Objective To investigate the effect of cinobufacini on inhibiting colorectal cancer metastasis by regula-ting the polarization of M2 macrophages.Methods THP-1 was induced into M0 type macrophages.The condi-tioned medium of HCT116 cells was collected to stimulate M0 type macrophages.The polarization of M2 type mac-rophages was observed by flow cytometry,real-time quantitative PCR and ELISA experiments.The conditioned me-dium of M0 type macrophages and HCT116-Mφ cells was collected to stimulate HCT116 cells.The ability of migra-tion and invasion was observed by wound healing assay and Transwell assay.The effect of cinobufacini on the via-bility of HCT116 cells was detected by CCK-8 assay.The conditioned medium of HCT116 and HCT116+cinobufa-cini was collected to stimulate M0 type macrophages.The polarization of M2 type macrophages was observed by flow cytometry,real-time quantitative PCR and ELISA experiments.The conditioned media of HCT116-Mφ cells and(HCT116+cinobufacini)-Mφ cells were collected to stimulate HCT116 cells.The changes of migration and inva-sion ability were observed by wound healing assay and Transwell assay.Results After stimulation of M0 type mac-rophages in HCT116 cell conditioned medium,the morphology of M0 macrophages turned into fusiform cells,the proportion of CD11b+CD206+cells increased,and the expression of M2 macrophage markers IL-10 and TGF-β in-creased.The migration and invasion ability of HCT116 cells were significantly enhanced after stimulation in the conditioned medium of HCT1 16-Mφ cells.After the addition of cinobufacini,not only the polarization proportion of M2 macrophages decreased,but also the metastatic effect mediated by M2 macrophages was inhibited.Conclusion HCT116 cells can induce the polarization of M2 macrophages,while cinobufacini can inhibit the tumor metastasis mediated by M2 macrophages by inhibiting the polarization of M2 macrophages.

Objective: To examine the association of hypertension onset age with diabetes, so as to provide insights into reducing the the risk of cardiovascular events. Methods: Permanent residents aged 35 to 75 years were selected through the program of early screening and comprehensive intervention for the high-risk cardiovascular disease population in Changning District and Baoshan District, Shanghai Municipality from 2016 to 2020. Demographic information, disease history, hypertension onset age, blood pressure and fasting blood glucose were collected through questionnaire surveys, physical examination and laboratory tests. The residents were divided into four groups based on the onset age of hypertension: <45, 45-<55, 55-<65 and ≥65 years old, and the residents with normal blood pressure were selected as control. The association of hypertension onset age with prediabetes and diabetes were identified using a multivariable logistic regression model. Results: A total of 25 228 residents were recruited, including 8 753 males (34.70%) and 16 475 females (65.30%). The prevalence of hypertension was 43.80%. There were 1 779, 3 274, 3 781 and 2 217 cases with hypertension onset age of <45, 45-<55, 55-<65 and ≥65 years old, respectively, and 14 177 residents with normal blood pressure. The prevalence of prediabetes and diabetes were 24.01% and 11.29%, respectively. Multivariable logistic regression analysis showed that after adjusting for confounding factors such as gender, marital status and educational level, compared with the normal blood pressure group, the risk of prediabetes was higher in the hypertension onset age groups of <45 (OR=1.345, 95%CI: 1.164-1.553), 45-<55 (OR=1.365, 95%CI: 1.212-1.536) and 55-<65 years old (OR=1.376, 95%CI: 1.239-1.527), and the risk of diabetes was higher in the hypertension onset age groups of <45 (OR=2.302, 95%CI: 1.906-2.775), 45-<55 (OR=2.349, 95%CI: 2.016-2.734), 55-<65 (OR=1.909, 95%CI: 1.667-2.184) and ≥65 years old (OR=1.315, 95%CI: 1.131-1.526). Conclusion There are statistically significant associations between hypertension onset age with prediabetes and diabetes.

Purpose To analyze the application value of enhanced T2* weighted angiography(ESWAN)quantitative parameters in predicting the invasiveness of cystic gland tumors.Materials and Methods A total of 81 patients with ovarian cystadenoma confirmed by pathological examination in Central Hospital of Xuancheng City,Anhui Province from June 2018 to June 2023 were retrospective selected.All patients underwent pelvic MRI examination(including ESWAN sequence).The ESWAN data was processed to obtain amplitude,phase,R2* and T2*values,and the quantitative intratumoral susceptibility signal(ITSS)ratio was automatically obtained using AnatomySketch software.According to the invasiveness of ovarian cystic gland tumors,they were divided into malignant cystic gland tumor group and benign cystic gland tumor group(including benign and borderline cystic gland tumors).The differences in various parameters between the two groups were compared,and the receiver operating curve was used to evaluate the predictive efficacy of each parameter on the invasiveness of ovarian cystic gland tumors.Results Among the 81 patients with ovarian cystic tumors,29 patients were in the malignant cystic tumor group,with an incidence rate of 35.80%.The CA-125,R2* values and ITSS ratio in the malignant cystic gland tumor group were higher than those in the benign cystic gland tumor group,and the differences were statistically significant(t=15.153,14.006,8.200,all P<0.05).The R2* value(OR=3.464,95%CI 1.712-7.008,P=0.001)and ITSS ratio(OR=8.376,95%CI 1.399-14.519,P=0.002)were independent risk factors for the occurrence of malignant ovarian cystadenoma(OR>1,P<0.05);the optimal critical values for R2* value,ITSS ratio and their combined prediction of malignant ovarian cystic tumors were 5.700,0.165 and 0.557,respectively.The area under the curve was 0.942,0.870 and 0.975,respectively.The sensitivity was 82.80%,82.80%and 89.70%,and the specificity was 96.20%,75.00%and 98.10%.Conclusion R2* value and ITSS ratio are independent predictive molecules for malignant cystic tumors,and their combination can enhance the predictive efficacy of invasiveness in ovarian cystic tumors.

Increasing evidences suggest the important role of calcium homeostasis in hallmarks of cancer, but its function and regulatory network in metastasis remain unclear. A comprehensive investigation of key regulators in cancer metastasis is urgently needed. Transcriptome sequencing (RNA-seq) of primary esophageal squamous cell carcinoma (ESCC) and matched metastatic tissues and a series of gain/loss-of-function experiments identified potassium channel tetramerization domain containing 4 (KCTD4) as a driver of cancer metastasis. KCTD4 expression was found upregulated in metastatic ESCC. High KCTD4 expression is associated with poor prognosis in patients with ESCC and contributes to cancer metastasis in vitro and in vivo. Mechanistically, KCTD4 binds to CLIC1 and disrupts its dimerization, thus increasing intracellular Ca²⁺ level to enhance NFATc1-dependent fibronectin transcription. KCTD4-induced fibronectin secretion activates fibroblasts in a paracrine manner, which in turn promotes cancer cell invasion via MMP24 signaling as positive feedback. Furthermore, a lead compound K279-0738 significantly suppresses cancer metastasis by targeting the KCTD4‒CLIC1 interaction, providing a potential therapeutic strategy. Taken together, our study not only uncovers KCTD4 as a regulator of calcium homeostasis, but also reveals KCTD4/CLIC1-Ca²⁺-NFATc1-fibronectin signaling as a novel mechanism of cancer metastasis. These findings validate KCTD4 as a potential prognostic biomarker and therapeutic target for ESCC.

OBJECTIVE：To study the composition and contents of flavonoids chemical components in waste material during industrialization of Pueraria thomsonii resources，and to provide reference for comprehensive development and reasonable utilization of the variety. METHODS ：Using“No. 2 Gange”of P. thomsonii from Jiangxi as objects ，UPLC-Q-TOF-MS and HPLC method were adopted to detect the components and contents of flavonoids in the root （with or without cortex ），cortex，flower， fibrous root ，stem，head and dregs （with or without cortex ）of P. thomsonii as well as dry matter of industrial wastewater （with or without cortex ）after precipitation of pueraria powder. RESULTS ：The linearity ，precision，repeatability，stability and recovery of the established method for content determination of 7 flavonoids（puerarin，daidzin，iridoxine-7-O-xylose glucoside ，genistin， iridin，daidzein and kakkalide ）were all in line with the requirements. Totally 12 kinds of flavonoids were identified ，among which the flavonoids in the root ，cortex，stem，fibrous root ，head and dregs of P. thomsonii as well as dry matter of industrial wastewater were the same ，mainly were puerarin ，daidzin，genistein，daidzein and malonyl-daidzein. The flower of P. thomsonii mainly included iridoxine- 7-O-xylose glucoside ，genistin，iridin，kakkalide，6″-O-xylosyldaidzein，but the components as puerarin ， daidzin and its aglycone were not be detected. The content of puerarin in the head of P. thomsonii was the highest （5.765％）. The contents of puerarin in root and dregs of P. thomsonii as well as dry matter of industrial waste-water in samples with cortex were all higher than in corresponding peeled sample. CONCLUSIONS ：The waste material from the industrialization of P. thomsonii resources contains a lot of flavonoids with rich species and high content ，and can be used as an important raw material for obtaining flavonoids such as puerarin.

Objective    To discuss the diagnosis and treatment of culture-negative aortic infective endocarditis. Methods    The clinical data of 73 patients with infective endocarditis of the aortic valve whose results of bacteria culture were negative from January 2013 to January 2018 were retrospectively analyzed, including 59 males and 14 females aged 14-71 (39.2±14.8) years. Results    Sixty seven (91.8%) patients received aortic valve replacement, 2 (2.7%) patients received the second operation in hospital, and 12 (16.4%) patients had concomitant mitral valvuloplasty. In-hospital death occurred in 8 (11.0%) patients. Postoperatively, 11 (20.7%) patients had a low cardiac output and 4 (11.0%) patients had heart block, and 1 patient required implantation of a permanent pacemaker. The 1- and 5- year survival rates were 92.3%±2.3% and 84.5%±4.5%, respectively. Conclusion    There are difficulties in the diagnosis and treatment of culture-negative infective endocarditis. Most of the affected patients are in a healed status, which could be a cause of negative culture results. In-hospital mortality in the patients is associated with a history of previous cardiac surgery, whereas the long-term survival rate is good for the patients after surgery.

Objective To firstly report the clinical features,diagnosis and treatment response of patients with anti-γ-aminobutyric acid type A receptor (GABAAR) encephalitis in China,thus raising neurologists' awareness of this emerging type of autoimmune encephalitis.Methods Specific anti-GABAAR autoantibodies in the serum and cerebrospinal fluid (CSF) of patients with suspected autoimmune encephalitis but negative for commercial available antibody tests were detected by live cell-based assay (CBA).The clinical features,laboratory examinations and treatment of two cases of autoimmune encephalitis with anti-GABAAR autoantibodies were analyzed,who admitted to Huashan Hospital,Fudan University between 2013 and 2014.Results By using live CBA,serum and CSF of the two patients diagnosed with possible autoimmune encephalitis both contained autoantibodies targeted to the GABAAR.These two patients had onset symptom of seizure or refractory seizures.Memory impairment,psychiatric symptoms and decreased consciousness were also presented.One patient was combined with mass in anterior superior mediastinum.Both patients had multifocal cortical and subcortical T2 /fluid attenuated inversion recovery-weighted images hyperintensity signal on brain magnetic resonance imaging.The two patients had poor response to antiepileptic drugs,but showed noticeable recovery with sufficient immunotherapeutic treatments.Conclusions Anti-GABAAR encephalitis is characterized by prominent epilepsy and multifocal abnormalities on brain magnetic resonance imaging.Autoantibodies specifically against GABAAR could be detected by CBA in this group of patients.Early diagnosis and immunotherapy are critical to improve clinical symptoms and outcomes of the disease.

OBJECTIVE： To provide reference for the development and sustainable utilization of TCM industry with regional characteristics. METHODS： Taking Shicheng county of Jiangxi province as an example， field investigation was carried out on Paeoniaceae suffruticosa planting base in the county， a few representative P. suffruticosa planting bases in the county were selected as sample points， and GPS was used to locate and record the location information of sample points. The remote sensing image was automatically extracted by computer， the artificial visual interpretation method was used to get P. suffruticosa planting area image. Then combined with the field inspection verification， P. suffruticosa planting area was obtained， and the investigation results were analyzed. RESULTS： Through remote sensing interpretation of the planting area of P. suffruticosa in Shicheng county， it was obtained that the total planting area of P. suffruticosa in Shicheng county was 42 597 951.505 square meters （63 864.995 mu） in 2018， accounting for about 33％ of the cultivated land area， which was 42.12％ higher than the conventional planting area of 44 936 mu in 2013. The distribution of P. suffruticosa planting in Shicheng county was mainly concentrated in Xiaosong town and Fengshan town in the north， and Daqu town and Pingshan town in the south. CONCLUSIONS： Remote sensing technology has the advantages of fast data acquisition， large amount of information， high accuracy and strong timeliness， which greatly avoids the complexity of work， saves a lot of manpower and material resources. The technology can provide technology support for obtaining the regional planting area and distribution information of TCM such as P. suffruticosa， dynamic monitoring， scientific warning of the market status of TCM， and guiding the large-scale， standardized and intensive development of TCM cultivation.

OBJECTIVE： To establish a method to determine the contents of rhynchophylline and isorhynchophylline in Uncaria rhynchophylla. METHODS： The separation degree of ionic liquid 1-butyl-3-methylimidazolium chloride （C4mimCl） as mobile phase additive was compared with that of mobile phase without additives and with traditional additive triethylamine （which damaged the chromatographic column）. The optimum concentration of C4mimCl was screened and the contents of rhynchophylline and isorhynchophylline in U. rhynchophylla from 4 habitats in Jiangxi province were determined by the newly established method. The determination was performed on Dikmatech Diamonsil Plus C18 column， the mobil phase was acetonitrile-buffer （0.1％ phosphoric acid+3.0 mmol/L C4mimCl）， gradient elution. UV detection wavelength was set at 245 nm and the flow rate was 1    mL/min. Sample size was 10 μL. RESULTS： When mobile phase had no additives or 3.0 mmol/L triethylamine and 3.0 mmol/L C4mimCl were added as additives， the separation of rhynchophylline from the front peak was 1.02， 1.23 and 1.72， and the separation from the back peak was 1.06， 6.00 and 4.25， respectively. The symmetry factors were 0.81， 0.86 and 1.13， respectively. The separation of isorhynchophylline from the front peak was 0.96， 3.89 and 4.05， and the separation from the back peak was 1.02， 2.34 and 2.36， respectively. The symmetry factors were 0.88， 0.81 and 0.96， respectively. The linear range of rhynchophylline and isorhynchophylline were 4.93-157.76 （r＝0.999 9） and 4.98-159.50 μg/mL （r＝1.000）， respectively. The quantitative limits were 0.486 4， 0.793 6 μg/mL， respectively. RSDs of precision， repeatability， stability and durability tests were all less than 5％ （n＝6）. The recovery rates were 102.9％-107.8％ （RSD＝1.7％，n＝6） and 95.4％-106.3％ （RSD＝3.9％，n＝6）， respectively. The content of rhynchophylline and isorhynchophylline in U. rhynchophylla from 4 habitats were 0.758-1.343         and 1.511-1.823 mg/g， respectively. CONCLUSIONS： Addition of C4mimCl into mobile phase can enhance its separation. Established HPLC method is rapid， accurate and reproducible， which can be used for content determination of rhynchophylline and isorhynchophylline in U. rhynchophylla.

Objective To investigate the diagnostic value of digital tomosynthesis in Schatzker classification of tibial plateau fractures.Methods A total of 43 patients with tibial plateau fractures who had underwent injured knee joints coronal tomosynthesis examinations and as well as digital radiography (DR) examinations including anteroposterior and lateral positions before the surgery were selected from January to June 2015.The imaging evaluation was performed by two diagnostic radiologists independently.Each radiologist consecutively performed Schatzker classification of the DR and tomosynthesis images of the knees of each patient.The consistent Schatzker classification results were finally given,while the inconsistent classification results were discussed.Recording the reading results of two methods and comparing the classification results of two methods with the subsequent intra-operative classification results,evaluating their consistency.Results Twenty-eight patients were included with 14 males and 14 females.The age ranged from 25 to 76 years old with an average of 48.5 years.Fifteen patients were excluded due to combined injuries and the low quality of imaging.Schatzker classification of tibial plateau fractures was performed with DR images,19 cases of fracture classification results were consistent with intra-operative classification,and 9 cases were inconsistent.Twenty-six cases of fracture classification results were consistent with intra-operative classification based on tomosynthesis images but 2 cases with inconsistent results.Intra-operative findings for each fracture were used as the gold standard for classification.The accuracy of the Schatzker classification for tibial plateau fractures were 68％ and 93％ in the two imaging techniques with significant difference (x2=5.143,P=0.016),respectively.The classification results of two imaging methods in 2 patients were both inconsistent with intra-operative classification.The fracture severity of 6 patients was underestimated when using DR images for interpretation,while 1 patient had a missed diagnosis of the lateral tibial plateau collapsed fracture.The consistency between the classification results of DR images as well as classification results of tomosynthesis images and intra-operative typing were moderately and highly consistent,respectively (Kappa coefficient were 0.604 and 0.908,respectively).Conclusion Schatzker classification of tibial plateau fractures was performed with DR images,the lateral tibial plateau collapsed fracture and the lateral plateau splitting fracture could be easily missed or misdiagnosed.However,tomosynthesis imaging could provide a higher accuracy.