ABSTRACT OBJECTIVE To establish the HPLC fingerprint of Paeoniae Radix Alba and investigate the spectrum-effect relationship between the fingerprint and the protection against vascular injury.METHODS The HPLC method was used to establish the fingerprint of Paeoniae Radix Alba. Lipopolysaccharide-induced human umbilical vein endothelial cells (HUVEC) and Tg(fli1:egfp) zebrafish models were used to evaluate in vivo and in vitro protective effects of 17 batches of Paeoniae Radix Alba extracts. Grey correlation degree and partial least squares method were used to analyze the spectrum-effect relationship between thefingerprint of Paeoniae Radix Alba and the protection effects.RESULTS The HPLC fingerprint of Paeoniae Radix Alba was constructed, and 11 common peaks were obtained, and the correlation was high, indicating that multiple components of Paeoniae Radix Alba may had synergistic effects on the protection of vascular endothelial cell activity. The correlation sequence with in vivo activitywasP6>P7>P10>P11>P9>P5>P3>P2>P8>P1>P4, and in vitro activity was P6>P4>P2>P3>P5>P1>P10>P9>P7>P11>P8, respectively. Peak 6 was identified as paeoniflorin. The regression coefficient of the partial least squares standard equation was positive, positively correlated with the protection of vascular endothelial cell activity and the vascular development in Tg(fli1:egfp) zebrafish, with VIP>1.0. Furthermore, the verification experiments of active ingredient showed that paeoniflorin could improve cell viability, migration, and tube formation, as well as promote vascular development in Tg(fli1:egfp) zebrafish in a dose-dependent manner. The above results indicated that paeoniflorin might be the major active component of Paeoniae Radix Alba for the protection effect on vascular endothelial cell.CONCLUSION The main active substance of Paeoniae Radix Alba in protecting against vascular inflammation and damage is paeoniflorin, which can provide reference for the quality control of medicinal materials.

ABSTRACT OBJECTIVE To explore the correlation between HPLC fingerprint and analgesic efficacy of Zhejiang vinegar Corydalis Rhizoma, and to screen out the material basis of analgesic effect of Zhejiang vinegar Corydalis Rhizoma.METHODS Established HPLC fingerprint of Zhejiang vinegar Corydalis Rhizoma and dysmenorrhea model in rats. The weight loss rate, writhing response, serum malondialdehyde(MDA), estradiol(E2), prostaglandin E2(PGE2) and prostaglandin F2α(PGF2α) levels were used as the evaluation indexes of analgesic efficacy. Combined with chemometrics, the main active components of analgesic effect of Zhejiang vinegar Corydalis Rhizoma and the important components with great contribution to the content were screened.RESULTS The fingerprints of different batches of Zhejiang vinegar Corydalis Rhizoma were established, and nine components were identified; compared with the blank group, the weight loss rate, writhing reaction, MDA, E2 and PGF2α levels in the model group were significantly increased. Compared with the model group, the above indexs in the administration group was decreased. Compared with the blank group, the PGE2 level in the model group was significantly decreased. Compared with the model group, the PGE2 level in the administration group was significantly increased. The vinegar Corydalis Rhizoma produced in Zhejiang had a good analgesic effect, and the main active components of its analgesic effect were protopine, palmatine hydrochloride, and dehydrocorydaline. The important components with greater contribution to the content were tetrahydropalmatine, protopine, palmatine hydrochloride and stylopine.CONCLUSION The efficacy of Zhejiang vinegar Corydalis Rhizoma is the result of the combined action of multiple components, and each component has a strong correlation with the pharmacodynamic indexes. This study provides a reference for the screening of analgesic material basis of Zhejiang vinegar Corydalis Rhizoma.

ABATRACT OBJECTIVE To utilize the pharmacophore model-molecular docking combined with the virtual screening strategy of free energy calculation and the chemical bioinformatics method of traditional Chinese medicine in cell biology experiments to investigate the components of Guiqi Baizhu prescription that target phosphatidylinositol 3-kinase(PI3K) and inhibit the proliferation of uveal melanoma(UM) cells. METHODS The pharmacophore model of PI3K inhibitor was constructed, and the compounds of Guiqi Baizhu prescription were virtual screened. The components that fit the pharmacophore model were calculated by molecular docking and binding free energy, and the potential inhibitory components were selected for biological experimental evaluation. The effects of potential inhibitory components on UM cell proliferation were detected by CCK-8 and clonal formation assay. Flow cytometry was used to detect the cell cycle and apoptosis of UM cells. The mitochondrial membrane potential of UM cells was detected using JC-10 staining. The expressions of PI3K and downstream pathway proteins were detected by Western blotting.RESULTS The pharmacophore model included 2 hydrogen bond receptors, 2 aromatic ring centers, and exclusion volumes. The results of the CCK-8 experiment showed that quercetin, tangerine, and nobiletin at concentrations of 10, 20, 40, 80 μmol·L−1, and cyrtin at concentrations of 20, 40, 80 μmol·L−1, were able to inhibit the proliferation of UM cells. The clonal formation experiment showed that quercetin, tangerine, nobiletin, and morusin, at different concentrations, could significantly inhibit the clonal proliferation of UM cells. Flow cytometry showed that UM cells were arrested in the G0/G1 phase by tangeretin and quercetin, while UM cells were arrested in the G2/M phase by nobiletin and morusin. The results of JC-10 staining showed that quercetin, nobiletin, tangeretin, and morusin could reduce the mitochondrial membrane potential of UM cells. Western blotting results showed that 4 compounds could target PI3K, but their downstream pathways were different.CONCLUSION Based on the method of chemical bioinformatics in traditional Chinese medicine, this study explores the material basis for the inhibition of UM cell proliferation by the Guiqi Baizhu prescription. It also provides insights for the modern development of traditional Chinese medicine prescription.

OBJECTIVE To evaluate the consistency between the quetiapine LC-MS/MS kit and the laboratory-built method(reference method) in the detection results of quetiapine therapeutic drug monitoring. METHODS A total of 120 remaining plasma samples were collected from patients receiving quetiapine therapeutic drug monitoring from March to October in 2021. The plasma concentration of quetiapine was detected by kit and reference method respectively. The analysis of correlations and consistency was performed by outlier analysis, linear regression and Bland-Altman method. RESULTS No outliers were detected. The linear regression equation was Y=1.018X+4.400(r=0.998), indicating a good correlation. The Bland-Altman plot analysis showed good agreement between the two measurements. CONCLUSION The detection results of quetiapine LC-MS/MS kit and reference method are in good agreement. The kit can be used for clinical quetiapine treatment drug monitoring.

OBJECTIVE To establish a UPLC-HRMS method for simultaneous determination of 43 chemical drugs in blood and apply the method to determine the content of 43 chemical drugs in blood of 100 abnormal death from Hangzhou. METHODS Proteins were precipitated using acetonitrile. After centrifugation, the supernatant was collected and dried under a nitrogen stream. The residue was reconstituted with the initial mobile phase, centrifuged, and the supernatant was filtered through a 0.22 μm microporous membrane for instrument analysis. Separation was performed using a C18(150 mm×2.1 mm, 3.0 μm) chromatographic column. The mobile phase consisted of 0.1% formic acid+5 mmol ammonium formate(phase A) and methanol+0.1% formic acid(phase B) with gradient elution. Mass spectrometric detection was carried out using an electrospray ionization source(HESI-II) with simultaneous positive and negative ion scanning and real-time tandem mass spectrometry scanning(Full MS/ddMS2). RESULTS The linearity of 43 chemical drugs within the range of 10 to 1000 ng·mL−1 was good, with r2 ranging from 0.9910 to 0.9998; the limit of quantification was 10 ng·mL−1; the matrix effect was between 79.4% and 99.7%; the method recovery rate was between 80.4% and 97.0%; the intra-day precision(RSD) ranged from 0.1% to 3.2%; and the inter-day precision(RSD) ranged from 0.6% to 9.8%. Using this method, 100 whole blood samples from the Hangzhou Public Security Judicial Identification Center were tested, with 2 samples detected, both of which contained sibutramine. CONCLUSION The method is sensitive and accurate for fast detection of 43 chemical drugs in human blood.

OBJECTIVE To explore the clinical efficacy of clarithromycin sustained-release tablets in the primary eradication of Helicobacter pylori. METHODS Retrospective analysis of the data of patients with primary eradication of Helicobacter pylori admitted to the outpatient department of Tongde Hospital of Zhejiang Province from January 2019 to December 2020 was conducted. They were divided into three groups according to the choice of clarithromycin dosage form and dosage, namely, clarithromycin tablets 500 mg bid treatment group(group A), clarithromycin sustained-release tablets 500 mg bid treatment group(group B), and clarithromycin sustained-release tablets 500 mg qd treatment group(group C). At least 4 weeks after the end of treatment in each group, telephone follow-up was conducted to compare and analyze the efficacy, compliance, recurrence rate, incidence of adverse reactions, and cost effectiveness ratio of different treatment schemes for eradication. RESULTS After eliminating lost visits, a total of 350 cases were included in this study, including 132 cases in group A, 101 cases in group B, and 117 cases in group C. The overall eradication rates in each group were 95.45%, 92.08%, and 97.44%, respectively. Six patients with low compliance were excluded (3 in group A, 3 in group B, and 0 in group C), with eradication rates of 95.35%, 92.86%, and 97.44%, respectively. There was no significant difference in the eradication rate, compliance, recurrence rate, and incidence of adverse reactions among the groups, but the cost effectiveness ratio in group C was the lowest. Taking group A as a reference, the incremental cost effectiveness ratio for group C was ‒156.459. CONCLUSION Clarithromycin sustained-release tablets can be safely and effectively used in the primary eradication treatment of patients with Helicobacter pylori infection, and can be used according to the recommended dosage in the instructions.

OBJECTIVE To compare the cost-utility of eight programmed death 1(PD-1)/programmed cell death-ligand 1(PD-L1) inhibitor combination regimens for first-line treatment of advanced non-small cell lung cancer(NSCLC) from the perspective of Chinese healthcare system. METHODS Relevant data were derived from a published network meta-analysis and randomized controlled trails, a three-state Markov model was established to analyze the cost-utility of eight immunotherapy combinations. The robustness of results were validated through sensitivity analyses and a series of scenario analyses was also conducted. RESULTS The incremental cost-utility ratio(ICUR) of the sintilizumab plus chemotherapy group and the tislelizumab plus chemotherapy group were ￥125143.88/quality adjusted life year(QALY) and ￥189609.64/QALY, respectively, which were less than the willingness-to-pay(WTP) threshold of ￥257094/QALY, and all the ICURs of other PD-1/PD-L1 inhibitor combination regimens exceeded the WTP threshold and were not economical. Scenario analyses found that even if the medical insurance reimbursement ratio reached 80%, the different combinations of pembrolizumab, nivolumab and atezolizumab were not economical. CONCLUSION Compared with other PD-1/PD-L1 inhibitor combination regimens, sintilizumab plus chemotherapy and tislelizumab plus chemotherapy have cost-utility advantages in the first-line treatment of advanced NSCLC, which can provide a certain reference for selecting a reasonable treatment plan for NSCLC patients.

OBJECTIVE To evaluate the levels of evidence and analyze the rationality for off-label use of tacrolimus in the kidney diseases in adults. METHODS By systematically reviewing the drug instructions, clinical guidelines and medical literature of tacrolimus in the kidney diseases in adults, screening the highest level of evidence, and an evaluation table based on evidence-based medical for off-label use of tacrolimus in the kidney diseases in adults was established. Based on the evaluation table, collect adult patients from the Department of Nephrology in Zhongda Hospital Southeast University who had a medication history of off-label use of tacrolimus from January 1, 2021 to December 31, 2022, and evaluated the rationality of application for tacrolimus. RESULTS A total of 19 indications for off-label use of tacrolimus in the kidney diseases in adults were listed, and their recommended levels were determined based on evidence. Among them, the recommended levels for common types of kidney diseases were higher. In addition, 194 adult patients with off-label use of tacrolimus were selected from the Department of Nephrology in Zhongda Hospital Southeast University, and their application recommended levels with "strongly recommended""moderately strongly recommended""weakly recommended" and "not recommended", were 67.0%, 12.9%, 15.0% and 5.1%, respectively. CONCLUSION Tacrolimus has a wide range of indications for off-label use in the kidney diseases in adults, but the evidence for most common types of kidney diseases are relatively sufficient and their use are reasonable.

Allergic rhinitis(AR) is an allergic inflammatory disease of the nasal mucosa in which the immune inflammatory response alters the local microenvironment of the nasal mucosa, causing mucus hypersecretion as one of the main pathological features of AR. Interleukin-13(IL-13) is the main inflammatory factor secreted by Th2 cells, it can be involved in AR mucus hypersecretion process by regulating Goblet cell proliferation and Mucin 5ac expression through various signaling pathways. Traditional Chinese medicine has obvious advantages in the treatment of AR and its mucus hypersecretion, while the IL-13-mediated signaling pathways are one of the important mechanisms in treating AR mucus hypersecretion. This article reviews the regulation of IL-13-mediated signaling pathways on AR mucus hypersecretion and the intervention effects of traditional Chinese medicine, which providing a theoretical basis for experimental research and new drug development in AR mucus hypersecretion.

With the high-speed growing demands for biomedical materials, graphene oxide(GO) and its functional derivatives show broad application prospects in the system of drug delivery, tumor therapy and nanobiology. GO has excellent hydrophilicity and easily modified surface properties, due to a large content of oxygen-containing functional groups on the GO surface. Meanwhile, the huge specific surface areas and unique π-electronic structures give GO adhesion and adsorption capacities. By means of π-π stacking, electrostatic interaction, hydrophobic interaction or covalent bonding, therapeutic agents can be effectively combined with GO to construct drug delivery systems. GO plays an important role in transdermal drug delivery systems due to their biocompatibility, antibacterial activity, and pro-wound healing activity. As a novel drug delivery system, GO nanomaterials can achieve targeted drug delivery, accumulate drug concentrations at the focal site, and improve drug delivery efficiency. Utilizing the promoting skin regeneration and wound healing properties of GO, several antibacterial materials and wound dressings are prepared for wound treatment. In addition, the special far-infrared resonance effect and electrothermal effect of GO result in heat and electric transfer. In other words, graphene oxide could control and promote transdermal absorption efficiency upon the stimuli of heat and electric. GO is expected to break through the limitation of low transdermal absorption rates in the transdermal drug delivery systems and achieve the purpose of enhancing the transdermal permeability of target molecules (especially macromolecules): ultimately improving bioavailability in vivo. This paper will introduce the structures, physicochemical properties, and biological activities of graphene oxide, summarize its application in transdermal drug delivery systems such as drug carriers, antibacterial materials, wound dressings and transdermal enhancers, and prospect its application in clinical medicine. We hope to provide new ideas and different point of views for the biomedical research of graphene oxide and derivatives. GO will become a representative biomaterial in the field of precision medicine and play a key role in the diagnosis and treatment of diseases.