AIM:To observe how total flavonoids of Pterocarya hupehensis Skan(PHSTF)affects the migra-tion and invasion of human rheumatoid fibroblast-like synoviocyte line MH7A.METHODS:The MH7A cells were divided into control group(without any treatment),low-,medium-and high-dose(6.25,12.5 and 25 mg/L,respectively)PHSTF groups,phosphatidylinositol 3-kinase(PI3K)inhibitor 740Y-P(10 μmol/L)group,and 740Y-P(10 μmol/L)+high-dose(25 mg/L)PHSTF group.The viability of the MH7A cells was determined by CCK-8 assay,while the migration and inva-sion were assessed by scratch and Transwell assays.The protein levels of matrix metalloproteinase-2(MMP-2),MMP-9,PI3K,p-PI3K,AKT and p-AKT were detected by Western blot.RESULTS:Compared with control group,the cell via-bility in PHSTF treatment groups was reduced(P<0.05),the cell wound healing area was significantly decreased(P<0.01),migratory and invasive cells in the lower chamber were significantly reduced(P<0.01),and the protein expres-sion of MMP-2 and MMP-9 and the ratios of p-PI3K/PI3K and pAKT/AKT were decreased(P<0.01).Compared with high-dose PHSTF group,the addition of PI3K/AKT pathway agonist 740Y-P significantly increased the migration and invasion ability of MH7A cells(P<0.01)and elevated the protein expression of MMP-2 and MMP-9 and the ratios of p-PI3K/PI3K and pAKT/AKT(P<0.01)under the treatment with PHSTF.CONCLUSION:Total flavonoids of Pterocarya hupehensis Skan could inhibit the migration and invasion of MH7A cells by regulating the PI3K/AKT signaling pathway.

Objective To compare the pharmacokinetic profiles of the two teriflunomide tablets in healthy Chinese subjects under fasting and fed conditions and to evaluate their bioequivalence and safety.Methods A randomized,open,single-dose,parallel trial design was used to enroll 31 and 32 healthy Chinese male subjects in the fasting and fed groups,who were randomized to a single oral dose of 14 mg of either reference or test preparation of teriflunomide tablets.The plasma concentrations of teriflunomide were determined using liquid chromatography-tandem mass spectrometry method,and Phoenix WinNonlin 8.1 software was used to calculate pharmacokinetic parameters and perform bioequivalence analysis.Results Subjects received a single oral dose of the reference and test formulations of teriflunomide.The main pharmacokinetic parameters of teriflunomide in the fasting group were as follows:Cmax were(2.14±0.27)and(2.27±0.33)μg·mL-1,AUC0-72h were(105.70±11.20)and(107.72±11.77)μg·mL-1·h,tmax was 1.49 and 0.99 h;the main pharmacokinetic parameters of teriflunomide in the fed group were as follows:Cmaxwere(1.83±0.17)and(1.75±0.22)μg·mL-1,AUC0-72h were(102.66±9.18)and(101.57±13.01)μg·mL-1·h,tmax was 4.01 and 4.99 h.The 90％confidence intervals for the geometric means of Cmax and AUC0-72h for reference and test preparations in the fasting and fed groups were in the range of 80％to 125％.Conclusion The pharmacokinetic characteristics of the 2 formulations were similar under fasting and fed administration conditions,with good bioequivalence and safety;Postprandial administration may delay the time to peak of the drug.

Objective: To assess the role of dynamic contrast-enhanced (DCE)-MRI of the extraocular muscles (EOMs) for determining the activity of thyroid-associated ophthalmopathy (TAO) and treatment response to glucocorticoids (GCs). Materials and Methods: We prospectively enrolled 65 patients with TAO (41 active, 82 eyes; 24 inactive, 48 eyes). Twenty-two active patients completed the GC treatment and follow-up assessment, including 15 patients (30 eyes) and 7 patients (14 eyes), defined as responsive and unresponsive, respectively. Model-free (time to peak [TTP], area under the curve [AUC], and Slope max) and model-based (Ktrans , Kep, and Ve) parameters of EOMs in embedded simplified histogram analyses were calculated and compared between groups. Multivariable logistic regression analysis was used to identify the independent predictors. The area under the receiver operating characteristic curve (AUROC) was used to evaluate the diagnostic performance. Results: Active patients exhibited significantly higher TTP at the 10th percentile (-10th), TTP-mean, and TTP at the 90th percentile (-90th); AUC-10th, AUC-mean, AUC-90th, and AUC-max; Ktrans -10th and Ktrans -mean; and Ve-10th, Ve-mean, Ve-90th, and Ve-max than inactive patients (P < 0.05). Responsive patients exhibited significantly lower TTP-min; higher Ktrans -mean and Ktrans -max; and higher Kep-10th, Kep-mean, and Kep-max than unresponsive patients (P < 0.05). TTP-mean and Ve-mean were independent variables for determining disease activity (P = 0.017 and 0.022, respectively). A combination of the two parameters could determine active TAO with moderate performance (AUROC = 0.687). TTP-min and Ktrans -mean were independent predictors of the response to GCs (P = 0.023 and 0.004, respectively), uniting which could determine the response to GCs with decent performance (AUROC = 0.821). Conclusion DCE-MRI-derived model-free and model-based parameters of EOMs can assist in the evaluation of TAO. In particular, TTP-mean and Ve-mean could be useful for determining the activity of TAO, whereas TTP-min and K trans -mean could be promising biomarkers for determining the response to GCs.

AIM To investigate the mechanism of triterpenoids quillaic acid and gypsogenin-3-O-glucuronide from Psammosilene tunicoides on tunicamycin-induced rheumatoid arthritis fibroblasts-like synoviocytes(RA-FLS)via the endoplasmic reticulum pathway.METHODS The research objects of tunicamycin-induced RA-FLS intervened with quillaic acid and gypsogenin-3-O-glucuronide had their cell proliferation activity detected;their level of tumor nerosis factor-α(TNF-α)detected by ELISA;their apoptosis detected by flow cytometry;their cell migration ability detected by Transwell experiment;their expressions of transcription activator 6(ATF-6),glucose regulatory protein 78(GRP78),C/EBP homologous protein(CHOP),cysteine protease protein-12(caspase-12)and anti-apoptosis Bcl-2 protein detected by Western blot;and their mRNA expressions of ATF-6,GRP78 and CHOP detected by RT-qPCR.RESULTS Compared with the model group,each group intervened with quillaic acid or gypsogenin-3-O-glucuronide displayed decreased levels of TNF-α(P＜0.01);weakened cell proliferation and migration ability(P＜0.01);increased apoptosis rate(P＜0.01);decreased protein expressions of ATF-6 and Bcl-2(P＜0.05,P＜0.01);and increased protein expressions of CHOP and caspase-12(P＜0.05,P＜0.01).In addition,decreased GRP78 protein expression in the low and medium dose groups(P＜0.05,P＜0.01);decreased mRNA expression of ATF-6,GRP78(P＜0.01)and increased CHOP mRNA expression(P＜0.01)in the medium dose groups of quillaic acid and gypsogenin-3-O-glucuronide were observed as well.CONCLUSION Quillaic acid and gypsogenin-3-O-glucuronide may play a protective role in rheumatoid arthritis by inhibiting the proliferation and migration of RA-FLS,inducing apoptosis and reducing the secretion of related inflammatory factors via endoplasmic reticulum signal pathway.

Off-label use means that the intended use of the drug is not included in the instructions approved by the National Medical Products Administration,including unapproved indication,dosage,the course of treatment,route of administration,or population.The formulation of Pharmaceutical Supply Services-Key Medications Management-Off-label Uses is based on relevant laws,regulations,normative documents,guidelines,literatures,and expert opinions,and follows the principles of scientificity,versatility,instructiveness,and operability.This standard regulates and standardizes the institutional and organizational construction,process management,and the whole process of quality management and evaluation improvement of off-label uses,which is the basis for medical institutions to carry out off-label uses management.This article introduced the formulation process of the off-label uses standard and analyzed the key contents of the standard,which would help medical institutions to better comply with and meet the requirements of this standard in the practice of off-label use management.

Drugs under special management include narcotic drugs,psychotropic drugs,toxic drugs for medical use,radiopharmaceuticals,and pharmaceutical precursor chemicals.Supervising and guiding the clinical use of drugs under special management is one of the important responsibilities of the Pharmaceutical Management and Drug Therapy Committee(Group)of medical institutions.The standard for drugs under special management is led by the Pharmaceutical Professional Committee of the China Hospital Association,which standardizes 16 key elements of organizational management,process management,and quality control management drugs under special management in medical institutions.It can guide the standardized implementation of Pharmaceuticals under special control work in various levels and types of medical institutions.This article elaborates on the methods and contents of formulating standards for Pharmaceuticals under special management,to provide reference and inspiration for medical institutions to carry out special drug drug management and daily related work.

The management of clinical application of antimicrobial drugs is an important part of the pharmaceutical management and pharmacy services in medical institutions.Based on national policies and regulations,this standard focuses on the whole life cycle of antimicrobial drugs in medical institutions.It is developed based on the principles of scientific validity,universality,guidance and operability,formed by sorting out problems,collecting opinions,expert argumentation and deliberation.It is the first group standard to standardize the clinical application management of antimicrobial drugs.This paper introduces and analyzes the team composition,problem sorting and compilation process,and various elements of the standard in the process of formulating the standard,and provide a reference for the majority of peers who use it.

Antineoplastic drugs refer to the drugs that act at the cellular and molecular levels to inhibit tumor growth or eliminate tumors through pathways such as cell killing,immune regulation,and endocrine regulation.Antineoplastic drugs generally including chemotherapeutic drugs,molecular targeted therapeutic drugs,immunotherapeutic drugs,and endocrine therapeutic drugs.The management and rational application of antineoplastic drugs in medical institutions are related to the safety of patient treatment.The standard for management of antineoplastic drugs use in clinical is compiled by the Pharmaceutical Affairs Committee of China Hospital Association,which specification requirements 18 key elements in the organizational management and system,medication management,drug monitoring and evaluation of antineoplastic drug management in healthcare institutions.This standard is applicable to all levels and types of healthcare institutions carrying out oncology diagnosis and treatment.This paper describes the methodology and basic content of the standard,hoping to providing a reference for medical institutions to carry out relevant work.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective To investigate the correlation between optimal placement depth(OPD)and physical measurement parameters in preterm infants receiving placement of peripherally inserted central catheter(PICC)through the great saphenous vein(GSV),and to establish a predictive formula for OPD during the placement of PICC through the GSV.Methods A retrospective analysis was performed for the preterm infants who received the placement of PICC through the GSV in the Neonatal Intensive Care Unit of the Third Xiangya Hospital of Central South University from December 2022 to February 2024.According to the site of puncture[GSV of the knee joint(KJ)or the ankle joint(AJ)],they were divided into a GSV-KJ placement group(n=38)and a GSV-AJ placement group(n=33).The infants were measured in terms of body weight(BW),body length,the length of the upper and lower parts of the body,head circumference,and abdominal circumference at the time of placement.The Pearson correlation analysis was used to investigate the correlation between the above variables and OPD.A predictive formula was established for OPD in the placement of PICC via the GSV in preterm infants,and the predicted residual between the predicted depth and the ideal OPD was compared between the conventional predictive formula and the new predictive formula.Results The Pearson correlation analysis showed that PICC OPD was significantly positively correlated with BW,body length,the length of the upper and lower parts of the body,head circumference,and abdominal circumference in both the GSV-KJ placement group and GSV-AJ placement group(P<0.05),with the highest degree of correlation between OPD and BW.The univariate linear regression analysis showed a linear relationship between PICC OPD and BW in both groups.The predictive formulas for OPD were as follows:GSV-KJ PICC OPD(cm)=13.1+2.7×BW(kg)and GSV-AJ PICC OPD(cm)=13.4+6.0×BW(kg),and the new predictive formulas had a significantly lower predicted residual than the conventional predictive formula(P<0.05).Conclusions OPD for PICC through the GSV is positively correlated with BW,and the prediction results of the new predictive formula based on BW are closer to the ideal OPD.