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08 January 2026, Volume 53 Issue 1 Previous Issue   

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Original Article

Research on the mechanism of targeting CD59 to inhibit proliferation， migration， and induce apoptosis in oral squamous cell carcinoma Yang Xinting, Ma Tengyu, Guan Shulong, Yang Mei, Jiang Zhou, Yang Xinru, Jiang Liangqian, Gao Meihua, Xu Yingjie, Cong Beibei 2026, 53 (1):  16-23.  doi: 10.3760/cma.j.cn371439-20250530-00002 Abstract ( 31 )   HTML ( 9 )   PDF (3111KB) ( 7 )   Save Objective To investigate the effects and mechanisms of targeting CD59 on the proliferation， migration， and apoptosis of oral squamous cell carcinoma （OSCC） cells. Methods Thirty patients with OSCC admitted to Qingdao Stomatological Hospital Affiliated to Qingdao University from September 2020 to September 2022 were selected as the research subjects. The expression of CD59 in their tumor tissues and paired adjacent normal tissues was detected by immunohistochemistry. CD59 expression was knocked down or overexpressed in HOK （normal oral keratinocytes） and SCC-9 （human tongue squamous cell carcinoma） cells via lentiviral transduction. Cells were divided into four groups： siCD59-C group （knockdown control）， siCD59 group （CD59 knockdown）， CD59 group （CD59 overexpression）， and CD59-C group （overexpression control）. Apoptosis was detected by flow cytometry； proliferation was evaluated via colony formation and CCK-8 assays； migration was examined by wound healing assay； and PI3K， Akt， and mTOR phosphorylation levels were detected by Western blotting. Results The immunohistochemical results showed that the expression of CD59 in OSCC tissues （334.06±72.50） was significantly higher than that in adjacent normal tissues （125.77±56.60； t=3.20， P=0.033）. The results of flow cytometry showed that the apoptosis rates of HOK cells in the siCD59-C group and the siCD59 group were 5.67%±0.83% and 6.92%±0.51%， respectively， with no statistically significant difference （t=2.23， P=0.089）. Compared with the siCD59-C group （17.79%±0.45%）， the apoptosis rate of SCC-9 cells in the siCD59 group （38.03%±0.64%） increased significantly （t=13.09， P<0.001）. The apoptosis rates of HOK cells in the CD59-C group and the CD59 group were 4.57%±0.31% and 5.25%±0.65%， respectively， with no statistically significant difference （t=1.66， P=0.172）. Compared with the CD59-C group （18.19%±0.45%）， the apoptosis rate of SCC-9 cells in the CD59 group （7.26%±0.28%） was significantly decreased （t=35.76， P<0.001）. The results of colony formation assay showed that the numbers of HOK cells clones formed in the siCD59-C group and the siCD59 group were 350.53±6.31 and 367.01±7.36， respectively， with no statistically significant difference （t=1.48， P=0.214）. Compared with the siCD59-C group （418.46±6.75）， the clone formation ability of SCC-9 cells in the siCD59 group （326.02±5.15） was significantly decreased （t=3.46， P=0.026）. The results of CCK-8 assay showed that the viability of HOK cells in the CD59-C group and the CD59 group were 2.72%±0.43% and 2.60%±0.66%， respectively， with no statistically significant difference （t=2.54， P=0.064）. Compared with the CD59-C group （1.21%±0.77%）， the proliferation ability of SCC-9 cells in the CD59 group （2.09%±0.45%） increased significantly （t=16.97， P<0.001）. The results of wound healing assay showed that 24 h after the scratch， the migration rates of HOK cells in the siCD59-C group and the siCD59 group were 15.01%±1.56% and 13.32%±2.08%， respectively， with no statistically significant difference （t=1.25， P=0.279）. Compared with the siCD59-C group （17.67%±1.53%）， the migration ability of SCC-9 cells in the siCD59 group （7.13%±1.22%） decreased significantly （t=9.17， P<0.001）. The results of Western blotting showed that there was no statistically significant difference in the phosphorylation levels of PI3K， Akt， and mTOR in HOK cells between the siCD59-C group and the siCD59 group （all P>0.05）. Compared with the siCD59-C group， the phosphorylation levels of PI3K， Akt， and mTOR in SCC-9 cells in the siCD59 group were significantly decreased （all P<0.001）. Conclusions CD59 expression is significantly upregulated in OSCC tissues. Knockdown of CD59 can promote apoptosis of OSCC cells， inhibit their proliferation and migration. The mechanism may be related to the inhibition of the activation of the PI3K/Akt/mTOR signaling pathway. Figures and Tables | References | Related Articles | Metrics

Predictive value of CONUT score combined with serum TLR-4 and NF-κB for radiation-induced lung injury in patients with thoracic malignancies undergoing radiotherapy Lei Shengfei, Qiu Jun, Wang Jianli 2026, 53 (1):  24-30.  doi: 10.3760/cma.j.cn371439-20250719-00003 Abstract ( 17 )   HTML ( 5 )   PDF (1155KB) ( 1 )   Save Objective To explore the predictive value of controlling nutritional status （CONUT） score combined with serum Toll-like receptor-4 （TLR-4） and nuclear factor-κB （NF-κB） for radiation-induced lung injury in patients with thoracic malignancies undergoing radiotherapy. Methods A total of 86 patients with thoracic malignancies （esophageal cancer， non-small cell lung cancer） undergoing radiotherapy for 6-7 weeks in People's Hospital of Hunan Province between June 2023 and June 2024 were selected as the research objects. Before radiotherapy， after 3 weeks of radiotherapy and at the end of radiotherapy， detection of serum TLR-4 and NF-κB， and evaluation of CONUT score were performed. At 1 month after radiotherapy， patients were divided into injury group and non-injury group according to presence or absence of radiation-induced lung injury， and differences in all indicators before and after radiotherapy were compared between the two groups. The correlation between CONUT score and serum TLR-4， NF-κB levels was evaluated by Pearson correlation analysis， and predictive value of each indicator for radiation-induced lung injury in different periods was evaluated by logistic regression and receiver operator characteristic （ROC） curve analysis. Results In the 86 patients at 1 month after radiotherapy， there were 21 cases with radiation-induced lung injury （injury group） and 65 cases without injury （non-injury group）. The proportions of smoking history （χ2=5.18， P=0.023）， combined chemotherapy （χ2=4.57， P=0.033） and radiotherapy dose ≥60 Gy （χ2=4.59， P=0.032） in injury group were higher than those in non-injury group. Before radiotherapy， there were no statistically significant differences in CONUT score [（2.65±0.83） points vs. （2.21±0.96） points] and levels of serum TLR-4 [（36.54±4.26） ng/L vs. （37.12±4.93） ng/L] and NF-κB [（14.19±2.69） ng/L vs. （14.26±1.36） ng/L] between injury group and non-injury group （t=1.88， P=0.063； t=0.48， P=0.630； t=0.16， P=0.875）. After 3 weeks of radiotherapy， CONUT score [（3.98±1.24） points vs. （3.25±1.02） points] and levels of serum TLR-4 [（49.26±5.17） ng/L vs. （42.86±5.12） ng/L] and NF-κB [（17.59±3.25） ng/L vs. （15.14±2.29） ng/L] were higher in injury group than non-injury group （t=2.70， P=0.008； t=4.97， P<0.001； t=3.83， P<0.001）. At the end of radiotherapy， CONUT score [（5.27±1.47） points vs. （3.51±1.09） points] and levels of serum TLR-4 [（53.57±6.95） ng/L vs. （44.16±4.19） ng/L] and NF-κB [（19.66±2.16） ng/L vs. （17.34±1.18） ng/L] were higher in injury group than non-injury group （t=5.89， P<0.001； t=7.52， P<0.001； t=6.28， P<0.001）， and all the three indicators of the two groups of patients at 3 weeks after radiotherapy and at the end of radiotherapy were all higher than those before radiotherapy （all P<0.05）. Pearson correlation analysis showed that CONUT score was positively correlated with the levels of serum TLR-4 and NF-κB at 3 weeks after radiotherapy and at the end of radiotherapy （r=0.53， P<0.001， r=0.44， P<0.001； r=0.57， P<0.001， r=0.47， P<0.001）. After correcting for confounding factors， logistic regression analysis showed that CONUT score at 3 weeks after radiotherapy （OR=5.73， 95%CI： 2.09-15.76， P=0.001） and at the end of radiotherapy （OR=6.40， 95%CI： 2.33-17.59， P<0.001）， along with the levels of serum TLR-4 （OR=6.51， 95%CI： 2.37-17.91， P<0.001； OR=7.07， 95%CI： 2.57-19.44， P<0.001） and NF-κB （OR=5.75， 95%CI： 2.09-15.81， P=0.001； OR=6.33， 95%CI： 2.30-17.42， P<0.001） were all independent factors for predicting radiation-induced lung injury in patients with thoracic malignancies undergoing radiotherapy. ROC curve analysis demonstrated that CONUT score at 3 weeks after radiotherapy （AUC=0.69） and at the end of radiotherapy （AUC=0.86）， along with serum levels of TLR-4 （AUC=0.77 and 0.89， respectively） and NF-κB （AUC=0.69 and 0.73， respectively）， both individually and in combination （AUC=0.90 and 0.97， respectively）， exhibited predictive value for radiation-induced lung injury in patients with thoracic malignancies undergoing radiotherapy. Furthermore， the AUC values of combined indicators at 3 weeks after radiotherapy and at the end of radiotherapy were higher than those of individual indicator alone. The AUC values of combined indicators at the end of radiotherapy exceeded those obtained at 3 weeks after radiotherapy （all P<0.05）. Conclusions The CONUT score at 3 weeks after radiotherapy and at the end of radiotherapy， as well as the levels of serum TLR-4 and NF-κB， all have predictive value for radiation-induced lung injury in patients with thoracic malignancies undergoing radiotherapy， and the predictive efficacy of combined detection with the above indicators at the end of radiotherapy is higher. Figures and Tables | References | Related Articles | Metrics

Efficacy and safety of tislelizumab combined with chemotherapy in the treatment of advanced esophageal cancer Yu Yunpeng, Dai Chunhua, Ling Rui 2026, 53 (1):  31-37.  doi: 10.3760/cma.j.cn371439-20250619-00004 Abstract ( 15 )   HTML ( 4 )   PDF (831KB) ( 4 )   Save Objective To retrospectively analyze the efficacy and safety of tislelizumab combined with chemotherapy in the treatment of advanced esophageal cancer. Methods A total of 128 patients with advanced esophageal cancer admitted to the Affiliated Hospital of Jiangsu University from March 2021 to June 2024 were selected as the study subjects. According to different treatment methods， they were divided into a conventional group （n=60， treated with paclitaxel liposome+nedaplatin） and a monoclonal antibody group （n=68， treated with paclitaxel liposome+nedaplatin+tislelizumab）. With 21 days as one cycle， a total of 4-6 cycles of chemotherapy were administered. The short-term efficacy， tumor markers and related factors， inflammatory factors， immune related indicators， quality of life-related score and safety of the two groups of patients were observed. Results After treatment， the objective response rate in the monoclonal antibody group （86.76%， 59/68） was higher than that in the conventional group （65.00%， 39/60）， with a statistically significant difference （χ2=8.42， P=0.004）. The levels of carcinoembryonic antigen （CEA）， cytokeratin 19 fragment antigen 21-1 （CYFRA21-1）， carbohydrate antigen （CA） 125， and squamous cell carcinoma antigen （SCC-Ag） in the monoclonal antibody group were （7.73±2.18） μg/L， （4.95±0.67） U/ml， （9.28±1.42） U/ml， and （0.50±0.16） μg/L， respectively， and those in the conventional group were （10.14±2.21） μg/L， （4.09±0.70） U/ml， （7.35±1.58） U/ml， and （0.68±0.22） μg/L， respectively， with statistically significant differences （t=6.20， P<0.001； t=7.10， P<0.001； t=7.28， P<0.001； t=5.34， P<0.001）. Moreover， the levels of CEA， CYFRA21-1， CA125， and SCC-Ag in both groups of patients after treatment were significantly lower than those before treatment （all P<0.05）. The levels of matrix metalloproteinase-9 （MMP-9） and vascular endothelial growth factor （VEGF） in the monoclonal antibody group were （118.28±10.47） ng/ml and （320.27±18.79） ng/L， respectively， and those in the conventional group were （126.75±14.51） ng/ml and （350.71±19.35） ng/L， respectively， with statistically significant differences （t=3.82， P<0.001； t=9.02， P<0.001）. The levels of MMP-9 and VEGF in both groups of patients after treatment were significantly lower than those before treatment （all P<0.05）. The levels of interleukin （IL）-6， C-reactive protein （CRP） and tumor necrosis factor-α （TNF-α） in the monoclonal antibody group were （5.46±1.26） ng/L， （7.89±1.45） mg/L， and （3.95±0.83） ng/L， respectively， and those in the conventional group were （8.66±2.13） ng/L， （9.51±1.64） mg/L， and （6.02±1.52） ng/L， respectively， with statistically significant differences （t=10.49， P<0.001； t=5.93， P<0.001； t=9.71， P<0.001）. The levels of IL-6， CRP， and TNF-α in both groups of patients after treatment were significantly lower than those before treatment （all P<0.05）. The T-cell subsets CD3+ and CD4+/CD8+ ratio in the monoclonal antibody group were （66.16±5.26）% and 1.52±0.25， respectively， and those in the conventional group were （58.41±5.17）% and 1.15±0.27， respectively， with statistically significant differences （t=8.39， P<0.001； t=8.05， P<0.001）. The T-cell subsets CD3+ and CD4+/CD8+ ratio in both groups of patients after treatment were significantly higher than those before treatment （all P<0.05）. Compared with before treatment， the Karnofsky performance status scores and the M. D. Anderson dysphagia inventory scores of both groups of patients were increased， and the scores in the monoclonal antibody group were significantly higher than those in the conventional group； the numerical rating scale scores of both groups were decreased， and the score in the monoclonal antibody group was significantly lower than that in the conventional group （all P<0.05）. The common adverse reactions in the two groups were leukopenia， nausea， fatigue， etc.， most of which were grade 1-2. The incidence of grade 3 adverse reactions was 10.00%（6/60） in the conventional group and 20.59%（14/68） in the monoclonal antibody group. No grade 4 adverse reactions occurred. There was no statistically significant difference in the total incidence of adverse reactions between the conventional group （78.33%， 47/60） and the monoclonal antibody group （75.00%， 51/68； χ2=0.20， P=0.657）. Conclusions Compared with chemotherapy alone， tislelizumab combined with chemotherapy in the treatment of advanced esophageal cancer can improve short-term efficacy with good safety. Figures and Tables | References | Related Articles | Metrics

Expression of ALDH6A1 in clear cell renal cell carcinoma and its impacts on proliferation， apoptosis， and invasion of renal cancer cells Zhang Xiaoxi, Cheng Chunlai 2026, 53 (1):  38-46.  doi: 10.3760/cma.j.cn371439-20250421-00005 Abstract ( 11 )   HTML ( 4 )   PDF (3667KB) ( 1 )   Save Objective To investigate the expression of aldehyde dehydrogenase 6 family member A1 （ALDH6A1） in clear cell renal cell carcinoma （ccRCC） and its effects on the proliferation， apoptosis， and invasion of renal cancer cells. Methods The Cancer Genome Atlas （TCGA） database was used to analyze the differences in ALDH6A1 mRNA expression levels between ccRCC patients and healthy individuals， as well as the correlation between ALDH6A1 mRNA expression and survival rate of patients. A total of 70 pairs of ccRCC tissues and adjacent tissues were collected from patients who received treatment at General Hospital of the Yangtze River Shipping between January 2021 and October 2024. Reverse transcription-quantitative PCR was performed to detect ALDH6A1 mRNA expression. Immunohistochemistry was used to analyze ALDH6A1 protein expression in ccRCC tissues. The expression of ALDH6A1 protein in different clinicopathological features of ccRCC was analyzed. The renal cancer cell line 786-O was cultured in vitro and divided into blank control group （control group）， ALDH6A1 overexpression group （OE-ALDH6A1 group） and negative control group （OE-NC group）. Cells proliferation was evaluated by CCK-8 assay and EdU assay. Flow cytometry was used to detect cells apoptosis and cells cycle distribution. Transwell chamber assay was used to analyze the migration and invasion abilities of the cells. Western blotting was used to analyze the protein expressions of ALDH6A1， cyclin-dependent kinase 4 （CDK4）， Ki-67， matrix metalloproteinase （MMP）-2， MMP-9， and transcription factor Twist in different cells. Results TCGA database analysis showed that the mRNA expression of ALDH6A1 in ccRCC tissues [15 168 （20 826）] was significantly lower than that in normal tissues [130 368 （296 513）， U=8 946.5， P<0.001]. Kaplan-Meier analysis showed that the 10-year survival rate of patients with high ALDH6A1 mRNA expression （72.13%， n=421） was significantly higher than that of patients with low ALDH6A1 mRNA expression （41.32%， n=112， χ²=8.33， P<0.001）. The relative mRNA expressions of ALDH6A1 in 70 cases of ccRCC tissues and adjacent tissues were 0.58±0.13 and 1.03±0.15， respectively， with a statistically significant difference （t=48.55， P<0.001）. The positive expression rates of ALDH6A1 protein were 32.86% （23/70） and 58.57% （41/70）， respectively， with a statistically significant difference （χ²=9.33， P=0.002）. There were statistically significant differences in the expression of ALDH6A1 in ccRCC tissues among patients with different pathological grades and TNM stages （χ²=4.51， P=0.034； χ²=6.99， P=0.008）. Compared with human normal renal tubular epithelial cells HK-2， the expressions of ALDH6A1 mRNA and protein in human renal cancer cells （786-O， 769-P， ACHN， A498） were all lower （all P<0.05）. Among them， the expression of ALDH6A1 mRNA and protein was the lowest in 786-O cells （all P<0.05）. The absorbance （A） values of 786-O cells in the control group， OE-NC group and OE-ALDH6A1 group were 0.65±0.06， 0.63±0.05 and 0.38±0.04， respectively. The EdU-positive rates were （48.34±5.21）%， （49.56±5.65）% and （27.34±3.28）%， respectively. The apoptosis rates were （2.15±0.43）%， （2.32±0.55）% and （33.46±4.36）%， respectively. The proportions of cells in the G0/G1 phase were （22.46±3.56）%， （23.16±3.72）% and （37.82±5.42）%， respectively. The proportions of cells in the S phase were （31.25±3.78）%， （32.89±3.61）% and （26.33±3.87）%， respectively. The proportions of cells in the G2/M phase were （46.29±5.15）%， （43.95±5.63）% and （35.85±4.21）%， respectively. The numbers of migration cells were 158.46±16.32， 155.62±15.48 and 84.23±9.65， respectively. The numbers of invasion cells were 142.35±15.21， 139.44±13.56 and 72.34±8.61， respectively， all with statistically significant differences （F=52.91， P<0.001； F=40.22， P<0.001； F=300.05， P<0.001； F=24.23， P<0.001； F=4.96， P=0.022； F=7.11， P=0.007； F=53.15， P<0.001； F=52.16， P<0.001）. Compared with the control group and OE-NC group， the A value of cells， the EdU-positive rate， the proportion of cells in the S phase and G2/M phase， and the number of migration and invasion cells in the OE-ALDH6A1 group were significantly decreased （all P<0.05）， while the apoptosis rate and the proportion of cells in G0/G1 phase were significantly increased （all P<0.05）. There were statistically significant differences in the relative expressions of CDK4， Ki-67， MMP-2， MMP-9， and Twist proteins among the control group， the OE-NC group and the OE-ALDH6A1 group （all P<0.001）. Compared with the control group and OE-NC group， the protein expressions of CDK4， Ki-67， MMP-2， MMP-9 and Twist in the OE-ALDH6A1 group were significantly decreased （all P<0.05）. Conclusions ALDH6A1 expression is down-regulated in ccRCC tissues and cells. Patients with high ALDH6A1 mRNA expression have a better prognosis. Overexpression of ALDH6A1 can inhibit the proliferation， migration， and invasion of renal cancer cells， and promote cell apoptosis by regulating the cell cycle and downregulating the expression of proteins related to the epithelial-mesenchymal transition process. Figures and Tables | References | Related Articles | Metrics

Review

Current status and challenges of neoadjuvant immunotherapy in malignant tumors Zhao Yuan, Yao Wentao 2026, 53 (1):  47-52.  doi: 10.3760/cma.j.cn371439-20250513-00006 Abstract ( 16 )   HTML ( 3 )   PDF (814KB) ( 7 )   Save Malignant tumors have become a significant challenge in global public health， posing substantial threats to both human health and societal development. Although current clinical treatment strategies continue to advance， the overall therapeutic effect still has significant limitations. Supported by innovative applications of immune checkpoint inhibitors and substantial evidence from both clinical trials and real-world studies， neoadjuvant immunotherapy is leading resectable tumor management into a new era of immunotherapy. However， ongoing research continues to identify crucial issues that require urgent solutions. Systematic analysis of the molecular mechanisms， clinical trial progress， and real-world applications of neoadjuvant immunotherapy is expected to reveal current therapeutic constraints and future development directions. Figures and Tables | References | Related Articles | Metrics

Research progress of HER2 ultra-low expression breast cancer Liu Xinlei, Li Yaru, Chen Shuning, Tang Shenghao, Qin Yan, Liu Yankui, Qi Xiaowei 2026, 53 (1):  53-56.  doi: 10.3760/cma.j.cn371439-20250225-00007 Abstract ( 14 )   HTML ( 4 )   PDF (808KB) ( 8 )   Save Current clinical research and practice have indicated that patients with low human epidermal growth factor receptor 2 （HER2） expression breast cancer can experience therapeutic advantages from treatments with novel antibody-drug conjugates （ADCs）. HER2 ultra-low expression in breast cancer is characterized by an immunohistochemical score of 0， with ≤10% of invasive tumor cells showing incomplete or faint membrane staining. This subgroup constitutes approximately 10%-15% of all breast cancer cases. In comparison to HER2-low expression， tumors with HER2 ultra-low expression display certain differences in clinicopathological characteristics， treatment responses， and prognostic outcomes. Paying attention to HER2 ultra-low expression status and taking corresponding measures can enable these patients to achieve better clinical efficacy. References | Related Articles | Metrics

Research progress on resistance mechanisms of anti-PD-1/PD-L1 therapy in advanced non-small cell lung cancer Li Ting, Zhou Qi, Zhang Qian, Chen Jie 2026, 53 (1):  57-61.  doi: 10.3760/cma.j.cn371439-20250319-00008 Abstract ( 15 )   HTML ( 2 )   PDF (831KB) ( 4 )   Save Although immune checkpoint inhibitor therapy based on anti-programmed death-1 （PD-1） and programmed death-ligand 1 （PD-L1） can significantly improve the survival prognosis of patients with advanced non-small cell lung cancer， primary and secondary drug resistance result in limited benefits for some individuals. The resistance mechanism of anti-PD-1/PD-L1 therapy is particularly complex and is influenced by multiple factors. A systematic review of the latest research results on the resistance mechanism to PD-1/PD-L1 immune checkpoint inhibitors can provide scientific basis for optimizing the treatment strategy of non-small cell lung cancer patients. References | Related Articles | Metrics

Research progress of the immunoscore system in gastric cancer Wang Yu, Li Yuanfei, Guo Yuntong 2026, 53 (1):  62-64.  doi: 10.3760/cma.j.cn371439-20250509-00009 Abstract ( 12 )   HTML ( 4 )   PDF (769KB) ( 6 )   Save The immunoscore system serves as a key indicator for evaluating the immune status and prognosis of cancer patients. Its prognostic evaluation and efficacy prediction function have been validated in various solid tumors. The immunoscore in gastric cancer is modulated by various factors, including the tumor microenvironment and the patient's intrinsic immune status. A comprehensive summary of its applications in prognosis prediction, selection of adjuvant therapeutic regimens, and treatment response assessment may offer novel perspectives and strategic guidance for the individualized management of gastric cancer. References | Related Articles | Metrics