Cyclodextrin-based metal-organic framework materials: Classifications, synthesis strategies and applications in variegated delivery systems.

Metal-organic frameworks (MOFs) are coordination compounds that possess an adjustable structure and controllable function. Despite their wide applications in various industries, the use of MOFs in the fields of food and biomedicine is limited mainly due to their potential biological toxicity. Researchers have thus focused on developing biocompatible MOFs to address this issue. Among them, cyclodextrin-based metal-organic frameworks (CD-MOFs) have emerged as a promising alternative. CD-MOFs are novel MOFs synthesized using naturally carbohydrate cyclodextrin and alkali metal cations, and possess renewable, non-toxic, and edible characteristics. Due to their high specific surface area, controllable porosity, great biocompatibility, CD-MOFs have been widely used in various delivery systems, such as encapsulation of nutraceuticals, flavors, and antibacterial agents. Although the field of CD-MOF materials is still in its early stages, they provide a promising direction for the development of MOF materials in the delivery field. This review describes classification and structural characteristics, followed by an introduction to formation mechanism and commonly used synthetic methods for CD-MOFs. Additionally, we discuss the status of the application of various delivery systems based on CD-MOFs. Finally, we address the challenges and prospects of CD-MOF materials, with the aim of providing new insights and ideas for their future development.

Comparison and development of advanced machine learning tools to predict nonalcoholic fatty liver disease: An extended study.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a public health challenge and significant cause of morbidity and mortality worldwide. Early identification is crucial for disease intervention. We recently proposed a nomogram-based NAFLD prediction model from a large population cohort. We aimed to explore machine learning tools in predicting NAFLD. METHODS: A retrospective cross-sectional study was performed on 15 315 Chinese subjects (10 373 training and 4942 testing sets). Selected clinical and biochemical factors were evaluated by different types of machine learning algorithms to develop and validate seven predictive models. Nine evaluation indicators including area under the receiver operating characteristic curve (AUROC), area under the precision-recall curve (AUPRC), accuracy, positive predictive value, sensitivity, F1 score, Matthews correlation coefficient (MCC), specificity and negative prognostic value were applied to compare the performance among the models. The selected clinical and biochemical factors were ranked according to the importance in prediction ability. RESULTS: Totally 4018/10 373 (38.74%) and 1860/4942 (37.64%) subjects had ultrasound-proven NAFLD in the training and testing sets, respectively. Seven machine learning based models were developed and demonstrated good performance in predicting NAFLD. Among these models, the XGBoost model revealed the highest AUROC (0.873), AUPRC (0.810), accuracy (0.795), positive predictive value (0.806), F1 score (0.695), MCC (0.557), specificity (0.909), demonstrating the best prediction ability among the built models. Body mass index was the most valuable indicator to predict NAFLD according to the feature ranking scores. CONCLUSIONS: The XGBoost model has the best overall prediction ability for diagnosing NAFLD. The novel machine learning tools provide considerable beneficial potential in NAFLD screening.

Role of [18F] fludeoxyglucose positron emission tomography in the selection of liver transplantation candidates in patients with hepatocellular carcinoma.

BACKGROUND: The Milan criteria are widely accepted among many centers. However, patients with hepatocellular carcinoma beyond the Milan criteria might still benefit from liver transplantation (LT) when tumor itself is not aggressive. [18F] fluorodeoxyglucose positron emission tomography/computed tomography imaging could provide useful information of tumor behaviors, which is helpful to predict the prognosis for many tumors. METHOD: In order to determine its role in candidate selection for LT, we therefore retrospectively analyzed 103 recipients with preoperative positron emission tomography (PET) findings. RESULTS: Positive PET findings (PET+) were significantly associated with tumor nodule numbers (P=0.013), tumor grade (P=0.025), macro- (P=0.002) and micro-vascular invasion (P=0.002), as well as the Milan criteria (P=0.018). PET+ patients had significantly increased risk of tumor recurrence post-LT compared to PET negative (PET-) patients (P=0.007). The 1-, 3-, and 5-year overall survival rate of PET- patients were 96.0%, 87.2% and 76.2%, compared to 74.7%, 55.4% and 49.9% in PET+ patients, respectively (P<0.05). The 1-, 3-, and 5-year recurrence-free survival rate of PET- patients were 91.8%, 81.9% and 76.0%, compared to 70.1%, 39.3% and 21.9% in PET+ patients, respectively (P<0.05). Recipients within the Milan criteria showed comparable 1-, 3-, and 5-year survival rates in comparison with those beyond the Milan criteria with a PET- findings (1-, 3-, and 5-year overall survival rates, 97.5%, 83.3%, and 83.3% vs 90.0%, 80.0%, and 66.7%, P= 0.123; 1-, 3-, and 5-year recurrence-free survival rates, 95.1%, 73.1%, and 73.1% vs 90.0%, 78.8%, and 65.6%, P=0.148). CONCLUSIONS: Certain patients with hepatocellular carcinoma and negative PET findings, who have exceeded the Milan criteria, are also eligible candidates for LT. Preoperative PET/CT imaging is an important marker, which should be incorporated in extended candidate selection criteria for LT.

Association between ADIPOQ gene polymorphisms and the risk of new-onset diabetes mellitus after liver transplantation.

BACKGROUND: New-onset diabetes after transplantation (NODAT) has become one of the major factors that affect the overall survival and long-term life quality in liver transplantation (LT) recipients. Previous studies found that the serum adiponectin concentration of diabetic patients is significantly lower than that of healthy subjects. Adiponectin regulates the blood glucose level by increasing body sensitivity to insulin through various mechanisms. In this study, we aimed to investigate the impact of diabetes related gene polymorphisms on the development of NODAT in liver recipients. METHODS: A total of 256 LT patients in a single-center were selected retrospectively for the study. Genomic DNA was extracted from explanted liver tissues, and tested for twelve diabetes mellitus associated single nucleotide polymorphisms by Sequenom MassARRAY. Modified clinical models in predicting NODAT were established and evaluated. RESULTS: The GG genotype of ADIPOQ rs1501299 gene polymorphism was significantly more frequent in NODAT than non-NODAT LT patients (56% vs 39%, P=0.014). Dominant model (GG vs GT+TT, P=0.030) and recessive model (GT+GG vs TT, P=0.005) also confirmed the genotype distribution difference between NODAT and non-NODAT groups. Age (OR=1.048, P=0.004), BMI (OR=1.107, P=0.041), and blood tacrolimus level at 1-month LT (OR=1.170, P=0.003) were clinical independent risk factors of NODAT. Furthermore, rs1501299 could improve the ability of clinical model in predicting NODAT (AUROC=0.743, P<0.001). CONCLUSION: ADIPOQ rs1501299 gene polymorphism is associated with an increased risk of NODAT, which should be added to the clinical models in predicting the occurrence of NODAT in LT recipients.

First case report of isolated penile mucormycosis in a liver transplantation recipient.

Mucormycosis is a rare but potentially lethal complication of liver transplantation. Most reported cases have involved rhinocerebral, pulmonary, gastrointestinal, or disseminated forms. We present herein the case of a 61-year-old male patient with hepatocellular carcinoma who developed isolated penile mucormycosis after orthotopic liver transplantation. Such a case has not been reported in the literature to date. Early diagnosis and timely surgical intervention combined with comprehensive treatment are the key factors for improving the survival rate in patients with mucormycosis.

[Risk factors of biliary complications after liver transplantation from donation after cardiac death].

OBJECTIVE: To analyze the risk factors for biliary complications of liver transplantation from donation after cardiac death (DCD). METHODS: Clinical data of 109 patients undergoing liver transplantation from DCD in First Affiliated Hospital of Zhejiang University School of Medicine from October 2010 to October 2013 were studied retrospectively. The risk factors of biliary complications following DCD liver transplantation were analyzed. RESULTS: Twenty-four (22%) patients developed biliary complications after DCD liver transplantation. Univariate analysis showed that biliary complications were associated with warm ischemia time (P<0.001) and length of ICU stay (P=0.013), but not associated with ABO blood types match (P>0.05). Administration of inotropic agents and fatty liver increased the trend of biliary complications. Multivariate analysis demonstrated that warm ischemia time and length of ICU stay were independent risk factors for predicting biliary complications. CONCLUSION: Warm ischemia time and days of ICU stay are independent risk factors for predicting biliary complications after DCD liver transplantation.

Risk factors of choledocholithiasis formation after liver transplantation.

Systematic study of risk factors for biliary stone post-liver transplantation is rarely performed. To investigate the risk factor of choledocholithiasis formation after liver transplantation, we conducted a case-control study. Fourteen patients were selected into a study group. The stones of the bile duct of the patients were confirmed and treated successfully by endoscopic retrograde cholangiopancreatography. For univariate analysis, we selected carefully some potential risk factors such as cold ischemia time, warm ischemia time, and biliary stricture. The results revealed that cold ischemia time and biliary stenosis were significant predictors. But multivariate analysis revealed that only biliary stenosis was a significant risk factor. In conclusion, biliary stenosis is a risk factor of bile duct stones formation after liver transplantation. Endoscopic retrograde cholangiopancreatography is effective and safe in the diagnosis or treatment of bile duct stones after liver transplantation.

Polymorphisms in cytokine genes and their association with acute rejection and recurrence of hepatitis B in Chinese liver transplant recipients.

BACKGROUND: Acute rejection (AR) and hepatitis B virus (HBV) recurrence after liver transplantation (LT) are the two major complications leading to chronic graft dysfunction. Genomic polymorphisms in interleukin (IL)-10, tumor necrosis factor (TNF)alpha and transforming growth factor (TGF)beta1 genes have been found to affect the susceptibility to certain diseases. However, the relationship between cytokine gene polymorphisms and risk of AR as well as HBV recurrence after LT in Han Chinese has not been reported. The objective of the present study was to investigate the association of polymorphisms within these cytokine genes with the risk of AR as well as HBV recurrence. METHODS: One hundred eighty six Chinese LT recipients in which 41 patients developed AR and 29 patients experienced HBV recurrence were enrolled; 151 age- and gender-matched healthy individuals were selected as controls. Single-nucleotide polymorphisms (SNPs) at loci of IL-10 -1082, -819, -592, and TNFalpha -308, -238, as well as TGFbeta1 -988, -800, -509, +869, and +915 were determined by using DNA sequencing and then confirmed by restriction fragment length polymorphism (PCR-RFLP). Analyses of linkage disequilibrium and haplotype frequency were performed using Haploview program. RESULTS: The -819 and -592 polymorphisms in the IL-10 gene were in complete linkage (r(2) = 1). Another linkage was found at -509 and +869 in the TGFbeta1 gene (r(2) = 0.66). A significant difference was observed in the distribution of allelic frequencies at position -819 and -592 in the IL-10 gene between ARs and non-ARs (p = 0.036, OR = 1.134, 95% CI 0.999-1.287 and p = 0.036, OR = 1.134, 95% CI 0.999-1.287, respectively). After adjustment for a Bonferroni correction, there was no significant difference between the polymorphism and AR (p >0.05). Furthermore, the overall genotype distribution between HBV recurrence patients and non-HBV recurrence patients was also not significantly different (p >0.05). CONCLUSIONS: Our study suggests that gene polymorphisms of IL10, TNFalpha, and TGFbeta1 do not have a major independent role in AR and HBV recurrence after LT and may not be risk factors of AR and HBV recurrence after LT in Chinese liver transplant recipients.

Genetic factors for individual administration of immunosuppressants in organ transplantation.

BACKGROUND: The immunosuppressive drugs used worldwide have a narrow therapeutic index, which results in a need to individualize the dose regimen for different recipients. The oxidative enzymes cytochrome P450 (CYP)3A and the drug efflux pump P-glycoprotein (P-gp) are two potential factors in the processes of metabolism. Pharmacogenetic study of immunosuppressive drugs has focused on these two enzymes. This review was undertaken to assess the role of single nuclear polymorphisms (SNPs) of these two enzymes in the individual administration of immunosuppressive drugs. DATA SOURCES: An English-language literature search was made using MEDLINE for articles on CYP3A and P-gp in organ transplantation. RESULTS: The SNPs of CYP3A and P-gp are closely correlated to the large variations of cyclosporine and tacrolimus dosage between different patients, although conflicting results were obtained by some authors. CONCLUSIONS: More studies should be conducted to elucidate further the pharmacogenetics of immunosuppressive drugs in organ transplantation, a deep understanding of which would provide an important step toward drug regimen individualization in the posttransplant therapy.

Impact of multidrug resistance 1 gene polymorphism on tacrolimus dose and concentration-to-dose ratio in Chinese liver transplantation recipients.

OBJECTIVE: To investigate whether the polymorphism of multidrug resistance 1 gene (MDR1) in the donors and liver transplantation recipients was correlated with interindividual variation in tacrolimus dose requirement and concentration-to-dose ratio. METHODS: The occurrence of MDR1 3435(C-->T) polymorphism was investigated by polymerase chain reaction followed by restriction fragment length polymorphism analysis in 50 liver transplant recipients and their corresponding donors. Doses (mg/kg body weight) and dose-adjusted trough levels (ng/mL per mg/kg body weight) were compared according to allelic status for MDR1. RESULTS: The MDR1 genotype CC was observed in 23 subjects (23%), whereas 64 (64%) were CT and 13 (13%) were TT. Tacrolimus doses required to achieve target blood concentrations were higher in the patients with MDR1 CC genotype than in the CT or TT genotype patients, and the dose-adjusted trough levels were lower. No significant differences were found in tacrolimus doses or dose-adjusted trough levels according to the donor's MDR1 genotype. CONCLUSION: Tacrolimus dose requirement and dose-adjusted trough levels were correlated with MDR1 3435 (C-->T) polymorphism, and MDR1 3435 (C-->T) polymorphism analysis is helpful to individualize tacrolimus administration.