Considerations on investigation on quality standard of Chinese patent medicine / 药学学报

Chinese patent medicine (CPM) is an important part of traditional and Chinese medicine (TCM). Its quality has direct impact on the safety and effectiveness of clinical use. The quality standard is the pivotal approach to guarantee the quality of CPM. Due to the complex material basis, multitudinous quality influencing factors and unveiled active ingredients, dose-effect relationship and action mechanism, the investigation on quality standard faces many difficulties. This paper surveys the current quality status of CPM and the general situation of CPM standards. At present, the dosing problem has the crucial impact on the quality of CPM. The current quality standard system of CPM is confirmed and the limitations are indicated. Based on the above analysis, the principles and considerations on investigation of quality standard are proposed as follows: ① Adhere to safety as the bottom line, strengthen the risk-control ability of the standard of CPM; ② Adhere to theory of TCM and comprehensive quality, improve the integrative control level of the CPM standard; ③ Emphasize technological development and innovation, promote the quality control competence of CPM standard; ④ Facilitate planning and coordination, optimize the management of the CPM standard system; ⑤ Reinforce investigation on evaluation method, develop grade evaluation standard, accelerate high-quality development of CPM. Finally, the future perspective on investigation of CPM quality standard is prospected.

Wandering rod: form lumbar spine into left pleural cavity with nerve irritated symptoms.

Spinal instrumented rod migrating from the surgical site to another remote site in the body is rare. Some cases result in organ or blood vessel injury. Most reported cases were asymptomatic until the finally injuries were generated. We report a unique case of spinal implant failure in which the rod moved from lumbar spine into chest 13 years post lumbar instrumentation. The migrated rod caused no damage to the organs in the pleural cavity but did cause an atypical pleural irritation syndrome which seemed to correlate with the mechanical irritation caused by the rod. These atypical symptoms of rod migration have not been reported previously.

Analysis and health risk assessment, including recommendation of limits for heavy metals and harmful elements in Chinese patent medicines / 药学学报

Heavy metals and other harmful elements in traditional Chinese medicines inflict serious damage on public health. Therefore, risk assessment of Chinese raw materials has gained increasing attention. To date, few reports have been published on the health risk assessment of heavy metals and harmful elements in Chinese patent medicines. To gain a comprehensive understanding of heavy metals and other harmful elements in Chinese patent medicines and to establish proper limits, residual Pb, Cd, As, Hg, Cu and Cr in 15 054 samples of 295 drugs was analyzed with regard to distribution and variation between elements and dosage forms. In addition, in accord with procedures including hazard identification, hazard characterization, exposure assessment and risk characterization, basic procedures and specific parameters for risk assessment of heavy metals and harmful elements in Chinese patent medicines were clarified based on the health risk assessment of 14 787 samples and 276 drugs. A method and equation for establishing residual limits is proposed. The results show that content and target hazard quotients (THQs) of the investigated elements in all samples showed a skewed distribution approaching 0. Content of Pb, As, Cu, Hg, Cd or Cr in the samples exceeded 100 mg·kg-1 and the content of Pb, As, or Cu in individual samples exceeded 1 000 mg·kg-1. THQs of 586 samples and four drugs were above 1. We believe that the health risk of Hg, Pb and As in Chinese patent medicines with dosage forms of pill, capsule, tablet and powder, especially those in raw powder preparations, warrant concern.

HPLC Determination of Four Flavonoids of Aurantii Fructus Immaturus in Niuhuang Qingwei Pills and Genetic Analysis of Medicinal Materials / 中国实验方剂学杂志

Objective: To establish an high performance liquid chromatography (HPLC) method for the simultaneous determination of four constituents in Niuhuang Qingwei pill (narirutin,naringin,hesperidin,and neohesperidin), and identify the source of Fructus Aurantii Immaturus. Method: The analysis was performed on a Waters CORTECS C18 column (4.6 mm×50 mm,2.7 μm), with acetonitrile-0.12% formic acid solution as the mobile phase for gradient elution. The flow rate was 0.5 mL·min-1, the detection wavelength was set at 283 nm, and the column temperature was 27℃. Result: 12 batches of Niuhuang Qingwei pills showed the different content of flavonoids as Citrus aurantium and C. sinensis. Narirutin,naringin,hesperidin and neohesperidin showed good linear relationships within the ranges of 5.47-2 735 ng (r=0.999 6),7.25-3 625 ng (r=0.999 5),8.41-4 205 ng (r=0.999 4) and 8.36-4 180 ng (r=0.999 5),and their average recoveries were 101.3% (n=6,RSD 2.9%),98.0% (n=6,RSD 1.8%),95.9% (n=6,RSD 0.8%) and 96.0% (n=6,RSD 1.1%), respectively. The contents of narirutin,naringin,hesperidin,neohesperidin and total flavonoids were 0.36-1.28,2.66-4.87,1.02-11.07,3.58-6.41,and 7.98-13.34 mg·g-1, respectively. Conclusion: The developed method was simple,accurate and reliable,which can be used to identify the source of Aurantii Immaturus Fructus and simultaneously determine the content of four flavonoids in Niuhuang Qingwei pills. It could provide basic research for quality control and composition comparison of 2 kinds of Niuhuang Qingwei pills, showing more comprehensive indicators and reference value for the quality standard improvement of Niuhuang Qingwei pill.

Limit Test of Camphor in Niuhuang Qingxin Pills (Prescription of the Bureau) / 医药导报

Objective To establish limit test method of camphor in Niuhuang qingxin pills (prescription of the bureau) . Methods The separation was performed on an HP-INNOWAX capillary column (0.25 mm×30 m, 0.25 μm) and the column temperature was 110 ℃ . The temperatures of the inlet and the FID detector were 200 and 230 ℃ , respectively. The flow rate of the carrier gas was 1.8 mL·min-1 and the split ratio was 10:1. The injection volume was 1 μL. Results Good linearity was obtained for camphor within the range of 1.65 to 165 μg·mL-1, and the average recovery of low, medium, high concentration were 99.12％, 99.56％ and 99.56％, respectively,with RSD were 1.01％,0.69％ and 0.38％, respectively. Trace camphor was found in 7 samples out of 38 samples from 9 manufactures. Conclusion The proposed method was accurate, sensitive and simple, and was suitable for quality evaluation and safety control of Niuhuang qingxin pills (prescription of the bureau) .

Pharmacological network-based study on quality control of Carthamus tinctorius L. for safflower injection / 药学学报

We determined a component-target-disease network for Carthamus tinctorius L. and the key compounds, identified by topological analysis, were related to vasculitis, coronary heart and cerebrovascular disease. Based on these compounds, the chromatographic fingerprint of Carthamus tinctorius L. was established. Firstly, 132 compounds were obtained from TCMID and TCMSP databases. Their targets were predicted in the PharmMapp and HemMapper databases. CardioGenBase, Therapeutic Target Database and DisGeNET databases were used to collect targets of vasculitis, coronary heart disease and cerebrovascular disease. The corresponding relationships between component and target protein were established by mapping. Finally, the "component-target-disease" network was built with Cytoscape software. The core network and key nodes were analyzed with the Cytohubba plug-in. The results showed that the 24 key compounds were alpha-tocopherol, adenosine, quinone chalcone pigments such as hydroxysafflor yellow A, safflower yellow, quercetin, kaempferol and other flavonoids, organic acids such as stearic acid, linolenic acid, coumaric acid and cinnamic acid. This resulting chromatographic fingerprint of Carthamus tinctorius L. showed good consistency, and the core chemical compounds obtained by topological analysis of the network of "component-target-disease", could be used as quality control markers. Our research provides a new approach for the identification of quality control indicators in Chinese medicinal materials.

Feasibility exploration of discriminating red yeast rice for different applications by secondary metabolite fingerprints / 药学学报

Though red yeast rice (RYR) has been used as medicine for centuries, few study has been reported about its biological activities related to traditional medicinal application and marketed RYR showed poor consistency in quality. In this study, with comprehensive investigation of their production processes and field acquisition samples including those from genuine producing area, an ultra performance liquid chromatographic (UPLC) method was firstly established to discriminate RYR for different applications based on their secondary metabolites fingerprint. It was performed on a CAPCELL CORE AQ column (100 mm×4.6 mm, 2.7 μm), with PDA (range: 200-650 nm, extracted: 237 nm) and ELSD detection. The mobile phase used was water (A) and acetonitrile (B) both containing 0.1% formic acid at gradient elution (0-15 min, 50% B→85% B (linear); 15-16 min, 85 % B→50% B (linear) and maintained until 21 min), with a flow rate of 0.5 mL∙min-1. The method established was fully validated in agreement with guidelines of Chinese Pharmacopeia. Common metabolites were found in RYR for same application and the fingerprints of RYR for food coloring or brewing from various manufacturers had similarities above 0.90. Meanwhile, significant differences were observed among the fingerprints for various applications and discrimination could be achieved by principal component analysis (PCA). Lovastatin was absence in RYRs for food coloring or brewing, and the fingerprint of traditional medicinal RYR was similar to that of RYR for brewing. However, standardization was required for RYR containing lovastatin because of their significant differences from various manufacturers in fingerprints and lovastatin content. The results demonstrated the feasibility to discriminate RYR for different applications by the secondary metabolites fingerprint method established in this study, which provides a scientific basis to investigate the relationship between biological activities of medicinal RYR and their corresponding secondary metabolites, and further aid their quality standardization and improvement.

Analysis and Discussion on Quality Standard of TCM Preparation in Guangdong Provincial Medical Institution Preparation Specification / 中国药房

OBJECTIVE： To provide reference for perfecting the quality standard revision of TCM preparations in medical institutions， and improving the quality standard of TCM preparations in medical institutions. METHODS： By sorting out the quality standards of TCM preparations in Guangdong provincial medical institution preparation specification， this paper summarized the main problems and put forward suggestions for improvement. RESULTS & CONCLUSIONS： There are 897 kinds of TCM preparations included in the Guangdong provincial medical institution preparation specification. The recent quality standards （2017 edition） have been greatly improved compared with those of the first edition （1985 edition）； however， there are still some problems in the overall quality control of preparations， quantitative control of indicative components， project specificity， source control of medicinal materials， control of medicinal materials not included in the Chinese Pharmacopoeia and quality standards of the same series of varieties. It is suggested that on the premise of considering both advancement and applicability， the quality control of the whole， local and toxic preparations of TCM hospitals should be strengthened， the detection methods with good specificity and reproducibility should be properly updated， the control of key parameters of production process should be strengthened， the quality standard of TCM preparations in medical institutions should be fully improved， so as to provide the products with safe， effective and controllable in quality products in medical institutions.

Research progress on chemical constituents and quality control of Tripterygium wilfordii preparations / 中国中药杂志

Tripterygium wilfordii preparations,with various biological activities such as immunosuppressive,anti-inflammatory and anti-cancer effects,are widely used in the treatment of autoimmune diseases such as rheumatoid arthritis,lupus erythematosus,and nephrotic syndrome. They have definite therapeutic effect,but often cause serious adverse reactions and result in damages to liver,kidney,blood,reproduction,and other systems due to their complex compositions,great toxicity,and narrow margin between the toxic and therapeutic dosages. At present,T. wilfordii preparations produced by different manufacturers exhibit large variations in clinical efficacy and side effects in account of their different chemical compositions and quality fluctuation due to differences in raw materials and production process. However,the existing quality standards are controversial in terms of index components and content limit,which cannot be effectively used for the overall quality control of the preparations. In this paper,the research progress on chemical constituents,quality standard and quality control methods of four T. wilfordii preparations including Tripterygium Tablets,Tripterygium Zongtie Tablets,Tripterygium Shuangceng Tablets and Tripterygium Glycosides Tablets was reviewed,in order to provide ideas and reference for the quality improvement of this type of preparations.

Determination and risk assessment of heavy metals and harmful elements residues in Niuhuang Qingwei Pills based on ICP-MS / 中国中药杂志

To achieve a comprehensive understanding of heavy metals and harmful elements residues in Niuhuang Qingwei Pills,49 samples from 18 manufactures were collected from 31 provinces in China.Risk assessment and control preparations were applied innovatively in evaluation of exogenous pollution in traditional Chinese Medicine.Determination methods for Pb,Cd,As,Hg and Cu were established by inductively coupled plasma mass spectrometry(ICP-MS).Based on the procedures including hazard identification,hazard characterization,exposure assessment and risk characterization,risk assessment was performed and residual limits for Pb,Cd,As,Hg and Cu in the drug were formulated.The results showed that the hazardous quotients(HQ) of the elements were decreased in the following order:Pb>As>Cu>Hg>Cd,and the total hazardous index(HI) of heavy metals and harmful elements in Niuhuang Qingwei Pills was above 1,implying health risk of the drug.Under the proposed limits,5 elements in the control preparation as well as Cd and Cu in the samples were within the limits range,but the excess rates of Pb,As and Hg in the samples were 12%,12% and 14%,respectively.For the first time,basic steps for risk assessment of Chinese patent medicine were established,which provided model and reference for risk assessment and limit formulation of other drugs.

Linking gut microbiota, metabolic syndrome and economic status based on a population-level analysis.

BACKGROUND: The metabolic syndrome (MetS) epidemic is associated with economic development, lifestyle transition and dysbiosis of gut microbiota, but these associations are rarely studied at the population scale. Here, we utilised the Guangdong Gut Microbiome Project (GGMP), the largest Eastern population-based gut microbiome dataset covering individuals with different economic statuses, to investigate the relationships between the gut microbiome and host physiology, diet, geography, physical activity and socioeconomic status. RESULTS: At the population level, 529 OTUs were significantly associated with MetS. OTUs from Proteobacteria and Firmicutes (other than Ruminococcaceae) were mainly positively associated with MetS, whereas those from Bacteroidetes and Ruminococcaceae were negatively associated with MetS. Two hundred fourteen OTUs were significantly associated with host economic status (140 positive and 74 negative associations), and 157 of these OTUs were also MetS associated. A microbial MetS index was formulated to represent the overall gut dysbiosis of MetS. The values of this index were significantly higher in MetS subjects regardless of their economic status or geographical location. The index values did not increase with increasing personal economic status, although the prevalence of MetS was significantly higher in people of higher economic status. With increased economic status, the study population tended to consume more fruits and vegetables and fewer grains, whereas meat consumption was unchanged. Sedentary time was significantly and positively associated with higher economic status. The MetS index showed an additive effect with sedentary lifestyle, as the prevalence of MetS in individuals with high MetS index values and unhealthy lifestyles was significantly higher than that in the rest of the population. CONCLUSIONS: The gut microbiome is associated with MetS and economic status. A prolonged sedentary lifestyle, rather than Westernised dietary patterns, was the most notable lifestyle change in our Eastern population along with economic development. Moreover, gut dysbiosis and a Western lifestyle had an additive effect on increasing MetS prevalence.

Author Correction: Regional variation limits applications of healthy gut microbiome reference ranges and disease models.

In the version of this article originally published, in the sentence "Applying the same approach to obesity (Fig. 2b), MetS (Fig. 2c) and fatty liver (Fig. 2d) yielded similar results," two figure panels were cited incorrectly. The data for obesity are in Fig. 2c, and the data for MetS are in Fig. 2b. The sentence has been updated with the correct citations in the print, PDF and HTML versions of the article.

Regional variation limits applications of healthy gut microbiome reference ranges and disease models.

Dysbiosis, departure of the gut microbiome from a healthy state, has been suggested to be a powerful biomarker of disease incidence and progression1-3. Diagnostic applications have been proposed for inflammatory bowel disease diagnosis and prognosis4, colorectal cancer prescreening5 and therapeutic choices in melanoma6. Noninvasive sampling could facilitate large-scale public health applications, including early diagnosis and risk assessment in metabolic7 and cardiovascular diseases8. To understand the generalizability of microbiota-based diagnostic models of metabolic disease, we characterized the gut microbiota of 7,009 individuals from 14 districts within 1 province in China. Among phenotypes, host location showed the strongest associations with microbiota variations. Microbiota-based metabolic disease models developed in one location failed when used elsewhere, suggesting that such models cannot be extrapolated. Interpolated models performed much better, especially in diseases with obvious microbiota-related characteristics. Interpolation efficiency decreased as geographic scale increased, indicating a need to build localized baseline and disease models to predict metabolic risks.

Acquisition technology for optical ground stations in satellite-ground quantum experiments.

To establish optical links between an optical ground station (OGS) and a quantum experiment satellite, a method of acquisition for the Micius satellite is proposed in this paper and the acquisition technological specification of the OGS system is analyzed. An acquisition strategy for the OGS is designed to meet the requirements of the quantum experiments. A method is designed to point accurately at the quantum satellite and improve the absolute pointing precision. The results show that the correction accuracy is better than 5 µrad, the acquisition time is less than 5 s, and the acquisition probability is 100% so far.

Application of radical method to evaluation of antioxidant activity of Vleriana jatamansi Jones / 药学学报

The antioxidant activities of Vleriana jatamansi Jones were investigated and the relationship between the antioxidant effect and the chemical structure was explored. The free radical scavenging test, 2,2-diphenyl-1-picrylhydrazyl (DPPH•), was used to evaluate the antioxidant activities of the extracts of Vleriana jatamansi Jones with 0−100% menthol as extraction solvents. The polar and nonpolar HPLC conditions were conducted to isolate the main chemical compositions. The DPPH• tests were used in analysis of the free radical scavenging activities. Under polar HPLC separation conditions, 5 kinds of compounds were detected:chlorogenic acid, 3,5-dicaffeoylquinic acid, 4,5-dicaffeoylquinic acid, hesperidin, and coffeic acid; under nonpolar HPLC separation conditions, acevaltrate, 1β-acevaltrate and valtrate were founded. Chlorogenic acid, 3,5-dicaffeoylquinic acid, and 4,5-dicaffeoylquinic acid presented high DPPH• free radical scavenging activities. The results of antioxidant activity suggested that the coffee acyl from chlorogenic acid-like compounds had a high DPPH• free radical scavenging ability. Our investigation indicated that structure of the ortho hydroxyl phenol of chlorogenic acid-like compounds play a significant role in antioxidant activities. In addition, this work can also provide method and theory reference for improving the antioxidant activities of Vleriana jatamansi Jones.

Determination of Borneol and Iso-borneol in Niuhuang Qingxin Pills ( Prescription of the Bureau) by GC / 中国药师

Objective: To establish a GC method for the determination of borneol and isoborneol in Niuhuang Qingxin pills ( pre-scription of the bureau). Methods: A capillary column HP-INNOWAX(30 m×0. 25 mm,0. 25 μm) was used and the column tem-perature was kept at 110 ℃. The temperature of the inlet and the FID was 200 ℃ and 230 ℃, respectively. The carrier gas was N2 and the flow rate of the carrier gas was 1. 8 ml·min-1. The split ratio was 10: 1, and the injection volume was 1 μl. Results: The linear response range of borneol and isoborneol was 0. 01-5. 09 μg·ml-1(r=0. 999 5) and 0. 01-5. 03 μg·ml-1(r=0. 999 1), re-spectively. And the average recovery was 99. 34% and 99. 24% with the RSD of 0. 59% and 0. 62% , respectively (n=6). Conclu-sion: The proposed method is accurate, sensitive and simple, and can be used for the quality control of Niuhuang Qingxin pills (pre-scription of the bureau).

Quality control of Guci tablets using UPLC-ELSD fingerprint analysis coupled with chemometrics / 中国中药杂志

Ultra-performance liquid chromatography-evaporative light scattering detection (UPLC-ELSD) fingerprint analysis method was established for quality control of Guci tablets. Chromatographic separation was performed on Waters Acquity UPLC BEH C₁₈ column (2.1 mm×100 mm, 1.7 μm) at 30 °C of column temperature. Acetonitrile-0.1% formic acid solution was adopted as mobile phase for gradient elution. The flow rate was set at 0.3 mL·min⁻¹, and the injection volume was 3 μL. Detection was carried out on an ELSD with a nitrogen pressure of 0.28 MPa, drift tube temperature of 60 °C, and gain of 400. A total of 39 batches of samples produced by six manufacturers were measured by using the above method and the data were analyzed by ChemPattern software. The peak present in more than 75% of the samples was defined as a common peak, and 30 common peaks were determined. Among them, 19 peaks were identified by rapid resolution liquid chromatography/tandem mass spectrometry (RRLC-MS/MS) method, 16 of which were confirmed by reference substances. The similarity of the tested samples was 0.47-0.98, suggesting that the quality of the samples from different manufacturers varied greatly. Furthermore, principal component analysis (PCA) and hierarchical analysis (HCA) were performed to clarify the main different components in samples. The results indicated that there might be some feeding problems about Paeoniae Radix Alba, Notoginseng Radix et Rhizoma, and Clematidis Radix et Rhizoma in a few manufacturers. This study provided some evidences for the overall quality control of Guci tablets, as well as its quality standard improvements.

Newton Output Blocking Force under Low-Voltage Stimulation for Carbon Nanotube-Electroactive Polymer Composite Artificial Muscles.

This is a study on the development of carbon nanotube-based composite actuators using a new ionic liquid-doped electroactive ionic polymer. For scalable production purposes, a simple hot-pressing method was used. Carbon nanotube/ionic liquid-Nafion/carbon nanotube composite films were fabricated that exhibited a large output blocking force and a stable cycling life with low alternating voltage stimuli in air. Of particular interest and importance, a blocking force of 1.5 N was achieved at an applied voltage of 6 V. Operational durability was confirmed by testing in air for over 30 000 cycles (or 43 h). The superior actuation performance of the carbon nanotube/ionic liquid-Nafion/carbon nanotube composite, coupled with easy manufacturability, low driving voltage, and reliable operation, promises great potential for artificial muscle and biomimetic applications.

Guideline principle and technical requirement for preparing traditional Chinese medicine reference drug / 中国中药杂志

Traditional Chinese medicine (TCM) reference drug is a new form of TCM standard reference substance. The purpose of this guideline is to guide the establishment of the reference drug and standardize its investigation and application in national drug standards. Definition of TCM reference drug was specified and relating guideline and technical requirement were introduced in this paper. Its application in quality control of TCM was analyzed and the developing train was proposed. There is a wide prospect for the application of reference drug in quality control of TCM. Thus it has practical significance to explore and conduct the quality evaluation system by using TCM reference drug as the reference substance.