ObjectiveTo investigate the effect of galvanic vestibular stimulation on stroke patients with lateropulsion. MethodsFrom February to October, 2023, 30 stroke patients with lateropulsion in the First Affiliated Hospital of Nanjing Medical University were divided into control group (n = 15) and experimental group (n = 15) randomly. The control group received routine rehabilitation and sham galvanic vestibular stimulation, and the experimental group received routine rehabilitation and true galvanic vestibular stimulation, for two weeks. They were assessed with Scale for Contraversive Pushing (SCP), subjective visual vertical (SVV), Line Cancellation Test (LCT), Star Cancellation Test (SCT), Berg Balance Scale (BBS), Holden Functional Ambulation Category (FAC) and Barthel Index (BI) before and after treatment. ResultsAll the indexes improved in both groups after intervention (|t| > 2.461, Z > 3.000, P < 0.05), except the SVV orientation, SVV certainty and SCT in the control group; while the SCP, SVV certainty, LCT and FAC were better in the experimental group than in the control group (|t| > 2.189, Z = -2.862, P < 0.05), and the differences before and after intervention were better in the experimental group than in the control group (|t| > 2.382, P < 0.05), except LCT. SCP was correlated with SVV orientation, SVV certainty, SCT, BBS, BI and FAC (|r| > 0.381, P < 0.05). ConclusionGalvanic vestibular stimulation can improve the lateropulsion, balance, walking function and activities of daily living in stroke patients, which may be related to improvement for spatial cognitive function, especially vertical perception.

Malignant insulinoma is a kind of rare and challenging neuroendocrine tumor. It is often accompanied by distant metastasis, among which liver metastasis is most common, and the prognosis is often non-promising. In this paper, we report a case of multiple liver metastases from malignant insulinoma. The patient, a 70-year-old male, was admitted to the hospital due to "episodic consciousness disorder for more than four months." Blood glucose monitoring revealed recurrent hypoglycemia in the early morning, after meals, and at night. Pancreatic perfusion CT and dynamic enhanced MRI of the liver revealed a mass in the uncinate process of the pancreatic head and multiple liver metastases. Percutaneous liver biopsy confirmed the diagnosis of insulinoma. After multidisciplinary discussions, hepatic artery embolization and radiofrequency ablation were performed in stages, in combination with everolimus treatment. Thereafter, the enhanced CT demonstrated that some liver metastases shrank. The patient had regular meals, and the blood sugar gradually increased and remained normal thereafter. This article discusses this case's clinical characteristics and multidisciplinary collaborative diagnosis and treatment, aiming to provide experience for the comprehensive clinical diagnosis and treatment of malignant insulinoma patients.

Objective To evaluate the bioequivalence of a single oral dose of ritonavir in fasted and fed conditions in healthy Chinese adult subjects with the test and reference formulations.Methods A single-center,open-label,randomized,single-dose,two-periods,two-sequence crossover design was used,and 64 subjects were enrolled in both the fasted and fed groups.The subjects received 100 mg of the test preparation or reference preparation orally per cycle,and the drug concentration of ritonavir in plasma was detected using the high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS)method.Pharmacokinetic parameters were estimated by a non-compartment model,and SAS 9.4 software was used for statistical analysis.Results Arithmetic mean values of the main pharmacokinetic parameters of the subject formulation of ritonavir tablets and the reference formulation in the fasting group:Cmax were(791.90±400.20)and(809.60±449.14)ng·mL-1;AUC0_t were(6 072.61±2 631.98)and(6 296.30±3 388.95)ng·h·mL-1;AUC0-∞ were(6 129.59±2 655.57)and(6 347.26±3 434.12)ng·h·mL-1,respectively.Arithmetic mean values of the main pharmacokinetic parameters of the subject formulation of ritonavir tablets and the reference formulation in the fed group:Cmax were(512.37±233.60)and(521.74±223.87)ng·mL-1;AUC0_t were(4 203.43±2 221.33)and(4 200.13±1 993.50)ng·h·mL-1;AUC0_∞ were(4 259.21±2 266.88)and(4 259.63±2 044.12)ng·h·mL-1.The 90％confidence intervals for the geometric mean ratios of Cmax,AUC0_t and AUC0_∞ of the prototype drug ritonavir in plasma after oral administration of 100 mg of the test and reference formulations of ritonavir tablets under fasting and fed conditions fell within the 80.00％to 125.00％equivalence interval.Conclusion The test and reference formulations of ritonavir tablets were bioequivalent under fasting and postprandial conditions.

Objective To investigate the factors influencing the pregnancy outcomes during frozen-thawed embryo transfer(FET)cycles in patients with polycystic ovary syndrome(PCOS).Methods A retrospective analysis was conducted on patients'data from 882 FET cycles.According to the pregnancy outcome,the patients were divided into non-implantation group(Group A),abortion group(Group B1)and live birth group(Group B2).Clinical data and laboratory parameters were compared among the three groups,and ordered Logistic regression analysis was used to study the factors influencing pregnancy outcomes after FET.Patients were also divided into four groups(C1-C4)based on the number of high-quality embryos obtained(0-3,4-6,7-10,≥11),and their clinical data and laboratory parameters were compared.Results The clinical pregnancy rate,live birth rate,and miscar-riage rate in the 882 treatment cycles were 71.09%(627/882),61.68%(544/882),and 13.24%(83/627),respectively.Single-factor analysis showed significant differences in body mass index(BMI),infertility type,hu-man chorionic gonadotropin(hCG)day estradiol(E2)level,number of retrieved oocytes,and number of high-quality embryos among Groups A,B1,and B2(P<0.05).Further multiple Logistic regression analysis revealed that BMI(OR=1.046,95%CI:1.001-1.093,P=0.044)and a history of previous pregnancy(OR=1.417,95%CI:1.030-1.950,P=0.032)were independent risk factors for successful FET in PCOS patients,while an in-creased number of high-quality embryos was an independent protective factor for successful pregnancy.Based on the results of Group B2,compared to Group A,OR=0.920,95%CI:0.880-0.962,P=0.000;compared to Group B1,OR=0.923,95%CI:0.862-0.988,P=0.022.Compared with the other three groups(C1-C3),the total amount of gonadotropin(Gn)in the C4 group was the lowest and the number of oocytes obtained was the high-est(P<0.05).Multiple comparisons showed that Group C4 had lower BMI,follicle-stimulating hormone(FSH),very low-density lipoprotein(vLDL)levels,a higher luteinizing hormone and follicle-stimulating hormone(LH/FSH)ratio compared to Group C1(P<0.05).Group C4 had lower fasting insulin(FINS)and homeostasis model assessment of insulin resistance(HOMA-IR)levels compared to Group C3,and higher high-density lipoprotein-cholesterol(HDL-C)and apolipoprotein A1(Apo A1)levels compared to Groups C2 and C3(P<0.05).Con-clusion BMI,the history of previous pregnancy and the number of high-quality embryos were both independent factors for predicting pregnancy outcomes in PCOS patients undergoing FET cycles.Patients with a higher number of high-quality embryos have a higher clinical pregnancy rate during FET cycles.

Objective To explore the effect of case-based learning(CBL)combined with PICOS(population,interventions,compari-sons,outcomes,study design)framework in undergraduate occupational therapy(OT)education. Methods A total of 43 junior students majoring in OT from School of Rehabilitation Medicine,Nanjing Medical Univer-sity,were taught the core courses of OT using CBL combined with PICOS framework,from February,2023 to June,2024.The Evidence-based Practice Competency Assessment Scale was used to investigate the students at the beginning and the end of the semester,respectively. Results At the end of the semester,students'self-assessments improved in areas such as the quality evaluation of litera-ture,identifying the best scientific evidence,evaluating the quality of papers,conducting practical analysis of re-search,applying PICOS to formulate clinical questions,assessing the primary association measurement methods of research results,understanding different levels of evidence,and familiarity with commonly used evidence-based practice databases(χ2>4.778,P<0.05).Self-assessment regarding uncertainty about the decision-making process or the different recommendation strengths for health interventions(χ2=7.938,P<0.01)was lower.Atti-tudes toward evidence-based practice,skill levels,and knowledge all improved. Conclusion The combined application of CBL and PICOS framework could improve the effect of undergraduate OT ed-ucation and enhance the evidence-based practice ability of OT students.

AP2 transcription factors belong to the AP2/ERF superfamily and are involved in the regula-tion of various biological processes in plant growth and development,as well as in response to biotic and abiotic stresses.However,studies on the AP2 transcription factor family of Perilla frutescens have not been reported.In this study,totally 18 AP2 family members were identified from the Perilla frutescens ge-nome and analyzed for gene structure,conserved motifs,and cis-acting elements using bioinformatics.WRINKLED1(WRI1)is a key regulator of lipid biosynthesis in many plant species and plays an impor-tant role in the regulation of lipid synthesis.Sequence comparison revealed that one member of WRI1 is highly homologous to AtWRI1 and contains two conserved AP2 domains,named PfWRI1.The expression levels of PfAP2 family genes were analyzed in different tissues of Perilla frutescens and at different stages of seed development in conjunction with the transcriptome data,and the results showed that PfWRI1 is highly expressed only in the seeds of Perilla frutescens,suggesting that PfWRI1 may be related to the de-velopmental process of the seeds.The overexpression vector of plant pCAMBIA1303-PfWRI1 was con-structed,and wild-type(Col)and mutant(wri1-1)Arabidopsis thaliana were transformed by Agrobacte-rium tumefaciens to obtain overexpression and complementation lines,respectively.The results showed that the expression of P fWRI1 led to an increase in oil content of Arabidopsis seeds by 8.90％-13.57％compared with Col,and promoted the accumulation of oleic acid(C18:1)and linoleic acid(18:2)and reduced the accumulation of palmitic acid(C16:0),arachidonic acid(C20:0),and cis-11-Eicosenoic acid(C20:1)in transgenic Arabidopsis seeds.In addition,PfWRI1 gene expression increased the ex-pression of glycolysis and fatty acid biosynthesis-related genes AtPKP-α,AtPKP-β1,AtBCCP2,AtSUS2,and AtLIP1.Taken together,PfWRI1 may promote lipid accumulation by increasing unsaturated fatty acid content through interaction with the above genes.

Aim To explore the improvement effect of Bazi Bushen capsule on thymic degeneration in SAMP6 mice and the possible mechanism.Methods Twenty 12 week old male SAMP6 mice were randomly divided into the model group(SAMP6)and the Bazi Busheng capsule treatment group(SAMP6+BZBS).Ten SAMR1 mice were assigned to a homologous control group(SAMR1).The SAMP6+BZBS group was oral-ly administered Bazi Bushen capsule suspension(2.8 g·kg-1)daily,while the other two groups were orally administered an equal amount of distilled water.After nine weeks of administration,the morphology of the thymus in each group was observed and the thymus in-dex was calculated;HE staining was used to observe the structural changes of thymus tissue;SA-β-gal stai-ning was used to detect thymic aging;flow cytometry was used to detect the proportion of thymic CD3+T cells in each group;Western blot was used to detect the levels of p16,Bax,Bcl-2,and cleaved caspase-3 proteins in thymus;immunofluorescence was applied to detect the proportion of cortical thymic epithelial cells in each group;ELISA was employed to detect IL-7 lev-els in thymus.Results Compared with the SAMP6 group,the thymic index of the SAMP6+BZBS group significantly increased(P＜0.05);the disordered thy-mic structure was significantly improved;the positive proportion of SA-β-gal staining significantly decreased(P＜0.01);the proportion of CD3+T cells apparently increased(P＜0.05);the level of p16 protein signifi-cantly decreased(P＜0.05);the level of Bcl-2 pro-tein significantly increased(P＜0.05),while the lev-el of cleaved caspase-3 protein markedly decreased(P＜0.05);the proportion of cortical thymic epithelial cells evidently increased;the level of IL-7 significantly increased(P＜0.01).Conclusions Bazi Bushen capsule can delay thymic degeneration,inhibit cell ap-optosis in thymus and promote thymic cell development in SAMP6 mice,which may be related to increasing the proportion of cortical thymic epithelial cells and promoting IL-7 secretion.

Objective To construct a new type of glucosamine/DNA composite nanostructure(NTGlcN)assembled without magnesium,verify whether or not glucosamine can mediate the assembly of DNA nanotubes(NT)and assess its effect on the function of Raw264.7 cells.Methods Utilizing the gradient annealing method with 3 DNA single strands Y1,Y2,and Y3,glucosamine(GlcN)was employed to mediate the assembly of DNA NT,resulting in the formation of glucosamine/DNA composite nanostructures.Atomic force microscopy(AFM)was used to observe the surface structure of the nanomaterial and dynamic light scattering(DLS)was used to measure its size.RAW264.7 cells were used in cell experiments.The cytotoxicity of GlcN and NTGlcN was assessed using CCK-8 assay.Flow cytometry and laser confocal microscopy were employed to investigate the cellular uptake efficiency of the nanostructures.The effects of NTGlcN and NTMg(Mg2+-assembled of DNA NT)on the expression levels of inflammatory cytokines(IL-1β,IL-6)in macrophages induced by lipopolysaccharides(LPS)were evaluated using RT-qPCR.Results GlcN successfully mediated the synthesis of NTGlcN,which exhibited good stability.AFM characterization results revealed that NTGlcN formed tubular particles that were uniformly distributed on the surface of mica.DLS measurements indicated that the diameter of NTGlcN was approximately 15.26±3.86 nm.Cell experiments demonstrated that,compared to NTMg,macrophages exhibited a higher cellular uptake efficiency for NTGlcN,with a higher cell survival rate following treatment with NTGlcN(P＜0.05).After NTGlcN treatment,the expression of inflammatory cytokines in LPS-induced macrophages was reduced(P＜0.05).Conclusion The glucosamine/DNA composite nanostructures have been successfully developed,possessing excellent stability,biocompatibility and cell uptake efficiency.NTGlcN is capable of reducing the cytotoxicity of GlcN and can suppress cellular inflammatory responses by decreasing the expression of inflammatory cytokines in RAW264.7 cells.

Objective To clone the full-length sequence,subcellular localization,and analyze the expression patterns of the β-caryophyllene synthase gene(AaCPS)of Artemisia argyi,in order to lay a foundation for the gene function analysis of sesquiterpene biosynthesis pathway in A.argyi.Methods The genes annotated as CPS were selected from the transcriptome data of A.argyi.The full-length cDNA sequence of the target gene was obtained by PCR,and the coding region was analyzed using bioinformatics.A prokaryotic expression vector was constructed and transformed into Escherichia coli competent cells to express recombinant protein.A green fluorescent protein(GFP)fused expression vector was constructed,and the subcellular localization of AaCPS was observed using Agrobacterium tumefaciens transient expression method in tobacco.Real-time quantitative PCR(qRT-PCR)was used to analyze the expression patterns of the AaCPS at different harvest times(April,May,June,July).Determination of β-caryophyllene by HS-SPME-GC-MS and correlation analysis.Results The AaCPS gene was cloned from A.argyi.The full-length open reading frame(ORF)was 1647 bp,encoding 548 amino acids.The molecular weight was 63 667 Da with a theoretical pI of 5.94.AaCPS contained conserved Terpen_synth and Terpen_synth_C domains.Phylogenetic analysis indicated that AaCPS was closely related to the CPS protein of Artemisia annua.SDS-PAGE showed the presence of target protein bands between 75 000-120 000 Da(containing 28 132 Da of the labeled protein),indicating successful expression of the AaCPS protein.The protein was found to be localized in the cytoplasm.As shown by qRT-PCR,the expression of AaCPS gene showed an upward trend,reaching the highest in July.The results of HS-SPME-GC-MS showed that the content of β-caryophyllene increased gradually from April to the highest in June.It is consistent with the trend of AaCPS gene expression from April to June.Conclusion Through the cloning and analysis of AaCPS gene,a foundation has been laid for further study of the functional identification of the AaCPS gene in the sesquiterpenes biosynthesis pathway in A.argyi.

Studies have shown that a variety of diseases such as cardiovascular disease, renal disease and cancer are closely related to trimethylamine oxide (TMAO). Clinically, abnormal elevation of TMAO has been used as an evaluation index of atherosclerosis (AS) prior to imaging. In this study, we investigated the effects of lipid metabolism disorders as well as pharmacological interventions on urinary TMAO using a hyperlipidemic golden gopher model. The study used 48 Syrian golden hamster modeled with a high-fat diet for 2 weeks, and then ezetimibe, simvastatin, ezetimibe and simvastatin groups were administered for 4 consecutive weeks, as well as the clinical trial drug, IMM-H007, for pharmacological intervention. The animal experiment was conducted in accordance with the regulations of the Ethics Committee for Experimental Animal Management and Animal Welfare of Institute of Materia Medica, Chinese Academy of Medical Sciences (approval number: SCXK (Beijing) 2021-0011). Urine from rats was analyzed for 2D band selective heteronuclear single quantum coherence (2D bs-HSQC) at week 2 and 4 after drug administration. The results indicated that, in comparison to the control group, the high-fat diet significantly elevated urinary TMAO levels in the model group of hamsters after both 2 and 4 weeks of treatment (P < 0.05). Urinary TMAO levels were significantly reduced (P < 0.05) in the model group after 2 or 4 weeks of intervention with ezetimibe, simvastatin, combination therapy, and IMM-H007, showing a marked decrease even after 2 weeks of treatment. The detection of TMAO could precede the measurement of serum biochemical indicators, facilitating earlier efficacy assessment. This study evaluated the modulatory effects of clinical drugs and clinical trial drugs on TMAO, which provides useful information for clinical drug use and drug research. It also provides a means of TMAO detection based on 2D NMR technology, which is helpful for the clinical application of TMAO detection index.