Research progress of antineoplastic drugs targeting platelets / 中国药理学通报

Platelets have long been recognized as key players in hemostasis and thrombosis; however, there is growing evidence that they are also involved in cancer. Preclinical and clinical studies have shown that platelets can promote tumorigenesis and metastasis through various crosstalks between platelets and cancer cells. Platelets play an active role in all stages of tumorigenesis, including tumor growth, tumor cell extravasation, and metastasis. In addition, thrombocytosis in cancer patients is associated with poor patient survival. Platelets are also well-placed to coordinate local and distant tumor-host interactions due to the a- bundance of microparticles and exosomes. Therefore, antitumor drugs targeting platelets have great development and application prospects. The following will review the research progress of anti-tumor drugs targeting platelets.

Total salvianolic acid combined with anti-PD-Ll inhibits development of breast cancer by regulating infiltration of myeloid macrophages / 中国药理学通报

Aim To explore the effect of total salvianolic acid (TSA) combined with anti-PD-Ll on the development of breast cancer by inhibiting the infiltration of myelogenous macrophages into tumors. Methods E0771 breast cancer subeutaneous tumor model was constructed. Twenty-five mice were randomly divided into control group, model group, total salvianolic acid group (TSA 10 g • kg

Advances in involvement of pericyte in tumour microenvironment in tumour metastasis / 中国药理学通报

Pericytes are essential components of vessel mural cells that function to regulate blood flow, clear or phagocytose debris, and are contractile cells enwrapping capillaries throughout the body. It controls vascular permeability and is involved in the development of blood vessels and is an important regulator and potential drug target of angiogenesis and vascular function. Pericytes are also thought to play a key role in the tumor microenvironment, especially during tumor growth and distal metastasis. Therefore,in this review we discuss the relationship between pericytes involved in tumor angiogenesis and tumor metastasis, as well as the use of targeted pericytes to treat tumors,with a view to providing a basis for subsequent studies.

Neuronal Histone Methyltransferase EZH2 Regulates Neuronal Morphogenesis, Synaptic Plasticity, and Cognitive Behavior in Mice / 神经科学通报·英文版

The histone methyltransferase enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2)-mediated trimethylation of histone H3 lysine 27 (H3K27me3) regulates neural stem cell proliferation and fate specificity through silencing different gene sets in the central nervous system. Here, we explored the function of EZH2 in early post-mitotic neurons by generating a neuron-specific Ezh2 conditional knockout mouse line. The results showed that a lack of neuronal EZH2 led to delayed neuronal migration, more complex dendritic arborization, and increased dendritic spine density. Transcriptome analysis revealed that neuronal EZH2-regulated genes are related to neuronal morphogenesis. In particular, the gene encoding p21-activated kinase 3 (Pak3) was identified as a target gene suppressed by EZH2 and H3K27me3, and expression of the dominant negative Pak3 reversed Ezh2 knockout-induced higher dendritic spine density. Finally, the lack of neuronal EZH2 resulted in impaired memory behaviors in adult mice. Our results demonstrated that neuronal EZH2 acts to control multiple steps of neuronal morphogenesis during development, and has long-lasting effects on cognitive function in adult mice.

The clinical effect of amniotic membrane patching in the treatment of recurrent macular hole associated with retinal detachment of high myopia / 中华眼底病杂志

Objective:To evaluate the safety and efficacy of amniotic membrane patching in the treatment of recurrent macular hole associated with retinal detachment of high myopia (MHRD).Methods:A prospective study. From March 2018 to January 2020, 11 patients (11 eyes) of recurrent macular hole associated with MHRD at the First Affiliated Hospital of Zhengzhou University were enrolled. Among them, there were 3 males (3 eyes), and 8 females (8 eyes). The average age was 63.64±5.82. The axis length (AL) was 29.10± 0.59 mm, and the logarithm of the minimum angle of resolution best corrected visual acuity (logMAR BCVA) was 2.23±0.57. Patients previously received pars plana vitrectomy (PPV) combined with internal limiting membrane stripping surgery, which was more than 1 time. All eyes underwent standard pars plana three-channel 23G PPV combined with amniotic membrane covering and silicone oil filling. The silicone oil was removed 6 months after surgery. Follow-up time was up to 3 months after silicone oil removal surgery. 1, 3, and 6 months after the operation, the same equipment and methods were used to conduct relevant examinations before the operation to observe the closure of the macular hole, retinal reattachment and changes in logMAR BCVA. The logMAR BCVA before and after surgery was compared by paired t test. Results:At 1, 3, and 6 months after the operation, the retinas of all eyes were anatomically repositioned, the macular holes were well closed, and the amniotic membrane was attached to the retina. At 3 months after the silicone oil removal operation, there was no recurrence of macular hole in all eyes; logMAR BCVA was 1.35±0.32. No serious complications occurred during and after surgery in all eyes.Conclusion:Amniotic membrane patching is a safe and effective method for recurrent macular hole associated with MHRD.

Status quo of and challenges for research on rust disease in medicinal plants / 中国中药杂志

Medicinal plants are beneficial to human health. However,most of the major producing regions of medicinal plants suffer from rust disease,which threatens the yield and quality of Chinese medicinal materials,thus causes huge economic loss,and hinders the sustainable development of the Chinese medicine industry. By the end of 2020,rust disease had been reported in medicinal plants of 76 species and 33 families. In the 76 species,79 rust pathogens were detected. The majority of these pathogens belonged to Puccinia( 33,39. 24%),Coleosporium( 14,15. 19%),and Aecidium( 11,13. 92%). Of these 79 rust pathogens,10 were autoecious and 13 were heteroecious. Through literature research,this study reviewed the symptoms,pathogen species,severity and distribution,prevalence and occurrence conditions,and control measures of rust disease in medicinal plants,and thereby summarized the research status of rust disease in medicinal plants and the gap with other plants,which is expected to serve as a reference for further research on rust disease in medicinal plants.

Advance of synergism of immune checkpoint blockade and anti-angiogenesis in cancer treatment / 中国药理学通报

Immune checkpoint inhibitor ( ICI) activates the host' s anti-tumor immune response by blocking negative regulatory immune signals. A series of clinical trials showed that ICI could effectively induce tumor regression in a subset of advanced cancer patients. Anti-angiogenesis drugs commonly used to block tumor angiogenesis can inhibit the growth of tumors, but they cannot improve the survival of patients with limitations in application such as drug resistance. Tumor immune response is closely related to angiogenesis. In turn, tumor angiogenesis highly depends on immunosuppressive microenvironment. Recent studies have indicated that ICI resistance could be alleviated by combination therapy with anti-angiogenesis treatment, and the efficacy of combination therapy was superior to that of monotherapy. The reciprocal regulation between tumor vascular normalization and immune reprogramming forms a reinforcing loop that reconditions the tumor immune microenvironment to induce durable antitumor immunity. This review clarifies the latest understanding of ICI combined anti-angiogenesis therapy and provides ideas for subsequent research.

Research progress on the role of immune cells in tumor hematogenous metastasis / 中国药理学通报

Tumor blood and lymphatic vessel growth are necessary conditions for tumor growth, progression and metastasis, which are closely related with infiltrating nnate as well as adaptive immune cells. On one hand, immune cells rely on adhesion molecules on vascular endothelial cells to penetrate into tumor tissues and show anti-tumor characteristics. On the other hand, they can regulate tumor angiogenesis and lymphangiogenesis by secreting chemokines and cytokines, playing an important role in the process of tumor blood metastasis. In addition, the role of immune cells in promoting tumor blood metastasis highlights the shortcomings of t anti-angiogenic therapy. Therefore, targeting immune cells and tumor angiogenesis improve the effect of therapeutic. Based on these, this article summarizes the effects of immune cells on blood and lymphatic vessels n tumor metastasis, as well as related anti-vascular and immune therapies, in order o provide deas for subsequent research.

The association between the thin-section computed tomography parameters and the invasion and histological subtypes of subsolid nodules measuring 1-2 centimeters in diameter as lung adenocarcinoma: a retrospective study from one single center / 中华胸心血管外科杂志

Objective:To investigate the association between the parameters of thin-section computed tomography and the invasion and histological subtypes of subsolid nodules measuring 1-2 centimeters in diameter as lung adenocarcinoma.Methods:We retrospectively reviewed the cases with subsolid nodules measuring 1-2 centimeters on thin-section computed tomography and histologically confirmed as lung adenocarcinoma.Results:A total of 135 patients were enrolled in this study, including 23 with pure ground glass nodules and 112 with part-solid ground glass nodule. We observed significant differences of nodule size, solid component size, consolidation-to-tumor ratio, nodule attenuation and attenuation ratio( P<0.0001). The receiver operating curve indicated certain predictive value of solid component size, nodule attenuation and attenuation ratio: AUC were 0.838(0.756-0.919)、0.823(0.729-0.917) and 0.820(0.726-0.914), respectively. Of the invasive adenocarcinoma, those with solid or micropapillary components merely showed a significance in solid component size( P=0.024). Conclusion:The parameters of thin-section computed tomography of 1-2 centimeters subsolid nodules showed significant differences in varied invasiveness of lung adenocarcinoma, and these could have certain predictive value.

Research progress on the role of Ang/Tie axis in angiogenesis and metastasis / 药学学报

The tumor contains abundant new vessels, which are unevenly distributed, irregular, and branch-disordered. Angiopoietin (Ang) and tyrosine kinase receptor Tie mediate stable maturation of angiogenesis. Ang1 mainly plays a role in promoting vascular stabilization, and Ang2 is highly expressed in vessels, which makes the structure and function of vessels abnormal. Leaked vessels provide opportunities for invasion and metastasis of circulating tumor cells. Targeting the Ang/Tie axis to correct the abnormal state of vessels and promote its normalization, combined with chemotherapy drugs or immunotherapy, play a synergistic effect against tumors. This article summarizes the role of Ang/Tie axis in tumor angiogenesis and metastasis, and it aims to provide new ideas and strategies for clinical treatment of tumors.

Virtual screen of effective AChE inhibitory constituents from Glycyrrhizae Radix et Rhizoma based on pharmacophore and molecular docking / 中国中药杂志

This research is to predict anti-Alzheimer's disease active constituents on the target of acetylcholinesterase(AChE) from Glycyrrhizae Radix et Rhizoma with the help of pharmacophore and molecular docking. AChE ligand-based pharmacophore model was set up and the molecular library of the constituents from Glycyrrhizae Radix et Rhizoma were established by collecting literature. Then the constituents from Glycyrrhizae Radix et Rhizoma were screen for the potential AChE inhibitory potency in silico through matching with the best pharmacophore model. The flexible docking was used to evaluate the interactions between compounds screened from pharmacophore model and AChE protein(PDB ID:4 EY7). The interactions were expressed including but not limited to CDOCKER interaction energy, hydrogen bonds and non-bonding interactions. The molecular library of Glycyrrhizae Radix et Rhizoma contains 44 chemical constituents. As for the pharmacophore model, six kinds of potential AChE inhibitory constituents from Glycyrrhizae Radix et Rhizoma were considered to be the promising compounds according to the results of searching 3 D database of pharmacophore model. The molecular docking was possessed and the interaction patterns were given to show the detail interactions. The compounds screening from the pharmacophore model were consistent with the existing studies to some degree, indicating that the virtual screen protocols of AChE inhibitory constituents from Glycyrrhizae Radix et Rhizoma based on pharmacophore and molecular docking was reliable.

Effect of Levosimendan on the prognosis in severe coronary disease patients undergoing coronary artery bypass grafting / 中华老年医学杂志

Objective To evaluate the effect of Levosimendan on the prognosis in patients with severe coronary heart disease after operation.Methods A total of 485 severe coronary disease patients undergoing coronary artery bypass grafting from Teda International Cardiovascular Hospital and the Cardiac Surgery Department of the First Affiliated Hospital of China Medical University from May 2014 to June 2016 were enrolled.Of them,45 cases receiving Levosimendan postoperatively were assigned to the Levosimendan group,and according to propensity score matching,another 45 cases were selected as the control group in this study.Clinical data before treatment had no difference between the groups (P ＞ 0.1).Postoperative prognosis was compared between the two groups.Results There were significant differences in heart rate,mean arterial pressure,central venous pressure,cardiac output and other hemodynamic parameters between the two groups 48h after operation.The heart ultrasound results showed that the left ventricular ejection fraction(IVEF) was increased [(0.53±0.12) ％vs.(0.46±0.09)％,t =2.594,P=0.002],the postoperative ventilation time was reduced [(46.8±11.3) h vs.(58.5±16.3) h,t=-2.031,P=0.045]and the onset of bowel sounds became early [(16.5±5.9) h vs.(18.7±10.1) h,t =1.592,P=0.039]in the levosimendan group than in the control group 48h after operation.The incidences of new-onset acute kidney injury(20 ％ and 40 ％,x2 =6.702,P =0.018),new-onset postoperative atrial fibrillation (15.6％ and 44.4％,x2 =6.156,P =0.023) and perioperative myocardial infarction(11.1 ％ and 33.3％,x2 =6.429,P =0.021) had significant differences between the two groups(P＜0.05),but there was no difference in ICU retention time,1-month mortality after operation,malignant arrhythmia incidence and auxiliary equipment use (P ＞ 0.05).Conclusions Levosimendan can improve the early prognosis of severe coronary disease patients undergoing coronary artery bypass grafting and reduce the occurrence of postoperative organ dysfunction.

A review of insight in patients with schizophrenia / 中国心理卫生杂志

Impairment of insight is considered as the hallmark of schizophrenia. Insight is a multidimensional and dynamic construct which appears to have intricate links with other symptom dimensions of the psychotic illness. A better appreciation of insight in psychosis could help us in gaining knowledge about etiology, prognosis and treatment-related facets of the disorder. This paper reviews researches on insight of schizophrenia. It focuses on the biological basis, assessment methods of insight, influencing factors and treatment methods. And outlook on future research direction.

Clinical observation of long-term sacral nerve stimulation for anal rectal pain after lumbar surgery / 局解手术学杂志

Objective To observed the clinical effect of long-term sacral nerve stimulation on anal rectal pain after lumbar surgery.Methods A total of 18 cases with functional anorectal pain (FARP) after lumbar surgery in our hospital from April 2015 to March 2018were selected, of whom 3 cases refuse to accept the treatment, the other 15 cases received sacral nerve electrical stimulation.The Pittsburgh Sleep Quality Index (PSQI) and simplified MPQ pain questionnaire were used to evaluate the clinical effect in preoperative and postoperative1 week, 1 month, 3 months, 6 months, 9 months and 1 year respectively.Results Fifteen cases of permanent sacral nerve stimulation before and after , The MPQ scale and PSQI of 15 patients with implantation of permanent sacral nerve stimulation in postoperative 1 week were better than those before implantation , the differences were significant( P＜ 0. 05) . In the MPQ scale , the PPI and PRI at 6 months after operation was better than those before implantation , the difference was statistically significant ( P ＜ O. 01 ) ; PSQI and V AS score after 2 months were better than those before implantation , the difference were statistically significant( P ＜ 0.01) , meanwhile in 1-year of follow-up , the PSQI and VAS score continued to decline , but the change was not obvious. Conclusion Long-term sacral nerve electrical stimulation in the treatment of lumbar anorectal pain has a good clinical effect , which can improve patients ' quality of life.

Genetic characteristics and clinical screening and treatment of retinoblastoma / 国际眼科杂志(Guoji Yanke Zazhi)

@#Retinoblastoma(RB)is the most common intraocular malignant tumor in children, which often occurs in infants and young children. It can damage the eyesight, eyeball and even life-threatening of children. The occurrence and development is closely related to the genome and epigenome. The treatment and prognosis of hereditary RB in all cases depends on the initial stage of the disease, and when the disease is diagnosed and treated early, the survival rate exceeds 95%. The survival rate of RB was less than 50% when extraocular dissemination occurred in late stage. Therefore, the treatment focus on RB is to save the lives of children through early tumor monitoring and prevention. The secondary goal is to preserve globe salvage and to preserve vision to the maximum extent possible. The research on RB genetics is helpful to find specific targets through gene screening, monitoring and search, which is very necessary to improve the survival rate of children and to research targeted therapy.

Exploration of the association between meteorological factors and incidence of hand, foot, and mouth disease based on the distributed lag non-linear model in Jiangyin / 中华疾病控制杂志

Objective To explore the effect of meteorological factors on the incidence of hand foot and mouth disease (HFMD) in Jiangyin City. Methods The distributed lag non-linear model (DLNM) was used to estimate the delayed and cumulative effects of meteorological factors on incidence of HFMD in Jiangyin from 2012 to 2017. Results A total of 21 791 HFMD cases were reported in Jiangyin City during 2012-2017. We observed significant correlations between the daily incidence of HFMD and daily mean temperature (rs=0.402, P<0.001), daily mean pressure (rs=-0.453, P<0.001), and daily mean relative humidity (rs=0.075, P<0.001), respectively. It was indicated that the maximum cumulative effect of daily mean temperature on the incidence of HFMD was 11 ℃ (RR=1.473, 95% CI: 1.99-1.974), and the impact on the onset of HFMD was acute and hightest at the first day (RR=1.090, 95% CI: 1.045-1.136). The cumulative effect on incidence of HFMD was highest at 85% daily relative humidity (RR=1.346, 95% CI: 1.154-1.571), and the impact on HFMD peaked on the 6th day (RR=1.023，95% CI: 1.015-1.031); The maximum cumulative effect of daily mean pressure with the incidence of HFMD was 1010.0 hpa (RR=1.221, 95% CI: 1.020-1.463), but no lag effect was observed at this level. Conclusions Meteorological factors have significant impact on the incidence of HFMD in Jiangyin City, and the effects of temperature and humidity are lagged.

MicroRNA-365 Knockdown Prevents Ischemic Neuronal Injury by Activating Oxidation Resistance 1-Mediated Antioxidant Signals / 神经科学通报·英文版

MicroRNA-365 (miR-365) is upregulated in the ischemic brain and is involved in oxidative damage in the diabetic rat. However, it is unclear whether miR-365 regulates oxidative stress (OS)-mediated neuronal damage after ischemia. Here, we used a transient middle cerebral artery occlusion model in rats and the hydrogen peroxide-induced OS model in primary cultured neurons to assess the roles of miR-365 in neuronal damage. We found that miR-365 exacerbated ischemic brain injury and OS-induced neuronal damage and was associated with a reduced expression of OXR1 (Oxidation Resistance 1). In contrast, miR-365 antagomir alleviated both the brain injury and OXR1 reduction. Luciferase assays indicated that miR-365 inhibited OXR1 expression by directly targeting the 3'-untranslated region of Oxr1. Furthermore, knockdown of OXR1 abolished the neuroprotective and antioxidant effects of the miR-365 antagomir. Our results suggest that miR-365 upregulation increases oxidative injury by inhibiting OXR1 expression, while its downregulation protects neurons from oxidative death by enhancing OXR1-mediated antioxidant signals.

Clinical efficacy of different treatments and their impacts on the quality of life of octogenarians with coronary artery disease / 中华医学杂志(英文版)

BACKGROUND@#Coronary artery disease (CAD) in octogenarians (age of ≥80 years) has a high risk of mortality and high medical expenses. Research shows that the prevalence of CAD is higher among octogenarians than that among younger people, but few such patients undergo percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). This study aimed to evaluate different treatments with respect to their clinical effects and impacts on quality of life of octogenarians with CAD.@*METHODS@#Data of 519 octogenarians with CAD consecutively treated at Beijing Anzhen Hospital, Capital Medical University (Beijing, China) from January 2010 to January 2016 were collected in this study. The patients were categorized into three groups based on the treatments they received: the PCI group (n = 292), CABG group (n = 110), and medical treatment group (n = 117). The followings were recorded during follow-up: clinical data, death (all-cause and cardiovascular-related), re-hospitalization time, Seattle Angina Questionnaire (SAQ) score, and occurrence of hemorrhagic events (cerebral bleeding, gastrointestinal bleeding, and dermal ecchymosis).@*RESULTS@#The median follow-up duration was 25.0 (25th, 75th percentile: 17.0, 55.5) months among 417 patients. The all-cause death rates (28.2% vs. 12.0% and 14.6%, respectively) and cardiovascular-related death rates (15.4% vs. 3.8% and 6.4%, respectively) were significantly higher in the medical treatment group than those in the PCI group and CABG group (all P < 0.05). The re-hospitalization rate for cardiovascular events was significantly lower in the CABG group than those in the PCI group and medical treatment group (3.8% vs. 12.8% and 14.9%, respectively) (χ = 8.238, P = 0.018). The SAQ scores of physical limitation, angina frequency, treatment satisfaction, and disease perception were significantly higher in the PCI group and CABG group than those in the medical treatment group (all P < 0.05). No significant difference in the angina stability score was observed among the three groups (F = 3.179, P = 0.204).@*CONCLUSION@#PCI and CABG result in reduced mortality and better quality of life in octogenarians with CAD.

Clinical efficacy of different treatments and their impacts on the quality of life of octogenarians with coronary artery disease / 中华医学杂志(英文版)

Background@#Coronary artery disease (CAD) in octogenarians (age of ≥80 years) has a high risk of mortality and high medical expenses. Research shows that the prevalence of CAD is higher among octogenarians than that among younger people, but few such patients undergo percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). This study aimed to evaluate different treatments with respect to their clinical effects and impacts on quality of life of octogenarians with CAD.@*Methods@#Data of 519 octogenarians with CAD consecutively treated at Beijing Anzhen Hospital, Capital Medical University (Beijing, China) from January 2010 to January 2016 were collected in this study. The patients were categorized into three groups based on the treatments they received: the PCI group (n = 292), CABG group (n = 110), and medical treatment group (n = 117). The followings were recorded during follow-up: clinical data, death (all-cause and cardiovascular-related), re-hospitalization time, Seattle Angina Questionnaire (SAQ) score, and occurrence of hemorrhagic events (cerebral bleeding, gastrointestinal bleeding, and dermal ecchymosis).@*Results@#The median follow-up duration was 25.0 (25th, 75th percentile: 17.0, 55.5) months among 417 patients. The all-cause death rates (28.2% vs. 12.0% and 14.6%, respectively) and cardiovascular-related death rates (15.4% vs. 3.8% and 6.4%, respectively) were significantly higher in the medical treatment group than those in the PCI group and CABG group (all P < 0.05). The re-hospitalization rate for cardiovascular events was significantly lower in the CABG group than those in the PCI group and medical treatment group (3.8% vs. 12.8% and 14.9%, respectively) (χ2 = 8.238, P = 0.018). The SAQ scores of physical limitation, angina frequency, treatment satisfaction, and disease perception were significantly higher in the PCI group and CABG group than those in the medical treatment group (all P < 0.05). No significant difference in the angina stability score was observed among the three groups (F = 3.179, P = 0.204).@*Conclusion@#PCI and CABG result in reduced mortality and better quality of life in octogenarians with CAD.

Anti-senescence effect and molecular mechanism of the major royal jelly proteins on human embryonic lung fibroblast (HFL-I) cell line / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Royal jelly (RJ) from honeybee has been widely used as a health promotion supplement. The major royal jelly proteins (MRJPs) have been identified as the functional component of RJ. However, the question of whether MRJPs have anti-senescence activity for human cells remains. Human embryonic lung fibroblast (HFL-I) cells were cultured in media containing no MRJPs (A), MRJPs at 0.1 mg/ml (B), 0.2 mg/ml (C), or 0.3 mg/ml (D), or bovine serum albumin (BSA) at 0.2 mg/ml (E). The mean population doubling levels of cells in media B, C, D, and E were increased by 12.4%, 31.2%, 24.0%, and 10.4%, respectively, compared with that in medium A. The cells in medium C also exhibited the highest relative proliferation activity, the lowest senescence, and the longest telomeres. Moreover, MRJPs up-regulated the expression of superoxide dismutase-1 (SOD1) and down-regulated the expression of mammalian target of rapamycin (MTOR), catenin beta like-1 (CTNNB1), and tumor protein p53 (TP53). Raman spectra analysis showed that there were two unique bands related to DNA synthesis materials, amide carbonyl group vibrations and aromatic hydrogens. These results suggest that MRJPs possess anti-senescence activity for the HFL-I cell line, and provide new knowledge illustrating the molecular mechanism of MRJPs as anti-senescence factors.