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08 October 2023, Volume 50 Issue 10 Previous Issue    Next Issue

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Guidelines · Consensus

Chinese expert consensus on issues related to radiotherapy management of cancer patients under the back ground of COVID-19 （2023 Edition） Radiation Oncology Treatment Physician Branch, Chinese Medical Doctor Association； Radiation Oncology Therapy Branch, Chinese Medical Association； Chinese Association of Radiation Therapy, China Anti-Cancer Association 2023, 50 (10):  577-584.  doi: 10.3760/cma.j.cn371439-20230706-00111 Abstract ( 88 )   HTML ( 29 )   PDF (837KB) ( 135 )   Save The ongoing COVID-19 pandemic has posed unprecedented challenges to global healthcare systems and has had a specific impact on the standard treatment of cancer patients worldwide， including radiotherapy. Resource constraints can lead to a decline in treatment capacity， and to reduce the risk of cancer patients being exposed to the novel coronavirus， the number of radiotherapy visits must be limited. Based on existing clinical evidence， radiation oncologists need to make radiotherapy decisions that reduce the risk of infection without compromising efficacy. The COVID-19 pandemic is nearing its end， but more infectious variants or other viruses may emerge and spread. Therefore， the Radiation Oncology Treatment Physician Branch of the Chinese Medical Doctor Association， the Radiation Oncology Therapy Branch of the Chinese Medical Association， and the Chinese Association of Radiation Therapy of the China Anti-Cancer Association refer to a number of relevant guidelines and the latest updates on patients with malignant tumors during the COVID-19 epidemic at home and abroad. According to China's national conditions， medical system and COVID-19 epidemic characteristics， the "Chinese expert consensus on issues related to radiotherapy management of cancer patients under the background of COVID-19 （2023 Edition）" is formulated. Figures and Tables | References | Related Articles | Metrics

Original Articles

Pemetrexed clinical trial for intrathecal injection chemotherapy based on cerebrospinal fluid pharmacokinetics in patients with leptomeningeal metastasis from lung adenocarcinoma Xie Yu, Zheng Shengnan, Huang Mingmin, Guo Aibin, Yin Zhenyu, Lin Yongjuan 2023, 50 (10):  585-591.  doi: 10.3760/cma.j.cn371439-20230612-00112 Abstract ( 119 )   HTML ( 30 )   PDF (770KB) ( 69 )   Save Objective To investigate the pharmacokinetics of cerebrospinal fluid pemetrexed following intrathecal injection chemotherapy in patients with leptomeningeal metastasis （LM） from lung adenocarcinoma and provide a basis for clinical intrathecal injection chemotherapy. Methods A total of 21 patients with lung adenocarcinoma LM who underwent pemetrexed intrathecal injection chemotherapy via Ommaya capsule at Nanjing Drum Tower Hospital， Aiffilitated Hospital of Nanjing University Medical School from November 2019 to November 2022 were collected， and divided into 30， 40 and 50 mg groups （n=10， n=4， n=7）according to pemetrexed dose. Cerebrospinal fluid was collected at 0， 0.5， 1， 2， 4， 6， 12， 24 and 48 h after the first intrathecal injection chemotherapy， and day 8 of each cycle for three groups. Reversed phase high performance liquid chromatography was used to determine the drug concentration in cerebrospinal fluid， to clarify the drug-related pharmacokinetic parameters， and to compare the differences in pemetrexed concentration among groups. Finally， cerebrospinal fluid pemetrexed concentration changes were observed and compared after different intrathecal injection chemotherapy cycles. Results There were statistically significant differences in cerebrospinal fluid drug concentrations of patients in three groups at 0， 0.5， 1， 2， 4， 6， 12， 24 and 48 h after the first intrathecal injection chemotherapy （30 mg group： F=20.56， P<0.001； 40 mg group： F=27.06， P<0.001； 50 mg group： F=28.63， P<0.001）， and there were statistically significant differences in the concentration of cerebrospinal fluid drugs in each dose group at 0.5， 1， 2， 4， 6 and 12 h compared to 0 h after intrathecal injection chemotherapy （all P<0.05）. Compared to the 30 mg group， cerebrospinal fluid drug concentrations in the 50 mg group increased at 1， 2， 4， 6， 12 and 24 h after intrathecal injection chemotherapy， with statistically significant differences （all P<0.05）. Pharmacokinetic analysis of cerebrospinal fluid pemetrexed showed that area under the concentration-time curve （AUC）0-∞ of the 30， 40 and 50 mg groups were （5 696.12±283.32）， （7 886.29±396.57）， and （14 202.70±440.19） h·mg/L， respectively， with a statistically significant difference （F=1 159.00， P<0.001）； AUC0-∞ increased in the 50 mg group compared to the 30 and 40 mg groups （both P<0.05）； AUC0-∞ increased in the 40 mg group compared to the 30 mg group （P<0.05）. The half-lives of three groups were （8.75±0.23）， （11.29±0.59） and （16.42±1.23） h， respectively， with a statistically significant difference （F=206.80， P<0.001）； half-life was longer in the 50 mg group compared to the 30 and 40 mg groups （both P<0.05）； half-life was longer in the 40 mg group compared to the 30 mg group （P<0.05）. The peak time of three groups were （1.55±0.10）， （1.00±0.01）， （1.43±0.11） h， respectively， with a statistically significant difference （F=48.11， P<0.001）； the peak time was shorter in the 40 and 50 mg groups compared to the 30 mg group （both P<0.05）. Clearance of three groups were （7.02±2.46）， （5.80±1.25） and （3.66±1.32） L/h， respectively， with a statistically significant difference （F=6.02， P=0.009）； clearance was decreased in the 50 mg group compared to the 30 mg group （P<0.05）. The peak concentration of three groups were （540.45±32.25）， （820.75±46.47） and （1 014.78±64.96） mg/L， respectively， with a statistically significant difference （F=207.70， P<0.001）； peak concentration increased in the 50 mg group compared to the 30 and 40 mg groups （both P<0.05）； peak concentration increased in the 40 mg group compared to the 30 mg group （P<0.05）. Cerebrospinal fluid drug concentrations were dynamically monitored after 4 cycles of intrathecal injection chemotherapy， in which cerebrospinal fluid pemetrexed concentrations in 30 mg group were （13.76±4.79）， （11.41±7.08）， （9.41±2.59） and （7.86±4.02） mg/L， respectively； 40 mg group were （14.45±6.59）， （12.87±15.73）， （11.24±2.48） and （9.09±3.38） mg/L， respectively； 50 mg group were （12.94±10.34）， （9.72±7.62）， （8.15±8.17） and （4.34±4.21） mg/L， respectively. There was a statistically significant difference in cerebrospinal fluid drug concentrations among different intrathecal injection chemotherapy cycles in 30 mg group （F=4.04， P=0.016）， and the cerebrospinal fluid drug concentration decreased in cycles 3 and 4 compared to cycle 1 （both P<0.05）. There were no statistically significant differences in cerebrospinal fluid drug concentrations among different treatment cycles in 40 and 50 mg groups （F=0.28， P=0.837； F=3.57， P=0.066）. Conclusion Reversed phase high performance liquid chromatography method can effectively detect the pemetrexed concentration in cerebrospinal fluid； dynamic monitoring of cerebrospinal fluid pemetrexed concentration can provide a basis for the dosage and the treatment cycle of intrathecal injection chemotherapy in LM patients with lung adenocarcinoma. Figures and Tables | References | Related Articles | Metrics

Identification of critical radioresistance genes in esophageal squamous cell carcinoma by whole exome sequencing Chen Zhiming, Chen Junjie, Li Li, Ding Qian, Han Yunan, Zhao Hongyu 2023, 50 (10):  592-599.  doi: 10.3760/cma.j.cn371439-20220916-00113 Abstract ( 97 )   HTML ( 21 )   PDF (1870KB) ( 45 )   Save Objective To compare the genetic spectrums of esophageal squamous cell carcinoma （ESCC） patients with different prognosis after postoperative radiotherapy and to screen the genetic variants associated with radiotherapy resistance. Methods A total of 32 ESCC patients who received radical surgery and postoperative adjuvant radiotherapy in Affiliated Hospital of Nantong University from January 2015 to December 2019 were selected as the study objects. According to whether there was any recurrence in the radiation field within 1 year， they were divided into a recurrence group （radiotherapy resistance group， n=16） and a stable group （radiotherapy sensitive group， n=16）. Genomic DNA was extracted from patients and high-throughput sequencing was performed using whole exome sequencing （WES） technology. Biological information analysis software Trimmomatic， BWA and Picard were used to process the data and the alignment files were obtained by GATK comparison， then Vardict software was used to screen out various genetic variants from the sequencing data. The disease free survival （DFS） and overall survival （OS） were estimated by Kaplan-Meier method. Cox proportional hazard regression model was used to analyze the independent risk factors of DFS and OS of ESCC patients. Results After quality control of the sample data， 26 patients were finally included in this study for follow-up analysis， 13 in each of the recurrence and stable groups. The median tumor mutation burden of non-silent tumors in the whole group was 0.95 mutations/Mb. The substitution types of mutant bases were mainly C>T conversion， followed by C>G transmutation. The genetic variants with the highest frequency were single nucleotide polymorphism （SNP） （75.1%）， deletion mutation （13.7%） and insertion mutation （10.5%）. The number of tumor-specific mutations in the recurrence group was slightly higher than that in the stable group （median mutation number was 36 and 34， respectively）， and the top ten gene profiles of mutation frequency were significantly different between the two groups. In the recurrence group， 392 unique mutated genes were detected， and the top five were MUC19， NPIPA5， EPPK1， FLG and FOXG1. In the stable group， 192 unique mutation genes were detected， and the top five were TCHH， WNK1， AIM1L， COL6A5 and DPCR1. The median DFS and OS were 15.0 months （95%CI： 10.1 months-not reached） and 26.2 months （95%CI： 19.8 months-not reached） in the recurrence group respectively， and no recurrence or metastasis occurred in the stable group. Univariate analysis showed that GRIK2 （χ2=6.81， P=0.009）， MUC4 （χ2=4.25， P=0.039）， MUC5B （χ2=4.03， P=0.045）， PRRG1 （χ2=5.15， P=0.023） gene mutations， 3p deletion （χ2=4.16， P=0.041） and 14q deletion （χ2=7.09， P=0.008） were correlated with DFS. FLG （χ2=6.41， P=0.011）， NPIPA5 （χ2=4.57， P=0.033）， PKD1L2 （χ2=6.41， P=0.011）， FOXG1 （χ2=4.57， P=0.033） gene mutations， 3p deletion （χ2=3.88， P=0.049）， 14q deletion （χ2=5.66， P=0.017） and 18p deletion （χ2=3.85， P=0.050） were associated with OS. Multivariate analysis showed that 14q deletion （HR=3.65， 95%CI： 1.18-11.32， P=0.025） was an independent risk factor for DFS of ESCC patients with postoperative adjuvant radiotherapy， and FLG （HR=8.94， 95%CI： 1.52-52.74， P=0.016）， NPIPA5 （HR=6.36， 95%CI： 1.23-33.03， P=0.028） gene mutation and 14q deletion （HR=3.82， 95%CI： 1.18-12.31， P=0.025） were independent risk factors for OS of ESCC patients with postoperative adjuvant radiotherapy. Conclusion The WES results suggest that the types and rates of gene mutations of the ESCC patients with postoperative adjuvant radiotherapy in the recurrence and stable groups are basically the same， but the mutation spectrum of the two groups is significantly different. FLG， NPIPA5 gene mutations and 14q deletion can be used as molecular markers to predict the prognosis of ESCC patients treated with postoperative adjuvant radiotherapy. Figures and Tables | References | Related Articles | Metrics

Predictive value of baseline peripheral blood inflammatory biomarkers for prognosis in patients with advanced hepatocellular carcinoma treated with immunotherapy combined with targeted therapy Jiang Shan, Xu Yangtao, Liu Xin, Chen Wenliang, Xu Ximing 2023, 50 (10):  600-607.  doi: 10.3760/cma.j.cn371439-20230704-00114 Abstract ( 94 )   HTML ( 34 )   PDF (1599KB) ( 63 )   Save Objective To investigate the prognostic value of baseline peripheral blood inflammatory biomarkers for prognosis in patients with advanced hepatocellular carcinoma （HCC） receiving immunotherapy combined with targeted therapy. Methods The clinical data of a total of 120 patients with advanced HCC who received immunotherapy combined with targeted therapy at Cancer Center of Renmin Hospital of Wuhan University from December 2019 to March 2022 were analyzed retrospectively. Receiver operating characteristic （ROC） curve was used to calculate the optimal cut-off values of neutrophil-to-lymphocyte ratio （NLR）， platelet-to-lymphocyte ratio （PLR）， lymphocyte-to-monocyte ratio （LMR）， systemic immune inflammation index （SII） and prognostic nutritional index （PNI）. According to the optimal cut-off values， the study objects were divided into high value group and low value group. The Kaplan-Meier method was used for survival analysis. Cox proportional hazard regression model was applied to analyze the factors associated with prognosis. Results By the end of follow-up， 74 patients died and 46 survived. The median follow-up time was 23.0 months， the median overall survival （mOS） was 15.6 months， and the median progression-free survival （mPFS） was 13.1 months. ROC curve analysis showed that the optimal cut-off values of NLR， PLR， SII， LMR and PNI were 3.45， 131.87， 626.21， 2.12 and 43.30， respectively. The mPFS （18.3 months vs. 8.7 months） and mOS （26.6 months vs. 10.9 months） of patients in the low-NLR group （n=75） were longer than those of the high-NLR group （n=45）， and there were statistically significant differences （χ2=55.64， P<0.001； χ2=64.14， P<0.001）. The mPFS （17.9 months vs. 10.9 months） and mOS （24.5 months vs. 13.5 months） of patients in the low-PLR group （n=55） were longer than those of the high-PLR group （n=65）， and there were statistically significant differences （χ2=5.27， P=0.023； χ2=11.84， P<0.001）. The mPFS （18.0 months vs. 10.7 months） and mOS （25.7 months vs. 12.8 months） of patients in the low-SII group （n=75） were longer than those of the high-SII group （n=45）， and there were statistically significant differences （χ2=24.46， P<0.001； χ2=25.42， P<0.001）. The mPFS （18.2 months vs. 10.9 months） and mOS （26.6 months vs. 13.2 months） of patients in the high-LMR group （n=56） were longer than those of the low-LMR group （n=64）， and there were statistically significant differences （χ2=19.25， P<0.001； χ2=19.92， P<0.001）. The mPFS （17.9 months vs. 10.9 months） and mOS （25.4 months vs. 13.4 months） of patients in the high-PNI group （n=62） were longer than those of the low-PNI group （n=58）， and there were statistically significant differences （χ2=13.69， P<0.001； χ2=19.07， P<0.001）. Univariate analysis showed that Barcelona clinic liver cancer （BCLC） stage （HR=1.83， 95%CI： 1.17-2.87， P=0.008）， Child-Pugh grade （HR=2.21， 95%CI： 1.47-3.34， P<0.001）， modified albumin-bilirubin （mALBI） grade （HR=1.35， 95%CI： 1.01-1.81， P=0.045）， extrahepatic metastases （HR=2.18， 95%CI： 1.47-3.25， P<0.001）， NLR （HR=1.40， 95%CI： 1.28-1.54， P<0.001）， PLR （HR=1.00， 95%CI： 1.00-1.01， P=0.001）， SII （HR=1.00， 95%CI： 1.00-1.00， P<0.001）， LMR （HR=0.64， 95%CI： 0.51-0.79， P<0.001） and PNI （HR=0.95， 95%CI： 0.93-0.98， P=0.001） were correlated with PFS； BCLC stage （HR=2.18， 95%CI： 1.21-3.91， P=0.009）， Child-Pugh grade （HR=2.57， 95%CI： 1.61-4.09， P<0.001）， Eastern Cooperative Oncology Group performance status score （HR=1.59， 95%CI： 1.01-2.51， P=0.044）， mALBI grade （HR=1.60， 95%CI： 1.17-2.17， P=0.003）， extrahepatic metastasis （HR=2.51， 95%CI： 1.59-3.96， P<0.001）， NLR （HR=1.45， 95%CI： 1.32-1.60， P<0.001）， PLR （HR=1.01， 95%CI： 1.01-1.01， P<0.001）， SII （HR=1.01， 95%CI： 1.01-1.01， P<0.001）， LMR （HR=0.57， 95%CI： 0.40-0.72， P<0.001） and PNI （HR=0.92， 95%CI： 0.89-0.96， P<0.001） were correlated with OS. Multivariate analysis showed that extrahepatic metastasis （HR=1.78， 95%CI： 1.10-2.87， P=0.018） and NLR （HR=1.46， 95%CI： 1.24-1.73， P<0.001） were independent influencing factors for PFS； extrahepatic metastasis （HR=2.09， 95%CI： 1.21-3.61， P=0.009）， NLR （HR=1.56， 95%CI： 1.29-1.88， P<0.001）， SII （HR=1.00， 95%CI： 1.00-1.00， P=0.025）， LMR （HR=0.59， 95%CI： 0.45-0.78， P=0.008） and PNI （HR=0.93， 95%CI： 0.88-0.99， P=0.013） were independent influencing factors for OS. Conclusion NLR and extrahepatic metastasis can be regarded as important indicators to predict PFS in patients with advanced HCC receiving immunotherapy combined with targeted therapy， and NLR， SII， LMR， PNI and extrahepatic metastasis can be regarded as important indicators to predict OS in patients with advanced HCC receiving immunotherapy combined with targeted therapy. High NLR， high SII， low LMR， low PNI and extrahepatic metastasis indicate poor prognosis of HCC patients. 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Effect of regional lymph node diameter on postoperative recurrence in pancreatic cancer patients Kui Guoju, Huang Jiangbin, Zhang Wenhua, Yang Limin 2023, 50 (10):  608-613.  doi: 10.3760/cma.j.cn371439-20230328-00115 Abstract ( 55 )   HTML ( 12 )   PDF (872KB) ( 32 )   Save Objective To investigate the effect of the average diameter of regional lymph node on tumor recurrence after operation of pancreatic head adenocarcinoma without lymph node metastasis. Methods Clinical data of 49 patients with pancreatic head adenocarcinoma admitted to the 909th Hospital of Joint Logistic Support Force from January 2017 to June 2019 were retrospectively analyzed. The receiver operating characteristic （ROC） curve was used to analyze the average regional lymph node diameter for predicting the optimal threshold of tumor recurrence. The relationship between the average diameter of regional lymph nodes， recurrence and clinicopathological features were analyzed. The influencing factors of tumor recurrence 3 years after surgery were analyzed by logistic regression. Results All 49 patients with pancreatic head adenocarcinoma were divided into a relapse group （n=29） and a no-recurrence group （n=20） based on whether the tumor recurred or not， and the recurrence rate was 59.18%. ROC curve analysis showed that the best threshold of average regional lymph node diameter for predicting tumor recurrence was 0.635 cm， the area under the curve was 0.82， the sensitivity was 0.69， and the specificity was 0.85. The average diameter of regional lymph nodes increased in patients with tumor diameter ≥2 cm （t=-2.12， P=0.040）， tumor with moderate and poorly differentiation （t=-2.24， P=0.013）， vascular invasion （t=-3.47， P=0.001）， nerve invasion （t=-3.75， P<0.001）， capsular invasion （t=-4.25， P<0.001）， and tumor recurrence （t=-4.42， P<0.001）. Univariate analysis showed that tumor diameter （χ2=5.98， P=0.015）， tumor stage （χ2=3.88， P=0.049）， tumor differentiation （χ2=5.98， P=0.015）， vascular invasion（χ2=3.84，P=0.050）， capsular invasion （χ2=5.79， P=0.016）， average lymph node diameter （χ2=15.61， P<0.001）， and postoperative chemotherapy （χ2=3.89， P=0.049） were all related to whether the tumor recurred or not in patients with pancreatic head adenocarcinoma 3 years after surgery. Multivariate analysis results showed that tumor diameter ≥2 cm （OR=2.72， 95%CI： 1.46-11.28， P=0.016）， tumor with moderate and poorly differentiation （OR=2.22， 95%CI： 1.23-6.53， P=0.020）， capsular invasion （OR=2.30， 95%CI： 2.19-8.91， P=0.017）， and average lymph node diameter ≥0.635 cm （OR=7.93， 95%CI： 1.25-50.31， P=0.002） were all independent influencing factors for tumor recurrence in pancreatic head adenocarcinoma patients 3 years after surgery. Conclusion In patients with pancreatic head adenocarcinoma without lymph node metastasis， tumor diameter ≥2 cm， tumor with moderate and poorly differentiation， capsular invasion and average lymph node diameter ≥0.635 cm are independent risk factors for postoperative tumor recurrence. Patients with the average diameter of regional lymph nodes ≥0.635 cm increase the possibility of tumor recurrence after surgery， which can be used as the basis for postoperative evaluation and has certain clinical application value. Figures and Tables | References | Related Articles | Metrics

Differential diagnosis value of D-dimer before operation in renal oncocytoma and chromophobe renal cell carcinoma Qian Weiwei, Xu Shen, Kong Qi 2023, 50 (10):  614-617.  doi: 10.3760/cma.j.cn371439-20230612-00116 Abstract ( 61 )   HTML ( 15 )   PDF (871KB) ( 32 )   Save Objective To explore the differential diagnosis value of preoperative D-dimer in renal oncocytoma （RO） and chromophobe renal cell carcinoma （Ch-RCC）. Methods From January 2015 to April 2022 in the Second Hospital of Anhui Medical University， clinical data of 47 cases of rare renal tumors were collected. According to postoperative pathology， patients were divided into RO group （15 cases） and Ch-RCC group （32 cases）. General clinical data and preoperative blood indicators were analyzed. Receiver operator characteristic （ROC） curve and area under the curve （AUC） were performed to evaluate the differential diagnosis value of D-dimer between RO and Ch-RCC. Results There were no significant differences between two groups in gender （χ2=0.41， P=0.522）， age （t=0.50， P=0.618）， hypertension （χ2<0.01， P=0.994）， diabetes （P=0.541）， smoking history （χ2=1.67， P=0.196）， tumor laterality （χ2=0.67， P=0.414）. Besides， preoperative D-dimer was significantly higher in the Ch-RCC group [0.47 （0.29，0.77） μg/ml] in comparison with RO group [0.21 （0.19，0.27） μg/ml]， with a statistically significant difference （Z=4.44， P<0.001）. In addition， there were no significant differences in hemoglobin （t=-1.61， P=0.116）， platelet （t=0.26， P=0.800）， leucocyte （t=0.10， P=0.921）， neutrophil （t=-0.87， P=0.390）， lymphocyte （Z=0.82， P=0.418）， monocyte （Z=1.43， P=0.153）， neutrophil-lymphocyte ratio （Z=0.09， P=0.927）， platelet-lymphocyte ratio （t=0.42， P=0.676）， and lymphocyte-monocyte ratio （Z=-0.96， P=0.338） between Ch-RCC group and RO group. ROC curve analysis showed that when the cut-off value of preoperative D-dimer was 0.78 μg/ml， the AUC for differential diagnosis of RO and Ch-RCC was 0.90 （95%CI： 0.82-0.99， P<0.001）， with a sensitivity of 0.78 and a specificity of 1.00. Conclusion Preoperative level of D-dimer is significantly increased in Ch-RCC patients， which exhibits favourable preoperative differential diagnosis value between Ch-RCC and RO. Figures and Tables | References | Related Articles | Metrics

Reviews

Research progress of NADPH oxidase 2 in malignant tumors Liu Xiaojie, Huang Junxing 2023, 50 (10):  618-621.  doi: 10.3760/cma.j.cn371439-20230428-00117 Abstract ( 130 )   HTML ( 25 )   PDF (721KB) ( 92 )   Save Reduced nicotinamide adenine dinucleotide phosphate （NADPH） oxidase 2 （Nox2） acts as a source of reactive oxygen species， which participates in and influences normal physiological function of human body. Nowadays， many studies have found that Nox2 is related to prognosis of patients， drug resistance and molecular targeted therapy in various malignant tumors， such as acute myeloid leukemia， gastric cancer， colorectal cancer， ovarian cancer， lung cancer and esophageal cancer. What's more， it may be a novel biomarker and a potential therapeutic target for malignant tumors. References | Related Articles | Metrics

Research progress of memantine hydrochloride in the treatment of radiation-induced cognitive dysfunction and its combined application with vitamins Wang Jin, Li Ruoyang, Zhao Xuewei, Li Hui, Zhou Zhiguo, Zhao Jingxia 2023, 50 (10):  622-626.  doi: 10.3760/cma.j.cn371439-20230418-00118 Abstract ( 91 )   HTML ( 14 )   PDF (763KB) ( 33 )   Save Radiation-induced cognitive dysfunction （RICD） has an insidious onset and there is a lack of effective prevention and treatment measures. The efficacy of memantine hydrochloride as a classical treatment drug is limited， and it is inevitable to seek multi-target combination drugs. In recent years， the protective effect of vitamin E and vitamin D on cognitive function has been widely recognized. Several basic studies have shown that vitamin E can play a role in the combination of medication by protecting neurons and reducing the adverse effects caused by memantine hydrochloride； Vitamin D and memantine hydrochloride have also become a hot topic of research due to their significant synergistic effects. The combination of memantine hydrochloride and vitamin therapy is expected to bring additional benefits to RICD patients. References | Related Articles | Metrics

SPRY4-IT1 and breast cancer Yan Xuemin, Wu Xiaoyong, Zhang Jiayi, Wen Jinxu, Wang Yuexin 2023, 50 (10):  627-630.  doi: 10.3760/cma.j.cn371439-20230616-00119 Abstract ( 79 )   HTML ( 14 )   PDF (752KB) ( 41 )   Save Long non-coding RNA （lncRNA） is an RNA molecule that does not code to express proteins， and plays an important role in the occurrence and development of a variety of tumors. As an lncRNA， SPRY4-IT1 is highly expressed in breast cancer tissues， and can be used as an upstream and downstream regulator of breast cancer， promoting the progression of breast cancer， and is closely related to breast cancer stage and prognosis. In-depth study of the molecular mechanism associated with SPRY4-IT1 and breast cancer can provide new ideas for discovering biomarkers for early diagnosis of breast cancer， assessing disease prognosis and finding targeting sites. References | Related Articles | Metrics

Application of targeted therapy combined with immune checkpoint inhibitors in the treatment of HER2 positive advanced gastric cancer Yu Xiaopeng, Feng Qingqing, Zhao Wenfei, Zhao Wenwen, Wei Hongmei 2023, 50 (10):  631-635.  doi: 10.3760/cma.j.cn371439-20230428-00120 Abstract ( 81 )   HTML ( 20 )   PDF (762KB) ( 47 )   Save Human epidermal growth factor receptor 2 （HER2）， programmed death-1 and programmed death-ligand 1 are related to the proliferation， invasion and metastasis of various tumor cells. A variety of antibodies and small molecule drugs targeting HER2 have achieved considerable results in clinical practice. Immune checkpoint inhibitors targeting programmed death-1 and programmed death-ligand 1 have significant effects in clinical application. In the KEYNOTE-811 trial， the combination of immune checkpoint inhibitors and targeted therapy has achieved encouraging results in HER2-positive advanced gastric cancer. References | Related Articles | Metrics

Research progress of locoregional interventional therapies combined with immune checkpoint inhibitors for intermediate-advanced hepatocellular carcinoma Tian Jinming, Yang Jijin 2023, 50 (10):  636-640.  doi: 10.3760/cma.j.cn371439-20230428-00121 Abstract ( 96 )   HTML ( 18 )   PDF (761KB) ( 48 )   Save According to the International Agency for Research on Cancer （IARC） of the World Health Organization， the number of people with primary liver cancer is predicted to exceed 1 million per year by 2025， making it a major threat to human life and health. According to "Standardization for Diagnosis and Treatment of Hepatocellular Carcinoma （2022 edition）" issued by the National Health Commission of China， locoregional interventional therapy represented by ablation and transcatheter arterial chemoembolization （TACE） has become the main treatment for unresectable intermediate-advanced hepatocellular carcinoma （HCC）， in which the indications for TACE include patients with stage Ⅰb to Ⅲb HCC. Locoregional interventional therapy has been proved to have a clear immune activation effect， and with the gradual promotion of immune checkpoint inhibitors in clinical trials and applications at home and abroad， the combination therapy of locoregional intervention and immune checkpoint inhibitors has shown a more effective objective response rate， slower progression time and longer survival， bringing new hope to patients with inoperable intermediate-advanced HCC. References | Related Articles | Metrics