With the rapid development of social economy and the continuous improvement of human living standard, the incidence, fatality and recurrence rates of cardiovascular disease (CVD) are increasing year by year, which seriously affects people's life and health. Conventional therapeutic drugs have limited improvement on the disability rate, so the search for new therapeutic drugs and action targets has become one of the hotspots of current research. In recent years, the therapeutic role of the natural compound rosmarinic acid (RA) in CVD has attracted much attention, which is capable of preventing CVD by modulating multiple signalling pathways and exerting physiological activities such as antioxidant, anti-apoptotic, anti-inflammatory, anti-platelet aggregation, as well as anti-coagulation and endothelial function protection. In this paper, the role of RA in the prevention of CVD is systematically sorted out, and its mechanism of action is summarised and analysed, with a view to providing a scientific basis and important support for the in-depth exploration of the prevention value of RA in CVD and its further development as a prevention drug.

Aim To investigate the protective effect of Jujing formula on retina of mice with dry age-related macular degeneration(AMD).Methods The mouse model of dry AMD was induced by intraperitoneal in-jection of sodium iodate,and the prognosis was given to the Jujing formula.Retinal thickness was detected by optical coherence tomography(OCT),the retinal morphological changes were observed by hematoxylin-eosin(HE)staining,and the apoptosis of retinal cells was detected by in situ terminal transferase labeling(TUNEL)staining.Combination of tumor necrosis fac-tor-α(TNF-α),interleukin-6(IL-6)and interleukin-1β(IL-1 β)in eyeballs and serum,superoxide dis-mutase(SOD),glutathione(GSH)and malondialde-hyde(MDA)were evaluated to assess the protective effects of Jujing formula on retinal injury in mice with dry AMD.Results The results of OCT,HE and TUNEL staining showed that Jujing formula significant-ly improved the retinal injury induced by sodium iodate in mice with dry AMD,increased the retinal thickness(P＜0.05),reduced the apoptosis of retinal cells(P＜0.01),and increased the levels of GSH,IL-6 and SOD activity in eyeballs and serum(P＜0.01).The levels of TNF-α,IL-6,IL-1β and MDA were reduced(P＜0.01).Conclusions Jujing formula has certain therapeutic effects on retinal injury in dry AMD,which may be related to inhibiting inflammatory response and enhancing antioxidant capacity.

Objective To explore the effects of dihydromyricetin on the proliferation,apoptosis,and invasion of endometrial cancer(EC)cells and its possible mechanisms.Methods Ishikawa cells in the logarithmic growth phase were taken and divided into the control group,20 μmol/L dihydromyricetin intervention group,40 μmol/L dihydromyricetin intervention group,and 80 μmol/L dihydromyricetin intervention group,which were treated with different final concentrations of dihydromyricetin(0 μmol/L,20 μmol/L,40 μmol/L,80 μmol/L).Then,CCK-8 assay and flow cytometry were used to detect the effects of dihydromyricetin on the cell proliferation and apoptosis.Transwell experiment was used to detect the effect of dihydromyricetin on the cell invasion.qRT-PCR and Western blot were used to detect the effects of dihydromyricetin on the cell expression of miR-21 and PTEN.Results Compared with the control group,the cell proliferation inhibition rate and apoptosis rate in the dihydromyricetin intervention group were significantly increased(P<0.05),and gradually increased with the increase of dihydromyricetin concentration(P<0.05).Compared with the control group,the numbers of migration and invasion cells in the dihydromyricetin intervention group were significantly decreased(P<0.05),and gradually decreased with the increase of dihydromyricetin concentration(P<0.05).Compared with the control group,the cell expression of miR-21 in the dihydromyricetin intervention group was significantly decreased(P<0.05),and gradually decreased with the increase of dihydromyricetin concentration(P<0.05),the expression levels of PTEN mRNA and protein were significantly increased(P<0.05),and gradually increased with the increase of dihydromyricetin concentration(P<0.05).Conclusion Dihydromyricetin can inhibit the growth and metastasis of EC cells,and the inhibitory effect is positively correlated with its concentration.The mechanism may be related to the effect of dihydromyricetin on the miR-21/PTEN signaling pathway of EC cells.

MicroRNAs(miRNAs)are small non-coding RNAs that are closely associated with the occur-rence and progression of tumors and other diseases.However,miRNAs require high-sensitivity and high-specificity detection due to their low abundance,high sequence homology,and rapid degradation.The RNA-cleaving deoxyribozyme(RCD)is a functional single-stranded DNA molecule that enables specific cleavage of substrates to release miRNAs that can be recycled with the assistance of metal ions,prompting cyclic signal amplification.Recently,developing new methods based on RCD catalytic amplification for miRNA high-sensitivity detection has become the focus of researchers.Based on combing with the various new technologies and materials in miRNA biosensors,this study classifies and reviews the new methods for detecting miRNAs based on deoxyribozyme catalytic amplification developed in recent years.We sepa-rate these miRNA detection strategies into three categories:RCDs combined with DNA self-assembly,i-sothermal amplification,and nanomaterials.We explore the basic principles of each approach,the latest research advancements,and application scenarios in biomedical sensors and medical detection.This re-view provides a foundation and reference for further research of highly sensitive and accurate miRNA de-tection strategies.

AIM To investigate the protective effect of Mongolian medicine Naru-3 on rat rheumatoid arthritis(RA)using imaging method.METHODS With the rats divided into the normal group,the model group,the positive medicine group,and the low,medium and high dose Naru-3 groups(0.1,0.2 and 0.4 g/kg),the rat model of collagen-induced arthritis(CIA)was established by immune induction method.After 4 weeks of corresponding drug administration,the rats had their changes of arthritis index(AI)level and body weight observed;their serum levels of VEGF,TNF-α and IL-1 detected by ELISA;their synovial hyperplasia and neovascularization evaluated by high-frequency ultrasound and contrast-enhanced ultrasound(CEUS);their bone destruction of ankle joint evaluated by X-ray and high-resolution micro-CT;and their synovial membrane and expressions of CD31,VEGF,TNF-α and IL-1 β observed by HE and immunohistochemistry.RESULTS Compared with the model group,the Naru-3 groups displayed increased rat weight(P＜0.05);no significantly changed AI score(P＞0.05);and overally decreased levels of serum VEGF,TNF-α,synovial membrane thickness,blood flow signal by power Doppler imaging(PDI)and contrast intensity revealed,X-ray score,and CD31 expression(P＜0.05),in addition to the decreased level of IL-1 and HE score in high-dose group(P＜0.05).CONCLUSION Naru-3 is protective to the joint tissue in rat model of RA through alleviating synovitis,bone erosion and delaying the progress of the disease by inhibiting synovial neovascularization and inflammatory cytokines.

Objective: To construct a nonsuicidal selfinjury (NSSI) risk prediction model for middle school students using different machine learning algorithms and evaluate the models effectiveness, so as to provide guidance for the prevention and control of NSSI in campus. Methods: In March 2023, a total of 3 372 middle and high school students from schools in Nanchang, Fuzhou and Shangrao cities in Jiangxi Province were selected by combining stratified random cluster sampling and convenient sampling methods. Questionnaire surveys were conducted using various instruments including general information questionnaire, Selfesteem Scale, Ottawa Selfinjury Scale, Social Support Assessment Scale, Chinese Version of the Olweus Bullying Questionnaire, Event Attribution Style Scale, Adolescent Resilience Scale, and Adolescent Life Events Scale. Data were divided into training set (n=2 361) and test set (n=1 011) at a ratio of 7∶3, and variables were selected based on univariate and LASSO regression results. Four machine learning algorithms including namely random forest, support vector machine, Logistic regression and XGBoost, were used to construct NSSI risk prediction models, and the models performance was evaluated and compared using metrics including area under curve (AUC), sensitivity, specificity, positive predictive value, negative predictive value and F1 score. Results: The detection rate of NSSI among middle school students was 34.4%. Univariate analysis showed that there were statistically significant differences in NSSI detection rates among middle school students of different grades, genders, registered residence locations, whether they were class cadres and four types of bullying (physical, verbal, relational bullying and cyberbullying) (χ2=27.17, 15.81, 11.54, 4.63；68.22, 140.63, 77.81, 13.95, P<0.05). NSSI was included as the dependent variable in the LASSO regression model for variable screening, and the results regression identified 10 predictive variables including grade level, selfesteem, subjective support, support utilization, verbal bullying, emotional control, interpersonal relationships, punishment, loss of relatives and property, and health and adaptation issues. The AUC values of random forest, support vector machine, Logistic regression, and XGBoost algorithms were 0.76, 0.76, 0.76 and 0.77, respectively, with no statistically significant differences between pairwise comparisons (Z=-0.59-0.82, P>0.05). Sensitivity values were 0.62, 0.61, 0.62 and 0.61, respectively. Specificity values were 0.74, 0.78, 0.78 and 0.78, respectively. Positive predictive values were 0.56, 0.59, 0.60 and 0.59, respectively. Negative predictive values were 0.79, 0.79, 0.80 and 0.79, respectively. F1 scores were 0.59, 0.60, 0.61 and 0.60, respectively. Conclusions All four nonsuicidal selfinjury risk prediction models perform well, with the Logistic regression model slightly outperforming the others. Schools and parents should pay attention to the predictive factors corresponding to NSSI, so as to reduce the occurrence of NSSI among middle school students.

OBJECTIVE: To investigate a new noninvasive diagnostic model for nonalcoholic fatty liver disease (NAFLD) based on features of tongue images. METHODS: Healthy controls and volunteers confirmed to have NAFLD by liver ultrasound were recruited from China-Japan Friendship Hospital between September 2018 and May 2019, then the anthropometric indexes and sampled tongue images were measured. The tongue images were labeled by features, based on a brief protocol, without knowing any other clinical data, after a series of corrections and data cleaning. The algorithm was trained on images using labels and several anthropometric indexes for inputs, utilizing machine learning technology. Finally, a logistic regression algorithm and a decision tree model were constructed as 2 diagnostic models for NAFLD. RESULTS: A total of 720 subjects were enrolled in this study, including 432 patients with NAFLD and 288 healthy volunteers. Of them, 482 were randomly allocated into the training set and 238 into the validation set. The diagnostic model based on logistic regression exhibited excellent performance: in validation set, it achieved an accuracy of 86.98%, sensitivity of 91.43%, and specificity of 80.61%; with an area under the curve (AUC) of 0.93 [95% confidence interval (CI) 0.68-0.98]. The decision tree model achieved an accuracy of 81.09%, sensitivity of 91.43%, and specificity of 66.33%; with an AUC of 0.89 (95% CI 0.66-0.92) in validation set. CONCLUSIONS The features of tongue images were associated with NAFLD. Both the 2 diagnostic models, which would be convenient, noninvasive, lightweight, rapid, and inexpensive technical references for early screening, can accurately distinguish NAFLD and are worth further study.
Humans ; Non-alcoholic Fatty Liver Disease/diagnostic imaging* ; Ultrasonography ; Anthropometry ; Algorithms ; China

Objective To explore the efficacy and safety of recombinant human anti-severe acute respiratory syn-drome coronavirus 2(anti-SARS-CoV-2)monoclonal antibody injection(F61 injection)in the treatment of patients with coronavirus disease 2019(COVID-19)combined with renal damage.Methods Patients with COVID-19 and renal damage who visited the PLA General Hospital from January to February 2023 were selected.Subjects were randomly divided into two groups.Control group was treated with conventional anti-COVID-19 therapy,while trial group was treated with conventional anti-COVID-19 therapy combined with F61 injection.A 15-day follow-up was conducted after drug administration.Clinical symptoms,laboratory tests,electrocardiogram,and chest CT of pa-tients were performed to analyze the efficacy and safety of F61 injection.Results Twelve subjects(7 in trial group and 5 in control group)were included in study.Neither group had any clinical progression or death cases.The ave-rage time for negative conversion of nucleic acid of SARS-CoV-2 in control group and trial group were 3.2 days and 1.57 days(P=0.046),respectively.The scores of COVID-19 related target symptom in the trial group on the 3rd and 5th day after medication were both lower than those of the control group(both P＜0.05).According to the clinical staging and World Health Organization 10-point graded disease progression scale,both groups of subjects improved but didn't show statistical differences(P＞0.05).For safety,trial group didn't present any infusion-re-lated adverse event.Subjects in both groups demonstrated varying degrees of elevated blood glucose,elevated urine glucose,elevated urobilinogen,positive urine casts,and cardiac arrhythmia,but the differences were not statistica-lly significant(all P＞0.05).Conclusion F61 injection has initially demonstrated safety and clinical benefit in trea-ting patients with COVID-19 combined with renal damage.As the domestically produced drug,it has good clinical accessibility and may provide more options for clinical practice.

Objective To investigate the interventional effects of Icariin(IC A)combined with prednisone acetate tablets(PAT)in rats with steroid-resistant nephrotic syndrome(SRNS)model.Methods Male SD rats were used to construct the SRNS model with 2 injections of adriamycin(ADR),and were randomly divided into the model group,PAT group,ICA group,and the combined group,with 10 rats in each group after successful modeling;another 10 rats were taken as the blank group.The blank and model groups were given 0.9％NaCl;the PAT group was given 6.3 mg·kg-1·d-1 PAT;the ICA group was given 50 mg·kg-1·d-1 ICA;and the combined group was given 6.3 mg·kg-1·d-1 PAT+50 mg·kg-1·d-1 ICA.The volume of gavage of the five groups of rats was 1 mL·100 g-1,and the drug was administered once a day for 6 weeks.The renal function and blood lipid level of rats in each group were compared;the expression of calcium/calmodulin dependent protein kinase Ⅱ α(CaMK Ⅱα),cofilin-1 and F-actin were detected by Western blotting.Results Urinary protein quantification values at 8 weeks in blank,model,PAT,ICA and combined groups were(6.66±1.48),(178.38±8.96),(161.56±5.49),(157.13±8.32)and(96.90±5.05)mg·24 hi-1;serum creatinine levels were(30.90±1.79),(41.10±2.77),(34.90±2.03),(35.10±2.18)and(31.90±2.47)μmol·L-1;triglycerides levels were(0.87±0.14),(2.30±0.41),(1.94±0.44),(1.17±0.59)and(0.89±0.30)mmol·L-1;total cholesterol levels were(1.54±0.08),(2.53±0.22),(2.14±0.59),(2.27±0.31)and(1.93±0.32)mmol·L-1;the relative expression levels of CaMK Ⅱ α proteins were 0.88±0.09,0.65±0.06,0.71±0.08,0.76±0.07 and 0.88±0.08;the p-Cofilin-1/Cofilin-1 ratios were 0.56±0.27,2.52±0.04,0.75±0.02,0.91±0.20 and 0.53±0.05;the relative expression levels of F-actin protein were 0.93±0.01,0.64±0.01,0.75±0.02,0.80±0.01 and 0.85±0.00,respectively.The differences of the above indexes in the model group were statistically significant compared with those in the blank group and the combined group(all P＜0.05).Conclusion ICA combined with PAT can improve renal function,lipid levels,improve renal histopathological structure,and promote skeletal protein remodeling in SRNS rats by regulating CaMK Ⅱ α/Cofilin-1/F-actin pathway.

Objective To study the common basis and association between sickness behaviour and occurrence of classical symptoms of kidney yang deficiency of rats with adriamycin nephropathy.Methods The SD rats were given adriamycin by tail-vein injection for 2 times(4.0 and 3.5 mg·kg-1,one week apart)to construct the model of nephrotic syndrome with Chinese medicine symptom of kidney yang deficiency.After successful modeling,the model rats were randomly divided into adriamycin group(ADR group),corticosterone group(CORT group)and hydrocortisone group(HYD group),with 12 rats per group;another 12 normal rats were taken as normal group.In the HYD group,25 mg·kg-1·d-1 HYD was administered for 14 d to establish kidney yang deficiency model with simple hypothalamus-pituitary-adrenal cortex(HPA)axis inhibition.CORT group was adding 25 μg·mL-1 corticosterone to the water for 6 weeks,and the others drinking water supplied.The levels of urinary 17-hydroxy steroid were measured by enzyme linked immunosorbent assay.Glucocorticoid receptor(GR)and nuclear factor-kappa B(NF-κB)protein expression levels in kidney and hypothalamus were detected by Western blotting.Results In the normal,ADR,CORT and HYD groups,the urinary 17-hydroxysteroid levels were(19.14±1.94),(10.07±1.62),(20.30±1.55)and(14.23±2.37)μg·L-1;the relative expression levels of GR protein in hypothalamic were 0.63±0.05,0.11±0.05,0.85±0.08 and 0.35±0.06;the relative expression levels of NF-κB protein in hypothalamic were 0.06±0.03,0.96±0.03,0.59±0.01 and 0.23±0.04;the relative expression levels of GR protein in kidney tissue were 0.94±0.06,0.06±0.02,0.40±0.02 and 0.09±0.08;the relative expression levels of NF-κB protein in kidney tissue were 0.07±0.05,0.81±0.12,0.72±0.07 and 0.49±0.08,respectively.Compared with the ADR and HYD groups,the above indexes in the normal group were statistically significant(P＜0.05,P＜0.01).And compared with the ADR group,the relative expression levels of NF-κB protein in renal tissue with CORT group were not statistically significant(P＞0.05),but the other indexes in CORT group were statistically significant(all P＜0.01).Conclusion HPA axis dysfunction with GR damaged and activated inflammatory levels are the common basis for the combination of typical symptoms of kidney yang deficiency and sickness behaviour which characterised by"deficiency and cold syndrome".