Objective To examine the association between the polymorphisms of brain-derived neurotrophic factor (BDNF)gene with heroin dependence.Methods Genomic DNA was isolated from the venous blood leukocytes of 308 unrelated patients with heroin dependence and 31 7 healthy individuals.Seven single nucleotide polymorphisms (SNPs)were genotyped using MassARRAY system.Data were analyzed using HaploView 4.0 and SPSS 20.0 software.Results There was a significant difference in the genotype frequency of rs6265 between heroin dependence group and healthy control group (χ2 =1 5.1 5 1,P =0.001).The rs6265 G allele was significantly higher than in controls (χ2 =9.864,P =0.002,OR =1.429,95% CI =1.143 -1.786).Furthermore,there was also a significant difference in the genotype frequency of rs13306221 between heroin dependence group and control group (χ2 =7.699,P =0.006).The rs13306221 G allele was significantly higher than in controls (χ2 =7.137,P =0.008,OR =0.539,95% CI =0.340-0.853).Strong linkage disequilibrium (LD)was observed in one block (D’> 0.9;r 2 >0.8),and significantly less G-G haplotype frequency of block 1 (χ2 =4.546;P =0.033)was found in heroin dependence group. Conclusion Our findings support the role of BDNF rs6265 and rs13306221 polymorphisms in heroin dependence and may guide future studies to identify other genetic risk factors for heroin dependence.

Objective To study the effects of Weibimei and its Chinese medicine portions(cortex frangulae, fennel powder, acorus tatarinowii, glycyrrhizae and asparagus) on cell cycle regulation in gastric cancer cells and growth inhibition in gastric cancer Xenografts.Methods Gastric cancer SGC-7901 cells were normally cultured and treated with Weibimei, extractum glycyrrhizae, cortex frangulae, fennel powder, acorus tatarinowii and asparagus.Then, the proliferation of SGC-7901 cells were detected by MTT assay, their effect on SGC-7901 cell cycle were measured by flow cytometry, and the expression of cell cycle related proteins were examined by Western blot.Animal models of SGC-7901 cells xenografts in nude mice were constructed to evaluate the growth inhibition effects of Weibimei and its Chinese medicine portions, and the expression of STAT3,p-STAT3, Cyclin D1, Bcl-2 and Survivin in gastric tumors were detected by immunohistochemical assays.Results Weibimei and its three kinds of Chinese medicine portions, cortex frangulae, fennel and acorus tatarinowii could obviously inhibit the proliferation of SGC-7901 cells, compared to control group, with a statistical significant difference (P<0.05).The cell cycle of SGC-7901 was arrested at G1 phase with cortex frangulae, fennel and acorus tatarinowii treatment, the expression of Cyclin A, B, D, E were decreased significantly (P<0.05).However, no significant effects was found in glycyrrhizae or asparagus group.Xenografts tumor sizes in Weibimei, cortex frangulae, fennel or acorus tatarinowi groups were much smaller than that in saline group or Triple Therapy group (three-kinds-drugs-combination for the treatment of gastric ulcer) (P<0.05).Xenografts experiments showed that the tumor growth in nude mice in Weibimei, cortex frangulae, fennel or acorus tatarinowi groups were significantly smaller than that in control group or in Triple Therapy Group (P<0.05), and phosphorylated STAT3, and STAT3 signaling targeted genes, including Bcl-2, Cyclin D1 and Survivin were all significantly down-regulated by immunostaining.Conclusion Weibimei and its Chinese medicine portions including cortex frangulae, fennel and acorus tatarinowii can could significantly inhibit the growth of SGC-7901 cells proliferation and arrested the cell cycle of G1 phase in vitro, and inhibit gastric cancer xenografts in nude mice in vivo.

Objective To evaluate the effect of Eucommia on hyperlipidemia and related indexes in rats, and provide animal data useful for the clinical experimental studies on hyperlipidemia.Methods Seventy-two healthy male SD rats were used in this study.One group of 12 rats fed with normal diet was chosen as normal control group, and other 60 rats were fed with high fat diet for two weeks to generate rat models of hyperlipidemia.48 of the hyperlipidemic model rats were taken and divided randomly into 4 groups, including model group, high dose Eucommia, moderate dose Eucommia, and low dose Eucommia groups.The last three groups were gavaged different dose of Eucommia, respectively.Druing this period, the other groups except the normal control group were fed with high fat diet continuously.The levels of serum TC, TG, LDL-C, and HDL-C of rats were measured on day 30 and 45.Results The serum levels of TC and LDL-C of the rats in the model group were obviously higher than those in the normal control group.The rat models of hyperlipidemia were established successfully.The three dose groups had a tendency of lowing blood lipid after 30 days.At 45 days, the levels of serum TC and LDL-C in the low and high dose groups were lower than those in the model group (P<0.01, P<0.05), (P<0.01, P<0.01).TG in the high, moderate and low dose groups were lower than that in the model group (P<0.01, P<0.01, P<0.01), but the level of the serum HDL-C was not significantly lower than that in the model group (P>0.05, P>0.05, P>0.05).Conclusions Eucommia in a dose of 0.43 g/kg, 0.86 g/kg and 1.71 g/kg administered for 30 days have a tendency to reduce the level of serum TC, TG, and LDL-C.When Eucommia is administered in a dose of 0.43 g/kg, 1.71g/kg and 3.42 g/kg for 45 days, it shows an adjuvant hypolipidemic effect.

Objective: To investigate the risk factors for central lymph node metastasis (CLNM) and lateral cervical lymph node metasta-sis in papillary thyroid carcinoma (PTC) patients. Methods: We retrospectively reviewed 1,835 PTC patients who underwent central lymph node dissection or thyroidectomy with lateral cervical lymph node dissection between January and November 2016 at Tianjin Medical University Cancer Institute and Hospital. Univariate and multivariate logistic regression models were used to analyze related factors that may affect lymph node metastasis in PTC patients. Results: Of the 1,835 patients included in this study, 1,007 (54.88%) pa-tients had CLNM and 371 (20.22%) patients had lateral cervical lymph node metastasis. In the univariate analysis, the following were identified as risk factors for CLNM and lateral cervical lymph node metastasis (P<0.05): male sex, age<45 years, primary tumor size>10 mm, multifocality,anti-thyroglobulin (anti-Tg) levels >100.00 IU/mL and ,Tg>130.70 μg/L. Anti-thyroid peroxidase antibody (anti-TPO) level>100.00 IU/mL is a protective factor that reduces the risk of CLNM. However, CLNM is a risk factor for lateral cervical lymph node metastasis in PTC patients. Multivariate analysis revealed that male sex, age<45 years, primary tumor size>10 mm, multifocality, and anti-TG levels>100.00 IU/mL were associated with an increased risk of CLNM in PTC patients. Anti-TPO levels>100.00 IU/mL are protective factors for CLNM. The male sex, age<45 years, tumor size>10 mm, multifocality, Tg levels>130.70 ug/L, anti-TG levels>100.00 IU/mL, and CLNM are risk factors for lateral lymph node metastasis. Conclusions: Thus, men aged<45 years with a multifocal primary tumor>10 mm in size and with anti-Tg levels>100.00 IU/mL are more likely to develop CLNM and lateral cervical lymph node metastasis; patients with CLNM are more likely to develop lateral cervical lymph node metastasis. However, patients with anti-TPO lev-el>100 IU/mL are less likely to develop CLNM.

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 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.

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.

Alcohol abuse is a serious public health problem and biomedical safety problem that can lead to a variety of neuropsychiatric disorders. In recent years, numerous studies have shown that alcohol can induce structural and functional disregulation in the basolateral amygdala (BLA). Alcohol exposure and withdrawal can cause negative emotion such as anxiety and fear, primarily mediated by glutamatergic neurons and inhibitory γ-aminobutyric acid ergic(GABAergic) interneurons in the BLA. Glutamatergic neurons are responsible for excitatory neurotransmitter glutamate release, while γ-aminobutyric acid ergic(GABAergic) interneurons provide feedback inhibition to suppress BLA function and alleviate negative emotions. However, alcohol intake can disrupt the balance of glutamatergic-GABAergic neural network, altering neuron excitability and subsequently leading to the generation of anxiety and fear. Moreover, alcohol also interferes with the corticotropin-releasing factor(CRF) system within the BLA, increasing the release of CRF, further stimulating anxiety-related emotions. Additionally, alcohol affects BLA-related neural circuits, such as BLA →medial prefrontal cortex, BLA →nucleus accumbens, and BLA →bed nucleus of the stria terminali pathways, thereby impacting anxiety-like behaviors.This review discusses the progress of neural signaling and circuits within the BLA in mediating alcohol-induced negative emotions, aiming to further elucidate the neurobiological mechanisms underlying anxiety triggered by alcohol exposure and withdrawal, in order to provide theoretical basis for clinical treatment in the future.

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.

Currently,human health due to corona virus disease 2019(COVID-19)pandemic has been seriously threatened.The coronavirus severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike(S)protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19.However,the efficacy is compromised by the SARS-CoV-2 evolvement and mutation.Here we report the SARS-CoV-2 S protein receptor-binding domain(RBD)inhibitor licorice-saponin A3(A3)could widely inhibit RBD of SARS-CoV-2 variants,including Beta,Delta,and Omicron BA.1,XBB and BQ1.1.Furthermore,A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells,with EC50 of 1.016 pM.The mechanism was related to binding with Y453 of RBD deter-mined by hydrogen-deuterium exchange mass spectrometry(HDX-MS)analysis combined with quan-tum mechanics/molecular mechanics(QM/MM)simulations.Interestingly,phosphoproteomics analysis and multi fluorescent immunohistochemistry(mIHC)respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 mitogen-activated protein kinase(MAPK)path-ways and rebalancing the corresponding immune dysregulation.This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.