Geniposide， the primary active component of the traditional Chinese medicine Gardeniae Fructus， is a water-soluble iridoid glycoside. Pharmacological studies have demonstrated that geniposide exhibits various biological activities， including hepatoprotective， anti-inflammatory， analgesic， neuroprotective， antidepressant effects， and inhibitory activity against ischemia-reperfusion injury. Recent research has revealed its promising potential in preventing and treating diseases such as atherosclerosis and osteoporosis， indicating broad application prospects. Numerous in vitro and in vivo studies indicate that the pharmacodynamic mechanisms of geniposide are primarily associated with the inhibition of inflammatory responses and oxidative stress， improvement of lipid metabolism， and regulation of apoptosis. However， due to its high water solubility and rapid metabolism in vivo， geniposide suffers from low oral bioavailability， which limits its therapeutic efficacy and clinical application. In recent years， various formulations， such as creams， cubic liquid crystals， hydrogels， and liposomes， have been developed to address its bioavailability issues. This article reviewed the latest research progress on the pharmacological activities and formulation development of geniposide by analyzing domestic and international literature from the past decade， aiming to provide a theoretical basis for further research， development， and utilization of geniposide and its formulations.

ObjectiveTo prepare triptolide-Chuanxiong Rhizoma extract ethanol transfersomes（TP-CX@TESs）， conduct its quality evaluation， and investigate its in vitro anti-inflammatory efficacy and the underlying mechanisms. MethodsTP-CX@TESs was prepared via the ultrasonic injection method. With encapsulation efficiency and particle size as evaluation indicators， Box-Behnken design-response surface methodology（BBD-RSM） was employed to optimize the formulation process. The TP-CX@TESs prepared under the optimal process was characterized and evaluated for in vitro transdermal performance. A lipopolysaccharide（LPS）-induced RAW264.7 cell inflammation model was established. After 24 h of drug intervention， the levels of inflammatory factors such as nitric oxide（NO）， interleukin-6（IL-6）， and tumor necrosis factor-α（TNF-α） in the cell supernatant were detected. Western blot was used to determine the protein expression levels of Janus kinase 2（JAK2）， signal transducer and activator of transcription 3（STAT3）， and α7 nicotinic acetylcholine receptor（α7nAChR）， and real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） was applied to measure the mRNA expression levels of JAK2， STAT3， the encoding gene of α7nAChR（CHRNA7）， and nuclear transcription factor-κB（NF-κB）. ResultsResults of BBD-RSM showed that the optimal formulation for preparing TP-CX@TESs was as follows：egg yolk lecithin content of 2.3%， ethanol volume fraction of 30%， and ratio of polysorbate-80 to egg yolk lecithin of 2∶5. Microscopic characterization revealed that TP-CX@TESs exhibited a spherical-like structure with a particle size of （105.60±3.85） nm， a polydispersity index of 0.19±0.03， and a Zeta potential of （-15.89±0.98） mV. The encapsulation efficiencies of triptolide， ferulic acid， and ligustilide were （76.88±4.40）%， （78.84±4.40）%， and （65.88±0.06）%， respectively. Both in vitro release and transdermal penetration of triptolide， ferulic acid， and ligustilide in TP-CX@TESs all followed the first-order kinetic model， showing a certain sustained-release property. Experimental results in RAW264.7 cells indicated that TP-CX@TESs significantly inhibited the release of NO， TNF-α， and IL-6（P<0.01）， remarkably upregulated the protein expression levels of STAT3 and α7nAChR（P<0.01）， increased the mRNA expression level of CHRNA7， and significantly downregulated the mRNA expression level of NF-κB（P<0.05， P<0.01）. ConclusionThe optimized formulation process of TP-CX@TESs is simple and feasible， along with favorable in vitro release property， good transdermal permeability， and excellent in vitro anti-inflammatory activity， the mechanism is related to the inhibition of NF-κB.

ObjectiveTo prepare triptolide-Chuanxiong Rhizoma extract ethanol transfersomes（TP-CX@TESs）， conduct its quality evaluation， and investigate its in vitro anti-inflammatory efficacy and the underlying mechanisms. MethodsTP-CX@TESs was prepared via the ultrasonic injection method. With encapsulation efficiency and particle size as evaluation indicators， Box-Behnken design-response surface methodology（BBD-RSM） was employed to optimize the formulation process. The TP-CX@TESs prepared under the optimal process was characterized and evaluated for in vitro transdermal performance. A lipopolysaccharide（LPS）-induced RAW264.7 cell inflammation model was established. After 24 h of drug intervention， the levels of inflammatory factors such as nitric oxide（NO）， interleukin-6（IL-6）， and tumor necrosis factor-α（TNF-α） in the cell supernatant were detected. Western blot was used to determine the protein expression levels of Janus kinase 2（JAK2）， signal transducer and activator of transcription 3（STAT3）， and α7 nicotinic acetylcholine receptor（α7nAChR）， and real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） was applied to measure the mRNA expression levels of JAK2， STAT3， the encoding gene of α7nAChR（CHRNA7）， and nuclear transcription factor-κB（NF-κB）. ResultsResults of BBD-RSM showed that the optimal formulation for preparing TP-CX@TESs was as follows：egg yolk lecithin content of 2.3%， ethanol volume fraction of 30%， and ratio of polysorbate-80 to egg yolk lecithin of 2∶5. Microscopic characterization revealed that TP-CX@TESs exhibited a spherical-like structure with a particle size of （105.60±3.85） nm， a polydispersity index of 0.19±0.03， and a Zeta potential of （-15.89±0.98） mV. The encapsulation efficiencies of triptolide， ferulic acid， and ligustilide were （76.88±4.40）%， （78.84±4.40）%， and （65.88±0.06）%， respectively. Both in vitro release and transdermal penetration of triptolide， ferulic acid， and ligustilide in TP-CX@TESs all followed the first-order kinetic model， showing a certain sustained-release property. Experimental results in RAW264.7 cells indicated that TP-CX@TESs significantly inhibited the release of NO， TNF-α， and IL-6（P<0.01）， remarkably upregulated the protein expression levels of STAT3 and α7nAChR（P<0.01）， increased the mRNA expression level of CHRNA7， and significantly downregulated the mRNA expression level of NF-κB（P<0.05， P<0.01）. ConclusionThe optimized formulation process of TP-CX@TESs is simple and feasible， along with favorable in vitro release property， good transdermal permeability， and excellent in vitro anti-inflammatory activity， the mechanism is related to the inhibition of NF-κB.

BACKGROUND:Type 2 diabetes mellitus impairs renal function,and studies have shown that exercise interventions can protect the kidneys.Irisin can protect renal function in diabetic nephropathy patients by restoring autophagy through inhibition of the phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR)signaling pathway. OBJECTIVE:To explore whether exercise can restore autophagy and ameliorate renal injury by inhibiting over-activation of the renal PI3K/Akt/mTOR signaling pathway,as well as to analyze the differences in the effects of different modalities of exercise. METHODS:Six-week-old Sprague-Dawley rats were randomly divided into a blank control group(normal rats)and a diabetic group,and then the diabetic group was randomly divided into a diabetic model group,a moderate-intensity continuous exercise group,and a high-intensity intermittent exercise group after successful modeling using high-fat,high-sugar feeding plus intraperitoneal administration of low-dose 1%streptozotocin(30 mg/kg).The two exercise groups were subjected to 8 weeks of exercise intervention with different exercise intensities.The fasting blood glucose concentration was detected by glucose oxidase method,glycated hemoglobin levels was measured using a kit,serum insulin concentration was detected by Elisa method,and insulin resistance index was calculated.Gene expression of PI3K,AKT,mTOR,Beclin-1,podocin,and nephrin was detected by RT-PCR.Protein expression of mTOR and autophagy marker proteins LC3-1,LC3-2,and Beclin-1 was detected by western blot RESULTS AND CONCLUSION:Fasting blood glucose and glycosylated hemoglobin levels were highly significantly increased,insulin resistance levels were significantly increased,and insulin levels were significantly decreased in type 2 diabetic rats.Both exercises resulted in highly significant decreases in fasting blood glucose and glycosylated hemoglobin levels,significant decreases in insulin resistance levels and significant increases in insulin levels in type 2 diabetic rats.Insulin levels were significantly higher in the high-intensity intermittent exercise group compared with the moderate-intensity continuous exercise group.The expression of podocin and nephrind genes was significantly reduced in type 2 diabetic rats and two different forms of exercise significantly the gene expression.There was a further trend toward an increase in gene expression of podocyte-associated proteins in the moderate-intensity continuous exercise group compared with the high-intensity intermittent exercise group,but there was no significant difference.The mRNA and protein expression of PI3K,AKT and mTORC1 in kidney tissues of type 2 diabetic rats were significantly increased,and the expression of autophagy marker proteins Beclin-1 and LC3-2 and LC3-2/LC3-1 were significantly decreased.Both different forms of exercise significantly decreased the mRNA and protein expression of PI3K,AKT,and mTORC1,and significantly increased the autophagy marker proteins Beclin-1,LC3-2,and LC3-2/LC3-1 in renal tissues.Compared with the moderate-intensity continuous exercise group,there was a trend toward further decreases in mRNA expression of PI3K,AKT,and mTORC1 and protein expression of mTOR,and a trend toward further elevation of Beclin-1,LC3-2,and LC3-2/LC3-1 in the high-intensity intermittent exercise group,but only Beclin-1 showed a significant difference between groups.In summary,renal podocyte injury in type 2 diabetes mellitus with suppressed autophagy is closely related to aberrant activation of the PI3K/AKT/mTORC1 signaling pathway.Both moderate-intensity continuous exercise and high-intensity intermittent exercise can protect the diabetic kidney,reduce podocyte damage,and restore renal podocyte autophagy,which may be achieved by inhibiting the excessive activation of the PI3K/AKT/mTOR signaling pathway.High-intensity intermittent exercise shows a trend toward more favorable restoration of autophagy compared with moderate-intensity continuous exercise,but with a slight decrease in podocyte protein expression.

Objective To explore the predictive value of serum high-mobility group box protein B1(HMGB1)and soluble receptor for advanced glycation end-products(sRAGE)in the occurrence and short-term prognosis of sepsis-associated encephalopathy(SAE).Methods Clinical data of 228 patients with sepsis were retrospectively analyzed.According to the presence of SAE,patients were divided into the SAE group(96 cases)and the non-SAE group(132 cases).General clinical data,laboratory test results,Acute Physiology and Chronic Health Evaluation Ⅱ(APACHEⅡ)scores,Sequential Organ Failure Assessment(SOFA)scores and serum HMGB1 and sRAGE levels were compared between the two groups.Multivariate Logistic regression analysis was performed to determine factors influencing SAE occurrence.Receiver operating characteristic(ROC)curves were plotted to evaluate the predictive ability of HMGB1,sRAGE and the HMGB1/sRAGE ratio to predict the occurrence and short-term prognosis of SAE.Kaplan-Meier survival curves were used to compare the 28-day mortality rates of SAE patients with different HMGB1 and sRAGE expression levels.Results Compared to the non-SAE group,patients in the SAE group exhibited elevated serum HMGB1 levels,decreased sRAGE levels and an increased HMGB1/sRAGE ratio(P＜0.05).The areas under the curve(AUC)for predicting SAE using HMGB1,sRAGE and the HMGB1/sRAGE ratio were 0.826(95%CI:0.770-0.872),0.682(95%CI:0.617-0.742)and 0.895(95%CI:0.848-0.932),respectively,indicating predictive value.Among the 96 SAE patients,52(54.2%)died within 28 days.There were no statistically significant differences in HMGB1,sRAGE and the HMGB1/sRAGE ratio between surviving and deceased patients(P＞0.05).Similarly,there were no significant differences in 28-day mortality rates between SAE patients with different HMGB1 or sRAGE expression levels.Conclusion Elevated serum HMGB1 and reduced sRAGE are of significant value in the auxiliary diagnosis of SAE,but have limited clinical predictive value for short-term prognosis.

Objective:To explore drug detoxification motivation in methamphetamine-dependent female youth and its relationship with time perspective,perceived social support and emotion regulation strategies.Methods:To-tally 200 methamphetamine-dependent female youths under compulsory isolation were assessed with the Drug De-toxification Motivation Scale,Zimbardo Time Perspective Inventory-Chinese(ZTPI-C),Emotion Regulation Scale(ERS),and Perceived Social Support Scale(PSSS).Results:Multiple linear regression analysis showed that drug detoxification motivation scores were positively correlated with the scores of ERS reevaluation and expression inhi-bition,PSSS family support scores and level of education(β=0.24,0.16,0.20,0.16).Conclusion:Time perspec-tive,perceived social support and emotion regulation strategies are closely related to drug detoxification motivation in methamphetamine-dependent female youth.

Benign prostatic hyperplasia(BPH)is the main reason of causing lower urinary tract symptoms(LUTS)in middle-aged and elderly men,and LUTS can disrupt patients'sleep patterns and interfere with their daily life.With the development of aging,BPH has produced a significant impact on public health,and caused serious social problems and economic burdens.There are various technical approaches for medical devices used in treating BPH,including laser,electrosurgery,focused ultrasound,microwave,stent,and liquid jet removal system,etc.This article summarized the pathogenesis,clinical manifestations,and general overview for guidelines of diagnosis and treatment for BPH.It also reviewed the guiding principle of Food and Drug Administration(FDA)for medical devices used in treating BPH,and focused on analyzing the main contents of non-clinical study,animal study(including animal model,test method,observation time points and evaluation indicators)and clinical study(including selection for control groups,inclusion and exclusion criteria,study endpoint and study duration),so as to provide some enlightenments for the verification,validation and technical evaluation for such products.

Objective To explore the factors influencing cognitive frailty in elderly inpatients with chronic heart failure(CHF)during hospitalisation,8 prediction models were developed with various machine learning algorithms to identify the best model as a guidance for medical staff on clinical interventions.Methods Convenience sampling method was used to select 650 elderly CHF inpatients who stayed in our hospital between September 2023 and June 2024 as the study objects in the cross-sectional investigation.A total of 607 patients had completed the study.The patients were divided into a cognitive frailty group and a non-cognitive frailty group according to the presence or absence of cognitive frailty.Variables were initially screened using univariate analysis and stepwise Logistic regression.The total sample was then randomly divided into a training set(n=424)and a testing set(n=183)of a 7:3 ratio.Eight predictive models were created using the algorithms of neural network(NN),k-nearest neighbour(KNN),linear discriminant analysis(LDA),support vector machine(SVM),naive Bayes(NB),logistic regression,decision tree(DT)and random forest(RF)on the training set.The predictive performance of the models was compared using the data of the testing set.Results The prevalence of cognitive frailty in elderly CHF inpatients was 48.3%.Results of Logistic regression showed that age,marital status,education,body mass index,multi-morbidity,nutritional status,medication,frequency of weekly exercise and the living conditions were the key factors(P<0.05).The overall accuracy in classification of the eight predictive models ranged from 0.803 to 0.847,with F1-values of 0.778 to 0.833,precision of 0.848 to 0.897,and recall rate of 0.700 to 0.778.The area under the receiver operating characteristic curve was 0.820 to 0.901.Conclusion Of the eight predictive models,the prediction model created with LDA shows the best performance and prediction in terms of comprehensive prediction metrics,while the prediction model created with NN shows the worst performance in comprehensive prediction.

Objective:To understand the current status and influencing factors for science and technology ethics awareness among medical postgraduates, explore scientific cultivation path, and provide empirical evidence for higher medical colleges to carry out science and technology ethics education.Methods:The study adopted a cluster sampling method and designed a questionnaire. A total of 2 095 medical postgraduates from Hebei Medical University participated in the survey from June to December 2023. SPSS 24.0 was used for non-parametric tests, and the ordered logistic regression analysis was used to explore the influencing factors.Results:A total of 1 992 valid questionnaires were collected, with a valid response rate of 95.08% (1 922/2 095). The qualified rate of science and technology ethics awareness among medical postgraduates was 90.76% (1 808/1 992), with 48.24% (961/1 992) of students falling into the good interval and 16.21% (323/1 992) falling into the excellent interval. The regression analysis showed that sex, academic category, students' attention to science and technology ethical issues, and understanding of ethical principles were significant influencing factors for medical postgraduates' science and technology ethics awareness ( P<0.05). Conclusions:The science and technology ethics awareness of medical postgraduates is at a medium level. Higher medical colleges should start from the needs and adhere to the direction of lifelong education to build a multi-subject, all-round, and all-process cultivation path. They can help students cultivate ethical awareness by improving the educational system, building a scientific teaching system, and creating a social education atmosphere. They can also help students internalize ethical norms and externalize them in their behaviors, and ensure that they can maintain ethical sensitivity in scientific and technological activities, thereby cultivating high-quality new medical and health professionals who can anticipate scientific and technological risks and assume ethical responsibilities.

Objective:To assess the cytotoxicity of self-adhesive resin cement RelyXTM U200 on human periodontal ligament fibro-blasts(HPDLFs)under different light treatment modes.Methods:The self-adhesive resin cement RelyXTM U200 was cured by immediate light(A),intermittent light(B),delayed light(C)and no light(D)treatment respectively.The HPDLFs were cultured with the specimen extracts under different light modes.The proliferation ability and apoptosis level of the cells in the groups were detected by CCK-8 test and flow cytometry apoptosis test.SPSS 20.0 software was used to analyze the cytotoxicity of specimens to HPDLFs.Results:At 24 h after light treatment the cytoxicity(grade)of group A,B,C and D was 1,2,3 and 4,at 72 h 1,2,2 and 3,respectively.At 72 h,the apoptosis index(％)of the cells in A,B,C and D groups was 6.38％±0.94％,16.34％±1.67％,24.13％±1.43％and 38.34％±2.75％respecitvely.Conclusion:The cytotoxicity of self-adhesive resin cement is the greatest under no light treatment mode and the least under immediate light treatment mode.