Fatty liver is associated with significant liver inflammation and increases the burden of advanced fibrosis in chronic HBV infection.

BACKGROUND: Concurrent non-alcoholic fatty liver disease (NAFLD) is common in patients with chronic HBV infection. But the impact of fatty liver on the histologic progression of HBV infection remains controversial. METHODS: Consecutive HBV-infected patients who underwent liver biopsy between 2016 and 2021 were included. Alcohol consumption and other types of viral hepatitis were excluded. All biopsies were scored for grading and staging by Scheuer's score, and the steatosis was scored as an estimate of the percentage of liver parenchyma replaced by fat. Logistic regression analyses were applied to assess the associated factors for significant liver inflammation (G ≥ 2), significant fibrosis (S ≥ 2) and advanced fibrosis (S ≥ 3). RESULTS: Among the 871 HBV-infected patients, hepatic steatosis was prevalent in 255 patients (29.28%). Significant liver inflammation was present in 461 patients (52.93%). Significant fibrosis was observed in 527 patients (60.51%), while advanced liver fibrosis was observed in 171 patients (19.63%). Patients with concomitant NAFLD were more likely to have significant liver inflammation and advanced fibrosis. Fatty liver was an independent risk factor for significant liver inflammation (OR: 2.117, 95% CI: 1.500-2.988), but it could not predict the development of fibrosis. Especially, in HBV-infected patients with persistent normal ALT (immune tolerant and inactive carrier phase), the presence of significant liver inflammation was higher in NAFLD than those without NAFLD. The prevalence of advanced liver fibrosis was higher in NAFLD than non-NAFLD only in the immune tolerant phase, while NAFLD did not increase fibrosis burden in other stages of HBV infection. We developed a predictive model for significant liver inflammation with the area under receiver operating characteristic curve (AUROC) of 0.825, and a model for significant fibrosis with the AUROC of 0.760. CONCLUSIONS: NAFLD is independently associated with significant liver inflammation, and increases the burden of advanced liver fibrosis in HBV-infected patients. The influence of NAFLD on the degree of liver inflammation and fibrosis is different in distinct clinical phases of chronic HBV infection.

Acute Hepatitis E Induced the First Episode of Immune-Mediated Thrombotic Thrombocytopenic Purpura: The First Case Report.

Purpose: Hepatitis E virus infection mainly presents with liver-related symptoms, and multiple studies have shown that hepatitis E virus infection can also induce extrahepatic-related symptoms. Thrombotic thrombocytopenic purpura is an uncommon and fatal thrombotic microangiopathy characterized by severe thrombocytopenia, organ damage, and microangiopathic haemolytic anaemia. We report the first case in which acute hepatitis E induced the first episode of immune-mediated thrombotic thrombocytopenic purpura. Patients and Methods: A 53-year-old male was admitted to our emergency department with fever, thrombocytopenia, and abnormal liver function. Laboratory tests revealed significant bilirubin, AST, and ALT elevations, renal impairment, positive anti-HEV IgM and IgG antibody results, schistocytes on the blood smear, 0% ADAMTS-13 activity, and positive ADAMTS13 inhibitor results. He was diagnosed with acute hepatitis E, which induced the first episode of immune-mediated thrombotic thrombocytopenic purpura. Results: After receiving treatment with plasmapheresis, glucocorticoid medication, rituximab, and other supportive medicines, the patient's physiological circumstances and laboratory indicators improved, and a 4-month follow-up revealed no abnormalities. Conclusion: This is a unique case report of an acute hepatitis E-induced immune-mediated thrombotic thrombocytopenic purpura initial episode. This case report offers evidence that hepatitis E virus infection can cause thrombotic thrombocytopenic purpura. In patients with abnormal liver function and thrombocytopenia, we advise screening for hepatitis E or thrombotic thrombocytopenic purpura.

Preoperative and postoperative clinical signatures of postgastrectomy venous thromboembolism in patients with gastric cancer: A retrospective cohort study.

BACKGROUND: This study aimed to identify preoperative and postoperative risk factors of venous thromboembolism (VTE) after gastrectomy in gastric cancer (GC) patients. METHODS: 757 GC patients underwent gastrectomy at our institution and 246 patients with elevated postoperative D-dimer levels who received Doppler ultrasonography of lower/upper extremity veins were enrolled. Clinicopathological factors data were collected, and the differences in clinicopathological factors between postoperative VTE (+) and VTE (-) groups were analyzed. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors of postgastrectomy VTE. RESULTS: Of 246 patients with elevated postgastrectomy D-dimer concentrations, 74 patients showed thrombosis in lower/upper extremity veins. Among preoperative factors, age, WBC level, D-dimer concentration, and blood glucose level were significantly higher in the postoperative VTE (+) group. Among the postoperative factors, hemoglobin level was significantly lower in the postoperative VTE (+) group. Among the pathological factors, tumor stage, depth of invasion and TNM classification indicated higher malignancy in the postoperative VTE (+) group. Univariate logistic regression analysis indicated age, preoperative blood glucose level, postoperative hemoglobin level, tumor stage, depth of invasion, and TNM classification as the independent risk factors for postgastrectomy VTE, whereas multivariate logistic regression analysis revealed age and tumor stage as independent risk factors for postgastrectomy VTE. CONCLUSION: Our study revealed that age, preoperative blood glucose level, postoperative anemia, and tumor malignancy were independent risk factors for GC patients exhibiting postgastrectomy VTE. Therefore, the perioperative monitoring, assessment and management of risk factors are important in achieving better outcomes after gastrectomy.

Three-years misdiagnosis of Niemann Pick disease type B with novel mutations in SMPD1 gene as Budd-Chiari syndrome.

BACKGROUND: The chronic visceral subtype of acid sphingomyelinase deficiency, commonly known as Niemann Pick disease type B (NPDB), is a relatively rare autosomal recessive genetic disorder that is caused by mutations in the SMPD1 gene. NPDB with sea-blue histiocytes (SBH) clinically mimics Budd-Chiari syndrome (BCS), as it lacks specific clinical characteristics. This makes its diagnosis difficult. CASE PRESENTATION: Here, we report a case of NPDB with SBH that was misdiagnosed as BCS for three years. A 20-year-old female with abdominal distension, hepatosplenomegaly, and haematological anomalies was initially diagnosed with BCS based on her imaging finding of a thin hepatic vein and rapid blood flow at the confluence of the hepatic vein and inferior vena cava. Her bone marrow cytology found sea-blue histiocytes. Liver biopsy showed foamy cytoplasm in hepatocytes surrounded by numerous Kupffer cells. Sequencing analysis of the SMPD1 gene led to the finding of two missense mutations in the heterozygous state: C.829 T > C (p.Trp277Arg) in exon 2 (novel) and c.1805G > A (p.Arg602His) in exon 6 (already described). These findings established the diagnosis of NPDB. CONCLUSION: The patient presented with hepatosplenomegaly, haematological anomalies, and dyslipidaemia. Thus, NPDB should be considered following the exclusion of related diseases. The diagnosis of NPDB was suspected by clinical symptoms and routine laboratory tests and was confirmed by liver biopsy and gene sequencing. The novel mutation c.829 T > C in exon 2 of the SMPD1 gene has never been reported and needs to be further investigated.

Metabolic dysfunction is associated with steatosis but no other histologic features in nonalcoholic fatty liver disease.

BACKGROUND: Recently, nonalcoholic fatty liver disease (NAFLD) has been renamed metabolic-associated fatty liver disease (MAFLD). Based on the definition for MAFLD, a group of non-obese and metabolically healthy individuals with fatty liver are excluded from the newly proposed nomenclature. AIM: To analyze the histologic features in the MAFLD and non-MAFLD subgroups of NAFLD. METHODS: Eighty-three patients with biopsy-proven NAFLD were separated into MAFLD and non-MAFLD groups. The diagnosis of MAFLD was established as hepatic steatosis along with obesity/diabetes or evidence of metabolic dysfunction. The histologic features were compared according to different metabolic disorders and liver enzyme levels. RESULTS: MAFLD individuals had a higher NAFLD activity score (P = 0.002) and higher severity of hepatic steatosis (42.6% Grade 1, 42.6% Grade 2, and 14.8% Grade 3 in MAFLD; 81.8% Grade 1, 13.6% Grade 2, and 4.5% Grade 3 in non-MAFLD; P = 0.007) than the non-MAFLD group. Lobular and portal inflammation, hepatic ballooning, fibrosis grade, and the presence of nonalcoholic steatohepatitis (NASH) and significant fibrosis were comparable between the two groups. The higher the liver enzyme levels, the more severe the grades of hepatic steatosis (75.0% Grade 1 and 25.0% Grade 2 in normal liver function; 56.6% Grade 1, 39.6% Grade 2, and 3.8% Grade 3 in increased liver enzyme levels; 27.8% Grade 1, 27.8% Grade 2, and 44.4% Grade 3 in liver injury; P < 0.001). Patients with liver injury (alanine aminotransferase > 3 × upper limit of normal) presented a higher severity of hepatocellular ballooning (P = 0.021). Moreover, the grade of steatosis correlated significantly with hepatocellular ballooning degree (r = 0.338, P = 0.002) and the presence of NASH (r = 0.466, P < 0.001). CONCLUSION: Metabolic dysfunction is associated with hepatic steatosis but no other histologic features in NAFLD. Further research is needed to assess the dynamic histologic characteristics in NAFLD based on the presence or absence of metabolic disorders.

Lnc524369 promotes hepatocellular carcinoma progression and predicts poor survival by activating YWHAZ-RAF1 signaling.

BACKGROUND: Liver cancer is one of the most highly malignant cancers, characterized by easy metastasis and chemoradiotherapy resistance. Emerging evidence indicates that long noncoding RNAs (LncRNAs), including Lnc524369, are highly involved in the initiation, progression, radioresistance, and chemoresistance of hepatocellular carcinoma (HCC). However, the function of Lnc524369 remains unclear. AIM: To explore the function of Lnc524369 in HCC. METHODS: To investigate the effect of Lnc524369, tissue from 41 HCC patients were analyzed using CCK8, migration, and invasion assays. Lnc524369 and YWHAZ (also named 14-3-3ζ) mRNA were detected by qPCR, and YWHAZ and RAF1 proteins were detected by western blot in liver cancer cell lines and human HCC tissues. The Cancer Cell Line Encyclopedia (CCLE) databases, STRING database, Human Protein Atlas database, and the TCGA database were used for bioinformatic analysis. RESULTS: Lnc524369 was significantly upregulated in the nucleus of liver cancer cells and human HCC tissues. Overexpression of Lnc524369 was associated with the proliferation, migration, and invasion of liver cancer cells. YWHAZ and RAF1 proteins and YWHAZ mRNA were overexpressed in liver cancer, which could be attenuated by overexpression of Lnc524369. Lnc524369 and its downstream target YWHAZ and RAF1 proteins were negatively associated with overall survival time. CONCLUSION: Lnc524369 might be a promising target of HCC as it can enhance liver cancer progression and decrease the overall survival time of HCC by activating the YWHAZ/RAF1 pathway.

Clinical implications of exosome-derived noncoding RNAs in liver.

Exosomes, one of three main types of extracellular vesicles, are ~30-100 nm in diameter and have a lipid bilayer membrane. They are widely distributed in almost all body fluids. Exosomes have the potential to regulate unknown cellular and molecular mechanisms in intercellular communication, organ homeostasis, and diseases. They are critical signal carriers that transfer nucleic acids, proteins, lipids, and other substances into recipient cells, participating in cellular signal transduction and material exchange. ncRNAs are non-protein-coding genes that account for over 90% of the genome and include microRNAs (miRNAs), long ncRNAs (lncRNAs), and circular RNAs (circRNAs). ncRNAs are crucial for physiological and pathological activities in the liver by participating in gene transcription, posttranscriptional epigenetic regulation, and cellular processes through interacting with DNA, RNA, or proteins. Recent evidence from both clinical and preclinical studies indicates that exosome-derived noncoding RNAs (ncRNAs) are highly involved in the progression of acute and chronic liver diseases by regulating hepatic lipid metabolism, innate immunity, viral infection, fibrosis, and cancer. Therefore, exosome-derived ncRNAs have promising potential and clinical implications for the early diagnosis, targeted therapy, and prognosis of liver diseases.

Pneumocystis jirovecii and Legionella pneumophila coinfection in a patient with diffuse large B-cell lymphoma: A case report.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is a common non-Hodgkin's lymphoma. R-CHOP is a protocol for long-term chemotherapy for DLBCL patients. Long-term chemotherapy can lead to low immunity and increase the risk of opportunistic pathogen infections in immunocompromised patients. CASE SUMMARY: We report a case of coinfection with Pneumocystis jirovecii (P. jirovecii) and Legionella pneumophila (L. pneumophila) in a patient with DLBCL. The patient was a 40-year-old female who was diagnosed with DLBCL and was admitted due to pulmonary infection. P. jirovecii and L. pneumophila were detected in her bronchoalveolar lavage fluid by hexamine silver staining, isothermal amplification and metagenomic sequencing. CONCLUSION: To the best of our knowledge, this is the first case of P. jirovecii and L. pneumophila coinfection found in a DLBCL patient. Clinicians should be aware of the risk of complicated infection in patients undergoing long-term chemotherapy.

Diagnosis and treatment of an inborn error of bile acid synthesis type 4: A case report.

BACKGROUND: Inborn error of bile acid synthesis type 4 is a peroxisomal disease with impaired bile acid synthesis caused by a-methylacyl-CoA racemase (AMACR) gene mutation. The disease is usually found in children with mild to severe liver disease, cholestasis and poor fat-soluble vitamin absorption. At present, there is no report of inborn errors of bile acid synthesis type 4 in adults with liver disease and poor fat-soluble vitamin absorption. CASE SUMMARY: A 71-year-old man was hospitalized in our department for recurrent liver dysfunction. The clinical manifestations were chronic liver disease and yellow skin and sclera. Serum transaminase, bilirubin and bile acid were abnormally increased; and fat-soluble vitamins decreased. Liver cirrhosis and ascites were diagnosed by computed tomography. The patient had poor coagulation function and ascites and did not undergo liver puncture. Genetic testing showed AMACR gene missense mutation. The patient was diagnosed with inborn error of bile acid synthesis type 4. He was treated with ursodeoxycholic acid, liver protection and vitamin supplementation, and jaundice of the skin and sclera was reduced. The indicators of liver function and the quality of life were significantly improved. CONCLUSION: When adults have recurrent liver function abnormalities, physicians should be alert to genetic diseases and provide timely treatment.

The effects of core stability training in nurses with nonspecific low back pain.

ABSTRACT: To investigate the effect of core stability training on nonspecific low back pain (NSLBP) in nurses.The data were collected retrospectively by reviewing the patient's medical records and pain questionnaires in our rehabilitation center. A total of 40 nurses with NSLBP were included and divided into observation group and control group. Each group were given routine health education for NSLBP. Core stability training was performed in observation group for 4 weeks. Surface electromyography (sEMG) evaluation of erector spine and multifidus muscle, pain Numeric Rating Scale (NRS) and Japanese Orthopaedic Association (JOA) scores were evaluated and analyzed before and 4 weeks after intervention.There was no significant difference of NRS score and JOA score between two groups before intervention (P > .05, respectively). The NRS and JOA scores were significantly improved in both two groups after 4 weeks of intervention (P < .05, respectively). Moreover, the improvement of NRS and JOA scores in the observation group were better than those of the control group (P < .05, respectively). No significant difference of average electromyography (AEMG) or median frequency (MF) were noted between the healthy side and the affected side in both groups before or after intervention (P > .05, respectively). After 4 weeks of intervention, the AEMG of the healthy and the affected side of the two groups showed an improved trend without significant difference (P > .05, respectively). The MF of affected side was significantly higher 4 weeks after intervention than those before treatment in the observation and control group (P < .05, respectively).Core stability training can alleviate pain, improve the fatigue resistance of the core muscles and the balance of the functions of bilateral multifidus muscles in nurses with NSLBP.

Multicenter analysis and a rapid screening model to predict early novel coronavirus pneumonia using a random forest algorithm.

ABSTRACT: Early determination of coronavirus disease 2019 (COVID-19) pneumonia from numerous suspected cases is critical for the early isolation and treatment of patients.The purpose of the study was to develop and validate a rapid screening model to predict early COVID-19 pneumonia from suspected cases using a random forest algorithm in China.A total of 914 initially suspected COVID-19 pneumonia in multiple centers were prospectively included. The computer-assisted embedding method was used to screen the variables. The random forest algorithm was adopted to build a rapid screening model based on the training set. The screening model was evaluated by the confusion matrix and receiver operating characteristic (ROC) analysis in the validation.The rapid screening model was set up based on 4 epidemiological features, 3 clinical manifestations, decreased white blood cell count and lymphocytes, and imaging changes on chest X-ray or computed tomography. The area under the ROC curve was 0.956, and the model had a sensitivity of 83.82% and a specificity of 89.57%. The confusion matrix revealed that the prospective screening model had an accuracy of 87.0% for predicting early COVID-19 pneumonia.Here, we developed and validated a rapid screening model that could predict early COVID-19 pneumonia with high sensitivity and specificity. The use of this model to screen for COVID-19 pneumonia have epidemiological and clinical significance.

Effects of Online Home Nursing Care Model Application on Patients with Traumatic Spinal Cord Injury.

OBJECTIVE: This study aims to explore the effects of an online home nursing care model application on patients with traumatic spinal cord injury (TSCI). METHODS: Eighty patients with TSCI discharged from the hospital between January 2015 and January 2018 were included in the study. The patients were randomly divided into two groups: the control group and the observation group (n = 40, each). The patients in the control group were given routine discharge guidance, while the patients in the observation group were given online home nursing care. The Oswestry Disability Index (ODI), Medical Outcomes Study 36-item short-form health survey (MOS SF-36), and complication-incidence rate were used to evaluate the efficiency of the online home nursing care model. RESULTS: There were no differences in the ODI and MOS SF-36 scores between the two groups at discharge. However, the ODI and MOS SF-36 scores in the observation group showed significant improvement compared with the control group (p < 0.05) during the most recent follow-up. The incidence of complications, such as constipation, joint stiffness, muscle atrophy, foot drop, and pressure sores, were significantly lower in the observation group than in the control group (p < 0.05). CONCLUSION: The online home nursing care model can reduce complication incidence, alleviate dysfunction, and improve the quality of life of patients with TSCI.

Hepatocellular carcinoma progression in hepatitis B virus-related cirrhosis patients receiving nucleoside (acid) analogs therapy: A retrospective cross-sectional study.

BACKGROUND: Antiviral therapy cannot completely block the progression of hepatitis B to hepatocellular carcinoma (HCC). Furthermore, there are few predictors of early HCC progression and limited strategies to prevent progression in patients with HBV-related cirrhosis who receive nucleos(t)ide analog (NA) therapy. AIM: The study aim was to clarify risk factors and the diagnostic value of alpha-fetoprotein (AFP) for HCC progression in NA-treated hepatitis B virus (HBV)-related cirrhosis patients. METHODS: In this retrospective cross-sectional study, we analyzed the clinical data of 266 patients with HBV-related cirrhosis who received NA treatment between February 2014 and April 2020 at Zhejiang Provincial People's Hospital. The patients were divided into two groups, 145 who did not progress to HCC (No-HCC group), and 121 who progressed to HCC during NA treatment (HCC group). The logistic regression analysis was used to analyze the risk factors of HCC progression. The diagnostic value of AFP for HCC was evaluated by receiver operating characteristic (ROC) curve analysis. RESULTS: Univariate analysis showed that age ≥ 60 years (P = 0.001), hepatitis B and alcoholic etiology (P = 0.007), smoking history (P < 0.001), family history of HBV-related HCC (P = 0.002), lamivudine resistance (P = 0.011), HBV DNA negative (P = 0.023), aspartate aminotransferase > 80 U/L (P = 0.002), gamma-glutamyl transpeptidase > 120 U/L (P = 0.001), alkaline phosphatase > 250 U/L (P = 0.001), fasting blood glucose (FBG) ≥ 6.16 (mmol/L) (P = 0.001) and Child-Pugh class C (P = 0.005) were correlated with HCC progression. In multivariate analysis, age ≥ 60 years [hazard ratio (HR) = 3.089, 95% confidence interval (CI): 1.437-6.631, P = 0.004], smoking history (HR = 4.001, 95%CI: 1.836-8.716, P < 0.01), family history of HBV-related HCC (HR = 6.763, 95%CI: 1.253-36.499, P < 0.05), lamivudine resistance (HR = 2.949, 95%CI: 1.207-7.208, P = 0.018), HBV DNA negative (HR = 0.026, 95%CI: 0.007-0.139, P < 0.01), FBG ≥ 6.16 mmol/L (HR = 7.219, 95%CI: 3.716-14.024, P < 0.01) were independent risk factors of HCC progression. ROC of AFP for diagnosis of HCC was 0.746 (95%CI: 0.674-0.818). A cutoff value of AFP of 9.00 ug/L had a sensitivity of 0.609, and specificity of 0.818 for diagnosing HCC. CONCLUSION: Age ≥ 60 years, smoking history, family history of HCC, lamivudine resistance, HBV DNA negative, FBG ≥ 6.16 mmol/L were risk factors of HCC progression. Serum AFP had limited diagnostic value for HCC.

Primary bone anaplastic lymphoma kinase positive anaplastic large-cell lymphoma: A case report and review of the literature.

BACKGROUND: Primary bone lymphoma (PBL) is an uncommon extranodal disease that represents approximately 1%-3% of lymphomas. Anaplastic lymphoma kinase (ALK) positive anaplastic large-cell lymphoma (ALCL) is an extremely rare type of PBL. The aim of this report is describe the symptoms, diagnosis, and treatment of primary bone ALK-positive ALCL. CASE SUMMARY: A 66-year-old man presented to our hospital with neck and shoulder pain and intermittent fever that lasted for 1 mo. After extensive evaluation, positron emission tomography-computed tomography (CT) examination showed multiple osteolytic bone lesions without other sites lesions. CT-guided biopsy of the T10 vertebral body was performed, and the pathology results showed that neoplastic cells were positive for ALK-1, CD30, and CD3. A diagnosis of primary bone ALK positive ALCL was ultimately made. The patient was in partial response after four cycle soft cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy, and we planned to repeat the biopsy and radiological examination after completion of the fifth cycle of therapy. CONCLUSION: Primary bone ALK positive ALCL is a rare disease and physicians should keep in mind that ALCL can present with isolated osseous involvement without nodal involvement, and lymphoma should be considered in the differential diagnosis of primary bone lesions.

A rapid screening model for early predicting novel coronavirus pneumonia in Zhejiang Province of China: a multicenter study.

Novel coronavirus pneumonia (NCP) has been widely spread in China and several other countries. Early finding of this pneumonia from huge numbers of suspects gives clinicians a big challenge. The aim of the study was to develop a rapid screening model for early predicting NCP in a Zhejiang population, as well as its utility in other areas. A total of 880 participants who were initially suspected of NCP from January 17 to February 19 were included. Potential predictors were selected via stepwise logistic regression analysis. The model was established based on epidemiological features, clinical manifestations, white blood cell count, and pulmonary imaging changes, with the area under receiver operating characteristic (AUROC) curve of 0.920. At a cut-off value of 1.0, the model could determine NCP with a sensitivity of 85% and a specificity of 82.3%. We further developed a simplified model by combining the geographical regions and rounding the coefficients, with the AUROC of 0.909, as well as a model without epidemiological factors with the AUROC of 0.859. The study demonstrated that the screening model was a helpful and cost-effective tool for early predicting NCP and had great clinical significance given the high activity of NCP.

Membrane Derived Vesicles as Biomimetic Carriers for Targeted Drug Delivery System.

Extracellular vesicles (EVs) are membrane vesicles (MVs) playing important roles in various cellular and molecular functions in cell-to-cell signaling and transmitting molecular signals to adjacent as well as distant cells. The preserved cell membrane characteristics in MVs derived from live cells, give them great potential in biological applications. EVs are nanoscale particulates secreted from living cells and play crucial roles in several important cellular functions both in physiological and pathological states. EVs are the main elements in intercellular communication in which they serve as carriers for various endogenous cargo molecules, such as RNAs, proteins, carbohydrates, and lipids. High tissue tropism capacity that can be conveniently mediated by surface molecules, such as integrins and glycans, is a unique feature of EVs that makes them interesting candidates for targeted drug delivery systems. The cell-derived giant MVs have been exploited as vehicles for delivery of various anticancer agents and imaging probes and for implementing combinational phototherapy for targeted cancer treatment. Giant MVs can efficiently encapsulate therapeutic drugs and deliver them to target cells through the membrane fusion process to synergize photodynamic/photothermal treatment under light exposure. EVs can load diagnostic or therapeutic agents using different encapsulation or conjugation methods. Moreover, to prolong the blood circulation and enhance the targeting of the loaded agents, a variety of modification strategies can be exploited. This paper reviews the EVs-based drug delivery strategies in cancer therapy. Biological, pharmacokinetics and physicochemical characteristics, isolation techniques, engineering, and drug loading strategies of EVs are discussed. The recent preclinical and clinical progresses in applications of EVs and oncolytic virus therapy based on EVs, the clinical challenges and perspectives are discussed.

The limiting factors of oncolytic virus immunotherapy and the approaches to overcome them.

Oncolytic virus (OV) immunotherapy is characterized by viruses which specifically target cancer cells and cause their cytolysis. They provide a unique and promising new tool for the eradication of cancer as they interact with and affect the tumor microenvironment (TME), vasculature, and immune system. Advancements of genetic engineering have allowed for these viruses to be armed in such a way to have enhanced targeting, strong immunomodulation properties, and an ability to modify the TME. However, there are still major limitations in their use, mostly due to difficulties in delivering the viral particles to the tumors and in ensuring that the immunomodulatory properties are able to stimulate the host immune response to mount a complete response. Using novel delivery systems and using OVs as a complementary therapy in a combinatorial treatment have shown some significant successes. In this review, we discuss the major issues and difficulties in using OVs as anti-tumor agents and some of the strategies put in place so far to overcome these limitations. KEY POINTS: • Oncolytic viruses (OVs) infect cancer cells and cause their cytolysis. • The major limitations in using OVs as anti-tumor therapy were discussed. • The potential strategies to overcome these limitations were summarized.