Drugs under special management include narcotic drugs,psychotropic drugs,toxic drugs for medical use,radiopharmaceuticals,and pharmaceutical precursor chemicals.Supervising and guiding the clinical use of drugs under special management is one of the important responsibilities of the Pharmaceutical Management and Drug Therapy Committee(Group)of medical institutions.The standard for drugs under special management is led by the Pharmaceutical Professional Committee of the China Hospital Association,which standardizes 16 key elements of organizational management,process management,and quality control management drugs under special management in medical institutions.It can guide the standardized implementation of Pharmaceuticals under special control work in various levels and types of medical institutions.This article elaborates on the methods and contents of formulating standards for Pharmaceuticals under special management,to provide reference and inspiration for medical institutions to carry out special drug drug management and daily related work.

Objective·To analyze and explore the influencing factors that lead to cognitive deterioration in individuals with elevated fasting blood glucose(FBG)and the metabolic clues associated with changes in the risk of cognitive deterioration.Methods·Data from the Alzheimer's Disease Neuroimaging Initiative(ADNI)database were downloaded,and the samples with FBG and follow-up data were selected from the database.Clinical information,including age,gender,body mass index,education years,apolipoprotein E4(APOE4)genotype and race,and corresponding metabolic indicator data,including amino acids,fatty acids,proteins and others were obtained.Based on the FBG levels and diagnosis of cognitive impairment stages in Alzheimer's disease,the subjects were categorized into four groups:normal FBG without/with cognitive deterioration,and elevated FBG without/with cognitive deterioration.The univariate analysis method,the Cox proportional hazards model,orthogonal projections to latent structures discriminant analysis(OPLSDA),and Spearman correlation analysis were employed for data analysis.Results·A total of 1 317 subjects were included,among which 1 153 had normal FBG level(>3.9 mmol/L and<6.1 mmol/L)and 164 had elevated FBG level(≥6.1 mmol/L).In the normal FBG group,275 subjects showed cognitive deterioration,while in the elevated FBG group,53 subjects showed cognitive deterioration.Univariate analysis revealed significant differences in gender and race between the normal FBG and elevated FBG group,and significant differences in age,gender,and APOE4 genotype between the groups with and without cognitive deterioration(all P<0.05).Cox regression analysis indicated that primary influencing factors for cognitive deterioration were APOE4 positivity,elevated FBG,and increasing age in order(HR=2.22,HR=1.38,HR=1.02;all P<0.05).In the analysis of baseline metabolic indicators in the groups without and with cognitive deterioration,as well as metabolic indicators before and after cognitive deterioration at different FBG levels,the results of the analysis of variance revealed that in the cognitively deteriorated population,the ratio of phospholipids carried by high-density lipoproteins(HDL)to total lipids was significantly higher;low-density lipoprotein(LDL)particle concentration and the lipids carried by LDL were significantly higher after cognitive deterioration.Correlation analysis showed that valine and leucine were significantly correlated not only with FBG level but also with phosphorylated tau(pTau)level in the plasma in the cognitively deteriorated population.Cholesterol and the ratio of phospholipids to total lipids carried by HDL were significantly correlated with pTau levels in cerebrospinal fluid(CSF).Conclusion·Compared to the individuals with normal FBG level,those with high FBG level have a significantly higher risk of cognitive deterioration.Additionally,different metabolic indicators show significant differences between the groups without and with cognitive deterioration,as well as metabolic indicators before and after cognitive deterioration at different FBG levels.Overall,LDL and its lipid content,and HDL-carried phospholipids show an increasing trend during cognitive deterioration,and the branched-chain amino acids valine and leucine are significantly correlated with pTau levels in CSF and plasma,suggesting that these metabolic markers may play an important role in cognitive deterioration.

Objective To investigate the clinical application of perioperative human serum albumin(HSA)in cardiac surgery in multiple regions in China,and to evaluate the rationality of its clinical application in conjunction with the clinical guidelines,in order to provide a reference for promoting the rational application of HSA.Methods The medical records of patients who underwent cardiac surgery from April to June 2019 in eight hospitals across the country were retrospectively collected.The statistical information on patients'general information,the dosage,course of treatment,and cost of HSA,and the serum albumin level before and after medication was analyzed to evaluate the use of HSA.Relevant evaluation criteria were established,and the rationality of its medication was evaluated.Results Data from a total of 449 patients were included for analysis,the appropriate rate of medication was 81.1％.The course of medication was mostly＞2-5 days and the total amount of HSA was mostly 50-99 g.The main purpose of medicaiton were improving colloid osmotic pressure,reducing exudation to improve interstitial edema,postoperative volume expansion.Conclusion Clinical attention should be paid to ensure the rational application of HSA in cardiac surgery during the perioperative period and prevent the abuse of blood products.

Purpose/Significance Based on big data,a cardiovascular and cerebrovascular electronic medical record(EMR)analy-sis platform is developed.By utilizing imaging data analysis techniques and clinical document analysis techniques,the platform provides patients with precise diagnosis,treatment plans,scientific administration,prognosis prediction,smart health education prescriptions and other precise services.Method/Process The medical ontology,knowledge rules and knowledge graph for cardiovascular and cerebrovas-cular diseases are developed and constructed by using Protégé.On the basis of constructing a knowledge graph,a knowledge base for clinical diagnosis,treatment,pathological analysis and prognosis judgment of cardiovascular and cerebrovascular diseases is formed.A EMR analysis platform for cardiovascular and cerebrovascular diseases is designed based on the knowledge base.Result/Conclusion The designed cardiovascular and cerebrovascular EMR analysis platform is conducive to providing personalized diagnosis and treatment plans for different populations,and providing patients with various precise diagnosis and treatment services.

Objective To investigate the effect of atractylone on the viability and apoptosis of hepatoma HepG2 cells and its mechanism of action. Methods Hepatoma HepG2 cells were selected and divided into low-, middle-, and high-dose atractylone groups (5, 10, and 20 μmol/L), and the cells in the control group were added with an equal volume of DMSO. MTT colorimetry was used to measure the viability of HepG2 cells after treatment with different concentrations of atractylone; flow cytometry was used to measure the apoptosis rate and mitochondrial membrane potential of HepG2 cells; the DCFH-DA fluorescent probe labeling method was used to measure the level of reactive oxygen species (ROS) in HepG2 cells; Transwell assay was used to evaluate the effect of atractylone on the migration ability of HepG2 cells; Western blot was used to measure the protein expression levels of Bcl-2, Bax, and cleaved caspase-3. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t -test was used for comparison between two groups. Results After 24 and 48 hours of treatment with atractylone, compared with the control group, the low-, middle-, and high-dose atractylone groups had a tendency of reduction in cell viability (all P < 0.05), with a half inhibitory concentration of 26.19 μmol/L in atractylone treatment of HepG2 cells for 72 hours. The low-, middle-, and high-dose atractylone groups had a significantly higher apoptosis rate than the control group (14.34%/29.32%/50.12% vs 0.32%, all P < 0.05). Compared with the control group, the low-, middle-, and high-dose atractylone groups had a significant increase in the fluorescence intensity of ROS in HepG2 cells (all P < 0.05). After 48 hours of treatment with atractylone, compared with the control group, the low-, middle-, and high-dose atractylone groups had a significant reduction in the number of migrated cells (132.67±18.36/57.00±9.26/31.00±2.45 vs 258.11±38.54, P < 0.05). Compared with the control group, the low-, middle-, and high-dose atractylone groups had a significant reduction in the expression of the anti-apoptotic factor Bcl-2 and significant increases in the expression of the apoptotic factors Bax and cleaved caspase-3 (all P < 0.05). Conclusion Atractylone can induce the apoptosis and inhibit the migration of HepG2 cells, which provides an experimental basis for further development and utilization of atractylone.

Objective:To investigate the availability, prices and affordability of essential medicines in pediatric population across China, in the hope of improving rational use of medicines.Methods:A multicenter cross-sectional survey of medicine prices, availability and affordability was conducted in 17 provinces, municipalities and autonomous region across east, south-central part, west and north of China. Data on 42 medicines used in pediatric population, both original and generic, were collected in 55 public hospitals from May 26 to June 2, 2017. Availability was expressed as the percentage of hospitals with stock of the target medicine on the day of data collection,and median price ratio (MPR) was the ratio of price upon investigation to international reference. Based on national minimum daily wage, affordability represents the number of working days needed to earn the expense which covers a standard course using the target medicine. Statistical software SPSS 13.0 was applied for descriptive analysis of availability, MPR and affordability.Results:Mean Availability of original and generic medicine was 33% and 32%, with median MPR being 5.43 and 1.55. Among the 19 medicines with price information for both original and generic product, the median MPR was 7.73 and 2.04 respectively. Regarding the five medicines used to treat four common pediatric diseases (pneumonia,peptic ulcer, congenital hypothyroidism, refractory nephrotic syndrome), the affordability was 0.63 (0.16-6.17) d for generic medicine, and 1.03 (0.16-11.53) d for its original counterpart.Conclusions:The availability to both original and generic products of the 42 medicines used in pediatric population was low in China. The prices of generic medicines seem to be lower and affordability higher than those of original medicines. There is an urgent need to improve the availability and affordability of pediatric medicines.

Objective: To investigate the effects of heparin on the secretion of monocyte chemotactic protein-1 (MCP-1) in human umbilical vein endothelial cells (HUVEC) and the adhesion of monocytes to endothelial cells stimulated by lipopolysaccharide (LPS). Methods: HUVEC were cultured in vitro, and the cells between generation 4 and 5 were used for the experiments. The cells were divided into phosphate buffer saline (PBS) control group, heparin control group, LPS group, and heparin+LPS group. The LPS group was challenged with LPS 10 mg/L; the PBS control group was added with the same amount of PBS; the heparin group was added with 10 kU/L unfractionated heparin; the heparin+LPS group was treated with 10 kU/L unfractionated heparin 15 minutes before LPS stimulation. The cells were harvested at 6 hours and 12 hours after LPS stimulation in each group, and the MCP-1 mRNA expression was determined by real-time fluorescent quantitative reverse transcription-polymerase chain reaction (qRT-PCR). After incubation with each group, the fluorescent dyelabeled human monocyte cell line THP-1 was cultured with each group for 1 hour in the dark, and the adhesion density of THP-1 and HUVEC was observed under fluorescence microscope. Results: Compared with the PBS control group, the MCP-1 mRNA expression significantly increased at 6 hours and 12 hours after LPS stimulation and peaked at 6 hours, then decreased gradually, but remained significantly higher than the PBS control group at 12 hours [2^-ΔΔCt: 16.41 (15.03, 18.00) vs. 1.00 (0.80, 1.26) at 6 hours, 9.27 (8.11, 9.85) vs. 1.00 (0.84, 1.20) at 12 hours, both P < 0.05]. Heparin preconditioning significantly reduced LPS-induced MCP-1 mRNA expression [2^-ΔΔCt: 2.06 (1.72, 2.46) vs. 16.41 (15.03, 18.00) at 6 hours, 2.46 (2.19, 4.56) vs. 9.27 (8.11, 9.85) at 12 hours, both P < 0.05]. There was no significant difference in MCP-1 mRNA expression between the heparin control group and the PBS control group [2^-ΔΔCt: 1.47 (1.29, 1.65) vs. 1.00 (0.80, 1.26) at 6 hours, 2.69 (2.58, 2.77) vs. 1.00 (0.84, 1.20) at 12 hours, both P > 0.05]. Fluorescence microscopy observation showed that LPS stimulation could promote the adhesion of THP-1 to HUVEC; heparin preconditioning could inhibit the adhesion of THP-1 to HUVEC stimulated by LPS. Conclusion Heparin preconditioning could inhibit the MCP-1 mRNA expression , thereby reduce the adhesion of THP-1 to HUVEC, thus play a protective role in sepsis.

OBJECTIVE: To investigate the effects of heparin on the secretion of monocyte chemotactic protein-1 (MCP-1) in human umbilical vein endothelial cells (HUVEC) and the adhesion of monocytes to endothelial cells stimulated by lipopolysaccharide (LPS). METHODS: HUVEC were cultured in vitro, and the cells between generation 4 and 5 were used for the experiments. The cells were divided into phosphate buffer saline (PBS) control group, heparin control group, LPS group, and heparin+LPS group. The LPS group was challenged with LPS 10 mg/L; the PBS control group was added with the same amount of PBS; the heparin group was added with 10 kU/L unfractionated heparin; the heparin+LPS group was treated with 10 kU/L unfractionated heparin 15 minutes before LPS stimulation. The cells were harvested at 6 hours and 12 hours after LPS stimulation in each group, and the MCP-1 mRNA expression was determined by real-time fluorescent quantitative reverse transcription-polymerase chain reaction (qRT-PCR). After incubation with each group, the fluorescent dyelabeled human monocyte cell line THP-1 was cultured with each group for 1 hour in the dark, and the adhesion density of THP-1 and HUVEC was observed under fluorescence microscope. RESULTS: Compared with the PBS control group, the MCP-1 mRNA expression significantly increased at 6 hours and 12 hours after LPS stimulation and peaked at 6 hours, then decreased gradually, but remained significantly higher than the PBS control group at 12 hours [2^-ΔΔCt: 16.41 (15.03, 18.00) vs. 1.00 (0.80, 1.26) at 6 hours, 9.27 (8.11, 9.85) vs. 1.00 (0.84, 1.20) at 12 hours, both P < 0.05]. Heparin preconditioning significantly reduced LPS-induced MCP-1 mRNA expression [2^-ΔΔCt: 2.06 (1.72, 2.46) vs. 16.41 (15.03, 18.00) at 6 hours, 2.46 (2.19, 4.56) vs. 9.27 (8.11, 9.85) at 12 hours, both P < 0.05]. There was no significant difference in MCP-1 mRNA expression between the heparin control group and the PBS control group [2^-ΔΔCt: 1.47 (1.29, 1.65) vs. 1.00 (0.80, 1.26) at 6 hours, 2.69 (2.58, 2.77) vs. 1.00 (0.84, 1.20) at 12 hours, both P > 0.05]. Fluorescence microscopy observation showed that LPS stimulation could promote the adhesion of THP-1 to HUVEC; heparin preconditioning could inhibit the adhesion of THP-1 to HUVEC stimulated by LPS. CONCLUSIONS Heparin preconditioning could inhibit the MCP-1 mRNA expression , thereby reduce the adhesion of THP-1 to HUVEC, thus play a protective role in sepsis.
Cells, Cultured ; Fibrinolytic Agents ; Heparin ; Human Umbilical Vein Endothelial Cells ; Humans ; Lipopolysaccharides ; Monocytes

The gut-brain axis (GBA) is a nerve-endocrine mediated bidirectional communication system between the gut and brain, which links the cognition and emotion in brain to peripheral intestinal function. In recent years, many researches have showed that colonized intestinal microbiota plays an important role in the communication between gut and brain. On one hand, microbiota can influence the development and function of brain via GBA. On the other hand, brain can also change the composition of gut microbiota. These findings gradually become a novel medical research highlight, i.e. the microbiota-gut-brain axis. This paper reviews the interaction between gut microbiota and brain via GBA in order to provide supports for studying functions of gastrointestinal tract and brain, as well as the treatment of related diseases.

Objective To determine the effect of unfractionated heparin (UFH) on lipopolysaccharide (LPS)-induced expression of chemokines and nuclear factor-κB (NF-κB) signaling pathway. Methods Human pulmonary microvascular endothelial cells (HPMECs) were cultured in vitro, and the cells between passages 3 and 5 were used in the experiments. The cells were divided into control group, LPS challenge group, 1 kU/L or 10 kU/L UFH+LPS group, and NF-κB inhibitor N-tosyl-L-lysyl chloromethyl-ketone (TLCK) group (TLCK+LPS group). HPMECs in LPS challenge group were treated with 10 mg/L LPS. UFH pretreatment with different dosages groups were treated with 1 kU/L or 10 kU/L UFH 15 minutes before LPS challenge. Cells in the TLCK+LPS group were treated with 10 μmol/L of TLCK 30 minutes before the addition of LPS, and HPMECs in control group were treated with an equal volume of phosphate-buffered saline (PBS) instead. The cells were harvested 1 hour after LPS challenge, and the nuclear translocation of NF-κB was determined by immunofluorescence assay to detect the effect of UFH on NF-κB activation. The levels of interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) in cell culture supernatants were determined by enzyme linked immunosorbent assay (ELISA) 3 hours and 6 hours after LPS challenge to detect the effect of UFH on LPS induced expression of chemokines and its mechanism of effect on NF-κB signaling pathway in HPMECs. Results ① In the control group, NF-κB was mostly located in the cytosol as shown by immunofluorescence. Treatment of HPMECs with LPS significantly increased the translocation of NF-κB from the cytosol to nucleus. UFH suppressed LPS-induced NF-κB activation both in 1 kU/L and 10 kU/L dosages, and 10 kU/L UFH gave even better results. ② Compared with control group, the levels of IL-8 and MCP-1 in the supernatants in LPS challenge group were significantly increased at 3 hours and 6 hours after LPS challenge [IL-8 (ng/L): 387.1±26.4 vs. 23.8±8.1 at 3 hours, 645.5±69.6 vs. 125.7±18.7 at 6 hours; MCP-1 (ng/L): 3 654.9±467.9 vs. 721.6±61.3 at 3 hours, 8 178.5±792.6 vs. 1 324.7±148.7 at 6 hours, all P < 0.05]. Compared with that of LPS challenge group, in 1 kU/L and 10 kU/L UFH pretreatment groups, the levels of IL-8 and MCP-1 were significantly decreased [IL-8 (ng/L): 315.3±24.8, 275.8±31.1 vs. 387.1±26.4 at 3 hours, 557.8±43.3, 496.9±38.7 vs. 645.5±69.6 at 6 hours; MCP-1 (ng/L): 2 924.1±267.9, 2 668.3±522.6 vs. 3 654.9±467.9 at 3 hours, 7 121.7±557.2, 6 563.9±576.4 vs. 8 178.5±792.6 at 6 hours, all P < 0.05]. The results indicated that 10 kU/L UFH yielded better results. However, inhibition study using the known NF-κB inhibitor TLCK could decrease LPS-induced increase in IL-8 and MCP-1 levels [IL-8 (ng/L): 162.4±21.3 vs. 387.1±26.4 at 3 hours, 274.1±22.6 vs. 645.5±69.6 at 6 hours; MCP-1 (ng/L): 1 478.2±138.5 vs. 3 654.9±467.9 at 3 hours; 3 667.6±259.4 vs. 8 178.5±792.6 at 6 hours, all P < 0.05]. Conclusions The levels of IL-8 and MCP-1 were increased obviously in LPS treated HPMECs. UFH might suppress LPS-activated NF-κB signaling pathway, contributing to the inhibitory effects of chemokines in HPMECs.