Objective To investigate the effect of colquhounia root tablet(CRT)on hyperglucose-in-duced epithelial-mesenchymal transition(EMT)in renal tubular epithelial cells(HK-2),and to explore its possible action mechanism.Methods HK-2 was cultured in vitro,and HK-2 was divided into the following five groups:control group(CON group),hyperosmolar group(MA group),high glucose group(HG group),high sugar+CRT group(HG+CRT group),high sugar+phosphatidylinositol 3 kinase inhibitor group(HG+LY29400 group),high sugar+CRT+phosphatidylinositol 3 kinase inhibitor group(HG+CRT+LY29400).The real time immunofluorescence quantitative PCR(qPCR)was used to detect the mRNA ex-pression levels of E-cadherin,α-smooth muscle actin(α-SMA)and phosphatase and tensin homolog(PTEN)in each group.Western-blot was used to detect the protein expression levels of PTEN,phosphatidylinositol 3 kinase(PI3K),protein kinase B(Akt),phosphorylated protein kinase B(p-Akt),E-cadherin and α-SMA in each group.Results Compared with the CON group,the protein and mRNA expression levels of α-SMA,p-Akt protein expression level and p-Akt/Akt ratio in the HG group were increased,the protein and mRNA ex-pression levels of E-cadherin and PTEN were decreased,and the differences were statistically significant(P＜0.05).Compared with the HG group,the α-SMA protein and mRNA expression levels in the HG+CRT group were decreased,while the E-cadherin protein and mRNA expression levels were increased,and the differences were statistically significant(P＜0.05).Compared with the HG+CRT group,there was no significant differ-ence in the E cadherin,α SMA,PTEN,P13K and Akt protein expression levels and p-Akt/Akt ratio in the HG+CRT+LY29400 group had no significant differences(P＞0.05).while the expression level of p-Akt protein was increased,and the difference was statistically significant(P＜0.05).Conclusion In vitro,CRT could re-verse hyperglucose-induced renal tubular epithelial cell EMT via the PTEN/PI3K/Akt signaling pathway.

The paper summarizes the imaging evaluation methods for assessing the degree of carotid artery stenosis and analyzes the unique advantages and limitations of various imaging techniques in vascular imaging based on existing guidelines and consensus.The paper focuses on reviewing the clinical applications of several novel ultrasound technologies,including the use of advanced hemodynamic parameters such as blood flow dispersion(Tur index)and wall shear stress(WSS).Carotid artery stenosis is closely associated with cardiovascular disease.Although non-invasive and radiation-free ultrasound technology has certain limitations in diagnostic accuracy to a certain extent,with the continuous emergence of advanced functions such as ultrasound hemodynamics and vascular elasticity,the combination of multi-modality and multi-parameter ultrasound is expected to become an important method for efficient diagnosis of arterial stenosis in the future.

The efficient clinical treatment of oral squamous cell carcinoma(OSCC)is still a challenge that demands the development of effective new drugs.Phenformin has been shown to produce more potent anti-tumor activities than metformin on different tumors,however,not much is known about the influence of phenformin on OSCC cells.We found that phenformin suppresses OSCC cell proliferation,and promotes OSCC cell autophagy and apoptosis to significantly inhibit OSCC cell growth both in vivo and in vitro.RNA-seq analysis revealed that autophagy pathways were the main targets of phenformin and identified two new targets DDIT4(DNA damage inducible transcript 4)and NIBAN1(niban apoptosis regulator 1).We found that phenformin significantly induces the expression of both DDIT4 and NIBAN1 to promote OSCC autophagy.Further,the enhanced expression of DDIT4 and NIBAN1 elicited by phenformin was not blocked by the knockdown of AMPK but was suppressed by the knockdown of transcription factor ATF4(activation transcription factor 4),which was induced by phenformin treatment in OSCC cells.Mechanistically,these results revealed that phenformin triggers endoplasmic reticulum(ER)stress to activate PERK(protein kinase R-like ER kinase),which phosphorylates the transitional initial factor eIF2,and the increased phosphorylation of eIF2 leads to the increased translation of ATF4.In summary,we discovered that phenformin induces its new targets DDIT4 and especially NIBAN1 to promote autophagic and apoptotic cell death to suppress OSCC cell growth.Our study supports the potential clinical utility of phenformin for OSCC treatment in the future.

Endosomal TLRs (TLR3/7/8/9) are highly analogous innate immunity sensors for various viral or bacterial RNA/DNA molecular patterns. Among them, TLR7, in particular, has been suggested to be a target for various inflammatory disorders and autoimmune diseases including systemic lupus erythematosus (SLE); but few small-molecule inhibitors with elaborated mechanism have been reported in literature. Here, we reported a well-characterized human TLR7-specific small-molecule inhibitor, TH-407b, with promising potency and negligible cytotoxicity through a novel binding mechanism. Notably, TH-407b not only effectively inhibited TLR7-mediated pro-inflammatory signaling in a variety of cultured cell lines but also demonstrated potent inflammation suppressing activities in primary peripheral blood mononuclear cells (PBMCs) derived from SLE patients. Furthermore, TH-407b showed prominent efficacy in vivo, improved survival rate and ameliorated symptoms of SLE model mice. To obtain molecular insights into the TH-407b derivatives' inhibition mechanism, we performed the structural analysis of TLR7/TH-407b complex using cryogenic electron microscopy (cryo-EM) method. As an atomistic resolution cryo-EM structure of the TLR family, it not only of value to facilitate structure-based drug design, but also shed light to methodology development of small proteins using EM. Significantly, TH-407b has unveiled an inhibition strategy for TLR7 via stabilizing its resting/inactivated state. Such a resting state could be generally applicable to all TLRs, rendering a useful method for targeting this group of important immunological receptors.

Objective:To explore the diagnostic value of contrast-enhanced mammography (CEM) and MRI in differentiating benign and malignant breast lesions based on the 2013 breast imaging reporting and data system (BI-RADS) lexicon and the supplement on CEM.Methods:The clinical and imaging data of 83 patients with breast lesions from March 2019 to April 2022 in the Third Affiliated Hospital of Soochow University were retrospectively analyzed. Totally 100 breast lesions from 83 female patients aged 28 to 78 (49±14) years, were divided into benign lesions (50 lesions) and malignant lesions (50 lesions) according to the pathological results. The t-test, χ 2 test and Fisher′s exact test were used to compare the differences of clinical and imaging features between benign and malignant lesions, and these imaging features which had statistical differences were established CEM and MRI models by multivariate logistic regression analysis respectively. The receiver operating characteristic curves and the area under the curve (AUC) were used to assess the diagnostic efficacy of two models in differentiating benign and malignant breast lesions. Using the DeLong test compared the AUC. Results:Multivariate logistic regression analysis showed that associated features (OR=9.075,95%CI 1.430-57.570, P=0.019), lesion conspicuity (OR=6.180,95%CI 2.608-14.646, P<0.001), mass margin (OR=2.193,95%CI 1.405-3.422, P=0.001) and calcification distribution (OR=2.147,95%CI 1.157-3.986, P=0.015) were independent predictors of differentiating benign and malignant breast lesions in CEM, and then the predictive model of CEM was constructed. Time-signal intensity curve (OR=9.230, 95%CI 3.178-26.805, P<0.001), associated features (OR=5.289,95%CI 1.343-20.831, P=0.017) and mass margin (OR=2.192,95%CI 1.336-3.597, P=0.002) were independent predictors of differentiating benign and malignant breast lesions in MRI, and the predictive model of MRI was constructed. The AUC of CEM and MRI models for differentiating benign and malignant breast lesions were 0.947 and 0.930 respectively, and two models were no significant difference ( Z=0.68, P=0.494). Conclusion:The diagnostic efficacy of CEM and MRI in differentiating benign and malignant breast lesions is comparable based on the 2013 BI-RADS lexicon and the supplement on CEM.

Objective:To analyze the relationship between PD-L1 expression and the degree of infiltration of different types of TILs in triple-negative breast cancer, and the correlation with other pathological features to explore their clinical significance.Methods:Tumor tissues of 199 patients with triple-negative breast cancer in our hospital were selected, and the expression of PD-L1 and the distribution of TILs were analyzed using immunohistochemistry and counted using Image software. The relationship between CD8 +TILs, CD4 +TILs and PD-L1 expression was analyzed and compared, and survival analysis and correlation analysis between PD-L1 expression and pathological information were performed. Results:The density of CD4 + TILs ( χ2=8.75, P=0.003) and CD8 + TILs ( χ2=6.32, P=0.009) infiltration was higher in the PD-L1-positive group compared to that of the PD-L1-negative group. Among PD-L1-positive patients, patients with higher TILs infiltration compared to low infiltrating TILs could achieve longer overall survival time, and the difference was statistically significant ( P1=0.012, P2=0.023, P3=0.010). Patient PD-L1 expression was positively correlated with the number of positive lymph nodes, tumor stage, and ki-67 expression ( Pa=0.032, Pb=0.006, Pc=0.042), and was not related to age or tumor diameter ( Pd=1.031, Pe=0.672) . Conclusions:PD-L1 expression in triple negative breast cancer predicts higher infiltration of CD4 +TILs and CD8 +TILs, while higher infiltration of CD4 +TILs and CD8 +TILs predicts a relatively good survival prognosis.PD-L1 expression is associated with multiple pathological clinical factors and deserves further study to make PD-L1, TILs and other indicators better benefit triple-negative breast cancer patients.

Based on the resutls of literature review and interviews of experts, two rounds of Delphi surveys were conducted. The mean, importance ratio, coefficient of variation and coordination coefficient were used for assessment of survey from multiple perspectives, and finally form a framework model of factors affecting the efficacy of Tuina therapy. A total of 37 experts were selected for questionnaire surveys, the positive coefficients of experts' participatation in the first round and second round were 92.5% and 80.0%, respectively. The overall coordination coefficient in the second round is 0.68. The items were included into the consensus meeting if the importance ratio of items were equal to and more than 80%. After the expert consensus meeting, 22 items were included to form a framework model of factors affecting the efficacy of Tuina therapy, and summarized as 5 major influencing factors, including diagnostic factors, treatment factors, prognostic factors, patient factors, and doctor-patient communication. This framework can guide and help young Tuina practitioners to improve clinical efficacy. It is also clearly pointed out that the effect of Tuina for pain is not only related to disease diagnosis or manipulation, but also related to home exercise, health care, and doctor-patient communication.

Objective: To explore the association between aggression and social support and their gender differences among Chinese adolescence, and to provide a scientific reference for preventing and reducing aggressive behaviors of adolescents. Methods: Conducted a cross sectional survey of 15 623 adolescents in 5 provinces in China, namely, HeiLongjiang, Hubei, Anhui, Guangdong and Yunnan Province. And the Chinese version of the Adolescent Social Support Scale was employed to assess the aggression and social support, life events, psychological characteristics, family condition and demographic characteristics among adolescents. Results: The prevalence of self reported high level of aggression was 23.5%(3 670/15 623). Males reported higher rate of high level aggression than females (24.4% vs 22.5%, χ 2=19.30, P <0.01). Significant association between aggression and social support was identified in univariate analysis ( χ 2=620.68, P <0.01). After controlling for potential confounders, aggression was also significantly negatively associated with social support ( OR =1.27-1.84), and there was dose response relationship between them( P < 0.05 ). Furthermore, the association between aggression and social support was similar among male participants and female participants ( ROR =1.02-1.10, P >0.05). Conclusion The findings indicate that aggression is associated with social support both in male and female adolescents. Improving the social support for adolescents can reduce their aggressive behaviors.

Objective: To investigate the incidence of adolescent depressive symptoms in primary and secondary schools in Guangzhou and the effect of gestational complications on adolescent depression, so to provide scientific basis for depression prevention among adolescent. Methods: Stratified cluster random sampling method was used to select 808 primary and secondary schools in 11 districts of Guangzhou. A total of 96 756 parents of adolescents aged 10-20 were surveyed for adolescents depressive symptoms and maternal gestational complications. Results: The parental reported rates of mild, moderate and major depressive symptoms of adolescents were 5.5%, 3.5%, and 0.5%, respectively. Univariate analysis showed that the severity of adolescent depression symptoms had statistical significance with maternal gestational hypertension, gestational diabetes mellitus, cholestasis, hypothyroidism, hyperthyroidism, gestational anemia and viral hepatitis ( χ 2=12.42~158.91， P <0.01). Multivariate Logistic regression showed that maternal gestational diabetes mellitus ( OR =1.41, 95% CI =1.18- 1.68 ), hypothyroidism during pregnancy ( OR =1.61, 95% CI = 1.15-2.26), and hyperthyroidism during pregnancy ( OR =1.40, 95% CI =1.03-1.91), anemia during pregnancy ( OR = 1.46 , 95% CI =1.35-1.59), and viral hepatitis during pregnancy ( OR =1.67, 95% CI =1.38-2.02) were positively correlated with the severity of adolescent depression symptoms reported by parents( P <0.05). Conclusion Gestational diabetes mellitus, gestational hypothyroidism, gestational hyperthyroidism, gestational anemia and gestational viral hepatitis are associated with adolescent depressive symptom.

Objective: To analyze household determinants of adolescents non suicidal self injury(NSSI), and to provide scientific basis for NSSI intervention amogn adolescents. Methods: Using stratified random cluster sampling method, 15 623 middle school students aged 11-20 were selected from Heilongjiang, Anhui, Hubei, Yunnan, and Guangdong provinces, and non suicidal self injury and related household determinants were investigated by questionnaire. Results: The survey showed that 28.8% of people who had NSSI in the past year accounted;among them,17.6% had 1-4 times(occasional self injury) and 11.2% had 5 times or more(repeated self injury) univariate results showed that whether they were an only child, family type, educational level of the main caregiver, family rearing style, family monthly income per capita, and whether there was a family history of mental illness was associated with adolescents NSSI ( χ 2=6.30-12.16, P <0.05); multivariate Logistic regression analysis showed that whether one child or family parenting style is still significantly related to occasional NSSI( OR =1.11,1.34, P <0.05)after controlling for gender, age, grade, ethnicity, emotional control, resilience, loneliness and social support; whether it is an only child, educational level of the main caregiver and family parenting style are still significantly related to repeated NSSI ( OR =1.19，0.69，1.57， P <0.05); stratified analysis by region shows that the influencing factors of NSSI in adolescents in each region are different. Conclusion Family factors such as the only child and the education level of the main caregiver may be related to the occurrence of adolescents NSSI, but there are regional differences in the family impact of NSSI.