Eight compounds were isolated and purified from the ethyl acetate part of 70% acetone extract of Rehmannia glutinosa by various chromatographic techniques such as silica gel, MCI gel CHP-20, ODS, Toyopearl HW-40C, combined with TLC and semi-preparative HPLC. Their structures were elucidated by modern spectroscopy techniques (NMR, MS, UV, IR), and identified as neomartynoside A (1), osmanthuside B₆ (2), martynoside (3), isomartynoside (4), (E)-p-hydroxycinnamic acid (5), caffeic acid (6), ferulic acid (7), and methyl caffeate (8). Compound 1 is a new phenylethanol glycoside, which was identified as neomartynoside A. Compound 2 was isolated from Rehmannia glutinosa for the first time. In addition, compounds 2, 6 and 7 significantly increased relative glucose consumption, showing potential hypoglycemic activity.

Based on the strategy of metabolomics combined with bioinformatics, this study analyzed the potential allergens and mechanism of pseudo-allergic reactions (PARs) induced by the combined use of Reduning injection and penicillin G injection. All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine (approval number: YFYDW2020002). Based on UPLC-Q-TOF/MS technology combined with UNIFI software, a total of 21 compounds were identified in Reduning and penicillin G mixed injection. Based on molecular docking technology, 10 potential allergens with strong binding activity to MrgprX2 agonist sites were further screened. Metabolomics analysis using UPLC-Q-TOF/MS technology revealed that 34 differential metabolites such as arachidonic acid, phosphatidylcholine, phosphatidylserine, prostaglandins, and leukotrienes were endogenous differential metabolites of PARs caused by combined use of Reduning injection and penicillin G injection. Through the analysis of the "potential allergen-target-endogenous differential metabolite" interaction network, the chlorogenic acids (such as chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, and isochlorogenic acid A) and β-lactam allergens in the combination of the two may be mainly regulated by PLD1, PLA2G12A and CYP1A1. The three upstream signal target proteins mainly activate the arachidonic acid metabolic pathway, promote the degranulation of mast cells, release downstream endogenous inflammatory mediators, and induce PARs.

Objective To investigate the toxicokinetic differences of 3,4-methylenedioxy-N-methylamphetamine(MDMA)and its metabolite 4,5-methylene dioxy amphetamine(MDA)in rats af-ter single and continuous administration of MDMA,providing reference data for the forensic identifica-tion of MDMA.Methods A total of 24 rats in the single administration group were randomly divided into 5,10 and 20 mg/kg experimental groups and the control group,with 6 rats in each group.The ex-perimental group was given intraperitoneal injection of MDMA,and the control group was given intraperi-toneal injection of the same volume of normal saline as the experimental group.The amount of 0.5 mL blood was collected from the medial canthus 5 min,30 min,1 h,1.5 h,2 h,4 h,6 h,8 h,10 h,12 h after administration.In the continuous administration group,24 rats were randomly divided into the experi-mental group(18 rats)and the control group(6 rats).The experimental group was given MDMA 7 d by continuous intraperitoneal injection in increments of 5,7,9,11,13,15,17 mg/kg per day,respectively,while the control group was given the same volume of normal saline as the experimental group by in-traperitoneal injection.On the eighth day,the experimental rats were randomly divided into 5,10 and 20 mg/kg dose groups,with 6 rats in each group.MDMA was injected intraperitoneally,and the con-trol group was injected intraperitoneally with the same volume of normal saline as the experimental group.On the eighth day,0.5 mL of blood was taken from the medial canthus 5 min,30 min,1 h,1.5 h,2 h,4 h,6 h,8 h,10 h,12 h after administration.Liquid chromatography-triple quadrupole tandem mass spectrometry was used to detect MDMA and MDA levels,and statistical software was employed for data analysis.Results In the single-administration group,peak concentrations of MDMA and MDA were reached at 5 min and 1 h after administration,respectively,with the largest detection time limit of 12 h.In the continuous administration group,peak concentrations were reached at 30 min and 1.5 h af-ter administration,respectively,with the largest detection time limit of 10 h.Nonlinear fitting equations for the concentration ratio of MDMA and MDA in plasma and administration time in the single-administration group and continuous administration group were as follows:T=10.362C-1.183,R2=0.974 6;T=7.397 3C-0.694,R2=0.961 5(T:injection time;C:concentration ratio of MDMA to MDA in plasma).Conclusions The toxicokinetic data of MDMA and its metabolite MDA in rats,obtained through single and continuous administration,including peak concentration,peak time,detection time limit,and the relationship between concentration ratio and administration time,provide a theoretical and data foundation for relevant forensic identification.

Macroporous adsorption resin, MCI, Toyopearl HW-40C and silica gel column chromatography combined with the semi-preparative HPLC were used to isolate and purify the water extract of Cornus officinalis. And the structures of compounds were identified by HRESIMS, NMR, IR, UV and ECD. A total of twelve compounds were isolated from the fruits of Cornus officinalis. They were identified as neolignan B (1), 2,3-dihydro-7-methoxy-2-(4′-hydroxy-3′-methoxyphenyl)-3a-O-β-D-xylopyranosyloxymethyl-5-benzofuranpropanol (2), cornucadinoside A (3), 3,4-dihydroxyacetophenone (4), n-butyl gallate (5), 3-hydroxybenzoic acid (6), n-butyl quininate (7), 5-hydroxymaltol (8), 2-furolic acid (9), 5-hydroxymethylfurfural (10), 5-(methoxycarbonyl)-2-pyrrolidone (11), and dimethyl malate (12). Compound 1 is a new biphenyl lignan, named as neolignan B. Compounds 2, 4, 5, 7-9 and 11 were isolated from Cornus officinalis for the first time.

Objective To evaluate the efficacy of selective curettage when apical lesions are adjacent or involved to important struc-tures in endodontic microsurgery(EMS).Methods A total of 264 patients who underwent EMS in the Department of Endodontics,The Affiliated Stomatological Hospital of Nanjing Medical University from January 2021 to January 2023 were selected as the research subjects.The cases of EMS were divided into selective curettage group(SC-EMS)and conventional curettage group(C-EMS).In SC-EMS group,patients with apical lesions involving or adjacent to important structures(mental foramen,mandibular neural tube,naso-palatine neural canal,maxillary sinus,nasal base and adjacent vital pulp teeth)were included,and the adjacent areas around impor-tant structures were selectively cureted.In C-EMS group,patients with apical lesions adjacent to important structures were treated with conventional apical curettage.The postoperative follow-up was 12 months,and the postoperative symptoms and imaging examinations of the patients were observed,and the efficacy was evaluated.The failure cases were examined after tooth extraction and preoperative path-ological review to analyze the causes of failure.Results The success rate of SC-EMS group is 90.2%,and the success rate of C-EMS group is 95.4%.The rate of success in C-EMS group was higher,but there was no statistical difference between the two groups(P＞0.05).Root fracture is the important causes for the failure of the two groups.There were 6 cases of short-term discomfort and 2 cases of long-term discomfort after SC-EMS.The C-EMS group didn't meet any short-term or long-term discomfort case.Conclusion Selective curettage has no significant effect on the success rate of EMS surgery,and is an effective method to protect important structures during surgery.Short-term discomfort may occur after surgery,and irreversible pulp damage of adjacent teeth occurs in a few cases.

Aim To investigate the therapeutic effect of luteolin(LUT)on myasthenia gravis(MG)rats and its mechanism.Methods Female Lewis rats were di-vided into five groups:C group,MG group,low dose luteolin group(L-LUT),medium dose luteolin group(M-LUT)and high dose luteolin group(H-LUT),with 12 rats in each group.Rats in C group were nor-mal control rats.Rats in other groups were MG model rats induced by subcutaneous injection of Rα97-116.Rats in C group and MG group were intragastrically fed with 1 mL corn oil.Rats in L-LUT group,M-LUT group and H-LUT group were intragastrically infused with 1 mL 10,20 and 40 mg·kg-1 luteolin solution,respectively.The administration period was four weeks.Lennon grading method was used to score clini-cal symptoms,and EMG evoked potential instrument was used to detect the attenuation rate of low frequency repetitive nerve stimulation(RNS).The morphology of skeletal muscle was observed by hematoxylin eosin(HE)staining.The levels of serum AChR antibody(AChR-Ab),interferon gamma(IFN-γ)and interleu-kin-4(IL-4)were detected by ELISA method.The activity of superoxide dismutase(SOD)in skeletal muscle was detected by visible spectrophotometry,and glutathione peroxidase(GSH-Px)and malondialde-hyde(MDA)were detected by micromethod.The mR-NA levels of peroxisome proliferator-activated receptorγ coactivator-1α(PGC-1α),nuclear respiratory factor 1(NRF1)and mitochondrial transcription factor A(TFAM)in skeletal muscle were measured by qRT-PCR.The protein expression levels of AMP-activated protein kinase α(AMPKα)and p-AMPKα in skeletal muscle were detected by Western blot.Results Com-pared with C group,Lennon score and RNS decay rate in MG group increased,AChR-Ab and IFN-γ levels increased,skeletal muscle showed obvious injury,SOD and GSH-Px levels decreased,MDA levels in-creased,p-AMPKα protein expression levels and PGC-1α,NRF1 and TFAM mRNA levels decreased(P＜0.05).Compared with MG group,Lennon score and RNS decay rate in L-LUT group and M-LUT group M and H-LUT group decreased,AChR-Ab and IFN-γlevels decreased,skeletal muscle damage was allevia-ted,SOD and GSH-Px levels increased,MDA levels decreased,p-AMPKα protein expression levels and PGC-1α,NRF1 and TFAM mRNA levels increased(P＜0.05).Conclusion The mechanism of luteolin in treating MG rats may be related to correcting the bal-ance of Th1/Th2 cells and activating AMPK.

Objective To construct a big data sharing platform for clinical scientific research to solve the problems of clinical research in decentralized application systems and data sharing safety.Methods A clinical research information data usage management system was developed through the formulation of management methods in line with the actual situation of the institution,normalized standard data usage processes and a data usage service team.Then a clinical scientific research big data sharing platform including the components for sharing environment construction,research application integration,data desensitization and encryption and file management was established based on the existing hospital systems,the requirements of clinical research data usage management and the habits of clinical researchers.Results The platform realized the balance between open sharing of clinical research data and data security control,which improved the efficiency of clinical researchers while reducing data security risks during data transmission and data analysis.Conclusion The clinical scientific research big data sharing platform meets the needs of clinical scientific research application and data security management,and provides references for the co-construction-sharing of medical big data resources.[Chinese Medical Equipment Journal,2024,45(4):27-31]

Objective To evaluate the efficacy and safety of brexpiprazole in treating acute schizophrenia.Methods Patients with schizophrenia were randomly divided into treatment group and control group.The treatment group was given brexpiprozole 2-4 mg·d-1 orally and the control group was given aripiprazole 10-20 mg·d-1orally,both were treated for 6 weeks.Clinical efficacy of the two groups,the response rate at endpoint,the changes from baseline to endpoint of Positive and Negative Syndrome Scale(PANSS),Clinical Global Impression-Improvement(CGI-S),Personal and Social Performance scale(PSP),PANSS Positive syndrome subscale,PANSS negative syndrome subscale were compared.The incidence of treatment-related adverse events in two groups were compared.Results There were 184 patients in treatment group and 186 patients in control group.After treatment,the response rates of treatment group and control group were 79.50％(140 cases/184 cases)and 82.40％(150 cases/186 cases),the scores of CGI-I of treatment group and control group were(2.00±1.20)and(1.90±1.01),with no significant difference(all P＞0.05).From baseline to Week 6,the mean change of PANSS total score wese(-30.70±16.96)points in treatment group and(-32.20±17.00)points in control group,with no significant difference(P＞0.05).The changes of CGI-S scores in treatment group and control group were(-2.00±1.27)and(-1.90±1.22)points,PSP scores were(18.80±14.77)and(19.20±14.55)points,PANSS positive syndrome scores were(-10.30±5.93)and(-10.80±5.81)points,PANSS negative syndrome scores were(-6.80±5.98)and(-7.30±5.15)points,with no significant difference(P＞0.05).There was no significant difference in the incidence of treatment-related adverse events between the two group(69.00％vs.64.50％,P＞0.05).Conclusion The non-inferiority of Brexpiprazole to aripiprazole was established,with comparable efficacy and acceptability.

AIM To study the chemical constituents from flower buds of Magnolia biondii Pamp.and their in vitro acetylcholinesterase inhibitory activities.METHODS The 50% acetone extract from the flower buds of M.biondii was isolated and purified by Diaion HP-20,Toyopearl HW-40C,ODS and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The in vitro acetylcholinesterase inhibitory activities of these compounds were determined according to previous method established by research group.RESULTS Seventeen compounds were isolated and identified as crassifolioside(1),magnoloside B(2),rutin(3),isoquercitrin(4),quercetin(5),northalifoline(6),cordysinin B(7),thymidine(8),indazole(9),dihydrodehydrodiconiferyl alcohol(10),aesculetin(11),C-veratroylglycol(12),3,4-dihydroxyphenylethanol(13),3-methoxy-4-hydroxyphenylethanol(14),3,4-dihydroxybenzoic acid(15),2,4,6-trimethoxyphenol(16),syringic acid(17).CONCLUSION Compounds 1-17 are isolated from this plant for the first time,none of which show acetylcholinesterase inhibitory activities at the concentration of 20 μmol/L.

Protein phosphorylation modification is an important mechanism of physiological regulation that is closely related to protein biological functions. In particular, protein kinases are responsible for catalyzing the phosphorylation process of proteins, and phosphatases are responsible for catalyzing the dephosphorylation process of phosphorylation-modified proteins, which together mediate the achievement of dynamic and reversible phosphorylation modifications of proteins. Abnormal phosphorylation levels of proteins contribute to the development of many diseases, such as cancer, neurodegenerative diseases, and chronic diseases. Therefore, rational design of small molecules to regulate protein phosphorylation is an important approach for disease treatment. Based on the mechanism of protein phosphorylation regulation, small molecule drug design strategies can be classified into three types, protein kinase modulators, phosphatase modulators, and bifunctional molecules with proximity-mediated mechanism. This review emphasizes the above three small molecule design strategies for targeting protein phosphorylation regulation, including molecular design ideas, research progress and current challenges, and provides an outlook on small molecule modulators targeting protein phosphorylation modification.