The attenuating and potentiating effects of traditional Chinese medicine in immune checkpoint therapy / 中国临床药理学与治疗学

Immunotherapy has become a global focus in cancer clinical practice and scientific research. In the past two years, PD-1\PD-L1 and CTLA-4 inhibitors, especially Nivolumab, Pembrolizumab, Atezolizumab and Lpilimumab, have been used in non-small cell lung cancer, colon cancer. Promising results have been obtained in malignancies such as melanoma and urinary tract cancer. Traditional Chinese medicine has a long history in China. Modulating immune checkpoints has certain advantages in treating malignant tumors, and it has shown good efficacy in improving its adverse events. This article reviews the role of traditional Chinese medicine in regulating immune checkpoints and improving adverse reactions and its application prospects in immunomodulatory treatment.

Establishment and Application of in vitro and in vivo Model of Disseminated Tumor Cells with Dormancy / 肿瘤防治研究

Postoperative asymptomatic patients with early cancer (lung cancer) have dormant disseminated tumor cells (DTCs) in their metastatic target organs, and the proliferation of these DTCs is the key link leading to clinical metastasis. The development of therapeutic agents to maintain DTCs dormant or eradicate dormant DTCs will prevent tumor metastasis and break through the bottleneck of improving the overall efficacy of treating malignant tumors. This paper reviews the methods of establishing in vitro and in vivo research models of DTCs with dormant characteristics to promote the understanding of dormant DTCs and improve the research and development efficiency of anti-tumor metastasis drugs.

Comparative study on the ability of active ingredients in Jinfukang to decrease neutrophils recruiting by lung cancer circulating tumor cells / 中国临床药理学与治疗学

AiM: To observe the recruitment effect of lung cancer circulating tumor cells (CTCs) on neutrophils, and find out the effective components of jinfukang in inhibiting the recruitment of neutrophils by CTCs. METHODS: The ability of human lung adenocarcinoma circulating tumor cells CTC-TjH-01 cells to recruit neutrophils from whole blood leukocytes, and the effect of jinfukang and its six active ingredients on the recruitment of neutrophils by CTCs was detected by flow cytometry. CCK-8 assay was used to observe cell viability to determine the concentration of action; transwell chemotaxis assay was used to detect the effect of six active ingredients on the chemotaxis of CTC-TjH-01 cells to neutrophils. RESULTS: CTCTjH-01 cells could increase the recruitment of neutrophils compared to blank control (p < 0.01); after the effect of jinfukang, the neutrophils recruited by CTC-TjH-01 cells decreased (p < 0.01). Trigonelline and Ophiopogonin W reduced neutrophil recruitment to CTC-TjH-01 cells at concentrations that had no effect on cell viability (p < 0.01), trigonelline had the best effect; the chemotaxis of CTC-TjH-01 cells to neutrophils was weakened by trigonelline, astragaloside IVz and Ophiopogon pol-ysaccharide (p < 0.05), and trigonelline had the best effect. CONCLUSiON: jinfukang can inhibit the recruitment of neutrophils by circulating tumor cells, and trigonelline, an effective monomer with "Fuzheng" effect in jinfukang, can significantly inhibit the recruitment of neutrophils by circulating tumor cells in lung cancer, which proves that trigonelline may have the potential to inhibit lung cancer metastasis through targeting neutrophils.

Effect of fixed-time artificial insemination on corpus luteum gene expression at the day 16 and 25 pregnancy of gilt.

Utilization of female livestock can be optimized by application of Fixed-Time Artificial Insemination (FTAI), which plays an important role in large-scale livestock production. However, molecular mechanism of FTAI affecting reproductive performance remains unclear. To investigate the effects of FTAI on corpus luteum in 16 and 25 days of pregnancy gilts, 12 pregnancy gilts were selected from Altrenogest + PMSG + GnRH (APG) group and control group. The number of left and right CL in APG group were significantly higher than control (p < 0.05). Furthermore, result showed the number of differentially expressed genes between 16APG group and 16 C group was obviously larger than that between 25APG and 25 C group (2394 vs. 1476). Up regulated genes in APG were mainly associated with cytokine production and secretion, cell communication and transport (day 16) and angiogenesis, cell cycle and cell-cell signaling (day 25). The expression of differentially expressed genes (RPL10, CYP17A1, DCN, IL18, LDLR and PRLR) in luteal tissue were verified by real-time PCR. In summary, APG program significantly improve reproductive efficiency of gilts through up regulation of cytokine production/secretion, cell communication and transport in Day 16 pregnancy and angiogenesis, cell cycle and cell-cell signaling at Day 25 pregnancy in porcine.

Jinfukang Inhibits Lung Cancer Metastasis by Regulating Immune Senescence / 肿瘤防治研究

Objective To explore the effect of immune senescence on lung cancer metastasis and reveal the mechanism of Fuzheng traditional Chinese medicine Jinfukang in the prevention and treatment of the metastasis. Methods A lung metastasis model of Lewis lung cancer cells was established in C57BL/6 mice with different ages (15 months, 6 months, and 2 months). Mice in the 6-month-old group were given Jinfukang intragastrically for 42 days. Pulmonary metastasis was analyzed by in vivo imaging, anatomical microscopic observation, and HE staining. The proportion of memory T cells and NK cells in peripheral blood was detected by flow cytometry. Results The lung metastatic tumor formation rate of 15-month-old and 6-month-old mice was significantly higher than that of 2-month-old mice (all P < 0.05). Abundance of CD4+T cells in peripheral blood was positively correlated with age (2-month-old vs. 6-month-old, P=0.041; 2-month-old vs.15-month-old, P=0.041; 6-month-old vs.15-month-old, P=0.953). The abundance of NK cells was negatively correlated with age (2-month-old vs. 6-month-old, P=0.009; 2-month-old vs.15-month-old, P=0.009; 6-month-old vs. 15-month-old, P=0.574). However, the survival time of mice in the Jinfukang group was longer (P > 0.05) and the level of NK cells in peripheral blood was significantly higher (P=0.029) than those in the normal saline group. Conclusion Immune senescence can promote the metastasis of lung cancer. The prolongation of the survival time of mice administered with Jinfukang may be related to delaying immune senescence and increasing the number of NK cells.

Dormancy and Survival Mechanism of Disseminated Tumor Cell and Its Role in Prevention and Treatment of Solid Tumor Metastasis / 肿瘤防治研究

The prevention and treatment of tumor metastasis can significantly improve the survival of patients with solid tumors. However, there is still a lack of effective drugs for the prevention and treatment of metastasis. The main reason is that the existing intervention and therapeutic drugs are difficult to achieve precise prevention and treatment of metastasis. Due to disseminated tumor cells (DTCs) already exist in the metastatic target organs of early postoperative patients, they are difficult to be detected with existing imaging techniques, and there is a lack of effective intervention drugs and efficacy evaluation systems. When DTCs grow to be detectable by imaging, the patient is already in the advanced stage of cancer, which has become a bottleneck restricting the breakthroughs in metastasis prevention and treatment. This paper reviews the dormancy and survival mechanism of DTCs in metastatic target organs and its intervention strategies, in order to promote the curative effect of metastasis prevention and treatment.

MicroRNAs are potential regulators of the timed artificial insemination effect in gilt endometrium.

To determine effects of timed artificial insemination (TAI) hormonal treatments on reproductive performance of gilts/sows and explore molecular mechanisms, gilts (TAI: 90; Control:149; Total: 239) and sows (TAI: 370; Control: 492) were utilized. Results indicated the estrus/farrowing rate and number of piglets born alive and weaned in the TAI group were greater than in the control group for both gilts and sows. To explore the molecular mechanism for TAI hormonal effects, the small RNA of the gilt endometrium at 16 and 25 of gestation were sampled and sequenced to determine potential functions of microRNA (MiRNA); 358 known and 142 novel MiRNAs were detected. With comparison of TAI and control groups, there were 54 differentially abundant MiRNAs, and functional analysis results indicated "binding," "protein/ion binding," and "immune response" were mostly enriched. In addition, representative MiRNAs were selected based on criteria including being regulated on both day 16 and 25 of gestation (ssc-miR-10a-5p, ssc-miR-345-5p, ssc-miR-370) along with reproduction-related target genes (ssc-miR-424-5p, ssc-miR-142-5p). Furthermore, target genes of selected MiRNAs were screened, and functional enrichment of those genes also indicated that the "binding" and "immune response" were mainly enriched. Results from the present study confirmed TAI-hormonal treatments improved estrous/farrowing rate and number of piglets born alive/weaned of gilts/sows and that hormonal treatment regimens leading to behavioral estrus at timed artificial insemination in gilts results in microRNA patterns in the endometrium that are more supportive of pregnancy. Results contribute valuable information for future studies of effects of TAI hormonal treatments on pig reproductive performance.

Research Advances of Circulating Tumor Cells in Lung Cancer / 肿瘤防治研究

Metastasis is the main factor leading to the death of patients with lung cancer, and active prevention is the key to improve the efficacy of treatment. Circulating tumor cells (CTCs) play an important role in initiating metastasis. They trigger a series of metastatic cascade reactions at the moment of shedding from the primary focus, and finally colonize and proliferate in the distant target organs. In recent years, the detection technology of lung cancer CTCs has been continuously optimized. It can not only count CTCs, but also identify different subsets. CTCs detection of lung cancer can be used for early screening, the prediction of prognosis after surgery and chemoradiotherapy and the evaluation of curative effect of targeted immunotherapy. Dynamic monitoring of tumor heterogeneity is helpful to adjust personalized treatment plan and achieve the accurate treatment of cancer. Tian Jianhui's research group established the world's first circulating tumor cell line of human lung adenocarcinoma, integrated it into the theory of "positive deficiency and toxin" in the subclinical core pathogenesis of lung cancer, and actively promoted the construction of a specific research platform for lung cancer, in order to improve the research, prevention and control efficiency of lung cancer metastasis.

Research Progress of Strengthening Health Qi to Treat Cancer by Regulating Tumor Immunity / 肿瘤防治研究

Traditional Chinese medicine attaches great importance to the health Qi in the prevention and treatment of malignant tumors and emphasizes the concept of "harmonizing yin and yang until a balance is reached". Professor Liu Jiaxiang has established an academic system of "strengthening the health Qi to treat cancer" characterized by "putting people first" and "protecting the health Qi", emphasizing the regulation of the body's internal resistance (including immunity) to prevent and treat malignant tumors. The tumor immunotherapy has been proven effective in the field of pan-cancer and is considered as the most possible cure for cancer. This article deeply studies the scientific connotation of "health Qi" of human body and its role in tumor pathogenesis from the perspective of tumor immunology, which will promote the mutual promotion and integration of traditional Chinese medicine and oncology, and further improve the efficiency of prevention and control of malignant tumors in China through the integration of traditional Chinese and Western medicine.

The crosstalk between immunosenescence and tumor pathogenesis / 中国肿瘤临床

Immunosenescence is the decline in the structure and function of the body's immune system that involves organs, cells, im-mune factors, and regulatory networks. Decreased immunity and immune clearance, caused by immunosenescence, are key contribu-tors to tumorigenesis. This article begins by introducing the concept of immunosenescence and provides a comprehensive description of the relationship between immunosenescence and tumorigenesis. We also discuss the influence of the various components of the immune system on tumor incidence. Finally, the article provides ideas for immunosenescence intervention aimed at the prevention and treatment of cancer.

Characterization and comparative analyses of transcriptomes for in vivo and in vitro produced peri-implantation conceptuses and endometria from sheep.

An increasing number of reports indicate that in vitro fertilization (IVF) is highly associated with long­term side effects on embryonic and postnatal development, and can sometimes result in embryonic implant failure. While high­throughput gene expression analysis has been used to explore the mechanisms underlying IVF-induced side effects on embryonic development, little is known about the effects of IVF on conceptus-endometrial interactions during the peri-implantation period. Using sheep as a model, we performed a comparative transcriptome analysis between in vivo (IVO; in vivo fertilized followed by further development in the uterus) and in vitro produced (IVP; IVF with further culture in the incubator) conceptuses, and the caruncular and intercaruncular areas of the ovine endometrium. We identified several genes that were differentially expressed between the IVO and IVP groups on day 17, when adhesion between the trophoblast and the uterine luminal epithelium begins in sheep. By performing Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, we found that, in the conceptus, differentially expressed genes (DEGs) were associated mainly with functions relating to cell binding and the cell cycle. In the endometrial caruncular area, DEGs were involved in cell adhesion/migration and apoptosis, and in the intercaruncular area, they were significantly enriched in pathways of signal transduction and transport. Thus, these DEGs are potential candidates for further exploring the mechanism underlying IVF/IVP-induced embryonic implant failure that occurs due to a loss of interaction between the conceptus and endometrium during the peri-implantation period.

Progress on metastasis induced by myeloid-derived suppressor cells to promote circu-lating tumor cell / 中国肿瘤临床

Circulating tumor cells (CTCs), as the seeds of tumor metastasis, manage to escape from immune clearance both in microen-vironment and in peripheral blood. CTCs can also facilitate formation of pre-existing environment, which is the crucial step in metasta-sis. Myeloid-derived suppressor cells (MDSC), as a group of immunosuppressive cells derived from bone marrow cells, may play a key role in this process. In this review, the progress in MDSC and its role in the formation, survival, and immune escape of CTCs were exten-sively discussed to explore a new target for tumor immunotherapy.

Immunosenescence and its role in cancer / 国际肿瘤学杂志

Immunosenescence is a biological process featured by the structural and functional decline of immunity in ageing people,which favors the carcinogenesis by rendering the body's immune surveillance and tumor escape.Decreasing clearance of tumor cells by macrophages and natural killer cell reflects the immunosenescence of innate immune,also,the tumor antigen presentation ability of dendritic cell is decreased.While,the decline of the CD8 + T cells cytotoxic effect and the secretion of tumor growth factor accounts for the immunosenescence of adaptive immunity.Intervention of immunosenescence may produce the novelty ideas of prevention and treatment of cancer.

Th e clinci al significance of circulating tumor cells in lung cancer / 实用肿瘤学杂志

Metastasis is the leading cause of death in patients with lung cancer .Circulating tumor cells (CTCs)play a key role in the process of distant metastasis .In recent years,research results have shown that CTCs may become a emerging marker and new target in the treatment of lung cancer .In this article,we elaborate the clinical significance of CTCs in lung cancer from the way of diagnosis and clinical staging ,metastasis and recur-rence,individual treatment and prognosis and so on ,so that we can provide a new direction for the treatment of lung cancer .

Chemotherapy in conjunction with traditional Chinese medicine for survival of elderly patients with advanced non-small-cell lung cancer: protocol for a randomized double-blind controlled trial / 中西医结合学报

Traditional Chinese medicine (TCM) is considered an important complementary therapy with beneficial effects for cancer patients. Elderly patients with non-small-cell lung cancer (NSCLC) are a complex patient group with increasing co-morbidity and shrinking physiological reserve, and may derive substantial benefit from the supportive aspects of TCM. Researchers from Shanghai Longhua Hospital found that qi and yin deficiency is a common syndrome in patients with stage III or IV lung cancer. This project was designed to study the combination of single-agent chemotherapy with TCM methods of benefiting qi and yin in elderly patients with advanced NSCLC.

Cytokeratin distribution and expression during the maturation of mouse germinal vesicle oocytes after vitrification.

Cytokeratin (CK) is a type of the cytoskeleton that increases cell stabilization during oocyte maturation. This study was conducted to investigate the effect of vitrification on the distribution and expression of CK during mouse oocyte maturation. Germinal vesicle (GV) oocytes were randomly allocated into three groups: (1) untreated (fresh), (2) exposed to vitrification solution (VS) without being plunged into liquid nitrogen (CPA exposure), or (3) vitrified using the open-pulled straw (OPS) method (vitrification). The oocytes were then incubated for 0 h, 6h (metaphase I (MI) stage), and 10h (metaphase II (MII) stage). The CK distribution in the oocytes at the GV, MI, and MII stages was observed by immunofluorescence, and the expression at the MII stage oocytes derived from vitrified GV oocytes was detected by Western blotting. The CK distribution in the GV oocytes (88.5%) displayed a cortical pattern in the fresh group, whereas a granular pattern was mainly found at the MI (86.7%) and MII (93.5%) stages. In the CPA exposure group, 90.3% of the GV oocytes were observed to display the cortical pattern, and 69.2% of the MI oocytes and 92.9% of the MII oocytes showed the granular pattern. In the vitrification group, most oocytes (GV, 88.9%; MI, 100%; MII, 93.3%) exhibited the cortical pattern. The CK fluorescence intensities of the MII stage oocytes in both the fresh (59.27) and CPA exposure (60.05) group were significantly higher than that of the vitrification (26.53) group (p<0.05). Western blotting showed that the CK expression in the MII oocytes derived from vitrified GV oocytes was significantly lower (p<0.05) than in the control. In conclusion, OPS vitrification affects the normal CK distribution pattern during oocyte maturation and results in decreased CK expression in MII oocytes derived from vitrified GV oocytes.

Focus on Major Difficult Diseases, Improve Capability of Independent Innovation of Chinese Medicine---National Clincal Research Base (Malignant Tumor) Construction / 世界科学技术-中医药现代化

From the development of national clinical research base of traditional Chinese medicine ( TCM ) in Longhua Hospital, Shanghai University of Traditional Chinese Medicine, we made a success of construction, such as planning and foundation , curative effect , study protocol , standards , platform establishment . From the thinking to results , we made knowledge of the situation in order to provide references for the further building of clinical research base of TCM .

Effects of Feiji Formula on lung cancer metastasis in mice / 中西医结合学报

OBJECTIVE: To observe the effects of Feiji Formula, a compound traditional Chinese herbal medicine, on lung cancer metastasis in mice. METHODS: The lung cancer metastasis model of mice was established in this experiment study. Twenty-four mice were randomly divided into three groups: untreated group, cisplatin group and Feiji Formula group. Mice in the Feiji Formula group were treated with Feiji Formula decoction; in cisplatin group, with cisplatin by intraperitoneal injection; and in the untreated group, with normal saline (NS). After twenty-day treatment, the body and tumor weights as well as the number of metastatic tumors in both lungs of each mouse were measured. RESULTS: The body weight of mice in cisplatin group was significantly less than that of Feiji Formula group and untreated group (P<0.01); the tumor weight of mice in cisplatin group and Feiji Formula group was markedly lower than that of untreated group (P<0.01); and the number of metastatic tumors in cisplatin group and Feiji Formula group was markedly lower than that of the untreated group (P<0.01), no significant difference between the Feiji Formula group and cisplatin group in terms of the weights and the numbers of metastatic tumors in bilateral lungs. CONCLUSION: Feiji Formula can suppress tumor growth and decrease the number of lung metastatic tumors in the mice, and maintain the body weight of the mice.

Restoration of endothelial function after reperfusio injury by tetrahydrobiopterin / 中国介入心脏病学杂志

Objective To evaluate the influence of tetrahydrobiopterin on NO and MDA concentration and SOD activity as well as the myocardial infarction area. Methods Twenty-four rabbits were divided into three groups randomly: control group,MI/R group and BH 4 group. After occlusion of the left anterior descending coronary artery of a rabbit for 60 minutes followed by 90 minutes of reperfusion (ischemia/reperfusion),NO and MDA and SOD concentrations were measured and the myocardial infarction area was caculated. Results Compared with control group,the NO concentration in MI/R group was markedly decreased [(28?10) ?mol/L vs (116?17) ?mol/L,P 0.05];There was significant difference between MI/R and BH 4 groups in infarction area,too. [(18?4)% vs (16?4)%,P

Effect of tetrahydrobiopterin on lipid peroxidation in hypercholesterol rabbits / 第二军医大学学报

This paper is to observe the effect of tetrahydrobiopterin (BH 4) on lipid peroxidation in hypercholesterol rabbits.A total of 24 rabbits were randomly divided into 4 groups:normal diet(group A),BH 4 plus hypercholesterol diet(group B),VitE plus hypercholesterol diet(group C) and hypercholesterol diet(group D). After 30 d,serum total cholesterol(TC), superoxide dismutase (SOD) and malondialdehyde (MDA) were determined.The amount of TC in group A was lower than that in other groups( P