Cinobufagin disrupts mitosis and microtubule polymerization via targeting KATNB1 in cancer cells / 药学学报

Huachansu is a traditional Chinese medicine widely used in the clinic for cancer therapy, while the underlying mechanism is not fully clarified. This study was to investigate the targets and mechanisms of cinobufagin (CBG), an active component of Huachansu, in terms of blocking mitosis of cancer cells. Propidium iodide (PI) DNA staining was used to analyze the effect of CBG on cell cycle. The effect of CBG on mitosis of cancer cells was examined by α-tubulin and pericentrin staining after synchronization by a double thymidine block. Tubulin turbidity, tubulin polymerization and α‍-tubulin immunofluorescence assays were used to evaluate the effect of CBG on microtubule polymerization. CRISPR/Cas9 gene-editing technology was used to knockout microtubule-severing protein Katanin regulatory subunit B1 (KATNB1) in HCT116 cells, and the inhibitory effect of CBG on wild-type cells and knockout cells was measured by CCK-8. The engagement of CBG with KATNB1 was measured by CETSA and DARTS assays. The effect of CBG on KATNB1 protein and mRNA level was examined by Western blot and real-time PCR, respectively. Our data showed that CBG arrested HCT116 cell cycle at the G2/M phase, disrupted mitosis and induced centriole overduplication. CBG significantly inhibited tubulin polymerization in vitro and in vivo. The cytotoxicity of CBG inhibition on HCT116 was significantly attenuated upon KATNB1 depletion. Moreover, CBG bound to KATNB1 and decreased its protein level, while mutated KATNB1 weakened this effect. In conclusion, CBG inhibited microtubule polymerization via targeting KATNB1, thereby disrupting mitosis in cancer cells.

Establishment and application of quality evaluation method for Xiaochaihu Granules based on calibrator samples / 中国中药杂志

With reference to the production process documented in Chinese Pharmacopoeia, this paper prepared the calibrator samples of Xiaochaihu Granules from multiple batches and established a method for fingerprint analysis and content determination that could be used to evaluate Xiaochaihu Granules available in market. Multiple batches of Chinese herbal pieces contained in Xiaochaihu Granules were collected for preparing the calibrator samples according to the process in Chinese Pharmacopoeia. Following the establishment of fingerprints for calibrator samples by UHPLC, the method for determining the contents of saikosaponin B2, saikosaponin B1, baicalin, wogonoside, baicalein, liquiritin, glycyrrhizin G2 and glycyrrhizic acid in Xiaochaihu Granules was established. The experimental results showed that the fingerprints of calibrator samples had 26 common peaks, covering the chemical compounds of main herbs Bupleuri Radix, Scutellariae Radix, Changii Radix, Glycyrrhizae Radix et Rhizoma, and Rhizoma Zingiberis Recens. The similarity of fingerprints for 47 batches of Xiaochaihu Granules from 31 companies with the calibrator sample fingerprint ranged from 0.74 to 0.99, indicating good applicability of the established fingerprint. The contents of main components baicalin, saikosaponin B2, and glycyrrhizic acid in Xiaochaihu Granules were within the ranges of 22.917-49.108 mg per bag(RSD 19%), 0.28-2.19 mg per bag(RSD 62%), and 0.897-6.541 mg per bag(RSD 41%), respectively. The quality difference in saikosaponin B2, and glycyrrhizic acid among different manufacturers was significant. The fingerprint analysis and content determination method for calibrator samples of Xiaochaihu Granules prepared according to the production process in Chinese Pharmacopoeia has been proved suitable for evaluating the quality of Xiaochaihu Granules from different manufacturers. Saikosaponin B2, glycyrrhizic acid, and liquiritin should be added as content control indicators for Xiaochaihu Granules, aiming to further improve the product quality.

Research progress on chemical constituents and pharmacological activities of seabuckthorn and prediction of its Q-markers / 中国中药杂志

Seabuckthorn contains flavonoids, tannins, terpenoids, polysaccharides, and vitamins, which have anti-inflammation,anti-oxidation, liver protection, anti-cardiovascular disease, anti-aging, immune enhancing, anti-tumor, and anti-bacterial activities.We reviewed the papers focusing on the chemical constituents, pharmacological activities, and utilization of seabuckthorn. The quality markers(Q-markers) of seabuckthorn were predicted and analyzed based on original plant phylogeny, chemical composition correlation, traditional medicinal properties, pharmacodynamic correlation, traditional and extended efficacy, pharmacokinetics, metabolic processes, and measurable components. With this review, we aim to provide theoretical reference for the quality control and quality standard establishment of seabuckthorn, so as to promote the rational exploitation and utilization of seabuckthorn resources, and improve the healthy and sustainable development of seabuckthorn industry.

Comparative effectiveness and safety of 32 pharmacological interventions recommended by guidelines for coronavirus disease 2019: a systematic review and network meta-analysis combining 66 trials / 中华医学杂志(英文版)

BACKGROUND@#The global pandemic coronavirus disease 2019 (COVID-19) has become a major public health problem and presents an unprecedented challenge. However, no specific drugs were currently proven. This study aimed to evaluate the comparative efficacy and safety of pharmacological interventions in patients with COVID-19.@*METHODS@#Medline, Embase, the Cochrane Library, and clinicaltrials.gov were searched for randomized controlled trials (RCTs) in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)/SARS-CoV. Random-effects network meta-analysis within the Bayesian framework was performed, followed by the Grading of Recommendations Assessment, Development, and Evaluation system assessing the quality of evidence. The primary outcome of interest includes mortality, cure, viral negative conversion, and overall adverse events (OAEs). Odds ratio (OR) with 95% confidence interval (CI) was calculated as the measure of effect size.@*RESULTS@#Sixty-six RCTs with 19,095 patients were included, involving standard of care (SOC), eight different antiviral agents, six different antibiotics, high and low dose chloroquine (CQ_HD, CQ_LD), traditional Chinese medicine (TCM), corticosteroids (COR), and other treatments. Compared with SOC, a significant reduction of mortality was observed for TCM (OR = 0.34, 95% CI: 0.20-0.56, moderate quality) and COR (OR = 0.84, 95% CI: 0.75-0.96, low quality) with improved cure rate (OR = 2.16, 95% CI: 1.60-2.91, low quality for TCM; OR = 1.17, 95% CI: 1.05-1.30, low quality for COR). However, an increased risk of mortality was found for CQ_HD vs. SOC (OR = 3.20, 95% CI: 1.18-8.73, low quality). TCM was associated with decreased risk of OAE (OR = 0.52, 95% CI: 0.38-0.70, very low quality) but CQ_HD (OR = 2.51, 95% CI: 1.20-5.24) and interferons (IFN) (OR = 2.69, 95% CI: 1.02-7.08) vs. SOC with very low quality were associated with an increased risk.@*CONCLUSIONS@#COR and TCM may reduce mortality and increase cure rate with no increased risk of OAEs compared with standard care. CQ_HD might increase the risk of mortality. CQ, IFN, and other antiviral agents could increase the risk of OAEs. The current evidence is generally uncertain with low-quality and further high-quality trials are needed.

Effect of Modified Shengmaiyin on Children with Acute Lymphocyte Leukemia of Deficiency of Both Qi and Blood / 中国实验方剂学杂志

Objective:To observe the regulatory effect of modified Shengmaiyin adjuvant chemotherapy on the nutritional status and immune function of children with acute lymphocyte （ALL）. Method:One hundred children with ALL chemotherapy were randomly divided into observation group and control group. Both groups were given VDLD regimen as the induction therapy and CAM regimen as the early therapy. Control group was given Shengmaiyin orally， 10 mL/time， 3 times/day. Observation group was given modified Shengmaiyin orally， 1 does/day. The course of treatment for both groups was 3 months. Micro-nutrition assessment （MNA） was carried out before and after treatment， and serum total protein （TB）， albumin （ALB）， prealbumin （PAB）， T cell CD4⁺， CD8⁺， immunoglobulin G （IgG）， IgM， IgA levels were detected before and after treatment. The ratio of CD4⁺/CD8⁺ was calculated. The traditional Chinese medicine （TCM） syndrome before and after treatment and the piper fatigue scale （PFS-R） and universal core scale of children's quality of life （PedsQL） were scored. The changes of white blood cells （WBC）， red blood cells （RBC）， hemoglobin （Hb） and platelets （PLT） were evaluated before and after treatment. Result:The nutritional status of the observation group was better than that of the control group after treatment （<italic>Z</italic>=2.018， <italic>P</italic><0.05）. The observed fatigue was lighter than that of the control group （<italic>Z</italic>=2.029， <italic>P</italic><0.05）. The MNA score of the observation group was higher than that of the control group （<italic>P</italic><0.01）. The scores of PFS-R and deficiency of both Qi and blood were lower than those of the control group （<italic>P</italic><0.01）. The CD4⁺levels and CD4⁺/CD8⁺ levels of TB， ALB and PAB in the observation group were higher than those in the control group （<italic>P</italic><0.01）， while the CD8⁺ was lower than the control group （<italic>P</italic><0.01）. The IgM and IgA levels in the observation group were higher than those in the control group （<italic>P</italic><0.01）. The RBC， Hb and PLT levels of the observation group were higher than those of the control group （<italic>P</italic><0.01）. Conclusion:Modified Shengmaiyin can be used as adjuvant therapy for children with ALL chemotherapy by improving nutritional status， immune function and immune balance， reducing clinical symptoms， promoting the recovery of hematopoietic system and improving the quality of life.

Research Progress in Pharmacology of Xiaoyaowan / 中国实验方剂学杂志

In traditional Chinese medicine， it is believed that the spleen is the foundation of acquired nature and the source of Qi and blood. All life activities of a person since birth depend on the water and grain essence transported by spleen and stomach. The liver helps the spleen to strengthen the movement， the liver and spleen cooperate with each other. The liver and the spleen are invigorated， so that the Qi and blood are sufficient. The external energy can nourish the limbs， muscles and fur. The Qi and blood can be supplied to the internal organs， meridians and bones， and the body can be nourished both inside and outside to strengthen the acquired foundation. Emotional dissatisfaction can lead to stagnation of liver Qi， loss of spleen Qi， failure to dredge Qi， and deficiency of spleen Qi， forming the syndrome of liver depression and spleen deficiency. Its clinical manifestations include the symptoms of liver Qi stagnation such as depression， stamina， and chest fullness， as well as symptoms of spleen deficiency such as anorexia， abdominal distension， loose stools. Xiaoyaowan is an effective classic prescription for the treatment of liver stagnation and spleen deficiency syndrome， which is based on the dosage form of Xiaoyaosan in Prescriptions of the Bureau of Taiping People's Welfare Pharmacy. It has the effect of relieving depression， nourishing blood and invigorating spleen. In modern research， it has been found that Xiaoyaowan has good curative effect in the treatment of endocrine diseases， liver diseases， immune diseases， and neurological diseases， etc. It was praised by the famous medical scientist YE Tian-shi in the Qing Dynasty as "the holy medicine for women"， with a wide range of significant curative effects gynecology. Progress has been also made in pharmacological research. In this article， we have searched and consulted the relevant literature reports of Xiaoyaowan in recent years， summarized the key directions of the pharmacological research literature， and proposed deficiencies to provide relevant basis for the in-depth study of Xiaoyao pill in the future.

Network Pharmacology Study of Astragaloside Ⅳ in Treatment of Ischemic Stroke / 中国实验方剂学杂志

Objective:To study the mechanism of astragaloside Ⅳ in the treatment of ischemic stroke by means of network pharmacology. Method:The targets of astragaloside Ⅳ were predicted using Swiss Target Prediction platform， and the targets of ischemic stroke were retrieved using GeneCards， Therapeutic Target Database （TTD）， Traditional Chinese Medicine Integrated Database （TCMID） and Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） databases. The potential targets of astragaloside Ⅳ acting on ischemic stroke were obtained by the intersection of the targets of astragaloside Ⅳ and ischemic stroke. STRING platform was used to build protein-protein interaction （PPI） network， and eigenvalues were calculated through network topology analysis to screen core targets. Gene Ontology （GO） analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway analysis were performed on the related targets in DAVID database. Finally， molecular docking verification was conducted to further clarify the core targets of astragaloside Ⅳ acting on ischemic stroke. Result:The 44 common targets were obtained after the intersection of the targets of astragaloside Ⅳ and ischemic stroke. PPI network topology analysis showed that RAC-alpha serine/threonine-protein kinase （Akt1）， renin （REN）， epidermal growth factor receptor （EGFR）， vascular endothlial growth factor A （VEGFA） and neuronal proto-oncogene tyrosine-protein kinase （SRC） were the core targets of astragaloside Ⅳ in the treatment of ischemic stroke. Enrichment analysis results of KEGG pathway showed that the pathways of astragaloside Ⅳ acting on ischemic stroke involved the neuroactive ligand-receptor interaction pathway， cGMP-PKG signaling pathway， calcium signaling pathway， Rap1 signaling pathway， PI3K/Akt signaling pathway， etc. Conclusion:Astragaloside Ⅳ may promote angiogenesis and inhibit platelet activity by acting on Akt1， REN， EGFR， VEGFA， SRC， thus improving cerebral blood flow. It can also inhibit the apoptosis of ischemic brain tissue cells and inflammation to reduce the damage of nerve function， and finally treat ischemic stroke. This study provides ideas and guidance for further exploring the mechanism of astragaloside Ⅳ in the treatment of ischemic stroke.

Research Progress of Role of Autophagy in Rheumatoid Arthritis and Traditional Chinese Medicine Intervention / 中国实验方剂学杂志

For rheumatoid arthritis， glucocorticoids or immunosuppressive agents are currently used in clinical treatment， but long-term use of these drugs has large side effect on humans， and immunosuppressive agents are expensive. To a certain extent， its wide application is limited. The treatment of rheumatoid arthritis with traditional Chinese medicine（TCM） has a long history and little toxic and side effect， but its specific mechanism of action needs further exploration. The process of autophagy is an active biological process in which cells themselves are stimulated by the outside world through intracellular signal transduction to maintain a stable internal environment. Its abnormality is involved in the occurrence of many diseases. At present， studies have shown that abnormal autophagy is closely related to the occurrence and development of rheumatoid arthritis， which can interfere with the pathological changes of RA pannus formation， synovial inflammation and bone destruction and affect the disease process. In recent years， many studies have found that traditional Chinese medicine and its active ingredients can affect the pathological development of rheumatoid arthritis by regulating autophagy. This article investigates the relevant literature on the intervention of rheumatoid arthritis by regulating autophagy through using TCM， with a view to providing new ideas for basic research， new drug development and clinical treatment of rheumatoid arthritis.

Preparation of personalized traditional Chinese medicine condensed water pill without excipients based on correlation between concentrate viscosity and molding quality / 中国中药杂志

To explore the correlation between concentrate viscosity and molding quality of personalized traditional Chinese medicine(TCM) condensed water pill, this study established a concentrate viscosity characterization method with rotational rheometry. Seven model prescriptions were respectively concentrated to different degrees and the viscosity of each concentrate was determined. The pre-sence of 'viscosity jump' in the middle stage of 'flag hanging' of all the model prescriptions implied that there might be an ideal viscosity range in the preparation of condensed water pill. The further study of 22 model prescriptions demonstrated that the optimum viscosity range of concentrate was 5-15 Pa·s(25 ℃) for approximately 82% of the prescriptions. About 18% of the prescriptions had a wide range, which might be caused by the high proportions of mineral and crustacean drugs in the crushing part and sugar and fibrous drugs in the decocting part. This study clarified the optimum viscosity range for concentrates of personalized TCM condensed water pills and achieved a preparation technology without any excipient, laying a foundation for the on-line control of the preparation.

Effect of auricular point sticking therapy on perioperative pain in patients with partial lung resection / 中国针灸

OBJECTIVE@#To observe the analgesic effect of auricular point sticking therapy during the perioperative stage in the patients with partial lung resection.@*METHODS@#A total of 92 patients with partial lung resection were randomized into an auricular point group (31 cases, 1 case dropped off), the sham-auricular point group (30 cases) and a medication group (31 cases, 1 case dropped off). The routine medication for analgesia was provided in all of the three groups. In the auricular point group, 1 day before operation, the auricular point sticking therapy was applied at shenmen (TF@*RESULTS@#In 8, 16, 24, 48 h and 72 h after operation, VAS scores in the auricular point group were lower than those in the sham-auricular point group and the medication group separately (@*CONCLUSION@#Auricular point sticking therapy relieves perioperative pain, shortens analgesic time, releases anxious and depressive emotions and reduces postoperative adverse reaction in the patients with partial lung resection. The analgesic mechanism is probably related to the increase of plasma concentration of β-endorphin.

Comparison on Pharmacodynamics of Atractylodis Macrocephalae Rhizoma and Atractylodis Rhizoma from Four Different Sources on Rats with Qi Deficiency / 中国实验方剂学杂志

Objective:The effects of Atractylodes lancea， A. coreana， A. japonica， A. chinensis and Atractylodis Macrocephalae Rhizoma on spleen-Qi deficiency rats were compared. Method:A model of spleen-Qi deficiency was induced in rats by diet and overwork.The rats are given different suspensions of A.japonica， A.chinesis， A.coreana， A.lancea and Atractylodis Macrocephalae Rhizoma To test the indicators of the digestive system， immune system and antioxidant enzyme system related to spleen deficiency.Compare the similarities and differences between Atractylodis Macrocephalae Rhizoma and Atractylodis Rhizoma from four different sources. Result:All the drug-administered groups can increase the levels of γ interferon （IFN-γ）， gastric secrete element（GAS），serum amylase （AMS） and catalase（CAT） in rats with spleen-deficiency syndrome，in addition to the CAT index， the other indicators of the A. coreana， A.japonica， and A.lancea were significantly increased（P<0.05）. The MTL content of the A.chinesis， A.lancea， A.coreana and A.japonica increased and was significant（P<0.05）. The SDH content of A.japonica.and A.chinesis increased， and the difference was not significant.The increase of GSH-Px in the A.chinesis is significant（P<0.05）. All the drug-administered groups can reduce the content of IgG， TNF-α and MDA in rats with spleen deficiency and deficiency syndrome. Among them， the IgG content of the A.chinesis. and the A.lancea was significantly decreased（P<0.05）. The content of TNF-α in A.japonica group was significantly decreased（P<0.05）. The content of MDA in the A.chinesis， the A.lancea， the A.coreana，the A.japonica and the Atractylodis Macrocephalae Rhizoma were significantly decreased（P<0.05）.The decrease of IL-6 in the A.lancea was significant（P<0.05）. Conclusion:Four different sources of Atractylodes Rhizome and A.macrocephala have certain therapeutic effects on spleen-deficiency rats with deficiency syndrome.The therapeutic effect of A.lancea and A.japonica is basically the same，regulating the absorption，secretion and elimination of inflammation in the digestive system of rats with spleen deficiency A.coreana， A.chinesis， and Atractylodis Macrocephalae Rhizoma have certain regulatory effects in the digestive system， digestive tract inflammation， and antioxidant enzymes.

Discussing Differences of Different Traditional Chinese Medicine Schemes of COVID-19 Based on Principle of "Treatment in Accordance with Three Categories of Etiologic Factors" / 中国实验方剂学杂志

Since the outbreak of corona virus disease-2019 (COVID-19), the timely intervention of Chinese medicine has played an important role， it can significantly improve the clinical symptoms of patients, alleviate fever, cough, shorten the course of disease and reduce the conversion rate of mild disease to severe disease， moreover, it has obvious advantages in improving survival rate, prognosis and quality of life in patients. In order to make better use of the therapeutic effect of Chinese medicine and overcome the epidemic situation as soon as possible, various provinces, municipalities and autonomous regions have introduced local Chinese medicine treatment schemes in accordance with the geography, climate and epidemic situation. In this article, we have analyzed the similarities and differences among treatment schemes from the perspective of three factors, and it is believed that the onset season is the same for this disease, and the differences between treatment schemes mainly depend on geographical and climatic factors. The results showed that in seven regions of China, the early symptoms in warm and humid regions such as Central China, South China, East China and Southwest China were characterized by "wet, warm, hot, and toxic", and treatment schemes mainly adopted the recipes with clearing heat and detoxifying, strengthening spleen and removing dampness functions. The early symptoms in cold regions such as Northeast China, North China, and Northwest China were mostly characterized by "cold, wet, wind, and toxic", and the therapeutic recipes emphasized on the effects of expelling wind and cold, removing toxicity and dampness. Among them, the national plan with the Hubei epidemic situation as an important reference has gradually evolved from a single syndrome attribute of each period to both cold and hot syndromes with multiple treatment methods. With the development of the disease, epidemic toxin and toxic heat in the lungs are the main characteristics in the medium term, when the treatment mainly focuses on purging heat and removing toxins. In severe cases and advanced stage, internal block and outward desertion are the main symptoms, when the treatment mainly focuses on block dredging and relieving desertion. In the recovery period, deficiency of lung and spleen Qi, and deficiency of Qi and Yin are the main symptoms, when the treatment is mainly used to invigorate the spleen, tonify the lungs, and nourish Qi and Yin. The physical factors are mostly reflected in the prevention program, so they are rarely mentioned in the treatment program. The Chinese medicine treatment schemes of COVID-19 in different regions show obvious differences. It is of great significance to analyze these differences and sum up the corresponding laws for the differential prevention and treatment of infectious diseases like COVID-19.

Syndrome Differentiation-based Treatment of COVID-19 Based on Theory of Wenyilun / 中国实验方剂学杂志

The outbreak of corona virus disease-2019 (COVID-19) in Wuhan, China, in December 2019, is highly contagious and epidemic, and belongs to the category of "plague" in traditional Chinese medicine, which seriously threatens human life and health. In the face of this sudden public health event, based on the theory of Wenyilun, this paper analyzes the onset characteristics, transmission, and syndrome differentiation-based treatment of COVID-19 in clinical practice. According to the characteristics of this epidemic, the pathogeny of COVID-19 is "epidemic pathogenic factors", and the pathogenesis is that the epidemic suppresses the dampness. Its transmission follows the regularity of "nine transmissions between exterior and interior" recorded in Wenyilun, which can be divided into sequential transmission and reverse transmission. The course of the disease has certain regularity and stages. In the early stage, the pathogen hides in the pleurodiaphragmatic interspace, and the epidemic suppresses the dampness， the treatment shall reach the pleurodiaphragmatic interspace, clear the dampness and turbidness, diffuse the lungs and dredging the lung meridian. In the middle stage, the pathogen can be transmitted to the exterior， the treatment shall be pungent in flavor and cool in property and could relieve the exterior syndrome, so as to remove the pathogen by shivering and sweating. If the dampness toxin enters the interior and be transmitted into the heat, and caused damage to the lung meridian, obstruction of Qi in the lungs, interior excess and heat accumulation, the treatment shall dredge bowel and purge heat, and expel the pathogen out. Any delay in treatment, mistreatment or excessive pathogen can lead to pathogenic invasion into the pericardium, and cause delirium, dysphoria, reversal cold of limbs, barely palpable pulse and other critical manifestations of internal blocking causing external depletion. The treatment shall focus on both attack and supplement, open blocking and relieve depletion. In the recovery period, due to the residual pathogen and the Yin and Qi impairment caused by fever, the treatment shall prevent the recurrence of the residual pathogen, nourish Yin and blood, and restore the vital energy. During the treatment, WU You-ke put forward three principles of "removing the pathogen as the priority, and then avoiding false sweating, and caring for the spleen and stomach". The theory of Wenyilun has a systematic understanding of the pathogeny, pathogenesis, and syndrome differentiation-based treatment of "the epidemic", and provides valuable experience for fight against plagues in later generations, which is also of great significance for the prevention and treatment of COVID-19.

Mechanism of Inflammatory Storm Induced by Novel Coronavirus Pneumonia and Intervention Measures of Traditional Chinese Medicine / 中国实验方剂学杂志

Some patients with corona virus disease-2019 (COVID-19) experienced a severe exacerbation of the disease due to the occurrence of inflammatory storm during the development of the disease. They are complicated with acute respiratory distress, multiple organ dysfunction syndrome and other serious complications, with a poor prognosis and a high mortality. For the inflammation storm, western medicine mostly adopts glucocorticoids, nutritional support, artificial ventilation assistance and other measures at present. The development of artificial liver, blood purification therapy, extracorporeal membrane oxygenation and other technologies have also reduced the mortality of patients to some extent. However, due to the high requirements for equipment, the measures have not yet been widely carried out. From the perspective of traditional Chinese medicine(TCM), the basic pathogenesis of COVID-19 is epidemic toxin invasion, lung and spleen being affected by pathogens, damaging vital Qi, and pathological properties involving dampness, heat, poison, stasis and deficiency. At the stage of inflammation storm, the pathogens are abundant, while the vital Qi is deficient， and the pathogens occlude lung, and disturb the heart and mind, and blood stasis and toxicity are combined with Qi-Yin deficiency. In severe cases, even both Yin and Yang exhaustion occurs. At present, a number of studies have shown that a variety of Chinese herbal medicines have multi-target immunomodulatory effect on viral pneumonia and cytokine storm. TCM participates in whole process of the occurrence and development of inflammation storm, mainly eliminating pathogens in early stage, controlling inflammation and blocking occurrence of inflammation storm， eliminating pathogens and strengthening the body resistance to eliminate the pathological products of the inflammation storm, and promoting the dissipation and absorption of inflammation in the middle stage， and saving lives in late stage by benefiting Qi and relieving depletion, and restoring Yang and rescuing from collapse. On the basis of pathophysiological mechanism of COVID-19 inflammation storm and the theory of TCM syndrome differentiation and treatment, this paper summarized the pharmacological studies on intervention on inflammatory storm with relevant Chinese herbal medicine, Chinese medicine prescriptions and Chinese medicine preparations, and discussed the intervention measures of TCM in different development stages of inflammatory storm, in expectation of providing the guidance for clinical treatment.

Psychological Adjustment During Outbreak of COVID-19 Based on Traditional Chinese Medicine Emotion Therapy / 中国实验方剂学杂志

The outbreak of corona virus disease-2019 (COVID-19) not only endangers the public life and health, but also poses threats to the public mental health. Under the atmosphere of tension and fear, the public often produces adverse emotional reactions to psychological stress, and even has extreme behaviors, which seriously affects physical and mental health. Traditional Chinese medicine （TCM） emotional therapy is based on the TCM consciousness theory in adherence to the holistic view of "integration of mind and body". It adopts safe and effective emotional conditioning methods to regulate mood, eliminate bad emotions, maintain mental health, and enhance the body's immunity to achieve the effect of treating or preventing physical and mental diseases. It has differentiated applications in many medical fields, such as post-traumatic stress disorder, generalized anxiety disorder, cancer and hospice, with good clinical efficacy. By analyzing the theoretical origin, research status, application range of TCM sentiment therapy, as well as the current public psychological state of the COVID-19 epidemic, we innovatively proposed TCM sentiment therapies, such as calm emotion method, diversion of attention method, suggestive induction method, obedient mind method, music delight method, TCM refreshing method and auricular pressing method, and comprehensively applied them in the public psychological adjustment during the outbreak, with the aim to provide rational and effective psychological guidance, help the public to correctly understand various bad emotions during the outbreak, enhance their abilities to cope with it and adjust psychological problems, maintain a good mentality, and pass the epidemic period smoothly. At the same time, in order to make better use of the advantages of TCM sentiment therapy and benefit the public, it is advocated to widely apply TCM sentiment therapy in similar public health events and public psychological care in the daily life, for the purpose of preventing before disease outset and preventing progress of disease, and effectively protecting the physical and mental health of the people.

A systematic pharmacological investigation of pharmacologically active ingredients in Toujie Quwen granules for treatment of COVID-19 / 南方医科大学学报

OBJECTIVE@#To explore the pharmacologically active ingredients in granules (TJQW) for treatment of coronavirus disease 2019 (COVID-19) in light of systemic pharmacology.@*METHODS@#We performed database search, literature mining and drug-like index screening to identify the bioactive components in TJQW, the positive drugs for disease treatment and their therapeutic targets. The core disease target was investigated based on the cross-linking interaction of the bioactive components, positive drug and potential disease target, and the target proteins at the key nodes were analyzed by GO and KEGG analyses. Based on the therapeutic targets for COVID-19, virtual screening was conducted to screen the compounds in TJQW and construct the network cross-linking the key bioactive molecules in TJQW, key node targets of the disease, and the related biological pathways.@*RESULTS@#We identified 159 compounds in TJQW and obtained 18 core proteins based on the cross-linking of the bioactive components, positive drugs and disease targets. The key node targets consisted of 22 targets including the latest 4 COVID-19 proteins. Virtual screening results showed that at least 14 compounds could bind with the core disease target proteins. The material basis of TJQW for COVID-19 treatment was explained in multi-pathway, multi-component and multi-target perspectives. In terms of the structural characteristics of the compounds, we screened the top 30 molecules with strong binding with the target proteins, among which flavonoids were the predominant components.@*CONCLUSIONS@#This investigation reveals the therapeutic mechanism of TJQW for COVID-19 involving multiple components, targets and pathways from the perspective of key bioactive molecules, disease key node targets and related biological pathways. We screened 30 active precursors from TJQW, which provides reference for the clinical application and further development of TJQW.

Effects of Electroacupuncture on Brain Function of APP/PS1 Mice: A Functional Magnetic Resonance Imaging Study / 中国康复理论与实践

Objective:To investigate the effects of electroacupuncture at Baihui (DU20) and Shenting (DU24) on brain function of APP/PS1 mice. Methods:Sixteen 4-month-old APP/PS1 mice in the same litter were randomly divided into model group (n = 8) and electroacupuncture group (n = 8). Eight transgenic negative mice in the same litter were as control group. The electroacupuncture group accepted electroacupuncture at Baihui and Shenting for 16 weeks. They were assessed with Object Recognition Test before and after intervention, and observed under small animal functional magnetic resonance imaging with regional homogeneity (ReHo) analysis. Results:Compared with the control group, the discrimination ratio decreased in the model group after intervention (P < 0.05), while it increased in the electroacupuncture group compared with that in the model group (P < 0.05). Compared with the control group, ReHo of right basal forebrain and left hippocampus decreased in the model group before intervention. Compared with the control group, ReHo decreased in bilateral hippocampus group and increased in retrosplenial cortex in the model group after intervention; while it increased in bilateral hippocampus and motor cortex and decreased in anterior cingulate gyrus in the electroacupuncture group compared with that in the model group. Conclusion:Electroacupuncture at Baihui and Shenting may delay the decline of learning and memory ability in Alzheimer's disease model mice, which may relate to the regulation of functional activities in hippocampus.

Effects of Electroacupuncture on White Matter Fibers and Learning-memory Function in Rats with Vascular Dementia / 中国康复理论与实践

Objective:To observe the effect of electroacupuncture at Baihui (DU20) and Shenting (DU24) acupoints on white matter fiber and learning-memory function in rats with vascular dementia (VD). Methods:Sprague-Dawley rats were randomly divided into operation group and sham group (n = 8). The operation group accepted two-vessel occlusion, while the sham group only separated the bilateral common carotid arteries without ligation. The rats modeled successfully were randomly divided into model group (n = 8), non-acupoint group (n = 8) and electroacupuncture group (n = 8). The electroacupuncture group accepted electroacupuncture at Baihui and Shenting, and the non-acupoint group accepted electroacupuncture at axillary non-acupoint, once a day for 28 days. All the rats were tested with object recognition test before and after intervention, while the white matter fibers were observed with Diffusion Tensor Imaging. Results:Compared with the sham group, the preference coefficients of the model group, the non-acupoint group and the electroacupuncture group decreased before intervention (P< 0.05), and there was no significant difference among the later three groups (P> 0.05). The preference coefficients increased in the electroacupuncture group compared with the model group after intervention (P< 0.05). The fractional anisotropy (FA) of corpus callosum, cingulate gyrus and hippocampus decreased in the model group, the non-acupoint group and the electroacupuncture group compared with the sham group before intervention. FA of hippocampus, cingulate gyrus, corpus callosum and external capsule increased in the electroacupuncture group compared with the model group after intervention. Conclusion:Electroacupuncture at Baihui and Shenting can improve learning-memory function of VD rats, which may be related with repairment of white matter fibers in prefrontal cortex, hippocampus and others.

Anticancer effects of curzerenone against drug-resistant human lung carcinoma cells are mediated via programmed cell death, loss of mitochondrial membrane potential, ROS, and blocking the ERK/MAPK and NF-κB signaling pathway.

PURPOSE: The main objective of the current study was to examine the anticancer effects of Curzerenone - a naturally occurring sesquiterpene against gemcitabine-resistant lung carcinoma cells. The effects of Curzerenone on mitochondrial-mediated apoptosis, ROS, and ERK/MAPK and NF-kB signalling pathways were also investigated in the present study. METHODS: Cell proliferation was evaluated by MTT assay. Apoptosis was detected by acridine orange (AO)/ethidium bromide (EB) and DAPI staining as well as flow cytometry using annexin V apoptosis assay. The effects on reactive oxygen species (ROS) as well as mitochondrial membrane potential (MMP) were examined by flow cytometry. Protein expression was examined by western blotting. RESULTS: It was found that Curzerenone induced potent antiproliferative effects against the gemcitabine-resistant lung cancer cells and exhibited an IC50 of 24 µM. The anticancer effects of curzerenone were due to the induction of apoptosis which was also associated with alteration of apoptosis-related proteins (Bax,Bcl-2). Curzerenone also caused ROS-mediated alterations in the MMP. Curzerenone induced cell death in gemcitabine-resistant lung cancer cells by activating p38 MAPK/ERK signalling pathway while NF-kB pathway was inhibited in a dose-dependent manner. CONCLUSIONS: In conclusion, the current results strongly indicate that Curzerenone may prove a potential anticancer drug candidate against drug-resistant lung cancer.

Expert consensus statement on Danshen Chuanxiongqin Injection in clinical practice / 中国中药杂志

Danshen Chuanxiongqin Injection is a commonly used medicine in cerebral infarction and coronary heart disease,which is recommended by many disease guidelines/consensus for cardiovascular and cerebrovascular diseases. However,there are irrational drug using in clinic,which affects the efficacy and brings safety risks. Based on clinical research evidence and expert experience,recommendations/consensus suggestion are determined through the nominal group method. The expert consensus recommends the indications,intervention time for treatment,route of drug administration,usage and dosage,course of treatment and introduces the safety in clinical application,which could provide reference for clinical use of Danshen Chuanxiongqin Injection.