1.Expression and Clinical Significance of PLCβ4 Gene in Hepatocellular Carcinoma Analyzed Based on TCGA Database and Experimental Validation
Limei WEN ; Yali GUO ; Qiang HOU ; Dongxuan ZHENG ; Wu DAI ; Xiang GAO ; Jianhua YANG ; Junping HU
Cancer Research on Prevention and Treatment 2025;52(6):502-510
Objective To analyze the PLCβ4 gene mRNA expression and its clinical significance in hepatocellular carcinoma (HCC) based on TCGA database. Methods Based on the data on 424 clinical samples (including 374 cases of HCC tissues and 50 cases of nontumor liver tissues) in the TCGA database, Kaplan–Meier method, Cox regression analysis, and immune infiltration analysis were performed to evaluate the relationship between PLCβ4 gene and the clinical characteristics and survival prognosis of HCC patients. Correlation analysis between PLCβ4 gene and 24 types of immune cells was applied to investigate the relationship between PLCβ4 gene and immune cell infiltration and mRNA expression level of TP53 gene, a high-frequency mutation gene in HCC. In addition, paraffin sections of highly, moderately, and poorly differentiated tumor tissues and normal liver tissues from HCC patients were collected. The histopathological observation was carried out via HE staining method, and the expression levels of PLCβ4 and Ki-67 proteins in each clinical sample were verified through the immunohistochemical method. Results The expression level of PLCβ4 gene in HCC was significantly higher than that in normal tissues (P<0.01), and all patients in the PLCβ4 high-expression group had a significantly longer overall survival than those in the low-expression group (P<0.05), which suggested that PLCβ4 substantially affected the prognosis of HCC patients. Correlation analysis showed that the expression level of PLCβ4 gene was highly correlated with immune cell infiltration and the expression level of TP53 gene. As verified by clinical sample experiments, HE staining experiments and immunohistochemical results revealed that PLCβ4 gene expression in HCC tissue samples was significantly higher than that in normal tissues (P<0.001), and it was negatively correlated with the degree of differentiation. Conclusion PLCβ4 may serve as an independent prognostic factor in HCC and is expected to be a novel molecular target for HCC treatment.
2.Application of nursing intervention based on information-knowledge-attitude-practice model in preventing radiodermatitis in tumor radiotherapy patients
Junping ZHANG ; Xinzhai DONG ; Zheng LI ; Fang ZHAO
Chinese Journal of Practical Nursing 2024;40(1):13-19
Objective:To explore the effect of nursing intervention based on information-knowledge-attitude-practice model (IKAP) in preventing radiodermatitis in tumor radiotherapy patients.Methods:This was a quasi-experimental study. A total of 72 patients who received radiotherapy in the Department of Oncology, the Second Hospital of Shanxi Medical University from August to October 2022 were selected and divided into the experimental group and the control group with 36 patients in each group by randomized digits table method. The control group received routine nursing, while the experimental group received nursing based on the IKAP. The self-management efficacy, radiodermatitis, self-perceived burden and quality of life of patients in the two groups were evaluated one day before and at the end of radiotherapy.Results:Thirty-five patients from each group completed the study. There were 11 males and 24 females in the control group, aged (58.09 ± 7.33) years old. There were 13 males and 22 females in the experimental group, aged (58.06 ± 7.28) years old.There was no statistically significant difference in self-management efficacy, self-perceived burden, and quality of life scores between the two groups of patients before intervention (all P>0.05). After intervention, the self-management efficacy,self-perceived burden, and quality of life scores of the experimental group were (106.89 ± 3.78), (18.69 ± 2.21), and (8.09 ± 1.27) points, respectively, the control group was (80.69 ± 5.76), (29.97 ± 2.48), and (15.91 ± 2.37) points, respectively. The differences between the two groups were statistically significant ( t=2.50, 1.12, 7.24, all P<0.01). The incidence of radiodermatitis above grade 2 in the experimental group was 31.4%(12/35), which was lower than 60.0%(21/35) in the control group, the difference was statistically significant ( χ2=4.64, P<0.01). Conclusions:Nursing intervention based on IKAP can improve the self-management efficacy, reduce the self-perceived burden and the incidence of radiodermatitis, and further improve the quality of life of tumor radiotherapy patients.
3.Aerobic exercise upregulates the thioredoxin system and inhibits cardiomyocyte apoptosis in aging rats
Zheng XU ; Xiaoqin ZHAO ; Xiaodan CHEN ; Jiapu WANG ; Fenmiao BAO ; Liang YU ; Junping LI ; Yan WEI
Chinese Journal of Tissue Engineering Research 2024;28(34):5508-5515
BACKGROUND:Studies have shown that cardiomyocyte apoptosis is closely related to cardiac decompensation and the cardiac aging process.Appropriate exercise can alter heart pump function in patients with heart failure as well as attenuate aging-induced cardiomyocyte apoptosis,hypertrophy,and fibrotic damage. OBJECTIVE:To investigate the effects of long-term aerobic exercise on cardiomyocyte apoptosis and the thioredoxin system in aging rats. METHODS:Thirty-six male Sprague-Dawley rats were selected and divided into three age groups:3-month-old young group,9-month-old middle-aged group,and 18-month-old elderly group,with 12 rats in each group.Within each age group,rats were randomly assigned to sedentary and exercise subgroups(n=6 per group).The sedentary groups did not undergo any exercise intervention.The exercise groups were acclimated to a treadmill environment and subsequently subjected to treadmill exercise for 45 minutes per day,at a speed of 15 m/min,5 days per week for 10 weeks in total.At 24 hours after the final intervention,ELISA was employed to measure serum levels of cardiac troponin I and creatine kinase-MB in rats.TUNEL assay was utilized to detect cardiomyocyte apoptosis,while western blot assay was employed to assess the protein expression of Bax,Bcl-2,Caspase 3,thioredoxin-1,thioredoxin-2,thioredoxin reductase-1,thioredoxin reductase-2,thioredoxin-interacting protein,apoptosis signal-regulating kinase 1,and P38 mitogen-activated protein kinase in rat myocardial tissue. RESULTS AND CONCLUSION:Serum levels of cardiac troponin I and creatine kinase-MB in the elderly sedentary group were significantly higher than those in the young and middle-aged sedentary groups and elderly exercise group(P<0.01).Serum levels of cardiac troponin I and creatine kinase-MB in the elderly sedentary group were significantly higher than those in the young and middle-aged exercise groups and elderly exercise group(P<0.01).Positive apoptotic cells in rat myocardial tissue,along with increased protein expression of Bax and Caspase 3,exhibited an age-related upward trend,while Bcl-2 protein expression showed a declining trend.In comparison with the sedentary groups within each age category,the number of apoptotic cardiomyocytes and the expression of Bax and Caspase 3 proteins were reduced to different degrees,and the expression of Bcl-2 protein was increased to different degrees in the corresponding exercise groups.Compared with the young sedentary group,middle-aged sedentary group and elderly exercise group,elderly sedentary rats showed a significant decrease in the expression of myocardial thioredoxin 1,thioredoxin 2,thioredoxin reductase 1,and thioredoxin reductase 2 proteins(P<0.05,P<0.01).The expression of myocardial thioredoxin 1,thioredoxin 2,and thioredoxin reductase 2 proteins was lower in the elderly exercise group than in the young exercise group(P<0.05,P<0.01),while the expression of thioredoxin reductase 1 and thioredoxin reductase 2 proteins was lower in the elderly exercise group than in the middle-aged exercise group(P<0.01).The protein expression of thioredoxin-interacting protein,apoptosis signal-regulating kinase 1,and P38 mitogen-activated protein kinase in rat myocardium was significantly higher in the elderly sedentary group than the young sedentary group,middle-aged sedentary group and elderly exercise group(P<0.01).The protein expression of thioredoxin-interacting protein,apoptosis signal-regulating kinase 1,and P38 mitogen-activated protein kinase in rat myocardium was significantly higher in the elderly exercise group than the young exercise group and middle-aged exercise group(P<0.01).To conclude,aerobic exercise may enhance the anti-apoptotic effects of thioredoxin by down-regulating the expression of thioredoxin-interacting protein in aging rat hearts,leading to the downregulation of apoptosis signal-regulated kinase 1 and P38 mitogen-activated kinase protein,thereby alleviating myocardial cell apoptosis in aging rat hearts.
4.Comparison of Short-term Efficacy of Neoadjuvant Immunotherapy Combined with Chemotherapy and Surgery Alone for Locally Advanced Resectable Non-small Cell Lung Cancer
LI HAITIAN ; LIU QING ; LI BIN ; CHEN YUZHEN ; LIN JUNPING ; MENG YUQI ; FENG HAIMING ; ZHENG ZHIZHONG ; HUI YIMING
Chinese Journal of Lung Cancer 2024;27(6):421-430
Background and objective Lung cancer is the cancer with the highest incidence and mortality rates in China,and non-small cell lung cancer(NSCLC)accounts for 80%-85%of all malignant lung tumors.Currently,surgical treat-ment remains the primary treatment modality for lung cancer.In recent years,the effectiveness of immune checkpoint inhibi-tors for NSCLC has become a consensus,and neoadjuvant immunochemotherapy(nICT)has shown promising efficacy and safety in early to intermediate stage NSCLC.However,there are fewer studies related to nICT for locally advanced NSCLC.This study aims to evaluate the efficacy and safety of nICT therapy in locally advanced resectable NSCLC.Methods 85 con-firmed resectable stage ⅢA and ⅢB patients treated in the Department of Thoracic Surgery,Second Hospital of Lanzhou University,from January 2021 to April 2024,were divided into the nICT group(n=32)and the surgery alone group(n=53).Clinical baseline data,perioperative indicators,postoperative complications,imaging response rate,pathological response rate,incidence of adverse events,and quality of life were compared between the two groups.Results There were no statisti-cally significant differences in clinical baseline data between the two groups(P>0.05).Incidence of choosing thoracotomy was higher in the nICT group than in the surgery alone group(P=0.002).There were no significant differences in surgical time,intraoperative blood loss,number of dissected lymph nodes,duration of chest tube placement,postoperative hospital stay,and R0 resection rate between the two groups(P>0.05).The overall incidence of postoperative complications was 31.25%in the nICT group and 22.64%in the surgery alone group,with no statistically significant difference(P=0.380).In the nICT group,the objective response rate(ORR)was 84.38%,with 5 cases of complete response(CR)(15.63%),22 cases of partial response(PR)(68.75%),15 cases of pathological response rate(pCR)(46.88%),and 11 cases of major pathological reaponse(MPR)(34.38%).During nICT treatment,12 cases(37.50%)experienced grade 3 treatment-related adverse events,no death induced by adverse events or immune related adverse events.Moreover,the symptoms of the patients were improved after nICT treat-ment.Conclusion Neoadjuvant immunochemotherapy shows promising efficacy in locally advanced resectable NSCLC,with manageable treatment-related adverse events.It is a safe and feasible neoadjuvant treatment modality for locally advanced resectable NSCLC.
5.Mutation analysis of TNC gene in a familial hearing loss pedigree
Fei LIANG ; Junping LIU ; Xiaoyan ZHAN ; Binbin YANG ; Miao'an CHEN ; Yanhua ZHENG
Chinese Archives of Otolaryngology-Head and Neck Surgery 2024;31(11):712-716
OBJECTIVE Exploring the TNC gene mutations in a family with hereditary hearing loss and their relationship with clinical phenotypes.METHODS Draw the family pedigree chart,analyze the inheritance pattern,and assess the clinical phenotypes of family members using audiologic,imaging,and vestibular function tests.Perform whole exome sequencing on six members of the family to identify candidate mutations potentially related to hearing loss,and validate the distribution of these candidate mutations within the family and in normal controls using Sanger sequencing.RESULTS A heterozygous mutation c.5110G>T(p.Ala1704Ser)in exon 17 of the TNC gene on chromosome 9 was identified in the family.This mutation is associated with hereditary hearing loss.Carriers of this gene mutation all presented with normal hearing at birth and hearing decline during childhood;imaging examinations showed no abnormalities in the middle ear or inner ear structures.CONCLUSION This study reports for the first time the association between the heterozygous mutation c.5110G>T(p.Ala1704Ser)in the TNC gene and hereditary hearing loss,providing new evidence for molecular diagnosis and genetic counseling in cases of hereditary hearing loss.
6.Protective effect of liraglutide on acute lung injury in septic mice and its mechanism
Junping GUO ; Ran PAN ; Lijun WANG ; Yueliang ZHENG ; Mao ZHANG ; Guirong WANG
Chinese Journal of Emergency Medicine 2024;33(8):1134-1139
Objective:To explore the protective effects of liraglutide on acute lung injury in septic mice and its mechanisms.Methods:Thirty-six male FVB/NJ mice were randomly(random number) divided into three groups: control group (Control, n=12), acute lung injury group (ALI, n=12)and liraglutide intervention group (ALI+LIRA, n=12). Mice model of acute lung injury were prepared by intratracheal instillation of Pseudomonas aeruginosa suspension, while the control group were given intratracheal instillation of equal volume of physiological saline; the mice in ALI+LIRA group were received subcutaneous injection of liraglutide (2 mg/kg) 30 minutes post-induction, while both the mice in control group and ALI group were received subcutaneous injection of equal volume physiological saline. After 24 hours, the mice were euthanized, the lung tissues and bronchoalveolar lavage fluid (BALF) were collected, the lung pathological damage changes were evaluated by hematoxylin eosin staining, the expression of surfactant associated protein D (SP-D)in lung tissue were detected by immunofluorescence assay; total protein concentration in BALF were detected by BCA method, and the levels of interleukin-6 (IL-6) and tumor necrosis factor α(TNF-α)levels in BALF were measured by enzyme-linked immunosorbent assay(ELISA), the protein expression of SP-D in BALF and lung tissue were determined by Western blot. Statistical analysis was performed by SPSS software, and continuous variables were compared with one-way analysis of variance among the groups. Results:Compared with the control group, the mice in ALI group had higher lung histopathology injury score, higher total protein concentration, higher IL-6 and TNF-α levels in BALF, and had less SP-D positive cells in lung tissue; and also had lower expression of SP-D in both BALF and lung tissue, with statistical significance (all P<0.05). Compared with ALI group, the mice in ALI+LIRA group had lower lung histopathology injury score, lower total protein concentration, lower IL-6 and TNF- α levels in BALF, and had more SP-D positive cells in lung tissue; and also had higher expression of SP-D in both BALF and lung tissue, with statistical significance (all P<0.05). Conclusions:Liraglutide attenuates the severity of acute lung injury in septic mice, and its protective mechanism may be associated with the promotion of SP-D secretion.
7.Analysis of imaging and clinical features of phosphaturic mesenchymal tumor
Junping LAN ; Jiageng XIE ; Yushi PENG ; Yimin CHEN ; Zhe XIAO ; Hanzhe WANG ; Xiangwu ZHENG
Journal of Practical Radiology 2024;40(12):2029-2032
Objective To explore the clinical and imaging features of phosphaturic mesenchymal tumor(PMT).Methods The clinical presentations,laboratory examinations,and imaging manifestations of seven patients with PMT diagnosed by surgery and pathology were analyzed retrospectively.Results Among the 7 patients,four patients had clinical presentations of long-term fatigue and bone pain.All patients showed preoperative blood phosphorus reduction in varying degrees.X-ray examination showed systemic osteomalacia and osteoporosis,accompanied by multiple pathological fractures.On CT,the primary tumor appeared as a soft tissue density mass or a ground glass high-density nodule with irregular calcification and local bone destruction.MRI showed long T1,long T2 signal intensity,and irregular low signal foci were scattered in the T2WI fat-suppressed sequence.The enhanced scans showed moderate to significant inhomogeneous enhancement.One patient who underwent 18F-FDG PET/CT and two patients who underwent 18F-ALF-NOTA-Octreotide(18F-OC)PET/CT examinations showed varying degrees of radioactive concentration in the lesions.Conclusion The clinical presentations and laboratory examinations of patients with PMT have certain characteristics.Systemic osteomalacia with pseudofracture line,calcification matrix within the tumor,and significant inhomogeneous enhancement of the lesion are the key imaging features for diagnosing PMT.18F-OC PET/CT examination plays a crucial role in the systemic localization diagnosis of tumors.
8.Impact of pumpkin polysaccharides on hypoxia/reoxygenation-induced myocardial cell injury by regulating Nrf2/γ-GCS pathway
Wan ZHENG ; Shanshan YANG ; Yun LIN ; Junping WEI ; Yani YAN
Chinese Journal of Immunology 2024;40(9):1871-1875
Objective:To investigate the impact of pumpkin polysaccharide(PP)on hypoxia/reoxygenation(H/R)-induced myocardial cell(H9C2)injury by regulating Nrf2/γ-GCS pathway.Methods:HR cell models were established,and the concentration of pumpkin polysaccharide(PP)was determined.H9C2 cells were grouped into Control group,H/R group,pumpkin polysaccharide group(PP group,2 mg/L PP),Nrf2 inhibitor group(ML385 group,2.0 μmol/L ML385),and PP+ML385 group(2.0 mg/L PP+2.0 μmol/L ML385),the apoptosis,mitochondrial membrane potential changes,oxidative stress(LDH,MDA,SOD,ROS),the lev-els of inflammatory factors(TNF-α,IL-6,IL-1β)and the protein expressions of Nrf2 and γ-GCS in H9C2 cells were detected,respec-tively.Results:Compared with Control group,H/R group had changes in cell morphology,the cell injury and mitochondrial membrane potential decreased,the H9C2 cell viability,SOD and protein expression levels of Nrf2 and γ-GCS were significantly decreased,while the apoptosis rate,LDH,MDA,ROS,and levels of TNF-α,IL-6 and IL-1β were significantly increased(P<0.05);compared with H/R group,the cell injury in PP group was reduced,the mitochondrial membrane potential was restored,the H9C2 cell viability,SOD and protein expression levels of Nrf2 and γ-GCS were significantly increased,and the apoptosis rate,LDH,MDA,ROS,and levels of TNF-α,IL-6 and IL-1β were significantly decreased(P<0.05),the effect of ML385 was opposite to that of PP,and ML385 could reverse the antioxidant and anti-inflammatory effects of PP.Conclusion:PP up-regulates the Nrf2/γ-GCS pathway to exert antiox-idant and anti-inflammatory effects,and reduces H/R-induced H9C2 cell injury.
9.Prediction of invasiveness in follicular variant of papillary thyroid carcinoma using nomograms based on ultrasonic features
YuXin ZHENG ; Yajiao ZHANG ; Liyu CHEN ; Kefeng LU ; Jiangyan LOU ; Junping LIU ; Dong XU
Chinese Journal of Ultrasonography 2024;33(9):800-806
Objective:To explore the relationship between ultrasound characteristics and invasiveness in the follicular variant of papillary thyroid carcinoma (FVPTC), and to integrate multiple ultrasound parameters for visual assessment of predictive outcomes by using Nomogram.Methods:A total of 312 FVPTC patients who were pathologically confirmed through surgery in Zhejiang Cancer Hospital and Zhejiang Provincial People′s Hospital from January 2013 to December 2023 were retrospectively collected.Based on defined criteria, FVPTC patients were categorized into high-invasion and low-invasion groups. The dataset was divided into a training set and a validation set in a ratio of 7 to 3. Clinical information and ultrasound feature parameters were collected. Univariate and multivariate Logistic regression analyses were performed on the training set. A predictive model for FVPTC invasiveness was constructed based on ultrasound features. The model′s discriminative ability and calibration were evaluated in the validation set, and a nomogram was generated.Results:The training set included a total of 218 patients with FVPTC, among which 131 were classified as high invasive.The validation set consisted of 94 patients, with 53 cases of high invasive FVPTC patients. Multivariate logistic regression analysis on the training set revealed that tumor multifocality ( OR=6.505, P=0.016), hypoechoic ( OR=3.235, P=0.103), shape ( OR=0.521, P=0.049), and microcalcifications ( OR=2.479, P=0.004) were independent influencing factors for predicting invasiveness in FVPTC. In the training set, the area under the curve (AUC) of the ultrasound predictive model was 0.704 (95% CI=0.634-0.771), and in the validation set, the AUC was 0.650 (95% CI=0.531-0.770), indicated good discriminative ability.The calibration curve showed good alignment with the ideal curve, demonstrating favorable calibration performance. Conclusions:Ultrasound features provide valuable information for assessing the invasiveness of FVPTC, and the model constructed by combining ultrasound features demonstrates good predictive efficacy for the invasiveness of FVPTC.
10.Baicalin Induces Ferroptosis in Gastric Cancer Cells via p53-mediated SLC7A11 Down-regulation
Xiaolong YUAN ; Zheng WEI ; Junping ZHANG ; Rui ZHENG ; Rui CHAO ; Xiaoping CAI
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(6):71-78
ObjectiveTo explore the inhibitory effect of different concentration of baicalin (0, 100, 200, 400 μmol·L-1) on the proliferation of human gastric cancer SGC-7901 cells and the underlying mechanism. MethodSGC-7901 cells were treated with baicalin. Then methyl thiazolyl tetrazolium (MTT) assay was employed to examine the inhibitory effect of baicalin on the cells. At the same time, ferrostatin-1 (Fer-1) was added to observe the viability of cells after baicalin treatment. The expression of ferroptosis-related genes was detected by Real-time polymerase chain reaction (Real-time PCR) and Western blot. The content of malondialdehyde (MDA) and the level of glutathione (GSH) were detected respectively by MTT assay and enzyme-linked immunosorbent assay. The role of tumor protein 53 (p53)/solute carrier family 7 member 11 (SLC7A11) pathway in the regulation of ferroptosis was investigated respectively via overexpression and small interfering RNA (siRNA) methods. ResultCompared with the blank group, baicalin decreased the viability of SGC-7901 (P<0.05, P<0.01) in a dose- and time-dependent manner. The intervention of Fer-1 significantly alleviated the decrease of SGC-7901 cell viability caused by baicalin (P<0.01). In addition, compared with the baicalin group, Fer-1+baicalin group showed decrease in MDA content and the mRNA and protein levels of prostaglandin-endoperoxide synthase 2 (PTGS2) in the cells (P<0.01), and increase in GSH activity and mRNA and protein levels of glutathione peroxidase 4 (GPX4) (P<0.01). The protein level of SLC7A11 in the baicalin group was decreased compared with that in the blank group (P<0.05, P<0.01) in a dose-dependent manner. Compared with the baicalin group, the reactive oxygen species (ROS) level and MDA content in SLC7A11-overexpressing cells were significantly decreased after baicalin treatment (P<0.01), and the GSH activity was significantly increased (P<0.01). The fluorescence intensity of p53 in the cells of the baicalin group was increased compared with that of the blank group (P<0.01). Compared with the baicalin group, the expression level of p53 protein in the cells transfected with p53 siRNA was significantly decreased after baicalin treatment (P<0.01), and the expression level of SLC7A11 was significantly increased (P<0.01). ConclusionBaicalin can effectively inhibit the proliferation of SGC-7901 cells by regulating p53/SLC7A11-mediated ferroptosis.

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