1.Single cell sequencing data reveal the diagnostic and predictive value of DMKN in ovarian cancer
Yan GAO ; Mengcheng YAO ; Zhefeng LI ; Xiaoyang HAN ; Wentao YUE
Practical Oncology Journal 2023;37(6):478-484
Objective The aim of this study was to draw single-cell transcriptome profiles of high-grade serous ovarian cancer(HGSOC),borderline ovarian cancer(OC),and normal ovaries in order to identify biomarkers that can diagnose and predict the prognosis of OC.Methods The differentially expressed genes between HGSOC,borderline OC,and normal ovarian tissues were ana-lyzed using single-cell data sequenced(SRA database:PRJNA756768).The cell subsets associated with tumor progression were screened by functional enrichment,cell communication between different subsets was analyzed by Cellchat,and cell differentiation traj-ectories were explored by pseudotime analysis to finally determine the subsets most relevant to tumor progression.Combined with OC transcriptome data of OC from the Cancer Genome Atlas(TCGA)with patient prognosis,biomarkers for diagnosing and predicting sur-vival of OC patients were ultimately screened.Results After using t-distribution stochastic neighbor embedding(t-SNE)for di-mensionality reduction,nine cell subpopulations were obtained:endothelial cells,myeloid cells,fibroblasts,T cells,stromal cells,B cells,and 3 epithelial cell subpopulations(C1,C4,and C7).Further analysis revealed that copy number variation(CNV)in the C4 group had the highest score in HGSOC,higher than those of borderline OC and normal ovaries,and was negatively correlated with prognosis.DMKN was a key marker gene in this group.Transcriptome analysis of OC in the TCGA database showed a close correlation between DMKN and poor prognosis(P=0.026),and the diagnostic efficacy of DMKN for OC was significant(A UC=0.906).Con-clusion This study is based on single-cell sequencing data to screen for DMKN,which can effectively diagnose and predict the prognosis of OC.This study provides new ideas for the diagnosis and prognosis prediction of OC.
3.Predictive value of inflammatory markers in colorectal cancer
Zhefeng HE ; Yiyang WU ; Zhenjun LI ; Xiaojiang YING
Journal of International Oncology 2022;49(9):560-563
The cancer-associated systemic inflammatory response is one of the critical indicators of tumor progression. Serum systemic inflammatory markers, such as neutrophil-lymphocyte ratio, lymphocyte-monocyte ratio, systemic inflammation score, Glasgow prognostic score, prognostic nutritional index, C-reactive protein-albumin ratio, lymphocyte-C-reactive protein ratio, platelet-lymphocyte ratio, are associated with the prognosis of colorectal cancer (CRC) . Further research of the prognostic value of inflammatory marks in CRC can provide help for the prognosis of CRC.
4.GLDC regulates proliferation and apoptosis of ovarian cancer cells through PI3K/Akt/mTOR pathway
Zhefeng LI ; Jie LI ; Xiaoting ZHAO ; Wentao YUE
Journal of International Oncology 2021;48(12):716-722
Objective:To explore the mechanism of glycine dehydrogenase (GLDC) regulating the proliferation and apoptosis of ovarian cancer cells through PI3K/Akt/mTOR pathway.Methods:RNA interference method was used to silence the expression of GLDC in ovarian cancer cell lines HEY and SK-OV-3. The HEY and SK-OV-3 cells were divided into si-control group (transfected with siRNA-control), si-GLDC#1 group (trans-fected with siRNA-GLDC#1) and si-GLDC#2 group (transfected with siRNA-GLDC#2). The expression level of GLDC and the protein phosphorylation level of PI3K/Akt/mTOR were detected by Western blotting. Cell proli-feration, migration and apoptosis were detected by CCK-8 method, Transwell chamber test, cell scratch test and flow cytometry.Results:The relative expression levels of GLDC in the si-control group, si-GLDC#1 group amd si-GLDC#2 group of HEY cells were 1.00±0.01, 0.68±0.10, 0.80±0.08, and there was a statistically significant difference ( F=13.80, P=0.006). The relative expression levels of GLDC in the si-control group, si-GLDC#1 group and si-GLDC#2 group of SK-OV-3 cells were 1.02±0.01, 0.58±0.17, 0.60±0.25, and there was a statistically significant difference ( F=6.08, P=0.036). The absorbance ( A) values in the si-control group, si-GLDC#1 group and si-GLDC#2 group of HEY cells were 1.04±0.03, 0.91±0.02, 0.82±0.01 at 24 h after transfection, 1.53±0.13, 1.30±0.03, 1.29±0.07 at 48 h after transfection, 1.44±0.08, 1.25±0.01, 1.15±0.03 at 72 h after transfection, and there were statistically significant differences ( F=83.14, P<0.001; F=8.96, P=0.007; F=29.55, P<0.001). Further pairwise comparison showed that the proliferation abilities of the si-GLDC#1 and si-GLDC#2 group at 24, 48 and 72 h were significantly lower than those of the si-control group (all P<0.05). In HEY cells, the migration numbers of cells in the si-control group, si-GLDC#1 group and si-GLDC#2 group were 57.33±6.43, 27.67±5.13 and 30.67±2.31, and there was a statistically significantly difference ( F=32.88, P=0.001). The migration numbers of cells in the si-GLDC#1 group and si-GLDC#2 group were significantly lower than that in the si-control group ( P<0.001; P=0.001). Similar results were also observed in SK-OV-3 cells. In SK-OV-3 cells, the scratch healing rates in the si-control group, si-GLDC#1 group and si-GLDC#2 group were (51.27±1.59)%, (26.35±2.94)% and (26.34±7.69)%, and there was a statistically significant difference ( F=26.54, P=0.001). The scratch healing rates in the si-GLDC#1 group and si-GLDC#2 group were significantly lower than that in the si-control group (both P=0.001). In HEY cells, the apoptosis rates in the si-control group, si-GLDC#1 group and si-GLDC#2 group were (7.11±0.82)%, (10.44±1.50)%, (17.39±1.55)%, and there was a statistically significantly difference ( F=46.52, P<0.001). The apoptosis rates in the si-GLDC#1 group and si-GLDC#2 group were significantly higher than that in the si-control group ( P=0.022; P<0.001). Similar results were also observed in SK-OV-3 cells. In HEY cells, there was no significant difference in total PI3K protein in the si-control group, si-GLDC#1 group and si-GLDC#2 group ( F=0.54, P=0.631), but there were significant differences in pAkt/Akt and pmTOR/mTOR levels ( F=22.14, P=0.016; F=10.57, P=0.044). The pAkt/Akt and pmTOR/mTOR levels in the si-GLDC#1 group and si-GLDC#2 group were significantly lower than those in the si-control group ( P=0.015, P=0.008; P=0.039, P=0.023). Similar results were also observed in SK-OV-3 cells. Conclusion:In ovarian cancer cells, GLDC silencing can inhibit cell proliferation and promote apoptosis by inhibiting the PI3K/Akt/mTOR pathway.
5.A Neuronal Pathway that Commands Deceleration in Drosophila Larval Light-Avoidance.
Caixia GONG ; Zhenhuan OUYANG ; Weiqiao ZHAO ; Jie WANG ; Kun LI ; Peipei ZHOU ; Ting ZHAO ; Nenggan ZHENG ; Zhefeng GONG
Neuroscience Bulletin 2019;35(6):959-968
When facing a sudden danger or aversive condition while engaged in on-going forward motion, animals transiently slow down and make a turn to escape. The neural mechanisms underlying stimulation-induced deceleration in avoidance behavior are largely unknown. Here, we report that in Drosophila larvae, light-induced deceleration was commanded by a continuous neural pathway that included prothoracicotropic hormone neurons, eclosion hormone neurons, and tyrosine decarboxylase 2 motor neurons (the PET pathway). Inhibiting neurons in the PET pathway led to defects in light-avoidance due to insufficient deceleration and head casting. On the other hand, activation of PET pathway neurons specifically caused immediate deceleration in larval locomotion. Our findings reveal a neural substrate for the emergent deceleration response and provide a new understanding of the relationship between behavioral modules in animal avoidance responses.
6.Dose-effect relationships of bipolar radio frequency heating
Chao ZHANG ; Ping WANG ; Aifeng LIU ; Juntao ZHANG ; Guangbin YIN ; Zhefeng JIN ; Yuandong LI ; Shuo YANG ; Xiaodong WANG
Chinese Journal of Physical Medicine and Rehabilitation 2018;40(6):414-417
Objective To study the effect of the preset temperature,heating time and the spacing of radio frequency electrodes.Methods Fresh egg white was used to study the effects of heater spacing,temperature and heating time.Two electrodes were fixed to keep the needles perpendicular to the center of egg white confined on a square plate.Temperatures from 50 to 90℃ were tested with heating times of 60 and 120 seconds and electrode spac ings of 2.0,1.0,0.5 and 0.25 centimetres.The real-time temperature and the time to the appearance of a spindleshaped bridge between the electrodes was observed.The egg white's impedance and resistance,the lowest temperature of denaturation,and the mass (or volume) denatured at different time points were also observed.Results With an electrode spacing of 2 cm and the thermostat set at 63℃,the true electrode temperatures were 63.7 and 52.6℃,with the secondary electrode the cooler.Significant differences between the secondary electrode temperature and the preset temperature as well as the temperature between the primary and the secondary electrodes were observed.It was also found that different electrode spacing caused significant differences between the preset temperature and the primary as well as the secondary electrode temperature.Denaturation began at 56℃ with a spacing of 0.25 cm.At spacings of 0.25 and 0.50 cm,a spindle-shaped connection between the two electrodes was observed at temperatures above 70℃,but higher temperature was required at 1.00 and 2.00 cm.When the spacing was 0.25 cm and the preset temperature was 75℃,the denatured volume after 60 s of heating was 90.21+0.64 mm3.Heating for 120 s denatured 95.08+ 0.53 mm3 and two 60.s heatings 92.88+0.74 mm3,all significant differences.There were no significant differences in the resistance of the egg white before and after a single heating for 60 s,but after a single heating lasting 120 s it had increased significantly from 128.41+8.04 to 121.29±8.04 Ω.Conclusion Bipolar radio frequency heating can denature egg white.Higher temperature,longer heating and smaller electrode spacing heat more effectively.
7.Advances of research in cancer-associated inflammation and tumor microenvironments
Zhimin WEI ; Yufa SUN ; Gang LI ; Zhefeng LIU
Chinese Journal of Clinical Oncology 2018;45(21):1117-1121
Cancer-associated inflammation is one of the key features of cancer. Many cytokines are involved in inflammation and its regulation and play important roles in many factors affecting tumor biology. Inflammation participates in the construction of tumor mi-croenvironments (TMEs) by changing the homeostasis of tumor tissues. The interaction of cytokines secreted by TME-infiltrating cells forms a complex network of cytokines that play a role in tumor progression through various mechanisms such as inflammation promo-tion, immune editing, and immune escape. This review aims at analyzing the research progress on the relationship between inflamma-tion, cytokine networks, and TMEs
8.ω-3 polyunsaturated fatty acids inhibits RHO-ROCK1 signaling pathway in SGC7901 gastric cancer cells
Yiyan JIANG ; Yiwen JIANG ; Zhefeng LOU ; Dan HONG ; Zhengjing WEN ; Xiaolei YANG ; Suxia LI ; Longjin JIN
Journal of Chinese Physician 2018;20(11):1641-1646
Objective This study was aimed to investigate the effects of ω-3 polyunstaurated fatty acids (ω-3 PUFAs) on the growth of gastric cancer cells in nude mice,and to find whether the Ros homolog gene Rho-associated coiled-coil containing protein kinase 1 (RHO-ROCK1) signaling pathway is involved.Methods 16 BALB/C nude mice were injected subcutaneously with SGC7901 gastric cancer cells to establish the tumor-bearing mouse model.The mice were randomized:control group (normal saline) and intervention group (ω-3 PUFAs).The mRNA expression of Ros homolog gene family,member A (RHOA),RHOC,and ROCK1 in tumor tissue were detected by quantitative polymerase chain reaction (qPCR).Immunofluorescence and Western blot were used to detect RHOA,RHOC,and ROCK1 protein expression.Results The volume and weight of the tumors in the ω-3 PUFAs group were slightly smaller than that in the control group (P > 0.05).Compared to the control group,hematoxylin and eosin staining showed multifocal tumor necrosis in the ω-3 PUFAs group,while the tumors of the control group showed abundant blood supply.qPCR and Western blot showed that the mRNA and proteins expression of RHOA and ROCK1 in the ω-3 PUFAs group was significantly lower than those in the control group (P < 0.05).The immunofluorescence redults also showed that the expression of these proteins in the ω-3 PUFAs group was slightly lower than that in the control group.Conclusions These results suggested that ω-3 PUFAs may affect the growth of gastric cancer in nude mice by affecting the expression of RHOA,RHOC and ROCK1,thus inhibiting the excessive proliferation of gastric cancer cells and leading to tumor necrosis.
9.Relationship between degree of brain injury during perioperative period of liver transplantation and postoperative cognitive dysfunction
Yanxing ZHAO ; Ping CHI ; Yinghao CAO ; Zhefeng QUAN ; Kejun PENG ; Xin LI ; Xiaodong GUO ; Li SUN ; Haiyang LU ; Haili HE ; Dongmei MA
Chinese Journal of Anesthesiology 2018;38(2):138-141
Objective To evaluate the relationship between the degree of brain injury during the perioperative period of liver transplantation and postoperative cognitive dysfunction (POCD).Methods Thirtythree patients,undergoing elective liver transplantation,were enrolled in this study.Before induction of anesthesia (T0),at 5 min before blocking the portal vein (T1),5 min after opening the portal vein (T2),5 min after opening the hepatic artery (T3),and at 24 h after surgery (T4),blood samples were collected from the central vein for determination of the serum concentrations of S1O0β protein and neuron-specific enolase (NSE) by enzyme-linked immunosorbent assay.Patients were divided into POCD group and control group (group C) according to whether POCD happened within 7 days after surgery.Results Compared with the baseline value at T0,the serum concentrations of S100β protein were significantly increased at T2 and T3,and the serum concentrations of NSE was increased at T3 (P<0.05).There was no significant difference in serum concentrations of S100β and NSE at each time point between group POCD and group C (P>0.05).Conclusion The degree of brain injury during the perioperative period of liver transplantation is not the dominant factor for the development of POCD in the patients.
10.Multicenter postmarketing clinical study on using pegylated recombinant human gran-ulocyte-colony stimulating factor to prevent chemotherapy-induced neutropenia
Yuankai SHI ; Jianping XU ; Changping WU ; Yan ZHANG ; Junquan YANG ; Tao ZHOU ; Zheng LIU ; Weidong MAO ; Yiping ZHANG ; Wei WANG ; Zhonghe YU ; Lin WU ; Jianhua CHEN ; Juan WANG ; Yonghui AN ; Jianhui CAI ; Ming LIU ; Zhendong CHEN ; Qingshan LI ; Chaoying REN ; Zhiyong YANG ; Baolan LI ; Min ZHAO ; Zhefeng LIU ; Bin LIU
Chinese Journal of Clinical Oncology 2017;44(14):679-684
Objective: To investigate the efficacy and safety of using pegylated recombinant human granulocyte-colonystimulating factor (PEG-rhG-CSF) in preventing neutropenia in multiple chemotherapy cycles. Methods: A multicenter, prospective, open-label, singlearmstudy was designed. Patients with malignant tumors, such as lung, ovarian, and colorectal cancers, who received multiple cycles of chemotherapy with the prophylactic use of PEG-rhG-CSF for 2-4 consecutive cycles participated in the study. Results: After the prophylactic use of PEG-rhG-CSF, the incidence of grade IV neutropenia decreased from 4.76% (13/273) in the first cycle to 1.83% (5/273), 1.15% (2/174), and 2.08% (2/96) in subsequent cycles. Meanwhile, the incidence of grade III neutropenia decreased from 11.36% (31/ 273) in the first cycle to 6.23% (17/273), 2.87% (5/174), and 3.13% (3/96) in subsequent cycles. The incidence of febrile neutropenia (FN) during the first cycle was 0.73% (2/273). The duration of FN was 2 days in one case and 5 days in another case. FN was not observed during the second, third, or fourth cycle. After the secondary prophylactic use of PEG-rhG-CSF, the incidence of grade IV neutropenia decreased from 25% (7/28) to 3.57% (1/28), 0% (0/28), and 6.67% (1/15) in subsequent cycles. Meanwhile, the incidence of grade III neutropenia decreased from 71.43% (20/28) to 10.71% (3/28), 14.29% (4/28), and 0% (0/15) in subsequent cycles. The proportion of patients who received antibiotic therapy during the entire chemotherapy period was 10.48% (44/420). Conclusion: The application of PEG-rhG-CSF once per chemotherapy cycle can effectively reduce the occurrence of neutropenia in patients under multiple cycles of chemotherapy treatment with good safety.

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