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    25 February 2024, Volume 16 Issue 1 Previous Issue    Next Issue
    Inventory of tumor methylation marker research progress in 2023
    GE Shengyang, LI Wei, YU Wenqiang
    2024, 16 (1):  10-16.  doi: 10.3969/j.issn.1674-5671.2024.01.02
    Abstract ( 283 )   PDF   Save
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    Inventory of tumor protein marker research progress in 2023
    ZHOU Xinmeng, LIAO Qingqing, XIE Na, HUANG Canhua, SUN Xiaodong, ZHANG Yuanyuan
    2024, 16 (1):  23-31.  doi: 10.3969/j.issn.1674-5671.2024.01.04
    Abstract ( 198 )   PDF   Save
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    Inventory of tumor metabolic markers research progress in 2023
    CHEN Yao, LI Li, MIAO Hongming, YANG Fan
    2024, 16 (1):  38-42.  doi: 10.3969/j.issn.1674-5671.2024.01.06
    Abstract ( 234 )   PDF   Save
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    Effects of glycolysis in Gefitinib resistance in non⁃small cell lung cancer
    LI Nan, LU Chenyang, ZHU Ani, YANG Dongcai, MA Qian, YAN Fengqi, JIA Weihong
    2024, 16 (1):  50-55.  doi: 10.3969/j.issn.1674-5671.2024.01.08
    Abstract ( 181 )   PDF   Save
    Objective To investigate the changes and effects of glycolysis in Gefitinib resistance in non⁃small cell lung cancer (NSCLC) . Methods NSCLC parental cells PC⁃9 and A549 were cultured in vitro, and NSCLC Gefitinib⁃resistant cells PC⁃9⁃GR and A549⁃GR were constructed by the increasing concentration method. Cell resistance was identified by CCK⁃8 and colony formation assay. The glucose metabolism and lactate production levels were detected using glucose and lactate assay kits, respectively. qRT⁃PCR and Western blot were used to detect the mRNA and protein levels of the key enzymes in glycolysis. After inhibition of glycolysis by 2⁃deoxy⁃D⁃glucose, the viability of cells and the changes of drug resistance to Gefitinib were observed. Results Compared with parental cells, the resistance of PC⁃9⁃GR and A549⁃GR cells to Gefitinib was enhanced (all P<0.01), and glucose metabolism rate and lactate production level were increased (all P<0.01). The mRNA expression levels of HK2, LDHA and PFK and the protein levels of HK2 , LDHA, PFKP and PKM2 were increased (all P<0.001). The inhibitory effect of 2⁃DG on the activities of drug⁃resistant cells was more significant than on those of their respective parental cells (all P<0.05), and to some extent, it could enhance the killing effect of Gefitinib on drug⁃resistant cells. Conclusions Gefitinib resistance in NSCLC is accompanied by the activation of glycolysis, and is associated with increased expression of key enzymes in glycolysis. Inhibiting the levels or activities of glycolysis may be an effective measure to reverse the drug resistance of Gefitinib.
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    Anti⁃tumor effect of PI3K inhibitor Linperlisib on diffuse large B⁃cell lymphoma in vitro
    ZHANG Kaimin, HUANG Yujie, DUAN Ying, GUO Baoping, KE Qing, LIAO Chengcheng, CEN Hong
    2024, 16 (1):  56-61.  doi: 10.3969/j.issn.1674-5671.2024.01.09
    Abstract ( 165 )   PDF   Save
    Objective To investigate the anti⁃tumor effect of PI3K inhibitor YY⁃20394 on diffuse large B⁃cell lymphoma (DLBCL) in vitro and the underlying mechanism. Methods The effects of different concentrations of YY⁃20394 on the proliferation of SU⁃DHL⁃4 cells (GCB subtybe) and U2932 cells (ABC subtype) were detected by CCK⁃8, and the IC25, IC50 and IC75 at 24 h were calculated. The effects of different concentrations(IC25、IC50、IC75) of YY⁃20394 on the apoptosis of SU⁃DHL⁃4 cells and U2932 cells were detected by flow cytometry. High⁃throughput RNA sequencing technology (RNA⁃Seq) was used to detect the changes of gene expression in cells before and after drug action, and the differentially expressed genes were analyzed by KEGG enrichment analysis and GO fumction annotation analysis. Gene expression data of each group of cells were analyzed by GSEA enrichment. Results Under the treatment of YY⁃20394, the proliferation inhibition rate and apoptosis rate of SU⁃DHL⁃4 cells increased (P<0.05), whereas the proliferation and apoptosis ability of U2932 cells changed insignificantly (P>0.05). The results of KEGG enrichment analysis and GO function annotation analysis showed that the anti⁃tumor effect of YY⁃20394 on SU⁃DHL⁃4 cells involved several signaling pathways, among which the activities of PI3K⁃AKT, AMPK and JAK⁃STAT signaling pathways were down⁃regulated, and might play a role in affecting cell biological functions such as alcohol synthesis, whereas U2932 cells were not enriched with significantly different signaling pathways. GSEA enrichment analysis showed that the activation level of PI3K⁃AKT signaling pathway in SU⁃DHL⁃4 cells was significantly lower than that of U2932 cells. Conclusions The PI3K inhibitor YY⁃20394 induces anti⁃tumor effects on the SU⁃DHL⁃4 cells of GCB subtype by affecting related signaling pathways such as PI3K⁃AKT, but does not significantly influence the U2932 cells of ABC subtype.
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    Effects of manganese ion on proliferation and apoptosis of  liver cancer cells
    HE Ziyun, WANG Haolun, FAN Qianqing, LIU Zhihui
    2024, 16 (1):  62-66.  doi: 10.3969/j.issn.1674-5671.2024.01.10
    Abstract ( 207 )   PDF   Save
    Objective To investigate the effects of manganese ion (Mn2+) on the proliferation and apoptosis of liver cancer cells. Methods Hepatoma Huh7 and HepG2.2.15 cells were treated with different concentrations (1, 4, 16, 64, 256  and 1 024 μmol/L, respectively) of Mn2+ solutions, and the corresponding cells without Mn2+ solution treatment were used as the control group. The cell proliferation was detected by CCK⁃8 assay and colony formation assay, and the apoptosis rate was detected by flow cytometry. Results The results of CCK⁃8 assay showed that compared with the control group, the cell proliferation activity of Huh7 cells was decreased under the treatment of all the conentrations of Mn2+ solution except the one of 1 μmol/L (all P<0.05); the proliferation activity of HepG2.2.15 cells was significantly decreased under the treatment of all the conentrations of  Mn2+ solutions except those of 1 μmol/L and 4 μmol/L (all P<0.0001), and with the increase of Mn2+ concentration, the inhibition of cell proliferation in both groups was more and more significant. The results of colony formation assay showed that the colonies number of Huh7 cells was decreased under the treatment of all the Mn2+ solution except those of 1 μmol/L and 4 μmol/L (all P<0.01); the colonies number of HepG2.2.15 cells was decreased under the treatment of all the Mn2+ solution except the one of 1 μmol/L (all P<0.0001), and with the increase of Mn2+ concentration, the colonies number of cell decreased significantly. The results of apoptosis experiment showed that the apoptosis rates of Huh7 cells and HepG2.2.15 cells treated with 64 μmol/L and 1 024 μmol/L Mn2+ solution (respectively) were significantly different (all P<0.01), and the apoptosis rates increased with the increase of Mn2+ concentration. Conclusion Mn2+ can inhibit the proliferation and colony formation of liver cancer cells and induce apoptosis.
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    Analysis of the epidemiological characteristics and disease burden of malignant tumors in Guangxi, 2019#br#
    ZHOU Zihan, LI Qiulin, YU Jiahua, RONG Minhua, CAO Ji, GE Lianying, TANG Weizhong, YU Hongping
    2024, 16 (1):  67.  doi: 10.3969/j.issn.1674-5671.2024.01.11
    Abstract ( 486 )   PDF   Save
    Objective To analyze the epidemiological characteristics and disease burden of malignant tumors in Guangxi in 2019, and to provide reference for prevention and treatment of malignant tumors. Methods According to the tumor data reported by 56 cancer registration areas in Guangxi in 2019, the incidence, age⁃standardized rate by Chinese standard population (ASRC rate) of incidence, mortality and ASRC rate of mortality were calculated to analyze the incidence and mortality of malignant tumors in Guangxi in 2019. The indicators such as disability adjusted life years (DALYs) and years of life lost (YLLs) were calculated to assess the disease burden of malignant tumors. Results A total of 71,430 new cases of malignant tumors were reported in 56 cancer registration areas in Guangxi in 2019, with a crude incidence rate of 219.87/105, ASRC rate of incidence was 172.17/105; 45,485 mortality of malignant tumors were reported, with a crude mortality rate of 140.01/105, ASRC rate of mortality was 105.25/105. Cancers resulted in 660,930.15 DALYs in Guangxi in 2019, YLLs accounted for 97.4% of DALYs, the DALYs rate was 2,034.40 /105. In 2019, the incidence, mortality and DALYs rate of malignant tumors in Guangxi showed the characteristics of men higher than women, and urban areas higher than rural areas. In addition, in the 5 geographical areas of Guangxi, the highest incidence, mortality and DALYs rate of malignant tumors were in the north, south and west areas of Guangxi, respectively. The cancer of the liver, lung, female breast, colorectum, cervix, stomach, nasopharynx, uterus, prostate and thyroid were the top 10 for malignant tumors incidence, accounting for 75.3% of total cancer cases. The cancer of liver, lung, colorectum, stomach, female breast, cervix, nasopharynx, esophagus, leukemia and brain were the 10 leading causes of cancer deaths, accounting for 82.1% of total cancer deaths. Conclusions In 2019, the disease burden of malignant tumors in Guangxi is still at a high level, with significant regional differences and gender differences. The liver cancer, lung cancer, colorectum cancer, female breast cancer, cervix cancer and nasopharynx cancer are still the major malignant tumor for prevention and treatment in Guangxi. In addition, the incidence of thyroid cancer rises to the 10th place, more attentions should be paid and preventive measures should be taken early.
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     Expression of UBQLN2 gene in colon cancer and its immunoregulatory role  
    SUN Guangyuan, WANG Xiaoyuan, XIANG Xiao, REN Yanli, YIN Jie, HU Zhijie, WU Xueliang, XUE Jun
    2024, 16 (1):  76-83.  doi: 10.3969/j.issn.1674-5671.2024.01.12
    Abstract ( 141 )   PDF   Save
     Objective To investigate the expression of UBQLN2 gene in colon cancer and its immunoregulatory function. Methods Colon cancer and their matched paracancer tissues surgically removed in the First Affiliated Hospital of Hebei North University from January 2021 to June 2023 were collected. The expression of UBQLN2 was detected by transcriptome sequencing, the expression level of UBQLN2 mRNA was detected by qRT⁃PCR, and the expression of UBQLN2 protein was detected by immunohistochemical. The relationship between the expression of UBQLN2 and the clinical pathological characteristics and prognosis of colon cancer patients was analyzed. Multicolor immunofluorescence was used to detect the co⁃expression of UBQLN2 and TGF⁃β. Single⁃cell transcriptome sequencing and TCGA database were used to verify the expression of UBQLN2 in colon cancer and its relationship with immunosuppressive factors, TGF⁃β and prognosis of colon cancer. Results Transcriptome analysis showed that UBQLN2 gene was significantly overexpressed in colon cancer tissues, and its mRNA expression level was higher than that in cancer⁃adjacent tissues (P<0.01). The relative expressions of UBQLN2 mRNA in 275 colon cancer tissues and 41 paracancer tissues which collected from TCGA database were also significantly higher in colon cancer tissues than that in cancer⁃adjacent tissues (P<0.001). Immunohistochemical results showed that UBQLN2 was mainly expressed in the cytoplasm, and the positive expression intensity of UBQLN2 protein in colon cancer tissues was obviously higher than that in  cancer⁃adjacent tissues. The results of qRT⁃PCR showed that UBQLN2 mRNA expression in colon cancer tissues was significantly higher than that in cancer⁃adjacent tissues (P<0.001). Pathway enrichment analysis showed that the tumor proliferation pathway was significantly up⁃regulated, and the immune activation pathway was significantly down⁃regulated in the UBQLN2 high expression group. Moreover, compared with UBQLN2 low expression group, UBQLN2 high expression group had higher immune escape score (P<0.05), lower expression of CD8+ T cell specific markers, smaller immune recruitment factors and immune killer factors (all P<0.05), and higher expression of immune depletion molecules (all P<0.05). The expressions of TGF⁃β, IL10, ARG1 and other immunosuppressive cytokines in UBQLN2 high expression group were higher than those in UBQLN2 low expression group (all P<0.05), and UBQLN2 was positively correlated with TGF⁃β expression (r=0.280, P<0.0001); UBQLN2 and TGF⁃β were co⁃expressed in tumors. Patients with both high expression of TGF⁃β and UBQLN2 had worse prognosis than those with both low expression (P=0.004). Single⁃cell transcriptome sequencing showed that colon cancer with high expression of UBQLN2 was highly expressed TGF⁃β and the microenvironment was immunosuppressed. Conclusions UBQLN2 is highly expressed in colon cancer and associated with poor prognosis. Colon cancer with high expression of UBQLN2 may inhibit the killing activity of CD8+T cells by releasing TGF⁃β cytokines and realizing immune escape. UBQLN2 may be a potential molecular target for the treatment of colon cancer.
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    Expression of HLA-DRA protein in hepatocellular carcinoma and its clinical significance
    CHEN Kun, YANG Hui, LIU Zijia, ZHANG Xiaolin, XU Zhuoyi, LIU Bing, ZHAO Yubao, DING Lu, DENG Yang
    2024, 16 (1):  84-89.  doi: 10.3969/j.issn.1674?5671.2024.01.13
    Abstract ( 89 )   PDF   Save
    Objective To investigate the expression of human leukocyte antigen⁃DRA (HLA⁃DRA) in hepatocellular carcinoma (HCC) and its relationship with clinicopathological characteristics and prognosis. Methods A total of 273 pairs of HCC tissues and corresponding paracancerous tissues were retrospectively analyzed. The  expression of HLA⁃DRA protein were detected by immunohistochemistry method, and the clinicopathological characteristics of patients with different HLA⁃DRA protein expression levels were compared. The overall survival (OS) and recurrence⁃free survival (RFS) of patients with different HLA⁃DRA expression levels were compared by Log⁃rank method. Cox proportional hazards regression was used to assess the factors affecting OS and RFS of HCC patients after hepatectomy. Results The high expression rate of HLA⁃DRA protein in HCC tissues was lower than that in paracancerous tissues (39.19% vs 72.89%, χ2 =62.927, P<0.001). The high HLA⁃DRA expression level was associated with AFP (alpha fetoprotein)>400 μg/L, cirrhosis, BCLC B/C stage, non⁃capsule/incomplete capsule, microvascular invasion (all P<0.05). The OS rate (χ2 =4.336, P=0.037) and RFS rate (χ2 =13.396, P<0.001) of HCC patients with high HLA⁃DRA expression were higher than those with low HLA⁃DRA expression. High expression of HLA⁃DRA protein was an independent protective factor for postoperative OS (HR=0.657, 95%CI: 0.492-0.898, P=0.021) and RFS (HR=0.668, 95%CI: 0.549-0.857, P=0.008) in HCC patients. Conclusions The high expression rate of HLA⁃DRA protein in HCC tissues is lower than that in paracancerous tissues, and its high expression is an independent protective factor for prognosis of HCC patients.
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    Efficacy and safety of hepatic arterial infusion therapy sequential capecitabine and PD⁃1 inhibitor in the treatment of unresectable hilar cholangiocarcinoma
    LIU Song, ZHANG Yonghui, WANG Qingdong, LI Long, YU Guangji
    2024, 16 (1):  90-95.  doi: 10.3969/j.issn.1674-5671.2024.01.14
    Abstract ( 167 )   PDF   Save
    Objective To investigate the efficacy and safety of hepatic arterial infusion therapy sequential capecitabine and PD⁃1 inhibitor in the treatment of unresectable hilar cholangiocarcinoma. Methods The clinical data of 34 patients of unresectable hilar cholangiocarcinoma admitted to Linyi Cancer Hospital from October 2019 to October 2021 were retrospectively analyzed. All patients received hepatic arterial infusion therapy sequential capecitabine and PD⁃1 inhibitor. The patient received 2-6 cycles of mFOLFOX7⁃hepatic arterial infusion chemotherapy (HAIC) and PD⁃1 inhibitor arterial infusion therapy, and then received capecitabine monotherapy and intravenous drip with PD⁃1 inhibitor. The objective response rate (ORR) and disease control rate (DCR) as well as adverse reactions of patients were observed, and the overall survival (OS) and its influencing factors were analyzed. Results A total of 155 interventional treatments were performed in 34 patients, with an average of (4.56±1.61) times. After 2 cycles of intervention treatment, the ORR and the DCR were 61.76% (21/34) and 97.06% (33/34), respectively. After the whole intervention treatment, the overall ORR was 82.35% (28/34), and the DCR was 100.00% (34/34). The median follow⁃up time was 17.5 months, and the median OS was 20.0 months (95%CI: 15.0-25.0 months). The adverse reactions related to HAIC mainly included fever, abdominal pain, nausea and vomiting, and hematological toxicity caused by chemotherapy drugs, all of which were grade 1-2. The adverse reactions related to PD⁃1 inhibitor treatment mainly included fatigue, rash, body surface capillary hyperplasia, all of which were≤grade 3. Multivariable Cox regression analysis showed that periductal infiltrating was a risk factor for OS (HR=2.051, 95%CI: 1.039-4.407, P=0.038) , and 5-6 cycles of intervention treatments  was a protective factor for OS (HR=0.465, 95%CI: 0.219-0.853, P=0.006). Conclusions Hepatic arterial infusion therapy sequential capecitabine and PD⁃1 inhibitor are effective in the treatment of unresectable hilar cholangiocarcinoma with controllable adverse reactions, in which the growth pattern classification and the number of intervention treatments may affect the survival rate of patients.

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    Application of 3D printing compensation film in postoperation radiotherapy of immediate breast reconstruction for breast cancer
    WANG Yong, ZHOU Yuling, ZHOU Qionghui, ZENG Biao, HU Ying
    2024, 16 (1):  96-100.  doi: 10.3969/j.issn.1674-5671.2024.01.15
    Abstract ( 151 )   PDF   Save
    Objective To analyze the efficacy of the 3D printing compensation film in the postoperation radiotherapy for breast cancer patients after immediate breast reconstruction. Methods A total of 11 patients who underwent immediate breast reconstruction after modified radical mastectomy in Hunan Cancer Hospital from November 2021 to May 2022 were selected. The same sequence was used to perform CT positioning scanning after covering the 3D printing compensation film and the commercial compensation film, and the air gap, target area and organs at risk were delineated. Two intensity modulated radiation therapy (IMRT) plans were designed with the same parameters (Plan A: 3D printing compensation film; Plan B: commercial compensation film). The differences between the two plans were analyzed with respect to air gap, homogeneity index (HI), new conformity index (nCI), the mean dose (Dmean), V5, V20, V30 of the lung on the affected side lung, the cardiac dose V30 and the healthy side breast Dmean. Results  The air gap volume of Plan A was smaller than that of Plan B [(8.029±2.542) cm3 vs (20.048±4.372) cm3, t=-5.300, P<0.001]. Compared with those of Plan B, the HI [(0.134±0.008) % vs (0.161±0.016) %, t=-2.246, P=0.049], the healthy breast Dmean [(159.909±17.925) cGy vs (173.364±19.248) cGy, t=-2.343, P=0.041] and the lung on the affected side lung V20 [(25.782±0.876) % vs (26.373±0.836) %,t=-2.334, P=0.042) of Plan A were decreased, and the nCI was increased [0.79% (IQR: 0.77%-0.83%) vs 0.78% (IQR: 0.75%-0.81%), Z=-2.316, P=0.021], but there was no significant difference in cardiac dose V30, and the affected side lung Dmean, V5 and V30 (all P>0.05). Conclusions In patients with immediate breast reconstruction after radiotherapy for breast cancer, the 3D printing compensation film has advantages over the commercial compensation film with respect to fitness to skin, dose distribution and uniformity in the target area, improving the epidermal dose while reducing the dose of exposure to organs at risk, and has certain potential value in clinical application.
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    Analysis of hepatitis B virus serum markers in 92,031 cancer patients
    HUANG Hao, LIANG Jingjing, TAO Yifeng, PAN Xiaolan, FANG Min
    2024, 16 (1):  101-106.  doi: 10.3969/j.issn.1674-5671.2024.01.16
    Abstract ( 145 )   PDF   Save
    Objective To investigate the status and characteristics of hepatitis B virus (HBV) infection in cancer patients. Methods The detection results of the HBV serum markers of 92,031 patients diagnosed with cancer in Guangxi Medical University Cancer Hospital from July 26, 2017 to September 18, 2023 were retrospectively analyzed. The patients were grouped into the liver cancer (LC) group and the non⁃liver cancer (non⁃LC) group, and the proportion of patients with uninfected (all negative or Anti⁃HBs positive), ordinary infected (except for Anti⁃HBs, any test positive) and occult hepatitis B virus infection (OBI; HBsAg negative, serum or liver tissue HBV DNA positive) were compared and analyzed statistically. Results The total HBV infection rate of 92,031 cancer patients was 73.75% (67,876/92,031), among which the total HBV infection rate of patients with liver cancer was 97.65% (8,922/9,137), and that of patients without liver cancer was 71.12% (58,954/82,894). The total HBV infection rate in the LC group was significantly higher than that in the non⁃LC group (all P<0.001). The positive rates of HBsAg, HBeAg, Anti⁃HBe and Anti⁃HBc in the LC group were significantly higher than those in the non⁃LC group (all P<0.001), whereas the positive rate of Anti⁃HBs in the LC group was lower than that in the non⁃LC group (P<0.001). There were 20 and 27 combination patterns of serum markers in the LC group and the non⁃LC group, respectively, among which the constituent ratios of 14 patterns were significantly different between the two groups (all P<0.001). There were 7 combination patterns of OBI serum in both groups, and the constituent ratios of 5 patterns were statistically different between the two groups (all P<0.05). Conclusions HBV infection status and serological combination patterns of cancer patients are complex, and distinguishing between liver cancer and non⁃liver cancer for HBV infection statistics is more conducive to the evaluation of HBV infection in cancer patients.

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    Construction of a prognostic model for predicting hepatocellular carcinoma by necroptosis⁃ related long non⁃coding RNAs biomarkers
    HUANG Qiongqing, LIANG Zhengui, HUANG Qiqi, OU Chao
    2024, 16 (1):  107-113.  doi: 10.3969/j.issn.1674-5671.2024.01.17
    Abstract ( 135 )   PDF   Save
    Objective To construct a prognostic prediction model for hepatocellular carcinoma based on necroptosis⁃related long non⁃coding RNAs (NRLs). Methods Transcript data and clinical information of hepatocellular carcinoma were downloaded from the TCGA database. The LASSO⁃Cox model was used to construct a prognostic prediction model, the predictive value of the model was evaluated by receiver operating characteristic (ROC) curve and calibration curve, and gene set enrichment analysis (GSEA) and immune infiltration analysis were performed. The differential expression of the four NRLs between hepatocellular carcinoma cells Huh7 and normal hepatocytes MIHA was confirmed by qRT⁃PCR. Results A prognostic prediction model was constructed for hepatocellular carcinoma based on four NRLs, including AL117336.2, MKLN1⁃AS, FOXD2⁃AS1, and LINC01224. The risk score constructed based on the training set was an independent factor on prognosis (HR=1.275, P<0.001). The AUCs of 1⁃, 3⁃ and 5⁃year OS predicted by the risk model were 0.816, 0.747 and 0.752, respectively, in the training set, and 0.713, 0.621 and 0.626, respectively, in the testing set. Patients were classified into high and low risk groups based on the median risk score, and the overall survival rate of the high risk group was lower than that of the low risk group in both the training set and the testing set (all P<0.05). In addition, there were significant differences in the degree of immune cell infiltration and the expression of immune checkpoint molecules between the two groups (all P<0.01). qRT⁃PCR results showed that the expression levels of the four NRLs were higher in hepatocellular carcinoma cells Huh7 than in normal hepatocytes MIHA (all P<0.05). Conclusions The NRLs model has been successfully constructed to predict the prognosis of patients with hepatocellular carcinoma, and the constructed model has potential value for guiding clinical treatment.
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    Lung cancer screening and early diagnosis: advances from imaging to biomarkers
    HE Shuang, TIAN Jin, Long Lin, ZHAO Lili, XIAO Jun
    2024, 16 (1):  120-126.  doi: 10.3969/j.issn.1674-5671.2024.01.19
    Abstract ( 336 )   PDF   Save
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