Designs andmethodologies to recreate in vitro human gutmicrobiota models

The human gut microbiota is widely considered to be a metabolic organ hidden within our bodies,playing a crucial role in the host’s physiology.Several factors affect its composition,so a wide variety of microbes residing in the gut are present in the world population.Individual excessive imbalances in microbial composition are often associated with human disorders and pathologies,and new investigative strategies to gain insight into these pathologies and define pharmaceutical therapies for their treatment are needed.In vitro models of the human gut microbiota are commonly used to study microbial fermentation patterns,community composition,and host-microbe interactions.Bioreactors and microfluidic devices have been designed to culture microorganisms from the human gut microbiota in a dynamic environment in the presence or absence of eukaryotic cells to interact with.In this review,we will describe the overall elements required to create a functioning,reproducible,and accurate in vitro culture of the human gut microbiota.In addition,we will analyze some of the devices currently used to study fermentation processes and relationships between the human gut microbiota and host eukaryotic cells.

An oxygenating colloidal bioink for the engineering of biomimetic tissue constructs

Ensuring a sufficient oxygen supply is pivotal for the success of bioprinting applications since it fosters tissue integration and natural regeneration.Variation in oxygen concentration among diverse tissues necessitates the precise recreation of tissue-specific oxygen levels in imprinted constructs to support the survival of targeted cells.Although oxygen-releasing biomaterials,such as oxygen-generating microparticles(OMPs),have shown promise for enhancing the oxygen supply of microenvironments in injured tissues,whether this approach is scalable for large tissues and whether tissue-specific bioinks with varying OMP concentrations remain printable remain unknown.This study addresses this critical gap by introducing an innovative class of engineered oxygenated bioinks that combine colloidal-based microgels with OMPs.We report that incorporating nanosized calcium peroxide(nCaO_(2))and manganese oxide nanosheets(nMnO_(2))into hydrophobic polymeric microparticles enables precise modulation of oxygen release while controlling hydrogen peroxide release.Moreover,the fabrication of oxygenating and cytocompatible colloidal gels is achieved using an aqueous two-phase system.This study thoroughly evaluates the fundamental characteristics of the resulting bioink,including its rheological behaviors,printability,shape fidelity,mechanical properties,and oxygen release properties.Moreover,this study demonstrates the macroscopic scalability and cytocompatibility of printed constructs produced via cell-laden oxygenating colloidal bioinks.By showcasing the effectiveness of extrusion-based bioprinting,this study underscores how it can be used to fabricate biomimetic tissues,indicating its potential for new applications.The findings presented here advance the bioprinting field by achieving scalability with both high cell viability and the possibility of mimicking specifically oxygenated tissues.This work thereby offers a promising avenue for the development of functional tissues with enhanced physiological relevance.

Role of the immune microenvironment in bone,cartilage,and soft tissue regeneration:from mechanism to therapeuticopportunity

Bone,cartilage,and soft tissue regeneration is a complex spatiotemporal process recruiting a variety of cell types,whose activity and interplay must be precisely mediated for effective healing post-injury.Although extensive strides have been made in the understanding of the immune microenvironment processes governing bone,cartilage,and soft tissue regeneration,effective clinical translation of these mechanisms remains a challenge.Regulation of the immune microenvironment is increasingly becoming a favorable target for bone,cartilage,and soft tissue regeneration;therefore,an in-depth understanding of the communication between immune cells and functional tissue cells would be valuable.Herein,we review the regulatory role of the immune microenvironment in the promotion and maintenance of stem cell states in the context of bone,cartilage,and soft tissue repair and regeneration.We discuss the roles of various immune cell subsets in bone,cartilage,and soft tissue repair and regeneration processes and introduce novel strategies,for example,biomaterial-targeting of immune cell activity,aimed at regulating healing.Understanding the mechanisms of the crosstalk between the immune microenvironment and regeneration pathways may shed light on new therapeutic opportunities for enhancing bone,cartilage,and soft tissue regeneration through regulation of the immune microenvironment.

Endoscopic ultrasound artificial intelligence-assisted for prediction of gastrointestinal stromal tumors diagnosis:A systematic review and meta-analysis

BACKGROUND Subepithelial lesions(SELs)are gastrointestinal tumors with heterogeneous malignant potential.Endoscopic ultrasonography(EUS)is the leading method for evaluation,but without histopathological analysis,precise differentiation of SEL risk is limited.Artificial intelligence(AI)is a promising aid for the diagnosis of gastrointestinal lesions in the absence of histopathology.AIM To determine the diagnostic accuracy of AI-assisted EUS in diagnosing SELs,especially lesions originating from the muscularis propria layer.METHODS Electronic databases including PubMed,EMBASE,and Cochrane Library were searched.Patients of any sex and>18 years,with SELs assessed by EUS AIassisted,with previous histopathological diagnosis,and presented sufficient data values which were extracted to construct a 2×2 table.The reference standard was histopathology.The primary outcome was the accuracy of AI for gastrointestinal stromal tumor(GIST).Secondary outcomes were AI-assisted EUS diagnosis for GIST vs gastrointestinal leiomyoma(GIL),the diagnostic performance of experienced endoscopists for GIST,and GIST vs GIL.Pooled sensitivity,specificity,positive,and negative predictive values were calculated.The corresponding summary receiver operating characteristic curve and post-test probability were also analyzed.RESULTS Eight retrospective studies with a total of 2355 patients and 44154 images were included in this meta-analysis.The AI-assisted EUS for GIST diagnosis showed a sensitivity of 92%[95%confidence interval(CI):0.89-0.95;P<0.01),specificity of 80%(95%CI:0.75-0.85;P<0.01),and area under the curve(AUC)of 0.949.For diagnosis of GIST vs GIL by AI-assisted EUS,specificity was 90%(95%CI:0.88-0.95;P=0.02)and AUC of 0.966.The experienced endoscopists’values were sensitivity of 72%(95%CI:0.67-0.76;P<0.01),specificity of 70%(95%CI:0.64-0.76;P<0.01),and AUC of 0.777 for GIST.Evaluating GIST vs GIL,the experts achieved a sensitivity of 73%(95%CI:0.65-0.80;P<0.01)and an AUC of 0.819.CONCLUSION AI-assisted EUS has high diagnostic accuracy for fourth-layer SELs,especially for GIST,demonstrating superiority compared to experienced endoscopists’and improving their diagnostic performance in the absence of invasive procedures.

Targeting epigenetic mechanisms in amyloid-β-mediated Alzheimer’s pathophysiology:unveiling therapeutic potential

Alzheimer’s disease is a prominent chronic neurodegenerative condition characterized by a gradual decline in memory leading to dementia.Growing evidence suggests that Alzheimer’s disease is associated with accumulating various amyloid-βoligomers in the brain,influenced by complex genetic and environmental factors.The memory and cognitive deficits observed during the prodromal and mild cognitive impairment phases of Alzheimer’s disease are believed to primarily result from synaptic dysfunction.Throughout life,environmental factors can lead to enduring changes in gene expression and the emergence of brain disorders.These changes,known as epigenetic modifications,also play a crucial role in regulating the formation of synapses and their adaptability in response to neuronal activity.In this context,we highlight recent advances in understanding the roles played by key components of the epigenetic machinery,specifically DNA methylation,histone modification,and microRNAs,in the development of Alzheimer’s disease,synaptic function,and activity-dependent synaptic plasticity.Moreover,we explore various strategies,including enriched environments,exposure to non-invasive brain stimulation,and the use of pharmacological agents,aimed at improving synaptic function and enhancing long-term potentiation,a process integral to epigenetic mechanisms.Lastly,we deliberate on the development of effective epigenetic agents and safe therapeutic approaches for managing Alzheimer’s disease.We suggest that addressing Alzheimer’s disease may require distinct tailored epigenetic drugs targeting different disease stages or pathways rather than relying on a single drug.

Antibodies Targeting a Conserved Surface Polysaccharide Are Protective Against a Wide Range of Microbial Pathogens Producing b-1-6-Linked Poly-N-Acetylglucosamine(PNAG)

The b-1-6-linked poly-N-acetylglucosamine(PNAG)polymer is a conserved surface polysaccharide produced by many bacteria,fungi,and protozoan(and even filarial)parasites.This wide-ranging expression makes PNAG an attractive target for vaccine development,as it potentially encompasses a broad range of microorganisms.Significant progress has been made in discovering important properties of the biology of PNAG expression in recent years.The molecular characterization and regulation of operons for the production of PNAG biosynthetic proteins and enzymes have been studied in many bacteria.In addition,the physiological function of PNAG has been further elucidated.PNAG-based vaccines and PNAG-targeting antibodies have shown great efficacy in preclinical research.Furthermore,clinical tests for both vaccines and antibodies have been carried out in humans and economically important animals,and the results are promising.Although it is not destined to be a smooth road,we are optimistic about new vaccines and immunotherapeutics targeting PNAG becoming validated and eventually licensed for clinical use against multiple infectious agents.

N-acetylserotonin alleviates retinal ischemia-reperfusion injury via HMGB1/RAGE/NF-κB pathway in rats

AIM:To observe the effects of N-acetylserotonin(NAS)administration on retinal ischemia-reperfusion(RIR)injury in rats and explore the underlying mechanisms involving the high mobility group box 1(HMGB1)/receptor for advanced glycation end-products(RAGE)/nuclear factor-kappa B(NF-κB)signaling pathway.METHODS:A rat model of RIR was developed by increasing the pressure of the anterior chamber of the eye.Eighty male Sprague Dawley were randomly divided into five groups:sham group(n=8),RIR group(n=28),RIR+NAS group(n=28),RIR+FPS-ZM1 group(n=8)and RIR+NAS+FPS-ZM1 group(n=8).The therapeutic effects of NAS were examined by hematoxylin-eosin(H&E)staining,and retinal ganglion cells(RGCs)counting.The expression of interleukin 1 beta(IL-1β),HMGB1,RAGE,and nod-like receptor 3(NLRP3)proteins and the phosphorylation of nuclear factorkappa B(p-NF-κB)were analyzed by immunohistochemistry staining and Western blot analysis.The expression of HMGB1 protein was also detected by enzyme-linked immunosorbent assay(ELISA).RESULTS:H&E staining results showed that NAS significantly reduced retinal edema and increased the number of RGCs in RIR rats.With NAS therapy,the HMGB1 and RAGE expression decreased significantly,and the activation of the NF-κB/NLRP3 pathway was antagonized along with the inhibition of p-NF-κB and NLRP3 protein expression.Additionally,NAS exhibited an anti-inflammatory effect by reducing IL-1βexpression.The inhibitory of RAGE binding to HMGB1 by RAGE inhibitor FPS-ZM1 led to a significant decrease of p-NF-κB and NLRP3 expression,so as to the IL-1βexpression and retinal edema,accompanied by an increase of RGCs in RIR rats.CONCLUSION:NAS may exhibit a neuroprotective effect against RIR via the HMGB1/RAGE/NF-κB signaling pathway,which may be a useful therapeutic target for retinal disease.

Upper Gastrointestinal Cancers in Rwanda: Epidemiological, Clinical and Histopathological Features in Patients Presenting to a Tertiary Referral Hospital

Background: Scant data on upper gastrointestinal cancers in Rwanda exist to guide potential prevention efforts. We evaluated the epidemiological, clinical and histopathological data among patients with gastric and esophageal tumors at a tertiary Referral Hospital in Rwanda. Methodology: We performed a retrospective review of histologically-confirmed esophageal and gastric cancers in adults age ≥ 18 yrs. old presenting to a university teaching hospital (Centre Hospitalier Universitaire de Butare) from 2014-2019. Variables included age at diagnosis, sex, clinical presentation, tumor location and histopathological type. Results: There were 149 upper gastrointestinal cancers, of which 137 (92%) were gastric and 12 (8%) were esophageal. Gastric cancer patients had a mean age at presentation of 56.9 ± 12.3 years (range 21 - 87). Presenting symptoms were epigastric pain (78.8%), weight loss (53.3%), post-prandial vomiting (52.6%), early satiety (29.9%), epigastric mass (24.8%), hematemesis (19.7%) and melena (16.8%). The location was antrum 50.3%, corpus 21.8%, fundus 8%, and cardia 8%. Tumor type was adenocarcinoma in 94.1%. Helicobacter pylori infection was present in 108 (78.8%). Esophageal cancer patients had a mean age of 54.4 ± 9.5 years (range 35 - 72). Presenting symptoms were dysphagia (100%) and weight loss (83%). The most common site was lower third esophagus (9/12), and adenocarcinoma cancer subtype accounted for 5/12 (41.6%) cases. Conclusion: Gastric adenocarcinoma was the most commonly diagnosed upper gastrointestinal cancers and was associated with a high prevalence of H. pylori infection. This study lays the foundation for future work to improve cancer outcomes in Rwanda.

In-hospital outcomes and readmission in older adults treated with percutaneous coronary intervention for stable ischemic heart disease

Background Percutaneous coronary intervention(PCI)for stable ischemic heart disease(SIHD)in older adults requires a metic-ulous assessment of procedural risks and benefits,but contemporary data on outcomes in this population is lacking.Therefore,we examined the risk of near-term readmission,bleeding,and mortality in high-risk cohort of older adults undergoing inpatient PCI for SIHD.METHODS We analyzed the National Readmissions Database from 2017 to 2018 to identify index hospitalizations in which PCI was performed for SIHD.Patients were stratified into those≥75 years old(older adults)and those<75 years old.The primary outcome was 90-day readmission.Secondary outcomes included in-hospital mortality,hospital length of stay(LOS),and total hospital charge.RESULTS A total of 74,516 patients underwent inpatient PCI for SIHD,of whom 24,075 were older adults.Older adult patients had higher odds of in-hospital mortality(OR=2.00,95%CI:1.68-2.38),intracranial hemorrhage(OR=2.03,95%CI:1.24-3.34),and gastrointestinal hemorrhage(OR=1.72,95%CI:1.43-2.07)during index hospitalization,with longer LOS and in-hospital charge.Older adults also experienced a higher hazard of 90-day readmission for any cause(HR=1.61,95%CI:1.57-1.66)and car-diovascular causes(HR=1.84,95%CI:1.77-1.91).CONCLUSION Older adults undergoing inpatient PCI for SIHD were at increased risk for in-hospital mortality,periprocedural morbidities,higher cost,and readmissions compared with younger adults.Understanding these differences may improve shared decision-making for patients with SIHD being considered for PCI.

Endosonography in the diagnosis and management of pancreatic cysts

Rapid advances in radiologic technology and increased cross-sectional imaging have led to a sharp rise in incidental discoveries of pancreatic cystic lesions. These cystic lesions include non-neoplastic cysts with no risk of malignancy, neoplastic non-mucinous serous cystadenomas with little or no risk of malignancy, as well as neoplastic mucinous cysts and solid pseudopapillary neoplasms both with varying riskof malignancy. Accurate diagnosis is imperative as management is guided by symptoms and risk of malignancy. Endoscopic ultrasound(EUS) allows high resolution evaluation of cyst morphology and precise guidance for fine needle aspiration(FNA) of cyst fluid for cytological, chemical and molecular analysis. Initially, clinical evaluation and radiologic imaging, preferably with magnetic resonance imaging of the pancreas and magnetic resonance cholangiopancreatography, are performed. In asymptomatic patients where diagnosis is unclear and malignant risk is indeterminate, EUSFNA should be used to confirm the presence or absence of high-risk features, differentiate mucinous from non-mucinous lesions, and diagnose malignancy. After analyzing the cyst fluid for viscosity, cyst fluid carcinoembryonic antigen, amylase, and cyst wall cytology should be obtained. DNA analysis may add useful information in diagnosing mucinous cysts when the previous studies are indeterminate. New molecular biomarkers are being investigated to improve diagnostic capabilities and management decisions in these challenging cystic lesions. Current guidelines recommend surgical pancreatic resection as the standard of care for symptomatic cysts and those with high-risk features associated with malignancy. EUSguided cyst ablation is a promising minimally invasive, relatively low-risk alternative to both surgery and surveillance.

Life and death at the mucosal-luminal interface: New perspectives on human intestinal ischemia-reperfusion

Intestinal ischemia is a frequently observed phenomenon. Morbidity and mortality rates are extraordinarily high and did not improve over the past decades. This is in part attributable to limited knowledge on the pathophysiology of intestinal ischemia-reperfusion(IR) in man, the paucity in preventive and/or therapeutic options and the lack of early diagnostic markers for intestinal ischemia. To improve our knowledge and solve clinically important questions regarding intestinal IR, we developed a human experimental intestinal IR model. With this model, we were able to gain insight into the mechanisms that allow the human gut to withstand short periods of IR without the development of severe inflammatory responses. The purpose of this review is to overview the most relevant recent advances in our understanding of the pathophysiology of human intestinal IR, as well as the(potential) future clinical implications.

Endoscopic therapy for weight loss: Gastroplasty, duodenal sleeves, intragastric balloons, and aspiration

A new paradigm in the treatment of obesity and metabolic disease is developing. The global obesity epidemic continues to expand despite the availability of diet and lifestyle counseling, pharmacologic therapy, and weight loss surgery. Endoscopic procedures have the potential to bridge the gap between medical therapy and surgery. Current primary endoscopic bariatric therapies can be classified as restrictive, bypass, spaceoccupying, or aspiration therapy. Restrictive procedures include the USGI Primary Obesity Surgery Endolumenal procedure, endoscopic sleeve gastroplasty using Apollo Over Stitch, Trans Oral GAstroplasty, gastric volume reduction using the ACE stapler, and insertion of the TERIS restrictive device. Intestinal bypass has been reported using the EndoB arrier duodenal-jejunal bypass liner. A number of space-occupying devices have been studied or are in use, including intragastric balloons(Orbera, Reshape Duo, Heliosphere BAG, Obalon), Transpyloric Shuttle, and Sati Sphere. The Aspire Assist aspiration system has demonstrated efficacy. Finally, endoscopic revision of gastric bypass to address weight regain has been studied using Apollo Over Stitch, the USGI Incisionless Operating Platform Revision Obesity Surgery Endolumenal procedure, Stomaphyx, and endoscopic sclerotherapy. Endoscopic therapies for weight loss are potentially reversible, repeatable, less invasive, and lower cost than various medical and surgical alternatives. Given the variety of devices under development, in clinical trials, and currently in use, patients will have multiple endoscopic options with greater efficacy than medical therapy, and with lower invasiveness and greater accessibility than surgery.

Adult iatrogenic ureteral injury and strictureeincidence and treatment strategies

Iatrogenic ureteral injuries and strictures are relatively common complication of pelvic surgery and radiation treatment.Left untreated they are associated with severe shortand long-term complications such as urinoma,septic state,renal failure,and loss of a renal unit.Treatment depends on timing of diagnosis,as well as extent of injury,and ranges from simple endoscopic management to complex surgical reconstruction under usage of pedicled grafts.While recent advances in ureteral tissue engineering are promising the topic is still underreported.Historically a domain of open surgery,laparoscopic and robotic-assisted approaches have proven their feasibility in small case series,and are increasingly being utilized as means of reconstructive surgery.This review aims to give an outline of incidence and treatment of ureteral injuries and strictures in light of the latest advances.

Therapeutic uses of animal biles in traditional Chinese medicine:An ethnopharmacological,biophysical chemical and medicinal review

Forty-four different animal biles obtained from both invertebrates and vertebrates (including human bile) have been used for centuries for a host of maladies in traditional Chinese medicine (TCM) beginning with dog, ox and common carp biles approximately in the Zhou dynasty (c. 1046-256 BCE). Overall, different animal biles were prescribed principally for the treatment of liver, biliary, skin (including burns), gynecological and heart diseases, as well as diseases of the eyes, ears, nose, mouth and throat. We present an informed opinion of the clinical efficacy of the medicinal uses of the different animal biles based on their presently known principal chemical components which are mostly steroidal detergent-like molecules and the membrane lipids such as unesterified cholesterol and mixed phosphatidylcholines and sometimes sphingomyelin, as well as containing lipopigments derived from heme principally bilirubin glucuronides. All of the available information on the ethnopharmacological uses of biles in TCM were collated from the rich collection of ancient Chinese books on materia medica held in libraries in China and United States and the composition of various animal biles was based on rigorous separatory and advanced chemical identification techniques published since the mid-20th century collected via library (Harvard’s Countway Library) and electronic searches (PubMed and Google Scholar). Our analysis of ethnomedical data and information on biliary chemistry shows that specific bile salts, as well as the common bile pigment bilirubin and its glucuronides plus the minor components of bile such as vitamins A, D, E, K, as well as melatonin (N-acetyl-5-methoxytryptamine) are salutary in improving liver function, dissolving gallstones, inhibiting bacterial and viral multiplication, promoting cardiac chronotropsim, as well as exhibiting anti-inflammatory, anti-pyretic, anti-oxidant, sedative, anti-convulsive, anti-allergic, anti-congestive, anti-diabetic and anti-spasmodic effects. Pig, wild boar and human biles diluted with alcohol were shown to form an artificial skin for burns and wounds one thousand years ago in the Tang dynasty (618-907 CE). Although various animal biles exhibit several generic effects in common, a number of biles appear to be advantageous for specific therapeutic indications. We attempt to understand these effects based on the pharmacology of individual components of bile as well as attempting to identify a variety of future research needs.

Iliac vein compression syndrome: Clinical, imaging and pathologic findings

May-Thurner syndrome(MTS) is the pathologic compression of the left common iliac vein by the right common iliac artery, resulting in left lower extremity pain, swelling, and deep venous thrombosis. Though this syndrome was first described in 1851, there are currently no standardized criteria to establish the diagnosis of MTS. Since MTS is treated by a wide array of specialties, including interventional radiology, vascular surgery, cardiology, and vascular medicine, the need for an established diagnostic criterion is imperative in order to reduce misdiagnosis and inappropriate treatment. Although MTS has historically been diagnosed by the presence of pathologic features, the use of dynamic imaging techniques has led to a more radiologic based diagnosis. Thus, imaging plays an integral part in screening patients for MTS, and the utility of a wide array of imaging modalities has been evaluated. Here, we summarize the historical aspects of the clinical features of this syndrome. We then provide a comprehensive assessment of the literature on the efficacy of imaging tools available to diagnose MTS. Lastly, we provide clinical pearls and recommendations to aid physicians in diagnosing the syndrome through the use of provocative measures.

MicroRNA-218 is upregulated in gastric cancer after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy and increases chemosensitivity to cisplatin

AIM: To investigate the molecular mechanisms of miRNA in advanced gastric cancers (AGCs) before and after cytoreductive surgery (CRS) + hyperthermic intraperitoneal chemotherapy (HIPEC).

Endoscopic submucosal dissection of gastric tumors: A systematic review and meta-analysis

AIM: To systematically review the medical literature in order to evaluate the safety and efficacy of gastric endoscopic submucosal dissection(ESD).METHODS: We performed a comprehensive literature search of MEDLINE, Ovid, CINAHL, and Cochrane for studies reporting on the clinical efficacy and safety profile of gastric ESD.RESULTS: Twenty-nine thousand five hundred and six tumors in 27155 patients(31% female) who underwent gastric ESD between 1999 and 2014 were included in this study. R0 resection rate was 90%(95%CI: 87%-92%) with significant between-study heterogeneity(P < 0.001) which was partly explained by difference in region(P = 0.02) and sample size(P = 0.04). Endoscopic en bloc and curative resection rates were 94%(95%CI: 93%-96%) and 86%(95%CI: 83%-89%) respectively. The rate of immediate and delayed perforation rates were 2.7%(95%CI: 2.1%-3.3%) and 0.39%(95%CI: 0.06%-2.4%) respectively while rates of immediate and delayed major bleeding were 2.9%(95%CI: 1.3-6.6) and 3.6%(95%CI: 3.1%-4.3%). After an average follow-up of about 30 mo post-operative, the rate of tumor recurrence was 0.02%(95%CI: 0.001-1.4) among those with R0 resection and 7.7%(95%CI: 3.6%-16%) among those without R0 resection. Overall, irrespective of the resection status, recurrence rate was 0.75%(95%CI: 0.42%-1.3%).CONCLUSION: Our meta-analysis, the largest and most comprehensive assessment of gastric ESD till date, showed that gastric ESD is safe and effective for gastrictumors and warrants consideration as first line therapy when an expert operator is available.

Treatment-related gastrointestinal toxicities and advanced colorectal or pancreatic cancer:A critical update

Gastrointestinal toxicities(GIT), including oral mucositis,nausea and vomiting, and diarrhea, are common side effects of chemotherapy and targeted agents in patients with advanced colorectal cancer and pancreatic cancer. Being often underreported, it is still difficult to precisely establish their burden in terms of both patient's quality of life and cancer care costs. Moreover, with the use of more intensive upfront combination regimens, the frequency of these toxicities is rapidly growing with a potential negative effect also on patient's outcome, as a result of dose reductions, delays or even discontinuation of active treatments. Thus, identifying patients at higher risk of developing GIT as well as an optimal management are paramount in order to improve patient's compliance and outcome. After the description of the main treatment-induced GIT, we discuss the current knowledge on the pathophysiology of these side effects and comment the scales commonly used to assess and grade them. We then provide a critical update on GIT incidence based on the results of key randomized trials conducted in patients with metastatic colorectal cancer and advanced pancreatic cancer.

Epidemiologic studies of particulate matter and lung cancer

Particulate matter(PM) plays an important role in air pollution, especially in China. European and American researchers conducted several cohort-based studies to examine the potential relationship between PM and lung cancer and found a positive association between PM and lung cancer mortality. In contrast, the results regarding PM and lung cancer risk remain inconsistent. Most of the previous studies had limitations such as misclassification of PM exposure and residual confounders, diminishing the impact of their findings. In addition, prospective studies on this topic are very limited in Chinese populations. This is an important problem because China has one of the highest concentrations of PM in the world and has had an increased mortality risk due to lung cancer. In this context, more prospective studies in Chinese populations are warranted to investigate the relationship between PM and lung cancer.

Lipid dysregulation in hepatitis C virus, and impact of statin therapy upon clinical outcomes

The hepatitis C virus(HCV) is one of the most common causes of chronic liver disease and the leading indication for liver transplantation worldwide. Every aspect of the HCV life cycle is closely tied to human lipid metabolism. The virus circulates as a lipid-rich particle, utilizing lipoprotein cell receptors to gain entry into the hepatocyte. It has also been shown to upregulate lipid biosynthesis and impair lipid degradation, resulting in significant intracellular lipid accumulation and circulating hypocholesterolemia. Patients with chronic hepatitis C(CHC) are at increased risk of hepatic steatosis, fibrosis, and cardiovascular disease including accelerated atherosclerosis. HMG Co A Reductase inhibitors, or statins, have been shown to play an important role in the modulation of hepatic steatosis and fibrosis, and recent attention has focused upon their potential therapeutic role in CHC. This article reviews the hepatitis C viral life cycle as it impacts host lipoproteins and lipid metabolism. It then describes the pathogenesis of HCV-related hepatic steatosis, hypocholesterolemia and atherosclerosis, and finally describes the promising anti-viral and anti-fibrotic effects of statins, for the treatment of CHC.