Clinical Efficacy of Chonglian Oral Liquid on COVID-19 Patients / 中国实验方剂学杂志

ObjectiveTo observe the effect of Chonglian oral liquid on inflammatory and immune markers as well as the clinical outcomes of patients with mild-to-moderate corona virus disease 2019（COVID-19） and comprehensively evaluate its efficacy and safety. MethodA clinical randomized controlled trial （RCT） was conducted， involving 120 confirmed cases of mild-to-moderate COVID-19. The patients were randomly divided into two groups， with 55 cases in the observation group and 56 cases in the control group. According to the updated diagnosis and treatment protocol， the control group received standard western medical treatment， while the observation group received Chonglian oral liquid in addition to standard western medical treatment. Both groups were treated continuously for 10 days. The traditional Chinese medicine （TCM） syndrome scores， syndrome efficacy， fever abatement time， nucleic acid negative conversion time， inflammatory and immune markers， improvement in imaging findings， clinical outcomes， and occurrence of adverse events were compared between the two groups. ResultBoth groups showed a significant decrease in TCM syndrome scores after treatment （P<0.01）. Compared with the control group after treatment， the observation group exhibited a more significant improvement in cough， dry throat， sore throat， fatigue， and muscle pain （P<0.05）. The total effective rate in the observation group was 100% （55/55）， significantly higher than 98.21% （55/56） in the control group （Z=3.707， P<0.01）. The observation group also showed a significantly shorter duration of fever abatement and nucleic acid negative conversion compared with the control group after treatment （P<0.05）. Both groups had a significant increase in lymphocyte count （LYM）， lymphocyte percentage （LYM%）， mature T lymphocytes （CD3+）， and helper/inducer T lymphocytes （CD4+） after treatment （P<0.01）. Compared with the control group after treatment， the observation group showed greater improvement in these markers （P<0.05）. In terms of inflammatory markers， both groups had a significant decrease compared with those before treatment （P<0.01）. The observation group exhibited lower levels of high-sensitivity C-reactive protein （hs-CRP）， interleukin-6 （IL-6）， and procalcitonin （PCT） than the control group after treatment （P<0.05）. There was no statistically significant difference in imaging efficacy evaluation and clinical outcomes between the two groups. No adverse events were reported in either group during the treatment period. ConclusionChonglian oral liquid combined with standard western medical treatment significantly improves clinical symptoms， shortens fever abatement and nucleic acid negative conversion time， regulates immune function， and inhibits inflammatory responses in patients with mild-to-moderate COVID-19， leading to improved clinical efficacy.

Screening of active components and preliminary mechanism exploration of Lycii Fructus for improving osteoporosis based on the zebrafish model / 药学学报

Juvenile zebrafish were used to screen the active components of Lycii Fructus for improving osteoporosis. The screening results were further verified by zebrafish adult osteoporosis model and the action mechanism was explored. Prednisolone was used as the inducer to build osteoporosis models of juvenile and adult zebrafish, and 9 groups of samples of different extracts and chemical parts of Lycii Fructus were given. Alizarin red staining was applied for observing the scale matrix mineralization and bone resorption. The activities of osteoblasts and osteoclasts were detected using alkaline phosphatase (ALP) and tartrate resistant acid phosphatase (TRAP/TRACP) staining. The expressions of bone metabolism-related genes alp, osteoprotectin (opn), osteoblast specific transcription factor (sp7), cathepsin K (ctsk), tracp, and Runt family transcription factor 2b (runx2b) in each group were determined using quantitative polymerase chain reaction. The results showed that all components of Lycii Fructus improved the formation area of the first vertebrae, the staining light density value, and the number of vertebrae joints in juvenile zebrafish and the Lycium barbarum polysaccharide (LBP) treatment group exerted the best effect. In addition, LBP prevented the formation of bone resorption lacunae in zebrafish scales, increased ALP activity, decreased TRAP activity, up-regulated the alp, sp7, and opn genes, and lowered the expressions of ctsk and tracp genes. In conclusion, LBP regulated the activity of osteoblasts and osteoclasts, reduced bone resorption, promoted bone formation and enhanced bone density, which might be the main anti-osteoporosis active fraction of Lycii Fructus. This study provided modern scientific evidence for the scientific connotation of the traditional effect of "strengthening bones and muscles" of Lycii Fructus, provided the reference for the evaluation of the anti-osteoporosis activity of traditional Chinese medicine based on zebrafish adult model, and provided beneficial enlightenment for the bone health needs of the aging society population.

Discussion on the Formation and Prevention Strategies of Chemotherapy Resistance of Malignant Tumor Based on “Yin Fire” Theory / 中医杂志

Chemotherapy is currently the main clinical treatment method for malignant tumors， and chemotherapy resistance is the main factor leading to chemotherapy failure and malignant tumor recurrence and metastasis. The cha-racteristics of malignant tumors formation were regarded as similar to the “Yin Fire” theory， manifested that deficiency of original qi as the foundation of malignant tumors， imbalance of original qi and yin fire as the internal cause of malignant tumor progression， and the internal environment of phlegm-blood stasis-toxicity-deficiency caused by yin fire promoted the formation of chemoresistance. In the treatment of chemoresistance of malignant tumors， traditional Chinese medicine should focus on treating disease before its onset by tonifying the spleen and strengthening the middle， nou-rishing the original qi， and reinforcing healthy qi and anti-cancer； during the treatment， the clinicians should regulate the qi and detoxify to clear yin fire， and improve the internal environment. Summarily， the strategies were adjusting the balance of internal environment of original qi and yin fire， and conducting a comprehensive treatment during the whole process， to provide new ideas for the treatment of chemoresistance of malignant tumors with traditional Chinese medicine.

Humic Acids Inhibit Platelet Activation to Reduce Venous Thromboembolism in Mice.

Objective: We aimed to investigate the effects of the natural product humic acids (HA) on platelet activation and development of venous thromboembolism (VTE) in mice and further explore the relevant mechanism. Methods: Eight-week C57BL/6 mice were randomly assigned to three groups: sham operation group (n = 7), VTE group (n = 8), and VTE + HA group (n = 10). Thrombi were harvested to hematoxylin-eosin staining to evaluate the thrombolysis and recanalization of the thrombus. In addition, flow cytometry was performed to detect the expression levels of protein disulfide isomerase on endothelial-derived exosomes and glycoprotein IIb/IIIa on the surface of the activated platelets surface in plasma. Furthermore, the protein expression level of glycoprotein IIb/IIIa in thrombus was determined by immunohistochemistry and immunofluorescence. Results: The length of thrombosis in the VTE + HA group was significantly shorter than that in the VTE group (P = 0.040). No significant differences were observed in thrombolysis and recanalization between the VTE + HA group and the VTE group (P > 0.05). The content of protein disulfide isomerase carried by endothelial-derived exosomes was significantly increased in the VTE group (P = 0.008) but significantly reduced by native humic acids (P = 0.012). Compared with the VTE group, the expression of glycoprotein IIb/IIIa on activated platelet surface in the VTE + HA group was significantly decreased (P = 0.002). The concentration of plasmatic P-selectin in the VTE group was significantly higher than that in the VTE + HA group (P < 0.001). Conclusion: We demonstrate that HA possess a pharmacological property that decreases venous thrombus formation in mice. The underlying mechanism is that HA could inhibit the expression of glycoprotein IIb/IIIa on the activated platelets surface by suppressing endothelial-derived exosomes carrying on protein disulfide isomerase, thereby blocking platelet activation.

Identification of anti-Parkinson's Disease Lead Compounds from Aspergillus ochraceus Targeting Adenosin Receptors A2A.

Two novel alkaloids compounds together with fifteen know metabolites were identified from Aspergillus ochraceus. The stereochemistry features of the new molecules were determined via HRESIMS, NMR, ECD, and XRD analyses. Amongst these, compounds two compounds exhibited potential efficacy as anti-Parkinson's disease with the EC50 values of 2.30 and 2.45 µM, respectively. ADMET prediction showed that these compounds owned favorable drug-like characteristics and safe toxicity scores towards CNS drugs. Virtual screening analyses manifested that the compounds exhibited not only robust and reliable interactions to adenosine receptors A2A , but also higher binding selectivity to A2A receptors than to A1 and A3 receptors. Molecular dynamics simulation demonstrated the reliability of molecular docking results and the stability of the complexes obtained with the novel compounds and A2A receptors in natural environments. It is the first time that anti-PD lead compounds have been identified from Aspergillus ochraceus and targeting adenosine A2A receptors.

Research Progress of Traditional Chinese Medicine in Improving Pathogenesis of Depression / 中国实验方剂学杂志

Depression is a kind of psychoaffective disorder，which is mainly characterized by persistent depression and mood disorders. It is related to many factors such as abnormal expression of neurotransmitters，secretion of inflammatory cytokines，changes in neuronal pathways，persistent disorder of hypothalamus-pituitary-adrenal （HPA） axis，changes of intestinal flora environment，abnormal mitochondria structure，and many other factors，which cause serious damage to human health. At present，western medicine is mainly treated with antidepressant drugs in clinical practice，which can exert short-term efficacy，but long-term use will cause adverse side effects. Traditional Chinese medicine（TCM） emphasizes the holistic view of psychosomatic integration and has rich clinical practice experience，which gives it a certain therapeutic advantages in the prevention and treatment of depression. Moreover，modern research has shown that TCM has played an important role in the prevention and treatment of depression through its multi-target，multi-mechanism and multi-pathway mode of action. In recent years，the study on TCM in treating depression has been deepening，and more and more TCM and TCM compounds have been proved to be able to regulate and improve the pathogenesis of depression and play an antidepressant role. Therefore，this paper systematically sorted out the research literature on TCM in improving the pathogenesis of depression in the past 5 years，and summarized and elaborated these literature according to the following topics：TCM affects the expression of neurotransmitters and their receptors，improves the plasticity of nerve cells and related signaling pathways，regulates the secretion of inflammatory factors and improves the disorder of HPA axis， TCM regulats intestinal flora environment to relieve depression， TCM adjusts the mitochondrial function of TCM to relieve depression. The study found that most of the TCM exert the antidepressant effect mainly by affecting the expression of neurotransmitters and improving neural signaling pathways，while the research on Chinese medicinals regulating and improving the intestinal flora environment and mitochondrial function is relatively rare，which needs further research to provide reference for better exploration of depression in the future.

Anti-PD-1/PD-L1 Blockade Immunotherapy Employed in Treating Hepatitis B Virus Infection-Related Advanced Hepatocellular Carcinoma: A Literature Review.

Hepatitis B virus (HBV) infection is regarded as the main etiological risk factor in the process of hepatocellular carcinoma (HCC), as it promotes an immunosuppressive microenvironment that is partially mediated by the programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) signaling pathway. The tumor microenvironment (TME) of HBV-related HCC is indeed more immunosuppressive than microenvironments not associated with viruses. And compared to TME in hepatitis C virus (HCV) infected HCC, TME of HBV-related HCC is less vascularized and presents different immune components resulting in similar immunosuppression. However, few studies are focusing on the specific side effects and efficacy of PD-1/PD-L1 blockade immunotherapy in HBV-related HCC patients, as well as on the underlying mechanism. Herein, we reviewed the basic research focusing on potential TME alteration caused by HBV infection, especially in HCC patients. Moreover, we reviewed PD-1/PD-L1 blockade immunotherapy clinical trials to clarify the safety and efficacy of this newly developed treatment in the particular circumstances of HBV infection. We found that patients with HBV-related HCC displayed an acceptable safety profile similar to those of non-infected HCC patients. However, we could not determine the antiviral activity of PD-1/PD-L1 blockade because standard anti-viral therapies were conducted in all of the current clinical trials, which made it difficult to distinguish the potential influence of PD-1/PD-L1 blockade on HBV infection. Generally, the objective response rates (ORRs) of PD-1/PD-L1 blockade immunotherapy did not differ significantly between virus-positive and virus-negative patients, except that disease control rates (DCRs) were obviously lower in HBV-infected HCC patients.

Nutrition and metabolism status alteration in advanced hepatocellular carcinoma patients treated with anti-PD-1 immunotherapy.

PURPOSE: The aim of this study was to evaluate the nutrition and metabolism status alteration during immunotherapy in advanced hepatocellular carcinoma (HCC) patients. METHODS: Patients with advanced HCC who participated in the clinical trials of single-agent anti-PD-1 immunotherapy or sorafenib were retrospectively included. We analyzed self-comparison of the nutritional and metabolic indices of patients in the anti-PD-1 and sorafenib treatment group. We conducted mutual-comparison of the mentioned indices between the disease progression group and disease control group among anti-PD-1 treatment patients. We further analyzed those indices with statistical differences by partial correlation and survival analysis. RESULTS: Both self-comparison before and after treatment in the anti-PD-1 group and mutual-comparison of disease progression and the control group showed significant differences in multiple indices, but we did not observe significant differences in the sorafenib group. Strikingly, albumin (ALB)/prognostic nutritional index (PNI, calculated by serum albumin and lymphocyte count) decreased distinctly in the immunotherapy disease progression group patients. However, changes in ALB/PNI were not significant in disease progression patients from the sorafenib group or in the disease control patients with immunotherapy. Partial correlation analysis suggested that ALB and PNI were positively correlated with the efficacy of immunotherapy. Furthermore, survival analysis showed that the median progression-free survival and median overall survival of patients in the ALB/PNI decreased group were significantly shorter than those of patients from the ALB/PNI increased group. CONCLUSION: Anti-PD-1 immunotherapy might alter the nutritional and metabolic status in advanced HCC patients. We also should pay attention to the nutritional and metabolic status of patients when drug resistance is detected.

A survey of multiple pesticide residues in pollen and beebread collected in China.

Honeybees, as major pollinators, make vital contributions to humans and ecosystems. Worryingly, a phenomenon known as honeybee colony losses has been reported in recent years. One of the factors underlying the occurrence of honeybee colony losses is exposure of honey bees to pesticide residues in their food, which cause detrimental sublethal effects and may lead to the collapse of their colonies. In this paper, 189 pollen samples and 226 beebread samples collected from five major beekeeping areas in China were analyzed from spring 2016 to autumn 2017. The most common active ingredient residues found include the insecticides (imidacloprid, thiamethoxam, fenpropathrin, bifenthrin and chlorpyrifos), the acaricides (coumaphos and fluvalinate) and the fungicides (carbendazim and triadimefon). Our data shows that the residual level of three chemicals (i.e. imidacloprid, thiamethoxam and chlorpyrifos) was higher in pollen than in beebread. Moreover, contamination of pollen and beebread was most serious in spring and in the middle and lower reaches of the Yellow River Area of China. Our data lay the foundation for the risk assessment of pesticides on honeybees in China.

Multi-Residue Analysis of Pesticide Residues in Crude Pollens by UPLC-MS/MS.

A multi-residue method for the determination of 54 pesticide residues in pollens has been developed and validated. The proposed method was applied to the analysis of 48 crude pollen samples collected from eight provinces of China. The recovery of analytes ranged from 60% to 136% with relative standard deviations (RSDs) below 30%. Of the 54 targeted compounds, 19 pesticides were detected. The major detection rates of each compound were 77.1% for carbendazim, 58.3% for fenpropathrin, 56.3% for chlorpyrifos, 50.0% for fluvalinate, 31.3% for chlorbenzuron, and 29.2% for triadimefon in crude pollen samples. The maximum values of each pesticide were 4516 ng/g for carbendazim, 162.8 ng/g for fenpropathrin, 176.6 ng/g for chlorpyrifos, 316.2 ng/g for fluvalinate, 437.2 ng/g for chlorbenzuron, 79.00 ng/g for triadimefon, and so on. This study provides basis for the research on the risks to honeybee health.

Fluoride Exposure, Follicle Stimulating Hormone Receptor Gene Polymorphism and Hypothalamus-pituitary-ovarian Axis Hormones in Chinese Women / 生物医学与环境科学（英文）

The effects of fluoride exposure on the functions of reproductive and endocrine systems have attracted widespread attention in academic circle nowadays. However, it is unclear whether the gene-environment interaction may modify the secretion and activity of hypothalamus-pituitary- ovarian (HPO) axis hormones. Thus, the aim of this study was to explore the influence of fluoride exposure and follicle stimulating hormone receptor (FSHR) gene polymorphism on reproductive hormones in Chinese women. A cross sectional study was conducted in seven villages of Henan Province, China during 2010-2011. A total of 679 women aged 18-48 years were recruited through cluster sampling and divided into three groups, i.e. endemic fluorosis group (EFG), defluoridation project group (DFPG), and control group (CG) based on the local fluoride concentration in drinking water. The serum levels of gonadotropin releasing hormone (GnRH), follicle stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) were determined respectively and the FSHR polymorphism was detected by real time PCR assay. The results provided the preliminary evidence indicating the gene-environment interaction on HPO axis hormones in women.

Experimental study on electric impedance of acupuncture based on the midnight-noon ebb-flow theory / 中国针灸

<p><b>OBJECTIVE</b>Relationship among three point selection methods based on the midnight-noon ebb-flow theory, namely Najia fa (day- prescription of acupoints), Nazi fa (hour-prescription of acupoints) and Yangzi Shike Zhuxue fa (point-open method based on the mother and son relation as well as the hours and its divisions), were approved in the article, which provided the scientific validity of the correlation among three point selection methods of midnight-noon ebb-flow theory.</p><p><b>METHODS</b>Electric impedance on relevant acupoints of 30 health subjects on the period of the day of Zishi (from 11:00 p.m. to 1:00 a.m.), Maoshi (from 5:00 a.m. to 7:00 a.m.), Wushi (from 11:00 a.m. to 1:00 p.m.) and Youshi (from 5:00 p.m. to 7:00 p.m.) were tested with NQ-1B conductivity meter. And statistical analysis was made on the testing results.</p><p><b>RESULTS</b>The daily average value of the method of Najia fa in 1 circle of the midnight-noon ebb-flow theory was 0.459omega, the value of the method of Nazi fa was 0.553omega, and the Yangzi Shike Zhuxue fa was 0.533omega. At the same time, it presented a tendency of first raising and then declining from Zishi to Youshi with the peak appears at Maoshi and the valley at Youshi. The differences of comparison of the average electric impedance between Najia fa and Nazi fa, Najia fa and Yangzi Shike Zhuxue fa were considered statistical significant (both P < 0.001). When 2 values of different methods within the same hours were compared, the value difference between Najia fa and Nazi fa in the time period of Wushi and the difference between Najia fa and Yangzi Shike Zhuxue fa in the time period of Wushi were considered statistical significant (P < 0.001, P < 0.01).</p><p><b>CONCLUSION</b>The changing tendency of electric impedance of different point selection methods based on midnight-noon ebb-flow theory is similar, however, with weak relevance. Moreover, obvious differences can still be found in point location and time selection.</p>

Antifugal susceptibility testing and antifugal traditional Chinese medicines screening of oral Candida isolated from head and neck cancer patients treated with radiotherapy or chemotherapy / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To evaluate the sensitivity and resistance of pathogenic oral Candida spp. isolated from head and neck cancer patients treated with radiotherapy or chemotherapy to antifungal agents. To screen antifugal agents from Chinese traditional and herbal drugs by NCCLS M27-A2 method.</p><p><b>METHODS</b>Using YBC Test Kit to identify 20 clinical oral Candida isolated from head and neck cancer patients treated with radiotherapy or chemotherapy. The in vitro susceptibilities of 20 oral Candida spp. to 5-flucytosine (5-FC), itraconazole (ITR), fluconazole (FLU), the extracts of 6 Chinese traditional and herbal drugs (caltrop, honeysuckle flower, dandelion, green tea, pine bark, red trefoil) and utility componets of 7 Chinese traditional and herbal drugs (sophorcarpidine, aloperine, archin, glycyrrhizic acid, glycosides of white peony root, glycosides of baikal skullcap root, hydrochloric berberine) were determined by NCCLS M27-A2 method.</p><p><b>RESULTS</b>The proportion of no-C. albicans in all Candida spp. were 25%. All strains were sensitive to 5-flucytosine, 25% stains were resistant to fluconazole and 40% stains were resistant to itraconazole. In all agents from Chinese traditional and herbal drugs, glycosides of white peony root and hydrochloric berberine (C20H18CINO4) exhibited antifungal activity, especially to C. glabrates.</p><p><b>CONCLUSION</b>The proportion of no-C. albicans in all oral Candida spp. isolated from head and neck cancer patients treated with radiotherapy or chemotherapy was pretty high. NCCLS M27-A2 micro-dilution method is a reliable and reproducible method and can be used to screen antifugal agents from Chinese traditional and herbal drugs.</p>

Inhibitory Effect of Chinese Herbal Compound Dongju on Tongue Carcinogenesis in Rats / 上海第二医科大学学报

Objective To examine the inhibitory effect of Chinese herbal Compound Dongju on 4-nitroquinoline 1-oxide(4NQO)-induced tongue carcinogenesis in rats. Methods A total of 85 Wistar rats were divided into four groups: model group(n=35),administration group(n=35),normal control group(n=5) and herb control group(n=10).4NQO dissolved in drinking water was administered orally to induce tongue carcinogenesis in rats.The herb compound was injected into the stomach of the rats during oral carcinogenesis.Rats were sacrificed at 9,13,20,24 and 32 weeks from the beginning of the experiment.The tongues of the rats were dissected for gross and histological assessment,and SP immunohistochemical method was also employed to detect the expression of cyclin D1 in the specimens. Results Compared with the model group,the incidence of dysplasia and the positive rate of cyclin D1 were suppressed by Compound Dongju(P