Malignant tumors are currently seriously endangering human health and life， which has become one of the main causes of death in China. In modern Western medicine， they are mainly tackled by surgery， chemotherapy， and radiotherapy， but the death toll continues to rise year by year. At present， most of the anti-tumor chemotherapeutics used in clinical practice have toxic and side effects， affecting the anti-tumor efficacy and the conditions after treatment. Long-term medication will also induce drug resistance， making the good anti-tumor effect difficult to be achieved. With the vigorous development of traditional Chinese medicine （TCM）， it has played a crucial role in the fight against tumors. It is believed in TCM that "heat toxin" is one of the important causes of tumors. Therefore， the methods of clearing away heat and removing toxin are often emphasized in the treatment of tumors， and the resulting outcomes are satisfactory. There are many Chinese herbs and Chinese herbal compounds classified into the heat-clearing and toxin-removing type. Xihuangwan， a classic heat-clearing prescription， is composed of Calculus Bovis， Moschus， Olibanum， and Myrrh and has the effects of clearing away heat， removing toxin， eliminating edema， and dissipating mass， which is mainly used to treat carbuncle， pustule， scrofula， multiple abscess， and cancer caused by heat-toxin obstruction. In modern clinical practice， it has been employed in patients with lung cancer， breast cancer， gastric cancer， liver cancer， colorectal cancer， and other malignant tumors， especially during the advanced stage， as a routine or adjuvant treatment for alleviating their clinical symptoms and improving their quality of life. The main active components of Xihuangwan are pentacyclic triterpenoids （such as masticinic acids）， volatile oils， steroids （like porcine deoxycholic acid）， and bilirubin， which have been proved effective in anti-tumor. This paper reviewed the prescription source， pharmaceutical research， clinical anti-tumor research， and pharmacological mechanisms of Xihuangwan， which has provided reference for further expanding the anti-tumor applications of Xihuangwan and enhancing its secondary development.

Angiotensin Receptor Antagonists ; Angiotensin-Converting Enzyme 2 ; Betacoronavirus ; COVID-19 ; Cardiovascular Agents/pharmacology* ; Cardiovascular Diseases ; Coronavirus Infections/physiopathology* ; Humans ; Pandemics ; Peptidyl-Dipeptidase A/physiology* ; Pneumonia, Viral/physiopathology* ; SARS-CoV-2

Objective To investigate the effect of safflower yellow injection on atherosclerosis in rabbits with hyperlipidemia.Methods Ninety-six New Zealand rabbits were randomly divided into four groups:the control group, model group, safflower yellowtest group (10.9, 5.45 and 2.725 mg/kg) and the positive control (atorvastatin) group. The control group was fed with normal feed, while the other three groups were fed with high fat diet for 8 weeks, combined with intraperitoneal injection of vitamin D3, to establish hyperlipidemia model. Then, the three-dosage safflower yellow-test groups were given intraperitoneal injection of safflower yellow (10.9, 5.45 and 2.725 mg/kg), respectively, the positive control group was given atorvastatin calcium[2 mg/ (kg·d) ]by intragastric administration, and the control and model groups were orally given an equal volume of normal saline, all once a day every day for 8weeks. After 16 h fasting following the last administration, the body weight, total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), oxidized low density lipoprotein (OX-LDL), matrix metalloproteinases 9 (MMP-9), tissue inhibitors of metalloproteinase 1 (TIMP-1), apolipoprotein E (ApoE), low density lipoprotein receptor (LDL-R), and scavenger receptor class B type1 (SR-B1) levels were measured. The morphological changes of thoracic aortas were examined by HE staining. Results At the 16 th week, compared with the control group, the body weight as well as the TC, TG, LDL-C, OX-LDL, MMP-9, HIF-1α, VEGF, VCAM-1 and PF4 level were all increased significantly (P＜0.05), while the level of HDL-C, ApoE, LDL-R, and SR-B1 decreased significantly (P＜0.05), accompanied with the atherosclerotic changes in the thoracic aortas indicated by the HE staining in the model group. Compared with the model group, the body weight as well as the TC, LDL-C, OX-LDL, MMP-9, HIF-1α, VEGF, VCAM-1 and PF4 level were decreased significantly (P＜0.05), and the TIMP-1 level increased (P＜0.05) in all of the three-dosage safflower yellow-test groups. Meanwhile, compared with the model group, in the 10.9 and 5.45 mg/kg safflower yellow groups, the TG level were decreased and the ApoE and SR-B1 levels were increased significantly (P＜0.05). On the other hand, the LDL-R level significantly increased only in the safflower yellow 10.9 mg/kg group (P＜0.05). HE staining showed a significant reduction in atherosclerorotic changes of the thoracic aorta in the safflower yellow-test groups. Conclusion Safflower yellow may inhibit the progression of atherosclerosis by regulating the lipid metabolism and MMP-9/TIMP-1 balance and also by inhibiting the HIF-1α, VEGF, VCAM-1 and PF4 expression.

To summary and analyze the prescription rules of Professor Chen Baogui, a famous traditional Chinese medicine (TCM) doctor, for treating epigastric fullness. Professor Chen Baogui's prescriptions for treating epigastric fullness were collected and the treatment data were input into traditional Chinese medicine inheritance support system (TCMISS) to analyze the rules of the prescriptions by using data mining methods. Based on the screened 214 cases, the treatment experience of Professor Chen Baogui for treating epigastric fullness was summarized and analyzed. It was found that Professor Chen gave priority to recuperation of Qi activity. The results of four properties and five tastes showed Professor Chen's medication compatibility rules: one was simultaneous use of cold and warm drugs, and the other was simultaneous use of pungent drugs for dispersion and bitter drugs for purgation. In drug use, the basic prescriptions had the efficacy of promoting Qi circulation and regulating viscera function, additionally with the drugs with functions of eliminating digestion and inducing stagnation, activating blood circulation to dissipate blood stasis, replenishing Qi and nourishing Yin, tranquilizing mind, strengthening muscles and bones according to the TCM syndrome type. The clinical experience of Professor Chen for treating epigastric fullness was objectively summarized with the help of TCMISS, which was significant for analyzing and inheriting academic thinking and medication experience from famous TCM doctors.
Data Mining ; Digestion ; drug effects ; Drug Prescriptions ; standards ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Medicine, Chinese Traditional ; Stomach ; drug effects

The aim of this paper was to observe the function of bone marrow mesenchymal stem cell (BMSC) transplantation in process of liver injury induced by carbon tetrachloride (CCl₄) and the intervention effect of Yiguanjian (YGJ), a compound of Chinese herbal medicine. Wistar rats were randomly divided into five groups: normal group, model group, cell transplantation (CT) group, YGJ group and cell transplantation plus Yiguanjian (CTY) group. Liver injury was induced through subcutaneous injection with CCl₄ at a dose of 3 mL·kg⁻¹ body weight for 4 weeks, twice a week. They were injected for a total of 9 times. After the first injection with CCl₄, rats in the CT group and CTY group were injected with the third-generation BMSCs at dose 1×10⁶ (suspended in 1 mL saline solution) via tail vein. Rats in the YGJ and CTY groups were also intragastrically administered with Yiguanjian once a day. Rat serum ALT and AST activities were increased significantly on the second day after injection with CCl₄, while BMSC transplantation and Yiguanjian decreased their activities. After 4 weeks of injection with CCl₄, serum ALT, AST and -GT activities, and serum TNF- and IL-6 expressions were increased, while TBIL were decreased in model rats compared with normal rats. Meanwhile, liver cells edema, plasmatic loose, and numerous lipid droplets were observed in rats of the model group. BMSC transplantation aggravated liver injury compared with model rats, which was manifested by decreasing SOD activity, increased MDA, TG, TNF- and IL-6 levels, and aggravated necrosis level of hepatocytes, fusion of lipid droplets, and collagen deposition in liver tissue. Yiguanjian decreased liver injury induced by CCl₄ alone and CCl₄ plus BMSC transplantation. SRY gene hybridization method was used to detect the positive SRY expressions in heart, liver, spleen, lung and kidney, especially in liver, while Yiguangjian decreased liver SRY expression. Wnt and -catenin showed high expressions in rats of normal group, which were decreased significantly in rats of models group, while Yiguanjian increased their expressions. In conclusion, BMSC transplantation could exacerbate liver injury, while Yiguanjian could protect liver injury induced by CCl₄ and BMSC transplantation, which was related to decreasing the homing of BMSCs to liver and up-regulating Wnt/-catenin signaling pathway.
Animals ; Bone Marrow ; Carbon Tetrachloride ; Chemical and Drug Induced Liver Injury ; therapy ; Drugs, Chinese Herbal ; pharmacology ; Liver ; Liver Cirrhosis, Experimental ; therapy ; Mesenchymal Stem Cell Transplantation ; Rats ; Rats, Wistar ; Wnt Signaling Pathway

OBJECTIVETo investigate the effect of metronomic chemotherapy of low dose phosphoramide combined with prednisolone (CP metronomic chemotherapy) on proliferation and apoptosis of RPMI 8226 cells, and to explore its regulating effect on Notch1/NF-κB signaling pathways.

METHODSExperiment was divided into the DMSO control group, and the phosphoramide mustard (PM) group, the prednisolone group, the phosphoramide mustard plus prednisolone group (the CP group). RPMI 8226 cells were treated with different drugs, CCK-8 method was used to detect cell proliferation, flow cytometry was used to detect the cell cycle and apoptosis, reverse transcription PCR was used to detect Notch1 and NF-κB mRNA expression level.

RESULTSCompared with DMSO control group, RPMI8226 cell proliferation inhibition rate in all the PM, prednisolone and CP groups increased significantly with prolonging of time (r of 0.994,0.996,0.999, respectively, P<0.001). And at the same time, the inhibitory rate of cell proliferation was significantly different; the cell inhibitory rate in PM group was lowest, that in CP group was highgest, that in prednissone group was intermediate (P<0.01). After 48 hours, compared with the DMSO control group, the G/Gcell proportion in treatment group increased significantly, S phase cell proportion decreased significantly, especially in PM and CP groups. The G/M phase cell proportion increased in PM group, while reduced in the prednisolone and the CP groups. After 48 hours, compared with the DMSO control group, RPMI 8226 cell apoptosis rate increased as follow: in PM, pre-dnisolone and CP group(P<0.01). After 48 hours, compared with the DMSO control group, Notch1 and NF-κB mRNA expression in the prednisolone, the PM and the CP group decreased significantly(P<0.001).

CONCLUSIONCP metronomic chemotherapy can significantly reduce RPMI 8226 cell proliferation, promote RPMI 8226 cell apoptosis, arrest RPMI 8226 cells mainly in the G/Gphase, and significantly reduce Notch1 and NF-κB expression levels. It is suggested that Notch1/NF-κB signaling pathways is involved in CP metronomic chemotherapy for MM.

To observe the effect of calycosin on the proliferation and activation of primary hepatic stellate cells (HSCs) in rats, and prove calycosin shows the effects through peroxisome proliferator-activated receptor γ(PPARγ) and farnesoid X receptor (FXR). The results indicated that calycosin could inhibit HSC proliferation and expressions of activation marker smooth muscle actin-α and type I collagen. With the increase in HSC activation time, FXR expression reduced, but with no notable impact from calycosin. Calycosin could up-regulate PPARγ expression and its nuclear transition in a concentration-dependent manner. Its prohibitory effect on HSC activation could be blocked by PPARγ antagonist. In conclusion, calycosin could inhibit HSC activation and proliferation, which may be related with the up-regulation of PPARγ signal pathway.
Animals ; Cell Proliferation ; drug effects ; Cells, Cultured ; Drugs, Chinese Herbal ; pharmacology ; Hepatic Stellate Cells ; cytology ; drug effects ; metabolism ; Isoflavones ; pharmacology ; Male ; PPAR gamma ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, Cytoplasmic and Nuclear ; genetics ; metabolism ; Up-Regulation ; drug effects

Establishment of quality management system (QMS) plays a critical role in the clinical data management (CDM). The objectives of CDM are to ensure the quality and integrity of the trial data. Thus, every stage or element that may impact the quality outcomes of clinical studies should be in the controlled manner, which is referred to the full life cycle of CDM associated with the data collection, handling and statistical analysis of trial data. Based on the QMS, this paper provides consensus on how to develop a compliant clinical data management plan (CDMP). According to the essential requirements of the CDM, the CDMP should encompass each process of data collection, data capture and cleaning, medical coding, data verification and reconciliation, database monitoring and management, external data transmission and integration, data documentation and data quality assurance and so on. Creating and following up data management plan in each designed data management steps, dynamically record systems used, actions taken, parties involved will build and confirm regulated data management processes, standard operational procedures and effective quality metrics in all data management activities. CDMP is one of most important data management documents that is the solid foundation for clinical data quality.
Clinical Trials as Topic ; Data Collection ; standards ; Database Management Systems ; standards ; Information Storage and Retrieval ; standards

OBJECTIVETo observe the effect of Yiguan Decoction (YGD) on differentiation of bone marrow mesenchymal stem cells (BMSCs) into hepatocyte-like cells in vitro.

METHODSRat BMSCs were isolated using whole bone marrow adherent method. The properties of BMSCs were identified by analyzing the expression of surface cytokines by flow cytometry. The third passage cells were differentiated into fat cells to identify their features. BMSCs were incubated with hepatocyte growth factor (HGF) plus fibroblast growth factor 4 (FGF4) or YGD containing serum YGD for 21 days. The mRNA expression of alpha-fetoprotein (alphaAFP), albumin (Alb), and hepatocyte nuclear factor 4alpha (HNF4alpha) were detected by real time PCR. Expression of AFP and cytokeratin 18 (CK18) protein was detected by cell immunofluorescence. Glycogen synthesis was observed using periodic acid-Schiff stain (PAS). CK18, Wnt 3alpha, and alphacatenin protein expressions were detected by Western blot.

RESULTSHigh expression of CD90, CD29, and CD44, and low expression of CD34 and CD11b were observed in BMSCs isolated by whole bone mar- row adherent method, and numerous lipid droplets were observed in BMSCs using oil red O staining. Both YGD containing serum and growth factor stimulated the expression levels of Alb, AFP, HNF4alpha mRNA and CK18 protein. The down-regulated expression of Wnt 3alpha and beta-catenin could be detected at 21 days after induction. The synthesized glycogen granule could be seen. Down-regulated Wnt 3alpha and beta-catenin expression could also be observed.

CONCLUSIONYGD could induce the differentiation of rat BMSCs into hepatocyte-like cells, which was related to down-regulating Wnt/beta-catenin signal pathway.

Animals ; Bone Marrow Cells ; cytology ; drug effects ; Cell Differentiation ; drug effects ; Cells, Cultured ; Drugs, Chinese Herbal ; pharmacology ; Hepatocytes ; cytology ; Male ; Mesenchymal Stromal Cells ; cytology ; drug effects ; Rats ; Rats, Sprague-Dawley ; Wnt Signaling Pathway

OBJECTIVETo observe the changes in the expressions of somatomedins in the prostate epithelial cells in anoxic condition.

METHODSWe cultured prostate epithelial cell line RWPE-1 in vitro. At 4, 8, 12, 24, 48 hours after seeding of the cells, we determined the gene and protein expressions of the epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), transforming growth factor-beta (TGF-beta), insulin-like growth factor-1 (IGF-1) and vascular endothelial growth factor (VEGF) in the prostate epithelial cells by RT-PCR and ELISA, respectively.

RESULTSWith the increase of time, the expressions of the EGF, bFGF, TGF-beta, IGF-1 and VEGF genes were obviously up-regulated, more significantly in the anoxic than in the normoxic prostate epithelial cells. Take FGF mRNA, its expression level was 0.14 +/- 0.01 in the anoxic and 0. 12 +/- 0.01 in the normoxic prostate epithelial cells at 8 hours (P = 0.01), but increased to 0.29 +/- 0.01 and 0.14 +/- 0.01, respectively, at 48 hours (P < 0.001). The expression of the TGF-beta protein was also more significantly increased in the anoxic than in the normoxic prostate epithelial cells, 0.32 +/- 0.01 versus 0.26 +/- 0.01 at 4 hours (P = 0.017) and 1.56 +/- 0.13 versus 0.87 +/- 0.06 at 48 hours (P < 0.001). The other 4 somatomedins showed no significant differences in their protein expressions between anoxic and normoxic conditions.

CONCLUSIONAnoxia can up-regulate the gene expressions of somatomedins and increase the secretion of TGF-beta in prostate epithelial cells.

Cell Hypoxia ; Cell Line ; Epithelial Cells ; metabolism ; Gene Expression Regulation ; Humans ; Male ; Prostate ; cytology ; Somatomedins ; metabolism ; Transforming Growth Factor beta ; metabolism ; Up-Regulation