OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

Objective:The distribution characteristics of intrathecal drugs and the limitation of current catheterization techniques make traditional intrathecal analgesic treatment nearly useless for refractory craniofacial pain,such as trigemina neuralgia.This technical guideline aims to promote the widespread and standardize the application of intra-prepontine cisternal drug delivery via spinal puncture and catheterization. Methods:A modified Delphi approach was used to work for this guideline.On the issues related to the intra-prepontine cisternal targeted drug delivery technique,the working group consulted 10 experts from the field with 3 rounds of email feedback and 3 rounds of conference discussion. Results:For the efficacy and safety of the intra-prepontine cisternal targeted drug delivery technique,a consensus was formed on 7 topics(with an agreement rate of more than 80%),including the principles of the technique,indications and contraindications,patient preparation,surgical specifications for intra-prepontine cisternal catheter placement,analgesic dosage coordination,analgesic management,and prevention and treatment of complications. Conclusion:Utilizing the intra-prepontine cisternal drug infusion system to manage refractory craniofacial pain could provide advantages in terms of minimally invasive,secure,and effective treatment.This application can not only alleviate the suffering of individuals experiencing the prolonged pain but also support the maintenance of quality of life and dignity in their final moments,justifiing its widespread dissemination and standardized adoption in domestic and international professional fields.

Objective To investigate the current situation of Staphylococcus aureus contamination in raw and cooked meat and dairy products in Wuhan, and analyze the enterotoxins production and antimicrobial resistance of isolated bacterial strains. Methods The detection of Staphylococcus aureus was performed according to GB4789.10-2016 National Food Safety Standard. Staphylococcus aureus enterotoxin (SE) PCR kit and ELISA were used for SEA-E type detection. Broth dilution and PCR method were used for drug sensitivity test. Results A total of 13 strains of Staphylococcus aureus were isolated from 202 samples, and the isolation rate of Staphylococcus aureus in the raw and cooked meat and dairy products was 6.43%. The detection rate of Staphylococcus aureus was 9.82% (11/112) in raw meat, and 4% (2/50) in cooked meat products. There was no detection in dairy products. Of the 13 isolated strains, 6 strains were found to have enterotoxins, with a toxin production rate of 46.15% (6/13). Among the 6 strains of enterotoxin producing Staphylococcus aureus, 4 strains were classified as type A, C, D, and AB, respectively. The isolated strains were generally resistant to tetracycline and sulfonamide drugs, and the detection rate of resistant genes was more than 60%. The resistance rate to penicillin and erythromycin exceeded 50%, and the dominant resistance spectrum was the detection of 3 strains of single-resistant (PEN) Staphylococcus aureus (25.08%, 3/13), followed by 2 strains of five-fold resistance (PEN-ERY-CLI-SXT-GEN), and double resistance Staphylococcus aureus (PEN-ERY) (15.38%, 2/13). Genetic testing was consistent with phenotypic testing. Conclusion In 2020, there was a certain degree of contamination of Staphylococcus aureus in raw and cooked meat products in Wuhan, with 13 isolated strains and 6 strains producing enterotoxins. It is necessary to remain vigilant about the potential food risks of raw and cooked meat products, and strengthen the supervision of the safety risks of raw and cooked meat products.

Based on the focal adhesion kinase(FAK)/steroid receptor coactivator(Src)/extracellular regulated protein kinase(ERK) pathway, this study explored the effects of Xihuang Pills on angiogenesis, invasion, and metastasis in prostate cancer. Liquid chromatography-tandem mass spectrometry(LC-MS/MS) was used to analyze and identify the active ingredients of Xihuang Pills. Bioinformatics techniques, including R language and Perl programs, were employed to analyze the interactions between prostate cancer-related targets and the potential targets of Xihuang Pills. A subcutaneous transplantation tumor model of prostate cancer was established in nude mice using PC3 cells to verify the efficacy and molecular mechanisms of Xihuang Pills. In vitro cellular experiments, including cell proliferation assays(CCK-8), Transwell assays, scratch assays, real-time quantitative reverse transcription PCR, and Western blot, were used to detect the effects of Xihuang Pills on the proliferation, invasion, and migration of prostate cancer cells, as well as on FAK/Src/ERK pathway-related targets. LC-MS/MS identified 99 active ingredients in Xihuang Pills, including gallic acid, gentisic acid, artemisinin, corilagin, phenylbutazone-glucoside, thujic acid, and arecoic acid B. Network pharmacological analysis of the active ingredients in Xihuang Pills revealed that the FAK/Src/ERK signaling pathway was a key pathway in its anti-prostate cancer effects. In vivo and in vitro experiments confirmed that Xihuang Pills significantly inhibited the proliferation, invasion, and migration of PC3 and LNCaP cells, suppressed the growth of PC3 subcutaneous tumors, and reduced the protein expression levels related to the FAK/Src/ERK signaling pathway. In conclusion, the inhibition of angiogenesis, invasion, and metastasis by regulating the FAK/Src/ERK pathway is one of the mechanisms by which Xihuang Pills exert anti-prostate cancer effects.
Humans ; Male ; Prostatic Neoplasms/enzymology* ; Drugs, Chinese Herbal/chemistry* ; Animals ; Mice ; Cell Proliferation/drug effects* ; Mice, Nude ; Cell Movement/drug effects* ; Cell Line, Tumor ; src-Family Kinases/genetics* ; Neovascularization, Pathologic/metabolism* ; Neoplasm Metastasis ; Neoplasm Invasiveness ; Focal Adhesion Kinase 1/genetics* ; Extracellular Signal-Regulated MAP Kinases/genetics* ; MAP Kinase Signaling System/drug effects* ; Focal Adhesion Protein-Tyrosine Kinases/genetics* ; Signal Transduction/drug effects* ; Angiogenesis

Based on the androgen receptor(AR)/mammalian target of rapamycin(mTOR)signaling pathway, the effects of Xihuang Pills-medicated serum on the proliferation and apoptosis of prostate cancer LNCaP cells were investigated. The drug-containing serum of SD rats was prepared by intragastric administration of Xihuang Pills suspension. The effects of low-, medium-, and high-dose Xihuang Pills-containing serum on the in vitro proliferation of LNCaP cells were detected by cell counting kit-8(CCK-8). Flow cytometry was used to detect the apoptosis level of LNCaP cells after intervention with different concentrations of Xihuang Pills. Protein expression of cleaved cysteinyl aspartate-specific proteinase caspase-3(cleaved caspase-3), B-cell lymphoma-2(Bcl-2), and AR as well as the phosphorylation level of mTOR protein were detected by Western blot. The results showed that compared with the blank serum, the drug-medicated serum could blunt the activity of LNCaP cells. Low-, medium-, and high-dose Xihuang Pills-containing serum could significantly increase the cell apoptosis rate, increase the expression of cleaved caspase-3 protein, decrease the expression of Bcl-2 protein, reduce the expression of AR protein, and down-regulate the level of phosphorylated mTOR(p-mTOR). To study the effect of Xihuang Pills on the growth of LNCaP cells in vivo, different doses of Xihuang Pills were used to intervene in the subcutaneous graft model in nude mice inoculated with LNCaP cells. The expression levels of AR, mTOR, p-mTOR, Bcl-2, and cleaved caspase-3 were detected by Western blot. The results showed that the volumes of subcutaneous graft tumor in the low-dose, medium-dose, and high-dose Xihuang Pills groups significantly decreased compared with that in the model group. The weight of subcutaneous transplanted tumor in each group with drug intervention was significantly lower than that in the model group. Compared with the model group, the low-dose, medium-dose, and high-dose Xihuang Pills groups showed increased cleaved caspase-3 protein expression, decreased Bcl-2 and AR protein expression, and reduced p-mTOR protein expression. Further experiments showed that AR agonist R1881 could block the anti-proliferation and pro-apoptotic effects of Xihuang Pills. The mechanism of Xihuang Pills against prostate cancer is related to the inhibition of the AR/mTOR signaling pathway, inhibition of LNCaP cell proliferation, and induction of apoptosis in cancer cells.
Humans ; Male ; Mice ; Rats ; Animals ; Caspase 3/metabolism* ; Mice, Nude ; Cell Line, Tumor ; Rats, Sprague-Dawley ; Signal Transduction ; TOR Serine-Threonine Kinases/metabolism* ; Prostatic Neoplasms/pathology* ; Cell Proliferation ; Apoptosis ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Mammals/metabolism*

Humans ; Melanoma ; Metaplasia ; Mucous Membrane ; Nasopharynx

ObjectiveTo study on the correlation between the apparent color， near-infrared spectroscopy and dynamic changes of index constituent content of samples during the processing of steamed Notoginseng Radix et Rhizoma， and to provide reference for the processing process optimization and quality control of this decoction piece. MethodSamples were dried and crushed by setting three steaming temperature gradients of 100-105， 114-118， 130-136 ℃， and sampled at steaming times of 1， 2， 4， 8， 12， 24 h， respectively. The effects of different steaming temperatures and times on the color and absorption of steamed Notoginseng Radix et Rhizoma at different infrared wavelengths were observed， and principal component analysis and cluster analysis were performed on the obtained data by R 4.1.0 and SPSS 21.0 software to observe the changes in color and infrared absorption characteristics of samples. High performance liquid chromatography （HPLC） was employed to determine the content changes of notoginsenoside R₁， ginsenoside Rg₁， ginsenoside Rb₁， ginsenoside Re， 20（S）-ginsenoside Rg₃ and 20（R）-ginsenoside Rg₃ before and after steaming of Notoginseng Radix et Rhizoma， mobile phase was acetonitrile （A）-water （B） for gradient elution （0-30 min， 19%A； 30-60 min， 19%-44%A； 60-78 min， 44%-74%A； 78-80 min， 74%-100%A； 80-86 min， 100%A； 86-87 min， 100%-19%A； 87-95 min， 19%A） with the detection wavelength of 203 nm. ResultDuring the steaming process of Notoginseng Radix et Rhizoma， with the increase of steaming temperature and time， the b^* （yellow-blue value）， L^* （brightness）， △E^* （comprehensive color difference value） of sample powder showed a decreasing trend， while the a^* （red-green value） showed an increasing trend， and the color gradually deepened from gray to brown and dark black. There was no significant difference in the infrared absorption between raw and steamed Notoginseng Radix et Rhizoma sample powder in the low and medium wavelength bands， but significant difference in the infrared absorption of high band， especially in the band of 9 600-10 000 cm^-1. HPLC showed that the contents of the original components （notoginsenoside R₁， ginsenoside Rg₁， Re and Rb₁） decreased and 20（S）-ginsenoside Rg₃ and 20（R）-ginsenoside Rg₃ were newly produced after steaming of Notoginseng Radix et Rhizoma. The content proportion of these six index components reached the best when the steaming temperature at 130-136 ℃ and the steaming time of 1 h. ConclusionThe color and infrared absorption of samples are affected by the dynamic changes of chemical composition during the steaming process， and the composition change is the result of the joint influence of steaming temperature and time. In this paper， through multi-dimensional analysis of the apparent color indexes， the change pattern of near-infrared absorption characteristics and the index components of the samples， the different process parameters of steamed Notoginseng Radix et Rhizoma were evaluated holistically， and the quality transfer pattern of its processing process was initially revealed， which can provide scientific basis for processing optimization and quality evaluation of steamed Notoginseng Radix et Rhizoma.

Since "the implementation of good clinical practice"(GCP), especially after 2015, the overall quality of new drug cli-nical trials in China has made significant progress, but compared with developed countries, there are still some obvious quality problems in clinical trials in China. Clinical trials of new drugs of traditional Chinese medicine are an important part of clinical trials of new drugs in China. In addition to some common problems in all clinical trials, there are also some special quality problems. In terms of security data, such as the collection of human safety data is not standardized, the management and judgment of unexpected serious adverse reactions(SUSAR) were not professional and timely, the relationship between adverse events and trial drug was not fully judged by investigator, In terms of effective data, such as primary efficacy outcome of the scale cannot be traced, TCM syndrome data cannot meet the requirements of "source data" in the revised GCP and the quality of traditional Chinese medicine placebo is not high, in terms of overall quality system construction, the sponsors and research institutions have not established a quality assurance system that conforms to the characteristics of new drug research of traditional Chinese medicine, etc. The quality of clinical trials of new drugs of traditional Chinese medicine is based on the current GCP and ICH-GCP in China, we should also consider the characteristics of clinical trials of new traditional Chinese medicine drugs, and formulate targeted quality control measures according to the characteristics of these new drugs of traditional Chinese medicine, to improve the overall quality of clinical trials of new drugs of traditional Chinese medicine in China, which has important strategic significance for promoting the research and development of new drugs of traditional Chinese medicine in China.
China ; Clinical Trials as Topic ; Consensus ; Drugs, Chinese Herbal/therapeutic use* ; Humans ; Medicine, Chinese Traditional ; Quality Control

Solid preparations account for more than 50% of traditional Chinese medicines(TCM). TCM powder is an important raw material for solid preparations of TCM. Its powder properties directly affect the quality of solid preparations, and even clinical safety and effectiveness. Particle design technology based on the characteristics of powder in TCM is an important means to improve and enhance the quality of solid preparations. This study summarized the relevant principles, methods, characteristics, classification, equipment, and other elements of particle design technology in recent years, analyzed the difficulties in its application in the field of TCM powder, and proposed the strategies in conjunction with the development of computer data mining. The present study is expected to provide a reference for the suitability of particle design in the field of TCM powder.
Drugs, Chinese Herbal ; Medicine, Chinese Traditional ; Powders ; Technology

Targeting the deficiencies of Lingzhu Powder, this study introduced the particle design technology to improve its quality. Based on the mechanism of particle design for powder and the characteristics of solvent evaporation method, composite particles consisting of Succinum, Cinnabaris, and artificial Bovis Calculus were prepared. And the powder properties of composite particles and physical mixtures as well as the content uniformity of toxic components were investigated for exploring the technological advantages of particle design in improving the quality of Lingzhu Powder. The results showed that the composite particles prepared using solvent evaporation method and particle design technology were micro-particles, and the stable agglomerate structure could be observed under SEM. Composite particles exhibited better fluidity and compliance in oral intake than physical mixtures. The differences in chromatism, bulk density, and content uniformity of the composite particles were smaller than those of physical mixtures, and the corresponding RSD values \[4.8%, 1.8%, 3.4%(bilirubin), and 0.63%(HgS), respectively\] were smaller. The solvent evaporation combined with particle design technology can be utilized to significantly improve the quality of Lingzhu Powder, which has provided new ideas for the optimization of the quality of traditional Chinese medicinal powder.
Particle Size ; Powders ; Solvents ; Technology