Objective:To investigate the predictive value of infiltrating zone contrast-enhanced ultrasound(CEUS) gradient features in Nottingham grading and pathologically true infiltration of invasive ductal carcinoma(IDC).Methods:A retrospective analysis was performed on 78 female breast cancer patients (95 masses) confirmed by surgical and pathology in the Affiliated Hospital of Jiangsu University from July 2019 to June 2022, which were divided into Grade-Ⅰ (22 masses), Grade-Ⅱ (28 masses), and Grade-Ⅲ (45 masses) according to the Nottingham histological grading system. The differences in the maximum diameter of the infiltration zone and the characteristic parameters of the gradient of the inner and outer edges of the infiltration zone among the three groups of masses were compared, and the differential gradient features among them were analyzed by multivariate ordered Logistic regression and ROC curves. The relationship between the differential gradient characteristics of the infiltration zone and the pathologically true infiltration of the mass was further explored.Results:The univariate analysis showed statistically significant differences among the three groups for peak-arrival time gradient (ΔTTP), ascending branch slope gradient (ΔRS), peak intensity gradient (ΔPI) and area gradient under the curve (ΔAUC) (all P<0.05). Multiple ordered logistic regression analysis showed that ΔTTP, ΔPI and ΔAUC had independent influences on the histologic grading of IDC (all P<0.05), and the area under the curve for the combination of the three in predicting IDC histology grades Ⅰ, Ⅱ and Ⅲ was 0.692, 0.705 and 0.765, respectively. In addition, the maximum diameter of pathologically true infiltration of the mass was positively correlated with ΔTTP ( r=0.621, P<0.05) and negatively correlated with ΔPI ( r=-0.605, P<0.05) and ΔAUC ( r=-0.719, P<0.05). Conclusions:Infiltration zone CEUS gradient features are effective in predicting the histologic grade of IDC and strongly correlate with the degree of pathologically true infiltration of the mass.

ObjectiveTo investigate the differences in clinical efficacy of different medication regimens of Wangbi Tablets （尪痹片） for knee osteoarthritis （KOA） in a real-world setting， providing a basis for rational clinical use of Wangbi Tablets. MethodsA prospective registry study was conducted， involving 2，999 KOA patients registered in 30 hospitals nationwide from January 26th， 2019， to December 17th， 2021. Based on the use of Wangbi Tablets during the observation period， patients were divided into a monotherapy group （1，507 cases） and a combination therapy group （1，492 cases）， and the combination group can be further divided into Wangbi Tablets plus Chinese medicine （CM）， Wangbi Tablets plus western medicine （WM）， and Wangbi Tablets plus Chinese and western medicine （CM+WM） subgroups. The baseline data of patients in the monotherapy group and the combination group were compared， including age， gender， body weight， medication time， clinical stage， K-L grade， and others. Efficacy indicators included the Visual Analog Scale （VAS） score， Western Ontario and McMaster Universities Osteoarthritis Index （WOMAC） score， and EuroQol five-dimensional （EQ-5D） health index， which were evaluated before and after 4-， 8- and 12-week treatment， and the difference before and after treatment was calculated after 4， 8 and 12 weeks of treatment. The difference between the baseline and 12 weeks of treatment of all the above indicators was used as the dependent variables， and gender， age， body mass index （BMI）， course of disease， K-L grade， and clinical stage were used as independent variables， when multiple linear regression was taken to explore the influencing factors of the efficacy. At the same time， the occurrence of major symptoms （including morning stiffness， joint swelling， soreness of waist and knees， fear of wind， and fear of cold） was counted， and the disappearance of symptoms at each time point was counted after 4， 8， and 12 weeks of treatment. ResultsAt baseline， there were no statistically significant differences in gender and age distribution between the monotherapy and combination therapy groups （P＞0.05）； the proportion of patients in the acute stage and recovery stage was higher in the monotherapy group than in the combination therapy group， while the proportion in the remission stage was lower （P＜0.05）； the VAS score was higher in the monotherapy group， and the EQ-5D index was lower （P＜0.01）， with no statistically significant difference in total WOMAC score between the two groups （P＞0.05）. Compared to those measured before treatment and at previous timepoint， the VAS score and WOMAC total score significantly decreased in both groups， while EQ-5D value increased （P＜0.05）. The difference in VAS score between baseline and after 12-week treatment was higher in the monotherapy group than the combination group， while the differences in WOMAC total score and EQ-5D value between baseline and after 4-， 8- and 12-week treatment were higher in the combination group （P＜0.05）. Multiple linear regression showed that VAS score before treatment had greatest impact on pain improvement （P＜0.01）， and compared to Wangbi Tablets monotherapy， the combination of Wangbi tablets with WM or CM had larger associations with pain improvement （P＜0.05）； and Wangbi Tablets had better efficacy when the course of treatment was ＞28 days （P＜0.01）. Wangbi Tablets plus WM had a better effect on improving the overall function of the knee joint than Wangbi Tablets alone （P＜0.01）； and the efficacy of Wangbi Tablets with a course of treatment ＞28 days was better （P＜0.05）. The improvement of quality of life of patients in the attack and remission stages was more obvious than that in the recovery stage （P＜0.01）； Wangbi Tablets plus WM or CM had a better effect on improving quality of life than Wangbi Tablets alone （P＜0.05）. Before treatment， the proportion of patients with morning stiffness， soreness of waist and knees， fear of wind and chills in the monotherapy group was higher than that in the combination group （P＜0.01）. The proportion of main symptoms in both groups decreased after 4， 8 and 12 weeks of treatment （P＜0.05）. After 4 weeks of treatment， the disappearance rate of each main symptom in the combination group was higher than that in the monotherapy group， and after 12 weeks of treatment， the disappearance rate of fear of wind in the monotherapy group was higher than that in the combination group， while the disappearance rate of joint swelling and soreness of waist and knees was lower （P＜0.05）. ConclusionWangbi Tablets， whether used alone or in combination with other medications， is effective throughout the course of KOA， with greater benefits in improving joint function and quality of life during the acute and remission stages compared to the recovery stage. Combination therapy had a faster onset of effect， but began to converge with monotherapy after 8 weeks. The best efficacy was observed with the combination of Wangbi Tablets with WM， followed by combination with CM.

Objective To investigate the clinical prognosis value of serum microRNA(miR)-138-5p and miR-212-5p levels in prostate cancer.Methods A total of 95 cases of prostate cancer patients admitted to the First Hospital of Handan from July 2020 to June 2021 were collected.Based on follow-up records for two years after surgery,these patients were separated into a poor prognosis group(n=52)and a good prognosis group(n=43),and 48 healthy volunteers who underwent a physical examination at the hospital were collected as the healthy control group.In addition,quantitative real-time fluorescence-PCR(qRT-PCR)was applied to detect the relative expression levels of miR-138-5p and miR-212-5p in the serum of study subjects,and the clinical data of the patients were collected and analyzed.Multivariate COX regression was applied to analyze factors that affected the prognosis of prostate cancer patients.The predictive value of serum miR-138-5p and miR-212-5p for the prognosis of prostate patients was tested,and receiver operating characteristic(ROC)curves were plotted.Pearson method was applied to analyze the correlation between the expression of serum miR-138-5p and miR-212-5p and the Gleason score.Results Compared to the healthy control group,the serum levels of miR-138-5p(0.88±0.10,0.83±0.09 vs 1.01±0.10),and miR-212-5p(0.75±0.09,0.71±0.08 vs 1.02±0.11)were lower in the good prostate cancer prognosis group and poor prostate cancer prognosis group,and the differences were significant(t=14.021,22.275;9.825,18.063,all P＜0.05).The prognosis of prostate cancer patients was related to TNM staging,bone metastasis,tissue differentiation degree,preoperative PSA level,and Gleason score(x2=4.417～7.187,t=14.235,all P＜0.05).Serum miR-138-5p[HR(95％CI):0.871(0.785～0.966)],and miR-212-5p[HR(95％CI):0.822(0.725～0.932)]were protective factors for poor prognosis(all P＜0.05).While Gleason score[HR(95％CI):1.253(1.026～1.530)],TNM stage[HR(95％CI):1.224(1.024～1.463)],bone metastasis[HR(95％CI):1.398(1.036～1.887)],tissue differentiation degree[HR(95％CI):1.520(1.146～2.016)]and PSA level[HR(95％CI):1.426(1.094～1.858)]were all risk factors for poor prognosis(all P＜0.05).The AUC(95％CI)of serum miR-138-5p and miR-212-5p were 0.883(95％CI:0.801～0.940)and 0.863(95％CI:0.777～0.925),respectively.Serum miR-138-5p and miR-212-5p were negatively correlated with the Gleason score(r=-0.610,-0.420,all P＜0.05).Conclusion Serum miR-138-5p and miR-212-5p levels are elevated in patients with poor prostate cancer prognosis and may have a certain auxiliary predictive value for prostate cancer patient prognosis.

Benign biliary strictures is a common complication of hepatobiliary surgery and disease. For conventional benign biliary stenosis, endoscopic treatment or percutaneous intervention can usually achieve a more satisfactory therapeutic effect, but for refractory benign biliary stenosis that cannot pass the guide wire or the above treatments all have failed, the clinical treatment is quite difficult. Compared with traditional surgery, magnetic compression anastomosis has the advantages of convenient operation, low risk of complications, and low recurrence rate, and can be used as a treatment for refractory benign biliary strictures. In this article, we review the research progress of magnetic compression anastomosis in the treatment of refractory benign biliary strictures.

ObjectiveTo explore the underlying mechanism by which the Chinese medicine compound Yitangkang granule（YTK） treats diabetic kidney disease （DKD） by observing its effects on podocyte autophagy through the regulation of phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/forkhead transcription factor O1 （FoxO1） signaling pathway mediated by silent information regulator 1 （SIRT1） via advanced glycation end products （AGE）/receptor for AGE （RAGE） axis. MethodNinety-six 8-week-old healthy male SPF-grade Wistar rats were selected and randomly divided into blank control group （B）， model control group， high-dose YTK （40 g·kg^-1）， medium-dose YTK （20 g·kg^-1）， low-dose YTK （10 g·kg^-1）， and Western medicine control （20 mg·kg^-1 losartan） groups. The DKD rat model was established by high-fat diet feeding combined with intraperitoneal injection of streptozotocin. After successful modeling， the rats in each group received the corresponding treatments for eight weeks. The levels of superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione peroxidase （GSH-Px）， and catalase （CAT） were measured according to the instructions of the respective assay kits. Hematoxylin and eosin （HE） staining was used to observe pathological changes in kidney tissues. Immunohistochemistry was employed to detect the average optical density values of α-smooth muscle actin （α-SMA）， fibronectin （FN）， desmin， and nephrin. Western blot analysis was used to measure the expression levels of PI3K， phosphorylated PI3K （p-PI3K）， Akt， phosphorylated Akt （p-Akt）， RAGE， SIRT1， Caspase-3， and FoxO1 proteins in kidney tissues of DKD rats. ResultCompared with the blank control group， the model group showed significantly lower levels of SOD， GSH-Px， and CAT， and significantly higher levels of MDA （P<0.01）. The rats exhibited severe kidney damage. The positive expression of podocyte marker proteins α-SMA， FN， and desmin increased significantly， while nephrin and podocin significantly decreased （P<0.01）. The expression levels of PI3K， p-PI3K， Akt， p-Akt， RAGE， and Caspase-3 proteins were significantly elevated， while SIRT1 and FoxO1 protein levels were significantly reduced （P<0.01）. Compared with the model control group， rats in the YTK treatment groups showed significantly higher levels of SOD， GSH-Px， and CAT， and significantly lower levels of MDA in serum （P<0.01）. The degree of kidney damage was reduced to varying extents. The average optical density values of podocyte marker proteins α-SMA， FN， and desmin were significantly decreased， while nephrin and podocin significantly increased （P<0.01）. The expression levels of PI3K， p-PI3K， Akt， p-Akt， RAGE， and Caspase-3 in kidney tissues were significantly reduced， while SIRT1 and FoxO1 expression levels significantly increased （P<0.01）. The Chinese medicine groups demonstrated a clear dose-response trend. ConclusionYTK may alleviate kidney pathological damage， reduce proteinuria， and protect kidney function in DKD rats， thereby delaying the progression of DKD by improving podocyte autophagy through the AGE-RAGE axis-mediated SIRT1 regulation of the PI3K/Akt/FoxO1 signaling pathway. Additionally， a dose-response relationship was observed in the Chinese medicine groups.

In 2009,the World Health Organization included snakebite on the list of neglected tropical diseases,acknowledging it as a common occupational hazard for farmers,plantation workers,and others,causing tens of thousands of deaths and chronic physical disabilities every year.This guideline aims to provide practical information to help clinical professionals evaluate and treat snakebite victims.These recommendations are based on clinical experience and clinical research evidence.This guideline focuses on the following topics:snake venom,clinical manifestations,auxiliary examination,diagnosis,treatments,and prevention.

Methods: CHB patients and healthy volunteers were enrolled from Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine between August 21, 2018 and December 31, 2020. They were divided into three groups: healthy group, LGDHS group, and latent syndrome (LP) group. Proteomic analysis using isobaric tags for relative and absolute quantitation (iTRAQ) was performed to identify differentially expressed proteins (DEPs). Metabolomic profiling via ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was applied to serum samples to detect differentially regulated metabolites (DMs). Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment were employed to explore dysregulated pathways. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were utilized to visualize group separation and identify key metabolites and proteins contributing to LGDHS differentiation. Receiver operating characteristic (ROC) curve analysis evaluated the diagnostic performance of key biomarkers, while logistic regression models assessed their predictive accuracy. P values were corrected for multiple tests using the Benjamini-Hochberg method to control the false discovery rate (FDR). Validation of potential biomarkers was conducted using independent microarray data and real-time quantitative polymerase chain reaction (RT-qPCR). Results: A total of 150 participants were enrolled, including healthy group (n = 45), LGDHS group (n = 60), and LP group (n = 45). 254 DEPs from proteomics data and 72 DMs from metabolomic profiling were identified by PCA and OPLS-DA. DEPs were mainly enriched in immune and complement pathways, while DMs involved in amino acid and energy metabolism. The integrated analysis identified seven key biomarkers: α1-acid glycoprotein (ORM1), asparagine synthetase (ASNS), solute carrier family 27 member 5 (SLC27A5), glucosidase II alpha subunit (GANAB), hexokinase 2 (HK2), 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR), and maltase-glucoamylase (MGAM). Microarray validation confirmed the diagnostic potential of these genes, with area under the curve (AUC) values for ROC analysis ranging from 0.536 to 0.759. Among these, ORM1, ASNS, and SLC27A5 showed significant differential ability in differentiating LGDHS patients (P = 0.016, P = 0.035, and P < 0.001, respectively), with corresponding AUC of 0.749, 0.743, and 0.759, respectively. A logistic regression model incorporating these three genes demonstrated an AUC of 0.939, indicating a high discriminatory power for LGDHS. RT-qPCR further validated the differential expression of ORM1 and SLC27A5 between LGDHS and LP groups (P = 0.011 and P = 0.034, respectively), with ASNS showing a consistent trend in expression (P = 0.928). Conclusion This study integrates multi-omics approaches to uncover the molecular mechanisms underlying LGDHS in CHB. The identification of biomarkers ORM1, ASNS, and SLC27A5 offers a solid basis for the objective diagnosis of LGDHS, contributing to the standardization and modernization of TCM diagnostic practices.

Background::Prenatal and postnatal factors may have joint effects on cardiovascular health, and we aimed to assess the joint association of birth weight and ideal cardiovascular health metrics (ICVHMs) prospectively in adulthood with incident cardiovascular disease (CVD).Methods::In the UK Biobank, 227,833 participants with data on ICVHM components and birth weight and without CVD at baseline were included. The ICVHMs included smoking, body mass index, physical activity, diet information, total cholesterol, blood pressure, and hemoglobin A1c. The Cox proportional hazards model was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) in men and women.Results::Over a median follow-up period of 13.0 years (2,831,236 person-years), we documented 17,477 patients with incident CVD. Compared with participants with birth weights of 2.5-4.0 kg, the HRs (95% CIs) of CVD among those with low birth weights was 1.08 (1.00-1.16) in men and 1.23 (1.16-1.31) in women. The association between having a birth weight <2.5 kg and CVD risk in men was more prominent for those aged <50 years than for those of older age ( P for interaction = 0.026). Lower birth weight and non-ideal cardiovascular health metrics were jointly related to an increased risk of CVD. Participants with birth weights <2.5 kg and ICVHMs score 0-1 had the highest risk of incident CVD (HR [95% CI]: 3.93 [3.01-5.13] in men; 4.24 [3.33-5.40] in women). The joint effect (HR [95% CI]: 1.36 [1.17-1.58]) could be decomposed into 24.7% (95% CI: 15.0%-34.4%) for a lower birth weight, 64.7% (95% CI: 56.7%-72.6%) for a lower ICVHM score, and 10.6% (95% CI: 2.7%-18.6%) for their additive interaction in women. Conclusions::Birth weight and ICVHMs were jointly related to CVD risk. Attaining a normal birth weight and ideal ICVHMs may reduce the risk of CVD, and a simultaneous improvement of both prenatal and postnatal factors could further prevent additional cases in women.

ObjectiveTo determine the mechanism of Yitangkang in correcting excessive apoptosis of skeletal muscle cells to improve insulin resistance （IR） by inhibiting the advanced glycation end product （AGE）/receptor for the advanced glycation end product （RAGE） signaling pathway. Method① In vitro experiments. Yitangkang-medicated serum was prepared. C2C12 cells were divided into a blank group， a model group， high-， medium-， and low-dose Yitangkang-medicated serum groups （40， 20， and 10 g·kg^-1）， and a RAGE inhibitor group. The IR model was induced by palmitic acid in C2C12 cells except for those in the blank group. After the corresponding intervention methods were conducted，the cell viability and glucose consumption level of each group were determined. In addition，the apoptosis rate was determined using flow cytometry. The mRNA and protein expression levels of the important apoptotic proteins ［B-cell lymphoma 2 （Bcl-2）， Bcl-2-associated X protein （Bax）， p53， cysteinyl aspartate-specific protease-3 （Caspase-3）， and cysteinyl aspartate-specific protease-9 （Caspase-9）］ were determined using Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot. ② In vivo experiments. Ninety-six eligible Wistar rats were divided into a blank group， a model group， high-，medium-，and low-dose Yitangkang groups （40， 20， and 10 g·kg^-1）， and a western medicine group （pioglitazone hydrochloride，1.35 mg·kg^-1）. The IR model was induced using high-glucose and high-fat feed for diabetes combined with intraperitoneal injection of low-dose streptozotocin （STZ） in animals and verified by the hyperinsulinemic-euglycemic clamp （HEC） test. After the model was determined successfully， the rats in each group were given intragastric administration of drugs as required. Terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） assay was performed to determine the number of positive apoptotic cells in the skeletal muscle tissues of rats in each group，while Real-time polymerase chain reaction（Real-time PCR） and Western blot were performed to determine the mRNA and protein expression levels of the important apoptotic proteins Bcl-2， Bax， p53， Caspase-3， and Caspase-9. Result① In vitro experiments. compared with the blank group， the model groups showed increased apoptosis rate of C2C12 cells and decreased cell viability and glucose consumption （P<0.01）. Compared with the model group， the Yitangkang-medicated serum groups and the RAGE inhibitor group showed decreased apoptosis rate of C2C12 cells and increased cell viability and glucose consumption （P<0.01）. Compared with the blank group， the model group showed decreased expression levels of Bcl-2 mRNA and protein in C2C12 cells and increased mRNA and protein expression levels of Bax， p53， Caspase-3， and Caspase-9 （P<0.01）. Compared with the model group， the Yitangkang-medicated serum groups and the RAGE inhibitor group showed increased expression levels of Bcl-2 mRNA and protein in C2C12 cells （P<0.01） and decreased mRNA and protein expression levels of Bax， p53， Caspase-3， and Caspase-9 （P<0.05， P<0.01）. ② In vivo experiments. The number of positive apoptotic cells in the skeletal muscle tissues of rats in the model group significantly increased as compared with that in the blank group （P<0.01）. The number of positive apoptotic cells in the skeletal muscle tissues of rats in the Yitangkang groups and the western medicine group decreased as compared with that in the model group （P<0.01）. Compared with the blank group， the model group showed decreased expression levels of Bcl-2 mRNA and protein in skeletal muscle tissues of rats and increased mRNA and protein expression levels of Bax， p53， Caspase-3， and Caspase-9 （P<0.01）. Compared with the model group， the Yitangkang groups and the western medicine group showed increased expression levels of Bcl-2 mRNA and protein in skeletal muscle tissues of rats （P<0.01） and decreased mRNA and protein expression levels of Bax， p53， Caspase-3， and Caspase-9 （P<0.05， P<0.01）. The medium-dose Yitangkang showed a similar effect as RAGE inhibitor， and the effect was equivalent to that of pioglitazone hydrochloride. ConclusionYitangkang can inhibit skeletal muscle cell apoptosis by inhibiting the AGE/RAGE signaling pathway.

Objective To investigate the HIV-1 genotype and distribution of newly diagnosed HIV-1 cases in Fujian Province in 2020, so as to provide insights into formulation of the precise AIDS control strategy in the province. Methods Newly diagnosed HIV-1 cases without antiretroviral therapy (excluding AIDS patients) were randomly sampled from each city of Fujian Province in 2020 at a proportion of 50% of the mean number of HIV-infected cases reported across 9 cities of Fujian Province during the past three years. Subjects’ demographic and epidemiological data were collected and blood samples were collected. The HIV-1 pol gene was amplified using nested reverse-transcription PCR assay, and the gene sequences were used for HIV-1 genotyping and phylogenetic analysis. The gene sequences were uploaded to the HIV Drug Resistance Database (http://hivdb.stanford.edu) for genotypic drug resistance assays, and the scores and level of HIV drug resistance were estimated using the HIVDB Algorithm version 9.5. Results A total of 1 043 newly diagnosed HIV-1 cases were reported in Fujian Province in 2020, and 936 gene sequences were successfully obtained following sequencing of blood samples. There were 9 HIV-1 genotypes characterized in blood samples from 936 newly diagnosed HIV-1 cases, with CRF07_BC (52.1%) and CRF01_AE (30.4%) as predominant subtypes, followed by CRF08_BC (4.9%), CRF55_01B (3.0%), subtype C (2.5%), subtype B (2.1%), CRF85_BC (1.7%), CRF59_01B (0.3%) and CRF65_CPX (0.1%), and unidentified subtypes were found in 26 blood samples. HIV-1 drug resistance was detected in 43 out of the 936 newly diagnosed HIV-1 cases, with 4.6% prevalence of HIV-1 drug resistance prior to therapy, and the highest drug resistance was found in the HIV CRF59_01B subtype, followed by in CRF08_BC, B, C, CRF01_AE, CRF07_BC and other subtypes, with a significant difference in the genotype-specific prevalence of HIV-1 drug resistance (χ² = 45.002, P < 0.05). Conclusions There was a HIV-1 genotype diversity in Fujian Province in 2020, and emerging recombinant and drug-resistant HIV-1 strains were detected and spread across patients and regions. Monitoring of HIV-1 genotypes is recommended to be reinforced for timely understanding of the transmission and spread of novel recombinant and drug-resistant HIV-1 strains.