[The effect of Hashimoto's thyroiditis on the diagnostic efficacy of ultrasound-guided fine needle aspiration cytology for thyroid nodules ≥ 1 cm].

Objective:To explore the diagnostic efficacy of ultrasound-guided fine needle aspiration cytology（US-FNAC） for thyroid nodules ≥1 cm, and the effect of Hashimoto's thyroiditis（HT） on it. Methods:The clinical data of 1027 cases of thyroid nodules ≥ 1 cm were retrospectively analyzed. Two-dimensional ultrasound, US-FNAC and BRAFV600E gene testing were performed. The postoperative pathological results were used as the criterion. The two dimensional ultrasound examination, clinical characteristics, follow-up results, and BRAFV600E were used to diagnosis for unoperated patients. The diagnostic efficiency of US-FNAC in HT（+） group and HT（-） group was compared, and the factors affecting the diagnostic efficiency were analyzed. Results:Of the 1027 nodules, the cytological results were nondiagnostic/unsatisfactory in 73 nodules（7.1%）, benign in 282（27.5%）, atypia of undetermined significance/follicular lesion of undetermined significance in 230（22.4%）, follicular neoplasm/suspicious for a follicular neoplasm in 20（1.9%）, suspicious for malignancy in 120（11.7%）, and malignant in 302（29.4%）. 515 cases underwent surgery. Among them, 495 were malignant and 20 were benign. 512 cases continued to be followed up without surgery, and the BRAFV600E of them were wild type. Combined with the two dimensional ultrasound examination, clinical features, and follow-up results, they were judged to be benign. The accuracy, sensitivity, specificity, positive predictive value, negative predictive value, false positive rate and the false negative rate the of US-FNAC were 98.7%, 98.4%, 99.3%, 99.5%, 97.5%, 0.7% and 1.6%, respectively. The accuracy, sensitivity and negative predictive value of the HT（+） group were 95.5%, 95.4% and 82.8%, respectively, which were lower than that of HT（-） group （99.5%, 99.4%, 99.2% ）（P=0.001, 0.018, P<0.001）. The false negative rate of the HT（+） group was 4.6%, higher than 0.6% of the HT（-） group（P=0.018）, and HT was an risk factor for increased FNR（OR=7.596, 95%CI: 1.452-39.740）. Conclusion:US-FNAC is an effective method for the diagnosis of thyroid nodules and it has high sensitivity and specificity in ≥ 1 cm nodules. However, the combination of HT reduces the diagnostic accuracy and HT is a risk factor for increased false negative rate.

Neuroprotective Effect of Low-Intensity Pulsed Ultrasound on the Mouse MPTP/MPP+ Model of Dopaminergic Neuron Injury.

Ultrasound mediated neuromodulation has been demonstrated to a safe treatment strategy in the field of neuroscience. In this study, low-intensity pulsed ultrasound (LIPUS) was used to treat Parkinson's disease (PD) models induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 1-methyl-4-phenylpyridinium (MPP+) to explore the possibility of ultrasound neuroprotective effect on PD. The results demonstrated that LIPUS treatment can attenuate the central neurotoxicity of MPTP in mice, reduce the loss of tyrosine hydroxylase positive neurons in the substantia nigra pars compacta and decrease the apoptosis in the section of substantia nigra. The movement and balance dysfunctions in PD mice were improved with LIPUS treatment. In addition, we demonstrated that LIPUS can inhibit the decreased activity and increased apoptosis of dopaminergic neurons induced by MPP+, restrain the accumulation of reactive oxygen species (ROS) and decrease of mitochondrial membrane potential caused by MPP+. Moreover, LIPUS stimulation alone did not cause any cytotoxicity and tissue damage in our study. Taken together, the protective and regulatory effects of LIPUS on dopaminergic neurons make it possible as a new, safe and noninvasive treatment for PD.

Optimizing the Catheter Care and Maintenance Strategy of Short-Term Catheterization among Hospitalized Patients in Microbiological Approach.

OBJECTIVE: To optimize the allocation of nursing resources, we investigate an alternative strategy for indwelling catheter cleaning. METHODS: The present study involved a total of 117 male patients and 54 female patients, who were catheterized after urinary surgery from Aug 2018 to Feb 2019. The samples of indwelling catheter cleaning solutions were divided by two parts for microbiological culture and microbiome analysis. RESULTS: No pathogenic bacteria were observed in the microbiological culture of the indwelling catheter cleaning samples from 24 h-uncleaned group and 48 h-uncleaned group. The microbiome analysis also showed no significant difference in bacterial diversity and quantity of the indwelling catheter cleaning solutions between the two groups. CONCLUSION: The indwelling catheter cleaning for male after urinary surgery can be prolonged to 48 h. The result of this study provided reliable basis for optimizing the allocation of clinical nursing resources.

Type I IFN expression is stimulated by cytosolic MtDNA released from pneumolysin-damaged mitochondria via the STING signaling pathway in macrophages.

Pneumolysin (Ply), a major virulence factor of Streptococcus pneumoniae (S. pn), affects the immunity of host cells during infection. It has been reported that Ply is involved in S. pn standard strain D39-induced interferon-ß (IFN-ß) expression; however, other findings suggest that recombinant Ply protein is incapable of triggering IFN-ß expression. Here, we demonstrated that purified Ply was capable of initiating oxidative damage to mitochondria, resulting in the subsequent release of mitochondrial deoxyribonucleic acid (mtDNA), which mediated IFN-ß expression in macrophages. Importantly, we determined that IFN-ß expression was regulated by stimulator of interferon genes (STING) signaling in response to Ply. In conclusion, our study identified that IFN-ß production was triggered by Ply in macrophages and mtDNA released from Ply-damaged mitochondria mediated this process, through the STING pathway. This is a novel mechanism by which S. pn modulates type I IFN response in macrophages.

Pathologically examining a minimum of three lymph nodes could better determine node negativity in patients with non-metastatic chromophobe renal cell carcinoma.

OBJECTIVE: To evaluate the prognostic value of lymph node (LN) involvement for patients with chromophobe renal cell carcinoma (chRCC) and ascertain the minimum number of LNs that need to be pathologically examined to reliably diagnose a patient with node negative chRCC. METHODS: From 2004 to 2014, non-metastatic chRCC patients receiving radical nephrectomy together with lymphadenectomy were identified from the Surveillance, Epidemiology and End Results (SEER) database. The primary outcome was overall survival (OS). RESULTS: Two hundred and forty-six patients received lymph node dissection during the surgery. Of the patients, 24 (10%) had pathologically confirmed positive LN. Multivariate Cox regression model showed that positive LN was an independent unfavorable predictor for OS (HR = 2.83, 95%CI = 1.14-6.98, P = 0.024). More importantly, LN(-) patients with at least three LNs dissected had significantly better OS compared with when 1-2 LNs were examined (P = 0.048). Multivariate analysis confirmed that in LN(-) patients, the examination of three or more LNs could independently predict better OS compared with patients with only 1-2 LNs dissected (HR≥3LNs = 0.362, 95% CI = 0.135-0.972, P = 0.044). Additionally, the likelihood of finding at least one positive LN was significantly higher on dissection of ≥3 LNs compared with examination of 1-2 LNs (15% vs 5%, P = 0.018). Decision curve analysis found a better clinical validity of the '3 LNs examined'-based classification compared with the traditional LN(-)/LN(+) classification. CONCLUSION: The proportion of positive LNs in chRCC was far from neglectable and LN metastasis could independently predict unfavorable OS. We recommended a minimum of three LNs should be pathologically examined in order to reliably determine node negative.

Protective Regulatory T Cell Immune Response Induced by Intranasal Immunization With the Live-Attenuated Pneumococcal Vaccine SPY1 via the Transforming Growth Factor-ß1-Smad2/3 Pathway.

Vaccine effectiveness is mainly determined by the mechanism mediating protection, emphasizing the importance of unraveling the protective mechanism for novel pneumococcal vaccine development. We previously demonstrated that the regulatory T cell (Treg) immune response has a protective effect against pneumococcal infection elicited by the live-attenuated pneumococcal vaccine SPY1. However, the mechanism underlying this protective effect remains unclear. In this study, a short synthetic peptide (P17) was used to downregulate Tregs during immunization and subsequent challenges in a mouse model. In immunized mice, increase in immune cytokines (IL-12p70, IL-4, IL-5, and IL-17A) induced by SPY1 were further upregulated by P17 treatment, whereas the decrease in the infection-associated inflammatory cytokine TNF-α by SPY1 was reversed. P17 also inhibited the increase in the immunosuppressive cytokine IL-10 and inflammatory mediator IL-6 in immunized mice. More severe pulmonary injuries and more dramatic inflammatory responses with worse survival in P17-treated immunized mice indicated the indispensable role of the Treg immune response in protection against pneumococcal infection by maintaining a balance among acquired immune responses stimulated by SPY1. Further studies revealed that the significant elevation of active transforming growth factor ß (TGF-ß)1 by SPY1 vaccination activated FOXP3, leading to increased frequencies of CD4+CD25+Foxp3+ T cells. Moreover, SPY1 vaccination elevated the levels of Smad2/3 and phosphor-Smad2/3 and downregulated the negative regulatory factor Smad7 in a time-dependent manner during pneumococcal infection, and these changes were reversed by P17 treatment. These results illustrate that SPY1-stimulated TGF-ß1 induced the generation of SPY1-specific Tregs via the Smad2/3 signaling pathway. In addition, SPY1-specific Tregs may participate in protection via the enhanced expression of PD-1 and CTLA-4. The data presented here extend our understanding of how the SPY1-induced acquired Treg immune response contributes to protection elicited by live-attenuated vaccines and may be helpful for the evaluation of live vaccines and other mucosal vaccine candidates.

5-aminolevulinic acid (5-ALA) fluorescence-guided Mohs surgery resection of penile-scrotal extramammary Paget's disease.

This report aims to evaluate the usefulness of 5-aminolevulinic acid (5-ALA) fluorescence-guided Mohs surgery resection of penile-scrotal extramammary Paget's disease for achieving maximum tumor resection. Between January 2014 and December 2015, 5 patients underwent surgical resection of a penile-scrotal extramammary Paget's disease in department of urology, Huashan hospital, Fudan University. All patients were coated with 5-ALA (concentration of 20%) throughout the scrotum and the visible range of the lesion plus a 2cm margin 3 hours before the induction of anesthesia. 5-ALA fluorescence was visualized using an ultraviolet (UV) light at 405 nm. Surgical margin was determined in a standardized manner. The extent of resection was evaluated on the basis of frozen and histology sections. If the fluorescence positive punctate lesions were found outside the resection range, we removed the lesions and sent them for pathological examination. All data were prospectively collected, and the short- and long-term outcomes of the treatment strategy were analyzed. Lesions in the blue light turns red after irradiation, the fluorescence-guided surgery delineated range is less than the naked eye, intraoperative frozen prompted negative margins, postoperative pathological diagnosis. A total of 31 scattered lesions were found. After biopsy pathology prompted four were positive. In conclusion, 5-ALA fluorescence-guided minimum range can be completely removed in penile-scrotal Paget's lesions, and it is able to detect distant scattered lesions.

Targeting of COX-2 expression by recombinant adenovirus shRNA attenuates the malignant biological behavior of breast cancer cells.

BACKGROUND: Cyclooxygenase-2 (COX-2), considered to have tumor-promoting potential, is highly expressed in a variety of tumors, including breast cancer. Since the functions and action mechanisms of COX-2 in breast cancer have not been fully elucidated, in the present study, the effects of target inhibiting COX-2 with recombinant adenovirus Ad-COX-2-shRNA on malignant biological behavior were investigated in representative cell lines. MATERIALS AND METHODS: Breast cancer MDA-MB-231 and MCF-7 cells were transfected with Ad-COX-2-shRNA and COX-2 expression was tested by RT-PCR and Western blotting. Changes in proliferation, apoptosis and invasion of breast cancer cells were detected with various assays including MTT, colony forming, flowcytometry and Transwell invasion tests. The expression of related proteins involved in the cell cycle, apoptosis, invasion and signaling pathways was assessed by Western blotting. RESULTS: COX-2 expression was significantly reduced in both breast cancer cell lines infected with Ad-COX-2-shRNA, with obvious inhibition of proliferation, colony forming rate, G2/M phase passage and invasion, as well as induction of apoptosis, in MDA-MB-231 and MCF-7 cells, respectively. At the same time, proteins related to the cell cycle, anti-apoptosis and invasion were significantly downregulated. In addition, c-myc expression and phosphorylation activation of Wnt/ß-catenin and p38MAPK pathways were reduced by the Ad-COX-2-shRNA. CONCLUSIONS: COX-2 expression is associated with proliferation, apoptosis and invasion of breast cancer cells, and its mechanisms of action involve regulating expression of c-myc through the p38MAPK and Wnt/ß-catenin pathways.

Potential enhancement of intravenous nano-hydroxyapatite in high-intensity focused ultrasound ablation for treating hepatocellular carcinoma in a rabbit model.

The aim of the present study was to evaluate the safety and efficiency of an intravenously delivered nano-hydroxyapatite (Nano-HA) solution into a rabbit model (Oryctolagus cuniculus) to determine the potential enhancement of high-intensity focused ultrasound (HIFU) for the ablation of hepatocellular carcinoma (HCC) in liver tissue. The present study clearly indicated that the intravenous delivery of large quantities of Nano-HA into the body of the rabbit model over relatively short periods of time may be absorbed by the hepatic reticuloendothelial system. Subsequent HIFU treatment for HCC, as well as intravenous Nano-HA, produced a rapid increase in temperature and an enlargement of the coagulated necrotic area during ablation in the in vivo and ex vivo environments. In addition, it was found that the therapeutic doses of Nano-HA produced mild and transient abnormalities in the normal renal function and hepatic enzymes during the first 24 h following administration. The results of the current study indicated that the combination of Nano-HA and HIFU may provide a safe and effective alternative to conventional surgical procedures.