Whether and how amarogentin suppresses the angiogenesis effect in liver cancer cells after insufficient radiofrequency ablation (iRFA) are still poorly studied.

The number of liver cancer stem cells (LCSCs) and the level of vascular endothelial growth factor A (VEGFA) were assessed in liver cancer tissue after iRFA. Then, CD133-positive cells were detected in iRFA models of HepG2 and Huh7 cell lines treated with amarogentin. Tube formation assays were applied to observe the antiangiogenesis effects of amarogentin. In addition, the angiogenesis-related molecules p53, delta-like ligand 4 (Dll4), and Notch1 were detected in the iRFA cells and mouse models treated with amarogentin.

The mRNA and protein expression levels of CD133 and VEGFA were significantly higher in the residual liver cancer tissue than in the liver cancer tissues treated by hepatectomy. Amarogentin then markedly decreased the percentage of CD133-positive cells in the iRFA model in both HepG2 and Huh7 cell lines. The number of tubules formed by human umbilical vein endothelial cells (HUVECs) was significantly decreased by amarogentin. Inversely, the antiangiogenesis effect of amarogentin was counteracted after p53 silencing in the iRFA cell models.

Amarogentin prevents the malignant transformation of liver cancer after iRFA via affecting stemness and the p53-dependent VEGFA/Dll4/Notch1 pathway to inhibit cancer cell angiogenesis.

Amarogentin prevents the malignant transformation of liver cancer after iRFA via affecting stemness and the p53-dependent VEGFA/Dll4/Notch1 pathway to inhibit cancer cell angiogenesis.Posing a threat to the ongoing leishmaniasis elimination efforts in the Indian subcontinent, L. donovani-induced cutaneous leishmaniasis (CL) has been recently reported in many countries. Sri Lanka reports a large focus of human cutaneous leishmaniasis (CL) caused by Leishmania donovani, a usually visceralizing parasite. Enhanced case detection, early treatment, and in-depth understanding of sequalae are required to contain the spread of disease. Visceralizing potential of dermotropic strains has not been fully ruled out. Sri Lankan strains have shown a poor response to established serological assays. The present concern was to develop an in-house serological assay and to determine the seroprevalence of CL for identifying visceralizing potential and its usefulness in enhancing case detection. Crude cell lysate of dermotropic L. donovani promastigotes-based indirect enzyme-linked immunosorbent assay (ELISA) was previously optimized. Assay was evaluated using sera from 200 CL patients, 50 endemic and 50 nonendeM-negative CL cases to enhance clinical case detection. Further studies are warranted to examine in-depth correlations, antigen profiles, comparison with other established serological tools, and usefulness in the detection of asymptomatic cases. (National patent LK/P/1/19697).The mammalian orosomucoid-like gene family (ORMDL), containing ORMDL1, ORMDL2, and ORMDL3, is the important regulator of sphingolipid metabolism, which is relevant to cell growth, proliferation, migration, and invasion. Since the role of ORMDL1 in cancers remained unclear, the main purpose of our study was to explore the expression patterns and prognostic values of ORMDL1 in different tumors, especially in cholangiocarcinoma (CHOL), lymphoid neoplasm diffuse large B cell lymphoma (DLBCL), acute myeloid leukemia (LAML), and thymoma (THYM). Bioinformatics tools including GEPIA, CCLE, LinkedOmics, cBioPortal, and TIMER databases were used. As a result, the expression levels of ORMDL1 in tumor tissues and normal tissues varied in different cancers, especially significantly upregulated in CHOL, DLBCL, LAML, and THYM. Moreover, ORMDL1 mRNA was also highly expressed in cell lines of DLBCL and LAML. Further studies showed that ORMDL1 overexpression was associated with poor prognosis in DLBCL, but not significant in CHOL, LAML, and THYM. Consistently, there were genetic alterations of ORMDL1 in DLBCL, and patients with genetic alterations indicated worse survival. Coexpressed genes and related biological events with ORMDL1 in DLBCL were found via LinkedOmics, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The relationship between ORMDL1 and cancer immune cells was investigated, and ORMDL1 expression was positively correlated with infiltrating levels of B cells. In conclusion, ORMDL1 is suggested to be a tumorigenic factor and considered as the potential therapeutic target and prognostic biomarker in DLBCL.

Neonatal jaundice is common a clinical problem worldwide. Globally, every year, about 1.1 million babies develop severe hyperbilirubinemia with or without bilirubin encephalopathy and the vast majority reside in sub-Saharan Africa and South Asia. Strategies and information on determinants of neonatal jaundice in sub-Saharan Africa are limited. So, investigating determinant factors of neonatal jaundice has paramount importance in mitigating jaundice-related neonatal morbidity and mortality.

. Hospital-based unmatched case-control study was conducted by reviewing medical charts of 272 neonates in public general hospitals of the central zone of Tigray, northern Ethiopia. The sample size was calculated using Epi Info version 7.2.2.12, and participants were selected using a simple random sampling technique. One year medical record documents were included in the study. Data were collected through a data extraction format looking on the cards. Data were entered to the EpiData Manager version 4.4.2.1 and exportedmportant since it was a cause of long-term complication and death in neonates.

Obstetric complication, low birth weight, birth asphyxia, RH-incompatibility, breastfeeding, and polycythemia were among the determinants of neonatal jaundice. Hence, early prevention and timely treatment of neonatal jaundice are important since it was a cause of long-term complication and death in neonates.Healthcare providers have disparate views of family presence during cardiopulmonary resuscitation; however, the attitudes of physicians have not been investigated systematically. This study investigates the patterns and determinants of physicians’ attitudes to FP during cardiopulmonary resuscitation in Saudi Arabia. A cross-sectional design was applied, where a sample of 1000 physicians was surveyed using a structured questionnaire. The study was conducted in the southern region of Saudi Arabia for over 11 months (February 2014-December 2014). The collected data was analyzed using the Pearson chi-square test. Spearman’s correlation analysis and chi-square test of independence were used for the analysis of physicians’ characteristics with their willingness to allow FP. 80% of physicians opposed FP during cardiopulmonary resuscitation. The majority of them believed that FP could lead to decreased bedside space, staff distraction, performance anxiety, interference with patient care, and breach of privacy. They also highlight FP to result in difficulty concerning stopping a futile cardiopulmonary resuscitation, psychological trauma to family members, professional stress among staff, and malpractice litigations. 77.9% mostly disagreed that FP could be useful in allaying family anxiety about the condition of the patient or removing their doubts about the care provided, improving family support and participation in patient care, or enhancing staff professionalism. Various concerns exist for FP during adult cardiopulmonary resuscitation, which must be catered when planning for FP execution.

Human adenoviruses (HAdVs) are commonly causing respiratory disease. We molecularly genotyped HAdV circulating in Chinese hospitalized children with respiratory infections and summarized the clinical profiles and common inflammatory biomarkers, so as to better determine their associations with disease severity.

Children with respiratory single HAdV infection cases that occurred from December 2017 to March 2019 were enrolled for a cross-sectional study. Clinical/laboratory features based on the genotypes of respiratory HAdV infection were reviewed for comparative analysis.

A total of 84 patients were enrolled, and HAdV types were identified from 82 patients. Species B (HAdV-7, 44%; HAdV-3, 43%, and HAdV-14, 5%) was the most common, followed by C (HAdV-2, 4% and HAdV-1, 1%) and E (HAdV-4, 1%). Severe HAdV infection and HAdV-7 infection groups were associated with significantly longer duration of fever and hospitalized days, higher morbidity of tachypnea/dyspnea, more pleural effusion, more respiratory rales, more frequently required mechanical ventilation, and significantly higher fatality rate. The elevated procalcitonin (PCT) and C-reactive protein (CRP) levels were significantly associated with severe HAdV infection.

HAdV-7 and HAdV-3 were the most common types among children with respiratory adenovirus infection; vaccines against these two genotypes are in urgent need. PCT and CRP are significantly associated with the severity of HAdV infection.

HAdV-7 and HAdV-3 were the most common types among children with respiratory adenovirus infection; vaccines against these two genotypes are in urgent need. PCT and CRP are significantly associated with the severity of HAdV infection.Cartilage defects in temporomandibular disorders (TMD) lead to chronic pain and seldom heal. Synovium-derived mesenchymal stem cells (SMSCs) exhibit superior chondrogenesis and have become promising seed cells for cartilage tissue engineering. However, local inflammatory conditions that affect the repair of articular cartilage by SMSCs present a challenge, and the specific mechanism through which the function remains unclear. Thus, it is important to explore the chondrogenesis of SMSCs under inflammatory conditions of TMD such that they can be used more effectively in clinical treatment. In this study, we obtained SMSCs from TMD patients with severe cartilage injuries. In response to stimulation with IL-1β, which is well known as one of the most prevalent cytokines in TMD, MMP13 expression increased, while that of SOX9, aggrecan, and collagen II decreased during chondrogenic differentiation. At the same time, IL-1β upregulated the expression of mTOR and decreased the ratio of LC3-II/LC3-I and the formation of autophagosomes. Further study revealed that rapamycin pretreatment promoted the migration of SMSCs and the expression of chondrogenesis-related markers in the presence of IL-1β by inducing autophagy. 3-Benzyl-5-((2-nitrophenoxy)methyl)-dihydrofuran-2(3H)-one (3BDO), a new activator of mTOR, inhibited autophagy and increased the expression of p-GSK3βser9 and β-catenin, simulating the effect of IL-1β stimulation. Furthermore, rapamycin reduced the expression of mTOR, whereas the promotion of LC3-II/LC3-I was blocked by the GSK3β inhibitor TWS119. Taken together, these results indicate that rapamycin enhances the chondrogenesis of SMSCs by inducing autophagy, and GSK3β may be an important regulator in the process of rapamycin-induced autophagy. Thus, inducing autophagy may be a useful approach in the chondrogenic differentiation of SMSCs in the inflammatory microenvironment and may represent a novel TMD treatment.

Literature shows platelet-rich plasma (PRP) to improve overall outcomes in orthopedics, dermatology, ophthalmology, gynecology, and plastic surgery. Data on oncological patients is very limited. Only one publication is available on PRP in breast cancer patients. This work evaluated PRP in sentinel node biopsy procedures for breast cancer patients in terms of complication rates and oncological short-term follow-up.

The evaluated PRP was ACP®, i.e., autologous conditioned plasma by Arthrex®. Between 2015 and 2018, 163 patients were offered to receive an ACP®/PRP injection in their lymph node biopsy site. Recruitment resulted in an approximate one-to-one ratio for analysis. Endpoints were major (revision) and minor (seroma, hematoma, and infection) complications rates as well as distant metastases, local recurrence, and overall survival. Median follow-up was 30 months.

Complication rates and oncological follow-up showed PRP to be applicable to use in a sentinel node biopsy scenario in breast cancer patients. There were 0 revisions in the ACP®/PRP group and 1.2% revisions in the control group (not significant). Oncological follow-up showed zero (0) distant metastases and local recurrences as well as a 100% 30-month overall survival.

This is the first analysis of ACP®/PRP used in breast cancer patients in a sentinel node biopsy setting worldwide. PRP does not seem to increase rates of local recurrence within this 30-month follow-up time frame. Also, trend towards decreasing complication rates could be shown.

This is the first analysis of ACP®/PRP used in breast cancer patients in a sentinel node biopsy setting worldwide. PRP does not seem to increase rates of local recurrence within this 30-month follow-up time frame. Also, trend towards decreasing complication rates could be shown.

Preeclampsia is a major cause of maternal and neonatal morbidity and mortality in sub-Saharan Africa. Evidence indicates that endothelial dysfunction is central to the pathogenesis of preeclampsia. This study assessed the level of the components of the arginine-nitric oxide pathway to evaluate endothelial dysfunction in normotensive pregnancies and pregnancies complicated with preeclampsia.

This case-control study was conducted among pregnant women who visited Comboni Hospital from January 2017 to May 2018. A total of 180 pregnant women comprising 88 preeclamptic women (PE) and 92 healthy normotensive pregnant women (NP) were recruited. Sociodemographic, clinical, and obstetric data were obtained using validated questionnaires. Blood pressure and anthropometrics were measured, and blood samples were collected for the estimation of nitric oxide (NO

), L-arginine, asymmetric dimethylarginine (ADMA), and 3-nitrotyrosine using an enzyme-linked immunosorbent assay technique.

The mean NO

(

= 0.010) and Lilability, L-arginine/ADMA ratio, and elevated levels of ADMA and 3-nitrotyrosine. Measurements of the levels of these parameters can help in the early prediction of endothelial dysfunction in preeclampsia. Exogenous therapeutic supplementation with L-arginine during pregnancy to increase the L-arginine/ADMA ratio should be considered to improve endothelial function in preeclampsia and pregnant women at risk of developing preeclampsia.The present study was to investigate the effect of mesenteric lymph duct drainage on lung inflammatory response, histological alteration, and endothelial cell apoptosis in septic rats. Animals were randomly assigned into four groups control, sham surgery, sepsis, and sepsis plus mesenteric lymph drainage. We used the colon ascendens stent peritonitis (CASP) procedure to induce the septic model in rats, and mesenteric lymph drainage was performed with a polyethylene (PE) catheter inserted into mesenteric lymphatic. The animals were sacrificed at the end of CASP in 6 h. The mRNA expression levels of inflammatory mediators were measured by qPCR, and the histologic damage were evaluated by the pathological score method. It was found that mesenteric lymph drainage significantly reduced the expression of TNF-α, IL-1β, and IL-6 mRNA in the lung. Pulmonary interstitial edema and infiltration of inflammatory cells were alleviated by mesenteric lymph drainage. Moreover, increased mRNA levels of TNF-α, IL-1β, IL-6 mRNA, and apoptotic rate were observed in PMVECs treated with septic lymph. These results indicate that mesenteric lymph duct drainage significantly attenuated lung inflammatory injury by decreasing the expression of pivotal inflammatory mediators and inhibiting endothelial apoptosis to preserve the pulmonary barrier function in septic rats.It has been reported that microRNA-206(miR-206) plays an important role in cancers and could be used as a prognostic biomarker. However, the results are controversial. Therefore, we summarize all available evidence and present a meta-analysis to estimate the prognostic value of miR-206 in various cancers. The relevant studies were collected by searching PubMed, EMBASE, and Web of Science databases until August 21, 2020. Hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were applied to explore the association between miR-206 and survival results and clinicopathologic features. Sources of heterogeneity were investigated by subgroup analysis and sensitivity analysis. Publication bias was evaluated using Egger’s test. Twenty articles involving 2095 patients were included in the meta-analysis. The pooled HR showed that low miR-206 expression was significantly associated with unfavourable overall survival (OS) (HR = 2.03, 95 CI% 1.53-2.70, P less then 0.01). In addition, we found that low miR-206 expression predicted significantly negative association with tumor stage (III-IV VS. I-II) (OR = 4.20, 95% CI 2.17-8.13, P less then 0.01), lymph node status (yes VS. no) (OR = 3.58, 95% 1.51-8.44, P = 0.004), distant metastasis (yes VS. no) (OR = 3.19, 95% 1.07-9.50, P = 0.038), and invasion depth (T3 + T4 vs. T2 + T1) (OR = 2.43, 95% 1.70-3.49, P less then 0.01). miR-206 can be used as an effective prognostic indicator in various cancers. Further investigations are warranted to validate the present results.

Endotoxin-associated acute kidney injury (AKI), a disease characterized by marked oxidative stress and inflammation disease, is a major cause of mortality in critically ill patients. Mitochondrial fission and pyroptosis often occur in AKI. However, the underlying biological pathways involved in endotoxin AKI remain poorly understood, especially those related to mitochondrial dynamics equilibrium disregulation and pyroptosis. Previous studies suggest that heme oxygenase- (HO-) 1 confers cytoprotection against AKI during endotoxic shock, and PTEN-induced putative kinase 1 (PINK1) takes part in mitochondrial dysfunction. Thus, in this study, we examine the roles of HO-1/PINK1 in maintaining the dynamic process of mitochondrial fusion/fission to inhibit pyroptosis and mitigate acute kidney injury in rats exposed to endotoxin.

An endotoxin-associated AKI model induced by lipopolysaccharide (LPS) was used in our study. Wild-type (WT) rats and PINK1 knockout (PINK1KO) rats, respectively, were divided into four gion to inhibit pyroptosis, which can alleviate endotoxin-induced AKI by PINK1.

HO-1 inhibits inflammation response and oxidative stress and regulates mitochondria fusion/fission to inhibit pyroptosis, which can alleviate endotoxin-induced AKI by PINK1.

The heat shock protein 90 (HSP90s) family is composed of molecular chaperones composed of four isoforms in humans, which has been widely reported as unregulated in various kinds of cancers. Nevertheless, the role of each HSP90s isoform in prognosis and immune infiltration in distinct subtypes of breast cancer (BRAC) remains unclear.

Public online databases including the Oncomine, UALCAN, Kaplan-Meier Plotter, Tumor IMmune Estimation Resource (TIMER), Gene Expression Profiling Interactive Analysis (GEPIA), GeneMANIA, and Database for Annotation, Visualization, and Integrated Discovery (DAVID) were integrated to perform bioinformatic analyses and to explore the possible associations among HSP90s gene expression, prognosis, and immune infiltration in BRAC.

The mRNA expression of all HSP90s members was elevated in distinct clinical stages and subtypes of BRAC, compared with the normal breast tissue (

< 0.05). Overexpressed HSP90AA1 was associated with poor prognosis, particularly, both short overall su anticancer immunity through pharmacological intervention of HSP90s.

This study demonstrated that HSP90s family genes were overexpressed and might be serve as prognostic biomarkers in subtypes of BRAC. It might be a novel breakthrough point of BRAC treatment to regulate immune infiltration in BRAC microenvironment for more effective anticancer immunity through pharmacological intervention of HSP90s.Three novel low molecular weight polysaccharides (RLP-1a, RLP-2a, and RLP-3a) with 9004, 8761, and 7571 Da were first obtained by purifying the crude polysaccharides from the fruits of a traditional Chinese medicinal herb Rosae Laevigatae. The conditions for polysaccharides from the R. Laevigatae fruit (RLP) extraction were optimized by the response surface methodology, and the optimal conditions were as follows extraction temperature, 93°C; extraction time, 2.8 h; water to raw material ratio, 22; extraction frequency, 3. Structural characterization showed that RLP-1a consisted of rhamnose, arabinose, xylose, glucose, and galactose with the ratio of 3.14  8.21  1  1.37  4.90, whereas RLP-2a was composed of rhamnose, mannose, glucose, and galactose with the ratio of 1.70  1  93.59  2.73, and RLP-3a was composed of rhamnose, arabinose, xylose, mannose, glucose, and galactose with the ratio of 6.04  26.51  2.05  1  3.17  31.77. The NMR analyses revealed that RLP-1a, RLP-2a, and RLP-3a contained 6, 4, and 6 types of glycosidic linkages, respectively. RLP-1a and RLP-3a exhibited distinct antioxidant abilities on the superoxide anions, 1,1-diphenyl-2-picrylhydrazyl (DPPH), and hydroxyl radicals in vitro. RLPs could decrease the serum lipid levels, elevate the serum high-density lipoprotein cholesterol levels, enhance the antioxidant enzymes levels, and upregulate of FADS2, ACOX3, and SCD-1 which involved in the lipid metabolic processes and oxidative stress in the high-fat diet-induced rats. These results suggested that RLPs ameliorated the high-fat diet- (HFD-) induced lipid metabolism disturbance in the rat liver through the peroxisome proliferator-activated receptor (PPAR) signaling pathway. Low molecular weight polysaccharides of RLP could be served as a novel potential functional food for improving hyperlipidemia and liver oxidative stress responses.Microwave and steam blanching as pretreatments to hot air drying of orange-fleshed sweet potato (OFSP) were studied. The air-drying experiment was performed at constant temperature of 70°C and airflow of 1.0 m/s. The effective moisture diffusivity varied from 1.5 × 10-9 to 4.4 × 10-9 m2/s, and 1.1 × 10-10 to 7.9×10-10 m2/s, for the microwave and blanched assisted hot air drying, respectively. The activation energy obtained for the various microwave-assisted hot air drying was 29.1 W/mm for 4 min, 68.1 W/mm for 3 min, and 79.7 W/mm for 2 min. Ascorbic acid degradation and formation of brown pigments in the OFSP slices were lower in microwave than in steam blanch-assisted drying. Microwave-assisted drying of OFSP is best governed by Page model, MR = exp(-ktn), while the blanch-assisted followed the logarithmic model, MR = a exp(-kt) + c. To produce better quality OFSP flour, it is recommended to cut the tubers into 3 mm slices, microwave at a power of 630 W for 2 min or blanch for 1 min, 43 seconds prior to hot air drying.[This corrects the article DOI 10.21037/atm.2020.03.229.].Despite significant therapeutic progress, gastric cancer remains among the most deadly forms of cancer encountered in clinical practice, and this remains true even in the context of declining incidence. Outcomes in advanced disease remain poor and therapy is rarely curative in this setting. As our understanding of tumor profile gains sophistication, a growing interest in targeted therapies and moreover the use of tumor profile to inform these therapies has developed in the hopes of altering nearly uniformly poor outcomes. A wide and growing array of molecular targets have been identified in the recent past. Targets of potential clinical interest include human epidermal growth factor receptor-2 (HER2), epidermal growth factor receptor (EGFR), poly(ADP-ribose) polymerase (PARP), mammalian target of rapamycin (mTOR), c-MET, and fibroblast growth factor receptor (FGFR). This advanced molecular understanding has been increasingly used to justify the off-label usage of targeted therapies, though the efficacy of this approach warrants careful consideration. While targeted agents have demonstrated efficacy across a wide range of malignancies, even with molecular profiling data, efficacy is not assured. It will also be demonstrated that even within the same malignancy, what holds true in the metastatic setting does not necessarily apply to the adjuvant or neoadjuvant setting. This review will assess the current evidence for the use of targeted therapies utilizing these biomarkers in the context of gastric and gastroesophageal (GE) junction cancers.Gastric and gastroesophageal junction (GEJ) cancer is one of the most common malignancy worldwide. In unresectable or metastatic disease, the prognosis is poor and is generally less than a year. Standard front-line chemotherapy includes two- or three-drug regimens with the addition of trastuzumab in HER2-positive disease. With an increased understanding of the biology of cancer over the past few decades, targeted therapies have made their way into the treatment paradigm of many cancers. They been examined in the first- and second-line settings in the treatment of gastroesophageal cancer though has yielded few viable treatment options. One success is ramucirumab either as monotherapy or in combination with paclitaxel is the preferred choice in second-line therapy. While immunotherapy has been considered a breakthrough in oncology over the past decade, the response rates in gastric and gastroesophageal cancers have been relatively low compared to other cancers, resulting in its limited approval and mostly reserved for second-line therapy or beyond. In this article, we will review the standard first- and second-line treatment regimens. Furthermore, this article will review the use of targeted therapies and immunotherapy in treatment of gastric and gastroesophageal cancers. Lastly, we will touch upon future treatment strategies that are currently under investigation.Gastric cancer is one of the most common cancers worldwide. While relatively uncommon in the United States, worldwide it is the 5th most common cancer diagnosed. Almost half of patients present with locoregional disease. Even with advanced surgical techniques and adjuvant perioperative treatment the prognosis for patients in this cohort is still dismal. Perioperative chemotherapy and/or radiation have been used in the last several decades in an attempt to improve outcomes in locally advanced resectable gastric cancer. In this article, we will review the development of these multimodal treatment strategies over the past two to three decades. We will compare these treatment modalities and their impact on survival outcomes. We will review the evidence for perioperative chemotherapy and radiotherapy, used in isolation and in combination. We will evaluate the evidence for these various treatment strategies and discuss how this impacts the current guidelines and recommendations. While advanced locoregional gastric cancer continues to carry significant mortality, several recent studies have added to the armament of treatment options and have seen significant improvement in progression free and overall survival in this patient population. Ongoing studies into perioperative management continue to investigate alternative treatment options and best practice for locally advanced resectable gastric cancer.Barrett’s esophagus (BE) is a condition resulting from an acquired metaplastic epithelial change in the esophagus in response to gastroesophageal reflux. BE is the only known precursor lesion to esophageal adenocarcinoma, and can progress from non-dysplastic BE (NDBE) to low grade dysplasia (LGD) and high grade dysplasia (HGD), and ultimately invasive carcinoma. Although the risk of developing esophageal adenocarcinoma (EAC) in NBDE is less than 0.5% per year, there has been a rising incidence of EAC in Western countries, which continue to drive efforts to optimize screening and surveillance methods. The current gold standard for diagnosis is esophagogastroduodenoscopy (EGD), and there has been significant interest in alternative, minimally invasive methods for screening which would be more readily accessible in the primary care setting. Surveillance endoscopy in 3-5 years is recommended for NDBE given the low progression to EAC. The mainstay of treatment for LGD and HGD is endoscopic eradication therapy (EET). Visible lesions are treated with endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD). Radiofrequency ablation (RFA) is considered first line therapy for flat dysplastic BE and cryotherapy has shown promising results as an alternate form of treatment for of dysplasia. The molecular progression of BE to EAC is a complex process involving multiple pathways involving genetic and epigenetic modifications. Genomic studies have further led to the understanding of the complex molecular landscape that occurs early and late in the disease process. Promising biomarker panels have been investigated to help with the diagnosis of BE as well as aid in the risk stratification of BE during surveillance. In addition, clinical prediction models have been developed to categorize BE patients in low, intermediate, and high risk for progression to HGD and EAC. Further clinical and translational research is needed to help refine markers and techniques in diagnosis, screening, and surveillance.Esophageal cancer (EC) and gastric cancer (GC) carry a high mortality rate. Unfortunately, a majority of patients are asymptomatic and at the time of diagnosis, the disease may invariably be in its advanced stages with limited curative options. Thus, it is imperative to recognize certain risk factors including gastroesophageal reflux disease (GERD), male gender, pre-existing Barrett’s esophagus, smoking history, obesity, Helicobacter pylori infection, atrophic gastritis among others for both EC and GC, intervene on time with screening and surveillance modalities if indicated and optimize treatment plans. With advances in endoscopic techniques, early neoplastic lesions are increasingly managed by gastroenterologists, offering an alternative to surgery. The gold standard for diagnosis of EC and GC is high definition endoscopy with adequate targeted biopsies. Endoscopic ultrasound (EUS) is a key in the staging of early cancers dictating the pathway for treatment options. We also play a key role in palliation cases with the aim to reduce the symptoms like nausea, vomiting and even when possible, restore oral intake and improve nutrition in both advanced GC and EC. This review article discusses the risk factors, diagnostic and endoscopic treatment modalities of early EC and GC and palliation of advanced cancer where gastroenterologists play a key role.The management of diseases such as cancer in developing countries are often suboptimal given a lack of resources and access to specialists and therapeutics. In March 2020, Syria descended into its ninth year of the war with a rising death toll and millions of Syrian refugees. Aside from the inherent dangers of war, cancer care during war is especially difficult with partially or non-functional infrastructure due to destruction, inconsistent electrical power, inaccessibility, or the inherent dangers of living in a war zone. Furthermore, limitations to therapeutics are exacerbated when supply chains responsible for bringing in essential medications such as chemotherapeutics are disrupted by international economic sanctions. Aleppo, Syria is the site of some of the fiercest fighting which ended in December 2016. Since then, Aleppo has made a slow recovery to rebuild its infrastructure while the war continues elsewhere in the country. In this article, we aim to highlight the challenges in the management of cancer, particularly esophageal cancer, during a time of war in Aleppo, Syria. We aim to discuss current challenges and limitations to care in a war zone. We will also touch upon areas of need for continued improvement in the care of cancer patient’s in Aleppo, Syria.Gastroesophageal cancers are some of the most common malignancies worldwide. A significant portion of patients are diagnosed with advanced or metastatic disease given the insidious nature of gastroesophageal cancers. In the instance where surgical resection for cure is no longer an option, the prognosis is poor and generally less than a year. Traditionally, standard front-line chemotherapy included two- to three-drug regimens with modest improvements in overall survival. Over the past two decades, with increased understanding of the biology of cancer, targeted therapies have been developed to stop the actions of molecules that are key in the growth and spread of cancer cells and have been successful in a number of cancers. In gastroesophageal cancer, these gains have been more modest with limited approval-trastuzumab being incorporated into front-line use in HER2-positive disease, and ramucirumab alone or in combination with paclitaxel becoming the preferred second-line regimen in progressive disease. However, with increased understanding of the biology of cancer, new and promising targeted therapies have emerged along with novel strategies in combining targeted therapies with traditional chemotherapy and immunotherapy. In this article, we will review the use of targeted therapies in the treatment of gastroesophageal cancer and touch upon future treatment strategies and therapeutics currently under investigation.Approximately 18,000 patients annually in the United States are diagnosed with adenocarcinoma or squamous cell carcinoma of the esophagus. These patients have numerous and complex symptoms, including pain, dysphagia, malnutrition and psychological symptoms due to location of the tumor and required treatments, and patients benefit from a comprehensive approach to care to effectively support their physical, emotional and spiritual needs. Palliative care is a medical subspecialty that focuses on providing comprehensive care for patients with any kind of advanced or serious illness to allow them to live well and fully for as long as possible in the face of that illness. In recent years, palliative care has become more widely available to patients with esophageal cancer and this is beneficial for patients with esophageal cancer given the severity of symptoms and complexities of needs. Primary oncology providers should provide basic palliative care including symptom management and clear communication, and palliative care specialists can provide additional support to extend the care of the primary clinician and treat the advanced and complex physical and psychological symptoms, as well as engaging in advance care planning. This paper outlines the key components of high-quality palliative care, including advanced care planning, symptom management and psychosocial support.Transanal minimally invasive surgery (TAMIS) is mainly used for benign tumors of the rectum, but there are few reports on treating malignant tumors of the rectum with a large volume. The aim of this study was to evaluate the feasibility and safety of TAMIS for resection of rectal malignant tumors. A 57-year-old patient was pathologically diagnosed as rectal malignancy before surgery. Computed tomography (CT), magnetic resonance imaging (MRI), fludeoxyglucose-18F (18F-FDG), and endoscopic mucosal biopsy were performed to assess the tumor location and preoperative size. There were no contraindications in all preoperative examinations. We applied TAMIS technology to perform the operation on this patient, And the operative time, the amount of blood loss, the length of hospital stay, the cost of hospital stay, surgical complications, postoperative complications and other relevant data were all collected. The operation was successful, the operation time was 45 min, 10 mL of intraoperative blood loss, and the length of stay was 3 days, a tumor of a maximum diameter of 4 cm being completely removed. There were no related complications or recurrence during postoperative follow-up. The pathological results were tubular villous adenoma with low-grade intraepithelial neoplasia, and a focal area of high-grade intraepithelial neoplasia. The pathological stage was T1N0M0. At 3-month follow-up there were no signs of recurrence. The patient was followed up for 5 years after the operation and there was no tumor recurrence or metastasis in other parts and no other discomfort. TAMIS is less commonly used in rectal malignancies, especially for tumors with larger diameters. We successfully performed complete resection of a 4-cm rectal malignant tumor with TAMIS. Given its low risk, low cost, simple operation, and few complications, TAMIS can be used for more indications of rectum diseases.Hyperprogressive disease (HPD) is a phenomenon defined as extremely rapid tumor progression within a short time following immunotherapy. To date, distinguishing which subgroups may be eligible for anti-PD-1/PD-L1 treatment has presented a clinical challenge. Moreover, no sufficiently convincing biomarkers of HPD have been identified. Herein, we present two cases of cancer patients who suffered from liver metastasis before immunotherapy. A 63-year-old man presented with cough and pain in right collarbone. He was finally diagnosed as suffering from right upper lobe adenocarcinoma with cTxN3M1c and stage IVB. First-line carboplatin plus pemetrexed chemotherapy combined with sintilimab anti-PD-1 was initiated after a multi-disciplinary discussion. In the second case, a 46-year-old female was diagnosed as moderately differentiated cervical squamous cell carcinoma. Widespread recurrence 2 years after extensive total hysterectomy for early cervical carcinoma. After six cycles of first-line chemotherapy and radiotherapy, the disease progressed and new-onset liver metastasis was detected. Pembrolizumab plus abraxane was administered as second-line therapy. After the first cycle of anti-PD-1 therapy, in both cases, an extremely rapid radiological progression was observed in the liver metastases with obvious symptoms, while the primary tumor site and other metastatic lesions remained stable or shrunken. These aberrations were confirmed as HPD. The risk of HPD appears to be higher in patients with liver metastases. We believe that further research will pave the way for the discovery of more significant biomarkers of HPD.Gallbladder cancer (GBC) is the most aggressive malignancy of the biliary tract with poor prognosis. Several targetable genetic alterations have been identified in GBC; however, responses to targeted therapy are disappointing. We report a case of a 58-year-old Chinese woman with GBC who was detected with a novel ALK genomic rearrangement and received crizotinib after progression from first-line chemotherapy. The patient was diagnosed with stage IV adenocarcinoma of the neck of the gallbladder and received oxaliplatin combined with capecitabine as first-line therapy. After four cycles of this chemotherapy regimen, the patient started to show obstructive jaundice, and progressive disease was evaluated. Biliary drainage surgery was performed to alleviate the symptoms of obstructive jaundice. Upon referral to our department, her archived tissue samples were submitted for next-generation sequencing (Burning Rock Biotech) and immunohistochemistry, which identified the presence of a novel AMBRA1-ALK rearrangement and ALK overexpression, respectively. Oral crizotinib was administered achieving partial response within two cycles of treatment, which lasted for 7 months. AMBRA1-ALK has not been previously reported in any solid tumors and its sensitivity to crizotinib is not well characterized. Moreover, ALK alterations have been rarely reported for GBC. This case suggests that a subset of GBC might be driven by aberrant ALK signaling, which could potentially be explored as a biomarker of therapeutic response to ALK inhibitors in GBC. Moreover, our case report contributes an incremental step in understanding the genetic heterogeneity in GBC and provides clinical evidence of the utility of next-generation sequencing in exploring actionable mutations to expand treatment choices in rare solid tumors including GBC.Hyponatremia is a common feature during the neurovisceral acute attacks which characterize hepatic porphyrias, as well as a sign of its severity. Therapeutic options for first-line acute attacks are intravenous administration of glucose and/or exogenous heme. The former treatment can aggravate hyponatremia by dilution and cause seizures; thus, the correction of hyponatremia must be carried out with extreme caution. This review summarizes recommendations for the management of hyponatremia during acute episodes of porphyria. Hyponatremia should be corrected slowly and seizures treated with medications in order to not exacerbate motor and sensory axonal neuropathy. The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is considered a frequent cause of hyponatremia in acute porphyrias and must be identified as a symptom of an acute porphyria attack. Tolvaptan produces aquaresis and is considered a safe drug in porphyria. However, its use has only been reported in isolated cases during a porphyria attack. The convenience and usefulness of this drug in acute porphyria are discussed.Tremendous progress has been achieved in understanding of the interaction between tumor microenvironment and intestinal flora in the past decades. Immune checkpoint inhibitors (ICIs) are a promising treatment strategy for advanced tumors, most prominently cytotoxic T-lymphocyte-associated protein (CTLA-4) and programmed cell death protein-1 (PD-1), its major ligand PD-L1, its beneficial to part of the population and obtaining excellent clinical results. However, the majority of patients do not respond or develop early progressive disease. Reached consensus by experts currently believe that the intestinal flora plays an important role in the explanation of the limited therapeutic effect of ICIs, there are differences in the composition of intestinal flora between patients with good response and patients with poor response, cloned mice by fecal microbiota transplantation (FMT) proved that the mice with transplanted feces from patients with good response can reduce tumor volume and obtain a better progress free survival (PFS). Therefore, „beneficial bacteria” seem to be enriched in the intestinal flora of patients who are well-responsive to ICIs and can be potentially used as a marker and cancer immunotherapeutic adjuvant of ICIs. In this review, we aim to summarize some of the studies demonstrating intestinal flora on tumor immunotherapy through anti-PD1, anti-PD-L1, anti-CTLA-4 and discuss possible mechanisms of this effect.Regenerative translational studies must include a longitudinal assessment of the changes in retinal structure and function that occur as part of the natural history of the disease and those that result from the studied intervention. Traditionally, retinal structural changes have been evaluated by histological analysis which necessitates sacrificing the animals. In this review, we describe key imaging approaches such as fundus imaging, optical coherence tomography (OCT), OCT-angiography, adaptive optics (AO), and confocal scanning laser ophthalmoscopy (cSLO) that enable noninvasive, non-contact, and fast in vivo imaging of the posterior segment. These imaging technologies substantially reduce the number of animals needed and enable progression analysis and longitudinal follow-up in individual animals for accurate assessment of disease natural history, effects of interventions and acute changes. We also describe the benefits and limitations of each technology, as well as outline possible future directions that can be taken in translational retinal imaging studies.Immunotherapy has become a powerful clinical strategy in cancer treatment. Immune checkpoint inhibitors (ICIs) have opened a new era for cancer immunotherapy. Nowadays, the number of immunotherapy drug approvals has increased, with numerous treatment options in clinical and preclinical development. However, there remain some obstacles to improve the efficacy of ICIs further. The tumor immune microenvironment (TIME) consists of cancer cell, immune cells and cytokines, et cetera. The dynamics of TIME determine the efficacies of ICIs. Although the ICIs showed manageable toxicity, immune-related adverse effects (irAEs) are still unignorable for clinicians. Since some primary resistance mechanisms exist in TIME, ICIs can only show effects in individual cancer patients. Even for the patients who responded, acquired resistance will occur to neutralize the effect of ICIs. Understanding how to increase the response rates and overcome the resistance to various classes of ICIs is the key to improving clinical efficacy. Besides the novel ICIs in development, there are some approaches to establish combination therapies are underway to improve further the efficacies of ICIs in treating cancer patients. Here, we describe the complicated TIME and state quo of ICIs to prospect the future of ICIs in cancer treatment.Radiological studies have an important role in the diagnosis and follow up of many infectious diseases. With current pandemic of Coronavirus disease 2019 (COVID-19) though the molecular analysis with reverse transcriptase polymerase chain reaction (RT-PCR) remains the cornerstone of diagnosis, the critical role of chest imaging including CT scan and baseline X-ray became apparent early in the course due to concern for less than optimal sensitivity of PCR testing. Delay in molecular diagnosis due to a shortage of testing kits and laboratory personnel also makes imaging an important modality in early diagnosis for appropriate triage and isolation decisions. CT scan technology is widely available in developed parts of the world but in developing countries, CT scanner is not widely available especially in rural settings. CT imaging usually requires patient movement to the radiology department and the scanner is not easy to disinfect. Point of care ultrasound (POCUS) has been used for many years in the assessment of critically ill patients in emergency departments and intensive care units. It is rapidly gaining popularity across many specialties and part of many general medicine training programs across the United States. It can be learned rapidly and with experienced hands, POCUS can help identify disease patterns in the lung parenchyma, and during the current pandemic has been gaining special attention. In this article, we review the most prominent imaging findings on chest X-ray and CT scan in patients with COVID-19. We also focus on the background and evolution of POCUS with studies showing the promising role of this diagnostic modality in COVID-19 infection. In addition, we describe step by step guidance on the use and disinfection of the portable ultrasound machine.Chimeric antigen receptor T-cell (CAR-T) therapy has achieved good therapeutic efficacy in the treatment of hematological malignancies. In August 2017, Novartis Kymriah (CAR-T cells targeting CD19) was approved by the FDA, indicating the real entry of CAR-T cell therapy into clinical applications and making CAR-T cell therapy the most attractive technology in the field of tumor treatment. In October 2017, the FDA approved the world’s second CAR-T cell therapy-Yescarta. The launch of these products has attracted wide attention to CAR-T cell therapy. CAR-T cell therapy has achieved significant effect in the treatment of tumors, however, CAR-T therapy also faces clinical problems, such as cytokine release syndrome (CRS), poor therapeutic efficacy in solid tumors, and high rates of tumor recurrence. At present, the side effects of CAR-T therapy have attracted a large amount of attention, which has resulted in investigations into strategy establishment. With a deepening understanding of CAR-T therapy and the continuous optimization of therapeutic regimens, its toxicity and side effects have been partially controlled. This study set out to analyze the problems in the clinical application of CAR-T therapy encountered in recent years and to introduce corresponding strategies, with the aim of providing a basis of reference for clinicians and scientists in the management of CAR-T therapy in clinical practice and in the CAR-T therapy research.Transfer RNA-derived small RNA (tsRNA)s are novel non-coding RNAs, expressed in a variety of tissues and organs. Two subtypes of tsRNAs have been reported tRNA-derived stress-induced RNA (tiRNA)s and tRNA-derived fragment (tRF)s. tsRNAs have been reported to play essential roles and possess different biological functions in a variety of physiological activities. Recently, tsRNAs have been implicated in a large number of diseases, such as cancers (including breast cancer, ovarian cancer, lung cancer, prostate cancer, colorectal cancer, etc.), neurological disorders, viral infections, metabolic diseases and angiogenesis-related diseases. Although the biological functions of tsRNAs are still poorly understood, correlations between dysregulated tsRNA expression and disease development have been recently reported. Additionally, their capabilities as potential biomarkers for disease diagnosis and prognosis have been revealed in clinical studies. In this review, we summarize the current knowledge of tsRNAs, and discuss their potential clinical applications as biomarkers in different diseases. Although the regulation of tsRNAs is similar to miRNAs in regards to the related physiological and pathological processes, the higher stability and expression levels of tsRNAs place them as ideal biomarkers for the diagnosis and prognosis in cancer and other diseases. Therefore, it is worth to verify the possibility and reliability of these reported tsRNAs as potential biomarkers for clinical applications in disease diagnosis and prognosis.Circular RNA (circRNA), as a cluster of endogenous non-coding RNA (ncRNA) with tissue-specific expression in various eukaryotic species, may be involved in a variety of human physiological and pathological processes. With the continuous development of high-throughput sequencing in recent years, circRNA has been increasingly widely studied and become a hot spot in the field of tumor research. The immune system plays a crucial and complex role in tumor development. It is not only capable of inhibiting tumor progression, but it can also create conditions suitable for tumor development, thereby promoting tumor progression. Moreover, through ncRNA, tumor immunotherapy, as an essential means of tumor therapy, may regulate tumor immunity to achieve the purpose of treatment. This article reviews the role of circRNA in tumor immunity to supply a sufficient theoretical basis for tumor immunotherapy.

Deep vein thrombosis (DVT) is an early postoperative complication. Thrombosis formation, which is potentially life-threatening, seriously affects the rehabilitation of patients after surgery. We aimed to establish a C57 mouse model of DVT and to examine the changes in the expression of Krüppel-like factor 15 (KLF15) and endothelial nitric oxide synthase (eNOS) in venous wall tissues, and we also investigated the regulatory relationship of KLF15 and eNOS in the thrombin-induced human umbilical vein endothelial cell (HUVEC) injury cell model.

The DVT model was established using the inferior vena cava (IVC) stenosis method. The expression levels of KLF15 and eNOS were analyzed using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). In cell experiments, the expression of KLF15 and eNOS was analyzed in the model of thrombin-induced HUVEC injury with KLF15 siRNA.

Compared to the control and sham-operated groups, KLF15 in the DVT group was upregulated, while eNOS was downregulated. The results of cell experiments revealed that KLF15 was downregulated in the thrombin+KLF15 siRNA group compared with the thrombin group.