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25 May 2021, Volume 42 Issue 5

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Invited Monographs

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Research on the progress in radiotherapy of lung cancer in 2020

Liu Jie, Li Xuanzong, Yu Jinming

2021, 42(5): 321-326. DOI: 10.3969/j.issn.2097-0005.2021.05.001

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As one of the main treatment methods, radiotherapy plays a very important role in all the stages for lung cancer. Outstanding results were achieved in radiotherapy in lung cancer during 2020. Radiotherapy combining with immunotherapy is still the research hot topic. Radiotherapy combined with targeted therapy, and the choice of radiotherapy dose and technology have attracted much attention. This article reviews the important research progress of radiotherapy in the treatment of lung cancer in 2020.

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Research directions worth paying attention to in tumor radiotherapy in the immune era

Liu Chengxin, Li Baosheng

2021, 42(5): 327-332. DOI: 10.3969/j.issn.2097-0005.2021.05.002

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Immunotherapy plays an increasingly important role in cancer treatment, especially immune checkpoint inhibitor therapy. However, due to low immunotherapy efficiency, a synergistic anti-tumor response may be produced through combined application with traditional tumor treatment methods. Among them immune combined radiotherapy is highly anticipated. Radiotherapy can directly or indirectly act on tumor cells by regulating the immune response in a variety of ways, such as inducing immunogenic cell death or changing the immune cell infiltration in the tumor microenvironment. Immunotherapy can also affect the effect of radiotherapy by regulating the infiltrating immune cells in the tumor microenvironment and the normalization of blood vessels. This article focuses on the interaction and theoretical basis between immunotherapy and radiotherapy, then analyzes in detail the effects of different doses and timely radiotherapy on immune response, and finally summarizes the problems and future development directions of radiotherapy under the influence of immunotherapy.

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Application of iron-based magnetic nanocarriers in tumor therapy

Niu Panhong, Wang Yan, Liu Yingying, Zhang Jie, Zhang Shuping, Liu Sijin

2021, 42(5): 333-339. DOI: 10.3969/j.issn.2097-0005.2021.05.003

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Nano-drug delivery for tumor therapy has promoted the development of nanomaterials in the realm of biomedicine. Among them, iron-based magnetic nanomaterials have the advantages of good magnetism, excellent biocompatibility, and easy functional modification of the surface. As a nanocarrier, iron-based magnetic nanomaterials have received extensive attention and achieved rapid development in tumor therapy. Although there is a systematic understanding of Fe ₃O ₄magnetic nanocarriers, the comprehensive and systematic understanding of iron-based magnetic nanoparticles carriers still needs to be strengthened. With the rapid development of tumor nano-drug delivery system design, it is urgent to systematically review the preparation process and mechanism of iron-based magnetic nanocarriers. In addition, ferroptosis, as a new type of cell death, receives much more attention in the role of occurrence and development of tumors and other chronic diseases, and the effect of iron-based magnetic nanoparticles on ferroptosis in tumor treatment applications remains to be elucidated. This review systematically introduces the development, types and preparation methods of iron-based magnetic nanometer drug-loading platforms, and detailedly summarizes the application of iron-based magnetic nanoparticles in the integration of tumor diagnosis and treatment, including magnetic field-assisted targeting, magnetic resonance imaging, and magnetocaloric therapy , and the mechanism of ferroptosis caused by the Fenton reaction is also iilustrated.

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Discovery, research and application of hydrogen biomedical effects

Zhao Min, Qin Shucun

2021, 42(5): 339-346. DOI: 10.3969/j.issn.2097-0005.2021.05.004

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Hydrogen has potential protective effects on cardiovascular, brain, tumor and other diseases through anti-inflammatory, anti-oxidation, anti-apoptosis, regulation of energy metabolism and biological enzyme activities, and has achieved preventive and therapeutic effect in preliminary clinical trials. Hydrogen as an supplement treatment has been provided by therapeutic protocols for novel corona-virus pneumonia, and has broad application prospects in the biomedical field. At present, the biological role of hydrogen has been widely concerned, and its unknown mechanism has been gradually discovered. However, the wide application of hydrogen medicine still has many challenges. This review focuses on the discovery of hydrogen biomedical effects, pleiotropic mechanism and clinical application, and describes the challenges and coping strategies of hydrogen biomedical research.

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Research progress of intestinal type 3 innate lymphoid cells

Wang Xin, Chen Zhengtao, Tang Hua

2021, 42(5): 347-357. DOI: 10.3969/j.issn.2097-0005.2021.05.005

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Innate lymphoid cells (ILCs) are a new class of innate immune cells that are an important component of the immune system and were discovered more than a decade ago. They play an important role in regulating the immune response and homeostasis. According to the different transcription factors expressed and cytokines secreted by ILCs, they can be divided into three distinct groups: ILC1s, ILC2s and ILC3s. Among them, ILC3s mainly exist in the intestinal tract, and maintain the immune homeostasis of the intestinal mucosa by participating in promoting the formation of lymphatic organs, maintaining the integrity of the epithelial barrier, regulating intestinal inflammation, and promoting antibacterial response. The author of this article reviews the development, characteristics and pathophysiological functions of ILC3s in the immune system of the intestine and summarizes the main research progress of ILC3s.

Basic Researches

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Mechanism effect of HMGB1-TLR4 and Müller cells in retinal angiogenesis

Sun Yuying, Xiao Ou, Huang Chunyu

2021, 42(5): 362-368. DOI: 10.3969/j.issn.2097-0005.2021.05.007

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Objective: To explore the role of HMGB1-TLR4 signal pathway and Müller cells in retinal neovascularization.Methods: The mice were divided into three groups: normoxic group, normal OIR model group and TLR4 gene knockout (TLR4 ^-/-) OIR model group. Retinal FITC-Dextran fluorescence perfusion and GS-isolectin B4 staining were used to evaluate the neovascularization. Immunofluorescence staining was used to observe the expression of HMGB1 in mouse retina, the co-expressions of HMGB1 and TLR4, and the co-expressions of TLR4 and GFAP. The mRNA expressions of HMGB1 in the retina of OIR mice in P12 and P17 groups were detected by PCR. Results: It was observed that the neovascularization area of P17 normal OIR mice was the largest, while that of TLR4 ^-/-OIR mice was relatively small, which suggested that TLR4 gene deletion could inhibit angiogenesis. The results of immunofluorescence staining showed that the expressions of HMGB1, TLR4 and GFAP in TLR4 ^-/-OIR mice were lower than those in normal OIR group. The results of PCR examination showed that the expression levels of HMGB1 in TLR4 ^-/-OIR mice at P12 and P17 were lower than those in normal OIR group. These results suggested that inhibition of HMGB1-TLR4 signal pathway could weaken the activation of Müller cells and reduce neovascularization.Conclusion: This study explores the mechanism of HMGB1-TLR4 activating Müller cells participating in neovascularization, and reveals the effect of HMGB1-TLR4 on retinal neovascularization by activating Müller cells. It is suggested that blocking HMGB1-TLR4 pathway can weaken the activity of Müller cells and provide a new method for the treatment of retinal neovascularization.

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Effect ofsalvianolicacid B on improving myocardium injury in diabetic rats with blood glucose fluctuation

Zhao Mengqiu, Ren Younan, Tao Shanjun, Zheng Shuguo

2021, 42(5): 369-374. DOI: 10.3969/j.issn.2097-0005.2021.05.008

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Objective: To investigate the improvement effect of salvianolicacid B (Sal B) on myocardial injury in diabetic rats with blood glucose fluctuation and the possible mechanisms implicated. Methods: Diabetes rat model was induced by streptozotocin (STZ) plus high fat and high sugar diet. All the rats except those in control group were subjected to intraperitoneal injection of insulin or intragastric administration of glucose at indicated time to induce blood glucose fluctuation, while those in Sal B groups were supplemented intragastrically with sal B 160 mg/kg and 80 mg/kg, respectively. Six weeks later, fasting blood glucose (FBG) and levels of mean daily blood glucose (MBG), standard deviation of blood glucose (SDBG), largest amplitude of glycemic excursion (LAGE) were collected to measure the stability of blood glucose. The primary histopathological changes of myocardium tissue were observed by HE staining. Serum levels of interleukin-6 (IL-6) and lactic dehydrogenase (LDH) and myocardial contents of interleukin-1β (IL-1β), interleukin-18(IL-18) and cysteine aspartic acid specific protease-1 (Caspase-1) were evaluated by ELISA. Total anti-oxidant capacity (TAC) of myocardium tissue was determined with commercially available kits. Protein levels of nuclear factor-κB (NF-κB) and NOD-like receptor 3 (NLRP3) in myocardium tissue were examined by Western blotting analysis.Results: After 6 weeks of blood glucose fluctuation, FBG, MBG, SDBG and LAGE of diabetic rats were all increased more significantly than those in control group ( P<0.01). Treatment with salvianolicacid B reduced level of FBG ( P<0.05). Compared with the model group, treatment with sal B evidently ameliorated pathological changes of myocardium, accompanied by a significant increase of total antioxidant capacity (P<0.01), as well as decrease in levels of LDH, IL-6, IL-1β and IL-18 ( P<0.05 or P<0.01). Sal B markedly down-regulated NF-κB nuclear translocation, protein expression of NLRP3 and activity of Caspase-1 in myocardium tissue ( P<0.05 or P<0.01). Conclusion: Treatment with sal B can evidently ameliorate myocardium injury in diabetic rats with blood glucose fluctuation, which might be derived from suppression of NF-κB/NLRP3/Caspase-1 signaling pathway and inflammatory response.

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Optimization of cellulase production process for solid-state fermentation of stem and leaf fromSalvia miltiorrhizaby endophytic fungus LZY9

Wang Yongdi, Qiu Mengjiao, Zhang Xiaohua, Wang Xin, Zhang Zhihao, Li Yanling, Chang Zhengyao

2021, 42(5): 375-379. DOI: 10.3969/j.issn.2097-0005.2021.05.009

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Objective: To further develop and utilize Salvia miltiorrhizaresources and optimize the technological conditions for cellulase production by solid-state fermentation. Methods: Using endophytic fungus LZY9 of Salvia miltiorrhizaas strain, on the basis of single factor experiment, response surface methodology was used to optimize the three factors of water content, inoculation amount and culture days of cellulase produced by solid fermentation of endophytic fungus LZY9, and the cellulase activity was determined by CMC sacylation method. Results: The optimum fermentation conditions of endophytic fungus LZY9 were as follows: water content was 5.0%, inoculum quantity was 60%, culture days was 5 days. Under the optimized conditions, the enzyme activity was 13.417 IU/g. The analysis of variance showed that there was no misfit factor in this experiment, and the three factors had obvious influence on the experimental results. Conclusion: This method is a new method for comprehensive utilization of stem and leaf wastes of Salvia miltiorrhiza on the ground.

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The expression of Orexin-A neurons in the hypothalamus of rats after sleep deprivation and its effect on learning and memory

Ni Liyan, Tang Jiyou

2021, 42(5): 380-384. DOI: 10.3969/j.issn.2097-0005.2021.05.010

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Objective: To investigate the expression of Orexin-A neurons in the hypothalamus of rats after sleep deprivation and its effect on learning and memory.Methods: Healthy adult male Wistar rats were randomly divided into cage control (CC), treadmill control (TC), sleep deprivation (SD) group. 72h total sleep deprivation was performed by intermittent treadmill. The expression of Orexin-A was observed by immunohistochemistry, and the spatial learning and memory ability was tested by Morris water maze test. Results: Compared with TC, the number of Orexin-A positive cells in hypothalamus of SD rats was significantly increased ( P<0.01). There was no significant difference between TC and CC group ( P>0.05). Compared with TC group, the escape latency and the times of crossing platform quadrant in SD group were significantly longer ( P<0.01), and there was no significant difference between TC group and CC group ( P>0.05). Conclusion: Sleep deprivation may impair spatial learning and memory in rats by inducing overexpression of Orexin-A in hypothalamus.

Clinical Researches

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Study on the difference in expression of CYP2C19 and GPⅡb/Ⅲa between patients with familial LAA atherosclerotic cerebral infarction and those with sporadic LAA cerebral infarction

Hao Rui, Xu Shuangshuang, Gao Min, Wang Yanhua, Lv Yuqin, Wang Na, Zhang Jingjun

2021, 42(5): 385-389. DOI: 10.3969/j.issn.2097-0005.2021.05.011

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Objective: To investigate the differences in expression of ADP, CYP2C19, P2Y12 receptors and GPⅡb/Ⅲa between patients with familial atherosclerotic (large-artery atherosclerosis, LAA) cerebral infarction and those with sporadic LAA cerebral infarction. Methods: Twenty-five patients with familial aggregated LAA cerebral infarction and sporadic LAA cerebral infarction were collected as family group and sporadic group respectively .Twenty-five healthy people were selected as control group. ADP protein expression, CYP2C19 gene, P2Y12 gene G52T locus and GPⅡb/Ⅲa protein expression were detected respectively. Results: There was significant difference in ADP expression between the family group and the control group; There was no significant difference between the family group and the sporadic group and between the sporadic group and the control group; Compared with the control group, the expression of CYP2C19 genes in the family group was significantly down-regulated, and the difference was statistically significant; Compared with the control group, the expression of CYP2C19 genes in the sporadic group had no significant difference in gene expression; The G52T loci of P2Y12 gene were significantly different between family group, sporadic group and control group. The expression of GPⅡb/Ⅲa in family group and control group was significantly up-regulated, and the difference was statistically significant. The difference in the expression of GPⅡb/Ⅲa. between family group and sporadic group and between sporadic group and control group was not significant; After 3 months of treatment, mRS scores of the family group and the sporadic group were compared, and the difference between the two groups was statistically significant. Conclusion: There are significant differences in ADP protein expression, CYP2C19 gene, P2Y12 gene G52T locus and GPⅡb/Ⅲa protein expression between family group and sporadic group.

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Meta-analysis of Shugan Jieyu Capsule combined with Escitalopram in the treatment of depression

Miao Shuai, Jiao Min, Xu Xiaoyan

2021, 42(5): 390-395. DOI: 10.3969/j.issn.2097-0005.2021.05.012

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Objective: To systemically evaluate shugan jieyu capsule combined with escitalopram efficacy and safety in the treatment of depression,and to provide reference for guiding its clinical application.Methods: Databases, including CNKI, WanFang, VIP and PubMed Data, were retrieved by two assessors independently so as to retrieve randomized controlled trials(RCTs)on Shugan Jieyu Capsule combined with escitalopram in treating depression.Data were extracted according to inclusion and exclusion criteria, and RevMan 5.3 software was used for quality evaluation and meta analysis of the included literature. Results: A total of 836 subjects were included in 10 RCTs. Meta analysis results showed that the experimental group (Shugan Jieyu Capsule combined with escitalopram) had better clinical efficacy, and the total response rate [OR=3.15,95%CI(2.08,4.79),P<0.000 01]was statistically significant compared with the control group (escitalopram alone). In trems of HAMD score before and after treatment, [MD=-3.03,95%CI(-4.59,-1.47),P=0.000 1], the difference was statistically significant.Results of adverse reaction incidence [OR=0.74,95%CI(0.50,1.08),P=0.12] showed that the difference was not statistically significant.Conclusion: Shugan Jieyu Capsule combined with escitalopram has a good effect in the treatment of depression, and can significantly reduce patients' HAMD score, which has a good application prospect.

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Effect of cisplatin intraperitoneal hyperthermic perfusion chemotherapy on apoptosis of human gastric cancer cell lines and its mechanism

Wang Fabao, Xia Zeliang, Chu Liang, Zhou Shaobo, Xu Zhaolong, Jiang Lei, Shan Erbo, Zhou Chaoyi

2021, 42(5): 396-400. DOI: 10.3969/j.issn.2097-0005.2021.05.013

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Objective: To preliminarily explore the effect of intraperitoneal hyperthermic perfusion of cisplatin on the apoptosis of human gastric cancer cell line (SGC-7901) and its mechanism.Methods: The four groups divided in the experiment were the control group, cisplatin group, hyperthermia group and hyperthermia chemotherapy group. CCK-8 was used to detect cell viability in each group, Hoechst staining method was used to detect cell apoptosis, flow cytometry was used to detect cell apoptosis rate, and Western blot was used to detect the expression levels of Caspase-3, Bcl-2, Bax and Bid proteins. Results: Compared with the control group, the cell viability of the cisplatin group, the hyperthermia group and the thermochemotherapy group was significantly reduced ( P<0.01), the apoptosis rate was significantly increased ( P<0.01), and the Caspase-3, Bax and Bid proteins were significantly increased High ( P<0.05 or P<0.01), Bcl-2 expression was down-regulated ( P<0.01). Compared with the cisplatin group and the hyperthermia group, the cell viability of the thermochemotherapy group was significantly reduced ( P<0.05), the apoptosis rate was significantly increased ( P<0.05), and the Caspase-3, Bax and Bid proteins were significantly increased ( P<0.05), the expression of Bcl-2 was significantly down-regulated ( P<0.05). There was no significant difference between the cisplatin group and the hyperthermia group ( P>0.05). Conclusion: Cisplatin intraperitoneal hyperthermic perfusion chemotherapy can promote the apoptosis of SGC-7901 cells by promoting the expression of Caspase-3, Bax and Bid and down-regulating Bcl-2.