OBJECTIVE To standardize the main processes and related technical links of the clinical comprehensive evaluation of drugs， and provide guidance and reference for improving the quality of comprehensive evaluation evidence and its transformation and application value. METHODS The construction of Guideline for the Workflow of Clinical Comprehensive Evaluation of Drugs was based on the standard guideline formulation method of the World Health Organization （WHO）， strictly followed the latest definition of guidelines by the Institute of Medicine of the National Academy of Sciences of the United States， and conformed to the six major areas of the Guideline Research and Evaluation Tool Ⅱ. Delphi method was adopted to construct the research questions； research evidence was established by applying the research methods of evidence-based medicine. The evidence quality classification system of the Chinese Evidence-Based Medicine Center was adopted for evidence classification and evaluation. The recommendation strength was determined by the recommendation strength classification standard formulated by the Oxford University Evidence-Based Medicine Center， and the recommendation opinions were formed through the expert consensus method. RESULTS & CONCLUSIONS The Guideline for the Workflow of Clinical Comprehensive Evaluation of Drugs covers 4 major categories of research questions， including topic selection， evaluation implementation， evidence evaluation， and application and transformation of results. The formulation of this guideline has standardized the technical links of the entire process of clinical comprehensive evaluation of drugs， which can effectively guide the high-quality and high-efficient development of this work， enhance the standardized output and transformation application value of evaluation evidence， and provide high-quality evidence support for the scientific decision-making of health and the rationalization of clinical medication.

Objective:To explore the expression and importance of Piezo1, E-cadherin, and Vimentin in nasal polyps patients. Methods:Thirty-five patients undergoing endoscopic sinus surgery under general anesthesia were streamed into 20 cases of nasal polyps（NP group） and 15 cases of simple septoplasty without any sinus disease（Control group）. Immunofluorescence staining and Western Blot were applied to detect the protein level of Piezo1, E-cadherin, and Vimentin in NP tissues and nasal polyp-derived primary human nasal epithelial cells（pHNECs）. Also, BEAS-2B cell lines were treated with human TGF-β1 protein to establish epithelial mesenchymal transition（EMT） model in vitro and quantitative real-time polymerase chain reaction were used to calculate Piezo1 and above biomarkers in the model. Results:Compared with control group, Piezo1 and Vimentin showed higher level while E-cadherin was lower in NP tissues and pHNECs.In EMT model in vitro, Piezo1 and Vimentin were demonstrated higher expression with decreased level of E-cadherin. Conclusion:The tendency of Piezo1 is consistent with the mesenchymal-related biomarker Vimentin, going against with epithelial-related biomarker E-cadherin, implying its involvement with EMT process in nasal polyps.
Humans ; Biomarkers/metabolism* ; Cadherins/metabolism* ; Chronic Disease ; Epithelial-Mesenchymal Transition ; Nasal Polyps/metabolism* ; Rhinosinusitis ; Sinusitis ; Transforming Growth Factor beta1/metabolism* ; Vimentin/metabolism*

OBJECTIVE To analyze the odor composition changes of two kinds of traditional Chinese medicine sachet （children type and adults type） with different placement time by using ultra-fast gasphase electronic nose technology. METHODS The change rule of sachet components at different storage times was analyzed by gas chromatography. At the same time， the qualitative results were obtained by combining electronic nose with Arochembase database. Discriminant factor analysis was used to analyze the overall odor composition differences of the two sachet samples. RESULTS A total of 10 odor compositions were identified in children-type sachet， including α-pinene and β-pinene as the functional index compositions； five odor compositions of children-type sachet disappeared after 0.25 days， and most of them disappeared after 7 days； the cumulative contribution rate of discriminant factor analysis was 99.225%. A total of 8 odor compositions were identified in adult-type sachets， including α-pinene and α-phellandrene as the functional index compositions； four odor components disappeared after the adult-type sachet was placed for 0.25 days； after 15 days of placement， the peak 6-8 disappeared， and the intensity of peak 5 decreased by 34.3% compared with 0 day of placement； the cumulative contribution rate of discriminant factor analysis was 91.965%. CONCLUSIONS With the extension of storage time， the smell and composition of the two traditional Chinese medicine sachets are decreasing. It is recommended that the use time of children-type sachet is 7 days， and that of adult-type sachet is 15 days.

Polymyxin B, which is a last-line antibiotic for extensively drug-resistant Gram-negative bacterial infections, became available in China in Dec. 2017. As dose adjustments are based solely on clinical experience of risk toxicity, treatment failure, and emergence of resistance, there is an urgent clinical need to perform therapeutic drug monitoring (TDM) to optimize the use of polymyxin B. It is thus necessary to standardize operating procedures to ensure the accuracy of TDM and provide evidence for their rational use. We report a consensus on TDM guidelines for polymyxin B, as endorsed by the Infection and Chemotherapy Committee of the Shanghai Medical Association and the Therapeutic Drug Monitoring Committee of the Chinese Pharmacological Society. The consensus panel was composed of clinicians, pharmacists, and microbiologists from different provinces in China and Australia who made recommendations regarding target concentrations, sample collection, reporting, and explanation of TDM results. The guidelines provide the first-ever consensus on conducting TDM of polymyxin B, and are intended to guide optimal clinical use.
Humans ; Anti-Bacterial Agents/therapeutic use* ; China ; Drug Monitoring/methods* ; Polymyxin B ; Practice Guidelines as Topic

OBJECTIVE To explore the mechanism of Kuaisong yin in the prevention and treatment of constipation. METHODS Slow transit constipation （STC） model was established with Compound difenoxylate tablet in mice and rats. Two batches of mice were divided into blank group， model group， positive control group （Maren soft capsule， 0.64 g/kg）， Kuaisong yin low-dose， medium-dose and high-dose groups （3.2， 6.4， 12.8 g/kg）， with 10 mice in each group. The effect of Kuaisong yin on constipation in mice was evaluated by intestinal propulsion experiment and defecation experiment. Rats were divided into blank group， model group， positive control group （Maren soft capsule，0.36 g/kg）， Kuaisong yin low-dose and high-dose groups （2.4， 4.8 g/kg）， with 7 or 8 rats in each group. They were given relevant medicine once a day for 1 week. The metabonomics of serum and urine of rats were analyzed by UPLC-Q-TOF-MS/MS technology. RESULTS Compared with model group， the ink propulsion rate and 5 h defecation volume of mice in Kuaisong yin high-dose group were significantly increased （P＜0.05）； the first defecation time of mice in Kuaisong yin medium-dose and high-dose groups was significantly shortened， and the quality of defecation was significantly reduced within 5 h （P＜0.05 or P＜0.01）. Serum metabonomics screened 16 compounds （such as proline， propionylcarnitine， hemolytic phosphatidylcholine， etc.） and 6 metabolic pathways （such as sphingomyelin metabolism， arginine and proline metabolism， sphingolipid biosynthesis-lactose and neolactone series）. Urine metabonomics screened 20 different metabolites （such as prostaglandin A2， L-valine， phosphatidylcholine， sphingomyelin， etc.） and 8 metabolic pathways （such as valine， leucine and isoleucine biosynthesis， sphingomyelin metabolism， pyruvate metabolism， etc.）. CONCLUSIONS Kuaisong yin can play a role in improving constipation by regulating different metabolites such as hemolytic phosphatidylcholine， phosphatidylcholine， prostaglandin A2， L-valine， proline， and regulating metabolic pathways such as multiple amino acid metabolism， sphingomyelin metabolism， etc.

OBJECTIVE To study the mechanism of Compound zaoren granule in improving insomnia. METHODS Forty-nine mice were divided into blank group， model group， positive control group 1 （Estazolam tablets 0.5 mg/kg），control group 2 （Shumian capsule 0.6 g/kg）， Compound zaoren granule low-dose， medium-dose and high-dose groups （2.5， 5， 10 g/kg）， with 7 mice in each group. The insomnia model was established by chronic unpredictable mild stress combined with 4-chloro-DL- phenylacetic acid. The behavioral changes of mice were investigated through open field test and pentobarbital sodium synergistic hypnosis experiment， as well as the pathomorphology of mice hypothalamus tissue was observed by HE staining. The metabonomics analysis and multivariate statistical analysis of serum in mice were performed by UHPLC-Q-TOF-MS/MS， and the differential metabolites were screened out； the metabolic pathway analysis was conducted based on MetaboAnalyst 5.0 database. RESULTS Compared with blank group， the total travelling distance， the number of entering the central region and the moving distance in the central region of the model group were significantly reduced （P＜0.05）， the proportion of total rest time was significantly increased （P＜0.05）， the sleep duration of mice was significantly shortened （P＜0.05）， and hypothalamic nerve cells damaged and severely vacuolated. Compared with model group， the total travelling distance of Compound zaoren granule low-dose and medium-dose groups were increased significantly and the proportions of total rest time of those groups were decreased significantly （P＜0.05）， and the sleep duration of mice in Compound zaoren granule high-dose group was prolonged significantly （P＜0.05）； the hypothalamic nerve cells of mice in each administration group recovered to varying degrees， and the hypothalamus histiocytes of mice in the Compound zaoren granules high-dose group were closer to those in the blank group. A total of 18 differential metabolites （such as phenylalanine， taurine， norvaline， methionine） and 4 important amino acid metabolic pathways （L-phenylalanine， tyrosine and tryptophan biosynthesis； taurine and hypotaurine metabolism； L-phenylalanine metabolism； cysteine and methionine metabolism） were identified through metabolomics analysis. CONCLUSIONS Compound zaoren granules can normalize the disordered metabolism in vivo by regulating differential metabolites such as phenylalanine， taurine， and four amino acid metabolic pathways， so as to improve insomnia.

Objective: To explore the association between dietary inflammatory index (DII) and metabolic syndrome (MetS) and its components among children aged 6-14 years in Beijing, so as to provide a reference for preventing MetS. Methods: A cross sectional study was carried out in 2 086 records of 1 832 children from the 2017 and 2019 Nutrition and Health Surveillance in Primary and Secondary school students of Beijing (NHSPSB). Three day consecutive 24 hour dietary recalls combined with weighing household cooking oils and condiments were used to collect dietary intake and calculate DII. MetS was diagnosed according to "Definition and Suggestion on the Metabolic Syndrome of Chinese Children and Adolescent". The Generalized estimating equations (GEEs) models were used to analyze the association between DII and the presence of MetS and its components (abdominal obesity, high triglyceride, low high density lipoprotein cholesterol, hypertension, and hyperglycemia). Results: The mean DII score was (1.64±1.07) for the included children. No significant association was found between DII scores and the likelihood of MetS (per 1 point increment: OR =1.16, 95% CI =0.92-1.48, P >0.05). In terms of the components of MetS, DII scores were positively associated with the odds of high triglyceride (per 1 point increment: OR =1.17, 95% CI =1.01-1.36, P <0.05). There was no statistically significant difference in the association among different age groups ( P >0.05). No significant associations were observed between DII and other MetS components( P >0.05). Conclusion DII scores may not be correlated with the risk of MetS, but proinflammatory diet might increase the risk of high triglyceride. DII score in childhood should be emphasized to identify and prevent MetS as soon as possible.

Objective To understand and improve the laboratory detection capacity of water manganese in testing organizations of Shaanxi Province． Methods The self-made manganese capacity testing samples were used as the reference in this proficiency testing program. The homogeneity of the samples was tested by single factor analysis of variance. The t-test method was used to evaluate the stability of the samples. The results of manganese in water provided by participant laboratories were analyzed by the robust statistical technique Z-score. Results A total of 136 laboratories participated in the proficiency testing program throughout the province. Among them, 129 laboratories (including retest laboratory) or 94.85% of total participating laboratories obtained satisfactory results. Conclusion The water quality monitoring agencies of our province had shown a strong detection capability for the determination of metal elements in drinking water, which ensures to provide safe water supply to the residents in Shaanxi Province.

The treatment of lower extremity chronic refractory ulcers requires a long time but with poor prognosis. Thus, many patients end up with amputations. The treatment of lower extremity chronic and recalcitrant ulcers and limb salvage has been a challenge worldwide. The Ilizarov technique based on the law of "tension-stress" brings a new hope in treating lower limb chronic and recalcitrant ulcers. The Ilizarov technique and distraction osteogenesis not only induce bone formation but also lead to angiogenesis and improved microcirculation. The Ilizarov technique consists of longitudinal distraction of long bone and tibia trans-verse transport (TTT) (proximal tibial corticotomy followed by transverse distraction). These two techniques have their own advantages and disadvantages with different indications in clinical application. Longitudinal distraction of long bone is mainly used for bone formation, such as large bone defects, osteonecrosis or bone infection (with or without soft tissue loss or ulcers). Because of only a partial osteotomy in TTT, the trauma is minor and their effects on limb instability are limited. Moreover, the procedure is simple with only a few minor complications. Thus, it is ideal in treating lower limb ischemic ulcers, such as diabetic foot ulcers, thromboangiitis obliterans (Buerger's disease), ulcers caused by atherosclerotic occlusion, arterial or venous ulcers, and trauma wounds. Several studies reported that TTT achieved high healing and limb salvage rates in treating severe diabetic foot ulcer. However, TTT could achieve lower recurrent rate. Thus, it is the most successful application in treatment of chronic ulcers. TTT also improves healing and limb salvage in treatment of thromboangiitis obliterans. However, the overall effects are limited than those in treating diabetic foot ulcer. For lower limb atherosclerosis occlusion, TTT induces regeneration of microvessles and consequently leads to ulcer healing. The effects are better than other conventional treatments. A combination therapy with vascularization is emphasized to attain the optimal long-term effects. The effects of TTT on lower limb recalcitrant ulcers still need to be validated in randomized control trial with larger sample size. Further, the mechanism of treatment needs to be explored by pilot studies which could show that this may be related to the formation of pro-angiogenetic factors and a rebalance of the inflammatory microenvironment during TTT.

OBJECTIVE：To esta blish the m ethod for identifying Schizonepeta tenusfolia from different habitats based on odor information. METHODS ：The odor of S. tenusfolia from different habitats were identified by Heracles Ⅱ ultra-fast gas phase electronic nose. Qualitative analysis was conducted according to obtained chromatographic information combined with AroChemBase database and Kovats retention index qualitative database. Principle component analysis （PCA）and discriminant factor analysis （DFA）were conducted by using Alpha Soft V 14.2 software，and cluster analysis （CA）was performed with SPSS 22.2 software. RESULTS ：There were 16 common peaks in 15 batches of S. tenusfolia from different habitats. After comparison with AroChemBase database and Kovates retention index qualitative database ，a total of 13 possible components were obtained. The possible components and sensory description information of S. tenusfolia from different habitats were basically the same ，but only the content was different. The chromatographic peak intensities of common peak No. 2 were in descending order as Anhui ＞ Gansu＞Henan＞Hebei＞Jiangsu，the chromatographic peak intensities of common peak No. 6 were in descending order as Anhui ＞ Hebei＞Gansu≈Henan＞Jiangsu，the chromatographic peak intensities of common peak No. 9 were in descending order as Anhui ＞ Gansu＞Henan＞Jiangsu＞Hebei，the chromatographic peak intensity of common peak No. 13 were in descending order as Anhui ≈ Gansu＞Hebei＞Jiangsu＞Henan，which represented the chromatographic peak intensity of methyl formate （peak No. 2），α-pinene （peak No. 6），3-nonone（peak No. 9）and α-terpineol（peak No. 13）were significantly different due to the change of habitats. PCA results showed that the cumulative contribution rate of the first two principal components was 96.807％. Results of DFA showed that contribution rates of discriminant factor 1 and discriminant factor 2 were 92.089％ and 3.982％. CA results showed that when the distance was 10，15 batches of samples could be clustered into 3 categories，B1-B5 and J 1-J3 into one category ，A1-A3 into one category ，G1，G2，N1 and N 2 into one category. The results were basically consistent with those of PCA and DFA. CONCLUSIONS：Ultra-fast gas phase electronic nose technology can be used to identify S. tenusfolia from different habitats rapidly. Methyl formate ，α-pinene，3-nonone and α-terpineol may be the key factors to distinguish S. tenusfolia from different habitats.