Vulvar microinvasive squamous cell carcinoma arising in vulvar intraepithelial neoplasia 3 complicated by genital warts and systemic lupus erythematosus: a case report

A patient suffering from long-term systemic lupus erythematosus attended with a complaint of recurrent genital warts. Perineal white-colored skin and a peri-anal papillary protrusion adjacent to the genital warts were biopsied and determined to be vulvar intraepithelial neoplasia (VIN) 3 and microinvasive squamous cell carcinoma (SCC), respectively. These lesions were locally excised. Human papillomavirus (HPV)-6 was detected in these lesions, including in the genital warts, while HPV-56 was detected only in the perineal VIN3 and peri-anal microinvasive SCC.

Functional regulation of the DNA damage-recognition factor DDB2 by ubiquitination and interaction with xeroderma pigmentosum group C protein

In mammalian nucleotide excision repair, the DDB1-DDB2 complex recognizes UV-induced DNA photolesions and facilitates recruitment of the XPC complex. Upon binding to damaged DNA, the Cullin 4 ubiquitin ligase associated with DDB1-DDB2 is activated and ubiquitinates DDB2 and XPC. The structurally disordered N-terminal tail of DDB2 contains seven lysines identified as major sites for ubiquitination that target the protein for proteasomal degradation; however, the precise biological functions of these modifications remained unknown. By exogenous expression of mutant DDB2 proteins in normal human fibroblasts, here we show that the N-terminal tail of DDB2 is involved in regulation of cellular responses to UV. By striking contrast with behaviors of exogenous DDB2, the endogenous DDB2 protein was stabilized even after UV irradiation as a function of the XPC expression level. Furthermore, XPC competitively suppressed ubiquitination of DDB2 in vitro, and this effect was significantly promoted by centrin-2, which augments the DNA damage-recognition activity of XPC. Based on these findings, we propose that in cells exposed to UV, DDB2 is protected by XPC from ubiquitination and degradation in a stochastic manner; thus XPC allows DDB2 to initiate multiple rounds of repair events, thereby contributing to the persistence of cellular DNA repair capacit

Topical insulin-like growth factor 1 treatment using gelatin hydrogels for glucocorticoid-resistant sudden sensorineural hearing loss: a prospective clinical trial

<p>Abstract</p> <p>Background</p> <p>Sudden sensorineural hearing loss (SSHL) is a common condition in which patients lose the hearing in one ear within 3 days. Systemic glucocorticoid treatments have been used as standard therapy for SSHL; however, about 20% of patients do not respond. We tested the safety and efficacy of topical insulin-like growth factor 1 (IGF1) application using gelatin hydrogels as a treatment for SSHL.</p> <p>Methods</p> <p>Patients with SSHL that showed no recovery to systemic glucocorticoid administration were recruited. We applied gelatin hydrogels, impregnated with recombinant human IGF1, into the middle ear. The primary outcome measure was the proportion of patients showing hearing improvement 12 weeks after the test treatment. The secondary outcome measures were the proportion of patients showing improvement at 24 weeks and the incidence of adverse events. The null hypothesis was that 33% of patients would show hearing improvement, as was reported for a historical control after hyperbaric oxygen therapy.</p> <p>Results</p> <p>In total, 25 patients received the test treatment at a median of 23 days (range 15-32) after the onset of SSHL, between 2007 and 2009. At 12 weeks after the test treatment, 48% (95% CI 28% to 69%; <it>P </it>= 0.086) of patients showed hearing improvement, and the proportion increased to 56% (95% CI 35% to 76%; <it>P </it>= 0.015) at 24 weeks. No serious adverse events were observed.</p> <p>Conclusions</p> <p>Topical IGF1 application using gelatin hydrogels is well tolerated and may be efficacious for hearing recovery in patients with SSHL that is resistant to systemic glucocorticoids.</p

Research and Design of a Routing Protocol in Large-Scale Wireless Sensor Networks

无线传感器网络，作为全球未来十大技术之一，集成了传感器技术、嵌入式计算技术、分布式信息处理和自组织网技术，可实时感知、采集、处理、传输网络分布区域内的各种信息数据，在军事国防、生物医疗、环境监测、抢险救灾、防恐反恐、危险区域远程控制等领域具有十分广阔的应用前景。 本文研究分析了无线传感器网络的已有路由协议，并针对大规模的无线传感器网络设计了一种树状路由协议，它根据节点地址信息来形成路由，从而简化了复杂繁冗的路由表查找和维护，节省了不必要的开销，提高了路由效率，实现了快速有效的数据传输。 为支持此路由协议本文提出了一种自适应动态地址分配算——ADAR（AdaptiveDynamicAddre...As one of the ten high technologies in the future, wireless sensor network, which is the integration of micro-sensors, embedded computing, modern network and Ad Hoc technologies, can apperceive, collect, process and transmit various information data within the region. It can be used in military defense, biomedical, environmental monitoring, disaster relief, counter-terrorism, remote control of haz...学位：工学硕士院系专业：信息科学与技术学院通信工程系_通信与信息系统学号：2332007115216

Characterization of human organic cation transporter 1 (OCT1/SLC22A1)- and OCT2 (SLC22A2)-mediated transport of 1-(2-methoxyethyl)-2-methyl-4,9dioxo-3-(pyrazin-2-ylmethyl)-4,9-dihydro-1h-naphtho[2,3-d]imidazolium bromide (YM155 monobromide), a novel small

Although YM155, which has a cationic moiety in its structure, is influxed into its pharmacologically effective site (cancer cells) and one of its eliminating organs (hepatocytes) in a transporter-mediated manner, the mechanism seems to be different between two cell types. The other eliminating organ is the kidney. In this study, the transport of

Dietary fermented products using koji mold and sweet potato-shochu distillery by-product promotes hepatic and serum cholesterol levels and modulates gut microbiota in mice fed a high-cholesterol diet

It has been reported that fermented products (FPs) prepared from sweet potato-shochu distillery by-product suppressed weight gain and decreased serum cholesterol levels in mice under normal dietary conditions. Furthermore, from the information gained from the above data regarding health benefits of the FPs, the aim of this study was evaluating the effects of dietary FPs on lipid accumulation and gut microbiota in mice with or without cholesterol-load in the diet. C57BL/6N mice were fed normal (CO) diet, CO with 10% FPs (CO + FPs) diet, cholesterol loaded (HC) diet, or HC with 10% FPs (HC + FPs) diet for 8 weeks. The mice were then euthanized, and blood samples, tissue samples, and feces were collected. The adipose tissue weight and liver triglyceride levels in the HC + FPs diet groups were significantly reduced compared to that in the HC diet groups. However, FPs significantly increased the serum non-high-density lipoprotein cholesterol (HDL-C) levels, the ratio of non-HDL-C to HDL-C and hepatic total cholesterol levels in mice fed cholesterol-loaded diet compared with that of the HC diet group. Since dietary FPs significantly decreased the protein expression levels of cholesterol 7 alpha-hydroxylase 1 in the HC + FPs diet groups, the cholesterol accumulation in FPs group may be explained by insufficient catabolism from cholesterol to bile acid. In addition, the dietary FPs tended to increase Clostridium cluster IV and XIVa, which are butyrate-producing bacteria. Related to the result, n-butyrate was significantly increased in the CO + FPs and the HC + FPs diet groups compared to their respective control groups. These findings suggested that dietary FPs modulated the lipid pool and gut microbiota

Ventricular arrhythmia events in heart failure patients with cardiac resynchronization therapy with or without a defibrillator for primary prevention

Abstract Background It is uncertain whether cardiac resynchronization therapy with a defibrillator (CRT‐D) provides better survival benefits than a CRT‐pacemaker (CRT‐P) in heart failure patients with a reduced ejection fraction (≦35%, HFrEF) treated with contemporary HF therapy. Methods We retrospectively analyzed the ventricular arrhythmia (VAs; sustained ventricular tachycardia/fibrillation) events in HFrEF patients who underwent CRT without a prior history of VAs or aborted sudden cardiac death before the CRT implantation. Between January/2010 and December/2020, a CRT device was implanted in 79 HFrEF patients (mean age: 69 ± 12 years, male: 57, ischemic cardiomyopathy: 16). CRT‐D and CRT‐P devices were implanted in 50 and 29 patients, respectively, at each physician's discretion. CRT‐Ds were indicated in younger patients than were CRT‐Ps (66 ± 12 vs. 73 ± 12 years, p = 0.03), but the gender distribution did not differ (female, 24% [12 of 50] vs. 35% [10 of 29], p = 0.44). The VA events during a median follow‐up of 3.5‐years (interquartile range [IQR]:1.6–5.5) and their predictors were analyzed. Results VA events occurred in 9 patients with CRT‐Ds (18%) and one with a CRT‐P (3%, p = 0.08). The VA event rate was significantly lower in patients without a prior non‐sustained ventricular tachycardia (NSVT: ≥3 beats; rate, ≥120 bpm; lasting <30 s, HR 0.05; 95% CI 0.01–0.30; p < 0.01) and females (HR 0.11; 95% CI 0.01–0.93; p = 0.04). Of note, no female patients without a prior history of NSVT experienced VA events. Conclusion HFrEF CRT candidates without a prior history of NSVT and females may obtain less benefit from a primary preventive defibrillator indication