The chemometrics analysis and integrated pharmacology approach to decipher the effect and mechanism between raw and processed cistanche tubulosa.

ETHNOPHARMACOLOGICAL RELEVANCE: Cistanche tubulosa (CT) is the dried fleshy stem with scaly leaves of Cistanche tubiflora (Schenk) Wight, which has the effects of tonifying the kidney-yang, benefiting the vital essence and blood, and moisturizing the intestines and laxatives. There are differences in the activity of CT before and after processing, but the mechanism of processing is not clear. AIM OF THE STUDY: The study aimed to compare the strength of action of CT before and after yellow-wine processing in the treatment of constipation and kidney yang deficiency and to identify the active ingredients responsible for the differences in activity before and after yellow-wine processing. MATERIALS AND METHODS: This study established the fingerprints of CT and PCT using HPLC to identify their shared components. Then efficacy of KYDS and FC were carried out to compare the differences between CT and PCT in terms of efficacy. Next, this study established the spectrum-effect relationship between the shared chemical components and the medical effects of CT and PCT using the gray correlation analysis and entropy methods. Ultimately, the activity of the analyzed chemical components was verified using the zebrafish model. RESULTS: CT was more effective than PCT in promoting intestinal peristalsis, regulating gastrointestinal hormone levels, and thus treating FC. PCT was more effective than CT in improving the level of hormone indexes of the hypothalamus-pituitary-target gland axis, replenishing blood, and enhancing immunity. Through the analysis of the spectrum-effect relationship, it was finally found that 5, 6, 12 (tubuloside A), and 13 (isoacteoside) might be more closely related to the activity of tonifying kidney yang, and peaks 9, 10, and 11 (acteoside) are more closely associated with the treatment of constipation, and peaks 3 (salidroside), 4, 1, 2 (geniposidic acid), and 8 (echinacoside) were associated with both kidney yang tonic and treatment of constipation. At the same time, an activity verification experiment showed that echinacoside, geniposidic acid, and salidroside were effective in the treatment of FC and KYDS, while acteoside was very effective in the treatment of FC, and tubuloside A was significant in supplementing the blood, which validated the spectrum-effect relationship analysis. CONCLUSION: This study proved that the raw CT had a better laxative effect, while the yellow-wine processed CT had a better kidney-yang tonic effect; moreover, spectrum-effect relationships were established to analyze the chemical components leading to changes in the activity of CT before and after yellow-wine processing.

Glycyrrhizae radix et rhizoma processing ameliorates adverse reactions of polygalae radix in zebra fish and rabbit models.

ETHNOPHARMACOLOGICAL RELEVANCE: Polygala tenuifilia Willd (Polygalaceae), a traditional Chinese medicine, has been used for a long time to treat various illnesses with serious adverse reactions. Glycyrrhizae radix et rhizoma processing is generally used to reduce the adverse reactions. AIM OF THE STUDY: The aim of this study was to validate the irritation caused by raw Polygalaceae (RPA), to investigate whether processed Polygalaceae (PGA) was less irritating, and to screen and validate irritant properties of virgaureagenin G (polygala acid, PA), 3,6'-disinapoylsucrose (DSS), Tenuifolia (TEN) and polygalaxanthone III (POL), which had pharmacologically active in Polygalaceae. Zebrafish model, Draize test and High-Performance Liquid Chromatography (HPLC) were utilized to achieve the aim. MATERIALS AND METHODS: Scanning Electron Microscopy (SEM) and optical microscope were used to determine the presence of calcium oxalate needle crystal in RPA and PGA. Zebrafish egg spinning changes and zebrafish embryo behavior were used for irritation validation, irritation comparison and irritant screening. For additional evidence, the Draize test, HE staining of rabbit eyes and ELISA kit were used. Finally, changes in the composition of RPA and PGA were investigated using HPLC. RESULTS: SEM and optical microscopy revealed no calcium oxalate needle crystals in Polygalaceae. RPA, PGA, PA and DSS were able to accelerate the spinning of zebrafish eggs and the movement of embryos, while TEN and POL were not. RPA, PGA, DSS and PA may cause rabbit eyes to become hyperemic and swollen, resulting in damage to the iris, cornea and conjunctiva and increased levels of interleukin-6 (IL-6) and interleukin-10 (IL-10). Comparatively, the effects caused by PGA were less severe than those caused by RPA. In addition, compared to RPA, PGA had lower levels of DSS and PA. CONCLUSIONS: RPA, PGA, DSS, and PA were irritating. However, processing and curing could reduce the irritation by reducing the levels of DSS and PA. DSS and PA could be two potential irritants of Polygalaceae.

Electroacupuncture ameliorates surgery-induced spatial memory deficits by promoting mitophagy in rats.

Background: This study sought to explore the mechanism underlying the therapeutic effects of electroacupuncture (EA) on spatial memory deficits caused by surgery. Methods: Hepatic apex resection was performed under propofol-based total intravenous anesthesia. Male Sprague-Dawley rats were subjected to EA treatment or EA + mitochondrial division inhibitor-1 (mdivi-1) treatment once a day for three consecutive days after surgery. The Morris water maze test was used to evaluate the spatial memory of the rats after surgery. Tissue from the hippocampus of each rat was frozen and used for transcriptomic and proteomic analyses to identify potential targets for EA treatment. Western blotting was used to confirm the protein expression levels. The levels of reactive oxygen species (ROS) and adenosine triphosphate (ATP) were detected using commercial kits. The rat mitochondria were then isolated, and the activity of mitochondrial complex V was assessed. Results: EA attenuated surgery-induced spatial memory deficits on postoperative day 3, while these effects were reversed by treatment with the mdivi-1 (P<0.05). Ribonucleic acid (RNA)-sequencing revealed that EA upregulated multiple metabolic pathways and the phosphatidylinositol 3­kinas/protein kinase B signaling pathway. The proteomic and western blotting results suggested that the EA treatment substantially downregulated coiled-coil-helix-coiled-coil-helix domain containing 3 (ChChd3) expression in the hippocampus. The EA treatment significantly increased the autophagy-related protein levels, including phosphatase and tensin homolog-induced kinase 1, Parkin, MAP1LC3 (LC3), and Beclin1, and inhibited the production of ROS and inflammatory cytokine interleukin-1ß in the hippocampus (P<0.05). Conclusions: These results suggest that EA ameliorates postoperative spatial memory deficits and protects hippocampus from oxidative stress and inflammation through enhanced autophagy in an animal model of perioperative neurocognitive disorders (PNDs).

Study on the explicitation of implicit knowledge and the construction of knowledge graph on moxibustion in medical case records of ZHOU Mei-sheng's Jiusheng / 中国针灸

To explore the methods of the explicitation of implicit knowledge and the construction of knowledge graph on moxibustion in medical case records of ZHOU Mei-sheng's Jiusheng. The medical case records data of Jiusheng was collected, the frequency statistic was analyzed based on Python3.8.6, complex network analysis was performed using Gephi9.2 software, community analysis was performed by the ancient and modern medical case cloud platform V2.3.5, and analysis and verification of correlation graph and weight graph were proceed by Neo4j3.5.25 image database. The disease systems with frequency≥10 % were surgery, ophthalmology and otorhinolaryngology, locomotor, digestive and respiratory systems. The diseases under the disease system were mainly carbuncle, arthritis, lumbar disc herniation and headache. The commonly used moxibustion methods were fumigating moxibustion, blowing moxibustion, direct moxibustion and warming acupuncture. The core prescription of points obtained by complex network analysis included Yatong point, Zhiyang(GV 9), Sanyinjiao(SP 6), Dazhui(GV 14), Zusanli(ST 36), Lingtai(GV 10), Xinshu(BL 15), Zhijian point and Hegu(LI 4), which were basically consistent with high-frequency points. A total of 6 communities were obtained by community analysis, corresponding to different diseases. Through the analysis of correlation graph, 13 pairs of strong association rule points were obtained. The correlation between Zhiyang(GV 9)-Dazhui(GV 14) and Yatong point-Lingtai(GV 10) was the strongest. The acupoints with high correlation with Yatong point were Zhiyang(GV 9), Lingtai(GV 10), Dazhui(GV 14), Zusanli(ST 36) and Sanyinjiao(SP 6). In the weight graph of the high-frequency disease system, the relationship of the first weight of the surgery system disease was fumigating moxibustion-carbuncle-Yatong point, and the relationship of the first weight of the ophthalmology and otorhinolaryngology system disease was blowing moxibustion-laryngitis-Hegu (LI 4). The results of correlation graph and weight graph are consistent with the results of data mining, which can be used as an effective way to study the knowledge base of moxibustion diagnosis and treatment in the future.

Mechanism of Sijunzi Decoction in treatment of Alzheimer's disease based on UPLC-Q-TOF-MS, network pharmacology, and experimental verification / 中国中药杂志

The study identified the blood-entering components of Sijunzi Decoction after gavage administration in rats by UPLC-Q-TOF-MS/MS, and investigated the mechanism of Sijunzi Decoction in treating Alzheimer's disease by virtue of network pharmacology, molecular docking, and experimental verification. The blood-entering components of Sijunzi Decoction were identified based on the mass spectra and data from literature and databases. The potential targets of the above-mentioned blood-entering components in the treatment of Alzheimer's disease were searched against PharmMapper, OMIM, DisGeNET, GeneCards, and TTD. Next, STRING was employed to establish a protein-protein interaction(PPI) network. DAVID was used to perform the Gene Ontology(GO) annotation and the Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment. Cytoscape 3.9.0 was used to carry out visual analysis. AutoDock Vina and PyMOL were used for molecular docking of the blood-entering components with the potential targets. Finally, the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt) signaling pathway enriched by the KEGG analysis was selected for validation by animal experiments. The results showed that 17 blood-entering components were detected in the serum samples after administration. Among them, poricoic acid B, liquiritigenin, atractylenolide Ⅱ, atractylenolide Ⅲ, ginsenoside Rb_1, and glycyrrhizic acid were the key components of Sijunzi Decoction in treating Alzheimer's disease. HSP90AA1, PPARA, SRC, AR, and ESR1 were the main targets for Sijunzi Decoction to treat Alzheimer's disease. Molecular docking showed that the components bound well with the targets. Therefore, we hypothesized that the mechanism of Sijunzi Decoction in treating Alzheimer's disease may be associated with the PI3K/Akt, cancer treatment, and mitogen-activated protein kinase(MAPK) signaling pathways. The results of animal experiments showed that Sijunzi Decoction significantly attenuated the neuronal damage in the hippocampal dentate gyrus area, increased the neurons, and raised the ratios of p-Akt/Akt and p-PI3K/PI3K in the hippocampus of mice. In conclusion, Sijunzi Decoction may treat Alzheimer's disease by activating the PI3K/Akt signaling pathway. The findings of this study provide a reference for further studies about the mechanism of action and clinical application of Sijunzi Decoction.

Inhibitory effect of chikusetsusaponin IVa on proliferation of triple negative breast cancer cells / 药学学报

Chikusetsusaponin IVa (CsIVa) is a natural active monomer of triterpene saponins in the Chinese herbal medicine of Panax japonicus, which has anti-inflammatory, anti-tumor and other effects. However, its function and mechanism in triple negative breast cancer (TNBC) remain unclear. This study investigated the inhibitory effect and mechanisms of CsIVa on the proliferation of triple negative breast cancer cell line MDA-MB-231. In this study, we found that CsIVa could significantly inhibit the proliferation of MDA-MB-231 cells and eliminate its potential toxic effect on normal breast cells (MCF-10A). The transcriptome sequencing results showed that the inhibition of proliferation of MDA-MB-231 cells by CsIVa was closely related to cell cycle and the pathway regulating cell cycle. Further studies confirmed that CsIVa blocked the cell cycle in G2/M phase by down-regulating the expression of cyclin dependent kinase 1 (CDK1), cyclin B1 and up-regulating the expression of cyclin dependent kinase inhibitor 1A (p21). Moreover, CsIVa can block cell cycle through inhibiting PI3K/AKT signal pathway. In conclusion, CsIVa regulates the expression of cell cycle related proteins (p21, CDK1, cyclin B1) via inhibiting the activity of PI3K/AKT signaling pathway, blocks TNBC cell cycle, and thus exerts its anti-tumor activity.

Short needling for knee osteoarthritis with blood stasis obstruction and its effect on serum inflammatory factors / 中国针灸

OBJECTIVE@#To compare the clinical efficacy and its effect on serum levels of tumor necrosis factor α(TNF-α), interleukin 1β(IL-1β), interleukin 6 (IL-6) and prostaglandin E2 (PGE2) between short needling (close-to-bone needling) and conventional acupuncture for knee osteoarthritis (KOA) with blood stasis obstruction.@*METHODS@#A total of 68 KOA patients with blood stasis obstruction were randomized into a short needling group (34 cases, 3 cases dropped off) and a conventional acupuncture group (34 cases, 3 cases dropped off). The same acupoints (Dubi [ST 35], Neixiyan [EX-LE 4], Binzhong [Extra], Liangqiu [ST 34], etc. on the affected side) were selected in the two groups. In the short needling group, short needling technique was adopted, the needles were slowly inserted and the needle bodies were shaken, thus gradually penetrated to the bone. In the conventional acupuncture group, conventional acupuncture was adopted, the needles were penetrated to the muscle. After qi-arrival, Dubi (ST 35) and Neixiyan (EX-LE 4), Zusanli (ST 36) and Liangqiu (ST 34) were connected with CMNS6-1 electronic acupuncture instrument, with disperse-dense wave, 2 Hz/10 Hz in frequency, the current intensity was based on patients' feeling, the needles were retained for 30 min, at the same time, the knee joint was irradiated for 30 min with a special electromagnetic wave apparatus in the two groups. Once every other day, 3 times a week for 4 weeks. Before and after treatment, the Western Ontario and McMaster Universities osteoarthritis index (WOMAC) score, knee joint pain visual analogue scale (VAS) score, inflammatory response related indexes (serum TNF-a, IL-1β, IL-6 and PGE2) and knee joint ultrasound were observed，and the clinical effect was evaluated in the two groups.@*RESULTS@#After treatment，the pain, stiffness, function scores and total scores of WOMAC were decreased as compared with those before treatment in the two groups (P<0.05), except for the pain score, the changes of above scores in the short needling group were greater than the conventional acupuncture group (P<0.05). After treatment, the VAS scores, serum levels of TNF-a, IL-1β, IL-6, PGE2 and knee joint synovium thickness, intra-articular effusion were decreased as compared with those before treatment in the two groups (P<0.05), the levels of TNF-a, IL-1β, IL-6 in the short needling group were lower than the conventional acupuncture group (P<0.05). The total effective rate in the short needling group was 87.1% (27/31), which was superior to 83.9% (26/31) in the conventional acupuncture group (P<0.05).@*CONCLUSION@#Short needling could improve the knee joint function, relieve the pain and inflammatory response, improve the knee joint synovium inflammatory response, reduce the knee joint intra-articular effusion for KOA patients, its effect is better than conventional acupuncture.

GAO Hong's clinical experience in treatment of tic disorder with acupuncture technique of cultivating the primary and regulating the mind / 中国针灸

The paper introduces the clinical experience of GAO Hong in treatment of tic disorder. GAO Hong believes that tic disorder results from the primary qi deficiency and mind disturbance. Acupuncture for cultivating the primary and regulating the mind is proposed specially for tic disorder. This acupuncture technique focuses on harmonizing and regulating governor vessel and conception vessel. In clinical practice, the conception vessel acupoints on the abdomen and the governor vessel acupoints on the head are selected particularly, e.g. Zhongwan (CV 12), Xiawan (CV 10), Qihai (CV 6) and Guanyuan (CV 4) on the abdomen; Baihui (GV 20), Shenting (GV 24), Benshen (GB 13) and Yintang (GV 24+) on the head. The needling sequence and the insertion depth are emphasized, which affect the curative effect and GV 20 is generally punctured first. Besides, considering to the type of disorder and the affected site, tic disorder is treated in view of both syndrome/pattern differentiation and symptom differentiation.

MA Hui-fang's experience in age-related macular degeneration treated with acupuncture at Jingming (BL 1) / 中国针灸

The paper introduces professor MA Hui-fang's experience in age-related macular degeneration treated with acupuncture at Jingming (BL 1). It is believed that the basic pathogenesis of this disease refers to liver and kidney insufficiency and weakness of spleen qi. Based on the academic ideas of yang qi and meridian-collateral system, the treatment principle is proposed as "invigorating yang qi, replenishing the liver and kidney and nourishing the spleen and stomach". Regarding acupoint selection, Jingming (BL 1) is specially used, combined with the 4 front-mu points (Zhongwan [CV 12], Guanyuan [CV 4] and bilateral Tianshu [ST 25]), as well as the empirical points for eye diseases (Jingming [BL 1], Baihui [GV 20] and Zulinqi [GB 41]). Concerning to needling technique, shuci (transport needling), fenci (intermuscular needling) and yuandaoci (distal needling) are dominated. Eventually, a set of unique therapeutic method has been accumulated through professor MA Hui-fang's clinical practice in treatment of age-related macular degeneration.

Correlations of Characteristics of Kidney Yang Deficiency Syndrome with Clinical Indicators and Risk Factors of Chronic Kidney Disease / 中国实验方剂学杂志

ObjectiveTo study the correlations of the characteristics of kidney Yang deficiency syndrome in patients with chronic kidney disease （CKD） with clinical indicators and to explore the risk factors of kidney Yang deficiency in CKD. MethodThe differentiation of traditional Chinese medicine （TCM） syndrome classified the 225 CKD patients who met the inclusion criteria into two groups： one group of kidney Yang deficiency syndrome （99 patients） and one group of non-kidney Yang deficiency syndrome （126 patients）. The symptoms， tongue manifestation， pulse manifestation， and accompanied symptoms of the kidney Yang deficiency syndrome group were recorded. The syndrome characteristics were summarized by factor analysis and clustering analysis. The levels of hemoglobin, red blood cell count, urinary protein, urinary glucose, creatinine, urea nitrogen and glomerular filtration rate were compared between the kidney Yang deficiency syndrome group, the non-kidney Yang deficiency syndrome group and the normal control group by ANOVA and non-parametric test. The binary logistic regression model was employed to analyze the correlations of lifestyle， body mass index （BMI） with syndrome. ResultThe high-frequency symptoms of CKD patients with kidney Yang deficiency syndrome were waist pain， fear of cold， favor of warm， lethargy， fear of cold at waist and knees， etc. The patients mainly presented deep pulse， thready pulse， or weak pulse， and the tongue with white coating， greasy coating， or thin coating. A total of 13 common factors were obtained， which can be classified into 5 categories. The patients with kidney Yang deficiency syndrome mainly had symptoms in limbs （especially lower limbs）， chest， bladder， fleshy exterior， and stomach， with the main manifestations of deficiency-cold， Qi deficiency， fluid retention， and blood stasis. The clustering analysis classified the patients into 11 categories， which reflected that kidney Yang deficiency syndrome mainly presented the symptoms of Qi deficiency， blood stasis， and fluid retention， with fleshy exterior， limbs， spleen， stomach， ears， mind， and bladder involved. The results of clustering analysis and factor analysis were consistent， both of which indicated that the patients were weak with deficiency-cold， accompanied by fluid retention and blood stasis. Frequency analysis also showed that common symptoms mainly included Qi deficiency， fluid retention， cold-dampness， and blood stasis. Compared with the non-kidney Yang deficiency group， the kidney Yang deficiency group showed a large proportion of patients in stage 3-5 CKD， elevated urea nitrogen （P<0.05）， decreased glomerular filtration rate， hemoglobin， and red blood cell count （P<0.05）， and increased qualitative grade of urine protein. In addition， the results of regression analysis showed that female， little or no exercise， and diet preference were the risk factors for kidney Yang deficiency syndrome in CKD （P<0.05）. ConclusionThe disease location and manifestations have correspondence in the CKD patients with kidney Yang deficiency syndrome. The TCM symptoms are correlated with clinical indicators. Hemoglobin， red blood cell count， glomerular filtration rate， urea nitrogen， and urine protein can reflect the connotation of kidney Yang deficiency syndrome in CKD to a certain extent. Additionally， related risk factors in life can affect the occurrence of kidney Yang deficiency syndrome in CKD.

Correlations of Characteristics of Kidney Yang Deficiency Syndrome with Clinical Indicators and Risk Factors of Chronic Kidney Disease / 中国实验方剂学杂志

ObjectiveTo study the correlations of the characteristics of kidney Yang deficiency syndrome in patients with chronic kidney disease （CKD） with clinical indicators and to explore the risk factors of kidney Yang deficiency in CKD. MethodThe differentiation of traditional Chinese medicine （TCM） syndrome classified the 225 CKD patients who met the inclusion criteria into two groups： one group of kidney Yang deficiency syndrome （99 patients） and one group of non-kidney Yang deficiency syndrome （126 patients）. The symptoms， tongue manifestation， pulse manifestation， and accompanied symptoms of the kidney Yang deficiency syndrome group were recorded. The syndrome characteristics were summarized by factor analysis and clustering analysis. The levels of hemoglobin, red blood cell count, urinary protein, urinary glucose, creatinine, urea nitrogen and glomerular filtration rate were compared between the kidney Yang deficiency syndrome group, the non-kidney Yang deficiency syndrome group and the normal control group by ANOVA and non-parametric test. The binary logistic regression model was employed to analyze the correlations of lifestyle， body mass index （BMI） with syndrome. ResultThe high-frequency symptoms of CKD patients with kidney Yang deficiency syndrome were waist pain， fear of cold， favor of warm， lethargy， fear of cold at waist and knees， etc. The patients mainly presented deep pulse， thready pulse， or weak pulse， and the tongue with white coating， greasy coating， or thin coating. A total of 13 common factors were obtained， which can be classified into 5 categories. The patients with kidney Yang deficiency syndrome mainly had symptoms in limbs （especially lower limbs）， chest， bladder， fleshy exterior， and stomach， with the main manifestations of deficiency-cold， Qi deficiency， fluid retention， and blood stasis. The clustering analysis classified the patients into 11 categories， which reflected that kidney Yang deficiency syndrome mainly presented the symptoms of Qi deficiency， blood stasis， and fluid retention， with fleshy exterior， limbs， spleen， stomach， ears， mind， and bladder involved. The results of clustering analysis and factor analysis were consistent， both of which indicated that the patients were weak with deficiency-cold， accompanied by fluid retention and blood stasis. Frequency analysis also showed that common symptoms mainly included Qi deficiency， fluid retention， cold-dampness， and blood stasis. Compared with the non-kidney Yang deficiency group， the kidney Yang deficiency group showed a large proportion of patients in stage 3-5 CKD， elevated urea nitrogen （P<0.05）， decreased glomerular filtration rate， hemoglobin， and red blood cell count （P<0.05）， and increased qualitative grade of urine protein. In addition， the results of regression analysis showed that female， little or no exercise， and diet preference were the risk factors for kidney Yang deficiency syndrome in CKD （P<0.05）. ConclusionThe disease location and manifestations have correspondence in the CKD patients with kidney Yang deficiency syndrome. The TCM symptoms are correlated with clinical indicators. Hemoglobin， red blood cell count， glomerular filtration rate， urea nitrogen， and urine protein can reflect the connotation of kidney Yang deficiency syndrome in CKD to a certain extent. Additionally， related risk factors in life can affect the occurrence of kidney Yang deficiency syndrome in CKD.

Discussion on Treatment of Recurrent Genital Herpes with Zhulingtang： Based on Thought of "Lower Energizer Resembling Drainage" / 中国实验方剂学杂志

Recurrent genital herpes is a sexually transmitted disease induced by herpes simplex virus（HSV）， mainly manifested as erythema， papules， vesicles， erosion， and exudation on the skin and mucosal membranes of the genital and anal area， accompanied by burning pain， or tingling. Factors leading to its recurrence are overworking， fever， alcohol consumption， infection， sexual activity， etc. At least 1 in 10 of the 15-49-year-old population are infected with herpes simplex virus-2. There is currently no available method to completely remove the herpes simplex virus and prevent its recurrence， and recurrence seriously affects the quality of life and psychological health of patients. According to the theory of traditional Chinese medicine （TCM）， the recurrence of genital herpes is mostly related to wind， dampness， heat， yin deficiency of liver and kidney， internal injuries due to emotional disorder， and dietary preference. TCM has advantages in reducing its recurrence rate. The lower energizer is closely related to skin diseases， and "lower energizer resembles drainage". Thus， the lower energizer is closely related to water and damp metabolism. Recurrent genital herpes occurs in the lower energizer and belongs to lower energizer diseases， and the fluid metabolism and qi movement in lower energizer are closely related to the occurrence of the disease. Based on thought of "lower energizer resembling drainage" and the clinical characteristics of recurrent genital herpes， this paper considered malfunction of lower energizer as its pathogenesis. Thus， smoothing the lower energizer according to the prevailing circumstances is particularly important and the treatment principle should be dispersing the pathogen from lower energizer without damaging yin. Zhulingtang （Treatise on Cold Damage and Miscellaneous Diseases） cures the difficulty in urination and thirst with desire to drink by smoothing the lower energizer. Thus， Zhulingtang was selected to treat recurrent genital herpes. This study is expected to provide a new idea for its clinical diagnosis and treatment.

Molecular Mechanism of Nardostachyos Radix et Rhizoma-Agrimoniae Herba in Treatment of Arrhythmia Based on Network Pharmacology / 中国实验方剂学杂志

ObjectiveTo explore the material basis and mechanism of Nardostachyos Radix et Rhizoma （NRER）-Agrimoniae Herba （AH）， the herbal pair effective in regulating the liver， invigorating Qi， and calming palpitations， in the treatment of premature ventricular contractions （PVCs） by network pharmacology and molecular docking. MethodThe chemical components and targets of NRER and AH were collected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） combined with relevant literature. GeneCards，Online Mendelian Inheritance in Man（OMIM），and DrugBank were used to predict the potential targets against PVCs. STRING platform was used for protein-protein interaction （PPI） analysis. Metascape platform was used for Gene Ontology（GO） and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analysis. Cytoscape 3.8.0 was used to construct the NRER-AH component-potential target-signaling pathway network. The main target proteins underwent molecular docking to the active components of NRER-AH by AutoDock 4.2.6. ResultThe targets of nine active components in NRER-AH （such as quercetin，kaempferol，and acacetin） against PVCs mainly involved tumor necrosis factor （TNF），mitogen-activated protein kinase 1（MAPK1），and protein kinase B1（Akt1）. The potential targets were mainly enriched in 26 signaling pathways，such as pathways in cancer and the advanced glycosylation end product （AGE）-receptor of advanced glycosylation end product（RAGE） signaling pathway. The results of molecular docking showed that the majority of the active components （92.59%） of NRER-AH had good binding activities with the main target proteins TNF，MAPK1，and Akt1. ConclusionThe active components of NRER-AH can regulate cardiac ion channels，resist inflammation， and combat oxidative stress to treat PVCs through multi-target and multi-pathway interventions. They can also improve symptoms related to depression and anxiety by inhibiting monoamine oxidase activity and protecting nerves from damage. This study is expected to provide research ideas and the theoretical basis for further exploring the material basis and mechanism of NRER-AH in the treatment of PVCs.

Research progress of traditional Chinese medicine extracts in intervention of fibrosis caused by silicosis / 环境与职业医学

Silicotic nodules and pulmonary fibrosis are histopathological appearance in silicosis patients after long-term inhalation of crystalline silica particles, and are difficult to reverse and recover. Research on the pathogenesis and treatment strategies of silicosis has significantly lagged behind medical progress and clinical needs, resulting in the disease remaining a thorny clinical problem. Traditional Chinese medicine extracts or compound preparations have become a hot issue in exploring silicosis treatment strategies in recent years. This paper described the main pathological processes of pulmonary fibrosis caused by silicosis, followed by introducing its main pathogenesis mechanisms, including transforming growth factor-β1 (TGF-β1)/Smad signaling pathway, oxidative stress reaction, apoptosis, and autophagy. In addition, it briefly described the research progress, targets, and intervention effects of selected traditional Chinese medicine extracts, which provides a scientific basis for the theoretical and clinical research of traditional Chinese medicine extracts in inhibiting pulmonary fibrosis. To change the clinical status quo of silicosis fibrosis which is difficult to control and reverse, the paper proposed that we can further explore the pathogenesis and progression mechanisms of silicosis and drug treatment strategy, and focus on the transformation of basic research into clinical practice.

Prediction of Q-markers of Citri Reticulatae Pericarpium volatile oil and GC-MS based quantitative analysis / 中国中药杂志

This study was designed to predict the Q-markers of Citri Reticulatae Pericarpium volatile oil and conduct quantitative analysis by GC-MS. The common components of Citri Reticulatae Pericarpium volatile oil were detected by GC-MS. The network pharmacology approaches were utilized for constructing the component-target network and protein-protein interaction(PPI) network, followed by the GO and KEGG pathway enrichment analysis to clarify the pharmacological effects of common components. Molecular docking was conducted to observe the biological activities of common components, thus identifying the Q-markers of Citri Reticulatae Pericarpium volatile oil. The obtained Q-markers were subjected to quantitative analysis by GC-MS. The GC-MS analysis of 19 batches of Citri Reticulatae Pericarpium volatile oil revealed three common components, namely, D-limonene, γ-terpinene, and myrcene. The common components were analyzed based on network pharmacology, and the results showed that Citri Reticulatae Pericarpium volatile oil mainly acted on the core targets GABRA1, GABRA6, GABRA5, GABRA3, and GABRA2 through D-limonene and γ-terpinene, with five important pathways such as nicotine addiction and GABAergic synapse involved. The core targets were mainly distributed in olfactory region, cerebral cortex, cerebellum, basal ganglia, hippocampus, and amygdala to exert the pharmacological effects. As revealed by molecular docking, D-limonene and γ-terpinene exhibited good biological activities, so they were identified as the Q-markers of Citri Reticulatae Pericarpium volatile oil. The results of quantitative analysis showed that the volume fraction of D-limonene was within the range of 0.77-1.03 μL·mL~(-1), and that of γ-terpinene within the range of 0.04-0.13 μL·mL~(-1). The prediction of D-limonene and γ-terpinene as the Q-markers of Citri Reticulatae Pericarpium volatile oil has laid an experimental foundation for the establishment of the quality evaluation standard for Citri Reticulatae Pericarpium volatile oil.

Effect of Erxian Decoction on proteomics and PI3K signaling pathway of osteoblasts stimulated by H2O2 / 中国中药杂志

The present study aimed to explore the effect of Erxian Decoction on proteomics of osteoblasts stimulated by hydrogen peroxide(H_2O_2) and its protective mechanism with the H_2O_2-induced cell model of oxidative stress. The primary osteoblasts were cultured from the skulls of newborn rats(within 24 hours) and divided into a control group, a model group, a Fosamax group, and an Erxian Decoction group. Blank serum was added in the control group and model group, and the drug-containing serum was added correspondingly to the remaining two groups. After 45 hours, H_2O_(2 )stimulation was conducted for three hours except for the control group, followed by protein extraction. Nano-LC-LTQ-Orbitrap system was used for protein detection, Protein Discovery for protein identification, and SIEVE for quantitative and qualitative analysis. Furthermore, following the blocking of PI3 K signaling pathway by LY294002(10 μmol·L~(-1)), a control group, a model group, an LY294002 group, an Erxian Decoction group, and an Erxian Decoction + LY294002 group were set up to observe the effect of Erxian Decoction on cell proliferation, alkaline phosphatase(ALP) activity, and the relative expression of BMP-2, OPG, p-Akt, p-FoxO1 of osteoblasts stimulated by H_2O_2 under LY294002 intervention. The results revealed that 78 differential proteins were discovered between the Erxian Decoction group and model group, which were involved in the regulation of PI3 K/Akt, glucagon, estrogen, insulin, and other signaling pathways. LY294002 blunted the promoting effect of Erxian Decoction on osteoblast proliferation and significantly down-regulated the expression of OPG and p-FoxO1, whereas its down-regulation on the expression of BMP-2 and p-Akt was not significant. Both LY294002 and Erxian Decoction increased the ALP activity of osteoblasts, which may be related to the cell state and the cell differentiation. The above results suggest that Erxian Decoction can protect osteoblasts stimulated by H_2O_2, with the PI3 K/Akt signaling pathway as one of the internal mechanisms.

Potential therapeutic effect of Saussureae Involucratae Herba on breast cancer and its mechanism based on network pharmacology / 中国中药杂志

As one of the most commonly diagnosed cancers in the world, female breast cancer is induced by the high level of estrogen. Saussureae Involucratae Herba(SIH), a gynecological medicinal, regulates estrogen-induced diseases. However, the therapeutic effect of SIH on breast cancer has not been reported. Therefore, this study aims to explore the potential efficacy of SIH on breast cancer based on in vitro experiment and network pharmacology. The inhibitory effect of SIH water extract on proliferation and migration of breast cancer MDA-MB-231 cells was examined. The result demonstrated SIH water extract significantly suppressed the proliferation of breast cancer cells(IC_(50)=6.47 mg·mL~(-1)) and also restricted the migration. A total of 39 components of SIH were retrieved from traditional Chinese medicine database(TCMD) and 160 targets of SIH were screened by target fishing with the PharmaDB database. The Online Mendelian Inheritance in Man(OMIM) was used to establish a 1 001-targets data set of breast cancer. Based on the overlaps(45) of targets between SIH and breast cancer, a protein-protein interaction(PPI) network was built to analyze the interactions among these targets with STRING platform and Cytoscape. Finally, through topology and GO and KEGG analysis, 8 targets, 101 pathways and 85 biological processes were found to involve the treatment of breast cancer by SIH. SIH may exert the anti-breast cancer effect by regulating cell cycle, inhibiting proliferation, migration and adhesion of cancer cells, and modulating estrogen receptor. This study clarified the mechanism of SIH in treating breast cancer, which lays a foundation for the further development of SIH.

Effect of acupuncture on intestinal flora and TLR4 in brain and intestinal tissues in rats with stress gastric ulcer / 中国针灸

OBJECTIVE@#To observe the effect of acupuncture at "Guanyuan" (CV 4) and "Xiajuxu" (ST 39) on intestinal flora and Toll-like receptors-4 (TLR4) in brain and intestinal tissue in rats with stress gastric ulcer (SGU), and to explore the possible mechanism of acupuncture for SGU.@*METHODS@#Thirty-one male SD rats were randomly divided into a blank group (@*RESULTS@#Compared with the blank group, the gastric mucosal damage index was significantly increased in the model group (@*CONCLUSION@#Acupuncture at "Guanyuan" (CV 4) and "Xiajuxu" (ST 39) could alleviate SGU in rats, and its mechanism may be related to increasing the diversity of intestinal flora, promoting the disorder of intestinal flora to normal, and reducing the overexpression of TLR4 in brain and intestinal tissues.

Drug screening and identification of key candidate genes and pathways of rheumatoid arthritis.

Rheumatoid arthritis (RA), which normally manifests as a multi­joint inflammatory reaction, is a common immunological disease in clinical practice. However, the pathogenesis of RA has not yet been fully elucidated. Rituximab (RTX) is an effective drug in the treatment of RA, however its therapeutic efficacy and mechanism of action require further investigation. Thus, the present study aimed to screen the candidate key regulatory genes and explain the potential mechanisms of RA. Gene chips of RA and normal joint tissues were analyzed and, gene chips of RTX before and after treatment were investigated. In the present study, strong evidence supporting the pathogenesis of RA and mechanism of action of RTX were also revealed. Differentially expressed genes (DEGs) were analyzed using the limma package of RStudio software. A total of 1,150 DEGs were detected in RA compared with normal joint tissues. The upregulated genes were enriched in 'interleukin­12 production', 'I­κB kinase/NF­κB signaling', 'regulation of cytokine production involved in immune response' and 'cytokine metabolic process'. Functional enrichment analysis showed that RTX was primarily involved in the inhibition of 'adaptive immune response', 'B cell activation involved in immune response' and 'immune effector process'. Subsequently, leukocyte immunoglobulin­like receptor subfamily B member 1 (LILRB1), a hub gene with high connectivity degree, was selected, and traditional Chinese medicine libraries were molecularly screened according to the structure of the LILRB1 protein. The results indicated that kaempferol 3­O­ß­D­glucosyl­(1→2)­ß­D­glucoside exhibited the highest docking score. In the present study, the DEGs and their biological functions in RA and the pharmacological mechanism of RTX action were determined. Taken together, the results suggested that LILRB1 may be used as a molecular target for RA treatment, and kaempferol 3­O­ß­D­glucosyl­(1→2)­ß­D­glucoside may inhibit the pathological process of RA.

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.