The role of iron metabolism and oxidative stress in the pathogenesis of endometriosis

Despite many years of extensive investigations and increasing number of studies, the pathogenesis of endometriosis remains unclear. Accumulated data suggests that disrupted iron metabolism may induce oxidative stress in the peritoneal cavity of endometriosis patients

Zwiększone stężenie białek ostrej fazy w płynie otrzewnowym kobiet z zaawansowaną endometriozą

Objectives: Most investigators agree that endometriosis is associated with a state of subclinical, non-infectious peritoneal inflammation. The objective of the study was to assess concentrations of two markers of the acute inflammatory phase proteins, haptoglobin and ceruloplasmin, in peritoneal fluid of endometriotic women. Material and methods: 229 women who underwent diagnostic or therapeutic laparoscopy were included in the study. Minimal, mild, moderate and severe endometriosis according to ASRM was confirmed in 119 women (study groups), whereas 110 patients suffered from simple serous or dermoid ovarian cysts (reference groups). Haptoglobin and ceruloplasmin concentrations in the peritoneal fluid samples aspirated during laparoscopy were measured using commercially available radial immunodiffusion kits. Results: The concentration of haptoglobin in the peritoneal fluid of women with endometriosis was significantly higher as compared to patients with serous and dermoid ovarian cysts. Significantly higher haptoglobin level was observed in patients with severe and moderate endometriosis as compared to women from both reference groups. No significant difference in the peritoneal fluid ceruloplasmin levels was found between patients with endometriosis and women from reference groups. However, it was noted that ceruloplasmin levels are higher in the subgroup of patients with severe endometriosis as compared to both reference groups and women with mild disease. Conclusions: Our results support the hypothesis that endometriosis is associated with subclinical inflammation within the peritoneal cavity. It may be speculated that pro-inflammatory stimuli strong enough to cause an increase in acute inflammatory phase proteins peritoneal fluid concentrations are observed only in the advanced stages of the disease.Cel pracy: Etiopatogeneza endometriozy nie jest do końca wyjaśniona, a większość badaczy zgadza się, że w płynie otrzewnowym kobiet chorych na tę chorobę stwierdza się subkliniczny proces zapalny pochodzenia nie-infekcyjnego. Celem pracy była ocena stężenia dwóch markerów, białek ostrej fazy zapalnej: haptoglobiny i ceruloplazminy w płynie otrzewnowym kobiet z endometriozą. Materiał i metody: Do badań włączono 229 kobiet, które przebyły diagnostyczną lub terapeutyczną laparoskopię. Endometriozę w stopniu minimalnym, łagodnym, umiarkowanym wg ASRM potwierdzono histologicznie u 119 kobiet (grupa badana). Pozostałe 110 pacjentek leczono z powodu prostych lub dermoidalnych torbieli (grupa referencyjna). Stężenia haptoglobiny i ceruloplazminy w próbkach płynu otrzewnowego oceniano przy użyciu komercyjnych zestawów do immunodyfuzji radialnej. Wyniki: Stężenie haptoglobiny w płynie otrzewnowym pacjentek z endometriozą było znacznie wyższe w porównaniu do pacjentek z grupy referencyjnej. Większe stężenie haptoglobiny dotyczyło podgrupy pacjentek z umiarkowaną i ciężką postacią choroby. Nie stwierdzono różnic w stężeniu ceruloplazminy w płynie otrzewnowym pacjentek z endometriozą w porównaniu do pacjentek z grupy referencyjnej. Jednakże wykazano, że stężenie ceruloplazminy jest większe w podgrupie pacjentek z ciężką postacią choroby w porównaniu do pacjentek z grupy referencyjnej i podgrupy pacjentek z łagodną postacią choroby. Wnioski: Wyniki naszych badań potwierdzają hipotezę o istnieniu subklinicznego stanu zapalnego w jamie otrzewnowej pacjentek z endometriozą. Wydaje się, że działanie silnych bodźców prozapalnych powodujących zwiększenie stężenia białek ostrej fazy w płynie otrzewnowym dotyczy jedynie pacjentek z zaawansowanymi postaciami choroby

Worldwide variations in COVID-19 vaccination policies and practices in liver transplant settings: results of a multi-society global survey

BackgroundDespite the WHO's report of 24 available SARS-CoV-2 vaccines, limited data exist regarding vaccination policies for liver transplant (LT) patients. To address this, we conducted a global multi-society survey (EASL-ESOT-ELITA-ILTS) in LT centers.MethodsA digital questionnaire assessing vaccine policies, safety, efficacy, and center data was administered online to LT centers.ResultsOut of 168 responding centers, 46.4%, 28%, 13.1%, 10.7%, and 1.8% were from European, American, Western Pacific, Southeast Asian, and Eastern Mediterranean Regions. Most LT centers prioritized COVID-19 vaccine access for LT patients (76%) and healthcare workers (86%), while other categories had lower priority (30%). One-third of responders recommended mRNA vaccine exclusively, while booster doses were widely recommended (81%). One-third conducted post-vaccine liver function tests post COVID-19 vaccine. Only 16% of centers modified immunosuppression, and mycophenolate discontinuation or modification was the main approach. Side effects were seen in 1 in 1,000 vaccinated patients, with thromboembolism, acute rejection, and allergic reaction being the most severe. mRNA showed fewer side effects (−3.1, p = 0.002).ConclusionCOVID-19 vaccines and booster doses were widely used among LT recipients and healthcare workers, without a specific vaccine preference. Preventative immunosuppression adjustment post-vaccination was uncommon. mRNA vaccines demonstrated a favorable safety profile in this population

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

Technical aspects of liver transplantation

This thesis concerns selected technical aspects of the complex surgical procedure to transplant a liver graft from deceased donors to a recipient with a liver failure. In Chapter 1 the complexity of the liver transplantation is explained and the aims and outlines of the thesis are presented. Chapter 2 gives an overview over the technical developments of the transplant procedure, which have taken place during the past four decades after the first liver transplantation in humans. Chapter 3 presents the results of the first reported open comparison between the outcomes of two liver transplant centers, the Transplantation and Surgical Clinic, Semmelweis University, Budapest, Hungary (SEB) and the the University Medical Center Groningen, Groningen, The Netherlands (UMCG). In both centers, perioperative red blood cell (RBC) transfusion rate was a significant predictor for patient survival. It was jointly concluded that measures to reduce blood loss by adapting the operation technique might lead to improved survival and reduced morbidity. Chapter 4 describes the results of the study comparing two techniques of liver transplantation, conventional (CON-OLT) and piggyback technique (PB-ES) in terms of patient and graft survival, operative parameters and postoperative complications. One-, 3- and 5-yr patient and graft survival were not different between the CON-OLT and PB-ES group. Apart from the higher number of patients with cholangitis and sepsis in CON-OLT group, morbidity, retransplantation rate and post-operative liver and kidney function were not different between the two groups. Results of this study show that both techniques are comparable in survival and morbidity; however PB-ES results in shorter anhepatic phases, revitalization time and warm ischemia time as well as less RBC use. As no consensus exists regarding the optimal reconstruction of the cavo-caval anastomosis in piggyback orthotopic liver transplantation (PB-LT) our experiences with the technique of end-to-side caval anastomosis are decribed in Chapter 5. Our experience indicates that PB-LT with ES cavo-cavostomy is a safe procedure, can safely be performed without the routine use of a TPCS, has a very low risk of venous outflow obstruction and can also be used effectively during retransplantations. Chapter 6 gives an overview about current techniques of revascularization in liver transplantation. The results of comparison of two reperfusion protocols, a sequential one with first portal vein reperfusion followed by arterial reperfusion (Seq group) and a simultaneous reperfusion protocol (SimR group) are presented in Chapter 7. Patient and graft survival at 1, 3, and 6 months and at 1 year did not differ between the SeqR group and the SimR group. RBC requirements were significantly higher in the SimR group in comparison to the SeqR group. Apart from a higher number of biliary anastomotic complications and abdominal bleeding complications in the SimR group in comparison to the SeqR group. In conclusion, no advantage of either of the 2 reperfusion protocols could be observed in this analysis, especially with respect to the incidence of ischemic type biliary lesions. Chapter 8 describes the results of liver transplantation in children with body weight below or equal to 10 kg transplanted with grafts from deceased donors. Cox regression analysis revealed that a need for retransplantation and urgent transplantation were important predictors for patient survival (p=0.04 and p=0.001, respectively). To assess whether the need for retransplantation can be influenced, all study variables were compared between surviving grafts and failed grafts. Cox regression analysis showed that only D/R weight ratio proved to be independent predictor for graft survival (p=0.004). After comparison of graft survival with the long rank test according to different D/R weight ratios (3.0-7.0), the cut-off point for significantly different graft survival approached 4.0. In summary, patient survival in children with a body weight below or equal to 10 kg is determined by urgent transplantation and the need for retransplantation. Graft loss and retransplantation in small children can be prevented by adequate size matching of donor and recipient whereby a D/R weight ratio below 4.0 seems to offer the favorable outcome.

Low-Density Lipoproteins Oxidation and Endometriosis

The etiopathogenesis of endometriosis still remains unknown. Recent data provide new valuable information concerning the role of oxidative stress in the pathophysiology of the disease. It has been proved that levels of different lipid peroxidation end products are increased in both peritoneal fluid (PF) and serum of endometriotic patients. We assessed the concentration of oxidized low-density lipoproteins (oxLDL) in PF of 110 women with different stages of endometriosis and 119 women with serous () or dermoid () ovarian cysts, as the reference groups. PF oxLDL levels were evaluated by ELISA. We found that concentrations of oxLDL in PF of endometriotic women were significantly higher compared to women with serous but not dermoid ovarian cysts. Interestingly, by analyzing concentrations of oxLDL in women with different stages of the disease, it was noted that they are significantly higher only in the subgroup of patients with stage IV endometriosis as compared to women with ovarian serous cysts. In case of minimal, mild, and moderate disease, PF oxLDL levels were similar to those noted in reference groups. Our results indicate that disrupted oxidative status in the peritoneal cavity of women with endometriosis may play a role in the pathogenesis of advanced stages of the disease

Disrupted iron metabolism in peritoneal fluid may induce oxidative stress in the peritoneal cavity of women with endometriosis

Introduction Data on the possible role of peritoneal fluid free radical-mediated oxidative damage in the pathogenesis of endometriosis still remains inconsistent. The aim of the study was to determine iron metabolism markers and their influence on oxidative stress arameters in the peritoneal fluid of women with endometriosis. Material and Methods 110 women with endometriosis and 119 patients with benign ovarian cysts were included in the study. All visible peritoneal fluid was aspirated during laparoscopy from the anterior and posterior cul-de-sacs. under direct vision to avoid blood contamination. Haemoglobin, iron, total oxidative status, and total antioxidant status were measured using standard colourimetric kits. Results Haemoglobin, iron levels, as well as total oxidative status values were significantly higher, whereas total antioxidant status values were significantly lower in the peritoneal fluid of patients with endometriosis, in comparison to the reference groups. No differences were observed in peritoneal fluid concentrations of all parameters measured in relation to the phase of the menstrual cycle. Conclusions Peritoneal fluid of women with endometriosis is characterized by disrupted iron metabolism. This is most likely related to an increased number of erythrocytes in the peritoneal cavity of endometriotic women, which leads to a higher concentration of haemoglobin in this environment. Impaired iron homeostasis may have a significant influence on the pathophysiology of peritoneal endometriosis by the direct impact of haemoglobin derivatives and/or formation of the pro-inflammatory and pro-oxidative environment. Peritoneal cavity oxidative stress occurs predominantly in women in advanced stages of the disease