High-performance liquid chromatography analysis of alkaloids in various parts of lotus extracts with ion mobility spectrometry and mass spectrometry dual detection.

Using high-performance liquid chromatography coupled with electrospray ionization-ion mobility spectrometry and mass spectrometry, we proposed a dual-detection method for the identification and profiling of alkaloids in various lotus parts including leaf, plumule, stem, seed epicarp, and receptacle. The eluent from high-performance liquid chromatography was split and conducted to electrospray ionization-ion mobility spectrometry and time-of-flight mass spectrometry separately to facilitate the compound identification. In total, 23 kinds of alkaloids were identified based on m/z, drift time, and retention time, including alkaloid isomers such as lirinidine, N-nornuciferine, and O-nornuciferine with identical m/z that are difficult to differentiate using mass spectrometry alone. Using this method, we investigated the changing dynamics of alkaloid accumulation in lotus leaves and lotus stems at different harvesting periods. The total alkaloid content showed an increasing trend with the growth and development of leave and stem. Overall, the developed dual detection method has the advantages of high peak capacity and high sensitivity compared with the conventional detection method and facilitates the identification of detected compounds.

Identification and analysis of differential miRNA-mRNA interactions in coronary heart disease: an experimental screening approach.

Objective: This aim of this study is to screen the differential molecules of kidney deficiency and blood stasis (KDBS) syndrome in coronary heart disease by high-throughput sequencing. In addition, the study aims to verify the alterations in the expression levels of miR-4685-3p and its regulated downstream, namely, C1QC, C4, and C5, using quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA), and to determine whether the complement and coagulation cascade pathway is the specific pathogenic pathway. Methods: Patients diagnosed with unstable angina pectoris with KDBS syndrome, patients with non-kidney deficiency blood stasis (NKDBS) syndrome, and a Normal group were recruited. The clinical symptoms of each group were further analyzed. Illumina's NextSeq 2000 sequencing platform and FastQC software were used for RNA sequencing and quality control. DESeq software was used for differential gene expression (DGE) analysis. qPCR and ELISA verification were performed on DGE analysis. Results: The DGE profiles of 77 miRNA and 331 mRNA were selected. The GO enrichment analysis comprised 43 biological processes, 49 cell components, and 42 molecular functions. The KEGG enrichment results included 40 KEGG pathways. The PCR results showed that, compared with the Normal group, the miR-4685-3p levels decreased in the CHD_KDBS group (P = 0.001), and were found to be lower than those observed in the CHD_NKDBS group. The downstream mRNA C1 regulated by miR-4685-3p showed an increasing trend in the CHD_KDBS group, which was higher than that in the Normal group (P = 0.0019). The mRNA C4 and C5 in the CHD_KDBS group showed an upward trend, but the difference was not statistically significant. ELISA was utilized for the detection of proteins associated with the complement and coagulation cascade pathway. It was found that the expression level of C1 was significantly upregulated in the CHD_KDBS group compared with the Normal group (P < 0.0001), which was seen to be higher than that in the CHD_NKDBS group (P < 0.0001). The expression levels of C4 and C5 in the CHD_KDBS group were significantly lower than the Normal group, and were lower than that in the CHD_NKDBS group (P < 0.0001). Conclusion: The occurrence of CHD_KDBS might be related to the activation of the complement and coagulation cascade pathway, which is demonstrated by the observed decrease in miR-4685-3p and the subsequent upregulation of its downstream C1QC. In addition, the expression levels of complement C4 and C5 were found to be decreased, which provided a research basis for the prevention and treatment of this disease.

Protective effects and regulatory mechanisms of Shen-shuai-yi recipe on renal fibrosis in unilateral ureteral obstruction-induced mice.

Renal fibrosis (RF) is a common pathological feature of chronic kidney disease (CKD), which remains a major public health problem. As now, there is still lack of chemical or biological drugs to reverse RF. Shen-shuai-yi Recipe (SSYR) is a classical Chinese herbal formula for the treatment of CKD. However, the effects and mechanisms of SSYR in treating RF are still not clear. In this study, the active constituents SSYR for treating RF were explored by UHPLC-Q-Orbitrap HRMS. Bioinformatics analyses were employed to analyze the key pharmacological targets and the core active constituents of SSYR in the treatment of RF. In experimental validation, vehicle or SSYR at doses of 2.12 g/kg/d and 4.25 g/kg/d were given by orally to unilateral ureteric obstruction (UUO) mice. 13 days after treatment, we detected the severity of renal fibrosis, extracellular collagen deposition and pre-fibrotic signaling pathways. Bioinformatics analysis suggested that signal transducer and activator of transcription 3 (STAT3) was the core target and lenticin, luteolin-7-O-rutinoside, hesperidin, kaempferol-3-O-rutinoside, and 3,5,6,7,8,3',4'-heptamethoxyflavone were the key constituents in SSYR for treating RF. SSYR significantly reduced the expressions of fibronectin (FN), α-smooth muscle actin (α-SMA), collagen-I and alleviated renal interstitial collagen deposition in UUO kidneys. In mechanism, SSYR potently blocked the phosphorylation of STAT3 and Smad3 and suppressed the expression of connective tissue growth factor (CTGF). Collectively, SSYR can ameliorate RF via inhibiting the phosphorylation of STAT3 and its downstream and reducing the collagen deposition, suggesting that SSYR can be developed as a novel medicine for treating RF.

Functional compounds of ginseng and ginseng-containing medicine for treating cardiovascular diseases.

Ginseng (Panax ginseng C.A.Mey.) is the dry root and rhizome of the Araliaceae ginseng plant. It has always been used as a tonic in China for strengthening the body. Cardiovascular disease is still the main cause of death in the world. Some studies have shown that the functional components of ginseng can regulate the pathological process of various cardiovascular diseases through different mechanisms, and its formulation also plays an irreplaceable role in the clinical treatment of cardiovascular diseases. Therefore, this paper elaborates the current pharmacological effects of ginseng functional components in treating cardiovascular diseases, summarizes the adverse reactions of ginseng, and sorts out the Chinese patent medicines containing ginseng formula which can treat cardiovascular diseases.

Oxidative Damage to BV2 Cells by Trichloroacetic Acid: Protective Role of Boron via the p53 Pathway.

This study aimed to investigate the neurotoxicity induced by trichloroacetic acid (TCA) and the possible protective mechanisms of boron (B). Mouse BV2 cells were treated with TCA (0, 0.39, 0.78, 1.56, 3.12, 6.25, or 12.5 mmol/L) and B (0, 7.8, 15.6, 31.25, 62.5, 125, 500, or 1,000 mmol/L) for 3 h and 24 h, respectively. Then, reactive oxygen species, and supernatant proinflammatory cytokine and protein levels were analyzed after 24 h of combined exposure. Beyond the dose-dependent decrease in the cellular viability, it clearly increased after B supplementation ( P < 0.05). Moreover, B decreased oxidative damage, and significantly down-regulated IL-6 levels and up-regulated TNF-ß production ( P < 0.05). B also decreased apoptosis via the p53 pathway. The present findings indicated that TCA may induce oxidative damage, whereas B mitigates these adverse effects by decreasing cell apoptosis.

Near-Infrared-Enpowered Nanomotor-Mediated Targeted Chemotherapy and Mitochondrial Phototherapy to Boost Systematic Antitumor Immunity.

Phototherapy is an important strategy to inhibit tumor growth and activate antitumor immunity. However, the effect of photothermal/photodynamic therapy (PTT/PDT) is restricted by limited tumor penetration depth and unsatisfactory potentiation of antitumor immunity. Here, a near-infrared (NIR)-driven nanomotor is constructed with a mesoporous silicon nanoparticle (MSN) as the core, end-capped with Antheraea pernyi silk fibroin (ApSF) comprising arginine-glycine-aspartate (RGD) tripeptides. Upon NIR irradiation, the resulting ApSF-coated MSNs (DIMs) loading with photosensitizers (ICG derivatives, IDs) and chemotherapeutic drugs (doxorubicin, Dox) can efficiently penetrate into the internal tumor tissues and achieve effective phototherapy. Combined with chemotherapy, a triple-modal treatment (PTT, PDT, and chemotherapy) approach is developed to induce the immunogenic cell death of tumor cells and to accelerate the release of damage-associated molecular patterns. In vivo results suggest that DIMs can promote the maturation of dendritic cells and surge the number of infiltrated immune cells. Meanwhile, DIMs can polarize macrophages from M2 to M1 phenotypes and reduce the percentages of immunosuppressive Tregs, which reverse the immunosuppressive tumor microenvironment and activate systemic antitumor immunity. By achieving synergistic effects on the tumor inhibition and the antitumor immunity activation, DIMs show great promise as new nanoplatforms to treat metastatic breast cancer.

Mobile monitoring of VOCs and source identification using two direct-inlet MSs in a large fine and petroleum chemical industrial park.

Mobile monitoring with direct-inlet MS (DI-MS), one of the most direct and effective ways to track emission sources, can effectively serve air quality management in chemical industrial parks (CIPs). Mobile monitoring using a high mass-resolution proton-transfer-reaction time-of-flight MS (HMR-PTR-TOFMS) and single-photon ionization time-of-flight MS (SPI-TOFMS) was conducted in a large fine and petroleum CIP in eastern China for three days. The high mixing ratios of aliphatic hydrocarbons (AHs), aromatics, oxygenated VOCs (OVOCs), and nitrogenous VOCs (NVOCs) were found in the northeast, middle, north, and northeast of the fine chemical industrial zone (FCIZ), respectively. OVOCs were the most abundant VOC group in this area. Abnormal emissions of aromatics were universal throughout the CIP. We discovered 38 characteristic VOCs by the HMR-PTR-TOFMS, mainly including C6-C10 aromatics, C2-C6 carbonyls, C2-C3 organic acids, and some NVOCs. The time series and spatial distribution of the TVOCs obtained by the two DI-MSs are generally consistent. A comparison of the speciated VOCs at the TVOC peak points illustrates that the characteristic VOCs obtained by different instruments differed significantly: PTR-TOFMS showed an advantage in measuring aromatics and OVOCs; SPI-TOFMS showed an advantage in measuring aromatics and some Ahs; offline GC-MS showed an advantage in measuring AHs, aromatics, some OVOCs, and halohydrocarbons. Similarities were compared between five positive matrix factorization (PMF) model-based fingerprints of VOCs in a previous study and observed profiles of VOCs from mobile monitoring. The emission sources of the five fingerprints were identified and validated: two were widely distributed, one was a chemical reagent production factory, one was an acrylic fiber production plant, and one was a pesticide factory. This study demonstrated methods for analyzing mobile monitoring data, characterizing the VOCs in the fine and petroleum CIP, correlating the results of stationary observation and mobile monitoring, and integrating the source tracing system with DI-MSs.

The Synergistic Effects of Astragalus mongholicus and Salvia miltiorrhiza on Coronary Heart Disease Identified by Network Pharmacology and Experiment.

BACKGROUND AND PURPOSE: Two Chinese herbal medicines Huang Qi (HQ, Astragalus mongholicus) and Dan Shen (DS, Salvia miltiorrhiza) are often combined to treat coronary heart disease (CHD). The purpose of this study was to identify the underlying synergistic effects and mechanisms of HQ and DS against CHD. METHODS: The active components and targets of HQ and DS, CHD-related genes, and the biological progression were analysed by network pharmacology. The myocardial infarction (MI) rat model was established by ligating the left anterior descending coronary artery. Cardiac function was detected by ultrasonic electrocardiography. The MI size, fibrosis, cardiac hypertrophy, lipid metabolism, blood viscosity, and coagulation indexes were analysed by histological staining or chemical methods, respectively. RESULTS: A total of 170 shared and specific seed genes of HQ and DS against CHD were identified. The shared and specific biological processes of HQ and DS against CHD were obtained. The LVEF and LVFS values significantly increased, the myocardium infarct size and fibrosis significantly decreased, the values of lipid metabolism indexes and blood viscosity indexes significantly reduced in the HQ + DS treatment group vs HQ or DS single treatment (P < 0.05); the LVEDd, LVEDs, and the CSA values significantly reduced in HQ single and HQ + DS treatment groups vs MI group (P < 0.05); the coagulation index (APTT, PT, TT, and FIB) values decreased significantly in the DS single and HQ + DS treatment groups vs MI group (P < 0.05). CONCLUSION: In MI rats, HQ and DS exhibited synergistic effects on improving cardiac function, reducing MI size, fibrosis, regulating hyperlipidaemia, and maintaining circulatory system homeostasis; HQ had the specific advantage of alleviating cardiac remodelling; DS had the specific advantage of regulating hypercoagulability. This study revealed that HQ and DS not only exerted synergistic effects but also exhibited complementary effects on CHD.

The Effectiveness and Safety of Bushen Huoxue Decoction on Treating Coronary Heart Disease: A Meta-Analysis.

OBJECTIVE: The aim of this meta-analysis was to systematically evaluate the effectiveness and safety of the traditional Chinese medicine (TCM) formula Bushen Huoxue Decoction (BSHXD) in treating coronary heart disease (CHD). METHODS: Randomized controlled trials (RCTS) of BSHXD in treating CHD were searched until March 2020, through six electronic databases: PubMed, Cochrane Library, CNKI, WanFang, SinoMed, and VIP. This study used the Cochrane Risk Test bias tool in the Cochrane Handbook to assess the quality of the methodology. Review Manager (RevMan) 5.3 was used to analyze the results. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria were applied in the classification of evidence quality. RESULTS: Ten RCTs involving 901 patients were finally included in this meta-analysis. It revealed that the effectiveness of BSHXD in treating CHD was significantly better than that of the conventional western medicine (CWM) treatment (P < 0.00001). The effective rate of BSHXD treatment group on ECG was also significantly higher than that of CWM group (P < 0.00001). The low-density lipoprotein cholesterol was decreased in the treatment groups compared with those in the control groups (P < 0.00001). There was also a reduction in frequency and duration of angina pectoris (P < 0.00001). There were no significant differences in TC level (P=0.08), TG level (P=0.86), and HDL level (P=0.76) between the treatment and control groups. Five studies had informed adverse events, including nausea and diarrhea. CONCLUSION: Our findings laid the foundation to the use of TCM Formula BSHXD in combination with conventional western medicine for treating CHD. However, due to the limitation of the quality of the included researches, in addition to potential reporting bias, the above conclusions still need verification by higher-quality and better-designed studies.

[Correlation between estrogen levels and coronary heart disease with kidney deficiency and intervention effect of kidney-tonifying traditional Chinese medicine].

With the process of urbanization and population aging in China, the burden of cardiovascular disease and the incidence of coronary heart disease among postmenopausal women have greatly increased. Studies have found that the incidence of coronary heart disease in postmenopausal women is closely related to the level of estrogen, but there are still difficulties of low efficiency and large side effects in current therapies. Kidney deficiency has a strong correlation with reproductive development and overall function. The clinical manifestations and characteristics of postmenopausal coronary heart disease patients conform to the pathogenesis of kidney deficiency in traditional Chinese medicine. The kidney-invigorating method has a good efficacy in treating postmenopausal coronary heart disease patients. This paper summarizes clinical and pharmacological evidences, expounds the relationship between kidney deficiency and the level of estrogen, and the pathological mechanism of the kidney-tonifying method in the treatment of coronary heart disease, and defines the clinical efficacy and advantages of the kidney-tonifying method. The method may become an effective method to prevent and treat postmenopausal coronary heart disease, and is expected to benefit patients with coronary heart disease better.

Health-related quality of life of hospitalized COVID-19 survivors: An initial exploration in Nanning city, China.

Understanding the health-related quality of life (HrQoL) of hospitalized COVID-19 survivors is an emerging global challenge arising from the current pandemic. A qualitative study of the experiences of sixteen hospitalized COVID-19 survivors from Nanning City, China, was conducted using semi-structured telephone interviews in May 2020. These first-hand accounts were critically and empirically analysed to identify emerging health and social issues, and provide potential solutions to improve survivors' quality of life. This in-depth, qualitative study of HrQoL for hospitalized COVID-19 survivors provides the first empirical evidence and conceptual framework with eight dimensions (physical symptoms, anxiety, trauma, economic loss, place-based identity, self-stigma, health self-interventions, and changing lifestyle) for understanding the physiological, psychological, socio-economic and health behavioral aspects of their daily lives. We argue that local and global governments should provide integrated healthcare, social and digital infrastructure to support this vulnerable group. More comparative and multi-disciplinary studies in this area are needed to generate academic standards of assessing health-related quality of life and produce good practice guidelines for promoting urban resilience in response to public health disasters.

Recovery of hypothalamus-pituitary-gonadal dysfunction after the treatment of suprasellar germ cell tumors.

OBJECTIVE: To investigate the incidence of hypothalamus-pituitary-gonadal (HPG) axis initiation/recovery after treatment and to identify predictive risk factors for noninitiation/recovery. METHODS: A total of 127 consecutive suprasellar germ cell tumor (GCT) patients managed at Peking Union Medical College Hospital (2006-2019) were retrospectively analyzed. Prepubertal patients (followed up until 13 years of age for girls and 14 years of age for boys) and patients with HPG dysfunction (followed up for 2 years) were divided into the initiation/recovery and noninitiation/recovery groups. RESULTS: Of the 127 suprasellar GCT patients, 75 met the follow-up criteria, 28 (37.3%) of whom experienced HPG axis initiation/recovery. Compared to the noninitiation/recovery group, the initiation/recovery group included more males and had shorter delayed diagnosis times, smaller tumor sizes, lower panhypopituitarism rates, thinner pituitary stalk widths, lower visual deficit rates, and higher serum testosterone and estradiol levels. The cutoff values of pituitary stalk width, tumor size, and delayed diagnosis time used to predict noninitiation/recovery were 6.9 mm, 6.9 mm and 1.7 years, respectively. Tumor size ≥6.9 mm (odds ratio (OR) = 7.5, 95% CI: 2.2-25.8, P = 0.001), panhypopituitarism (OR = 5.0, 95% CI: 1.4-17.6, P = 0.013), and delayed diagnosis time ≥1.7 years (OR = 5.7, 95% CI: 1.5-20.7, P = 0.009) were risk factors for noninitiation/recovery. CONCLUSIONS: Among suprasellar GCT patients, nearly one-third of prepubertal patients and patients with HPG dysfunction experience HPG axis initiation/recovery after treatment. Tumor size ≥6.9 mm, panhypopituitarism, and delayed diagnosis time ≥1.7 years were identified as predictive risk factors for noninitiation/recovery.

Preoperative autologous platelet pheresis reduces allogeneic platelet use and improves the postoperative PaO2/FiO2 ratio in complex aortic surgery: a retrospective analysis.

OBJECTIVES: An autologous platelet-rich plasma pheresis (aPP) strategy can harvest partial whole blood that is separated into erythrocytes, plasma and platelets, and can reduce blood loss and transfusion during cardiovascular surgery using cardiopulmonary bypass (CPB). However, the blood and organ conservation effects of this technique have not been confirmed in the context of complex aortic surgery. METHODS: Perioperative records of 147 adult patients who underwent complex aortic surgery were analysed retrospectively. RESULTS: All patients received regular blood conservation treatment, and 57 patients received aPP. Whether or not the participants were propensity matched, decreased platelet and cryoprecipitate transfusions were found in the aPP group (both P < 0.001), but there were non-significant differences in erythrocyte transfusion, Sequential Organ Failure Assessment scores and other outcomes when compared with the same parameters in the non-aPP group. The aPP group had a higher arterial oxygen partial pressure to inhaled oxygen concentration ratio on postoperative days 1, 2 and 7 than the non-aPP group (P < 0.001, P < 0.001 and P = 0.048, respectively). CONCLUSIONS: The utilization of aPP was associated with a reduction in allogeneic platelet and cryoprecipitate transfusions as well as minor lung-protective effects during complex aortic surgery using CPB.

Shengmai injection combined with conventional therapy in treating Adriamycin-related cardiotoxicity: A protocol for systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Tumor is a common and frequently-occurring disease that seriously threatens human health, and is one of the main causes of death. Adriamycin (ADM) is the most commonly used and effective anti-tumor chemotherapeutics in clinical practice, but they can cause severe cardiotoxicity, which obviously limits their clinical application. Shengmai injection is a modern injection form of traditional Chinese medicine widely used for heart failure, myocardial infarction, cardiogenic shock, and cardiotoxicity patients in China. Therefore, we design this systematic review and meta-analysis to assess the effectiveness and safety of Shengmai injection for treating ADM-related cardiotoxicity. METHODS: We will methodically search PubMed, EMBASE, Cochrane Library, Science Network, China National Knowledge Infrastructure, Wanfang Database, Chinese Journal Database, and China Biomedical Literature Database, in order to include randomized controlled trials which used Shengmai injection in treating ADM-related cardiotoxicity up to September 2020. The search strategies will use the following phrase: "Shengmai injection," "Adriamycin," "doxorubicin," "cardiotoxicity," "cardiomyopathy," "randomized controlled trial." The outcomes included cardiotoxicity rate, echocardiography, electrocardiogram, myocardial enzymes. Two researchers will independently select the study, extract the data and assess the quality by using Stata 14.0 and RevMan 5.3 software. The plan follows the preferred reporting items declared by the systematic review and meta-analysis plan, and the complete systematic review will follow the preferred reporting items for systematic reviews and meta-analysis (PRISMA) statement. CONCLUSION: The effectiveness and safety of Shengmai injection will be assessed in treating ADM-related cardiotoxicity which can give some evidence for clinical decision making. TRIAL REGISTRATION NUMBER: INPLASY202090040.

Effectiveness and safety of Suxiao Jiuxin pill in treating acute coronary syndrome: a systematic review and Meta-analysis.

OBJECTIVE: To evaluate the effectiveness and safety of Suxiao Jiuxin pill (SX) in acute coronary syndrome (ACS) treatment. METHODS: An extensive search of four English databases (Medline/PubMed, Cochrane Library, Embase, and World Health Organization International Clinical Trials Registration Platform) and four Chinese databases (Chinese National Knowledge Infrastructure, Wanfang, China Science and Technology Journal, and Chinese Biomedical Literature Service System) was performed. Randomized, controlled trials (RCTs) involving SX combined with conventional therapy versus conventional therapy were included. The extracted data included populations, interventions, outcomes, and risk of bias. The cardiovascular events served as the primary outcome. Review Manager 5.3 software was used for data analysis. Relative risks (RRs) with 95% confidence intervals (CIs) were the effect measure. RESULTS: A total of eight RCTs with 979 patients were included. There were 559 patients with unstable angina (UA) in six RCTs and 420 patients with acute myocardial infarction (AMI) in two RCTs. Our review showed that SX plus conventional therapy might reduce the incidence of the total endpoint (RR: 0.34, 95% CI: 0.17, 0.68, P = 0.002), with no obvious adverse events (RR: 1.29, 95% CI: 0.60, 2.77, P = 0.52) compared with conventional therapy for patients with UA. Additionally, SX plus conventional therapy also reduced the incidence of the total endpoint (RR: 0.35, 95% CI: 0.18, 0.68, P = 0.002) compared with conventional therapy in patients with AMI. SX plus conventional therapy also reduced the incidence of ventricular fibrillation (RR: 0.23, 95% CI: 0.10, 0.57, P = 0.001) compared with conventional therapy in patients with AMI. CONCLUSION: Our results suggest that SX is beneficial for treating patients with UA or AMI. However, our findings should be treated with caution because of the poor methodological quality of the included trials. Therefore, more multicenter, large-sample, high-quality RCTs are required to provide high-quality evidence.

Uncovering the protective mechanism of Huoxue Anxin Recipe against coronary heart disease by network analysis and experimental validation.

Coronary heart disease (CHD) is a leading cause of death and disability worldwide. Huoxue Anxin Recipe (HAR) is a novel Chinese Herbal Medicine formula of that has been used to treat CHD for several decades. Our previous study found that HAR had anti-oxidative effects, and could promote myocardial angiogenesis and improve cardiac function following myocardial infarction (MI) in rats. However, the active compounds, potential targets, and biological processes related to HAR have not been systematically investigated. Here, network pharmacology and experimental validation were used to study the protective mechanisms of HAR against CHD. We identified 124 active components, 124 verified targets, and 111 predictive targets. A total of 1192 genes related to CHD were identified by cDNA microarray and database analysis. A total of 47 putative targets of HAR against CHD were identified, including 32 verified targets and 15 predictive targets. ClueGo enrichment analysis identified 49 biological processes involved in the anti-CHD effects of HAR. Among them, the negative regulation of blood coagulation and regulation of collagen biosynthetic process were experimentally validated. After constructing a protein-protein interaction network and clustering with MECODE and ClusterONE, 162 key proteins (from ClueGo and clustering) were used to construct an internal interaction network. Complement C3 (C3), Fibrinogen alpha (FGA), Fibrinogen gamma (FGG), interleukin-6 (IL6), and Apolipoprotein A1 (APOA1) were the top 5 hub proteins identified by cytoHubber analysis. HAR limited the concentrations of C3, FGA, FGG, and IL6 and increased APOA1 levels. The results indicated that HAR could down-regulate blood coagulation, regulate collagen biosynthesis, inhibit peroxidation and inflammation injury, and promote cholesterol efflux. HAR could be a potential source of novel and effective drugs for CHD.

[Diagnosis and Treatment Recommendation and Exploration for Critical and Refractory Adverse Effects Related to Immunocheckpoint Inhibitors].

The application of immunological checkpoint inhibitors (ICIs) has modified many treatment strategies of malignant tumors, which has become a milestone in cancer therapy. The principle of action can be explained as "brake theory". After releasing the brakes by ICIs, unprecedented systemic toxicities, even some refractory and fatal immune-related adverse effects (irAEs) may develop. In this article, we summarized the recommended treatments of grade 3-4 severe irAEs in the latest European Society for Medical Oncology (ESMO), National Comprehensive Cancer Network (NCCN)/American Society of Clinical Oncology (ASCO), Society for Immunotherapy of Cancer (SITC) and Chinese Society of Clinical Oncology (CSCO) guidelines and consensus. We also performed a systemic review of case reports and reviews of irAEs up to May 20, 2019 in PubMed and Chinese journals. Successful applications of specific immunosuppressive drugs and stimulating factors beyond the above guidelines and consensus were supplemented and highlighted, including agents blocking interleukin 6 (IL-6), rituximab, anti-tumor necrosis factor-α (TNFα) monoclonal antibody (mAb), anti-integrin 4 mAb, Janus kinase inhibitors, thrombopoietin receptor agonists and antithymocyte globulin (ATG) etc. We put some concerns of using high-dose steroids for long-term, and emphasize the secondary infections, tumor progression, and unavailability of ICI re-challenge during steroid treatment. We propose the "De-escalation Therapy" principle for severe and refractory irAEs, and suggest that immunosuppressive drugs specifically targeting cytokines should be used as early as possible. Many irAEs in the era of immunotherapy are unprecedented compared with traditional chemotherapy and small-molecule targeted therapy, which is a big challenge to oncologists. Therefore, the establishment of multidisciplinary system is very important for the management of cancer patients.

Network Pharmacology-Based Prediction and Verification of the Targets and Mechanism for Panax Notoginseng Saponins against Coronary Heart Disease.

Coronary heart disease (CHD) is the worldwide leading cause for cardiovascular death. Panax notoginseng saponin (PNS), which is the main bioactive compound of panax notoginseng, has been generally accepted to exert a remarkable effect on CHD for a long time. However, to reveal the underlying treatment target and corresponding mechanism of PNS against CHD is still a substantial challenge. In this work, the targets and mechanism of PNS against CHD were successfully achieved by pharmacology-based prediction and experimental verification. 36 common targets were screened out through integrating the gene expression profile of CHD and the chemical-protein data of PNS. Then, two key nodes were further selected for verification by experiment after analyzing GO function, KEGG pathway, coexpression, and topology analysis. Results showed that PNS has protected the human umbilical vein endothelial cells from H2O2-induced oxidative stress by inhibiting early cell apoptosis via upregulating VEGFA mRNA expression. Therefore, our research has successfully pointed out one treatment target and apoptotic inhibition caused by PNS with method of integrating bioinformatics prediction and experimental verification, which has partially explained the pharmacological mechanism of PNS against CHD.

Sub-chronic Toxicity of Defoamer Used in Seawater Desalination.

OBJECTIVE: To explore the possible long-term health effects of the defoamer used in seawater desalination by sub-chronic toxicity testing. METHODS: Blood analysis, internal organ assessment, and histopathological examination were carried out in rats exposed to low, medium, and high (0.5, 1.0, and 2.0 g/kg BW, respectively) doses of defoamer for 90 days through oral administration. RESULTS: The high dose group showed decreased blood alanine aminotransferase and aspartate aminotransferase (P < 0.05). All doses resulted in a significant increase in albumin and decrease in globulin (P < 0.05). The direct bilirubin and indirect bilirubin were decreased in the medium and high dose groups (P < 0.05). All dose groups showed significant induction of alkaline phosphatase (P < 0.05). Pathological examination revealed a case of liver mononuclear cell infiltration in the medium dose group and three cases of liver congestion, steatosis of hepatic cells around the central vein, and punctate necrosis with multiple focal mononuclear cell infiltration in male rats administered the high dose. The No Observed Adverse Effect Level was 0.5 g/kg BW in rats, with albumin and total bilirubin as health effect indices. CONCLUSION: Long-term defoamer exposure may cause liver injury but has no significant impact on renal function in rats. The effect on blood cells in female rats was more prominent than that in male rats.

Cytotoxic phenolic constituents from Hypericum japonicum.

Nine undescribed compounds, including five xanthone derivatives, two flavonoids, one 2-pyrone derivative, and one undescribed naturally occurring compound, along with 30 known phenolic compounds, were isolated from Hypericum japonicum. In addition, hyperjaponols A and B were identified as racemates. The structures and absolute configurations of the undescribed compounds were determined by comprehensive MS, NMR spectroscopy, and electronic circular dichroism (ECD) calculations. The cytotoxic effects of the isolated compounds on two human tumour cell lines (HEL and MDA-MB-231) were evaluated by the MTT assay. Eighteen compounds showed good inhibitory activities against the HEL cell line, with IC50 values of 3.53-18.7 µM, while nine compounds exhibited moderate cytotoxicity against the MDA-MB-231 cancer cell line, with IC50 values ranging from 4.92 to 10.75 µM. Their preliminary structure-activity relationship of the isolated compounds was also discussed.