Central nervous system（CNS） disorders are characterized by complex pathological mechanisms and the presence of the blood-brain barrier（BBB）， which significantly limits the effectiveness of drug therapy. Traditional drug delivery modes include oral administration， intravenous injection and transdermal delivery， which have certain advantages， but it is difficult for the drugs to effectively cross the BBB. Therefore， it is crucial to find drug delivery modes that can efficiently traverse the BBB. Nasal drug delivery， as a non-invasive method， can realize the targeted delivery of drugs to the CNS via three pathways， including olfactory neurons， trigeminal neurons and blood circulation， and shows a broad application prospect in the treatment of CNS diseases. Numerous studies have further confirmed that nasal drug delivery combined with novel drug delivery systems such as lipid nanocarriers， nanoparticles， nanoemulsions and composite in situ gels can effectively load the active components of traditional Chinese medicine（TCM）， and significantly increase drug concentration in the brain， which provides new strategies for the treatment of CNS diseases. In this paper， the current status of drug delivery for CNS diseases was systematically sorted out， the characteristics of nasal drug delivery were discussed in depth， and the research progress of passive targeting， active targeting， and "guiding the meridian" drug delivery strategies for the nasal-to-brain transport of TCM active components was summarized and analyzed， which was aimed to provide references and insights for the development of drugs for CNS diseases and the application of TCM in nasal-to-brain delivery.

Central nervous system（CNS） disorders are characterized by complex pathological mechanisms and the presence of the blood-brain barrier（BBB）， which significantly limits the effectiveness of drug therapy. Traditional drug delivery modes include oral administration， intravenous injection and transdermal delivery， which have certain advantages， but it is difficult for the drugs to effectively cross the BBB. Therefore， it is crucial to find drug delivery modes that can efficiently traverse the BBB. Nasal drug delivery， as a non-invasive method， can realize the targeted delivery of drugs to the CNS via three pathways， including olfactory neurons， trigeminal neurons and blood circulation， and shows a broad application prospect in the treatment of CNS diseases. Numerous studies have further confirmed that nasal drug delivery combined with novel drug delivery systems such as lipid nanocarriers， nanoparticles， nanoemulsions and composite in situ gels can effectively load the active components of traditional Chinese medicine（TCM）， and significantly increase drug concentration in the brain， which provides new strategies for the treatment of CNS diseases. In this paper， the current status of drug delivery for CNS diseases was systematically sorted out， the characteristics of nasal drug delivery were discussed in depth， and the research progress of passive targeting， active targeting， and "guiding the meridian" drug delivery strategies for the nasal-to-brain transport of TCM active components was summarized and analyzed， which was aimed to provide references and insights for the development of drugs for CNS diseases and the application of TCM in nasal-to-brain delivery.

Hepatocellular carcinoma is the most common malignancy of the liver and poses serious health burdens on China and the whole world. However， most patients with hepatocellular carcinoma are already in the advanced stage at the time of diagnosis， with fewer opportunities for surgery and limited treatment options. In recent years， the advances in molecular targeted therapies have brought new hope for patients with advanced hepatocellular carcinoma. Among these therapies， lenvatinib is the second first-line drug after sorafenib approved by the US Food and Drug Administration for the treatment of advanced hepatocellular carcinoma， and it has attracted widespread attention for its powerful anti-tumor properties. However， the efficacy of lenvatinib is severely limited by its drug resistance. This article reviews the research advances in the molecular mechanisms of lenvatinib resistance in hepatocellular carcinoma and discusses possible ways to improve the efficacy of lenvatinib， so as to improve its efficacy.

Objective:To evaluate the diagnostic efficacy of prostate imaging recurrence reporting (PI-RR) system for detecting local recurrence after radical prostatectomy (RP) in prostate cancer (PCa) and to assess the consistency of the PI-RR scores assigned by different seniority radiologists.Methods:This study was a cross-sectional study. A total of 176 PCa patients who underwent multi-parametric MRI (mpMRI) for biochemical recurrence (BCR) after RP from July 2015 to October 2021 at the First Affiliated Hospital of Soochow University were retrospectively collected. The mpMRI images were reviewed and the PI-RR scores of the main lesions were assigned independently by six different seniority radiologists (2 junior, 2 senior and 2 expert radiologists). Following the reference standard determined by biopsy pathologic results, follow-up imaging, or prostate specific antigen levels, the patients were divided into two groups: 54 patients with local recurrence and 122 patients without local recurrence. The intraclass correlation coefficient ( ICC) and Kappa test were used to evaluate the consistency of the PI-RR scores by different seniority radiologists. The receiver operating characteristic (ROC) curve analysis was employed to evaluate the diagnostic efficacy of the PI-RR scores assessed by different seniority radiologists for detecting local recurrence of PCa after RP. The DeLong test was utilized to compare the areas under the ROC curve (AUC) of different seniority radiologist PI-RR scores and a false discovery rate (FDR) was applied to correct results using the Benjamini and Hochberg method. Sensitivity and specificity were calculated according to the cutoff value of PI-RR score≥3 or 4. Results:The ICC (95% CI) of all different seniority radiologists was 0.70 (0.64-0.76). The Kappa value was 0.528, 0.325 and 0.370 respectively between expert and senior radiologists, expert and junior radiologists, senior and junior radiologists. The AUC (95% CI) of junior, senior, and expert radiologists were separately 0.73 (0.65-0.81), 0.81 (0.74-0.88), and 0.86 (0.80-0.93). The AUC of the expert radiologist PI-RR score was higher than those of senior and junior radiologist PI-RR scores ( Z=2.22, 3.21, FDR P=0.039, 0.003). The PI-RR score of senior radiologist had higher AUC than that of junior radiologist ( Z=2.22, FDR P=0.026). With the PI-RR score of 3 or greater as a cutoff value, the sensitivity of junior, senior and expert radiologists were respectively 0.59, 0.65, and 0.78 and the specificity were 0.82, 0.93, and 0.95. With the PI-RR score of 4 or greater as a cutoff value, the sensitivity of junior, senior and expert radiologists were respectively 0.50, 0.54, and 0.69 and the specificity were 0.88, 0.96 and 0.97. Conclusion:PI-RR score can accurately diagnose local recurrence of PCa after RP. PI-RR score has a moderate inter-reader consistency across different seniority radiologists. And the diagnostic performance is influenced by the experience of radiologists.

This study was performed to explore the therapeutic effect of Xiezhuo Jiedu Formula on ulcerative colitis rats and its effects on β-catenin/FOSL2/ARID5A signaling pathway and macrophage polarization.Rats of ulcerative colitis was induced and divide into control group,model group,positive group(intervention with sulfasalazine),and low,medium and high-dose groups(intervention with Xiezhuo Jiedu Fang).After 14 days of intervention,the disease activity index(DAI)and colon mucosa damage index(CDMI)were calculated and used to evaluate the state of rats.HE staining was used to observe lesion tissue;ELISA was used to detect of serum levels of TNF-α and IL-6;flow cytometry was used to detect peripheral blood M1 and M2 macrophage content;RT-PCR was used to detect the mRNA expression of iNOS,CD206,and β-Catenin/FOSL2/ARID5A;immunohistochemistry was used to detect β-Catenin/FOSL2/ARID5A signaling pathway protein expression in colon tissue.Data showed that DAI score,CMDI score,and serum TNF-α and IL-6 in the low,medium,and high dose groups were significantly lower than the model group(P＜0.05).HE staining showed that the colon tissue damage and inflammatory infiltration in the low,medium,and high dose groups were slighter than those in the model group(P＜0.05).The rate of M1 type macrophages and iNOS mRNA in the low,medium,and high dose groups were significantly lower than those in the model group,while the rate of M2 type macrophages and CD206 mRNA were significantly higher than those in the model group(P＜0.05).The mRNA and protein expressions of β-catenin and FOSL2 in colon tissue of low,medium,and high dose groups were significantly higher than those of the model group,while the mRNA level and protein expression of ARID5A were significantly lower than that of the model group(P＜0.05).Taken together,Xiezhuo Jiedu formula can effectively alleviate the clinical symptoms,reduce inflammatory response,downregulate β-catenin/FOSL2/ARID5A expression,regulate macrophage polarization and promote disease recovery of ulcerative colitis in rats.

Objective To explore the value of a clinical-radiomics-deep learning(CRDL)fusion model based on biparametric mag-netic resonance imaging(bpMRI)in predicting biochemical recurrence(BCR)after radical prostatectomy(RP).Methods A retrospective analysis was conducted on 363 patients with prostate cancer(PCa)confirmed by RP pathology who underwent preoperative MRI,inclu-ding 84 cases experienced BCR(23.1％)and 279 cases did not experience BCR(76.9％).The patients were randomly divided into a training set(n=254)and a test set(n=109)in a ratio of 7∶3.Univariate Cox regression analysis was employed to select clinical variables related to BCR and the clinical model was constructed using backward stepwise multivariate Cox regression analysis.The radiomics features and deep learning(DL)features based on the DenseNet network were extracted.Radiomics and DL signatures were separately developed using least absolute shrinkage and selection operator(LASSO)-Cox regression algorithm.A CRDL fusion model was constructed by combining significant clinical features,DL signature and radiomics signature.The models'predictive performance for BCR was evaluated and compared using the concordance index(C-index).K-M survival curve and Log-rank test were used to assess the performance of CRDL fusion model in risk stratifica-tion of biochemical recurrence free survival(bRFS).Results In the test set,there was no statistically significant difference among C-index of radiomics signature,DL signature and clinical model(P＞0.05).The CRDL fusion model achieved a C-index of 0.83,higher than the clinical model,radiomics signature,and DL signature(P=0.03,0.01,and 0.03).K-M survival curve showed a significant difference in bRFS between low-risk and high-risk patients stratified by the CRDL fusion model[P＜0.000 1,hazard ratio(HR)=30.56,95％confidence interval(CI)10.64-87.75].Conclusion Radiomics signature and DL signature have comparable predictive per-formance for BCR after RP.The CRDL fusion model exhibits the best predictive efficacy for BCR,which is valuable for guiding postoperative treatment strategies in clinical practice.

Objective:To explore the impact of parenting style on social anxiety among college students, and examine the mediating effect of core self-evaluation.Methods:From November 2022 to January 2023, a total of 1 126 college students in Harbin were taken as research subjects.Interaction anxiousness scale(IAS), short-egna minnen betraffende upfostran-Chinese(s-EMBU-C) and core self-evaluations scale(CSES) were used for analysis. Data were analyzed using SPSS 26.0 software for correlation analysis and analysis of variance.AMOS 27.0 software was used for mediation effect test.Results:Social anxiety (42.31±8.23) was negatively correlated with positive parenting style (5.44±1.45) ( r=-0.072, P<0.05) and core self-evaluation (32.12±6.01) ( r=-0.350, P<0.01), while positively correlated with negative parenting style (7.40±1.74)( r=0.302, P<0.01). Core self-evaluation was positively correlated with positive parenting style ( r=0.362, P<0.01) and negatively correlated with negative parenting style ( r=-0.346, P<0.01).Parent parenting styles had a significant mean direct effect on social anxiety of college students ( βpositive=0.098, βnegtive=0.222).Mediation analyses indicated that core self-evaluation played a masking role between positive parenting styles and social anxiety, with an absolute value of 90.82% for the ratio of indirect(-0.089) to direct effects(0.098).Core self-evaluation had partial mediating effect on negative parenting styles, with direct effect and indirect effect accounting for 73.03% and 26.97% of the total effect, respectively. Conclusion:Parenting style can either directly affect college students' social anxiety or indirectly through the mediating effect of core self-evaluations, with core self-evaluations playing a masking role in the positive parenting styles pathway.

OBJECTIVE: To explore the genetic basis for 7 families with gonadal mosaicism for Duchenne muscular dystrophy (DMD). METHODS: For the 7 families presented at the CITIC Xiangya Reproductive and Genetic Hospital from September 2014 to March 2022, clinical data were collected. Preimplantation genetic testing for monogenic disorders (PGT-M) was carried out for the mother of the proband from family 6. Peripheral venous blood samples of the probands, their mothers and other patients from the families, amniotic fluid samples from families 1 ~ 4 and biopsied cells of embryos cultured in vitro from family 6 were collected for the extraction of genomic DNA. Multiplex ligation-dependent probe amplification (MLPA) was carried out for the DMD gene, and short tandem repeat (STR)/single nucleotide polymorphism (SNP)-based haplotypes were constructed for the probands, other patients, fetuses and embryos. RESULTS: The results of MLPA showed that the probands and the fetuses/probands' brothers in families 1 ~ 4, 5, 7 had carried the same DMD gene variants, whilst the probands' mothers were all normal. The proband in family 6 carried the same DMD gene variant with only 1 embryo (9 in total) cultured in vitro, and the DMD gene of the proband's mother and the fetus obtained through the PGT-M were normal. STR-based haplotype analysis showed that the probands and the fetuses/probands' brothers in families 1 ~ 3 and 5 have inherited the same maternal X chromosome. SNP-based haplotype analysis showed that the proband from family 6 has inherited the same maternal X chromosome with only 1 embryo (9 in total) cultured in vitro. The fetuses in families 1 and 6 (via PGT-M) were both confirmed to be healthy by follow up, whilst the mothers from families 2 and 3 had chosen induced labor. CONCLUSION Haplotype analysis based on STR/SNP is an effective method for judging gonad mosaicism. Gonad mosaicisms should be suspected for women who have given births to children with DMD gene variants but with a normal peripheral blood genotype. Prenatal diagnosis and reproductive intervention may be adapted to reduce the births of further affected children in such families.
Male ; Pregnancy ; Child ; Humans ; Female ; Muscular Dystrophy, Duchenne/diagnosis* ; Dystrophin/genetics* ; Mosaicism ; Exons ; Prenatal Diagnosis/methods* ; Nucleotides

Objective:To construct a clinical-radiomics model based on MRI, and to explore its predictive value for biochemical recurrence (BCR) after radical prostatectomy in prostate cancer patients.Methods:A total of 212 patients with prostate cancer who underwent radical prostatectomy in the First Affiliated Hospital of Soochow University from January 2015 to December 2018 and had complete follow-up data were retrospectively analyzed. The random toolkit of Python language was used to randomly sample the patients at a ratio of 7∶3 without replacement, and they were divided into a training set (149 cases) and a test set (63 cases). The endpoint of follow-up was BCR or at least 3 years. BCR occurred in 50 patients in the training group and 21 patients in the test group. The imaging features of the main lesion area in the preoperative T 2WI, diffusion-weighted imaging and apparent diffusion coefficient map of patients in the training set were extracted, and the unsupervised K means clustering algorithm was used to screen the features. The selected features were fitted by a multivariate Cox regression model, and the radiomics model was constructed. Univariate Cox regression analyses were used to screen the main clinical risk factors associated with BCR, and the clinical-radiomics model was constructed combined with RadScore. In the test set, the time-dependent receiver operating characteristic (ROC) curve was constructed, and the area under the curve (AUC) was calculated to evaluate the predictive efficacy of the radiomics model, clinical-radiomics model and prostate cancer risk assessment after radical resection (CAPRA-S) score for the occurrence of BCR. Harrell consistency index (C-index) was used to evaluate the model to predict BCR consistency. The calibration curve was used to evaluate the degree of variation of the model. The decision curve was used to evaluate the clinical application value of the prediction model. Results:A total of 26 radiomics features were screened to establish the radiomics model. The univariate Cox showed that the preoperative clinical features included preoperative prostate-specific antigen level (HR=1.006, 95%CI 1.002-1.009, P=0.001), Gleason score of biopsy (HR=1.422, 95%CI 1.153-1.753, P=0.001), clinical T stage (HR=1.501, 95%CI 1.238-1.822, P<0.001). The multivariate Cox showed that the RadScore was an independent predictor of BCR after radical prostatectomy (HR=51.214, 95%CI 18.226-143.908, P<0.001). The selected preoperative clinical features were combined with RadScore to construct a clinical-radiomics model. In the test set, the AUCs of the time (3 years)-dependent ROC curves of the radiomics model, the clinical-radiomics model, and the CAPRA-S score were 0.824 (95%CI 0.701-0.948), 0.841 (95%CI 0.714-0.968), and 0.662 (95%CI 0.518-0.806), respectively. The C-index of the radiomics model, clinical-radiomics model and CAPRA-S score were 0.784 (95%CI 0.660-0.891), 0.802 (95%CI 0.637-0.912) and 0.650 (95%CI 0.601-0.821), respectively. The calibration curve showed that the predicted probability and actual probability of BCR by radiomics model, clinical-radiomics model and CAPRA-S score were in good agreement (χ 2=7.64, 10.61, 6.37, P=0.465, 0.225, 0.498). The decision curve showed that the clinical net benefit of the clinical-radiomics model and the radiomics model was significantly higher than the CAPRA-S score. When the threshold probability was 0.20-0.30, 0.40-0.50, and >0.55, the clinical net benefit of the clinical radiomics model was higher than that of the radiomics model. Conclusions:The clinical-radiomics model can effectively predict the occurrence of BCR in patients with prostate cancer after radical prostate ctomy, and the prediction efficacy is better than the radiomics model and CAPRA-S score.

Objective To establish the quality standard of compound Yuhong suppository. Methods Angelica dahurica, colophony and Sophora flavescens Alt. were identified by thin layer chromatography（TLC）method. The contents of sulfadiazine and dyclonine hydrochloride were determined by HPLC with diode array detection method. The mobile phase was methanol-0.02 mol/L potassium dihydrogen phosphate (adjusted to pH 3.3 with phosphoric acid) for gradient elution. The detection wavelength was 280 nm for sulfadiazine and dyclonine hydrochloride. Results The three Chinese traditional medicines were identified by TLC with clear spots. The linear ranges of sulfadiazine and dyclonine hydrochloride were good in 12.40-99.20 μg/ml (r=0.999 9) and 2.56-20.48 μg/ml (r=0.999 9). The average recovery was (99.21±0.43) % (n=9) and (99.54±0.68) % (n=9). Conclusion This method is accurate, sensitive, and reproducible. It can be used as a standard method for the quality control of compound Yuhong suppository.