Isosteviol is a tetracyclic diterpenoid compound obtained by hydrolysis of natural stevia glycoside under acidic conditions. It has many pharmacological activities, such as anti-tumor, hypoglycemic, anti-inflammatory and antibacterial. Due to its low water solubility, low activity and low bioavailability, isosteviol has poor performance. In order to overcome these shortcomings, scholars have obtained a large number of isosteviol derivatives with novel structures and excellent activity. In this paper, we review the recent progress in the research on the structure modification, biological activity, structure-activity relationship and microbial transformation of isosteviol, in order to provide a reference for the development of new drugs of isosteviol and its derivatives.

Five flavonoid glycosides were isolated from the methanol and ethyl acetate fractions of the ethanol extract of Diphylleia sinensi by using various chromatographic methods, including silica gel, MCI gel, Sephadex LH-20, ODS and semi-preparative HPLC. The structures of the isolated compounds were identified as diphyflavonoid A (1), diphyflavonoid B (2), quercetin-3-O-β-D-glucopyranoside (3), kaempferol-3-O-β-D-glucopyranoside (4), kaempferol-3-O-(6″-O-acetyl)-β-D-glucopyranoside (5) by spectroscopy methods (1D NMR, 2D NMR, UV, IR, and MS). Compounds 1 and 2 were two new flavonoid glycosides, and compounds 3 and 5 were isolated from the genus Diphylleia for the first time.

Objective To investigate the effect and mechanism of transplantation of neuregulin1(NRG1)gene-modified bone marrow mesenchymal stem cells(BMSCs)on the repair of hemi-transected spinal cord injury(SCI)in rats.Methods Isolated and cultured rat BMSCs,followed by transfection with the NRG1 gene.The levels of NRG1 in BMSCs lysate and culture supernatant was deected by ELISA method,and the proliferation activity of the BMSCs was detected by cell counting method.Forty-three healthy 8-week-old SD rats were randomly divided into control group(n=10),SCI model group(n=10),BMSCs group(n=10),and NRG1-BMSCs group(n=13).After establishing the spinal cord hemisection model,animals received in-situ transplantation of BMSCs or NRG1-BMSCs.On the 1,7,14,21,and 28 days after transplantation,the hind limb motor function was evaluated using BBB score and inclined plate test;on the 7th day after transplantation,the migration and distribution of transplanted cells was monitored using a fluorescence microscope;on the 28th day after transplantation,the pathological changes of rat spinal cord tissues was examined using HE staining and Nissl staining;cell apoptosis using TUNEL staining,and levels of endoplasmic reticulum stress-related proteins[X-box binding protein 1(XBP1),C/EBP homologous protein(CHOP),activating transcription factor 4(ATF4),ATF6,glucose-regulated protein 78(GRP78)]and apoptosis-related proteins[B-cell lymphoma-2(Bcl-2)and Bcl-2-associated protein X(Bax)]in rat spinal cord tissues using Western blotting.Results BMSCs were successfully isolated,cultured,and transfected with the NRG1 gene.ELISA method results showed that the NRG1 contents in the NRG1-BMSCs lysate and culture supernatant were significantly higher than that of BMSCs in a time-dependent manner(P<0.05).The proliferation activity of NRG1-BMSCs was significantly higher than that of BMSCs(P<0.05).On the 21 and 28 days after transplantation,the BBB score and the slope angle of the inclined plate in NRG1-BMSCs group were higher than those in SCI model group or BMSCs group(P<0.05).However,it did not reverse to the level in control group(P<0.05).On the 28th day after transplantation,compared with the SCI model group and BMSCs group,neuronal pyknosis reduced,the Nissl body density increased,the expression levels of XBP1,CHOP,ATF4,ATF6,GRP78,and Bax,and the rate of TUNEL-positive cells significantly reduced in NRG1-BMSCs group(P<0.05),and the expression level of Bcl-2 significantly increased(P<0.05).Conclusion Transplantation of NRG1 gene-modified BMSCs can alleviate SCI and improve the recovery of motor function in rats.The mechanism may be related to promoting the proliferation activity of BMSCs,inhibiting cell apoptosis,and mitigating endoplasmic reticulum stress.

Objective To evaluate the value of multi-slice spiral computed tomography (CT) for diagnosing acute pulmonary embolism, and to provide a reference for the precise diagnosis of acute pulmonary embolism. Methods We enrolled a total of 102 patients pathologically diagnosed with acute pulmonary embolism from January 2019 to October 2023. All the patients underwent CT scanning of central and segmental pulmonary arteries with a GE 64-slice spiral CT scanner. The diagnostic efficacy of multi-slice CT scans for acute pulmonary embolism was evaluated with the pathological results as the gold standard. Results Of the 102 patients pathologically diagnosed with acute pulmonary embolism, multi-slice CT detected 92 cases, with an accuracy of 90.20% (92/102), including 17 cases (18.48%) of embolism in left pulmonary arteries, 31 cases (33.70%) of embolism in right pulmonary arteries, and 44 cases (47.82%) of embolism in both pulmonary arteries. Multi-slice CT visualized a total of 9905 pulmonary artery branches, and 304 of them (3.07%) had embolism, with the highest embolism rate in lobar arteries (43.89%). Conclusion Multi-slice spiral CT has high accuracy for diagnosing acute pulmonary embolism by directly and clearly visualizing embolism in the arteries of the lungs, which deserves clinical promotion.

【Objective】 To study the molecular mechanism of 95 samples of serological ABO subtypes. 【Methods】 A total of 95 samples with discrepancy between forward and reverse blood grouping were subjected to serological confirmation, and genotyped by polymerase chain reaction with sequence-specific primers (PCR-SSP). For those subtype alleles could not be detected by PCR-SSP, ABO gene exon 1-7 sequencing and gene single strand sequencing were performed successively to determine the mutation site and the gene location. 【Results】 A total of 34 ABO alleles were detected in 95 samples. Five common ABO alleles (ABO^*A1.01, ABO^*A1.02, ABO^*B.01, ABO^*O.01.01 and ABO^*O.01.02) and 29 rare ABO alleles were identified, including 16 named alleles by ISBT (ABO^*A2.01, ABO^*A2.05, ABO^*A2.13, ABO^*A3.07, ABO^*AW.37, ABO^*AEL.05, ABO^*B3.01, ABO^*B3.05, ABO^*BW.03, ABO^*BW.07, ABO^*BW.27, ABO^*BEL.03, ABO^*cisAB.01, ABO^*cisAB.05, ABO^*BA.02, ABO^*BA.04) and 5 named alleles by dbRBC(A223, B309, Bw37, Bel09, Bw40)and eight unnamed alleles [ABO^*B.01+ 978C>A, ABO^*A1.02+ 248A>T, ABO^*B.01+ 125dupT, ABO^*B.01+ (98+ 1G>A), ABO^*A1.02/ABO^*B.01+ 1A>G, ABO^*A1.02/ABO^*O.01.01+ 28G>T, ABO^*A1.02/ABO^*B.01+ 538C>T, ABO^*A1.02/ABO^*O.01.01+ 797insT] .The last four samples could not be verified by single strand because of insufficient samples. In 95 samples, 76 samples (21 named alleles of ISBT and dbRBC) were identified by PCR-SSP, and the remaining 19 samples were identified by exon 1-7 sequencing of ABO gene, of which 8 were identified as unnamed alleles, and the remaining 11 samples were not identified as subtype alleles. 【Conclusion】 The molecular genetic mechanism of 95 serological ABO subtypes was revealed, and 8 rare novel alleles were identified. The detection of ambiguous blood groups is influenced by factors such as patient pathology and physiology, therefore the combination of serological testing and genetic testing is suggested for the identification of ABO subtype.

Gallbladder carcinoma,a relatively rare malignancy within the biliary tract,presents a grave prognosis primarily due to asymptomatic early stages leading to advanced stage diagnosis and the absence of efficacious treatment options.Research has identified chronic inflammation,predom-inantly caused by gallstones,as a critical etiological factor.While surgical intervention offers potential curative outcomes in early stages,the majority of cases are identified too late for optimal surgical outcomes.Chemotherapy and targeted therapy,despite offering new therapeutic avenues,have not significantly improved overall survival rates.Thus,understanding the pathogenesis of gallbladder cancer,especially its association with key genetic and molecular pathways,is imperative for devising novel therapeutic strategies.This review delineates the epidemiology,pathogenesis,current treat-ment modalities,and research advancements in gallbladder cancer,aiming to provide innovative in-sights for clinical management and guide future research endeavors.

Activation of nuclear factor erythroid 2-related factor 2(Nrf2)by Kelch-like ECH-associated protein 1(Keap1)alkylation plays a central role in anti-inflammatory therapy.However,activators of Nrf2 through alkylation of Keap1-Kelch domain have not been identified.Deoxynyboquinone(DNQ)is a natural small molecule discovered from marine actinomycetes.The current study was designed to investigate the anti-inflammatory effects and molecular mechanisms of DNQ via alkylation of Keap1.DNQ exhibited signif-icant anti-inflammatory properties both in vitro and in vivo.The pharmacophore responsible for the anti-inflammatory properties of DNQ was determined to be the α,β-unsaturated amides moieties by a chemical reaction between DNQ and N-acetylcysteine.DNQ exerted anti-inflammatory effects through activation of Nrf2/ARE pathway.Keap1 was demonstrated to be the direct target of DNQ and bound with DNQ through conjugate addition reaction involving alkylation.The specific alkylation site of DNQ on Keap1 for Nrf2 activation was elucidated with a synthesized probe in conjunction with liquid chromatography-tandem mass spectrometry.DNQ triggered the ubiquitination and subsequent degra-dation of Keap1 by alkylation of the cysteine residue 489(Cys489)on Keap1-Kelch domain,ultimately enabling the activation of Nrf2.Our findings revealed that DNQ exhibited potent anti-inflammatory capacity through α,β-unsaturated amides moieties active group which specifically activated Nrf2 signal pathway via alkylation/ubiquitination of Keap1-Kelch domain,suggesting the potential values of targeting Cys489 on Keap1-Kelch domain by DNQ-like small molecules in inflammatory therapies.

Analyzing polysorbate 20(PS20)composition and the impact of each component on stability and safety is crucial due to formulation variations and individual tolerance.The similar structures and polarities of PS20 components make accurate separation,identification,and quantification challenging.In this work,a high-resolution quantitative method was developed using single-dimensional high-performance liquid chromatography(HPLC)with charged aerosol detection(CAD)to separate 18 key components with multiple esters.The separated components were characterized by ultra-high-performance liquid chro-matography-quadrupole time-of-flight mass spectrometry(UHPLC-Q-TOF-MS)with an identical gradient as the HPLC-CAD analysis.The polysorbate compound database and library were expanded over 7-time compared to the commercial database.The method investigated differences in PS20 samples from various origins and grades for different dosage forms to evaluate the composition-process relationship.UHPLC-Q-TOF-MS identified 1329 to 1511 compounds in 4 batches of PS20 from different sources.The method observed the impact of 4 degradation conditions on peak components,identifying stable components and their tendencies to change.HPLC-CAD and UHPLC-Q-TOF-MS results provided insights into fingerprint differences,distinguishing quasi products.

Objective To systematically evaluate the value of optical coherence tomography angiogra-phy (OCTA) for detecting the vessel density (VD) changes after open-angle glaucoma (OAG) surgery.Meth-ods The studies on OCTA for detecting the VD changes after OAG surgery were searched in the CNKI,WanFang,VIP,SinoMed,PubMed,Embase and Web of Science databases from the database establishment to May 2024.Literature screening,data extraction and risk of bias assessment of included studies were conducted independently by two reviewers.Descriptive analysis was adopoted for the systematic evaluation,the meta a-nalysis was conducted by using the R software and mean difference (MD) and its 95％CI were calculated.Re-sults A total of 13 studies were included,involving 472 patients with 500 tested eyes.The results of meta-a-nalysis showed that compared with pre-surgery,VD around the optic nerve head (ONH) and in nasal superi-or,temporal inferior,temporal superior,superior temporal and superior nasal regions at postoperative 6 months were significantly decreased.VD in the perimacular,perimacular superior hemisphere,permacular su-perior hemisphere,perimacular superior and permacular superior regions at postoperative 6 months were sig-nificantly increased.Conclusion OCTA could effectively detect the postoperative VD changes in the patients with OAG and predict postoperative visual function changes in glaucoma,and could serve as an effective test means for assessing the clinical treatment effect of the patients with OAG.

Objective:To observe the effect and safety of the traditional Chinese medicine(TCM)Linggui Formula(LGF)in the treatment of asthenospermia with kidney deficiency and blood stasis.Methods:This randomized controlled trial included 90 ca-ses of asthenospermia with kidney deficiency and blood stasis treated in our hospital from September 2022 to September 2023,45 by oral medication with LGF(the trial group)and the other 45 with oral levocarnitine solution(the control group),all for 12 weeks.We followed up the patients for 12 weeks,recorded the semen parameters,TCM syndrome scores,sexual hormone levels,pregnancy rates,and DNA fragmentation index(DFI)of the patients,and compared them between the two groups before and after treatment.Re-sults:Totally,82 of the patients completed the study,42 in the trial and 40 in the control group.After treatment,the patients in the trial group showed significant increases in the percentage of progressively motile sperm(PMS)(from[19.25±3.08]% to[38.57±4.99]%,P<0.05),total sperm motility(from[32.29±3.64]% to[46.50±4.77]%,P<0.05)and sperm concentration(from[83.9±37.2]to[95.1±34.9]×106/ml],P<0.05),and so did the controls in PMS(from[19.75±4.28]% to[34.46±5.07]%,P<0.05),total sperm motility(from[33.02±4.93]% to[43.11±4.72]%,P<0.05)and sperm concen-tration(from[85.2±39.7]to[88.1±35.2]×106/ml,P<0.05),all even more significant in the trial than in the control group(P<0.05).No statistically significant difference was observed in the semen volume either in the trial(from[3.38±0.38]to[3.24±0.45]ml,P>0.05)or in the control group(from[3.46±0.52]to[3.30±0.37]ml,P>0.05),or between the trial and control groups(P>0.05),or in the sexual hormone levels,pregnancy rates,and sperm DFI between the two groups before and after treatment(P>0.05).Both groups of patients had good safety profiles without serious adverse reactions.Conclusion:Linggui Formula can improve the percentage of PMS in asthenospermia patients with kidney deficiency and blood stasis,potentially enhancing pregnancy rates and with a good safety.