Objective To study the absorption and metabolism of four ethinylestradiol cocrystals (ethinylestradiol-piperazine,ethinylestradiol-nicotinamide, ethinylestradiol-tetramethylpyrazine and ethinylestradiol-imidazole) in rats,and to discuss the pharmacokinetic study method of ethinylestradiol cocrystals. Methods Female SD rats were administered ethinylestradiol or cocrystals orally at a dose of 5.0 mg·kg-1 (equal to ethinylestradiol).Blood samples were collected in batches at a specified time. Results Tmax of ethinylestradiol was 1 h,and the metabolism was completed within 24 h.Tmax of the four cocrystals was about 1.5 h,and the metabolism was completed within 48 h. The AUC of ethinylestradiol, ethinylestradiol-piperazine, AUC of ethinylestradiol-nicotinamide, ethinylestradiol-tetramethylpyrazine, ethinylestradiol-imidazole were (25.1±2.8), (28.3±1.5), (26.8±2.2), (24.2±4.4), and (23.6±2.5) h·ng·mL-1,respectively. Conclusion The drug release time of ethinylestradiol could be prolonged through the formation of cocrystals.The bioavailability of ethinylestradiol in rats was improved by the cocrystal preparation of ethinylestradiol-piperazine and ethinylestradiol-nicotinamide.
Objective To study the effects of Pulsatilla chinensis saponins (pulchinenosides) on intestinal flora diversity and composition in rats via high-throughput sequencing. Methods Twelve SD male rats were randomly divided into two groups:control group and treatment group.The treatment group was given pulchinenosides by gastric infusion every day.The control group was given blank solvent (sodium carboxymethyl cellulose solution).After treatment for 7 d,12 rat feces samples were collected and sent for microbial community diversity sequencing and interactive analysis.The sequencing results were analyzed by bioinformatics analysis software to compare the composition and structure of intestinal flora between the two groups. Results There were significant differences in intestinal flora composition between the two groups.Compared with the control group,the abundances of Akkermansia increased significantly (P<0.05),Desulfovibrio and Ruminococcaceae_UCG-013 decreased significantly (P<0.05). Conclusion The pulchinenosides can increase the abundance of some beneficial bacteria in intestinal flora of rats and decrease the abundance of some harmful bacteria in intestinal flora of rats,thus affecting the composition and proportion of intestinal flora of rats.
Objective To investigate the role of insulin-like growth factor binding protein-6 (IGFBP-6) protein in the treatment of clear cell renal cell carcinoma (ccRCC) by sunitinib. Methods Real-time quantitative polymerase chain reaction (RT-PCR) and Western blotting were used to compare human normal renal tubular epithelial cell lines (HK-2) differences in mRNA and protein expression between human renal clear cell carcinoma cell line (786-O).The 786-O cell line were treaded with sunitinib to observe the effect of sunitinib on IGFBP-6 mRNA and protein expression; Inhibited IGFBP-6 gene by small interfering RNA (siRNA),and the effect of this process on the proliferation of 786-O cells was observed. Results The mRNA and protein expression of IGFBP-6 in the HK-2 cell line decreased by 67.1% and 61.8% compared to the 786-O cell line, respectively, and the difference was statistically significant (P<0.01).The expression of IGFBP-6 gene mRNA and protein on 786-O were both increased after treated with sunitinib ( 50 μmol·L-1) for 24 hours,and the difference was statistically significant (P<0.01).Inhibited the IGFBP-6 gene expression by siRNA could reverse sunitinib against the effect of 786-O cell proliferation(P<0.01). Conclusion IGFBP-6 is related to the occurrence and development of ccRCC.At the same time,it may be a drug target for during sunitinib treatment for ccRCC.
Great progress has been made in tumor immunotherapy, among which immune checkpoint inhibitors are the most commonly used and concerned.With the wide clinical application,researchers gradually found that there are different response patterns in tumor immunotherapy,including durable response,pseudoprogression,hyperprogression,dissociated response and resistance,etc.The prognosis of different patterns varies greatly,and the therapeutic strategies are different accordingly.In clinical settings,different patterns should be carefully identified,meanwhile,corresponding treatment plan should be adjusted in time.This paper mainly introduces the characteristics and clinical treatment of various response patterns in tumor immunotherapy.
Immune checkpoint inhibitors(ICIs)have become a new standard treatment in a variety of malignant tumors which result in long-term survival.In a large number of clinical studies and clinical practices,some special populations have unsatisfactory efficacy, such as patientes with tobacco exposure, liver metastasis, hormone therapy, positive driver gene, symptomatic brain metastasis,elderly, and anemia. There results are controversial because lacking of sufficient.Therefore,we interpret the relevant research results of these 7 groups of people in order to put forward inference and suggestions for the clinical optimization when using of immune checkpoint inhibitors,to provide a reference for medical staffs and to bring more benefits to the patients.
With the development of tumor immunotherapy,it has been widely used in the clinical work.However,due to the particularity of the immunotherapy mechanism,there are some atypical responses to clinical immunotherapy,such as pseudoprogression,hyperprogression,delayed response,dissociated response.The traditional response evaluation criteria are biased for such responses. Regarding the mechanism,imaging evaluation methods,and blood markers of atypical responses,the evaluation criteria of immunotherapy efficacy are constantly developing and changing.From immune-related response criteria(irRC),immune-related RECIST (irRECIST),immuno-RECIST (iRECIST),PET response criteria in solid tumors (PERCIST) to immunotherapy-modified PERCIST (imPERCIST),there are markable progress in these evaluation criteria.However,the various evaluation standards are still in the exploration stage,and they have not reached the full recognition and recommendation of the guideline consensus.This article discusses the importance,complexity,and limitations of the evaluation criteria of immunotherapy efficacy,and puts forward the future development direction,with the hope to establish the precise immunotherapy evaluation standard and expand the benefiting population from immunotherapy through the joint efforts of all parties.
With the expanding use of immune checkpoint inhibitors (ICIs) in clinical practice,the management of immune-related adverse events (irAEs) has posed many safety challenges for clinicians.This study aims to summarize the management of severe or corticosteroid-refractory irAEs,including ICIs-related pneumonia,colitis,liver injury,central nervous system toxicity and myocarditis according current clinical practice,irAEs management guidelines and literature research.Meanwhile,this study also briefly describes the usage of some classic and newly-emergent immuno-inhibitors,providing a reference for the clinical management of irAEs.
Immune checkpoint inhibitors (ICIs) targeting programmed cell death-1 (PD-1) and its ligand (PD-L1) have transformed the traditional treatment pattern of malignant tumor.ICIs monotherapy has significantly improved long-term survival of some patients,but its efficient is low for all patient.Therefore,combined therapy is necessary for improving efficacy of immunotherapy.However,multiple patterns of combined have brought many confusions to doctors and patients.In this paper,we take non-small cell lung cancer (NSCLC) for example and focus on some hot-spot issues about ICIs-based combined therapy by analyzing clinical trial data and reviewing the progress of literature in this field.We hope to provide some ideas for the future research of optimization of ICIs-based combined therapy.
With the wide application of immune checkpoint inhibitors (ICIs),skin immune-related adverse events (irAEs) are common adverse reactions in clinic. Glucocorticoid is the main method of clinical treatment, which has obvious side effects. In traditional Chinese medicine,the skin adverse events caused by drugs belong to the category of "drug poison rash" and "drug rash". The skin irAEs caused by ICIs should also belong to this category. According to the principle of syndrome differentiation traditional Chinese medicine combined with glucocorticoid therapy can effectively shorten the course of disease,reduce the course of treatment and side effects of glucocorticoid drugs. This paper reviews the current progress of integrated traditional Chinese and clinical medicine in the treatment of skin irAEs caused by ICIs,and provides a medical record analysis.
Vaccination is an effective public health measure,but almost all vaccines can cause anaphylaxis. The pathogenesis of vaccine-related anaphylaxis includes IgE-mediated type anaphylaxis,IgG-mediated type Ⅱ anaphylaxis,immune complex and/or complement-mediated type Ⅲ anaphylaxis,cell-mediated type Ⅳ anaphylaxis and anaphylactoid reaction. Anaphylaxis caused by active ingredient of the vaccine are rare; and are usually caused by additional ingredients in vaccine preparations. Anaphylaxis is a clinical emergency,the personnel and environment providing immunization should meet the emergency treatment conditions of anaphylaxis and take active preventive measures. In order to strengthen the understanding of vaccine-related anaphylaxis,this article reviews the mechanism,prevention and treatment strategy of vaccine-related anaphylaxis.
Allergic reaction to medications is a type of adverse drug reaction mediated by the immune system,with both genetic and environmental components determining disease expression. Although drug allergy is rare,it is accidental and less predictable in most cases. Genetic polymorphisms analysis exerts great functions in the prevention and individualized treatment of drug allergic reaction with genetic screening and has become one of the hot topics on allergic susceptibility. This paper describes the mechanisms in drug anaphylaxis and reviews the correlation between drug allergic reaction and human leukocyte antigen (HLA), interleukin (IL), and high-affinity IgE receptor (FcεRI) gene polymorphisms published in recent years,in order to provide a theoretical foundation to further explore the genetic susceptibility of drug anaphylaxis.
Objective To analyze the demographocs,causative drugs,route of administration,outcomes,and the risk factors of death caused by allergic reaction.In order to provide reference for clinical safe medication in the future. Methods The case reports published in China Knowledge Network,WanFang Data Service Platform and Weipu.com were searched by computer with “Adverse drug reactions”“Allergic reaction”“Case report”“Anaphylactic shock”as keywords,the database was searched from January 1,2010 to October 31,2021. Results A total of 433 patients were included in 393 literstures.Most of the patients were complicated with respiratory diseases (30.7%),antibiotics were the main cause of allergic reaction (25.9%),followed by traditional Chinese medicine (17.6%).Patients with unknown allergic history had a significantly increased risk of death from drug-induced allergic reaction[OR=5.179,95%CI(2.585-10.376),P< 0.001].Antibiotics[OR=2.173,95%CI(1.079-4.377),P=0.030] and radiocontrast agents[OR=7.014,95%CI(2.619-18.784),P< 0.001] were high-risk drugs for allergic death.A total of 86 patients were died(19.9%),and the main cause of death was allergic shock (70.9%). Conclusion Allergic shock was the main cause of death from drug-induced allergy.The risk of death is significantly increased in patients with unknown allergic history,using of antibiotics and radiocontrast agents.So it is important to inquire patients’ allergic history before medication carefully and strengthen medication monitoring to ensure medication safety.
Anaphylactic shock is a severe allergic reaction of the body to antigenic substances, which caused by acute peripheral circulatory insufficiency. Its condition is serious and the mechanism is complex,which seriously endangers the life and safety of patients. In order to understand the research status and development trend of anaphylactic shock at home and abroad,the literatures related to anaphylactic shock at home and abroad in the past ten years were searched,and the quantity and annual distribution of literature, the distribution of literature types, the number of citations and the changing trend of high-frequency keywords were analyzed and compared.
Objective To systematically analyze the bibliometric characteristics and research hotspots of research articles on macrophages and aging,and to clarify the development trend and to explore the immune effect of macrophages in aging. Methods We searched Web of Science Core Collection database with "macrophage" and "aging or senescence" as keywords and limited to the title. The bibliometrics online analysis platform was used to analyze the status quo of international cooperation. CiteSpace was applied to analyze frequently cited references,and VOS viewer was used to analyze keywords and research hotspots. Results A total of 428 research papers meeting the requirements were included in this study. The first record began in 1970. The United States is not only the most productive country,but also has the closest cooperation and communication with other countries.Spain's Complutense University of Madrid was the institution with the most publications; Spanish scholar Monica De la Fuente is the most productive author;Mechanisms of Ageing and Development was the journal with the most publications. A total of 10 burst citations were analyzed,and based on keyword cluster analysis,6 related research clusters were found. Conclusion Research on the immune effect of macrophages in aging has received increasing attention recently. The research content is abundant and diverse,but it has not been applied to the treatment of age-related diseases,and the research needs to be further enhanced.
Aging is a life process,which related to multiple factors. In recent years,there are some studies show that total glucoside of paeony (TGP) and paeoniflorin (Pae),the main active constituent of TGP,exhibit anti-aging effects on various age-related disease (ARD). The investigation to the anti-aging effects and mechanisms of TGP and Pae is significant for improving the life quality of the elderly and slowing down the population aging. This article reviews the current possible mechanisms relate to TGP or Pae in ARD from multiple aspects, such as anti-inflammatory,immunomodulatory,sleep improving,biorhythm regulation and oxidative stress.
The research on human aging and the search for effective anti-aging drugs has become hot topics in the field of medicine at present. This paper reviews the research progress of some anti-aging drugs in recent years,including senolytics,drugs increasing autophagy and reducing age-related inflammation,drugs regulating energy metabolism, drugs targeting to an abnormally expressed gene, and natural products.
Metformin is a safe and effective drug for diabetes. In addition to its hypoglycemic effect,it also has the effects of protecting heart,anti-inflammatory and anti-cancer. In recent years,a number of cell and animal experiments have shown that metformin has anti-aging effects. The results of some clinical trials have also proved that metformin has a positive effect on the prevalence of age-related diseases,including cardiovascular diseases,cancer and neurodegenerative diseases. This article reviews the molecular mechanisms and clinical trials of metformin,and explores the potential of metformin in anti-aging.
In recent years,nanotechnology has been widely used in the diagnosis and treatment of diseases due to its rapid development.As a result,many new nanomaterials have been created in biomedical applications. Gold nanoparticles are considered as the most promising nanometer materials because of their unique characteristics in optics,electronics,sensing,and biochemistry. Functionalized gold nanoparticles can increase the level of intracellular uptake for gene therapy,targeted drugs to specific cells,biological sensing and diagnosis,and photothermal treatment of cancer. It has broad application prospects in the field of medicine.This article reviews the research progress of functionalized gold nanometer drug delivery systems in recent years,focusing on their ligand connection types and their applications in the field of medicine.
Colorants are widely used in the pharmaceutical industry,and the most commonly colorant classification and numbering system is the "Color Index".The dyeing of traditional Chinese medicine is explicitly prohibited in China,but there are no relevant laws and regulations on the use of colorants as excipients in drugs,while the US,the EU,and Japan all have relevant regulations to restrict the use of colorants.The colorant-related drug standards in China are mainly the detection methods of illegal dyeing in traditional Chinese medicine,and the multi-colorant detection methods reported in the literature are mainly the detection of food and traditional Chinese medicine,as well as the detection of a special matrix such as capsule shell or special colorants such as aluminum lakes.
Objective To establish a simultaneous determination method for 8 plant growth regulator residues in Rhizoma Anemarrhenae by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS-MS). Methods The separation was achieved on a Waters ACQUITY UPLC HSS T3 column (2.1 mm×100 mm,1.8 μm) with a gradient elution of 5 mmol·L-1 ammonium formate solution (A) -acetonitrile (B) at a flow rate of 0.3 mL·min-1,and the column temperature was 30 ℃. The samples were detected by electrospray ionization (ESI) in positive /negative modes and multiple reaction monitoring mode. Results The linear relationships of daminozide,chlormequat,mepiquat,gibberellic acid,4-nitrophenol sodium salt dehydrate,forchlorfenuron,paclobutr azol,uniconazole were good in the selected concentration range,and the correlation coefficients were all greater than 0.9991.The detection limit were from 0.001 to 0.03 ng·mL-1. The average recoveries were from 74.4% to 113.8%,and the RSDs were less than 3%. Among the 30 batches of sibling samples,chlormequat chloride was detected in 2 batches,and their contents were 6.3 and 3.8 μg·kg-1,respectively. Conclusion The method is simple e and high sensitive which can be used to detect the plant growth regulators residues in Rhizoma Anemarrhenae.
Objective To establish a high performance liquid chromatography-quantitative analysis of multi-components by single-marker(HPLC-QAMS) method for determination of brazilin,(±)protosappanin B,tetrahydrocolumbamine,tetrahydrocoptisine,tetrahydropalmatine,dehydrocorydaline,calycosin7-O-β-D-glucopyranoside,calycosin and formononetin in Mudan granules. Methods The analysis was performed on an Agilent Zorbax SB-C18 column(250 mm×4.6 mm,5 μm),mobile phase of acetonitrile-0.2% formic acid aqueous solution in a linear gradient mode. The flow rate was 1.0 mL·min-1.The detection wavelengths were set at 280 nm for brazilin,(±) protosappanin B,tetrahydrocolumbamine,tetrahydrocoptisine,tetrahydropalmatine and dehydrocorydaline;and 254 nm was used for calycosin7-O-β-D-glucopyranoside,calycosin and formononetin. The column temperature was 30 ℃. Tetrahydropalmatine was used as the internal standard. The relative correction factors (RCF) between the tetrahydropalmatine and other eight constituents were established and calculate the quantitation. Results Brazilin,(±)protosappanin B,tetrahydrocolumbamine,tetrahydrocoptisine,tetrahydropalmatine,dehydrocorydaline,calycosin7-O-β-D-glucopyranoside,calycosin and formononetin showed good linear relationships within the ranges of 4.91-98.20,3.57-71.40,1.03-20.60,2.39-47.80,1.62-32.40,1.79-35.80,1.06-21.20,0.58-11.60,1.86-37.20 μg·mL-1(r≥0.999 1),respectively. The average recoveries(RSD) were 100.01%(0.73%),99.17%(0.59%),97.93%(0.78%),98.81%(0.98%),98.78%(0.43%),97.74%(0.60%),96.99%(0.62%),96.96%(0.46%) and 99.28%(0.37%),respectively. There was no significant difference between the calculated values of HPLC-QAMS method and the measured values of the external standard method. Conclusion The HPLC-QAMS method is simple,accurate and reproducible,which can be used for simultaneous determination of brazilin,(±) protosappanin B,tetrahydrocolumbamine,tetrahydrocoptisine,tetrahydropalmatine,dehydrocorydaline,calycosin7-O-β-D-glucopyranoside,calycosin and formononetin in Mudan granules.
Objective To evaluate the efficacy and safety of erlotinib combined with gemcitabine in the treatment of pancreatic cancer. Methods We searched CNKI,Wanfang database,VIP,PubMed,EBSCO and Web of Science for randomized controlled trials which comparing the efficacy and safety of erlotinib plus gemcitabine versus gemcitabine alone in the treatment of pancreatic cancer,and extracted the data. RevMan 5.3 software were used for meta analysis. Results A total of 7 studies and 2011 patients with pancreatic cancer were included. Meta-analysis showed that the disease control rate of patients in erlotinib plus gemcitabine group was significantly higher than that in gemcitabine group [RR=1.44,95%CI(1.11,1.88),P=0.006]. However,the erlotinib plus gemcitabine group did not show significant advantages in overall survival [HR=0.90,95%CI(0.73,1.12),P=0.34],disease-free survival [HR=0.97,95%CI(0.83,1.14),P=0.72] and progression-free survival [HR=0.80,95%CI(0.56,1.15),P=0.23]. In terms of adverse events (grade 3/4),the risk of diarrhea [RR=3.85,95%CI(2.22,6.68),P<0.000 01] and rash [RR=7.70,95%CI(3.19,18.62),P<0.000 01] in erlotinib plus gemcitabine group was significantly higher than that in gemcitabine group. There was no statistically significant difference in the risk of neutropenia [RR=1.02,95%CI(0.87,1.20),P=0.81],thrombocytopenia [RR=1.21,95%CI(0.82,1.80),P=0.34],fatigue [RR=1.12,95%CI(0.78,1.61),P=0.55] and nausea [RR=1.48,95%CI(0.55,3.97),P=0.43] between the two groups. Conclusion Erlotinib combined with gemcitabine can improve disease control rate compared with gemcitabine alone in the treatment of pancreatic cancer,but it cannot improve the survival benefit,and it increases the risk of diarrhea and skin rash (grade 3/4).
Objective To investigate and analysis the application status of voriconazole in patients after liver transplantation,and to provide reference for clinical medication. Methods A retrospective statistical analysis was conducted in hospitalized patients after liver transplantation using voriconazole from 2016 to 2019. After discussion with clinicians and clinical pharmacists,the rationality use of voriconazole was evaluated according to drug labels,instructions,Chinese pharmacopoeia,and clinical therapeutic guidelines and literatures. Results A total of 295 patients were included. And 103 (34.92%) patients were less than 2 years old,younger than the recommended population in the drug label. In 192 cases of applicable population,6 cases (3.13%) had no indication of prophylactic drug use. A hundred and eighty-four cases (95.83%) were unsuitable for usage and dosage. Conclusion The clinical application of voriconazole in patients after liver transplantation need to be regulated. The dosage regimen,safety and efficacy of voriconazole in children younger than 2 years need to be further studied. It should be paid more attention to the blood concentration monitoring and individual medication.
Objective To analyze and summarize the hospitalization history of a critically ill elder patient with multiple system diseases taken care by a multidisciplinary team in the acute care unit for the elderly (ACE unit),in order to provide a reference the treatment of elder patients with polypharmacy. Methods The process of treatment,adverse drug reactions,and adjustment of medication regimen were analyzed. And some problems we met in the treatment were discussed,such as digoxin poisoning,warfarin drug interaction,atrial fibrillation controlling,and the conflict between anticoagulation therapy and the risk of bleeding. Results Under the multidisciplinary care,the patient reached the medication balance,avoided more adverse drug reactions, and discharged from hospital in the end. Conclusion A pharmacist attending in an ACE group will improve safety and rationality of the medication regimen and help those geriatric patients to recover.
Objective The quality management strategy of generic drugs of sustained-release microspheres is studied in order to lay foundation for future formulation and refinement of relevant laws and regulations,regulatory tools and technical standards. Methods Combing the key quality attributes in the development process of sustained-release microspheres and the current domestic status of research and development,it is proposed to apply the spatial distribution and existing form of drugs to the quality management of sustained-release microspheres. Results Through literature research,we have learned that the complex production process of sustained-release microspheres and the hard-to-control drug release behavior are huge challenges for quality control,and the spatial distribution and existing form of drugs have a great influence on the drug release. Conclusion It is suggested that the spatial distribution and existing form of drugs should also be listed as one of the technical requirements for quality control of generic drugs of sustained-release microspheres in order to improve the scientific nature of quality management.