Traditional Chinese Medicine (TCM), as a treasure of the Chinese nation, plays a significant role in maintaining public health. In 2019, the Central Committee of the Communist Party of China and the State Council proposed for the first time the establishment of a TCM registration and evaluation evidence system that integrates TCM theory, "personal experience" and clinical trials (referred to as the "Three-in-One" System) to promote the inheritance and innovation of TCM. Subsequently, the National Medical Products Administration issued several guiding principles to advance the improvement and implementation of this system. Owing to the complexity of its implementation, there are still differing understandings within the TCM industry regarding the positioning of the "Three-in-One" Registration and Evaluation Evidence System, as well as the connotation and value orientation of the "personal experience." To address this, Academician WANG Qi, President of the TCM Association, China International Exchange and Promotion Association for Medical and Healthcare and TCM master, led a group of academicians, TCM masters, TCM pharmacology experts and clinical TCM experts to convene a "Seminar on Promoting the Implementation of the ′Three-in-One′ Registration and Evaluation Evidence System for Chinese Medicinals." Through extensive discussions, an expert consensus was formed, clarifying the different roles of the TCM theory, "personal experience" and clinical trials within the system. It was further emphasized that the "personal experience" is the core of this system, and its data should be derived from clinical practice scenarios. In the future, the improvement of this system will require collaborative efforts across multiple fields to promote the high-quality development of the Chinese medicinal industry.

Objective:To investigate the clinical significance of soluble growth stimulating expression gene 2 protein (sST2) combined with neutrophil/lymphocyte ratio (NLR) in the prediction of nosocomial cardiovascular adverse events in patients with acute carbon monoxide poisoning (ACOP) myocardial injury.Methods:Patients with ACOP myocardial injury from January 2017 to December 2019 in Emergency Ward and EICU of Harrson International Peace Hospital, Hebei Medical University were enrolled. NLR was calculated by routine blood examination on admission, and sST2 (T 0sST2, T 3dsST2) was detected by ELISA on admission and at 3 days after admission. According to the occurrence of cardiovascular adverse events, the patients were divided into the event group and the non-event group. Logistic regression was used to analyze the risk factors of in-hospital cardiovascular adverse events. ROC curve was used to analyze the value of sST2, NLR, sST2 and NLR combined in predicting the occurrence of in-hospital cardiovascular adverse events in patients with ACOP myocardial injury. Results:Totally 255 patients with ACOP myocardial injury were included in the final analysis. NLR was (13.38±4.33) in the event group and (9.57±4.22) in the non-event group, T 3dsST2 was (61.59±22.67) ng/mL in the event group and (40.52±13.14) ng/mL in the non-event group, with statistically significant differences (all P<0.01). T 0sST2 was (265.34±89.95) ng/mL in the event group and (242.43±93.09) ng/mL in the non-event group, with no statistically significant difference ( P=0.333). Logistic regression analysis showed that NLR ( OR=1.270, 95% CI: 1.125-1.434, P<0.01) and T 3dsST2 ( OR=1.082, 95% CI: 1.052-1.114, P<0.01) were independent risk factors for nosocomial cardiovascular adverse events in patients with ACOP myocardial injury. The optimal cutoff value of T 3dsST2 was 44.5 ng/mL, and of NLR was 12.08. The sensitivity and specificity of dual T 3dsST2 and NLR in predicting nosocomial cardiovascular adverse events was 79.3% and 82.7%, respectively (AUC 0.857, Youden index 0.620). Conclusions:T 3dsST2 and NLR are independent risk factors for the nosocomial cardiovascular adverse events in patients with ACOP myocardial injury. The predictive cutoff values are 44.5 ng/mL for T 3dsST2 and 12.08 for NLR. Combination of T 3dsST2 and NLR has a practical predictive value for nosocomial cardiovascular adverse events in patients with ACOP myocardial injury.

Synthetic polymer hydrogel nanoparticles(NPs)were developed to function as abiotic affinity reagents for fibrinogen.These NPs were made using both temperature-sensitive N-isopropyl acrylamide(NIPAm)and L-amino acid monomers.Five kinds of L-amino acids were acryloylated to obtain functional mono-mers:L-phenylalanine(Phe)and L-leucine(Leu)with hydrophobic side chains,L-glutamic acid(Glu)with negative charges,and L-lysine(Lys)and L-arginine(Arg)with positive charges.After incubating the NPs with fibrinogen,y-globulin,and human serum albumin(HSA)respectively,the NPs that incorporated N-acryloyl-Arg monomers(AArg@NPs)showed the strongest and most specific binding affinity to fibrin-ogen,when compared with y-globulin and HSA.Additionally,the fibrinogen-AArg binding model had the best docking scores,and this may be due to the interaction of positively charged AArg@NPs and the negatively charged fibrinogen D domain and the hydrophobic interaction between them.The specific adsorption of AArg@NPs to fibrinogen was also confirmed by the immunoprecipitation assay,as the AArg@NPs selectively trapped the fibrinogen from a human plasma protein mixture.AArg@NPs had a strong selectivity for,and specificity to,fibrinogen and may be developed as a potential human fibrinogen-specific affinity reagent.

Objective:To investigate the predictive neutrophil/lymphocyte ratio (NLR) combined with soluble growth stimulating expression gene 2 protein (sST2) on in-hospital major adverse cardiovascular events (MACE) in patients with myocardial injury following moderate-severe acute carbon monoxide poisoning (ACOP).Methods:A single-cente prospective observational approach was conducted. Moderate-severe ACOP patients with myocardial damage from November 2016 to February 2020 in department of emergency medicine of Harrison International Peace Hospital Affiliated to Hebei Medical University were enrolled. The baseline data of the patients, NLR and sST2 (T0 sST2) on admission, sST2 at 3 days after admission (T3 d sST2), and the other myocardial injury and biochemical indicators were collected. According to whether MACE occurred, the patients were divided into MACE group and non-MACE group. The clinical data of the two groups were compared. Pearson correlation analysis was used to analyze the correlation of each index. Binary Logistic regression was used to analyze the independent risk factors of in-hospital MACE in patients with moderate-severe ACOP myocardial injury. The receiver operator characteristic curve (ROC curve) was drawn and area under ROC curve (AUC) was calculated to analyze the predictive value of NLR, sST2, and NLR combined with sST2 for the occurrence of in-hospital MACE in patients with moderate-severe ACOP myocardial injury.Results:A total of 278 patients with moderate-severe ACOP myocardial injury were included in the final analysis, and the incidence of MACE was 11.51% (32/278). Cardiac troponin I (cTnI), lactic acid (Lac), NLR, and T3 d sST2 in the MACE group were significantly higher than those in the non-MACE group [cTnI (μg/L): 0.83±0.15 vs. 0.46±0.37, Lac (mmol/L): 2.96±1.14 vs. 2.43±1.35, NLR: 13.14±4.37 vs. 9.49±4.21, T3 d sST2 (μg/L): 59.88±23.42 vs. 39.83±12.60, all P < 0.05], there was no significant difference in T0 sST2 between the MACE group and the non-MACE group (μg/L: 269.09±90.89 vs. 240.14±113.02, P > 0.05). Pearson correlation analysis showed that there were significantly positive correlations in NLR with acute physiology and chronic health evaluationⅡ(APACHEⅡ), T3 d sST2 with APACHEⅡ, and NLR with T3 d sST2 ( r values were 0.226, 0.209, 0.193, all P < 0.01). Binary Logistic regression analysis showed that T3 d sST2 and NLR were both independent risk factors for MACE in moderate-severe ACOP patients with myocardial injury [odds ratio ( OR) and 95% confidence interval (95% CI) respectively was 1.064 (1.039-1.090), 1.176 (1.066-1.298), both P < 0.01]. ROC curve analysis showed that the predictive efficacy of NLR combined with T3 d sST2 for the occurrence of in-hospital MACE in patients with ACOP myocardial injury (AUC = 0.876) was better than that of NLR (AUC = 0.754) and T3 d sST2 (AUC = 0.813). When the optimal critical value of NLR was 10.02 and that of T3 d sST2 was 43.50 μg/L, the sensitivity of predicting the occurrence of MACE in patients with moderate-severe ACOP myocardial injury was 69.8% and 86.2% respectively, and the specificity was 74.3% and 70.4%, respectively. The specificity and sensitivity of the combined detection was 83.4% and 79.8%, respectively. Conclusions:NLR and T3 d sST2 were independent predictors of in-hospital MACE in moderate-severe ACOP patients with myocardial injury, and combined application of NLR and T3 d sST2 had good predictive value. For patients with moderate-severe ACOP myocardial injury with NLR > 10.02 and T3 d sST2 > 43.50 μg/L, the occurrence of in-hospital MACE should be alert.

OBJECTIVE：To pre pare Glycyrrhetinic acid-modified docetaxel magnetic nanoparticles （GA-DTX-NGO/IONP- NPs），and to evaluate its physicochemical properties. METHODS ：Magnetic nano graphene oxide （NGO/IONP）was chosen as the anti-tumor drug carrier ，docetaxel（DTX）as the model drug and glycyrrhetinic acid （GA）as the target molecule. Firstly ，NGO/ IONP was synthesized by hydrothermal method and GA-CS was synthesized by amidation reaction. Fourier IR spectrometer ，DSC and vibration sample magnetic measuring instrument were used to characterize NGO/IONP and GA-CS. GA-DTX-NGO/IONP-NPs Huperzine A in the nicotinic acetylcholine receptor alleviates Aβ -induced 1-42 treatment of Alzheimer ’s disease and vascular dementia ：a neurotoxicity via downregulation of p 38 and JNK MAPK meta-analysis[J]. Evid Based Complement Alternat Med ， signaling pathways[J]. Neurochem Int ，2018. DOI ：10. 2014. DOI ：10.1155/2014/363985. 1016/j.neuint.2018.09.005. were prepared by the ion gelation method. TEM and particle size analyzer were used to observe and determine the morphology ， particle size and Zeta potential of GA-DTX-NGO/IONP-NPs ；the ultrafiltration-centrifugation method was used to determine encapsulation efficiency and drug loading amount ；the magnetic properties were investigated by investigating the state with or without external magnetic field ；the photothermal conversion test was carried out with laser irradiation of 808 nm. RESULTS ：NGO/ IONP and GA-CS were successfully synthesized ，and NGO/IONP exhibited superparamagnetism characteristics. GA-DTX-NGO/ IONP-NPs were spherical under TEM ，the particle size was （262.8±4.23）nm and the Zeta potential was （13.6±1.51）mV. The encapsulation rate and drug loading amount were （94.29±0.50）％ and（17.12±0.12）％，respectively. GA-DTX-NGO/IONP-NPs were black in appearance and evenly dispersed. Under the external magnetic field ，the magnetic nanoparticles could move directionally，showing good magnetic properties. GA-DTX-NGO/IONP-NPs showed a good concentration- and time-dependent photothermal conversion effect under 808 nm laser irradiation. CONCLUSIONS ：GA-DTX-NGO/IONP-NPs are successfully prepared. This study could provide some theoretical basis for the combined treatment of magnetic heating-chemotherapy for liver tumors.

OBJECTIVE： To establish a methaod for content determination of doxorubicin hydrochloride nano-liposomes， and to optimize its preparation technology. METHODS： The contents of doxorubicin hydrochloride nano-liposomes was determined by UV spectrophotometry. The membrane dispersion method was used to prepare doxorubicin hydrochloride nano-liposomes. Using particle size， encapsulation efficiency and drug-loading amount as indexes， the weight ratio of phospholipid to drug （mg/mg）， the weight ratio of phospholipid to cholesterol （mg/mg） and ultrasonic time （min） as factors， central composite design-response surface methodology was used to optimize the preparation technology. The photothermal conversion effect of doxorubicin hydrochloride nano-liposomes was investigated by near infrared irradiation. RESULTS： The linear range of doxorubicin hydrochloride were 1.01-16.16 μg/mL（r＝0.999 7）； precision， stability and reproducibility tests were all in line with the requirments of Chinese Pharmacopoeia. The optimal preparation technology included that the weight ratio of phospholipid to drug was 13.30 ∶ 1（mg/mg）； the weight ratio of phospholipid to cholesterol was 4.09 ∶ 1 （mg/mg）； the ultrasonic time was 10 min. Under this technology， the particle size and drug-loading amount of doxorubicin hydrochloride nano-liposomes were （200.5±25.1） nm and （11.02±0.20）％， relative errors of which to predicted value （196.3 nm， 10.68％） were 1.82％ and 1.63％. The consistency between measured value and predicted value was good. Doxorubicin hydrochloride nano-liposomes exhibited concentration- dependent and time-dependent photothermal conversion characteristics under near infrared irradiation at 808 nm. CONCLUSIONS： Established method is simple and good accuracy. The optimized preparation technology is simple and feasible.

OBJECTIVE： To establish the fingerprint of Maizao yishen granules， and to provide scientific basis for its further development. METHODS： HPLC method was adopted to establish the fingerprint by using 10 batches of Maizao yishen granules sa samples. The determination was performed on Venusil XBP C18（L） column with mobile phase consisted of acetonitrile-0.2％ phosphoric acid （gradient elution） at the flow rate of 1→0.7 mL/min at 7-10 min， 0.7→1 mL/min at 10-15 min and 1 mL/min at the rest of time. The detection wavelengths were set at 284 nm （0-7 min）， 330 nm （7-32 min） and 360 nm （32-45 min）. The column temperature was 25 ℃， and sample size was 10 μL. The fingerprint of Maizao yishen granules was established， and the similarity evaluation was performed by using “Similarity Evaluation System of TCM Chromatographic Fingerprints” （2004 A edition） software. Then， the common peaks were assigned and identified by comparing reference substance and control medicinal materials. RESULTS： The precision， stability （24 h） and repeatability of the methodological investigation were all good [RSD values of relative retention time and relative peak area of each chromatographic peak were less than 3％ （n＝6）]. The similarity of 10 batches of samples were all above 0.900. Seventeen common peaks were identified， of which common peak 1 and 6 came from Semen Raphani； common peak 7， 9， 14， 15 and 16 from Citrus reticulata； common peak 5， 10， 11， 12 and 13 came from Glycyrrhiza uralensis； common peak 2 came from C. reticulata， G. uralensis and Ziziphus jujuba； peak 3 came from G. uralensis and Semen Raphani； peak 8 came from Hordeum vulgare and Semen Raphani； peak 4 and 17 came from C. reticulata and G. uralensis. Peak 1 was identified as hesperidin and the peak 9 was identified as sinapine. CONCLUSIONS： Established fingerprint of Maizao yishen granules is accurate and reliable， and can be used for quality control of Maizao yishen granules.

OBJECTIVE： To prepare Adriamycin hydrochloride （DOX） magnetic thermosensitive liposome （MTSL）， investigate its physicochemical properties， magnetic effect and photothermal effect， so as to provide reference for tumor chemo- therapy and photodynamic/photothermal therapy. METHODS： Using DOX as model drug， TiO2@Fe3O4 as photosensitizers and magnetic materials， DOX-TiO2@Fe3O4-MTSL was prepared with membrane dispersion method. The morphology and dispersibility were observed； particle size and Zeta potential were detected； encapsulation efficiency of the liposome were determined by centrifugal ultrafiltration and HPLC. Its paramagnetism property was also detected by magnetometer. Compared with DOX solution， in vitro release behavior of the liposome was investigated by dialysis method， and the release curves at different temperatures （at 37， 43 ℃） were compared. The photothermal conversion effect of the liposome and the production of reactive oxygen species （ROS） in human breast cancer MCF-7 cells were investigated by near infrared laser irradiation at 808 nm. RESULTS： Prepared DOX-TiO2@Fe3O4-MTSL was brown-black with good water dispersion， and was spherical in shape and uniform in size under electron microscopy. Average particle size was 250.6 nm； polydispersity index was 0.107； Zeta potential was （－7.76±3.41）mV； encapsulation efficiency was （92.3±3.2）％. Under the external magnetic field， the liposome could move in a directional direction and had obvious paramagnetism. Compared with DOX solution， the liposomes released slowly and showed obvious sustained- release characteristics. Compared with at 37 ℃， the drug release of liposome speeded up significantly at 43 ℃.With the increase of laser （808 nm） irradiation time， the temperature of the liposome kept rising， which had obvious photothermal conversion effect and could induce the increase of ROS in MCF-7 cells. CONCLUSIONS： DOX-TiO2@Fe3O4-MTSL is prepared succe- ssfully， which has uniform appearance， good physical and chemical properties. It has obvious paramagnetism sustained release effect and photothermal conversion efficiency， and can promote ROS production in MCF-7 cells under near infrared laser irradiation at 808 nm.

Objective To optimize the formulation and process of liposome gel of total alkaloids of Sophoras Flavescentis Radix; To prepare the liposome gel of total alkaloids of Sophoras Flavescentis Radix and study its release mechanism.Methods Matrine liposomes was prepared by using film dispersion method; With entrapment efficiency and medicine loading as indexes, acid dye colorimetric method was used for the determination of matrine content in liposomes. Orthogonal design was used to optimize the formulation and the optimal formulation of liposomes was selected. Poloxamer-407 was set as the substrate preparation of matrine liposome gel. The transdermal rate of medicine gel and medicine liposome gel was investigated.Results Obtained through formulation and technology optimization of liposomes formation uniform, particle size was in the range of 100 nm to 400 nm, entrapment 74%, loading 26%. Preparation of liposome gel was transparent semisolid. In vitro results showed, cumulative release dose of matrine hydrogel was 6.34 mg/cm2 within 48 h; cumulative release doses of liposome gel of total alkaloids of Sophoras Flavescentis Radix was 6.97 mg/cm2 within 48 h; cumulative volume, steady-state penetration rate through skin and 48 h volume in the skin of the latter were significantly improved compared with that of the former. Conclusion Optimum preparation is reliable and practical. Liposome gel of total alkaloids of Sophoras Flavescentis Radix made by the preparation is with high quality, which can effectively delay the medicine release rate, increase the volume of medicine in human body.

Objective To investigate the clinical efficacies of Milrinone on cardiac function and blood-gas analytic indices in elderly patients with chronic heart failure.Methods During January 2013 to December 2016,50 elderly patients with chronic congestive heart failure admitted into the First People's Hospital of Qingdao Economic and Technological Development Zone were randomly selected and divided into the observation group (n=25) and the control group (n=25).The control group was given conventional treatment including diuretics,ACEI/ARBs,vasodilators,β-adrenergic receptor inhibitors and digitalis drugs,as well as anti-infection,fluid intake treatment and inhibiting the excessive activation of nerve-endocrine system.And Milrinone was taken as add-on to the therapy of control group in observation group.The changes in cardiac function,blood-gas analysis indices and adverse reactions were compared between the two groups.Results The total improvement rate of cardiac function was significantly higher in the observation group than in control group (92.0％ vs.76.0 ％,x2 =5.446,P＜ 0.05).The cardiac function indices,blood-gas analysis index and the level of CRP were significantly improved after treatment versus before treatment in both groups (all P＜0.05).And these improvements were significantly more superior in observation group than in control group (P＜0.05).Conclusions Milrinone can significantly improve the clinical efficacies in elderly patients with chronic heart failure.It can also improve the blood-gas indices and alleviate clinical symptoms,which seems to deserve more clinical application and promotion.