Band 11, Heft 3

Thrombolysis is not currently recommended in cirrhotic patients with acute portal vein thrombosis (PVT) in most guidelines, because of the exceedingly limited data and the perceived high risk of bleeding adverse events. However, in the few studies including patients with cirrhosis, the rate of success was high and that of adverse events was similar in patients with or without cirrhosis. Hence, thrombolysis might be a rescue therapeutic option in patients with cirrhosis and acute, symptomatic thrombosis of the portal venous system, unresponsive to anticoagulation, provided a suitable timing is kept, less than 30 days and, if possible, less than 14 days from the acute onset of portal vein thrombosis. In this review perspective article, I discuss the several potential approaches of thrombolysis, either local or systemic, alone or combined with mechanical procedures for thrombus removal, or as a complement to Transjugular Intrahepatic Portosystemic Shunt placement, with a focus on the more suitable timing of thrombolysis. However, the very limited available data preclude from performing firm recommendations, and decision to carry out thrombolysis must take into account both the occurrence of major contraindications and the current critical clinical setting. In the next future, large high-quality multicentre studies will hopefully be able to settle more firm indications and preferable techniques.

The surface of the small bowel mucosa is covered more than any other section of the digestive canal; however, the overall prevalence of small bowel tumors of the whole gastrointestinal tract is evidently low. Owing to the improvement in endoscopic techniques, the prevalence of small bowel tumors has increased across multiple countries, which is mainly due to an increase in duodenal tumors. Superficial non-ampullary duodenal epithelial tumors (SNADETs) are defined as tumors originating from the non-ampullary region in the duodenum that share similarities and discrepancies with their gastric and colorectal counterparts in the pathogenesis and clinicopathologic characteristics. To date, white light endoscopy (WLE) remains the cornerstone of endoscopic diagnosis for SNADETs. Besides, narrow-band imaging (NBI) techniques and magnifying endoscopy (ME) have been widely used in the clinic and endorsed by multiple guidelines and consensuses for SNADETs’ evaluation. Confocal laser endomicroscopy (CLE), endocytoscopy (ECS), and artificial intelligence (AI) are also up-and-coming methods, showing an exceptional value in the diagnosis of SNADETs. Similar to the endoscopic treatment for colorectal polyps, the choices for SNADETs mainly include cold snare polypectomy (CSP), endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD), and laparoscopic endoscopic cooperative surgery (LECS). However, owing to the narrow lumen, rich vascularity, weak muscle layer, abundant Brunner’s gland, and the hardship of endoscope control, the duodenum ranks as one of the most dangerous operating areas in the digestive tract. Therefore, endoscopists must anticipate the difficulties in endoscopic maneuverability, remain aware of the increased risk of complications, and then select the appropriate treatment according to the advantages and disadvantages of each method.

Ebola virus (EBOV) related health complications have presented a great threat to the healthcare system in the endemic regions. The outbreaks of 2013-2016 and 2018-2020 brought along a huge healthcare burden for the afected communities. Knowing the seriousness of the matter, a series of research experiments have been actively carried out to devise efective therapeutics, drugs, and vaccination protocols against the Ebola virus disease (EVD) in the past decade. The purpose of this piece of literature is to shed light on vaccination protocols being clinically evaluated for EVD. A methodological approach has been adopted to gather relevant data from the latest publications. The compiled data include the molecular mechanistic insights into Ebola infection and a brief overview of diferent vaccination strategies: inactivated and DNA vaccines, virus-like particles and replicons, reverse genetic and recombinant approaches, entry, ion, and gene expression inhibitors, and some repurposed drugs. This data will help the scientific community to get a comprehensive overview of therapeutic interventions against Ebola that could be related to modifying EBOV vaccines and designing other antiviral vaccinations. Having said that, further work in modern therapeutic design is pertinent to tackle and lessen the healthcare burden expected from such outbreaks in the future.

Chronic stress refers to continuous emotional changes and psychological pressure that individuals experience when they are unable to adjust and stabilize the internal environment over an extended period. It can increase the pressure on endocrine mediators and cytokines in the circulation, as well as tissues throughout the hypothalamic-pituitary-adrenaline (HPA) axis and sympathetic nervous system (SNS); thus, evolving the internal environment of the tumor. This review assesses several key issues, involving psychosocial factors, and integrates clinical, cellular, and molecular studies—as well as the latest research progress—to provide a mechanistic understanding regarding breast oncopsychology. We propose that chronic stress contributes to large individual diferences in the prognosis of breast cancer survivors because they change the basic physiological processes of the endocrine and immune systems, which in turn regulate tumor growth. The study of psychological and physiological reactions of breast cancer patients suggests a new idea for psychological intervention and clinical treatment for breast cancer patients.

Background and Objectives An increased risk of cardiovascular and metabolic diseases (CVMDs) among patients with cancer suggests a potential link between CVMD and cancer. The impact of CVMD on the survival time of patients with esophageal and gastric cancer remains unknown. We aimed to determine the incidence of CVMD and its impact on the longterm outcomes in esophageal and gastric cancer patients. Methods A total of 2074 cancer patients were enrolled from January 1, 2007 to December 31, 2017 in two hospitals, including 1205 cases of esophageal cancer and 869 cases of gastric cancer, who were followed up for a median of 79.8 and 79.3 months, respectively. Survival time was analyzed using the Kaplan–Meier method before and after propensity score matching. Results The incidence of CVMD in patients with esophageal and gastric cancer was 34.1% (411/1205) and 34.3% (298/869), respectively. The effects of hypertension, diabetes, and stroke on the long-term survival of esophageal and gastric cancer patients were not significant (all P > 0.05). The survival time was significantly longer in esophageal cancer patients without ischemic heart disease than in patients with ischemic heart disease, both before matching (36.5 vs. 29.1 months, P = 0.027) and after matching (37.4 vs. 27.9 months, P = 0.011). The survival time in gastric cancer patients without ischemic heart disease was significantly longer than in patients with ischemic heart disease, both before (28.4 vs. 17.5 months, P = 0.032) and after matching (29.5 vs. 17.5 months, P = 0.02). Conclusion The survival time of esophageal and gastric cancer patients with ischemic heart disease was significantly reduced compared to that of esophageal and gastric cancer patients without ischemic heart disease.

Background Primary biliary cholangitis (PBC) has been long associated with impairment of various aspects of health-related quality of life (HRQoL) with substantial differences among populations. This study evaluated for the first-time the HRQoL in Greek PBC patients in conjunction with clinical and laboratory parameters of patients. Methods We analyzed prospectively collected data regarding the HRQoL by using the PBC-40 and SF-36 questionnaires in 374 Greek PBC patients and 131 age- and sex-matched non-PBC controls. Results The PBC-40 questionnaire is a reliable tool for HRQoL assessment in Greek PBC patients (Cronbach's α > 0.7 for all domains). Implementation of PBC-40 and SF-36 demonstrated significant impairment of HRQoL in Greek PBC patients compared to controls ( P < 0.001 for all comparisons). Emotional dysfunction, social impairment, and fatigue (100%, 80.5% and 78%, respectively) were amongst those with the highest, while cognitive dysfunction (32%) with the least impact on quality of life. Fatigue was associated with female sex ( P = 0.02), longer disease duration ( P = 0.01), presence of cirrhosis ( P = 0.02) and positivity for PBC-specific ANA ( P < 0.05), while social dysfunction with increased age ( P < 0.001), longer disease duration ( P < 0.001) and presence of cirrhosis ( P = 0.004). Living in urban areas was linked to impaired social function ( P = 0.04), cognition ( P = 0.02), fatigue ( P = 0.04) and increased total PBC-40 score ( P = 0.01). Conclusions Implementation of PBC-40 and SF-36 revealed impaired HRQoL in Greek PBC patients with fatigue, social and emotional dysfunction exerting the highest impact. However, total, and individual PBC-40 scores were lower than that reported in studies from Northern/Central Europe and Canada. Deranged HRQoL was associated with severity of liver disease and presence of PBC-specific ANA.

Background and Objectives Acute graft-versus-host disease (aGvHD) remains a major complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methylprednisolone (MP; 1–2 mg/kg/day) remains the standard first-line therapy for aGvHD, although no response is detected in nearly one-half of the patients with aGvHD. This study aimed to investigate the feasibility of mini-dose methotrexate (MTX) combined with standard-dose MP as a front-line therapy for aGvHD. Materials and Methods A prospective Phase 2 clinical trial was performed to evaluate the safety and efficacy of 5 mg/m2 MTX combined with 1 mg/kg/day MP as the initial therapy in 31 patients with aGvHD. Moreover, the effects of MTX combined with MP were explored in a humanized xenogeneic murine model of aGvHD. Results The overall response and complete response rate at 7 days after the initial treatment were 100% and 83%, respectively. The overall response rate on day 28 was 87%. The complete response rates for aGvHD grades I, II, and III were 100% (6/6), 82% (18/22), and 66% (2/3), respectively. Grade 3 toxicities occurred in only three patients presenting with cytopenia. Importantly, MTX and MP demonstrated synergistic effects on ameliorating aGvHD in humanized xenogeneic murine model. Conclusion The current study suggests that mini-dose MTX combined with standard-dose MP could potentially become a novel first-line therapy for patients with aGvHD.

Background and Objectives Triptolide (TP) is known to impair testicular development and spermatogenesis in mammals, but the mechanism of the side effects still needs to be investigated. The aim of the research is to confirm whether TP can cause autophagy in TM3 Leydig cells and the potential molecular pathway in vitro. Methods TM3 Leydig cells are used to investigate the molecular pathway through Western blot, detection of apoptosis, transmission electron microscopy for autophagosomes and so on. Results The data show that TP treatment resulted in the decreasing of the viability of TM3 cells due to the increased apoptosis. Treated with TP, the formation of autophagosomes, the decrease in P62, and the increase in the conversion of LC3-I to LC3-II suggested the induction of autophagy. The induction of autophagy has accompanied the activation of the mTOR/P70S6K signal pathway. The viability of the TM3 cells was further inhibited when they were co-treated with autophagy inhibitor, chloroquine (CQ). Conclusion All these data suggest that autophagy plays a very important role in antagonizing TM3 cell apoptosis during the TP exposure.

Background and Objectives Treatment resistant hypertension (trHTN) is a common clinical problem faced by many clinicians. Laparoscopic adrenalectomy effectively trims blood pressure (BP) elevation secondary to various functional adrenal disorders. However, the impact of adrenalectomy on BP within trHTN patients has never been reported. Our present study aims to investigate the effect of adrenalectomy on BP management within trHTN patients, and to explore clinical predictors for postoperative BP normalization. Patients and Methods In our current study, 117 patients diagnosed with trHTN and performed with unilateral adrenalectomy were consecutively enrolled, demographic and medical information were documented for baseline data collection. BP was measured with a standard electronic sphygmomanometer twice a day. Long-term periodical interview was conducted and 109 (93.2%) enrolled patients were successfully followed-up at an averaged 36.2 months. Results At follow-up, 27/109 (25%) trHTN patients acquired BP normalization and 68/109 (62%) patients acquired BP improvement. Mean taking anti-hypertensive agents reduced from presurgical 4.24 to present 1.21 ( P < 0.01), along with 7.2 mmHg reduction in SBP ( P < 0.01). Image macro-adenoma and hypokalemia history were found to be the two strongest predictors for postoperative BP normalization. ( χ 2 = 28.032, P < 0.01). The incidence of adverse postoperative events was quite small. Conclusions In summary, this current study implicates that adrenalectomy is an efficacious and safe surgical strategy for BP management in trHTN patients. Patients with both unilateral macro-adenoma and hypokalemia are more prone to acquire postoperative BP normalization.

Background and Objectives Asthma is a chronic inflammatory airway disease and brings heavy economic and spiritual burdens to patients’ families and the society. Airway smooth muscle cells (ASMCs) afect the development of asthma by secreting cytokines, growth factors, and prostates. The stress-inducing protein, Sestrin2, plays a vital role in antioxidant defense. The aim of this study is to investigate the role of Sestrin2 in asthma and its corresponding molecular mechanism. Materials and Methods Airway remodeling was induced by construction of asthma rat model. Primary ASMCs were isolated through combining tissue block adherence and enzymatic digestion and identified by immunofluorescence staining. Gene expression was measured by quantitative real-time PCR (qPCR) and western blot (WB) experiments. Cell viability, proliferation, migration, and calcium flow of ASMCs were measured by Cell Counting Kit-8 (CCK-8), 5-ethynyl-deoxyuridine (EdU), Transwell, and Fluo-3AM, respectively. The binding of miR-182 and Sestrin2 3′-untranslated region (3′-UTR) was measured by luciferase reporter system and RNA-binding protein immunoprecipitation (RIP) analysis. Results Sestrin2 expression was upregulated in asthma rat model and cell model. Overexpression of Sestrin2 enhanced the growth, migration, and calcium flow, and inversely, repression of Sestrin2 was reduced in ASMCs from the asthma group. MiR-182, one of the microRNAs (miRNAs) that possesses the potential to regulate Sestrin2, was downregulated in ASMCs from the asthma group. Further experiments revealed that Sestrin2 was inhibited by miR-182 and that overexpression of Sestrin2 reversed the miR-182–induced inhibition of the cellular progression of ASMCs from the asthma group. This study further investigated the downstream signaling pathway of Sestrin2 and found that increased expression of Sestrin2 activated 5′-adenosine monophosphate-activated protein kinase (AMPK), leading to the inactivation of mammalian target of rapamycin (mTOR) and thus promoting the growth, migration, and calcium flow of ASMCs from the asthma group. Conclusion This study investigated the role of Sestrin2 for the first time and further dissected the regulatory factor of Sestrin2, ultimately elucidating the downstream signaling pathway of Sestrin2 in asthma, providing a novel pathway, and improving the understanding of the development and progression of asthma.

Background Fos-related antigen 2 ( FOSL2 ) plays a facilitative role in fibrotic disease; however, its role in renal fibrosis remains unclear. This study aimed to clarify the role and underlying mechanisms of FOSL2 in renal fibrosis. Methods Upregulated genes in unilateral ureteral obstruction (UUO)-injured kidneys were screened in Gene Expression Omnibus (GEO) databases, and overlapping genes were identified using Venn diagram software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed for these genes. The UUO-induced mouse model and transforming growth factor-β1 (TGF-β1)-induced cell model were used for the in vivo and in vitro studies. Results A total of 43 commonly upregulated genes were identified. GO and KEGG pathway analyses indicated that FOSL2 may be involved in fibrosis. Furthermore, FOSL2 was confirmed to be upregulated in UUO-injured kidneys and TGF-β1–induced cells. Knockdown of FOSL2 ameliorated interstitial fibrosis, extracellular matrix deposition, and epithelial-mesenchymal transition via the downregulation of fibronectin, α-smooth muscle actin (α-SMA), collagen type I ( Col1a1 and Col1a2 ), and Col5a1 and upregulation of E-cadherin . Bioinformatics analysis revealed that serum/glucocorticoid regulated kinase 1 ( SGK1 ) may be regulated by FOSL2 and involved in renal fibrosis. Further experiments confirmed that TGF-β1 enhanced SGK1 expression and transcription, which were reversed by FOSL2 silencing. Moreover, FOSL2 was bound to the SGK1 promoter, and SGK1 overexpression reversed the effects of FOSL2 silencing in TGF-β1–induced cells. Conclusion FOSL2 plays an essential role in promoting renal fibrosis in an SGK1 -dependent manner, and targeting the FOSL2 / SGK1 signaling axis may offer a potential strategy for the treatment of renal fibrosis.