Pediatric living donor liver transplant for Budd-Chiari syndrome using a cryopreserved pulmonary vein graft for retro-hepatic vena cava reconstruction: A case report.

INTRODUCTION: In pediatric patients with Budd-Chiari syndrome (BCS), living donor liver transplantation (LDLT) raises substantial challenges regarding IVC reconstruction. CASE PRESENTATION: We present a case of an 8-year-old girl with BCS caused by myeloproliferative syndrome with JAK2 V617F mutation. She had a complete thrombosis of the inferior vena cava (IVC) with multiple collaterals, developing a Budd-Chiari syndrome. She underwent LDLT with IVC reconstruction with a cryopreserved pulmonary vein graft obtained from a provincial biobank. The living donor underwent a laparoscopic-assisted left lateral hepatectomy. The reconstruction of the vena cava took place on the back table and the liver was implanted en bloc with the reconstructed IVC in the recipient. Anticoagulation was immediately restarted after the surgery because of her pro-thrombotic state. Her postoperative course was complicated by a biliary anastomotic leak and an infected biloma. The patient recovered progressively and remained well on outpatient clinic follow-up 32 weeks after the procedure. CONCLUSION: IVC reconstruction using a cryopreserved pulmonary vein graft is a valid option during LDLT for pediatric patients with BCS where reconstruction of the IVC entails considerable challenges. Early referral to a pediatric liver transplant facility with a multidisciplinary team is also important in the management of pediatric patients with BCS.

Berberine improves cognitive impairment by alleviating brain atrophy and promoting white matter reorganization in diabetic db/db mice: a magnetic resonance imaging-based study.

Diabetic cognitive impairment is a common complication in type 2 diabetes. Berberine (BBR) is an isoquinoline alkaloid that has been shown to have neuroprotective effects against diabetes. This study aimed to investigate the effect of BBR on the gray and white matter of the brain by using magnetic resonance imaging (MRI) and to explore the underlying mechanisms. The study used diabetic db/db mice and administered BBR (50 and 100 mg/kg) intragastrically for twelve weeks. Morris water maze was applied to examine cognitive function. T2-weighted imaging (T2WI) was performed to assess brain atrophy, and diffusion tensor imaging (DTI) combined with fiber tracking was conducted to monitor the structural integrity of the white matter, followed by histological immunostaining. Furthermore, the protein expressions of the phosphatidylinositol 3-kinase (PI3K)/ protein kinase B (AKT)/ glycogen synthase kinase-3ß (GSK-3ß) were detected. The results revealed that BBR significantly improved the spatial learning and memory of the db/db mice. T2WI exhibited ameliorated brain atrophy in the BBR-treated db/db mice, as evidenced by reduced ventricular volume accompanied by increased hippocampal volumes. DTI combined with fiber tracking revealed that BBR increased FA, fiber density and length in the corpus callosum/external capsule of the db/db mice. These imaging findings were confirmed by histological immunostaining. Notably, BBR significantly enhanced the protein levels of phosphorylated AKT at Ser473 and GSK-3ß at Ser9. Collectively, this study demonstrated that BBR significantly improved the cognitive function of the diabetic db/db mice through ameliorating brain atrophy and promoting white matter reorganization via AKT/GSK-3ß pathway.

Aneurysmal Subarachnoid Hemorrhage and Sex Differences: Analysis of Epidemiology, Outcomes, and Risk Factors.

BACKGROUND: The differences in outcomes after aneurysmal subarachnoid hemorrhage (aSAH) between the sexes have not been concretely determined. This study aimed to evaluate the differences in epidemiology, outcomes, and risk factors between male and female patients with aSAH. METHODS: We performed a multicenter, retrospective study of patients with aSAH from 2017 to 2020. We investigated the epidemiological differences between the two sexes. Propensity score matching (PSM) was used to compare short-term outcomes between the sexes. Binary logarithmic regression was performed to investigate the odds ratio (OR) for dependent survival in patients of different sexes. RESULTS: A total of 5,407 consecutive patients with aSAH were included in this study, and the female-to-male ratio was 1.8:1. The peak incidence of aSAH occurred in the 6th and 7th decades in males and females, respectively. There were more female patients with internal carotid artery or posterior communicating artery aneurysms (53.2%), and there were more male patients with anterior cerebral artery or anterior communicating artery aneurysms (43.2%). The incidence of multiple aneurysms was greater in female patients (21.5% vs. 14.2%, P < 0.001). There was no significant difference in outcomes before and after PSM at discharge. The dependent survival risk was related only to the clinical condition on admission in women. In addition, age > 50 years (OR 1.88, 95% confidence interval 1.17-3.02; P = 0.01) and hypertension (OR 1.81, 95% confidence interval 1.25-2.61; P = 0.002) were also risk factors for male patients. CONCLUSIONS: There were more female patients with aneurysms than male patients in this study. Most aneurysm locations were different between the two groups. There was no significant difference in discharge outcomes before and after PSM. The risk factors for dependent survival were different between female and male patients.

Biotransformation of antioxidant eriocitrin into characteristic metabolites by the gut microbiota.

Eriocitrin is a flavonoid glycoside with strong antioxidant capacity that has a variety of pharmacological activities, such as hypolipidemic, anticancer and anti-inflammatory effects. We found that the gut microbiota could rapidly metabolize eriocitrin. By using LC/MSn-IT-TOF, we identified three metabolites of eriocitrin metabolized in the intestinal microbiota: eriodictyol-7-O-glucoside, eriodictyol, and dihydrocaffeic acid. By comparing these two metabolic pathways of eriocitrin (the gut microbiota and liver microsomes), the intestinal microbiota may be the primary metabolic site of eriocitrin metabolism. These findings provide a theoretical foundation for the study of pharmacologically active substances.

The changes of intestinal microbiota and metabolomics during the inhibition of bladder cancer by liquiritigenin.

Liquiritigenin is a natural medicine. However, its inhibitory effect and its potential mechanism on bladder cancer (BCa) remain to be explored. It was found that it could be visualized that the transplanted tumours in the low-dose liquiritigenin -treated group and the high-dose liquiritigenin -treated group were smaller than those in the model group. Liquiritigenin treatment led to alterations in Lachnoclostridium, Escherichia-Shigella, Alistipes and Akkermansia. Non-targeted metabolomics analysis showed that a total of multiple differential metabolites were identified between the model group and the high-dose liquiritigenin-treated group. This provides a new direction and rationale for the antitumour effects of liquiritigenin.

Structural Engineering of BiVO4 /CoFe MOF Heterostructures Boosting Charge Transfer for Efficient Photoelectrochemical Water Splitting.

Boosting charge separation and transfer of photoanodes is crucial for providing high viability of photoelectrochemical hydrogen (H2 ) generation. Here, a structural engineering strategy is designed and synthesized for uniformly coating an ultrathin CoFe bimetal-organic framework (CoFe MOF) layer over a BiVO4 photoanode for boosted charge separation and transfer. The photocurrent density of the optimized BiVO4 /CoFe MOF(NA) photoanode reaches a value of 3.92 mA cm-2 at 1.23 V versus reversible hydrogen electrode (RHE), up to 6.03 times that of pristine BiVO4 , due to the greatly increased efficiency of charge transfer and separation. In addition, this photoanode records one onset potential that is considerably shifted negatively when compared to BiVO4 . Transient absorption spectroscopy reveals that the CoFe MOF(NA) prolongs charge recombination lifetime by blocking the hole-transfer pathway from the BiVO4 to its surface trap states. This work sheds light on boosting charge separation and transfer through structural engineering to enhance the photocurrent of photoanodes for solar H2 production.

Selective Defluoroalkylation and Hydrodefluorination of Trifluoromethyl Groups Photocatalyzed by Dihydroacridine Derivatives.

The selective functionalization of trifluoromethyl groups through C-F cleavage poses a significant challenge due to the high bond energy of the C(sp3)-F bonds. Herein, we present dihydroacridine derivatives as photocatalysts that can functionalize the C-F bond of trifluoromethyl groups with various alkenes under mild conditions. Mechanistic studies and DFT calculations revealed that upon irradiation, the dihydroacridine derivatives exhibit high reducibility and function as photocatalysts for reductive defluorination. This process involves a sequential single-electron transfer mechanism. This research provides valuable insights into the properties of dihydroacridine derivatives as photocatalysts, highlighting the importance of maintaining a planar conformation and a large conjugated system for optimal catalytic activity. These findings facilitate the efficient catalytic reduction of inert chemical bonds.

The survival and outcome of older patients with primary aneurysmal subarachnoid haemorrhage: a 2-year follow-up, multi-centre, observational study.

BACKGROUND AND PURPOSE: The management of older aneurysmal subarachnoid haemorrhage (aSAH) cases is a clinical challenge. This study aimed to analyse the survival and functional outcomes in older aSAH patients (age ≥ 70 years) to provide evidence for making treatment decisions for such patients. METHODS: We performed a 2-year follow-up analysis of the Chinese Multi-Centre Cerebral Aneurysm Database for older patients suffering from aSAH from 2017 to 2020. A survival analysis was used to investigate the mean survival and hazard ratios for death. Binary logarithmic regression was performed to investigate the odds ratio for independent survival and dependent survival. RESULTS: A total of 1,136 consecutive older patients with aSAH were assessed in this study, and 944 patients (83.1%) were followed up. The overall mean survival was 37.79 ± 1.04 months. A total of 380 (40.25%) patients died within 2 years after aSAH. In survival analysis, the predictors of mortality were older age, intracerebral haemorrhage (ICH) history, Hunt-Hess (H-H) grade, World Federation of Neurosurgical Societies (WFNS) grade and operative treatment decreased the risk of mortality compared to conservative treatment. In binary logarithmic regression, the predictors of dependent survival were hypertension, diabetes, WFNS grade. CONCLUSIONS: The risk for 2-year mortality after aSAH increases markedly with older age, ICH history, H-H grade and WFNS grade. Risk factors for 2-year dependent survival were associated with hypertension, diabetes and WFNS grade in older patients with aSAH. Operative treatment markedly decreased mortality but did not significantly decrease the morbidity of dependent survival compared to conservative treatment.

ISRIB inhibits the senescence of type II pulmonary epithelial cells to alleviate pulmonary fibrosis induced by silica in mice.

The role and mechanisms of integrated stress response inhibitor (ISRIB) on silicosis are still not well defined. In the present study, the effects of ISRIB on cellular senescence and pulmonary fibrosis in silicosis were evaluated by RNA sequencing, micro-computed tomography, pulmonary function assessment, histological examination, and Western blot analysis. The results showed that ISRIB significantly reduced the degree of pulmonary fibrosis in mice with silicosis and reduced the expression of type I collagen, fibronectin, α-smooth muscle actin, and transforming growth factor-ß1. Both in vivo and in vitro results showed that ISRIB reversed the expression of senescence-related factors ß-galactosidase, phosphor-ataxia telangiectasia mutated, phosphor-ataxia telangiectasia and Rad3-related protein, p-p53, p21, p16, and plasminogen activator inhibitor type 1. The aforementioned results were consistent with the sequencing results. These findings implied that ISRIB might reduce the degree of pulmonary fibrosis in mice with silicosis by inhibiting the cellular senescence of alveolar epithelial cell type II.

Staged Versus Synchronous Carotid Endarterectomy and Coronary Artery Bypass Grafting: A Meta-Analysis and Systematic Review.

BACKGROUND: There are several treatment options for patients with concomitant carotid and coronary artery disease, and it is difficult to identify an optimal treatment strategy that has consensus. Here, we performed a meta-analysis to compare the early and long-term outcomes of staged and synchronous carotid endarterectomy and coronary artery bypass grafting approaches. METHODS: We performed a meta-analysis that compared staged and synchronous carotid endarterectomy and coronary artery bypass grafting approaches between July 1976 and September 2021. PubMed, EMBASE, and the Cochrane Library were systematically searched for related articles. RESULTS: Nineteen studies were identified with a total of 39,269 and 30,066 patients in the synchronous and staged groups, respectively. Early mortality was lower in the staged group than in the synchronous group (odds ratio OR 1.256, 95% confidence interval CI 1.006-1.569, P= P < 0.05, I2 = 54.5%), and stroke rates were significantly higher in the synchronous group (OR 1.356, 95% CI 1.232-1.493, P < 0.05, I2 = 33.3%). The rate of myocardial ischemia was significantly higher in the staged group than in the synchronous group (OR 0.757, 95% CI 0.635-0.903, P < 0.05, I2 = 51.5%), and this meta-analysis also showed a significantly higher risk of transient ischemic attacks (TIAs) in the synchronous group (OR 1.335, 95% CI 1.055-1.688, P < 0.05, I2 = 0.00%). The secondary outcomes, including the rate of reoperation, were significantly lower for the staged procedure than for the synchronous procedure (OR 1.177, 95% CI 1.052-1.318, P < 0.05, I2 = 4.2%), and the rate of wound infection was significantly higher in the synchronous group than in the staged group (OR 0.457, 95% CI 0.403-0.519, P < 0.05, I2 = 0.0%). There was no significant difference in the rate of cardiac arrhythmia between the two groups (OR 0.544, 95% CI 0.265-1.117, P > 0.05, I2 = 12.7%). There was also no statistical significance in the long-term results regarding the incidence of stroke, myocardial ischemia, and mortality between the synchronous and staged groups (P > 0.05). CONCLUSIONS: Patients treated with the synchronous approach had a significantly higher risk of early mortality, stroke, TIA, wound infection, and reoperation and a lower risk of myocardial ischemia than those treated with the staged approach. There was no significant difference in the long-term results between the 2 groups.

Metabolites Analysis of Anti-Myocardial Ischemia Active Components of Saussurea involucrata Based on Gut Microbiota-Drug Interaction.

Saussurea involucrata has been reported to have potential therapeutic effects against myocardial ischemia. The pharmacological effects of oral natural medicines may be influenced by the participation of gut microbiota. In this study, we aimed to investigate the bidirectional regulation of gut microbiota and the main components of Saussurea involucrata. We first established a quantitative method for the four main components (chlorogenic acid, syringin, acanthoside B, rutin) which were chosen by fingerprint using liquid chromatography tandem mass spectrometry (LC-MS/MS), and found that gut microbiota has a strong metabolic effect on them. Meanwhile, we identified five major rat gut microbiota metabolites (M1-M5) using liquid chromatography tandem time-of-flight mass spectrometry (LC/MSn-IT-TOF). The metabolic properties of metabolites in vitro were preliminarily elucidated by LC-MS/MS for the first time. These five metabolites of Saussurea involucrata may all have potential contributions to the treatment of myocardial ischemia. Furthermore, the four main components (10 µg/mL) can significantly stimulate intestinal bacteria to produce short chain fatty acids in vitro, respectively, which can further contribute to the effect in myocardial ischemia. In this study, the therapeutic effect against myocardial ischemia of Saussurea involucrata was first reported to be related to the intestinal flora, which can be useful in understanding the effective substances of Saussurea involucrata.

Biotransformation of Liquiritigenin into Characteristic Metabolites by the Gut Microbiota.

The bioavailability of flavonoids is generally low after oral administration. The metabolic transformation of flavonoids by the gut microbiota may be one of the main reasons for this, although these metabolites have potential pharmacological activities. Liquiritigenin is an important dihydroflavonoid compound found in Glycyrrhiza uralensis that has a wide range of pharmacological properties, such as antitumor, antiulcer, anti-inflammatory, and anti-AIDS effects, but its mechanism of action remains unclear. This study explored the metabolites of liquiritigenin by examining gut microbiota metabolism and hepatic metabolism in vitro. Using LC-MS/MS and LC/MSn-IT-TOF techniques, three possible metabolites of liquiritigenin metabolized by the gut microbiota were identified: phloretic acid (M3), resorcinol (M4), and M5. M5 is speculated to be davidigenin, which has antitumor activity. By comparing these two metabolic pathways of liquiritigenin (the gut microbiota and liver microsomes), this study revealed that there are three main metabolites of liquiritigenin generated by intestinal bacteria, which provides a theoretical basis for the study of pharmacologically active substances in vivo.

[Expression and Role of PD-L1 in a Mouse Model of Necrotizing Enterocolitis].

Objective: To investigate the expression and role of programmed death ligand-1 (PD-L1) in a mouse model of necrotizing enterocolitis (NEC). Methods: A total of 20 wild-type C57 BL/6 J mice were randomly assigned to the control and the model groups. Mice in the control group were breastfed, while mice in the model group were given lipopolysaccharide, formula feeding, hypoxia, and cold stimulation for NEC induction. Then, the intestines of the mice were collected in order to assess the pathological changes through HE staining, to examine PD-L1 expression and localization with immunofluorescence co-localization, and to evaluate intestinal PD-L1 expression with Western blot. Peripheral blood was collected for flow cytometry to examine leukocyte subpopulations and their PD-L1 expression. On the other hand, 14 PD-L1 (+/+) mice and 14 PD-L1 (-/-) mice were randomly divided into their respective genotype control groups and model groups. The same induction method as was already mentioned was adopted for the model groups. The intestines of the mice were collected for HE staining to evaluate the pathological change and peripheral blood was collected to examine the expression of inflammatory factors. Results: The NEC mouse model was successfully constructed. PD-L1 was widely expressed in enterocytes and inflammatory cells in the mouse intestines and in T cells, monocytes, and neutrophils in peripheral blood. The expression of PD-L1 in NEC mouse intestines increased in comparison with that of the control group. In the peripheral blood of NEC mice, the proportion of T cells and monocytes and their PD-L1 expression showed no significant changes compared with those of the control group, while the proportion of neutrophils and their PD-L1 expression increased by about 140% and 150%, respectively, in comparison with those of the control group ( P<0.05). According to the results of the PD-L1 gene mouse experiment, the control groups of PD-L1 (+/+) mice and PD-L1 (-/-) mice showed no significant difference in their intestinal conditions and serum inflammatory factor levels, while the PD-L1 (-/-) NEC mouse had worse intestinal pathological changes and increased mean pathological scores compared with those of PD-L1 (+/+) NEC mouse ( P<0.05). In addition, serum interleukin (IL)-10 in PD-L1 (-/-) NEC mouse decreased by about 44% compared with that of PD-L1 (+/+) NEC mice, and chemokine (C-X-C motif) ligand 1/IL-6/IL-1ß all increased by more than 25% (all P<0.05). Conclusion: PD-L1 is widely expressed in inflammatory cells and enterocytes in mice. Knocking out PD-L1 aggravates the degree of NEC inflammation and intestinal pathological changes. PD-L1 plays a protective role by reducing inflammation in the pathogenesis of NEC, the mechanism of which may be related to the regulation of neutrophils/enterocytes.

Impact of a long-term air pollution exposure on the case fatality rate of COVID-19 patients-A multicity study.

Evidence in the literature suggests that air pollution exposure affects outcomes of patients with COVID-19. However, the extent of this effect requires further investigation. This study was designed to investigate the relationship between long-term exposure to air pollution and the case fatality rate (CFR) of patients with COVID-19. The data on air quality index (AQI), PM2.5, PM10, SO2 , NO2 , and O3 from 14 major cities in China in the past 5 years (2015-2020) were collected, and the CRF of COVID-19 patients in these cities was calculated. First, we investigated the correlation between CFR and long-term air quality indicators. Second, we examined the air pollutants affecting CFR and evaluated their predictive values. We found a positive correlation between the CFR and AQI (1, 3, and 5 years), PM2.5 (1, 3, and 5 years), and PM10 (1, 3, and 5 years). Further analysis indicated the more significant correlation for both AQI (3 and 5 years) and PM2.5 (1, 3, and 5 years) with CFR, and moderate predictive values for air pollution indicators such as AQI (1, 3, and 5 years) and PM2.5 (1, 3, and 5 years) for CFR. Our results indicate that long-term exposure to severe air pollution is associated with higher CFR of COVID-19 patients. Air pollutants such as PM2.5 may assist with the prediction of CFR for COVID-19 patients.

Anaemia and cerebrospinal fluid biomarkers of Alzheimer's pathology in cognitively normal elders: the CABLE study.

BACKGROUND: Anaemia has been reported to be associated with cognitive decline and Alzheimer's disease (AD), but the associations between anaemia and cerebrospinal fluid (CSF) AD biomarkers are still unknown. This study aimed to investigate the associations between anaemia and CSF AD biomarkers. METHODS: Participants were included from the Chinese Alzheimer's Biomarker and LifestylE (CABLE) study. The associations of anaemia and its severity with CSF AD biomarkers including ß-amyloid 1-42 (Aß42), total tau (t-tau) and phosphorylated tau (p-tau) were analysed by multiple linear regression models. Adjusted for age, gender, educational levels, APOE ε4 alleles, comorbidities (history of coronary heart disease, history of stroke, hypertension, diabetes mellitus, dyslipidaemia) and glomerular filtration rate. RESULTS: A total of 646 cognitively normal older adults, consisting of 117 anaemia patients and 529 non-anaemia individuals, were included in this study. Anaemia patients had lower levels of CSF Aß42 than individuals without anaemia (p = 0.035). Besides, participants with more severe anaemia had lower CSF Aß42 levels (p = 0.045). No significant association of anaemia with CSF t-tau and p-tau levels was found. CONCLUSION: Cross-sectionally, anaemia was associated with lower CSF Aß42 levels. These findings consolidated the causal close relationship between anaemia and AD.

Molecular Conditional Generation and Property Analysis of Non-Fullerene Acceptors with Deep Learning.

The proposition of non-fullerene acceptors (NFAs) in organic solar cells has made great progress in the raise of power conversion efficiency, and it also broadens the ways for searching and designing new acceptor molecules. In this work, the design of novel NFAs with required properties is performed with the conditional generative model constructed from a convolutional neural network (CNN). The temporal CNN is firstly trained to be a good string-based molecular conditional generative model to directly generate the desired molecules. The reliability of generated molecular properties is then demonstrated by a graph-based prediction model and evaluated with quantum chemical calculations. Specifically, the global attention mechanism is incorporated in the prediction model to pool the extracted information of molecular structures and provide interpretability. By combining the generative and prediction models, thousands of NFAs with required frontier molecular orbital energies are generated. The generated new molecules essentially explore the chemical space and enrich the database of transformation rules for molecular design. The conditional generation model can also be trained to generate the molecules from molecular fragments, and the contribution of molecular fragments to the properties is subsequently predicted by the prediction model.

Biotransformation of Timosaponin BII into Seven Characteristic Metabolites by the Gut Microbiota.

Timosaponin BII is one of the most abundant Anemarrhena saponins and is in a phase II clinical trial for the treatment of dementia. However, the pharmacological activity of timosaponin BII does not match its low bioavailability. In this study, we aimed to determine the effects of gut microbiota on timosaponin BII metabolism. We found that intestinal flora had a strong metabolic effect on timosaponin BII by HPLC-MS/MS. At the same time, seven potential metabolites (M1-M7) produced by rat intestinal flora were identified using HPLC/MS-Q-TOF. Among them, three structures identified are reported in gut microbiota for the first time. A comparison of rat liver homogenate and a rat liver microsome incubation system revealed that the metabolic behavior of timosaponin BII was unique to the gut microbiota system. Finally, a quantitative method for the three representative metabolites was established by HPLC-MS/MS, and the temporal relationship among the metabolites was initially clarified. In summary, it is suggested that the metabolic characteristics of gut microbiota may be an important indicator of the pharmacological activity of timosaponin BII, which can be applied to guide its application and clinical use in the future.

[Mechanism of Jinqi Jiangtang Tablets in treatment of pancreatic ß cell dysfunction based on network pharmacology and molecular docking technology].

The present study investigated the therapeutic efficacy and potential mechanism of Jinqi Jiangtang Tablets(JQJT) on pancreatic ß cell dysfunction based on network pharmacology and molecular docking technology. TCMSP platform was used to retrieve the chemical components and targets of the three Chinese herbal medicines of JQJT. The genes were converted to gene symbol by the UniProt, and its intersection with targets related to pancreatic ß cell function in GeneCards and CTD databases was obtained. The drugs, active components and common targets were imported into Cytoscape 3.8.2 to plot the drug-component-target network. The main effective components and targets were obtained by software analysis. The drug targets and targets related to pancreatic ß cell function were imported separately into the STRING platform for the construction of protein-protein interaction(PPI) networks. The two PPI networks were merged by Cytoscape 3.8.2 and the key targets were obtained by plug-in CytoNCA. The targets obtained from drug-component-target network and PPI networks were imported into DAVID for GO analysis and KEGG enrichment analysis. AutoDock was used to carry out molecular docking of main active components and core targets and Pymol was used to plot the molecular docking diagram. The results showed that there were 371 active components and 203 targets related to JQJT and 2 523 targets related to pancreatic ß cell damage, covering 136 common targets. The results revealed core targets(such as PTGS2, PTGS1, NOS2, ESR1 and RXRA) and effective key components(such as quercetin, kaempferol, luteolin, ß-carotene and ß-sitosterol). KEGG enrichment analysis indicated that apoptosis, inflammation, and other signaling pathways were mainly involved. Molecular docking results showed that the main active components could spontaneously bind to the targets. This study preliminarily revealed the mechanism of JQJT in improving pancreatic ß cell damage through multi-component, multi-target and multi-pathway, and provided a theoretical basis for JQJT in the treatment of pancreatic ß cell dysfunction.

Population pharmacokinetics of high-dose methotrexate in Chinese pediatric patients with medulloblastoma.

Methotrexate (MTX) pharmacokinetics has substantial inter-individual variability and toxicity. In children with medulloblastoma treated with high-dose methotrexate (HD-MTX), the pharmacokinetic properties of methotrexate have not been established. A total of 660 serum samples from 105 pediatric patients with medulloblastoma were included in a population pharmacokinetic (PPK) analysis of methotrexate by using the nonlinear mixed-effects modeling method. The basic one-compartment population pharmacokinetic model was established by NONMEM software and the first-order conditional estimation (FOCE) method, and the final covariate model was obtained by the stepwise regression method. Weight (WT), creatinine clearance (CrCL), and whether the treatment was combined with dexamethasone (DEX) were covariates that had significant effects on the clearance rate (CL) of the model. The pharmacokinetic equation of CL in the final covariate model was as follows: CLi = 9.23× (1 + 0.0005× (θCrCL -105.78)) × (1 + 0.0017× (θWT -16)) × eηcl,i (L/h), IF (θDEX ) CLi = 1.19× CLi (L/h). The estimation accuracy of all pharmacokinetic parameters were acceptable (relative standard error < 14.74%). The goodness-of-fit diagram and bootstrap tests indicated that the final PPK model was stable with acceptable predictive ability. The PPK model may be useful for determining personalized medication levels in pediatric medulloblastoma patients undergoing HD-MTX therapy.

Unconventional Method for Fabricating Valence Tautomeric Materials: Integrating Redox Center within a Metal-Organic Framework.

Due to the structural advantages displayed by Metal-Organic Frameworks (MOFs), integrating Valence Tautomerism (VT) systems within MOFs could be an effective strategy in order to break through the constraints of the traditional ones. Herein, we report the first successful integration of a VT system into a MOF termed VT-MOF-1. The structural characteristics of VT-MOF-1, such as dinuclear cobalt-catechol clusters and solvent-accessible pores, are both innovative and novel, potentially yielding new vitality within VT field. In addition, VT-MOF-1 exhibits specific behaviors responsive to temperature and different solvent molecules as n-butanol, tert-butanol, and isopropyl alcohol. The entropy values and configurations of the solvent molecules might be responsible for the tunable sensing behaviors.