Objective To investigate the neuroprotective effect of GJ-4 (extracted from traditional Chinese medicine Gardenia jasminoides J.Ellis) in MPTP-induced sub-acute Parkinson's disease (PD) mice model, and to explore the underlying mechanisms. Methods Male C57/BL6J mice were randomly divided into control group,MPTP model group,GJ-4-treated groups (25,50 and 100 mg·kg-1) and L-Dopa treated group.The subacute PD model was developed by intraperitoneal injection of MPTP.Mice in all three GJ-4 treated groups and the L-Dopa group were orally administrated corresponding substances while mice in control group and MPTP model group was given 0.5% CMC-Na at same dose.All substances were given once a day for consecutive 12 days.Immunohistochemistry was used to detect tyrosine hydroxylase (TH) positive neuron in substantial nigra. Western blot was employed to examine TH and iNOS protein expression in midbrain;The mRNA expression level of inflammatory cytokine TNF-α and IL-1β,apoptosis-related protein Bax and Bcl-2 in the midbrains of mice were examined by qPCR. Results Comparing with MPTP-challenged mice,the motor behaviors of mice administrated with GJ-4 50 mg·kg-1 and 100 mg·kg-1 significantly improved in a dose-related manner (P<0.05).Comparing with MPTP-challenged mice,GJ-4 100 mg·kg-1 could significantly increase the number of TH positive neuron in substantial nigra (P<0.01),TH protein expression in the midbrains of mice (P<0.01).And GJ-4 inhibit the mRNA expression of inflammatory cytokine TNF-α and IL-1β in mice midbrain (P<0.05),inhibited Bax mRNA expression (P<0.05) in mice midbrain, and elevated Bcl-2 mRNA expression (P<0.05) in mice midbrain. Conclusion GJ-4 exerts a neuroprotective effect on sub-acute PD mice.And the underlying mechanisms may be through inhibiting neuroinflammation and neuronal apoptosis in mice central nervous system.
Objective To prepare folic acid-human serum albumin-sorafenib nanoparticles (FA-HSA-SRF-NPs),and to evaluate their anti-hepatic tumor activity in vitro. Methods FA-HSA-SRF-NPs were prepared by the chemical cross-linking method,and their characterization was studied by a laser granulometer and a transmission electron microscope.The drug loading volume and encapsulation rate were calculated.The accumulation of FITC-FA-HSA in HepG2 cells was observed using a confocal microscope.The amount of sorafenib in HepG2 cells was quantitatively analyzed by the HPLC method.The cytotoxicity was evaluated by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay,and the proapoptotic effect of the nanoparticles to HepG2 cells was detected by flow cytometry and Western blotting analysis. Results The particle size of FA-HSA-SRF-NPs was (85.4±3.3) nm and the Zeta potential was (-22.47±0.90) mV,the drug loading volume and encapsulation rate were (3.83±0.26)% and (91.09±6.14)%,respectively,and the folate content in FA-HSA-SRF-NPs was (13.97±0.27) μg·mg-1 HSA.FA-HSA-SRF-NPs could accumulate in HepG2 cells,and the cytotoxicity and proapoptotic effect of which were significantly stronger than those of sorafenib. Conclusion FA-HSA-SRF-NPs possess better properties,and the anti-tumor activity in vitro was significantly better than that of sorafenib,suggesting that FA-HSA-SRF-NPs have potential value in the treatment of liver tumor in clinics.
Tumor-associated macrophages (TAMs) are essential parts of the tumor microenvironment and play a vital role in the occurrence and development of tumors.TAMs-targeted immunotherapy is one of the frontiers and hotspots of tumor therapy.Nano-drug-loaded systems provide new ideas and directions for targeted regulation of TAMs due to their enhanced permeability and retention(EPR ),intelligent response,targeted modification,and co-delivery of different drugs.This article briefly reviewed the new drug-loaded nanosystems for targeting TAMs.
Traditional vaccines have played an important role in preventing and treating infectious diseases.However,many problems,such as dissatisfied safety,low immunogenicity,poor stability,and limited durable immune responses,restricted further applications of traditional vaccines.Nano-delivery systems can improve antigen stability,target antigen-presenting cells,promote the maturation of antigen-presenting cells,and activate specific immune responses.Presently,a large number of studies developed efficient vaccines using nano-delivery systems.This review briefly summarized the application of nano-delivery systems to enhance the immune effects of vaccines.
In vitro dissolution is one of the critical quality attributes of nanomedicines,which can affect drug absorption,safety,therapeutic effect,and the in vivo and in vitro stability.The in vitro dissolution approaches of nanomedicines are usually composed of sampling separation,dialysis,flow cell and other methods.This review introduced and discussed the release properties and the in vitro dissolution methods of different nanomedicines.This review might assist to establish in order to provide references for establishing in vitro dissolution methods of nanomedicines.
Sonodynamic therapy (SDT),as a non-invasive,real-time,and safe therapeutic strategy,has gained extensive attention in treating tumors and other diseases.However,organic sonosensitizers face some problems,such as poor solubility,weak chemical stability,and non-negligible phototoxicity,which thus limit the SDT effect.On the other hand,inorganic nano-sonosensitizers possess excellent chemical stability and low phototoxicity,thus showing a promising application prospect of SDT.In addition,due to their unique physical and chemical properties,inorganic nano-sonosensitizers could be developed to combine with other antitumor therapeutic strategies,such as chemotherapy,photothermal therapy,chemodynamic therapy,immunotherapy,gas therapy,to improve the antitumor effect synergistically.This review aimed to form the perspective of chemical materials and pharmaceutics,provide ideas and inspirations for the design of functional inorganic nano-sonosensitizers as well as the establishment of multi-mode antitumor therapeutic strategies.
Prescription review is an important way to check ensure medication safety, as well as the basic responsibility of pharmacists.As one of group standards formulated by the Chinese Hospital Association, Pharmacy administration and Pharmacy practice in Healthcare institutions-Part 2-2:Pharmacy Practice-Prescription Review standardizes 15 key elements on the three aspects of basic requirement, review process, quality management and evaluation improvement for prescription review in medical institutions, and which can be used to guide the prescription review in various medical institutions at all levels.This paper aims to introduce the construction method formulation and main content of the standard, so as to deepen the understanding of peers on the standard,and to promote the implementation of the standard.
Medication reconciliation is a pharmaceutical service of comparing a patient's medication orders to all of the medications that the patient has been taking, and working with the medical staffs to adjust the plan and the inappropriate medicine.This reconciliation should be done by pharmacist at every critical transition of care, including the admission,transfer,and discharge.This standard was compiled by the Pharmaceutical Affairs Commission of the Chinese Hospital Association,and the process included problems identification,framework development,manuscript writing,opinions gathering,and standards development.This article is to describe the process of development medication reconciliation services standards,and interpret the standards by taking medication reconcilation for the elderly as an example.
Patient education is a process in which pharmacists provide patients with rational drug use guidance and popularize rational drug use knowledge and other pharmaceutical services.The formulation of patient education standards is based on relevant national laws, regulations, normative documents, guidelines, literatures and expert opinions, and follows under the principles of scientificity, versatility, instrutiveness and operability.This standard regulates and standardizes the basic requirements, service process and the whole process of quality management and evaluation improvement of patient education, which is the basis for pharmacy professionals in medical institutions to carry out patient education services.This article paper introduces the formulation process of the patient education standard and analyzes the key contents of the standard, which will help pharmacists better comply with and meet the requirements of this standard in the practice of patient education.
Home care pharmacy practice is a new form of pharmaceutical care, which provideds by pharmacists to patients drugs at home by pharmacists. In order to standardize this practice, the Chinese Hospital Association Pharmaceutical Specialzed Committee specially organized the specialists from First Affiliated Hospital of Naval Military Medical University, Beijing Jishuitan Hospital, West China Pharmaceutical College of Sichuan University, the First Affiliated Hospital of Chongqing Medical University and the First Affiliated Hospital of Zhejiang University Medical College to prepare the Home care pharmacy practice standard.This standard is based on the action plan for further improving medical services (2018-2020) and other policies.It is formulated based on the principles of coordination, universality, applicability and consistency.It is the first group standard in China to standardize the whole process of home care pharmacy practice through sorting out problems, collecting opinions and expert argumentation.This article expounds the formulation process of the home care pharmacy practice standard, and analyzes the content of the standard, so as to provide suggestions and guidance for primary medical and health institutions to carry out home care pharmacy practice, promote the quality of pharmaceutical care, and ensure the safety of patients' home medication.
Pruritus is one of the most common concomitant symptoms of a variety of skin diseases,which seriously affects the spirit and quality of life of patients.The Janus kinase (JAK) / signal transducer and activator of transcription (STAT) signal pathway plays an important role in the pathogenesis of pruritic inflammatory dermatosis.JAK inhibitor is a kind of new small molecule drugs that inhibits this pathway and has considerable potential in the treatment of pruritus.This paper reviewed the treatment of pruritic inflammatory dermatosis with JAK inhibitors by summarizing the relevant literature published in recent years.
Vancomycin is the first-class drug against methicillin-resistant Staphylococcus aureus (MRSA) infection.Due to its nephrotoxicity properties,there are significant differences in personal dosage among patients during vancomycin treatment,which also highly related with the vancomycin pharmacokinetic (PK) parameters of patients.It is important to use antibacterial drugs timely and reasonably. Combined with domestic and foreign guidelines,expert consensus,and related researches in past years, this article reviewed vancomycin pharmacokinetics,dosing changes during extracorporeal membrane oxygenation (ECMO) life support,in order to provide references for the clinical use of vancomycin among ECMO supported critically ill patients.
Corona virus disease 2019 (COVID-19),as an infectious disease caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2),spread rapidly across the world at the end of 2019.The rapid spread of COVID-19 has also prompted the scientific community to make unprecedented efforts to study the potential mechanism of viral infection and propose reasonable clinical applications to reduce the incidence of COVID-19.Favipiravir,an RNA-dependent RNA polymerase (RdRp) inhibitor,is approved in China for the treatment of COVID-19.This article outlines that favipiravir inhibits SARS-CoV-2 by binding to three key viral enzymes of SARS-CoV-2,RdRp,3-chymotrypsin-like protease (3CLpro),and Papain-like-protease (PLpro).And this paper reviewed the data of the molecular docking of favipiravir and the above-mentioned viral proteases of SARS-CoV-2.
Objective To develop the formulation of the compound Lithospermum erythrorhizon microemulsion based vaginal in situ gel,and to evaluate its quality. Methods Using isopropyl myristate(IPM)as oil phase,cremophor EL-35(EL-35)as surfactant,glycerol as co-surfactant,and poloxamer 407(P407)and poloxamer 188(P188)as temperature-sensitive materials,the compound Lithospermum erythrorhizon microemulsion based vaginal in situ gel was prepared.And then we investigated the characteristics,particle size,rheological properties and in vitro release characteristics of the microemulsion gel. Results The optimal gel formula was as followed: the concentration of P407 was 100 mg·mL-1 and P188 20 mg·mL-1.The average diameter was (23.23±0.29) nm.The in vitro diffusion method showed a zero-order release of the gel.And the drug release was determined by gel dissolution. Conclusion The preparation of compound Lithospermum erythrorhizon microemulsion gel is feasible in technique.The vaginal gel showed good behaviors of physicochemical properties and release properties in vitro.
Objective To establish a method for the application of high-performance liquid chromatography combined with quantitative analysis of multi-components by single-marker (HPLC-QAMS) technology in the quality evaluation of senkyunolide I,senkyunolide H,coniferyl ferulate,ligustilide,levistilide A,icariin,baohuosideⅠ,bisdemethoxycurcumin,demethoxycurcumin and curcumin in Ruhe Sanjie tablets. Methods Agilent TC-C18 chromatographic column (4.6 mm×250 mm,5 μm) was used to analyze of 70% methanol extract of Ruhe Sanjie tablets.The mobile phase was acetonitrile-0.6% acetic acid solution with gradient elution at a flow rate of 1.0 mL·min-1.The detection wavelength were set at 280 nm for senkyunolide I,senkyunolide H,coniferyl ferulate,ligustilide,levistilide A,icariin and baohuosideⅠ,and 420 nm for bisdemethoxycurcumin,demethoxycurcumin and curcumin.The column temperature was 30 ℃.Using icariin as an internal standard,the relative correction factors of the other nine constituents were calculated,after which the content determination was made. Results Ten components showed good linear relationships within the ranges of 0.99-39.60 μg·mL-1(r=0.999 7),0.56-22.40 μg·mL-1(r=0.999 5),28.82-1152.80 μg·mL-1(r=0.999 8),20.78-831.20 μg·mL-1(r=0.999 5),3.19-127.60 μg·mL-1(r=0.999 7),24.76-990.40 μg·mL-1(r=0.999 8),13.67-546.80 μg·mL-1(r=0.999 6),3.99-159.60 μg·mL-1(r=0.999 4),5.36-214.40 μg·mL-1(r=0.999 8),and 9.93-397.20 μg·mL-1(r=0.999 9),respectively.And the average recoveries (RSDs) of each components were 97.85%(0.82%),96.97%(1.03%),100.07%(0.62%),99.42%(1.34%),98.64%(0.80%),99.43%(1.13%),100.02%(0.67%),98.35%(0.97%),98.70%(1.23%) and 97.99%(1.65%),respectively.There was no difference between the measured results of external standard method (ESM) and the calculated results of one measurement and multiple evaluation method. Conclusion The established method is reliable,simple and sensitive,which meets the requirements of methodology verification. It can be used for the quality control of Ruhe Sanjie tablets.
Objective To establish an HPLC-MS/MS method for the determination of three genotoxic N-nitrosamine impurities (N-nitrosoethyl isopropylamine,N-nitroso diisopropylamine and N-nitroso dibutylamine) in irbesartan simultaneously. Methods Agilent120 PFP column (100 mm×2.1 mm,2.7 μm) was applied.The mobile phase was methanol (A)-0.1% formic acid (B) at a flow rate of 0.4 mL·min-1 with gradient elution.The column temperature was set as 40 ℃.And positive ion was used as the acquisition mode.The multiple reaction monitoring(MRM) was used as the monitoring mode. Results N-nitrosoethylisopropylamine,N-nitrosodiisopropylamine and N-nitrosodibutylamine had a good linear relationship within their respective linear ranges (R2≥0.999 7).The average recoveries were 95.13%,92.00% and 93.96%,respectively;and RSD were 4.22%,3.25% and 3.60%,respectively. Conclusion The method is simple,rapid,sensitive,accurate,and reproducible,which can be used for the detection of N-nitrosamine genotoxic impurities in irbesartan.
Objective To establish a method for determining timolol maleate and related substances in travoprost and timolol maleate eye drops by high-performance liquid chromatography (HPLC). Methods The determination was performed on Agilent Zobax SB-C18 column(4.6 mm×250 mm,5 μm) with mobile phase consisted of the mixed solution of methanol and water(300:700).The mobile phase contained 2.16 g sodium octance sulfonate and was adjusted to pH 3.0 with glacial acetic acid-methanol (gradient elution),the detection wavelength was 295 nm;the temperature of the column was 30 ℃;the flow rate was 1.0 mL·min-1. Results Under the optimized condition of HPLC chromatography,an excellent separation was achieved for timolol maleate and the impurities.The calibration curves for timolol maleate,impruity G(4-(morpholin-4-yl)-1,2,5-thiadiazol-3(2H)-one 1-oxide) and impurity D(4-(morpholin-4-yl)-1,2,5-thiadiazol-3-ol) revealed good linearities over the range of 0.1-1353 μg·mL-1(r=1.000 0),0.30-60.0 μg ·mL-1(r=1.000 0),0.28-56 μg · mL-1(r=1.000 0),respectively.The LODs of the above compounds were 1 ng,0.3 ng and 0.3 ng,respectively.The average recoveries of timolol maleate were 101.1%(RSD=0.23%). Conclusion The method is specific,accurate,and sensitive,which can be used for the determination of timolol maleate and related substances in travoprost and timolol maleate eye drops.
Objective To systematically evaluate the efficacy of different fluid therapies in preventing hypotension during anesthesia for cesarean section. Methods We searched databases and clinical trial websites including PubMed,EMBase,Cochrane library,CNKI,Wanfang and VIP.The researches were collected from database establishment to October 2020.We gathered randomized controlled trials (RCTs) of fluid therapy in preventing hypotension during anesthesia for cesarean section.Two researchers screened literature,extracted study data,and independently assessed the risk of bias of included RCTs.We employed RevMan software (version 5.4) for direct meta-analysis,and RStudio software (version 1.3.109 3) with the GeMTC program package for network meta-analysis. Results We finally gathered a total of 100 RCTs,including 8911 recipients,and six kinds of fluid therapies.Three kinds of crystalloid solutions included normal Ringer's injection,lactate Ringer's injection,and acetate Ringer's injection.And three kinds of colloid solutions included hydroxyethyl starch injection,gelatin injection and dextran injection.Moreover,0.9% sodium chloride injection was selected as a control intervention.The network meta-analysis indicated that efficacy for preventing hypotension was ordered as followed:dextran injection,hydroxyethyl starch injection,gelatin injection,acetate Ringer's injection,lactate Ringer's injection,and normal Ringer's solution.However,the number of included studies varied from different solutions,and the quality of included studies was low. Conclusion Based on current evidence,colloid injection was superior to crystalloid injection in preventing hypotension during anesthesia for cesarean section.The preferred selection was dextran injection for colloid injection,and acetate Ringer's injection for crystalloid injection.Moreover,patient's allergy history and renal function should also be considered in fluid therapy selection.
Objective To introduce the idea of designing and on-site application of the integrated intelligent equipment of pharmacy intravenous admixture services (PIVAS) in our hospital;and to evaluate its practical effect in reducing labor cost,lowering error occurrence,as well as improving work efficiency. Methods The main steps of the PIVAS work process included infusions log in/out,labeling,distributions,injections placing and infusion sorting,and modular hardware was designed for those steps.Through the hospital internal local area network (LAN) programmable modules,the logic controller interoperability control,and data interaction,we realized the functions of intelligent control and data traceability of PIVAS intelligent integrated equipment so as to achieve intelligent infusion log in/out,smart labeling,smart distribution,intelligent injections placing and intelligent sorting.Through statistical methods,its performance was evaluated by comparing working index of before and after implementing this system within one month. Results The number of staff to complete daily labeling and distribution decreased from 4 to 1 with the new system.The average time-consuming for each prescription’s labeling and placing reduced from (7.01±0.56) s to (6.54±0.44) s.There are no mistakes in labeling for both way handlings.The number of errors in monthly prescriptions of injections placing reduced from 6 to 1 after application this system;the monthly infusions sorting errors reduced from 12 to 2 pieces;the total sorting time shortened from (1.22±0.08) h to (0.91±0.06) h;And finished infusion sorting time per bag shortened from (4.24±0.34) s to (2.92±0.21) s.The data showed statistically different(P<0.01). Conclusion The comprehensive application of PIVAS integrated intelligent equipment reduces the input of human power and the error rate,improves the work efficiency,as well as reduces the labor intensity.
Objective To investigate and analyze the therapeutic drug monitoring (TDM) testing items,methods and sample sizes carried out by various institutions across China by questionnaires in 2021, and to provide a reference for the development of TDM testing items,testing kits and quality control activities such as external quality assessment. Methods Based on the network platform,the survey was initiated in the form of questionnaires.The returned questionnaires were checked and entered into Excel to establish a database,and invalid data were supplemented or eliminated.Then, based on the data of the locked library, the number of institutions, the detection methods adopted, the overall sample size and the detection amount of each drug variety under each category were summarized and analyzed by using a bar chart combined with a data table. Results ①TDM has a large clinical development demand, among which psychotropic drugs, antibacterial drugs, immunosuppressive drugs and anti-tumor drugs are the drug categories with a large amount of development.②There were various clinical testing methods based on immunoassay methods like chemiluminescence immunoassay (CLIA),electro-chemiluminescence immunoassay (ECLIA) and chromatographic analysis like high performance liquid chromatography (HPLC) and HPLC-tandem mass spectrometry (HPLC-MS/MS). Conclusion In China,the medical institutions have extensive need for TDM testing. At present,there are multiple testing methods being used in parallel among various institutions.At the same time, laboratory developed tests (LDT) represented by chromatographic analysis are widely used.Therefore,the improvement of the external quality evaluation and the indoor quality control method is still the focus of TDM quality management in the future.
Objective To provide references and suggestions for elevating the quality of China's drug clinical trials. Methods The GCP inspection results of drug regulatory agencies in the United States,European Union,United Kingdom,and Japan were collected,and common flaws in inspection reports were summarized. Results Each country (region)'s GCP inspection adopted the concept of risk management,optimizing inspection procedures,and improving allocations of regulation resources.In addition,the regular release of inspection reports helped stakeholders of clinical trials to obtain helpful information.The main flaws found in inspections focused on trial protocol,informed consent,investigational medicinal products management,and sponsor management. Conclusion China should effectively allocate regulation resources to clinical trials based on risk evaluation,and further emphasize responsibility of sponsors to enhance the quality of clinical trials.