Effects of Chaihu Shugan San on Brain Functional Network Connectivity in the Hippocampus of a Perimenopausal Depression Rat Model.

In this study, we used Chaihu Shugan San (CSS), a traditional Chinese herbal formula, as a probe to investigate the involvement of brain functional network connectivity and hippocampus energy metabolism in perimenopausal depression. A network pharmacology approach was performed to discover the underlying mechanisms of CSS in improving perimenopausal depression, which were verified in perimenopausal depression rat models. Network pharmacology analysis indicated that complex mechanisms of energy metabolism, neurotransmitter metabolism, inflammation, and hormone metabolic processes were closely associated with the anti-depressive effects of CSS. Thus, the serum concentrations of estradiol (E2), glutamate (Glu), and 5-hydroxytryptamine (5-HT) were detected by ELISA. The brain functional network connectivity between the hippocampus and adjacent brain regions was evaluated using resting-state functional magnetic resonance imaging (fMRI). A targeted metabolomic analysis of the hippocampal tricarboxylic acid cycle was also performed to measure the changes in hippocampal energy metabolism using liquid chromatography-tandem mass spectrometry (LC-MS/MS). CSS treatment significantly improved the behavioral performance, decreased the serum Glu levels, and increased the serum 5-HT levels of PMS + CUMS rats. The brain functional connectivity between the hippocampus and other brain regions was significantly changed by PMS + CUMS processes but improved by CSS treatment. Moreover, among the metabolites in the hippocampal tricarboxylic acid cycle, the concentrations of citrate and the upregulation of isocitrate and downregulation of guanosine triphosphate (GTP) in PMS + CUMS rats could be significantly improved by CSS treatment. A brain functional network connectivity mechanism may be involved in perimenopausal depression, wherein the hippocampal tricarboxylic acid cycle plays a vital role.

Mapa de evidências sobre a efetividade clínica da acupuntura: informe executivo. / Evidence map on clinical effectiveness of acupuncture: executive report

Este informe executivo apresenta os principais achados do mapa de evidências sobre os efeitos da Acupuntura para desfechos em saúde, que representa a evidência de 163 estudos de revisão que analisaram o efeito da acupuntura como intervenção para pelo menos um dos 96 desfechos de saúde organizados em 14 grupos: Câncer e Neoplasias; Dor; Doenças Cardiovasculares; Doenças Respiratórias; Doenças Reumáticas e Musculoesqueléticas; Doenças Nutricionais, Metabólicas e Endócrinas; Doenças do Sistema Nervoso; Dermatopatias; Gastroenteropatias; Indicadores Metabólicos e Fisiológicos; Oftalmopatias e Otorrinolaringopatias; Sinais e Sintomas; Transtornos Mentais; e Outros desfechos. No todo foram 201 associações entre acupuntura e os desfechos de saúde. Para cada associação intervenção-desfecho foi incluído o efeito reportado pelo estudo de revisão.

This executive report presents the main findings of the evidence map on the effects of acupuncture for health outcomes, representing evidence from 163 review studies that analyzed the effect of acupuncture as an intervention for at least one of the 96 health outcomes organized into 14 groups: Cancer and Neoplasms; Pain; Cardiovascular Diseases; Respiratory Diseases; Rheumatic and Musculoskeletal Diseases; Nutritional, Metabolic, and Endocrine Diseases; Diseases of the Nervous System; Dermatopathies; Gastroenteropathies; Metabolic and Physiological Indicators; Ophthalmopathies and Otorhinolaryngopathies; Signs and Symptoms; Mental Disorders; and Other outcomes. In total, there were 201 associations between acupuncture and health outcomes. For each intervention-outcome association, the reported effect by the review study was included.

Este informe ejecutivo presenta los principales hallazgos del mapa de evidencia sobre los efectos de la acupuntura en los resultados de salud, representando la evidencia de 163 estudios de revisión que analizaron el efecto de la acupuntura como intervención para al menos uno de los 96 resultados de salud organizados en 14 grupos: Cáncer y Neoplasias; Dolor; Enfermedades Cardiovasculares; Enfermedades Respiratorias; Enfermedades Reumáticas y Musculoesqueléticas; Enfermedades Nutricionales, Metabólicas y Endocrinas; Enfermedades del Sistema Nervioso; Dermatopatías; Gastroenteropatías; Indicadores Metabólicos y Fisiológicos; Oftalmopatías y Otorrinolaringopatías; Signos y Síntomas; Trastornos Mentales; y Otros resultados. En total, hubo 201 asociaciones entre la acupuntura y los resultados de salud. Para cada asociación intervención-resultados se incluyó el efecto informado por el estudio de revisión.

Guanxinning tablets improve myocardial hypertrophy by inhibiting the activation of MEK-ERK1/2 signaling pathway.

Myocardial hypertrophy may lead to heart failure and sudden death. As traditional Chinese medicine, Guanxinning tablets (GXN) have significant pharmacological effects in the prevention and treatment of cardiovascular diseases. However, the anti-cardiac hypertrophy efficacy of GXN and its mechanism of action are still unclear. Therefore, we established a heart failure rat model and isolated primary cardiomyocytes of neonatal rat to observe the protective effect of GXN on heart failure rat model and the intervention effect on myocardial cell hypertrophy, and to explore the possible mechanism of GXN preventing and treating myocardial hypertrophy. The results of in vivo experiments showed that GXN could significantly reduce the degree of cardiac hypertrophy, reduce the size of cardiomyocytes, inhibit the degree of myocardial remodeling and fibrosis, and improve cardiac function in rats with early heart failure. The results of in vitro experiments showed that GXN was safe for primary cardiomyocytes and could improve cardiomyocyte hypertrophy and reduce the apoptosis of cardiomyocytes in pathological state, which may be related to the inhibition of the over-activation of MEK-ERK1/2 signaling pathway. In conclusion, GXN may inhibit cardiac hypertrophy and improve early heart failure by inhibiting the over-activation of MEK-ERK1/2 signaling pathway.

Feeding Aquilaria sinensis Leaves Modulates Lipid Metabolism and Improves the Meat Quality of Goats.

Aquilaria (A.) sinensis is a medicinal plant widely grown in tropical South China. Given the abundant pruning waste of its leaves, the use of A. sinensis leaves is valuable. In this study, goats were fed a diet containing 20% A. sinensis leaves. Compared with the basal diet, feeding A. sinensis leaves to goats did not affect growth performance but considerably reduced the feeding cost. Strikingly, feeding A. sinensis leaves resulted in a significant decrease in the blood cholesterol levels (2.11 vs. 1.49 mmol/L, p = 0.01) along with a significant increase in the high-density lipoprotein levels (1.42 vs. 1.82 mmol/L, p = 0.01). There was also a tendency to lower the content of low-density lipoprotein levels in goats (0.78 vs. 0.45 mmol/L, p = 0.09). Furthermore, metabolomics analysis demonstrated that the reduction in cholesterol levels occurred in both the serum (0.387-fold change) and muscle (0.382-fold change) of goats during A. sinensis leaf feeding. The metabolic responses to feeding A. sinensis leaves suggest that the activation of lipolysis metabolism might happen in goats. These observed changes would be conducive to improving animal health and meat quality, ultimately benefiting human health.

Mechanism of Banxia Baizhu Tianma decoction to prevent the development of prehypertension and excessive phlegm-dampness syndrome in rats based on metabonomics technology / 药学学报

The alterations of serum biological endogenous chemicals in rats with phlegm dampness accumulation syndrome of prehypertension (PHT) were interfered by Banxia Baizhu Tianma decoction (BBT), and the metabolic regulatory pathway of BBT was clarified using serum metabonomics analysis. To replicate the rat model of prehypertension phlegm dampness syndrome, blood pressure, behavioral markers, and serum biochemical markers of rats were collected. BBT's effectiveness in controlling blood pressure and blood lipids was assessed, and changes in endogenous small molecules in rat serum were determined using UPLC-Q-Orbitrap MS metabolic analysis. The results showed that BBT could regulate 9 metabolites, including arachidonic acid, cholic acid, glycodeoxycholic acid, N-adenosyltyrosine, arginine, lysophosphatidylethanolamine (20:0/0:00), lysophospholipid (P-18:0), lysophospholipid (18:0), lysophospholipid (22:5(7Z,10Z,13Z,16Z,19Z)). MetaboAnalyst was used to analyze the metabolic pathway. There were 7 metabolic pathways closely related to the change of blood pressure in rats, among which arachidonic acid metabolic pathway was the most critical. The metabolism difference foreign body in the model rats tends to return to the normal level, which provides a research basis for the mechanism of BBT from the perspective of metabonomics. This study was approved by the Experimental Animal Welfare Ethics Review Committee of Shandong University of Traditional Chinese Medicine (approval number: SDUTCM20211103001).

Acupuncture-moxibustion for essential hypertension: an overview of systematic reviews / 针灸推拿医学（英文版）

Objective: To propose reasonable suggestions to promote the standardization of clinical studies by reviewing the systematic reviews and meta-analyses of acupuncture-moxibustion treatment of essential hypertension (EH). Methods: Computer retrieval was conducted through Excerpta Medica Database (EMBASE), PubMed, China National Knowledge Infrastructure (CNKI), Chongqing VIP Database (CQVIP), China Biology Medicine Disc (CBM), and Wanfang Academic Journal Full-text Database (Wanfang) to collect systematic reviews and meta-analyses relevant to treating EH with acupuncture-moxibustion therapy. The time range was from the database's inception till July, 2020. The studies were screened based on the inclusion and exclusion criteria and then data-extracted. The study's quality and evidence ratings were performed by referring to the preferred reporting items for systematic review and meta-analysis (PRISMA), a measurement tool to assess systematic reviews 2 (AMSTAR 2), and the grading of recommendations, assessment, development, and evaluation (GRADE). Results: A total of 14 studies, 10 in Chinese and 4 in English, published between 2012 and 2019, were included, involving 70 outcome measures. The methodological quality was rated as critically low, the reporting was relatively complete or had certain flaws, and the evidence strength was rated as low or very low. Conclusion: Regarding the acupuncture-moxibustion treatment of EH, the methodological quality and outcome measure evidence of existing systematic reviews and meta-analyses are relatively low, and the reporting quality also expects further improvements.

Characterization of the complete chloroplast genome of Polygonatum franchetii Hua, a Chinese endemic medicinal species, and phylogenetic relationships of Polygonatum / 药学学报

italic>Polygonatum franchetii Hua is a medicinal plant endemic to China from Polygonatum Mill. The chloroplast genomes of two P. franchetii individuals sampled from two different habitats were sequenced by using the DNBSEQ-T7 high-throughput sequencing platform. After assembly and annotation, the two complete chloroplast genomes were characterized, and then comparative and phylogenetic analyses were performed with other published chloroplast genome sequences from Polygonatum. The whole chloroplast genomes of the two P. franchetii individuals were 155 942 and 155 962 bp in length, with a large single copy region (LSC, 84 670 and 84 722 bp), a small single copy region (SSC, 18 564 and 18 566 bp) and a pair of reverse repeats (IRa/IRb, 26 354 and 26 337 bp), respectively. Both of them contained 113 genes, including 79 protein-coding genes (PCGs), 30 transfer RNA (tRNA) genes, and 4 ribosomal RNA (rRNA) genes. Comparative analyses showed that the genome length, the guanine and cytosine (GC) content, genes content and order were highly conserved between the two P. franchetii individuals and among different Polygonatum species. The detected repeat sequences, including dispersed repeats, tandem repeats and simple sequence repeats (SSRs), were also relatively similar in types and positions, though showing a slightly difference in number. No significant expansion or contraction of the inverted repeat regions was found. Sequences variation between the two P. franchetii individuals was lower than that among different Polygonatum species. Besides, coding sequences (CDS) showed less divergence than noncoding sequences, and sequence divergence of IRs regions was lower than that of the LSC and SSC regions, both intraspecifically and interspecifically. Eight sequences with high nucleotide diversity among different species were screened, all of which were found located in the LSC and SSC regions. Phylogenetic inference showed that all Polygonatum species clustered into a monophyletic clade with a 100% bootstrap value, within which, species in section Verticillata formed a distinct group, section Sibirica and section Polygonatum were sister groups. The two P. franchetii individuals grouped together and showed the closest phylogenetic affinity to P. stenophyllum Maxim., belonging to the section Verticillata. The chloroplast genome of P. franchetii and its phylogenetic position in Polygonatum were comprehensively investigated and clearly elucidated in this study, the results may lay a foundation for the resource development and utilization of P. franchetii, as well as further molecular identification and phylogenetic studies of medicinal Polygonatum species.

Component identification and analysis in vivo of Sanhan Huashi formula / 中国中药杂志

Sanhan Huashi formula(SHF) is the intermediate of a newly approved traditional Chinese medicine(TCM) Sanhan Huashi Granules for the treatment of COVID-19 infection. The chemical composition of SHF is complex since it contains 20 single herbal medicines. In this study, UHPLC-Orbitrap Exploris 240 was used to identify the chemical components in SHF and in rat plasma, lung and feces after oral administration of SHF, and heat map was plotted for characterizing the distribution of the chemical components. Chromatographic separation was conducted on a Waters ACQUITY UPLC BEH C_(18)(2.1 mm×100 mm, 1.7 μm) using 0.1% formic acid(A)-acetonitrile(B) as mobile phases in a gradient elution. Electrospray ionization(ESI) source was used to acquire data in positive and negative mode. By reference to quasi-molecular ions and MS/MS fragment ions and in combination with MS spectra of reference substances and compound information in literature reports, 80 components were identified in SHF, including 14 flavonoids, 13 coumarins, 5 lignans, 12 amino-compounds, 6 terpenes and 30 other compounds; 40 chemical components were identified in rat plasma, 27 in lung and 56 in feces. Component identification and characterization of SHF in vitro and in vivo lay foundations for disclosure of its pharmacodynamic substances and elucidation of the scientific connotation.

Guanxinning tablet inhibits the interaction between leukocyte integrin Mac-1 and platelet GPIbα for antithrombosis without increased bleeding risk.

Recent studies have showed that thrombosis is closely related to leucocytes involved in immunity. Interfering with the binding of leukocyte integrin Mac-1 and platelet GPIbα can inhibit thrombosis without affecting physiological coagulation. Mac-1-GPIbα is proposed as a potential safety target for antithrombotic agents. Guanxinning tablet (GXNT) is an oral Chinese patent medicine used for the treatment of angina pectoris, which contains phenolic acid active ingredients, such as salvianolic acids, ferulic acid, chlorogenic acid, caffeic acid, rosmarinic acid, tanshinol, and protocatechualdehyde. Our previous studies demonstrated that GXN exhibited significant antithrombotic effects, and clinical studies suggested that it did not increase bleeding risk. In addition, GXN exerted a significantly regulatory effect on immune inflammation. In the current study, we intended to evaluate the effects of GXN on bleeding events and explore the safety antithrombotic mechanism of GXN based on leukocyte-platelet interaction. First, we established a gastric ulcer model induced by acetic acid in rats and found that GXN not only did not increase the degree of gastrointestinal bleeding when gastric ulcer occurred, but also had a certain promoting effect on the healing of gastric ulcer. Second, in vitroexperiments showed that after pretreatment with GXN and activation by phorbol 12-myristate-13-acetate (PMA), the adhesion and aggregation of leukocytes with human platelets were reduced. It was also found that GXN reduced the expression and activation of Mac-1 in leucocytes, and inhibited platelet activation due to leukocyte engagement via Mac-1. Overall, the results suggest that GXN may be a safe antithrombotic agent, and its low bleeding risk mechanism is probably related to inhibited leukocyte-platelet aggregation and its interaction target Mac-1-GPIbα.

Influence of acupuncture needle physical-chemical properties on needling quality.

OBJECTIVES: This study analyzed the physical-chemical properties of three different brands of acupuncture needle, classified by acupuncturists as high (A), medium (B) and low (C) quality. METHODS: Experienced acupuncturists, rated, in terms of perceived needling quality, three acupuncture needle brands as high (A), medium (B) and low (C) quality. Next, scanning electron microscopy (SEM) images of the tip and surface finish of the needles of each brand were analyzed. A mechanical test was developed and performed to evaluate the compressive force required to insert the needles through a smooth surface (silicon). In addition, X-ray fluorescence spectroscopy (XRF) and dispersive energy spectroscopy (DES) were conducted to analyze the material composition of the needles and presence of oxidation. RESULTS: SEM images revealed that needle brands A and B presented a sharper tip and a more regular surface finish in comparison to brand C. In the insertion test, needle brands A and B had similar performance characteristics, with A requiring less force to penetrate the silicon device when compared to B, while C failed to penetrate the silicon and complete the test. The XRF analysis did not reveal any differences in material composition between the three brands. However, brand C exhibited particles embedded on the needle surface and DES confirmed oxidation. CONCLUSION: This study demonstrates that perceived needling quality by acupuncturists can be correlated with physical-chemical properties of the needles, especially those related to finishing quality of the tip and the surface of the needles.

Effectiveness of intravaginal electrical stimulation combined with electromyography biofeedback-mediated pelvic floor muscle training for postpartum symptomatic pelvic organ prolapse: protocol for the PROSPECT randomized trial.

BACKGROUND: Pelvic organ prolapse (POP) is seen in up to 30-70% of women presenting for routine gynecology care and 10% of women suffering from bothersome POP symptoms. Vaginal childbirth is one of the most prominent contributing factors for POP. Pelvic muscle training (PFMT) is considered effective to improve mild to moderate POP symptoms. In addition, higher-intensity, supervised PFMT aided by biofeedback and electrical stimulation may confer greater benefit. However, the long-term efficacy of the PFMT combined with electromyography biofeedback is unknown, which indicates the need for further evidence. METHODS: This multicenter randomized controlled trial compares the effectiveness and cost-effectiveness of conventional PFMT versus biofeedback-mediated PFMT plus neuromuscular electrical stimulation (NMES) for postpartum symptomatic POP women. The primary outcome is the proportion of patients with the improvement of at least one POP-Q stage at 36 months after randomization. The primary economic outcome measure is incremental cost per quality-adjusted life year at 36 months. Two hundred seventy-four women from four outpatient medical centers are randomized and followed up with pelvic floor examination, questionnaires, and pelvic ultrasonography imaging. All participants are arranged for three appointments over 12 weeks. NMES and electromyography biofeedback via intravaginal probe are added to PFMT for participants in the biofeedback-mediated PFMT group. Group allocation could not be blinded from participants and healthcare staff that deliver intervention but remain masked from medical staff that carry out PFM assessment. An intention-to-treat analysis of the primary outcome will estimate the difference of the proportion of POP-Q stage improvement between the trial groups right after the intervention, and during the follow-up until 36 months, using the chi-square test and multilevel mixed models respectively. A logistic regression analysis was used for adjusting for important baseline variables that are unbalanced. DISCUSSION: The trial results will provide evidence of the effectiveness of electromyography biofeedback-mediated PFMT in improving women's POP-Q staging, quality of life, and cost-effectiveness. TRIAL REGISTRATION: CCTR Registry ChiCTR210002171917 . Registered on March 6, 2019.

Acupoint Injection Decreases Anesthetic Cosumption during Combined Spinal-Epidural and Patient-Controlled Epidural Labor Analgesia.

OBJECTIVE: To explore if acupoint injection can improve analgesic effects or delivery outcomes in parturients who received combined spinal-epidural analgesia (CSEA) and patient-controlled epidural analgesia (PCEA) for labor analgesia. METHODS: A total of 307 participants were prospectively collected from July 2017 to December 2019. The participants were randomized into the combined acupoint injection with CSEA plus PCEA group (AICP group, n=168) and CSEA plus PCEA group (CP group, n=139) for labor analgesia using a random number table. Both groups received CSEA plus PCEA at cervical dilation 3 cm during labor process, and parturients of the AICP group were implemented acupoint injection for which bilateral acupoint of Zusanli (ST 36) and Sanyinjiao (SP 6) were selected in addition. The primary outcome was Visual Analogue Scale (VAS) score, and the secondary outcomes were obstetric outcomes and requirement of anesthetics doses. Safety evaluations were performed after intervention. RESULTS: The VAS scores were significantly lower in the AICP group than in the CP group at 10, 30, 60, and 120 min after labor analgesia (all P<0.05). The latent phase of the AICP group was shorter than that of the CP group (P<0.05). There were less additional anesthetics consumption, lower incidences of uterine atony, fever, pruritus and urinary retention in the AICP group than those in the CP group (all P<0.05). CONCLUSION: Acupoint injection combined CSEA plus PCEA for labor analgesia can decrease the anesthetic consumption, improve analgesic quality, and reduce adverse reactions in the parturients. (Registration No. ChiMCTR-2000003120).

The antifungal activity of caspofungin in combination with antifungals or non-antifungals against Candida species in vitro and in clinical therapy.

INTRODUCTION: Candida species have been regarded as global health threats due to their ability to cause invasive infections. It is challenging to treat Candida bloodstream infections, which are associated with high mortality levels. Monotherapy with antifungals is sometimes not effective against severe Candida infections, and combination therapy is needed in clinical practice. AREAS COVERED: This review was undertaken based on data from a PubMed search for English language reports published before March 2021 by using the terms 'caspofungin,' 'Candida species,' 'combination therapy,' 'antifungal effect,' and 'novel antifungal agent.' EXPERT OPINION: Combination therapy is an empirical strategy for treating refractory Candida infections. Caspofungin has been recommended to treat candidaemia. Caspofungin in combination therapy has some applications, while the efficacy of combination therapy in the treatment of refractory Candida infections needs more study, such as randomized controlled trials. In addition, novel compounds or drugs with potential antifungal activities have been examined, and some of them exhibit synergistic interactions with caspofungin. Thus, the antifungal activity of caspofungin in combination with antifungals or non-antifungals against Candida species in vitro and in clinical therapy is summarized.

Varieties and standards of Corydalis medicinal plants / 中国中药杂志

Through literature research and standard retrieval, Corydalis-derived medicinal materials, the origins, and related standards were summarized. Finally, 27 medicinal materials were screened out, involving 71 species(varieties). Among them, only 11 are recorded in Chinese Pharmacopoeia(2020), National Standard for Chinese Patent Drugs·Tibetan Medicine, Tibetan Medicine Standards, and other local standards, including Corydalis Bungeanae Herba and Corydalis Herba. The names and original plants of the medicinal materials are different in different standards, and the phenomena of "same medicinal material with different names" and "same name for different medicinal materials" are prominent. Most standards only include the traits, microscopic identification, and physico-chemical property identification, with unsound quality criteria. Thus, efforts should be made to strengthen the sorting of Corydalis medicinal plants, herbal textual research, and investigation of the resources and utilization. Moreover, via modern techniques, the chemical components and medicinal material basis of different original plants should be explored and sound quality standards should be established to improve the safety and quality of Corydalis-derived medicinal materials. Summarizing Corydalis medicinal plants, Corydalis-derived medicinal materials, and related standards, this study is expected to provide a reference for the standard formulation, quality evaluation, expansion of drug sources, and rational development and utilization of Corydalis resources.

Acupoint Injection Decreases Anesthetic Cosumption during Combined Spinal-Epidural and Patient-Controlled Epidural Labor Analgesia / 中国结合医学杂志

OBJECTIVE@#To explore if acupoint injection can improve analgesic effects or delivery outcomes in parturients who received combined spinal-epidural analgesia (CSEA) and patient-controlled epidural analgesia (PCEA) for labor analgesia.@*METHODS@#A total of 307 participants were prospectively collected from July 2017 to December 2019. The participants were randomized into the combined acupoint injection with CSEA plus PCEA group (AICP group, n=168) and CSEA plus PCEA group (CP group, n=139) for labor analgesia using a random number table. Both groups received CSEA plus PCEA at cervical dilation 3 cm during labor process, and parturients of the AICP group were implemented acupoint injection for which bilateral acupoint of Zusanli (ST 36) and Sanyinjiao (SP 6) were selected in addition. The primary outcome was Visual Analogue Scale (VAS) score, and the secondary outcomes were obstetric outcomes and requirement of anesthetics doses. Safety evaluations were performed after intervention.@*RESULTS@#The VAS scores were significantly lower in the AICP group than in the CP group at 10, 30, 60, and 120 min after labor analgesia (all P<0.05). The latent phase of the AICP group was shorter than that of the CP group (P<0.05). There were less additional anesthetics consumption, lower incidences of uterine atony, fever, pruritus and urinary retention in the AICP group than those in the CP group (all P<0.05).@*CONCLUSION@#Acupoint injection combined CSEA plus PCEA for labor analgesia can decrease the anesthetic consumption, improve analgesic quality, and reduce adverse reactions in the parturients. (Registration No. ChiMCTR-2000003120).

Effects of Qingre Huoxue Jiedu Formula on Nerve Growth Factor-Induced Psoriasis / 中国结合医学杂志

OBJECTIVE@#To elucidate the mechanisms of 4 effective components from a Chinese medicine formula, namely Qingre Huoxue Jiedu Formula (QHJ heat- and toxin-clearing and blood-activating formula), in the treatment of nerve growth factor (NGF)-induced psoriasis.@*METHODS@#Keratinocyte proliferation and T cell proliferation models were developed using NGF. An NGF solution (NGF+DMEM, 100 ng/mL) was added to all induced groups and treated groups and were cultured for 24 h, while a solution with NTRK1 antagonist (K252a+DEME, 300 nmol/L) was added and cultured for 1 h. The models were used to evaluate the effects of the treatment with each of the 4 components of QHJ, namely shikonin, paeonol, astilbin and ursolic acid. Cell apoptosis and proliferation were measured by flow cytometry analysis and CCK8 assay, respectively. The mRNA expression levels of Bax, Bcl-xl, and NGF receptor (NGFR) were assessed by quantitative real-time PCR (qRT-PCR) and Western blot analysis, respectively.@*RESULTS@#(1) All QHJ-treated groups showed significantly increased cell apoptosis and inhibition of cell proliferation compared with the NGF-induced groups (P<0.05). In addition, treatment with QHJ plus NTRK1 significantly enhanced cell apoptosis and inhibition of cell proliferation compared with cells treated with QHJ only (P<0.05), particularly in cells treated with ursolic acid. (2) QHJ-treated groups showed higher protein expression levels of Bax, Bcl-xl compared with other groups (P<0.05). Additionally, treatment with QHJ plus NTRK1 significantly increased the protein expression levels of Bax, Bcl-xl and NGFR compared with those treated with QHJ only (all P<0.05), especially in those treated with shikonin.@*CONCLUSION@#The action mechanism of QHJ on psoriasis might be through enhancing cell apoptosis and inhibition of cell proliferation, and upregulating the expression level of Bax, Bcl-xl and NGFR.

Observation of the efficacy and safety of the Song-Relaxing and Zhen-Vibrating abdomen manipulation for patients with prediabetes / 针灸推拿医学（英文版）

Objective: To observe the safety of the Song-Relaxing and Zhen-Vibrating abdomen manipulation in treating patients with prediabetes and its effects on blood glucose and lipid metabolism.Methods: One hundred and two patients with prediabetes were divided into a manipulation group and a control group according to the random number table method, with 51 cases in each group. All patients received the general behavioral intervention for prediabetes, with additional Song-Relaxing and Zhen-Vibrating abdomen manipulation in the manipulation group and oral metformin hydrochloride tablets in the control group. Both groups received the intervention for six months. Results: Fourteen patients dropped out during the treatment, and a total of 88 patients completed the trial, including 45 cases in the manipulation group and 43 cases in the control group. After the treatment, the prediabetes control rate was 93.3％ in the manipulation group and 74.4％ in the control group, and the difference between the two groups was statistically significant (P<0.05); no patient in the manipulation group progressed to diabetes, while the rate of conversion to diabetes in the control group was 6.9％, with a significant difference between the two groups (P<0.05). After the treatment, the body mass index (BMI), glycosylated hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), 2-hour postload plasma glucose (2hPG) level during an oral glucose tolerance test (OGTT), fasting insulin (FINS), homeostasis model assessment-2 of insulin resistance (HOMA2-IR), total cholesterol (TC), and triglycerides (TG) decreased in both groups versus baseline, with significant differences within the groups; the levels of all indicators were lower in the manipulation group than in the control group (P<0.05), and the differences between the two groups were more prominent at the sixth month (P<0.01). At the sixth month, the high-density lipoprotein cholesterol (HDL-C) in the manipulation group was increased, while there was no significant change in the control group. In the control group, three patients reported mild gastrointestinal reactions at the initial dosing, which improved after medication adjustment. No other adverse events were observed in either group. Conclusion: Both metformin hydrochloride tablets and the Song-Relaxing and Zhen-Vibrating abdomen manipulation can improve blood glucose and lipid metabolism and reduce insulin resistance and clinical discomfort in patients with prediabetes, but the Song-Relaxing and Zhen-Vibrating abdomen manipulation has higher efficacy and safety.

Mechanism of Arnebia euchroma Against Melanoma： An Exploration Based on Network Pharmacology and Experimental Verification / 中国实验方剂学杂志

ObjectiveTo preliminarily predict the active components， action targets， and signaling pathways of Arnebia euchroma in the treatment of melanoma based on network pharmacology and molecular docking， and to verify its possible mechanism of action in in vitro experiments. MethodThe active components and related targets of A. euchroma were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）SwissTargetPrediction and literature， and the targets related to melanoma from the GeneCards， Online Mendelian Inheritance in Man （OMIM）， and Comparative Toxicogenomics Database （CTD）. Following the construction of the protein-protein interaction （PPI） network of active components and related targets of A. euchroma and melanoma-related targets using STRING， Cytoscape 3.8.2 was used for screening and analyzing the nodes in the network of A. euchroma against melanoma. The intersections were subjected to gene ontology （GO） and Kyoto encyclopedia of genes and genomes （KEGG） enrichment analysis using DAVID 6.8. Acetyl alkannin， the active component in A. euchroma， was docked to the target by AutoDock Vina 1.1.2. The in vitro experiments were then carried out to verify the anti-melanoma effect of A. euchroma. ResultA total of 271 common targets of A. euchroma and melanoma were harvested， among which 23 were key targets， including matrix metalloproteinase-9 （MMP-9） and Janus kinase 2 （JAK2）. As revealed by KEGG enrichment analysis， A. euchroma mainly acted on Janus kinase/signal transduction and activator of transcription （JAK/STAT）， tyrosine kinase receptor （ErbB）， and vascular endothelial growth factor （VEGF） signaling pathways to resist melanoma. According to molecular docking， acetyl alkannin exhibited a good docking activity with JAK2， STAT3， VEGF， MMP-9， and E-cadherin receptors. The results of Western blot and Real-time quantitative polymerase chain reaction （Real-time PCR） showed that acetyl alkannin at different doses inhibited the protein and gene expression of JAK2， STAT3， VEGF， MMP-9， and E-cadherin in A375 cells （P<0.05）. ConclusionA. euchroma alleviates melanoma via multiple targets and multiple pathways， and it may exert the therapeutic effects by affecting the expression of such key target proteins as JAK2， STAT3， VEGF， MMP-9， and E-cadherin and inhibiting the invasion and metastasis of melanoma cells. This study has provided an experimental basis for the treatment of tumor with A. euchroma.

Mechanism of Sinitang against Myocardial Ischemia-reperfusion Injury： Prediction Based on Network Pharmacology and Verification by Cellular Experiments / 中国实验方剂学杂志

ObjectiveTo predict the mechanism of Sinitang in treating myocardial ischemia-reperfusion injury （MI/RI） based on network pharmacology and verify the prediction results by cellular experiments. MethodThe traditional Chinese medicine system pharmacology database and analysis platform （TCMSP） was employed for retrieval of the main components and potential targets of Sinitang. Online Mendelian Inheritance in Man （OMIM） and GeneCards were employed to obtain the targets of Sinitang in treating MI/RI. STRING was employed to construct the protein-protein interaction （PPI） network， and DAVID to perform gene ontology （GO） annotation and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment. Finally， cellular experiments were carried out to verify the predicted anti-MI/RI mechanism of Sinitang. ResultA total of 105 active ingredients and 234 targets of Sinitang were screened out， among which 116 targets were predicted to be involved in the treatment of MI/RI. The GO annotation gave 587 entries， including 417 biological process entries， 101 cell component entries， and 69 molecular function entries. The KEGG analysis enriched 125 signaling pathways， involving vascular endothelial growth factor （VEGF）， phosphoinositide 3-kinase/protein kinase B （PI3K/Akt）， forkhead box transcription factor O （FoxO）， hypoxia-inducible factor-1 （HIF-1） apoptosis and other signaling pathways. The results of cell viability assay showed that Sinitang increased the survival rate of H9C2 cells damaged by hypoxia/reoxygenation （H/R）. Sinitang decreased the levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and creatine kinase-MB （CK-MB） in H9C2 cells damaged by H/R. The results of flow cytometry demonstrated that Sinitang decreased the apoptosis rate of H9C2 cells damaged by H/R. Western blot showed that Sinitang down-regulated the expression of Bcl-2 related X protein （Bax） and up-regulated that of B-cell lymphoma-2 （Bcl-2） in H/R-injured H9C2 cells. ConclusionSinitang treats MI/RI in a multi-target and multi-pathway manner， which involves the signaling pathways associated with apoptosis.

Harvesting and Primary Processing in Fritillaria Medicinal Materials： A Review / 中国实验方剂学杂志

Chinese medicinal material from Fritillaria， Beimu in Chinese， is a commonly used antitussive and expectorant traditional Chinese herbal medicine， with the significant functions of clearing heat and moistening lung，resolving phlegm and relieving cough. Five kinds of Fritillaria were recorded in the 2020 edition of Chinese Pharmacopoeia， including Fritillariae Cirrhosae Bulbus， Fritillariae Ussuriensis Bulbus， Fritillariae Thunbergii Bulbus， Fritillariae Hupehensis Bulbus and Fritillariae Pallidiflorae Bulbus. At present， the reports on Fritillaria mainly focus on the pharmacological effect， chemical composition， identification of authenticity and other aspects， while there were few reports on harvesting and primary processing of original medicinal materials. Fritillaria medicines were perennial medicinal plant with various and complex varieties， their quality and curative effect were greatly affected by harvesting and processing in producing area. The processing method differed according to its variety. Fritillariae Cirrhosae Bulbus mainly from western Sichuan plateau， Fritillariae Pallidiflorae Bulbus from Xinjiang and Fritillariae Ussuriensis Bulbus from Northeast China were mostly harvested from June to July and sun dried directly or dried. But Fritillariae Thunbergii Bulbus and Fritillariae Hupehensis Bulbus from Yangtze River basin were harvested when the plants wilted at the beginning of summer， and auxiliary materials such as shell powder and lime must be added during the processing. At present， the drying methods of Fritillaria were still traditional， which is not suitable for large-scale production of cultivated products. Therefore， it is urgent to find a scientific， reasonable and efficient processing methods. Aimed at providing references for standardization production of Fritillaria， this paper made a textual research on the ancient and modern herbal literature， the Chinese Pharmacopoeia and other medicinal standards， combined with modern literature， the harvesting and processing methods of Fritillaria were sorted out and prospected.