A simplified fecal leukocyte esterase strip test results as a low cost, widely available, alternative bowel inflammation biomarker.

BACKGROUND: /Purpose: Leukocyte esterase strips have been widely used to detect the presence of leukocyte in human body fluids. We investigated the correlation between fecal leukocyte esterase (FLE) and fecal calprotectin (FC) levels and compared manual with machine automated interpretation of FLE level. METHODS: This prospective study enrolled inflammatory bowel disease and colitis patients in National Taiwan University Hospital from Dec 2021 to Feb 2022. FLE and FC measured using the same sample were compared with various FC cutoff values. The correlation between values indicated by the two tests was analyzed. Sensitivity, specificity, positive and negative predictive values, and area under the receiver operating characteristic curve (AUROC) were calculated using SAS. RESULTS: A total of 103 samples were analyzed. The correlation between FLE and FC level was moderate and positive (r = 0.3505, P = 0.0003). With an FLE reading more than 1+ indicating mucosa inflammation, when the FC cutoff was 50, 250, and 500 mg/kg, the sensitivities of FLE readings were 60.3 %, 74.3 %, and 84.6 %, respectively, and the specificities were 62.9 %, 58.8 %, and 58.4 %, respectively. With an FLE reading greater than 1+ indicating mucosa inflammation, FLE reflected FC with AUROC values at the optimal cutoff (500 mg/kg) of 0.72. No difference was noted between manual and machine readings for FLE. CONCLUSION: Positive FLE can predict FC levels of more than 500 mg/kg. The test is widely available, produces results on the same day, and is low cost; therefore, FLE should be further investigated for use in bowel inflammation monitoring.

Exacerbated gastrointestinal symptoms and long COVID in IBD patients with SARS-CoV-2 infection: A multi-center study from taiwan.

BACKGROUND/PURPOSE: Limited studies have addressed the exacerbation of symptoms and long COVID in inflammatory bowel disease (IBD) patients following non-severe COVID-19 infection, particularly with post-COVID-19 vaccination. We aim to investigate factors associated with exacerbated gastrointestinal symptoms (EGS) and long COVID in IBD patients with non-severe COVID-19, which is most common situation in daily practice. METHODS: This is an observational study by multiple centers in Taiwan from May 2020 to March 2023. We collected clinical manifestation, data, and medication information from IBD patients with non-severe COVID-19. EGS was defined as increased frequency of diarrhea, bloody stool, and abdomen pain within 14 days after SARS-COV-2 infection. Long COVID was defined following the guidelines of the World Health Organization. RESULTS: Out of 90 patients, most of them (88.9%) received at least standard two doses of COVID-19 vaccination and the majority (87.8%) were mild diseases of COVID-19.30% of patients experienced EGS during COVID-19 with higher ESR levels serving as a predictive factor (Odds ratio: 3.6, 95% confidence interval: 1.2-10.5, P = 0.02). 38.1% of those patients developed long COVID. The patients who experienced EGS during COVID-19 and with a history of longer IBD duration showed a significant association with long COVID (p = 0.03 and p = 0.02). CONCLUSIONS: Our study revealed that EGS and long COVID occurred in one third of IBD patients with non-severe COVID-19, even though most of them had received the standard plus booster vaccination. We identified associated factors for EGS and long COVID, emphasizing the importance of post-COVID-19 follow-up in IBD patients.

In situ vaccination followed by intramuscular poly-ICLC injections for the treatment of hepatocellular carcinoma in mouse models.

The efficacy of treatment for advanced hepatocellular carcinoma (HCC) has remained limited. Polyinosinic-polycytidylic acid-poly-L-lysine carboxymethylcellulose (poly-ICLC) is a synthetic double-stranded RNA that serves as a viral mimic and induces an immune response. Intratumoral (IT) poly-ICLC injections can induce an autovaccination effect and prime the immune system, whereas intramuscular (IM) injection of poly-ICLC can attract and maintain tumor-specific cytotoxic T lymphocytes in tumors. We found that IT injection of poly-ICLC upregulated the expression of CD83 and CD86 on conventional type 1 dendritic cells in tumors. Combination therapy with IT followed by IM injections of poly-ICLC significantly inhibited tumor growth and increased the tumor-infiltrating CD8+ T cells in two syngeneic mouse models of HCC. Depletion of CD8+ T cells attenuated the antitumor effect. An IFN-γ enzyme-linked immunospot of purified tumoral CD8+ T cells revealed a significant proportion of tumor-specific T cells. Finally, the sequential poly-ICLC therapy induced abscopal effects in two dual-tumor models. This study provides evidence that the sequential poly-ICLC therapy significantly increased infiltration of tumor-specific CD8+ T cells in the tumors and induced CD8+ T cell-dependent inhibition of tumor growth, as well as abscopal effects.

Anemia in inflammatory bowel disease course is associated with patients' worse outcome.

BACKGROUND: Purpose: Anemia affects the life quality of inflammatory bowel disease (IBD) patients, but no report from Asian about anemia screening and its impact previously. We aimed to explore the prevalence and impact of anemia among the IBD patients in Taiwan. METHODS: A retrospective study was conducted from January 2006 to February 2018 at National Taiwan University Hospital. Clinical characteristics and outcomes were analyzed. RESULTS: A total of 1604 IBD patients were enrolled [494 Crohn's disease (CD) and 1110 ulcerative colitis (UC)]. Overall, 95.3% (471/494) of CD and 87.9% (976/1110) of UC patients underwent anemia screening. Anemia screening rate in IBD patients significantly increased from 62.6% (162/259) in 2006 to 77.2% (838/1086) in 2017. The mean time from IBD diagnosis to anemia screening was 122.4 days in CD patients and even longer in UC patients at 216.2 days. Persistent anemia was found in 47.3% (548/1158) of the screened patients. Risk factors of persistent anemia included low body mass index [odds ratio (OR) = 1.96, p < 0.01], steroid [OR = 2.96, p < 0.01], thiopurine [OR = 2.62, p < 0.01], colectomy [OR = 6.3, p < 0.01], and small bowel resection [OR = 3.21, p < 0.05)] after IBD diagnosis. Compared with those without anemia, anemic IBD patients had higher admission (p < 0.01) and mortality rates (p < 0.01). CONCLUSION: The anemia screening rate was acceptable and increased over time in Taiwan. Since anemia is associated with worse outcomes, earlier survey and treatment of anemia in IBD patients is recommended.

Characteristics of primary signet ring cell carcinoma of colon and rectum: a case control study.

BACKGROUND: Primary signet ring cell carcinoma of the colon and rectum (PSRCCR) is rare, usually diagnosed at advanced stage with poor outcomes. We aimed to find possible diagnostic clues in order to help diagnosis. METHODS: A retrospective study of PSRCCR patients from 1993 to 2018 was reviewed at a single tertiary center. Colorectal adenocarcinoma patients as control group with 1:4 ratio was also enrolled. RESULTS: 18 patients with PSRCCR were identified. The prevalence rate was 0.16% (18 of 11,515). The mean age was 50.2 years-old in PSRCCR group and 63 years-old in non-SRCC colorectal cancer patients (p < 0.001). Diagnosis tool depends on colonoscopy were much less in PSRCCR group than control group (44.4% vs 93%, p < 0.001). SRCC patients had higher level of CEA (68.3 vs 17.7 ng/mL, p = 0.004) and lower level of Albumin (3.4 vs 4.3 g/dL, p < 0.001). The majority of PSRCCR tumor configuration was ulcerative and infiltrative. More PSRCCR pathology presented as high-grade carcinoma (66.7 vs 1.4%, p < 0.001) and lymphovascular invasion (77.8 vs 44.4%, p = 0.011) than control group. More PSRCCR patients were diagnosed at advanced stage (88.8 vs 40.3%, p = 0.001). Higher mortality was also noticed in PSRCCR group than control group (72.2 vs 20.8%, p < 0.001). CONCLUSION: For young patients with long segment colonic stenosis and ulcerative/ infiltrative mucosa but endoscopic biopsy failed to identify malignant cells, earlier operation or non-colon site biopsy is suggested for diagnosing the PSRCCR.

Zero COVID-19 infection in inflammatory bowel disease patients: Findings from population-based inflammatory bowel disease registries in Hong Kong and Taiwan.

BACKGROUND AND AIM: It is unsure whether inflammatory bowel disease (IBD) is a risk factor for novel coronavirus infection (COVID-19). METHODS: IBD patients were identified from population-based databases in Hong Kong and Taiwan from January 21, 2020, until April 15, 2020. RESULTS: Total 2954 and 2554 IBD patients were identified in Hong Kong and Taiwan, respectively. None had COVID-19. Pooled analysis showed that 65.3%, 39.1%, 4.3%, and 12.8% IBD patients in Hong Kong and 75.8 %, 51.4 %, 26.1%, and 52.3 % in Taiwan were on 5-aminosalicylates, immunomodulators, corticosteroids, and biologics, respectively. CONCLUSION: There were no reported cases of COVID-19 infection amongst IBD patients in Hong Kong and Taiwan. IBD patients should continue their usual medications during the COVID-19 pandemic.

Trends and risk factors of mortality analysis in patients with inflammatory bowel disease: a Taiwanese nationwide population-based study.

BACKGROUND: Inflammatory bowel disease (IBD) was emerging as a worldwide epidemic disease, and the advanced therapy changed the clinical course and possibly the outcomes. Our previous study reported a higher mortality rate from (IBD) in Taiwan than in Western countries. We proposed to analyze the trend and risk factors of mortality in order to improve the care quality of IBD patients. METHODS: This retrospective study was conducted to analyze data for January 2001 to December 2015 from a registered database, compiled by the Taiwan's National Health Insurance. RESULTS: Between 2001 and 2015, a total of 3806 IBD patients [Crohn's disease (CD): 919; ulcerative colitis (UC): 2887] were registered as having catastrophic illness, and 8.2% of these patients died during follow-up. The standardized mortality ratios (SMRs) of CD and UC were 3.72 (95% CI 3.02-4.55) and 1.44 (95% CI 1.26-1.65), respectively, from 2001 to 2015, respectively. A comparison of the periods of 2011-2015 and 2001-2005 revealed a decrease in the mortality rates from both UC and CD. Multivariate Cox proportional hazards analysis identified elderly individuals; sepsis and pneumonia were the risk factors for IBD mortality. The specific risk factors of mortality were liver cancer for UC and surgeries for CD. CONCLUSION: For further decreasing IBD-related mortality in Taiwan, we need to pay special attention toward elderly individuals, infection control, cancer screening and improvement in perioperative care.

Microbiota and gastrointestinal cancer.

Gut microbiota plays important roles in many diseases, including cancer. It may promote carcinogenesis by inducing oxidative stress, genotoxicity, host immune response disturbance, and chronic inflammation. Colorectal cancer, hepatocellular carcinoma, and gastric cancer are the major gastrointestinal tract cancers in Taiwan. The microbiota detected in patients with tubular adenoma and villous/tubulovillous polyps is different from that in healthy controls and patients with hyperplastic polyps. Normalization of the microbiota is observed in patients after colorectal cancer treatment. Furthermore, the liver is exposed to microbiota-associated molecular patterns (MAMPs), bacterial metabolites, and toxins, as it is anatomically connected to the gut via the portal vein. Patients with cirrhosis have significantly higher plasma endotoxin levels than healthy controls. Helicobacter pylori is a well-established risk factor for gastric cancer. Some nitrosating bacteria convert nitrogen compounds in gastric fluid to potentially carcinogenic N-nitroso compounds, which also contribute to gastric cancer development. Growing evidence demonstrates that gut microbiota promotes carcinogenesis. In this review, we discuss the mechanisms and types of microbiota changes involved in these gastrointestinal cancers and the future treatment choices.

Identification of risk factors for neoplastic colonic polyps in young adults with bloody stool in comparison with those without symptom.

BACKGROUND AND AIMS: The incidence and disease burden of colorectal cancer (CRC) in young adults were increasing. However, there was a dearth of advice on how to identify young population at risk for neoplastic colonic polyps (NCPs) and CRC. We aimed to identify risk factors for NCPs and CRC in young adults presenting with bloody stool. METHODS: A total of 1496 subjects younger than 40 years old who underwent colonoscopy due to bloody stool from 2005 to 2014 were enrolled in this retrospective study as the study group, and 1481 age-matched and gender-matched asymptomatic subjects who underwent colonoscopy for health checkup from 2011 to 2016 were enrolled as the control group at a tertiary center hospital. RESULTS: Multivariate analysis results showed that increasing age (odds ratio [OR] = 1.11, 95% confidence interval [CI]: 1.07-1.15, P < 0.001), higher body mass index (BMI) (OR = 1.07, 95%CI: 1.03-1.12, P = 0.001), diabetes mellitus (OR = 2.80, 95%CI: 1.06-7.42, P = 0.038), and positive family history of CRC (OR = 13.28, 95%CI: 5.70-30.97, P < 0.001) were identified as independent risk factors for NCPs in study group. The best cut-off values by receiver operating characteristic curve for age and BMI were 32 years old and 24.8 kg/m2 , respectively. More risk factors were associated with the higher risk for NCPs (OR = 2.17 every increasing one risk factor, P < 0.001). In the control group, no independent risk factors were identified. CONCLUSIONS: Adults aged ≤ 40 years with bloody stool who had increasing age (> 32 years old), higher BMI (> 24.8 kg/m2 ), diabetes mellitus, and positive family history of CRC had a higher detection rate of NCPs and CRC.

Cytomegalovirus colitis in hospitalized inflammatory bowel disease patients in Taiwan: a referral center study.

BACKGROUND: Colitis is exacerbated in patients with concurrent cytomegalovirus (CMV) infection and inflammatory bowel disease (IBD). We assessed the prevalence and clinical features of CMV colitis in hospitalized IBD patients. METHODS: A retrospective study reviewed the data from January 1, 1998 through December 31, 2013 compiled at the National Taiwan University Hospital. The CMV colitis patients' demographic data, clinical information, treatment regimens, pathologic findings, and outcome were analyzed. RESULTS: A total of 673 IBD patients were hospitalized during the study period. There were 312 patients diagnosed with Crohn's disease (CD) and 361 with ulcerative colitis (UC). CMV colitis was diagnosed as having positive inclusion bodies in colonic tissue. Six of the 312 CD patients (1.9%) and five of the 361 UC patients (1.4%) were diagnosed with CMV colitis. Compared to CD patients without CMV colitis, patients with CMV colitis were more often older (p < 0.005). Higher steroid usage was noted in the CMV positive group compared to age and gender matched CMV negative IBD patients (81.8% vs. 51.5%). Eight patients received ganciclovir treatment. Three patients who did not receive antiviral treatment had colitis flare-ups after the index admission. CONCLUSIONS: The prevalence of CMV colitis in hospitalized IBD inpatients was 1.6% in Taiwan. Two associated factors for CMV colitis in hospitalized IBD patients were that they were elderly in CD and were on higher doses of steroids. Routine histopathology studies and/or PCR for refractory colitis patients are suggested to diagnose CMV colitis. Once the diagnosis is made, antiviral treatment is recommended to decrease the colitis relapse rate.

Evolutionarily conserved protein ERH controls CENP-E mRNA splicing and is required for the survival of KRAS mutant cancer cells.

Cancers with Ras mutations represent a major therapeutic problem. Recent RNAi screens have uncovered multiple nononcogene addiction pathways that are necessary for the survival of Ras mutant cells. Here, we identify the evolutionarily conserved gene enhancer of rudimentary homolog (ERH), in which depletion causes greater toxicity in cancer cells with mutations in the small GTPase KRAS compared with KRAS WT cells. ERH interacts with the spliceosome protein SNRPD3 and is required for the mRNA splicing of the mitotic motor protein CENP-E. Loss of ERH leads to loss of CENP-E and consequently, chromosome congression defects. Gene expression profiling indicates that ERH is required for the expression of multiple cell cycle genes, and the gene expression signature resulting from ERH down-regulation inversely correlates with KRAS signatures. Clinically, tumor ERH expression is inversely associated with survival of colorectal cancer patients whose tumors harbor KRAS mutations. Together, these findings identify a role of ERH in mRNA splicing and mitosis, and they provide evidence that KRAS mutant cancer cells are dependent on ERH for their survival.

Flt-1 in colorectal cancer cells is required for the tumor invasive effect of placental growth factor through a p38-MMP9 pathway.

BACKGROUND: Placenta growth factor (PlGF), a dimeric glycoprotein with 53% homology to VEGF, binds to VEGF receptor-1 (Flt-1), but not to VEGF receptor-2 (Flk-1), and may function by modulating VEGF activity. We previously have showed that PlGF displays prognostic value in colorectal cancer (CRC) but the mechanism remains elucidated. RESULTS: Overexpression of PlGF increased the invasive/migration ability and decreased apoptosis in CRC cells showing Flt-1 expression. Increased migration was associated with increasing MMP9 via p38 MAPK activation. Tumors grew faster, larger; with higher vascularity from PlGF over-expression cells in xenograft assay. In two independent human CRC tissue cohorts, PlGF, MMP9, and Flt-1 expressions were higher in the advanced than the localized disease group. PlGF expression correlated with MMP9, and Flt-1 expression. CRC patients with high PlGF and high Flt-1 expression in tissue had poor prognosis. CONCLUSION: PlGF/Flt-1 signaling plays an important role in CRC progression, blocking PlGF/Flt-1 signaling maybe an alternative therapy for CRC.

A nationwide population-based study of the inflammatory bowel diseases between 1998 and 2008 in Taiwan.

BACKGROUND: The incidence of the inflammatory bowel diseases (IBD), ulcerative colitis (UC) and Crohn's disease (CD), has been increasing in Asia. We probed the nationwide registered database to assess the incidence, prevalence, gender distribution, age of diagnosis and the survival status of IBD patients in Taiwan. METHODS: A retrospective study was conducted to analyze the registered database compiled by the National Health Insurance provided by the Department of Health, Taiwan, from January 1998 through December 2008. RESULTS: A total of 1591 IBD patients were registered from 1998 to 2008 in Taiwan (CD: 385; UC: 1206). The incidence of CD increased from 0.19/100,000 in 1998 to 0.24/100,000 in 2008. The incidence of UC increased from 0.61/100,000 in 1998 to 0.94/100,000 in 2008. The prevalence of CD increased from 0.19/100,000 in 1998 to 1.78/100,000 in 2008. The prevalence of UC increased from 0.61/100,000 in 1998 to 7.62/100,000 in 2008. Male to female ratio for CD was 2.22 and 1.64 for UC. Age of registered for CD was predominantly between 20 to 39, and for UC between 30 to 49 years of age. The standardized mortality ratio (95% CI) was 4.97 (3.72-6.63) for CD and 1.78 (1.46-2.17) for UC, from 1998 to 2008 in Taiwan. CONCLUSIONS: Using the Taiwan nationwide database for IBD, the incidence and prevalence of IBD in Taiwan significantly increased from 1998 to 2008. The mortality rate was higher for CD patients than UC patients, and both were higher than the general population.

Green synthesis and characterization of silicate nanostructures coated with Pluronic F127/gelatin for triggered drug delivery in tumor microenvironments.

Thermo-/pH-sensitive nanocomposites based on mesoporous silicate MCM-41 (MSNCs) derived from rice husk ash were synthesized and characterized. MSNCs were coated with thermo-/pH-sensitive Pluronic® F127 and gelatin to form MSNCs@gp nanocomposites, serving as carriers for controlled release of the anticancer drug doxorubicin (Dox). The in vitro and in vivo antitumor efficacy of MSNCs@gp-Dox against liver cancer was evaluated. Fourier-transform infrared (FTIR) spectra confirmed the silica nature of MSNCs@gp by detecting the Si-O-Si group. Under acidic microenvironments (pH 5.4) and 42 °C, MSNCs@gp-Dox exhibited significantly higher Dox release (47.33 %) compared to physiological conditions. Thermo-/pH-sensitive drug release (47.33 %) was observed in simulated tumor environments. The Makoid-Banakar model provided the best fit at pH 7.4 and 37 °C with a mean squared error of 0.4352, an Akaike Information Criterion of 15.00, and a regression coefficient of 0.9972. Cytotoxicity tests have demonstrated no significant toxicity in HepG2 cells treated with various concentrations of MSNCs@gp, while MSNCs@gp-Dox induced considerable cell apoptosis. In vivo studies in nude mice revealed effective suppression of liver cancer growth by MSNCs@gp-Dox, indicating high pharmaceutical efficacy. The investigated MSNCs@gp-based drug delivery system shows promise for liver cancer therapy, offering enhanced treatment efficiency with minimal side effects.

Comparison of the magnetic resonance scoring systems for Crohn's disease activity: MaRIA, simplified MaRIA, and Nancy scores.

PURPOSE: The most widely used score for assessing the activity of Crohn's disease (CD) is the Magnetic Resonance Index of Activity (MaRIA) score, but it is time-consuming. The aim of this study was to compare the diagnostic accuracy of MaRIA score to the other two easily calculated scores. METHODS: Between January 2011 and May 2021, 67 patients with CD who underwent MRE and ileocolonoscopy within 2 weeks were enrolled. The MRE-based scores including the MaRIA score, simplified MaRIA (sMaRIA) score, and Nancy score for each colonic segment and terminal ileum were calculated and correlated with the ileocolonoscopic findings. The simplified endoscopic score for Crohn's disease (SES-CD) was considered the gold standard. RESULTS: A total of 343 intestinal segments were included in the analysis, of which 109 (31.8%) showed active inflammation on ileocolonoscopy. The areas under the receiver operating characteristic curve (AUC) of the MaRIA, sMaRIA, and Nancy scores for detecting active disease were 0.752, 0.764, and 0.765, respectively. In the sub-analysis for different indications, the MaRIA and sMaRIA scores showed a higher AUC (0.721 and 0.741) than the Nancy score (0.652) for disease monitoring. CONCLUSION: The sMARIA and Nancy scores showed comparable diagnostic accuracy to the MaRIA score, and thus could be used as alternatives to the MaRIA score. Furthermore, considering the range of application, especially for disease monitoring, the sMaRIA score may be more suitable for use in clinical practice.

Rheumatic manifestations of hepatitis C virus infection are associated with autoantibodies but not viremia.

BACKGROUND: To investigate the associations between extrahepatic manifestations, autoantibodies, and viremia in patients with hepatitis C virus (HCV) infection. METHODS: This cross-sectional study recruited patients with HCV infection from the outpatient department of a tertiary medical center in Northern Taiwan between January 2017 and August 2019. Autoantibody profiles and the clinical parameters of HCV infection were evaluated using laboratory tests, and a questionnaire was used to record extrahepatic manifestations. HCV infection status, including inactive HCV infection, active hepatitis, and cirrhosis, was defined according to abdominal ultrasonography findings and alanine transaminase levels. RESULTS: A total of 77 patients with HCV were recruited, with 19.5% and 16.9% of patients, respectively, presenting with arthritis and dry eyes. Autoantibody screening revealed rheumatoid factor (RF), antinuclear antibody (ANA), anti-Ro antibody, and anti-La antibody positivity in 20.8%, 23.4%, 13.0%, and 2.6% of the patients, respectively. The presence of RF was associated with arthritis, whereas the presence of ANA was associated with dry eyes but not dry mouth. Active hepatitis and HCV-related cirrhosis were associated with viremia, but not autoantibody profiles. CONCLUSION: In this single-center study, the prevalence of extrahepatic manifestations and autoantibodies did not differ in patients stratified by the HCV infection status. Rheumatic manifestations were associated with the presence of autoantibodies but not with viremia.

Epidemiology, Disease Course, and Clinical Outcomes of Perianal Fistulas and Fissures Crohn's Disease: A Nationwide Population-Based Study in Taiwan.

Background: Population-based data on the course of perianal disease in East Asian populations with Crohn's disease (CD) are limited. This study examined the prevalence, clinical course, and compared the outcomes of CD patients with perianal CD (pCD) versus without pCD in Taiwan. Methods: A nationwide population-based study was implemented from 2000 to 2017 by using the Taiwan National Health Insurance Research Database. Results: Of 2424 patients with CD, 358 (14.8%) patients with pCD were identified. Most patients with CD and pCD were men (79.3%). The mean age at CD diagnosis was lower in patients with pCD (33.7 years) than in those without pCD (44.9 years). Approximately half the patients with pCD received the pCD diagnosis at least 6 months before receiving a CD diagnosis. Approximately one-third (121/358) of patients with pCD had recurrent fistula; the median recurrence interval was 239 days. Compared with patients without pCD, patients with pCD had higher mean incidences of hospitalization (7.0 vs 3.8, P < .01), outpatient visits (13 vs 2.9, P < .01), and emergency room visits (10.3 vs 4.4, P < .01) over a 15-year period. Although patients with pCD had higher rates of healthcare utilization, their 15-year mortality rate was lower than that of those without pCD (6.1% vs 17.3%, P < .01). Conclusions: The period prevalence of pCD in Taiwanese patients with CD was 14.8%. Although patients with pCD required more intensive care and had greater healthcare utilization, they did not have inferior survival outcomes compared with those without pCD.

Magnetic boron nitride nanosheets-based on pH-responsive smart nanocarriers for the delivery of doxorubicin for liver cancer treatment.

A new drug delivery system (DDS) type complexing magnetic nanoparticles (MNP) along with boron nanosheets (BNN) coated with a pH-responsive polymer-polyethylene glycol (PEG) for the manageable loading/release of the anti-cancerous drug, doxorubicin (DOX), was created (MNP-BNN-PEG-DOX). The X-ray diffraction patterns of the nanocomposites displayed wide diffraction peaks for BNN at 25.1° and 42.3°, belonging to the (002) and (100) planes, correspondingly. Additionally, the characteristic peaks of Fe3O4 appeared at 30.5°, 35.9°, 43.6°, 54.1°, 57.5°, and 63.2°, belonging to the (220), (311), (400), (422), (511), and (440) crystal planes, correspondingly. Moreover, the magnetic properties of the nanocomposites revealed that the MNP-BNN remained magnetic after coating with PEG. The saturation magnetization (Ms) of the uncoated-MNP-BNN and MNP-BNN-PEG-1 were 49.4 and 42.3 emu g-1, respectively. Both in vitro and in vivo analyses shown that DDS might inhibit tumor growth, provoke cancer cell apoptosis, and reduce the cytotoxic effects of DOX. In vivo analysis demonstrated that after treatment with phosphate-buffered saline (PBS), MNP-BNN-PEG-1, free DOX, and MNP-BNN-PEG-1-DOX, the average tumor growth and weight were 1906, 1997, 1188, and 1043 nm and 0.17, 0.20, 0.13, and 0.07 g, respectively. The MNP-BNN-PEG-DOX nanoparticles could be an effective treatment and potential alternative for liver cancer therapy.

Synthesis and characterization of silica nanoparticles from rice ashes coated with chitosan/cancer cell membrane for hepatocellular cancer treatment.

Dual pH-sensitive smart nanocarriers based on silica nanoparticles (SNPs) extracted from rice husk ashes (RHAs) to effectively inhibit liver cancer cell proliferation were investigated. The SNPs were coated with chitosan (CH) and loaded with doxorubicin (DOX), then functionalized with cell membrane (CM) for homologous targeting ability. The FTIR spectra showed an absorption wave number at 1083 cm-1 which confirmed the existence of the SiOSi group, ratifying that the nanocarriers belong to silica species. The Korsmeyer-Peppas kinetic model reported R2 values of 0.996 and 0.931 for pH = 5.4 and pH = 7.4, respectively, demonstrating pH-responsive behavior of the nanocarriers. The cytotoxicity test confirmed that the HepG2 cell line treated with different SNP-CH-CM concentrations had no detectable significant cell toxicity, however, SNP-CH-DOX-CM induced greater cell death. In vivo tests revealed that SNP-CH-DOX-CM suppressed liver cancer growth in nude mice, demonstrating high pharmaceutical capability. Histological examination of vital organs showed that the targeted drug delivery system (DDS) had minor in vivo toxicity. In the light of its high treatment efficacy and minimal side effects, the investigated DDS is promising for the therapy of liver cancer.