characteristics of the ESCC patients was analyzed.Receiver operating characteristic(ROC)curve and Kaplan-Meier survival analysis were used to evaluate the value of RHCG in diagnosis and prognosis of the ESCC patients;univariate and multivariate COX regression analysis were used to determine the independent risk factors affecting the prognosis of the ESCC patients.Gene Expression Profiling Interactive Analysis(GEPIA2)database was used to analyze the expression of RHCG mRNA in various tumor tissues.The ESCC TE-1 cells were cultured and transfected in to 6-well cell culture plates with different Lipofectamine2000∶RHCG ratios;the cells in RHCG transfection group were transfected with weights of 2.0,2.5,and 3.0 μg for 24 and 48 h,respectively,and the cells in NC group transfected with empty vector as control.Western blotting method was used to detect the RHCG protein expression level in the TE-1 cells in various groups after transfection at different concentrations and verify the optimal transfection conditions;cell counting kit-8(CCK-8)assay was used to detect the proliferation activities of the TE-1 cells;plate clone formation assay was used to detect the colony formation numbers of the TE-1 cells;Transwell chamber assay was used to detect the numbers of migrating TE-1 cells.Results:Compared with adjacent normal tissue,the RHCG gene expression level in various cancer tissues including ESCC,glioblastoma multiforme,and head and neck squamous cell carcinoma was significantly decreased(P<0.05).RHCG protein was mainly located on the cell membrane of normal esophageal squamous epithelial cells;the RHCG protein expression intensity in ESCC tissues was lower than that in adjacent normal esophageal tissue(χ2=109.373,P<0.001),and the patients in RHCG low expression group had poorer differentiation than those in RHCG high expression group(P=0.041).The area under the curve(AUC)value of RHCG for diagnosing ESCC was 0.86,with sensitivity and specificity of 95.1%and 75.0%,respectively;the Kaplan-Meier survival analysis results showed that compared with high RHCG expression group,the patients in low RHCG expression group had shorter survival time and poorer prognosis[harard ratio(HR)=0.269,95%confidence interval(CI):0.113-0.639,P=0.020];the COX regression analysis results showed that low RHCG expression could serve as an independent risk factor affecting the prognosis of ESCC[HR=4.569,95%CI=1.315-15.877,P=0.017)].The Western blotting results verified that the optimal transfection condition was 3.0 μg RHCG plasmid for 48 h,at which time RHCG overexpression was optimal and RHCG protein expression level was highest.The CCK-8 assay results showed that compared with control group,the proliferation activity in RHCG overexpression group was decreased on the 4th day after cell seeding(P<0.001).In the TE-1 cells,the colony formation number of the TE-1 cells in RHCG over-expression group was lower than that in control group(t=17.70,P<0.001).The Transwell chamber assay results showed that compared with control group,the number of migrating cells in RHCG over-expression group was decreased(t=23.74,P<0.001).Conclusion:RHCG expression is decreased in ESCC tissues and associated with poor prognosis in ESCC patients;overexpression of RHCG can inhibit the proliferation and migration of the TE-1 cells,providing a theoretical basis for RHCG as a novel diagnostic and prognostic marker and therapeutic target for ESCC.
2.Relationship between morphometric parameters of the cerebral cortex and the efficacy of repetitive transcranial magnetic stimulation in treating tardive dyskinesia
Kesong LI ; Ning ZHANG ; Yali LIU ; Jingjing HUANG ; Ya LIU ; Yunzhao CHEN
Journal of Clinical Medicine in Practice 2025;29(1):39-43
Objective To investigate the relationship between morphometric parameters of the cerebral cortex and the efficacy of repetitive transcranial magnetic stimulation(rTMS)in the treatment of tardive dyskinesia(TD).Methods A total of 105 schizophrenic patients with TD undergoing basic treatment were enrolled,and randomly divided into group A(n=35),group B(n=35)and group C(n=35).Group A received rTMS at 1 Hz,group B received rTMS at 10 Hz,and group C received sham stimulation.All groups were treated for 12 weeks.The severity of TD was assessed using the Ab-normal Involuntary Movement Scale(AIMS)before and after treatment.The Repeatable Battery for the Assessment of Neuropsychological Status(RBANS)and the Positive and Negative Syndrome Scale(PANSS)in Chinese were used to evaluate patients'neuropsychological status and symptom severity.magnetic resonance imaging(MRI)was employed to scan the left prefrontal cortex of patients to obtain parameters of cortical thickness,surface area and volume.Pearson correlation analysis was used to an-alyze the relationship between cortical morphological parameters and the efficacy of rTMS for TD in pa-tients.Results After treatment,AIMS scores in the three groups were significantly lower than before treatment,and the group A was significantly lower than the group B and group C(P<0.05).After treatment,RBANS scores were significantly higher and PANSS scores were significantly lower in three groups than before treatment(P<0.05).After treatment,the RBANS score of the group A was significantly higher than that of the group B and group C,and the group B was significantly higher than the group C(P<0.05);the PANSS score of the group A was significantly lower than that of the group B and group C,and the group B was significantly lower than the group C(P<0.05).Af-ter treatment,cortical morphological parameters(cortical thickness,surface area and volume)in the group A and group B were significantly higher than before treatment,and the group A was signif-icantly higher than the group B(P<0.05).The therapeutic effect of the group A was positively correlated with cortical thickness,surface area and volume(P<0.05).Conclusion The morpho-metric parameters of the left prefrontal cortex are associated with the efficacy of rTMS in treating TD.The rTMS at 1 Hz can facilitate structural remodeling of the motor cortex,thereby improving treat-ment outcomes for TD patients.
3.Cellular FLICE-like inhibitory protein inhibits oxidative stress through activating the Nrf2/HO-1 signaling pathway to alleviate myocardial ischemia-reperfusion injury in rats
Gang ZHOU ; Yunzhao LI ; Hui WU ; Di LIU ; Dong ZHANG ; Qingzhuo YANG ; Yanfang LIU ; Yi LI
Chinese Journal of Emergency Medicine 2025;34(1):40-46
Objective:To investigate the role and mechanisms of cellular FLICE-like inhibitory protein (cFLIP) in mediating oxidative stress induced by myocardial ischemia-reperfusion injury (MI/RI) in rats.Methods:Forty-eight male Sprague-Dawley rats with body weight of 180-200 g, were randomly divided into 4 groups ( n=12 per group) using a random number table: sham operation group (sham group), ischemia-reperfusion group (I/R group), virus control group (I/R+Ad-NC group), and cFLIPL-overexpressing group (I/R+Ad-cFLIPL group). A myocardial ischemia-reperfusion injury (MI/RI) model was established by ligating the left anterior descending coronary artery for 30 min followed by 3 h of reperfusion. The left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) in rats were evaluated via echocardiography, and a biochemical analyzer was used to measure the serum lactate dehydrogenase (LDH) and creatine kinase isoenzyme (CK-MB) levels to evaluate the extent of myocardial injury. The 2,3,5- triphenyl tetrazolium chloride (TTC) staining method was used to detect the infarct area of the rat myocardium, and hematoxylin and eosin (HE) staining was performed to observe the morphology of the rat myocardial tissue. Commercial kits were used to measure the levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-px), and malondialdehyde (MDA). Dihydroethidium (DHE) staining was used to assess the number of reactive oxygen species (ROS)-positive cells in the myocardial tissue. Western blot analysis was performed to evaluate the protein expression of cFLIPL, Nrf2, and HO-1. Results:During MI/RI, compared with the sham group, the protein expression of cFLIPL was significantly decreased in the I/R group, and compared with the I/R+Ad-NC group, the protein expression of cFLIPL was significantly increased in the I/R+Ad-cFLIPL group (both P<0.05). Compared with sham group, the level of LDH, CK-MB, MDA, ROS-positive cell count, and myocardial infarct size were significantly increased, whereas the LVEF, LVFS, SOD, and GSH-px were significantly decreased in I/R group (all P<0.05). Compared to the I/R+Ad-NC group, the level of LDH, CK-MB, MDA, ROS-positive cell count, and myocardial infarct area were significantly decreased, whereas the LVEF, LVFS, SOD, and GSH-px were significantly increased in I/R+Ad-cFLIPL group (all P<0.05). Western blot revealed that compared with the sham group, the protein expression of Nrf2 and HO-1 in I/R group were significantly increased, and compared with the I/R+Ad-NC group, the protein expression of Nrf2 and HO-1 in the I/R + Ad-cFLIPL group were significantly increased (all P<0.05). Conclusion:Overexpression of cFLIPL can alleviate myocardial ischemia-reperfusion injury (MI/RI) in rats by activating the Nrf2/HO-1 signaling pathway to inhibit oxidative stress.
4.Clinical effect of multi-modality image fusion combined with intraoperative fluorescein sodium in the treatment of brain metastases from lung cancer
Zhong WANG ; Xiaojun ZHANG ; Ruijian ZHANG ; Zhitong HAN ; Weiran YANG ; Wenbo YANG ; Yunzhao CHEN ; Dong XING ; Junqing WANG ; Yuhui SONG
Clinical Medicine of China 2024;40(6):447-455
Objective:To explore the application and clinical efficacy of functional neural navigation multimodal image fusion technology combined with intraoperative fluorescein sodium in the surgery of lung cancer brain metastases.Methods:Forty patients with lung cancer and brain metastasis admitted to the Department of Neurosurgery of Inner Mongolia Autonomous Region People's Hospital from January 2020 to January 2024 were collected as the observation group. Another 40 patients with lung cancer brain metastases who underwent microscopic resection at Inner Mongolia Autonomous Region People's Hospital from January 2016 to December 2019 were selected as the control group. All patients received head CT examination, head MRI examination, MRI enhanced sequence and MRA, MRV and DWI sequence scanning before operation. Functional neural navigation system was used to perform preoperative multi-modal image fusion to realize three-dimensional display of tumor lesions, and display the position relationship between tumor and functional areas, conduction bundles and large blood vessels, so as to make preoperative navigation plan. After conducting a fluorescein sodium allergy test on the patient before surgery, a small dose of fluorescein sodium (2 mg/kg) was intravenously injected during the operation. During the operation, neuro navigation was combined with fluorescein sodium to perform tumor resection by displaying the boundary between tumor tissue and normal brain tissue under a Pentero 900 Zeiss microscope 560 fluorescence mode. Both groups collected tumor tissue samples for pathological classification and immunohistochemical analysis, comparing and analyzing differences in tumor resection degree, postoperative occurrence of new neurological dysfunction, postoperative muscle strength improvement, changes in KPS scores before and after surgery, and the occurrence of complications. The metric data that conforms to normal distribution is represented by xˉ± s, and the comparison of means between two groups is conducted using independent sample t-test. Calculate the percentage based on the count data, and compare the inter group rates using the χ2 test. P<0.05 indicates statistical significance of the difference. Results:Compared with the control group, the total tumor resection rate of observation group (75.0% (30/40) ) and KPS score of 3 months after surgery (82.5% (33/40)) were better than those of the control group (52.5% (21/40) and 60% (24/40)), and the differences were statistically significant ( χ2 value was 4.94 and 4.38, P values were 0.026 and 0.036). The rate of postoperative new neurological dysfunction in the observation group (22.5% (9/40)) was lower than that in the control group (45.0% (18/40)), and the difference between the two groups was statistically significant ( χ2=4.53, P=0.033). The length of hospital stay ((21.48±3.23) days), operation time ((216.65±56.76) points) and complication rate (37.5% (15/40)) in observation group were lower than those in control group ((22.43±2.34) days, (225.62±37.68) points, 45.0% (18/40)). However, the difference was not statistically significant ( t/ χ2 values were 1.51, 0.83, and 0.46, respectively; P values were 0.136, 0.408, and 0.496, respectively). The 12-month survival rate of observation group (67.5%(27/45) respectively was significantly higher than that of control group (40.0%(16/40) respectively, and the difference was statistically significant ( χ2=6.08, P=0.014). Conclusion:Functional neural navigation multimodal image fusion technology combined with intraoperative fluorescein sodium can accurately locate the tumor and determine the boundary relationship between the tumor and normal brain tissue during lung cancer brain metastasis surgery, improve tumor resection rate, enhance patient quality of life, and ultimately improve patient prognosis without increasing the risk of related complications.
5.Identification of USP2 as a novel target to induce degradation of KRAS in myeloma cells.
Yingying WANG ; Youping ZHANG ; Hao LUO ; Wei WEI ; Wanting LIU ; Weiwei WANG ; Yunzhao WU ; Cheng PENG ; Yanjie JI ; Jianfang ZHANG ; Chujiao ZHU ; Wenhui BAI ; Li XIA ; Hu LEI ; Hanzhang XU ; Leimiao YIN ; Wei WENG ; Li YANG ; Ligen LIU ; Aiwu ZHOU ; Yueyue WEI ; Qi ZHU ; Weiliang ZHU ; Yongqing YANG ; Zhijian XU ; Yingli WU
Acta Pharmaceutica Sinica B 2024;14(12):5235-5248
Inducing the degradation of KRAS represents a novel strategy to combat cancers with KRAS mutation. In this study, we identify ubiquitin-specific protease 2 (USP2) as a novel deubiquitinating enzyme of KRAS in multiple myeloma (MM). Specifically, we demonstrate that gambogic acid (GA) forms a covalent bond with the cysteine 284 residue of USP2 through an allosteric pocket, inhibiting its deubiquitinating activity. Inactivation or knockdown of USP2 leads to the degradation of KRAS, resulting in the suppression of MM cell proliferation in vitro and in vivo. Conversely, overexpressing USP2 stabilizes KRAS and partially abrogates GA-induced apoptosis in MM cells. Furthermore, elevated USP2 levels may be associated with poorer prognoses in MM patients. These findings highlight the potential of the USP2/KRAS axis as a therapeutic target in MM, suggesting that strategically inducing KRAS degradation via USP2 inhibition could be a promising approach for treating cancers with KRAS mutations.
6.Preliminary study on the expression and function of bone morphogenetics protein 7 in ESCC
Mengfei Sun ; Hongfang Huang ; Yuhang Dong ; Huakun Zhang ; Ziru Zhou ; Qi Sun ; Wenyan Guan ; Linyue Zhao ; Xiaobin Cui ; Yunzhao Chen ; Feng Li
Acta Universitatis Medicinalis Anhui 2023;58(6):995-1000,1010
Objective :
To analyze the expression and immune infiltration levels of the BMP7 gene ( BMP7) in e- sophageal squamous cell carcinoma(ESCC) .
Methods :
Initially,in 274 cases of ESCC and 242 cases of normal tissues,the level of BMP7 was verified by immunohistochemistry ,and the relationship between the expression difference and the survival cycle and clinical pathological characteristics of patients with ESCC was explored,and BMP7 overexpression plasmid transfection of ESCC cells was established,and the effect of BMP7 on the biological behavior of ESCC cells was examined by CCK-8,Clone,and Transwell.
Results :
BMP7 expression in normal e- sophageal tissues was higher than that of ESCC(P<0. 001) ,the expression level of BMP7 was correlated with the degree of differentiation of patients(P = 0. 006) and TNM staging(P <0. 001) ,and the survival of patients with high expression of BMP7 exceeded that of patients with low BMP7 (P = 0. 041) ,and the experiments of CCK-8 and Clone showed that the proliferation effect of cells in the overexpressed BMP7 group was lower than that of the control group.Transwell experiments confirmed that the cell invasion migration capacity of the overexpressed BMP7 group was less than that of the control one.The immune infiltration results showed that BMP7 was positively correlated with macrophages(P = 0. 008) and negatively correlated with γ-δT cells(P = 0. 028) .
Conclusion
BMP7 is low in ESCC and associated with poor prognosis and immune infiltration levels in patients.
7.A nomogram predictive model of ileus after radical cystectomy
Yunzhao AN ; Heng ZHANG ; Ye TIAN ; Lingyue AN ; Guangheng LUO
Journal of Modern Urology 2023;28(10):882-887
【Objective】 To analyze the risk factors of ileus after radical cystectomy, and to construct a nomogram predictive model accordingly. 【Methods】 Clinical data of patients who underwent radical cystectomy during Jan.2018 and Dec.2021 were collected. The risk factors related to postoperative ileus were assessed with Logistic univariate and multivariate regression analysis. After that, the predictive model was constructed and its specificity and accuracy were verified. 【Results】 A total of 326 patients were included, 65 of whom developed ileus. Statistical analysis showed that gender, lymph node dissection, serum creatinine and albumin were correlated with postoperative ileus. The area under the receiver operating characteristic curve of the model was 0.769 (95%CI:0.724-0.802). Bootstrap correction curve showed that the model had good prediction accuracy. 【Conclusion】 Male, lymph node dissection, elevated postoperative serum creatinine and postoperative blood albumin decrease are predictors of ileus. The nomogram predictive model based on these predictors can predict the probability of ileus after radical cystectomy.
8.Comparative analysis of EOS and CT in the measurement of tibial tubercle-trochlear groove spacing in patellar dislocation
Yonggang TANG ; Yunzhao BAI ; Bin YANG ; Tang HU ; Rong ZHANG ; Ye GENG
Journal of Practical Radiology 2023;39(12):2018-2021
Objective To expand the application of EOS in orthopedic diagnosis and treatment by comparing EOS and CT in the measurement of tibial tubercle-trochlear groove(TT-TG)distance of patellar dislocation.Methods The clinical and complete imaging data(EOS and CT)of 35 cases of patellar dislocation(dislocation group)and 35 cases of non-patellar dislocation(non-dislocation group)were analyzed retrospectively.Results The age difference between the dislocation group and the non-dislocation group was statistically significant(P<0.05).The TT-TG distance was measured by EOS in the dislocation group(20.19±1.05)mm and the non-dislocation group(13.33±1.17)mm,and the difference between the two groups was statistically significant(P<0.05).The TT-TG distance was measured by CT in the dislocation group(21.51±1.11)mm and the non-dislocation group(14.21±1.11)mm,and the difference between the two groups was statistically significant(P<0.05).Bland-Altman plot showed that only three cases were outside the 95%confidence interval.Conclusion Accurate TT-TG distance can be obtained by using EOS system in imaging evaluation of patients with patellar dislocation,which provides a new measurement method for diagnosis and treatment evaluation of patellar dislocation.
9.Cellular FLICE-like inhibitory protein alleviates myocardial ischemia/reperfusion injury via inhibiting necroptosis
Di LIU ; Hui WU ; Jun YANG ; Jian YANG ; Jiawang DING ; Jing ZHANG ; Yunzhao LI ; Gang ZHOU ; Dong ZHANG
Chinese Journal of Emergency Medicine 2022;31(3):349-355
Objective:To explore the regulatory effect of cellular FLICE-like inhibitory protein (cFLIP) on myocardial ischemia-reperfusion injury based on the RIPK1/RIPK3/MLKL-mediated necroptosis pathway.Methods:The cardiomyocyte hypoxia/reoxygenation (H/R) model was constructed by hypoxia for 4 h/reoxygenation for 12 h, and the rat ischemia reperfusion (I/R) model was constructed by ligating the left anterior descending artery for 30 min and reperfusion for 3 h. CCK-8 method was used to detect the viability of cardiomyocytes in each group. DAPI/PI double staining was used to observe changes in necrosis rate of myocardial cell. STRING database was used to predict the protein interaction network of cFLIP. TTC staining was used to detect the area of myocardial infarction in each group of rats, and the protein expression of cFLIPL, cFLIPS, p-RIPK1, p-RIPK3 and p-MLKL were detected by Western blot.Results:In cardiomyocyte H/R injury and myocardial tissue I/R injury, the protein expressions of cFLIPL and cFLIPS were significantly down-regulated, while the levels of p-RIPK1, p-RIPK3 and p-MLKL were increased significantly. Up-regulating the protein expression of cFLIPL and cFLIPS could significantly reduce the damage of cardiomyocytes and the rate of cell necrosis induced by H/R, and decrease the area of myocardial infarction caused by I/R. STRING database results showed that cFLIP had direct protein interactions with RIPK1 and RIPK3. Overexpression of cFLIP in cardiomyocyte and myocardial tissue significantly inhibited H/R or I/R induced the phosphorylation levels of RIPK1, RIPK3 and MLKL.Conclusions:Overexpression of cFLIP can significantly inhibit the RIPK1/RIPK3/MLKL-mediated necroptosis, thereby reducing myocardial cell damage and decreasing the area of myocardial infarction.
10.Comparison of percutaneous resection and laparoscopic deroofing of renal cysts
Yong LIU ; Xinjie WANG ; Shengjun MA ; Peng YU ; Lei LIU ; Yunzhao ZHANG ; Fang XIE ; Haiguang LIU ; Hanhua WANG ; Jun WANG
Chinese Journal of Urology 2017;38(1):5-8
Objective To compare the short term clinical efficacy of percutaneous resection and laparoscopic deroofing of renal cysts.Methods From October 2013 to June 2016,the data from 39 cases with renal cysts were followed for approximately 22 months (ranging 5-36 months).Patients were randomized into two groups.In the resectoscopic group(17 pts),the mean age of those patients was 57 years (ranging 34-81 years).The mean size of these cysts was 6.4cm (ranging 5.4-8.2 cm).The mean preoperative creatinine was 66.5μmol/L (ranging 38.1-108.8μ mol/L).The mean preoperative sodium was 141.4μ mol/L(ranging 135.6-145.1μmol/L).The mean preoperative potassium was 4.0μmol/L (ranging 3.4-4.7 μmol/L).In the latter laparoscope (22pts),the mean age of these patients was 60 years (ranging 46-73 years).The mean size of these cysts was 6.8cm (ranging 4.3-8.9cm).The mean preoperative creatinine was 74.8μmol/L (ranging 48.6-141.9μmol/L).The mean preoperative sodium was 141.5μmol/L(ranging 135.0-146.1 μmol/L).The mean preoperative potassium was 4.0μmol/L (ranging 3.1-4.8μmol/L).The operative time,blood loss,days of drainage,hospital stay and complications were compared with the two groups.Results All of the 39 cases were accepted the procedure successfully without open conversion.Compared the resectoscopic group with Laparoscopic,the mean operative time was 29.7 min (ranging 15-50 min) and 63.0min (ranging 20-1 00 min),mean blood loss was 36.6ml(ranging 10-80 ml) and 60.4ml(ranging 10-200 ml),days of drainage was 2.3 days and 3.1 days,hospital stay was 3.7 days and 5.1 days,the mean postoperative creatinine was 67.4 μmol/L(ranging 43.8-95.5 μmol/L) and 68.9μmol/L(ranging 46.5-157.6 μmol/L),the mean postoperative sodium was 141.2μmol/L(ranging 136.0-147.2 μmol/L) and 141.6 μmol/L(ranging 136.0-147.2 μmol/L),the mean postoperative potassium was 3.8 μmol/L (ranging 3.2-4.3 μmol/L) and 3.8μmol/L (ranging 3.3-4.3 μmol/L).The overall postoperative pathology was renal cysts.All cases were followed for approximately 19 months (ranging 6-35 months) and 22 months (ranging 5-36 months) in reseetoscopic and laparoscopic group respectively.No cysts recurrence was found by ultrasound.Conclusions Compared with laparoscopic deroofing,use of resectoscopic technology significantly enhances the possibility of achieving better intraoperative results in all patients with renal cysts.Percutaneous resection of simple renal cysts is safe and feasible.


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