Table of Content

Volume 28 Issue 5
26 May 2023

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Effects of geniposide metabolites genipin on induced HK-2 cells injury and NLRP3 pathway

SHI Mingzhu, YE Tianxiang, LIU Yixuan, LI Huifang

2023, 28(5):  481-488.  doi:10.12092/j.issn.1009-2501.2023.05.001

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AIM: To study the toxicity of genipin-a kind of geniposide metabolites induced human tubular epithelial cells HK-2 and its effect on NLRP3 pathway. METHODS: The dose of GP on HK-2 cells were preliminarily determined by CCK8 method, the apoptosis or necrosis rate of HK-2 cells was detected by Hoechst 33342/PI, the level of LDH release and reactive oxygen species was detected by Kits, and mitochondrial membrane potential and intracellular calcium ion concentration were detected by high content imaging. Real-time PCR detected mRNA levels of kindey injury factor-1, osteopontin, NLRP3, Caspase-1, interleukin 1β, and interleukin 18. RESULTS: Compared with the 0 μg/mL group, GP>50 μg/mL significantly reduced cell viability (P<0.05, P<0.01), and the IC50 value was 110.50 μg/mL. Set the control group, the low, medium and high dose groups of GP (50, 100, 200 μg/mL); Compared with the control group, the cell density decreased in the medium and high dose groups of GP, and the PI positivity, LDH release, ROS, Ca2+ concentration increased significantly, MMP decreased significantly, and KIM-1, OPN, NLRP3, Caspase-1, IL-1β and IL-18mRNA levels increased significantly (P<0.05, P<0.01). CONCLUSION: GP may activate NLRP3 by increasing ROS and Ca2+, decreasing MMP and causing HK-2 cell damage.

Improvement effect of crocin on cognitive impairment of Alzheimer's disease rats through DKK3 regulation of GSK-3 β/β-Catenin pathway

YANG Xiaojia, JIANG Meng, WU Min, ZHANG Yili, LV Lan, WU Yuanfen, WANG Xinyu, LIU Liquan

2023, 28(5):  489-497.  doi:10.12092/j.issn.1009-2501.2023.05.002

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AIM: To explore the improvement effect and mechanism of crocin on cognitive impairmrnt of Alzheimer's disease (AD) rats. METHODS: The hippocampus of SD rats were injected with Aβ 25-35 to establish AD model, then rats were randomly divided into AD group, AD+ low, medium, high dose of crocin groups (10, 20, 40 mg/kg) and AD + donepezil group (1 mg/kg), intraperitoneal injection treatment for 4 weeks, set sham group. Dark avoidance test and water maze test were used to evaluate the learning and memory abilities of rats, ELISA was used to detect serum Aβ content, HE staining and Tunel staining were used to determine pathological changes and neuronal apoptosis of hippocampus of rats, immunohistochemistry was used to detect the expression of Brdu, Dcx and NeuN in hippocampus of rats, and Western blot was used to detect the protein expression of Aβ, DKK3, β-catenin, p-GSK-3β/GSK-3β, Caspase-3, Bax, Bcl-2 in hippocampus of rats. RESULTS: Compared to sham group, the learning and memory abilities of AD group rats were decreased, serum Aβ content increased, the pathological change in hippocampus was serious, neuronal apoptosis was increased, the expression of Brdu, Dcx, NeuN were decreased, the protein expression of Aβ, DKK3, p-GSK-3β/GSK-3β, Caspase-3, Bax were increased, protein expression of β-catenin, Bcl-2 were decreased (P<0.01). Compared to AD group, after the treatment of doses of crocin and donepezil, the learning and memory abilities of AD rats were improved, serum Aβ content were increased, and the pathological change in hippocampus were alleviated, neuronal apoptosis were reduced, the expression of Brdu, Dcx, NeuN were decreased, the protein expression of Aβ, DKK3, p-GSK-3β/GSK-3β, Caspase-3, Bax were decreased, the protein expression of β-catenin, Bcl-2 were increased, notely, dose-dependent effect of crocin was significant. CONCLUSION: Crocin reduced neuronal apoptosis and mediated DKK3 to regulate GSK-3β/β-catenin pathway to improve the cognitive impairment of AD rats.

Pharmacokinetic interaction study between sorafenib and dapagliflozin in rats

HE Xueru, LI Ying, MA Yinling, FU Yuhao, XUN Xuejiao, DONG Zhanjun

2023, 28(5):  498-507.  doi:10.12092/j.issn.1009-2501.2023.05.003

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AIM: To explore the pharmacokinetic interactions between sorafenib and dapagliflozin in rats and to provide some theoretical basis for the rational clinical use of the two drugs. METHODS: An ultra-performance liquid chromatography-tandem mass spectrometry (UPLC/MS/MS) method was developed for the simultaneous determination of sorafenib and dapagliflozin. Male SD rats were randomly divided into 5 groups (6 rats in each group), including 100 mg/kg sorafenib group, 0.5 mg/kg dapagliflozin group, 1 mg/kg dapagliflozin group, and 100 mg/kg sorafenib combined with 0.5 mg/kg dapagliflozin group and 100 mg/kg sorafenib combined with 1 mg/kg dapagliflozin group, for sorafenib and dapagliflozin drug interaction study. All samples were analyzed using a validated UPLC/MS/MS method, and the main pharmacokinetic parameters were calculated by compartment model. RESULTS: 1 mg/kg dapagliflozin increased the Cmax, AUC0-t and AUC0-∞ of sorafenib by 52.5%, 38.1% and 37.7%, respectively, and 0.5 mg/kg dapagliflozin increased the AUC0-t and AUC0-∞ of sorafenib by 36.3% and 36.3%. CONCLUSION: Pharmacokinetic interactions may exist between sorafenib and dapagliflozin, active surveillance for treatment and toxicity should be required when the two drugs combined together in clinical practice.

Sequoiaflavone inhibits stem cell properties such as proliferation and invasion of gastric cancer cells by down-regulating PI3K/AKT signaling pathway

WANG Yan, ZHANG Jinhui, ZHAO Yongchen, LIU Hongxiang, LIU Yawei, MIAO Huanhuan, YANG Xincai

2023, 28(5):  508-513.  doi:10.12092/j.issn.1009-2501.2023.05.004

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AIM: To explore the molecular mechanism of sequoiaflavone affecting gastric cancer cells. MEHTODS: Gastric cancer cell line AGS cells were treated with gradient concentrations of sequoiaflavone, and then induced by PI3K/AKT signaling pathway activator. The optimal inhibitory concentration and time of semi-inhibitory concentration of red cedar flavonoid on AGS cells were detected by CCK-8, and the changes of cell proliferation, migration and invasion ability were detected by colony formation assay, transwell assay and wound healing assay. PI3K/AKT signal pathway related proteins p-PI3K, PI3K, p-AKT and AKT  were detected by western blot. RESULTS: Sequoiaflavone inhibited AGS cells in a concentration-dependent manner. The half inhibitory concentration was 0.5 mmol/L, the optimal treatment time was 48 h. The protein expression of p-PI3K and p-AKT was down regulated. The proliferation, migration and invasion of AGS cells were decreased after treated with sequoiaflavone. After treated with PI3K/AKT signal pathway activator, the protein expression level of p-PI3K and p-AKT was partially reversed, and the ability of cell viability, proliferation, migration and invasion was also partially improved. CONCLUSION: Inactivation of PI3K/AKT signaling pathway caused by sequoiaflavone inhibited gastric cancer cells proliferation, migration and invasion ability. 

Effects of recovered autologous blood transfusion on immune function and inflammatory response in patients with cesarean section

LI Yang, PAN Weizhong, ZHANG Xiaolu, YU Cuicui

2023, 28(5):  514-524.  doi:10.12092/j.issn.1009-2501.2023.05.005

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AIM: To investigate the effects of autotransfusion on immune function and inflammation in patients undergoing cesarean section. METHODS: Ninty patients with high risk hemorrhage (central placenta previa, cicatritic uterus, etc.) who underwent cesarean section were divided into three groups according to the amount of autoblood transfusion, with 30 cases in each group. The control group did not receive autologous blood transfusion, the group with a transfusion volume of 0-400 mL received autologous blood transfusion 0-400 mL, and the group with a transfusion volume of 400-800 mL received autologous blood transfusion 400-800 mL. Serum levels of HB, RBC, HCT, WBC, CD3+, CD4+ and CD8+ were detected before surgery (T0), immediately after surgery (T1), 24 h after surgery (T2), 48 h after surgery (T3), CD4+/CD8+ ratio was calculated, and serum levels of IL-2 and IL-6 were measured. The mean arterial pressure, heart rate, oxygen saturation, postoperative fever and length of stay were recorded. RESULTS: Compared with T0, the changes of CD3+, CD8+, CD4+/CD8+ ratio, IL-2 level, mean arterial pressure, heart rate and oxygen saturation were similar among the three groups at each time point after surgery (P>0.05). CD4+ in the 0-400 mL reinfusion group and the 400-800 mL reinfusion group was higher than that in T0 at T2 (P<0.05), and IL-6 and WBC in the three groups were higher than that in T0 at all time points after surgery (P<0.05). The levels of HB, RBC and HCT in the control group decreased at T1, while the levels of HB, RBC and HCT in the 0-400 mL and 400-800 mL reinfusion groups decreased at T2 (P<0.05). Comparison between groups: at the same time point after surgery, the ratio of CD3+, CD8+, CD4+/CD8+, IL-2, IL-6, HB, RBC, HCT, WBC, mean arterial pressure, heart rate, oxygen saturation, postoperative fever, length of hospital stay and other changes were similar among the three groups (P>0.05). CD4+ concentration in 0-400 mL reinfusion group and 400-800 mL reinfusion group was higher at T2 than that in control group (P<0.05). CONCLUSION: Autologous blood transfusion can not inhibit immune function, and even improve immune function in the short term. It will not aggravate the inflammatory response of the body, so it is safe and available.

Comparison of calculation results of five population pharmacokinetic analysis tools

HUANG Zhiwei, LI Yi, XU Xiaoyong, ZHANG Lei, SHEN Yifeng, LI Huafang

2023, 28(5):  525-535.  doi:10.12092/j.issn.1009-2501.2023.05.006

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AIM: To compare the results calculated by population pharmacokinetic analysis tools Phoenix NLME, Monolix, R nlmixr package and CPhaMAS cloud platform with the gold standard sofeware NONMEM. METHODS: Fifty sparse sampling data sets based on a one-compartment model and fifty dense sampling data sets based on a two-compartment model were simulated, and the above five analysis tools were used to calculate the population typical value, individual variability and individual pharmacokinetic parameters. RESULTS: The population typical value and individual variability calculated by CPhaMAS and Phoenix NLME had the highest matching degree with NONMEM, followed by nlmixr. Monolix had the lowest matching degree, but Monolix and nlmixr might be more robust. The correspondence between clearance and distribution volume was better than the absorption rate constant. Except the absorption rate constant calculated by Monolix and intercompartmental clearance calculated by nlmixr, the correlation coefficients of individual pharmacokinetic parameters calculated by all analytical tools were greater than 0.99. CONCLUSION: The results calculated by the above four population pharmacokinetic analysis tools are highly correlated with that of NONMEM.

Effects of single nucleotide polymorphism of drug metabolizing enzyme cytochrome P450 on the efficacy of inhaled cortisol hormone in asthmatic children

ZHU Li, WEI Bing, LIAO Shi'e, ZHANG Chao, ZHENG Xiaoyu, LIU Yajun

2023, 28(5):  536-543.  doi:10.12092/j.issn.1009-2501.2023.05.007

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AIM: To elucidate the relationship between childhood asthma susceptibility and clinical efficacy of inhaled glucocorticoids (ICS) in children with different genotypes of asthma by exploring rs776746 and rs15524 single nucleotide polymorphisms (SNPs) of cytochrome P450 enzyme 3A5 (CYP3A5) gene in asthmatic children and healthy children. METHODS: The CYP3A5 gene rs776746 and rs15524 polymorphic sites were detected in 79 children (Case group) with asthma of Han nationality and 100 healthy children (Control group) who met the inclusion criteria admitted to the Northern Theater General Hospital in Northeast China from October 2016 to October 2020, and genotype, allele and linkage analysis were performed. The case group was given inhaled glucocorticoids by nebulised inhalation for 3 months, and lung function and exhaled breath nitric oxide (FeNO) were measured at entry and after treatment, and asthma control score C-ACT/ACT was done after treatment, so as to compare the prevalence of different genotypes and the differences in the above test index scores. RESULTS: There was complete linkage disequilibrium at rs776746 and rs15524 loci. There were three genotypes of T/T, T/C and C/C at rs776746 locus of CYP3A5 gene. There were significant differences in the frequency of different genotypes between the case group and the control group (c2=9.121, P=0.010). The probability of asthma in T/C genotype was 6.345 times higher than that in T/T genotype (P=0.007), that in C/C genotype was 3.864 times higher than that in T/T genotype (P= 0.044), and that in variant type was 4.682 times higher than that in wild-type (P=0.011); There were three genotypes of A/A, A/G and G/G at rs15524 locus. There were significant differences in the frequency of different genotypes between the case group and the control group (c2=9.121, P=0.010). The probability of asthma of genotype A/A was 3.864 times higher than that of genotype G/G (P=0.044), and the probability of asthma of genotype A/G was 6.345 times higher than that of genotype G/G (P=0.007). When comparing the frequency of G/G and A/A+A/G in the case group and the control group, it was found that the probability of asthma of the latter was 4.682 times higher than that of the former (P=0.011). The improvement rate of the measured value of FEF50 and FEF75 at rs776746 was significantly higher than that of wild type (t=-2.499, -3.256, P=0.024, 0.019), and the improvement rate of the measured value of FEF50 and FEF75 at rs15524 was significantly lower than that of wild-type (t=3.380, 2.325, P=0.015, 0.042). The C-ACT/ACT score of rs776746 locus variant was significantly higher than that of wild-type group (t=0.571, P=0.037); There was no significant difference between wild-type and variant C-ACT/ACT scores at rs15524 locus (t=0.486, P=0.545). CONCLUSION: The rs776746 and rs15524 loci of CYP3A5 gene are the susceptibility loci of childhood asthma. The wild-type or variant of rs776746 and rs15524 loci are related to the improvement of small airway function after inhaled ICs treatment. Wild type or variant of rs776746 locus also affected asthma control.

Clinical efficacy of intracoronally targeted recombinant human urokinase  combined with percutaneous coronary intervention (PCI) in acute myocardial infarction (AMI) with high thrombus burden

CHEN Manxin, ZHANG Bingyu, DAI Min

2023, 28(5):  544-549.  doi:10.12092/j.issn.1009-2501.2023.05.008

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AIM: To study the effect of of intracoronally targeted recombinant human urokinase combined with percutaneous coronary intervention (PCI) in acute myocardial infarction (AMI) with high thrombus burden. METHODS: In this retrospective analysis study, 85 AMI patients with heavy thrombus burden admitted to Wuhu Second people's Hospital for percutaneous coronary intervention (PCI) from November 2020 to November 2022 were divided into observation group (n=37) and control group (n=48) according to different treatment methods.Recombinant human urokinase were used for coronary intervention in observation group. The control group was not treated with recombinant human urokinase. The myocardial injury markers troponinI (cTnI) and creatine kinase (CK) within 24 h after PCI, the percentage of segment resolution≥50% 1 h after PCI, intraoperative coronary lesions blood flow, the incidence of adverse cardiovascular events (MACE) during hospitalization,and cardiac function index ［left ventricular end diastolic (LVED), fractional shortening (FS), left ventricular ejection fraction (LVEF) level change one month discharge were compared between the two groups after PCI.RESULTS: After PCI, the levels value of cTnI and creatine kinase in the observation group at within 24 h after PCI were (69.35±16.31) ng/mL vs. (80.52±15.20) ng/mL, (3 136.27±1 952.52) U/L vs. (4 554.51±1 982.34) U/L, which were significantly lower than those in the control group (P<0.05); the postoperative TIMI blood flow level 3 was significantly higher than that in the control group (P<0.01), the percentage of segment resolution ≥50% 1 h after PCI were significantly higher than those control group (P<0.01); Comapared with control group, the the level of LVEF was[ (54.27±4.21)% vs. (48.20±3.12)%, FS[(29.21±2.10)% vs. (21.52±1.80)%], which were significantly higher than that in the control group at one month discharge (P<0.05); which was significantly lower than that in the control group at one month discharge, LVED[(47.27±4.15) mm vs. (56.67±4.30) mm ](P<0.05). There was no significant difference in the incidence of coronary vascular disease (MACE) between the two groups (P>0.05)．CONCLUSION: Intracoronally targeted application of recombinant human urokinase combined with percutaneous coronary intervention (PCI) has a significant effect on AMI with heavy thrombus burden, which can effectively improve cardiac function, coronary blood flow and myocardial reperfusion, and reduce myocardial damage without increasing the risk of MACE．

Diagnosis and individualized drug therapy for the rejection with hyperglycemia after liver Transplantation

CHEN Yining, XIAO Yun, HAN Xiaoyu, HUANG Lulu, MA Jingsheng, XIONG Hanbin, FU Yu, WANG Baolin, GUO Xiaohui, ZHONG Lin, AO Jiangen, HE Jiake

2023, 28(5):  550-555.  doi:10.12092/j.issn.1009-2501.2023.05.009

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AIM: To establish individualized drug therapy strategy for patients with rejection and hyperglycemia after liver transplantation. METHODS: Clinical pharmacist collaborated with the surgeons and participated in the diagnosis and treatment of rejection and hyperglycemia after liver transplantation. Taking together liver function, therapeutic drug monitoring, drug-drug interactions between tacrolimus and wuzhi capsule, individualized drug therapy was adapted to improve the prognosis. RESULTS: The patient recovered well and survived in good health till now. CONCLUSION: It is highly suggested that clinical pharmacists actively involved in treatment of more severe and difficult-to-treat disease and design the individualized dosing regimens. This will largely contribute in reduced adverse drug reaction, improved safety and effectiveness in drug use as well as the quality of life in the "post-transplantation era".

Pharmaceutical care of patients with antithrombotic therapy after transjugular intrahepatic portal shunt

LIU Xiumei, GUO Qianqian, FANG Yuan, CHEN Nan, QI Qi

2023, 28(5):  556-560.  doi:10.12092/j.issn.1009-2501.2023.05.010

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AIM: To explore the role of clinical pharmacist in the treatment of patients with transjugular intrahepatic portosystemic shunt. METHODS: Clinical pharmacist participated in the treatment of a patient with repeated oral bleeding after transjugular intrahepatic portal shunt followed treatment with multiple antithrombotic drugs, which assisted the physician to diagnose and adjust the antithrombotic treatment plan as well as provided the patient with whole-process pharmaceutical care and online management. RESULTS: Based on the inquiry about the patient's past and current medical history and medication consumption, the pharmacist considered that there was weak correlation between oral hemorrhage and antithrombotic drugs and advised for dentist inspection. Thereafter, the patient was diagnosed with chronic gingivitis. The dosage of warfarin was adjusted, and the pharmacists managed it online after discharge to achieve stable INR of the patient. In the later online follow-up, an abnormal increase of INR was encountered, By asking about the history of medication, it was considered that the increase in INR was related to taking amoxicillin capsules. Therefore, the pharmacist suggested to stop amoxicillin capsule and to gradually adjust the dose of warfarin to the original level to improve the treatment. CONCLUSION: The involvement of clinical pharmacists in clinical treatment facilitates comprehensive pharmaceutical care of patients, which plays a positive role in the efficacy and safety of medication therapy.

Optimization strategy of antibiotic dosing regimen in intensive care unit patients with augmented renal clearance

DANG Zilong, LIU Haiyang, ZHANG Yangfan, LIU Jinfeng, ZHANG Tianwei, LI Bin, GUO Hong, CHENG Wenyuan, XU Xiaohui, LI Yile, WEI Yuhui, WU Xin'an

2023, 28(5):  561-571.  doi:10.12092/j.issn.1009-2501.2023.05.011

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The incidence of augmented renal clearance (ARC) in intensive care patients (ICU) is exceptionally high, and these patients are often comorbid with infection. The occurrence of ARC will significantly increase the clearance rate of antibiotics, making it difficult for conventional doses to reach effective therapeutic concentrations and affect the patient's anti-infective treatment effect and prognosis. It can be seen that it is crucial to formulate a reasonable dosing regimen for ICU patients with ARC. Regrettably, few reports in China about the adjustment strategy of antibiotic dosing regimens for ARC patients. Therefore, this article reviews the domestic and foreign literature for reference to provide evidence for medical personnel to adjust the dose of antibacterial drugs for such patients.

Effects and mechanism of traditional Chinese medicine injection in prevention and treatment of cardiotoxicity induced by antineoplastic drugs

LI Yanyang, WANG Yunjiao, LV Shichao

2023, 28(5):  572-577.  doi:10.12092/j.issn.1009-2501.2023.05.012

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Traditional Chinese medicine injections for the prevention and treatment of cardiotoxicity of antineoplastic drugs was summarized, including Shengmai injection, Shenmai injection, Shenfu injection, Shenqi Fuzheng injection, Kangai injection, Huangqi injection, Xinmailong injection, Danhong injection, Danshen injection, Honghua injection, Kushen injection, Cinobufacin injection and Yinxingdamo injection. The mechanism of effect mainly includes inhibition of lipid peroxidation, reduction of calcium overload and anti-cardiomyocyte apoptosis, which provides the basis for the prevention and treatment of cardiotoxicity of anti-tumor drugs by traditional Chinese medicine.

Research progress of tenofovir alafenamide in blocking mother-to-child transmission of hepatitis B virus 

QI Linling, LIU Shourong

2023, 28(5):  578-582.  doi:10.12092/j.issn.1009-2501.2023.05.013

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Hepatitis B virus (HBV) infection is a global public health problem, and the prevention of mother-to-child transmission (MTCT) is an important intervention method. As a new nucleoside reverse transcriptase inhibitor, tenofovir alafenamide (TAF) has the characteristics of strong liver targeting and low peripheral blood exposure. Although it has been used in the treatment of chronic hepatitis B widely, its application in blocking mother-to-child transmission of HBV is still limited. This paper reviews the characteristics of TAF, the effects of TAF on infants and pregnant women, in order to provide new ideas for the prevention of mother-to-child transmission of HBV.

Progress in the prevention and treatment of traditional Chinese medicine based on the mechanism of intestinal injury of various chemotherapy

LI Shuang, HAN Shuzhen, DAI Yuting, XIU Minghui, DU Xianqin, HE Jianzheng, LIN Xingyao

2023, 28(5):  583-593.  doi:10.12092/j.issn.1009-2501.2023.05.014

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Intestinal injury is a common adverse reaction of clinical chemotherapy drugs, which limits the further application of chemotherapy drugs and causes serious physical and mental burden to patients. At present, the mechanism of chemotherapy-induced intestinal injury is complex, and traditional Chinese medicine has an excellent preventive effect. This article reviews the related mechanisms of intestinal flora imbalance, oxidative stress, inflammatory response, cell apoptosis, and immune damage caused by chemotherapy, and summarizes the role of traditional Chinese medicine in prevention and treatment of oxidative stress, inflammatory response, cell apoptosis , and immune damage.

Progress in clinical application of topical anesthesia

TAO Yijia, YANG Chun, LIU Cunming

2023, 28(5):  594-600.  doi:10.12092/j.issn.1009-2501.2023.05.015

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Topical anesthesia are being widely used in clinical diagnostic or therapeutic fields such as ophthalmology, ENT, dermatology, urology. It is defined as superficial loss of sensation in mucous membranes or skin, produced by direct application of penetrating local anesthetics. Topical anesthesia has the advantages of simple performance, high safety, quick recovery, which can effectively improve patient's satisfaction. In recent years, more and more attention has been paid to the concept of comfortable diagnosis and treatment. The new drugs and application methods of topical anesthesia are emerging constantly, special attention must be paid to their pharmacological characteristics and possible adverse reactions when using them. This article reviews the research progress of topical anesthesia in clinical application in order to provide reference for clinical practice.