Objective:To investigate the inpact of thyroid cancer-derived cancer-associated fibroblasts(CAF) autophagy on papillary thyroid cancer(PTC).Methods:CAF and normal fibroblasts were isolated from cancerous and adjacent normal thyroid tissues from four PTC patients. Expressions of fibroblast activation protein(FAP) and α-smooth muscle actin in cells were assessed. Conditioned medium of CAF and normal fibroblasts were prepared and used to culture PTC cells. The effects of CAF and normal fibroblasts on survival, proliferation, migration, invasion and iodine uptake of PTC cells were evaluated through cell proliferation assay, cell scratch assay, cell invasion assay, and cell iodine uptake assay. The autophagy level of CAF was also evaluated. Autophagy inhibition and activation were used to regulate the autophagy of CAF, and then their effects on PTC cell proliferation, migration and invasion were further evaluated. The in vivo effect of CAF autophagy on PTC xenograft tumor growth was evaluated.Results:CAF exhibited higher FAP expression and basal autophagy levels. PTC cells co-cultured with CAF-conditioned media showed enhanced proliferation, migration, invasion, and reduced iodine uptake. Autophagy inhibition reduced these effects, while autophagy activation further promoted them. In vivo, inhibiting CAF autophagy suppressed tumor growth.Conclusions:CAF promotes PTC cell malignancy through autophagy activation, enhancing proliferation, migration, and invasion while reducing iodine uptake.

Objective:To develop and evaluate a nomogram prediction model for poor outcome of lower extremity motor function in patients with acute ischemic stroke (AIS) at 90 days after onset.Methods:Patients with AIS admitted to Guangzhou Province Hospital of Chinese Medicine from January to October 2024 were included retrospectively. At 90 days after onset, Functional Ambulation Category (FAC) was used for outcome evaluation. ≥4 was defined as good outcome and <4 was defined as poor outcome. Multivariate logistic regression analysis was used to identify the independent predictive factors for poor outcome of lower extremity motor function, and develop a nomogram prediction model. The area under the receiver operating characteristic curve, calibration curve, and clinical decision curve were used to evaluate the predictive model. Results:A total of 325 patients with AIS were enrolled, including 214 males (65.8%), median aged 62 years (interquartile range, 54-71 years); 158 patients (48.6%) had poor outcome of lower extremity motor function. Multivariate logistic regression analysis showed that older age (odds ratio [ OR] 1.037, 95% confidence interval [ CI] 1.011-1.065]; P=0.007) and a higher baseline National Institutes of Health Stroke Scale (NIHSS) score ( OR 1.472, 95% CI 1.336-1.637; P<0.001) were the independent predictors of poor outcome, while intravenous thrombolysis ( OR 0.195, 95% CI 0.080-0.443; P<0.001) and early rehabilitation intervention ( OR 0.444, 95% CI 0.231-0.850; P=0.014) were the independent predictors of good outcome. The area under the receiver operating characteristic curve of the nomogram prediction model developed using the above factors was 0.906 (95% CI 0.872-0.940), indicating that the model had good discriminability. The calibration curve fits well with the ideal curve. The clinical decision curve showed that the model had stronger clinical practicality. Conclusion:The nomogram developed by age, intravenous thrombolysis, early rehabilitation intervention, and baseline NIHSS score can effectively predict the risk of poor outcome of lower extremity motor function in patients with AIS and has higher clinical value.

Objective:To investigate the inpact of thyroid cancer-derived cancer-associated fibroblasts(CAF) autophagy on papillary thyroid cancer(PTC).Methods:CAF and normal fibroblasts were isolated from cancerous and adjacent normal thyroid tissues from four PTC patients. Expressions of fibroblast activation protein(FAP) and α-smooth muscle actin in cells were assessed. Conditioned medium of CAF and normal fibroblasts were prepared and used to culture PTC cells. The effects of CAF and normal fibroblasts on survival, proliferation, migration, invasion and iodine uptake of PTC cells were evaluated through cell proliferation assay, cell scratch assay, cell invasion assay, and cell iodine uptake assay. The autophagy level of CAF was also evaluated. Autophagy inhibition and activation were used to regulate the autophagy of CAF, and then their effects on PTC cell proliferation, migration and invasion were further evaluated. The in vivo effect of CAF autophagy on PTC xenograft tumor growth was evaluated.Results:CAF exhibited higher FAP expression and basal autophagy levels. PTC cells co-cultured with CAF-conditioned media showed enhanced proliferation, migration, invasion, and reduced iodine uptake. Autophagy inhibition reduced these effects, while autophagy activation further promoted them. In vivo, inhibiting CAF autophagy suppressed tumor growth.Conclusions:CAF promotes PTC cell malignancy through autophagy activation, enhancing proliferation, migration, and invasion while reducing iodine uptake.

Objective:To investigate the mechanism of benzyl isothiocyanate(BITC) in the treatment of anaplastic thyroid cancer(ATC).Methods:Using network pharmacological analysis, key targets of BITC and ATC were screened, followed by GO and KEGG enrichment analysis. In order to validate the findings, AutoDock software was used to dock BITC and ATC key targets. BITC was applied to two ATC cell lines(8505C and CAL-62). Flow cytometry was used to analyze cell apoptosis. Autophagy inhibitors hydroxychloroquine sulfate(HCQ) and 3-methyladenine(3MA) were used in combination with BITC. Real-time quantitative PCR was conducted to detect the gene level of LC3B, while Western blotting was utilized to examine the expression of NF-κB, LC3B Ⅱ, Beclin-1, and Bcl-2. In animal experiments, a mouse tumor model was constructed using CAL-62 cells, treated with intraperitoneal injections of BITC(100 mg/kg) and normal saline respectively, administered every other day for a total of 21 days. Immunoblotting of tumor tissue was performed to detect the expression of LC3B Ⅱ, Bcl-2, Beclin-1, and NF-κB.Results:A total of 10 key targets with binding energies≤-4.0 kcal/mol were identified. KEGG analysis showed that these genes are mainly involved in NF-κB signaling pathway and apoptosis. BITC inhibited ATC cells with IC50 values of 27.56 μmol/L for 8505C and 28.30 μmol/L for CAL-62. The expression levels of NF-κB, Beclin-1, and Bcl-2 decreased, while LC3B Ⅱ and LC3B gene expression increased. Combining 3MA with BITC enhanced cell inhibition LC3B Ⅱ expression. HCQ increased LC3B Ⅱ expression without enhancing cell and viability inhibition. In the mouse tumor model, compared to the control group, the treatment group had higher LC3B Ⅱ and lower Bcl-2, Beclin-1, and NF-κB levels.Conclusion:BITC could inhibit the growth of ATC cells in vitro and in vivo, disrupt the autophagy degradation, and inhibit the NF-κB pathway.

Objective:To explore the feasibility of radical prostatectomy without biopsy for patients with highly suspected localized prostate cancer diagnosed by multiparametric magnetic resonance imaging (mpMRI) and 68Ga-PSMA PET/CT. Methods:Patients were enrolled in this single-arm prospective study from March 2019 to January 2022 in the Second Hospital of Tianjin Medical University. Eligible patients were aged ≤80 years with an Eastern Cooperative Oncology Group (ECOG) performance-status score of 0 or 1. Based on mpMRI and 68Ga-PSMA PET/CT, patients were diagnosed with highly suspected localized prostate cancer with no evidence of distant lymphatic, bone or visceral metastases. Patients were excluded if they had obvious important organs dysfunction, suspected metastatic lesions or history of other malignant tumor. After fully informed of the surgical risks and possibilities of final pathology, patients received laparoscopic or robot-assisted laparoscopic radical prostatectomy. According to final pathological results, the diagnostic accuracy of mpMRI and 68Ga-PSMA PET/CT was evaluated. Pathological features were compared between low 68Ga-PSMA PET/CT maximum standardized uptake value (SUV max) group (SUV max<10) and high SUV max group (SUV max≥10). Baseline characteristics were compared between clinically significant prostate cancer (CsPCa) and clinically insignificant prostate cancer (cisPCa) + high grade prostatic intraepithelial neoplasia (HGPIN) patients. Additional analysis of the correlation between baseline parameters and different subgroups including pathological stage, ISUP grades and risk groups were performed in CsPCa patients. Results:31 patients were enrolled. Median age was 68 (ranging 48-79)years old. Median BMI was 25.6(ranging 21.9-31.4)kg/m 2. Median prostate specific antigen (PSA) was 23.5 (ranging 5.6-94.7)ng/ml. Median prostate volume was 37.6(ranging 16.2-127.9)ml. Median PSA density (PSAD) was 0.56(ranging 0.11-2.86)ng/ml 2. Fifteen cases were scored prostate imaging reporting and data system (PI-RADS) 4 and 16 cases were scored PI-RADS 5. Median 68Ga-PSMA PET/CT SUV max was 13.3 (ranging 4.6-36.7). All surgeries were successfully accomplished without open conversion. Median postoperative hospitalization time was 5 (ranging 4-7)d. No major complication occurred perioperatively. Recovery of urinary continence was within 6 months in all patients. According to the final pathological results, 1(3.2%) patient was confirmed with HGPIN. 30 (96.8%) patients were confirmed with adenocarcinoma, including 26 (86.7%) patients with CsPCa and 4(13.3%) patients with cisPCa. Among prostate cancer cases, the pathological stage of 11(36.7%) was T 2 and 19(63.3%) was T 3. Four(13.3%) cases were with ISUP grade 1, 7(23.3%) cases were with ISUP grade 2, 7(23.3%) cases were with ISUP grade 3 and 12 (40.0%) cases were with ISUP grade≥4.Two(6.7%) cases were in low risk group, 3(10.0%) cases were in intermediate risk group and 25 (83.3%) cases were in high risk group. Twelve(40.0%) patients had positive surgical margins. Standard pelvic lymph node dissection was carried out in 18 (17 prostate cancer and 1 HGPIN) cases. Sixty-two lymph nodes were dissected and none of them was positive. The diagnostic accuracy of mpMRI and 68Ga-PSMA PET/CT was 96.8%(30/31) in prostate cancer. Compared to low SUV max group, patients in high SUV max group had higher ISUP grade ( P=0.003) but there was no significant difference in positive surgical margin, seminal vesical invasion or pathological stage ( P>0.05). Among CsPCa patients, 10 (38.5%) cases were scored PI-RADS 4 and 16(61.5%) cases were scored PI-RADS 5. Median 68Ga-PSMA PET/CT SUV max was 14.3 (range 6.1-36.7). Compared to cisPCa and HGPIN patients, a smaller median prostate volume (34.3 vs. 73.0 ml, P=0.006), higher median PSAD (0.70 vs. 0.13 ng/ml 2, P=0.001), higher rates of PI-RADS 5 patients (61.5% vs. 0, P=0.018) and higher 68Ga-PSMA PET/CT SUV max (14.3 vs. 6.1, P=0.001) were found in CsPCa patients. Subgroup analysis showed no significant difference between SUV max and pathological stage (25.5 vs. 13.9), ISUP grades (15.4 vs. 14.4 vs. 14.0) and risk groups (9.7 vs. 14.9) in CsPCa patients ( P>0.05). Conclusions:The diagnostic accuracy of mpMRI and 68Ga-PSMA PET/CT is high in prostate cancer. With efficient communication, radical prostatectomy without biopsy for patients with highly suspected localized prostate cancer diagnosed by mpMRI and 68Ga-PSMA PET/CT is safe.

Coronavirus disease 2019(COVID-19),which is caused by SARS-CoV-2,varies with regard to symptoms and mortality rates among populations.Humoral immunity plays critical roles in SARS-CoV-2 infection and recovery from COVID-19.However,differences in immune responses and clinical features among COVID-19 patients remain largely unknown.Here,we report a database for COVID-19-specific IgG/IgM immune responses and clinical parameters(named COVID-ONE-hi).COVID-ONE-hi is based on the data that contain the IgG/IgM responses to 24 full-length/truncated proteins corresponding to 20 of 28 known SARS-CoV-2 proteins and 199 spike protein peptides against 2360 serum samples collected from 783 COVID-19 patients.In addition,96 clinical parameters for the 2360 serum samples and basic information for the 783 patients are integrated into the database.Furthermore,COVID-ONE-hi provides a dashboard for defining samples and a one-click analysis pipeline for a single group or paired groups.A set of samples of interest is easily defined by adjusting the scale bars of a variety of parameters.After the"START"button is clicked,one can readily obtain a comprehensive analysis report for further interpretation.COVID-ONE-hi is freely available at www.COVID-ONE.cn.

Objective: Comparing the benefit of Abidor, lopinavir/ritonavir and recombinant interferon α-2b triple combination antiviral therapy and lopinavir/ritonavir and interferon dual combination antiviral therapy to hospitalized novel coronavirus pneumonia 2019 in Zhejiang province. Methods: A multi-center prospective study was carried out to compare the effect of triple combination antiviral therapy with dual combination antiviral therapy in 15 medical institutions of Zhejiang Province. All patients were treated with recombinant interferon α-2b (5 million U, 2 times/d) aerosol inhalation. 196 patients were treated with abidol (200 mg, 3 times/d) + lopinavir / ritonavir (2 tablets, 1 time/12 h) as the triple combination antiviral treatment group. 41 patients were treated with lopinavir / ritonavir (2 tablets, 1 time/12 h) as the dual combination antiviral treatment group. The patients who received triple combination antiviral therapy were divided into three groups: within 48 hours, 3-5 days and > 5 days after the symptom onset. To explore the therapeutic effects of triple combination antiviral drugs and dual combination antiviral drugs, as well as triple combination antiviral drugs with different antiviral initiate time. SPSS17.0 software was used to analyze the data. Results: The time of virus nucleic acid turning negative was (12.2 ± 4.7) days in the triple combination antiviral drug group, which was shorter than that in the dual combination antiviral drug group [(15.0 ± 5.0) days] (t = 6.159, P < 0.01 ). The length of hospital stay [12 (9, 17) d] in the triple combination antiviral drug group was also shorter than that in the dual combination antiviral drug group [15 (10, 18) d] (H = 2.073, P < 0.05). Comparing the antiviral treatment which was started within 48 hours, 3-5 days and > 5 days after the symptom onset of triple combination antiviral drug group, the time from the symptom onset to the negative of viral shedding was 13 (10,16.8), 17 (13,22) and 21 (18-24) days respectively (Z = 32.983, P < 0.01), and the time from antiviral therapy to the negative of viral shedding was (11.8±3.9) , (13.5±5.1) and (11.2±4.3) d. The differences among the three groups were statistically significant (Z=32.983 and 6.722, P<0.01 or<0.05). Conclusions The triple combination antiviral therapy of Abidor, Lopinavir/Litonavir and recombinant interferon α-2b showed shorter viral shedding time and hospitalization time compared with the dual combination antiviral therapy. The earlier the time to initiate triple antiviral treatment, the shorter the time of virus shedding.

Objective: To identify the characteristics including clinical features and pulmonary computed tomography (CT) features of heart failure and novel coronavirus pneumonia(COVID-19). Methods: This study was a retrospective study. A total of 7 patients with Heart failure and 12 patients with COVID-19 in the Second Xiangya Hospital of Central South University between December 1, 2019 and February 15, 2020 were enrolled. The baseline clinical and imaging features of the two groups were statistically analyzed. Results: There was no significant difference in age and sex between the two groups, but the incidence of epidemiological contact history, fever or respiratory symptoms in the COVID-19 group was significantly higher than that in the heart failure group (12/12 vs. 2/7, P=0.001; 12/12 vs. 4/7, P<0.001). While the proportion of cardiovascular diseases and impaired cardiac function was significantly less than that of the heart failure group(2/12 vs.7/7, P<0.001; 0/12 vs.7/7, P<0.001). For imaging features, both groups had ground-glass opacity and thickening of interlobular septum, but the ratio of central and gradient distribution was higher in patients with heart failure than that in patients with COVID-19 (4/7 vs. 1/12, P=0.04). In heart failure group, the ratio of the expansion of small pulmonary veins was also higher (3/7 vs. 0, P=0.013), and the lung lesions can be significantly improved after effective anti-heart failure treatment. Besides, there are more disease with rounded morphology in COVID-19 (9/12 vs. 2/7, P=0.048) . Conclusions More patients with COVID-19 have epidemiological history and fever or respiratory symptoms. There are significant differences in chest CT features, such as enlargement of pulmonary veins, lesions distribution and morphology between heart failure and COVID-19.

Objective:To compare the efficacy of the combination of abidol, lopinavir/ritonavir plus recombinant interferon α-2b (rIFNα-2b) and the combination of lopinavir/ritonavir plus rIFNα-2b for patients with COVID-19 in Zhejiang province.Methods:A multicenter prospective study was carried out to compare the efficacy of triple combination antiviral therapy and dual combination antiviral therapy in 15 medical institutions of Zhejiang province during January 22 to February 16, 2020. All patients were treated with rIFNα-2b (5 million U, 2 times/d) aerosol inhalation, in addition 196 patients were treated with abidol (200 mg, 3 times/d) + lopinavir/ritonavir (2 tablets, 1 time/12 h) (triple combination group) and 41 patients were treated with lopinavir/ritonavir (2 tablets, 1 time/12 h) (dual combination group). The patients who received triple combination antiviral therapy were further divided into three subgroups: <48 h, 3-5 d and >5 d according the time from the symptom onset to medication starting. The therapeutic efficacy was compared between triple combination group and dual combination group, and compared among 3 subgroups of patients receiving triple combination antiviral therapy. SPSS 17.0 software was used to analyze the data.Results:The virus nucleic acid-negative conversion time in respiratory tract specimens was (12.2±4.7) d in the triple combination group, which was shorter than that in the dual combination group [(15.0±5.0) d] ( t=6.159, P<0.01). The length of hospital stay in the triple combination group [12.0 (9.0, 17.0) d] was also shorter than that in the dual combination group [15.0 (10.0, 18.0) d] ( H=2.073, P<0.05). Compared with the antiviral treatment which was started within after the symptom onset of in the triple combination group, the time from the symptom onset to the viral negative conversion was 13.0 (10.0, 17.0), 17.0 (13.0, 22.0) and 21.0 (18.0, 24.0) d in subgroups of 48 h, 3-5 d and >5 d, respectively ( Z=32.983, P<0.01), while the time from antiviral therapy to viral negative conversion was (11.8±3.9), (13.5±5.1) and (11.2±4.3) d, respectively( Z=6.722, P<0.05). Conclusions:The triple combination antiviral therapy of abidol, lopinavir/litonavir and rIFNα-2b shows shorter viral shedding time and shorter hospitalization time, compared with the dual combination antiviral therapy; and the earlier starting triple combination antiviral therapy will result in better antiviral efficacy.

Objective Comparison of induction time on the proliferation of induced adipose-derived stem cells (ADSC) to differentiate into Schwann-like cells (iSC).Methods From March,2017 to October,2018,ADSCs were isolated from inguinal adipose tissue of healthy adult female SD rats.Flow cytometry was performed to detect ADSC positive markers CD29,CD90 and negative marker CD45.iSC induction medium was used to culture ADSC.S-100 and GFAP were detected by immunofluorescence staining to confirm that ADSC had differentiated into iSC.Morphological changes of cells were observed by inverted microscope on day 1st,4th,7th,10th,13rd,16th and 19th after induction.MTS assay was used to evaluate cell proliferation ability.Tunel staining was applied to assess cell apoptosis.Results Both S100 and GFAP were expressed in iSC.On day 7th,the cell proliferation rate was significantly slower than that before induction (A value was 0.330±0.020 vs.0.400±0.004,P＜0.05).It was negatively correlated with induction time.On day 19th,the proliferation rate of iSC was lower than 50％ of the proliferation rate before induction (A value was 0.016±0.003 vs.0.400±0.004,P＜0.05).Apoptosis of iSC was more obvious than ADSC at the same time point.Conclusion The proliferation ability of ADSC-induced iSC is optimal within 7 days after induction.