Temporal control in shell-core structured nanofilm for tracheal cartilage regeneration: synergistic optimization of anti-inflammation and chondrogenesis.

Cartilage tissue engineering offers hope for tracheal cartilage defect repair. Establishing an anti-inflammatory microenvironment stands as a prerequisite for successful tracheal cartilage restoration, especially in immunocompetent animals. Hence, scaffolds inducing an anti-inflammatory response before chondrogenesis are crucial for effectively addressing tracheal cartilage defects. Herein, we develop a shell-core structured PLGA@ICA-GT@KGN nanofilm using poly(lactic-co-glycolic acid) (PLGA) and icariin (ICA, an anti-inflammatory drug) as the shell layer and gelatin (GT) and kartogenin (KGN, a chondrogenic factor) as the core via coaxial electrospinning technology. The resultant PLGA@ICA-GT@KGN nanofilm exhibited a characteristic fibrous structure and demonstrated high biocompatibility. Notably, it showcased sustained release characteristics, releasing ICA within the initial 0 to 15 days and gradually releasing KGN between 11 and 29 days. Subsequent in vitro analysis revealed the potent anti-inflammatory capabilities of the released ICA from the shell layer, while the KGN released from the core layer effectively induced chondrogenic differentiation of bone marrow stem cells (BMSCs). Following this, the synthesized PLGA@ICA-GT@KGN nanofilms were loaded with BMSCs and stacked layer by layer, adhering to a 'sandwich model' to form a composite sandwich construct. This construct was then utilized to repair circular tracheal defects in a rabbit model. The sequential release of ICA and KGN facilitated by the PLGA@ICA-GT@KGN nanofilm established an anti-inflammatory microenvironment before initiating chondrogenic induction, leading to effective tracheal cartilage restoration. This study underscores the significance of shell-core structured nanofilms in temporally regulating anti-inflammation and chondrogenesis. This approach offers a novel perspective for addressing tracheal cartilage defects, potentially revolutionizing their treatment methodologies.

GIMAP7 inhibits epithelial-mesenchymal transition and glycolysis in lung adenocarcinoma cells via regulating the Smo/AMPK signaling pathway.

BACKGROUND: GTPase immunity-associated protein 7 (GIMAP7) has been previously recognized as a prognostic marker in pan-cancer. Our objective was to explore the function of GIMAP7 in the progression of lung adenocarcinoma (LUAD). METHODS: GIMAP7 was overexpressed by transfection with GIMAP7 plasmid, and knocked down using siRNAs. The biological functions of GIMAP7 were examined by employing CCK-8, EdU, colony formation, flow cytometry, wound healing, and transwell assays. The effects of GIMAP7 on the extracellular acidification rate (ECAR), oxygen consumption rate (OCR), lactate production, and glucose uptake were evaluated. In addition, the related mRNA and protein expression was detected employing immunohistochemical, western blot, and qRT-PCR. A xenograft tumor model was established in nude mice to evaluate the effects of GIMAP7 on tumor growth. RESULTS: GIMAP7 was lowly expressed in LUAD tissues and cells. GIMAP7 inhibited the proliferation, mobility, EMT, glycolysis, but promoted apoptosis in LUAD cells. Moreover, we also confirmed that GIMAP7 suppressed Smo/AMPK signaling in LUAD cells. By adding the Smo agonist SAG and AMPK agonist GSK621, the results of rescue experiments further verified that GIMAP7 played a role in LUAD inhibition through inhibition of the Smo/AMPK signaling pathway. Furthermore, the role of GIMAP7 in inhibiting tumor growth was verified in vivo. CONCLUSIONS: These results demonstrate that GIMAP7 could inhibit cell proliferation, mobility and glycolysis, but accelerate apoptosis via repressing the Smo/AMPK signaling pathway in LUAD.

Inulin-like polysaccharide ABWW may impede CCl4 induced hepatic stellate cell activation through mediating the FAK/PI3K/AKT signaling pathway in vitro & in vivo.

Studies have shown that terrestrial acidic polysaccharides containing carboxyl groups and seaweed sulfated polysaccharides have strong potential in anti-liver fibrosis. However, there is no investigation on the anti-liver fibrosis of fructan, a ubiquitous natural polysaccharide. The present study aimed to understand the effect of fructan in ameliorating carbon tetrachloride (CCl4)-induced liver fibrosis in mice. Here, an inulin-like fructan ABWW from Achyranthes bidentata Bl. was characterized by fructose enzymatic hydrolysis, methylation analysis, ESI-MS, and NMR. It was composed of →2)-ß-d-Fruf-(1→ and →2)-ß-d-Fruf-(1, 6→, terminated with →1)-α-d-Glcp and →2)-ß-d-Fruf residues. The biological studies showed that ABWW could improve liver damage and liver fibrosis induced by CCl4in vivo and inhibit hepatic stellate cell (HSC) activation and migration in vitro. We further demonstrated that ABWW inhibited LX2 activation via suppressing the FAK/PI3K/AKT signaling pathway. Hence, ABWW might be a potential novel active compound for anti-fibrosis new drug development.

Identification of epithelial-mesenchymal transition-related biomarkers in lung adenocarcinoma using bioinformatics and lab experiments.

BACKGROUND: Lung adenocarcinoma accounts for approximately 40% of lung cancer cases and poses a serious threat to human health. Therefore, there is an urgent need to identify central biomarkers in lung adenocarcinoma. METHODS: We first identified the EMT-associated genes in LUAD based on the TCGA cohort. Then we screened these 90 EMT-associated genes using univariate Cox regression analysis and LASSO regression analysis to develop a prognostic gene signature in the training set. The predictive performance of the gene signature was assessed in the validation set and multiple external test sets using the ROC cure, C index and log-rank tests. RT-PCR, western blot, wound healing assays, and siRNA methods were further used to investigate the role of PLEK2 in tumor behaviors. RESULTS: Eight genes (CCNB1, PLEK2, DERL3, C1QTNF6, DLGAP5, HMMR, GJB3, and SPOCK1) were eventually selected to develop an eight-gene signature. The 5-year AUC of the gene signature has a robust predictive ability both for predicting overall survival (0.774, 0.756, and 0.669 in the external test sets, respectively), and for progression free survival (0.774, 0.746, and 0.755 in the external test sets, respectively). C-index of the gene signature was 0.961 ± 0.005, 0.916 ± 0.011, and 0.868 ± 0.234 in the external test sets, respectively. Four genes (C1QTNF6, DLGAP5, HMMR, and PLEK2) were identified as key genes in LUAD progression, which were upregulated in the cancerous tissue compared with in the normal tissue (P < 0.001), and correlated with an unwanted prognosis in lung cancer (P < 0.05). PLEK2 was used as an example to explore its effect on LUAD progression in vitro using RT-PCR, western blot, CCK8, si-RNA and wound healing assay. Silencing of PLEK2 was shown to reduce proliferative and migrated ability of lung cancer cells via prohibition of autophagy. CONCLUSIONS: This study developed a novel EMT-related gene signature benefiting precision medicine, and identified four pivotal genes which can serve as therapeutic targets in LUAD. Four key genes can serve as molecular targets for patients with LUAD; silencing of PLEK2 was shown to reduce proliferative and migrated ability of lung cancer cells via prohibition of autophagy.

Improvement in cardiometabolic risk markers following an oatmeal diet is associated with gut microbiota in mildly hypercholesterolemic individuals.

Cardiovascular diseases have been the leading cause of death worldwide for decades. Some animal studies have indicated that oatmeal could improve gut microbiota and cardiometabolic risk markers. However, vivo evidence remained limited, especially in individuals with mild hypercholesterolemia. Our purpose was to explore the beneficial effects of oatmeal on serum lipids, oxidative stress and inflammation levels, and their correlations with gut microbiota and short-chain fatty acids (SCFAs) in mildly hypercholesterolemic individuals. The study was a randomized, single-blind, placebo-controlled trial. A total of 62 qualified participants were randomly divided into control group and oatmeal group with a 45-day follow-up. 16S rDNA and Gas-Chromatography Mass Spectrometry were employed respectively to measure the changes in gut microbiota and SCFAs at the start and the end of the intervention period. Cardiometabolic risk markers were assayed via commercial kits. The results suggested that oatmeal could significantly decrease serum total cholesterol (TC) (-8.59 %, p = 0.013), low density lipoprotein cholesterol (LDL-c) (-12.97 %, p = 0.004) and non-high density lipoprotein cholesterol (non-HDL-c) (-10.98 %, p = 0.040) level. In terms of oxidative stress, oatmeal significantly increased serum total antioxidant capacity (T-AOC) (21.98 %, p < 0.001), superoxide dismutase (SOD) (15.53 %, p = 0.044) levels and decreased concentration of malondialdehyde (MDA) (-19.11 %, p = 0.033) compared with control group. While no significant effect was observed in inflammatory factors. SCFAs results indicated that oatmeal could significantly increase serum acetic acid, propionic acid and valeric acid. The results of 16S rDNA showed that there was a significant difference in the alteration of ß-diversity between groups throughout the whole trial. Oatmeal resulted in the increases of Akkermansia, Dialister, Faecalibacterium, Barnesiella, Agathobacter, Lactobacillus and the decrease of Ruminococcaceae-MK4A214-group. Correlation analysis further suggested that the lipids regulation effect of oatmeal may be mainly mediated by Lactobacillus and Dialister, as well as some SCFAs (e.g., acetic acid and propionic acid), while Barnesiella and Akkermansia may play a crucial role in ameliorating oxidative stress level. In conclusion, despite of its small sample size, the present study is the first clinical trial performed in Chinese individuals with mild hypercholesterolemia to explore the effects of oatmeal on serum lipids, oxidative stress, inflammation levels, and gut microbiota. The results demonstrated that oatmeal could induce some beneficial changes in serum lipids, oxidative stress, gut microbiota composition and SCFAs. Correlation analysis further extended our understanding of the role of gut microbiota and SCFAs in improving cardiometabolic risk markers.

Log odds of positive lymph nodes is a robust predictor of survival and benefits from postoperative radiotherapy in stage IIIA-N2 resected non-small cell lung cancer.

BACKGROUND: The significance of postoperative adjuvant radiotherapy (PORT) on the survival of resected IIIA-N2 non-small cell lung cancer (NSCLC) remains controversial. Here, we aimed to determine the predictive value of the three nodal classifications which might aid in PORT decision-making. METHODS: A total of 4797 patients with stage IIIA-N2 resected NSCLC were identified in the Surveillance, Epidemiology and End Results (SEER) database and were grouped by whether PORT was administered. Survival analysis was used to identify the patient groups who can benefit from PORT. Multivariate analysis was performed to confirm the independent risk factors for lung cancer-specific survival (LCSS) and overall survival (OS). A validation cohort of 1184 patients from three medical centers in China were also included. RESULTS: PORT was not associated with better LCSS and OS in the entire cohort after propensity score matching (PSM). However, in the subgroups of positive lymph nodes 4 (PLN4), lymph node ratio 4 (LNR4), and log odds of positive lymph nodes 4 (LODDS4), PORT exhibited its role in improving LCSS (p < 0.05). Although the three nodal classifications were all identified as independent predictors of LCSS and OS, LODDS classification had the best discriminatory ability and prognostic accuracy for stage IIIA-N2 patients. Similar results were also obtained in the validation cohort. CONCLUSIONS: The LODDS classification not only exhibited the best prognostic performance in predicting LCSS and OS in stage IIIA-N2 disease, but also could help tailor individualized PORT.

Learning curve for uniportal video-assisted thoracoscopic anatomical segmentectomy.

BACKGROUND: Anatomical segmentectomy by uniportal video-assisted thoracoscopic surgery (U-VATS) is a delicate surgical procedure. Hitherto, only few studies have assessed the learning curves of anatomical segmentectomy by U-VATS, with varying data available. The present study aimed to investigate the learning curve and clinical advantages for U-VATS segmentectomy. METHODS: The medical records of patients who underwent U-VATS or non-U-VATS segmentectomy between August 2017 and May 2020 were retrospectively reviewed. Cumulative sum (CUSUM) analysis was employed to illustrate the learning curve of U-VATS segmentectomy. Perioperative parameters were used to determine the structural intervals of the learning curve, and to compare U-VATS and non-U-VATS segmentectomy. RESULTS: In total, 122 patients receiving U-VATS segmentectomy and 98 patients receiving non-VATS segmentectomy were included. Of these, 116 patients underwent successful U-VATS segmentectomy, while the other six patients underwent conversions. The structural intervals of 20-29 cases and 58-63 cases were determined as the threshold according to the CUSUM analyses. The learning process of U-VATS segmentectomy was therefore divided into three phases. Interestingly, the perioperative parameters differed significantly between Phases 1 and 3, including operative time (Op-T), postoperative hospital stays (Po-Hst), postoperative thoracic drainage (Po-D), and operative failure (Po-F) rates (P<0.05). Moreover, U-VATS segmentectomy in Phase 3 was associated with significantly shorter Po-Hst and Op-T, less Po-D, and reduced postoperative pain compared with non-U-VATS (P<0.05). CONCLUSIONS: U-VATS segmentectomy is an ideal alternative to non-U-VATS segmentectomy. Surgeons can preliminarily complete U-VATS anatomical segmentectomy after performing 20-29 cases, and can master the surgical techniques after completing 58-63 cases.

RGD peptide-decorated micelles assembled from polymer-paclitaxel conjugates towards gastric cancer therapy.

Development of polymer-drug conjugate capable of controlled drug release is urgently needed for gastric cancer therapy. Herein, arginine-glycine-aspartic acid (RGD)-decorated polyethylene glycol (PEG)-paclitaxel (PTX) conjugates containing disulfide linkage were synthesized. The amphiphilic PEG-PTX conjugates were found to assemble into micelles (RGD@Micelles), which would be decomposed under the reduction of glutathione (GSH) and finally release PTX in weakly acidic conditions characteristic of intracellular environment. The RGD@Micelles were spherical nanoparticles with an average hydrodynamic size of ˜50 nm, which were stable in physiological environment. The release of PTX from the micelles in response to GSH was investigated. In vitro cell assay suggested that the RGD@Micelles could target the gastric cancer cells and inhibit cell proliferation by inducing apoptosis. In vivo experiments indicated that the RGD@Micelles could be delivered to the tumor site and inhibit the tumor growth efficiently by releasing PTX inside the tumor cells. This type of micelles exhibited high therapeutic efficacy and low side effects, providing new insights into targeted drug delivery for gastric cancer therapy.

Expression of Synthetic Phytoene Synthase Gene to Enhance ß-Carotene Production in Scenedesmus sp. CPC2.

ß-carotene is a valuable pigment abundant in some microalgal species but the low ß-carotene productivity of microalgae has become the major obstacles against its commercialization. This work aims to improve the productivity of algae-based ß-carotene via genetic engineering approaches. First, a synthetic psy gene construct (891 bp) encoding 297 amino acids is expressed in Scenedesmus sp. CPC2 host to enhance the ß-carotene production. The synthetic psy gene is designed by considering the highest consensus of amino acids (i.e., 62% identity) from Chlamydomonas reinhardtii, Dunaliella salina, and Mariella zofingiensis. The original ß-carotene content in wild-type Scenedesmus sp. CPC2 is 10.8 mg g-1 -cell when grown on BG11 medium under 2% CO2 aeration, 150 µmol m-2 s-1 light intensity and 25°C. After transformation of the psy gene into the microalgal host, the ß-carotene content of the best recombinant strain (i.e., transformant CPC2-4) significantly increased to over 30 mg g-1 -cell. The optimal production of ß-carotene with the CPC2-4 recombinant strain was achieved when the strain is grown on BG11 medium amended with 0.075 g of MgSO4 , giving approximately 3-fold higher ß-carotene content than that of the wild-type strain. The best cellular ß-carotene content obtained (i.e., 31.8 mg g-1 ) is superior to most algae-based ß-carotene production performance reported in the literature.

Controllable release of nitric oxide and doxorubicin from engineered nanospheres for synergistic tumor therapy.

NaYF4:Yb,Er upconversion nanoparticles (UCNPs) capped with long-chain carboxylic acid were synthesized and then conjugated with chitosan (CS) in the aid of N-hydroxysuccinimide. The resultant nanocompound was integrated with doxorubicin (DOX) and Roussin's black salt (RBS), a photosensitive nitric oxide (NO) donor to produce stimuli-responsive UCNPs(DOX)@CS-RBS nanospheres as nanocarriers for controllable drug delivery. On the one hand, the encapsulated UCNPs can efficiently absorb NIR photons and convert them into visible photons to trigger NO release. On the other hand, the entrapped DOX can be released at lowered pH from the swollen nanospheres caused by stretched oleoyl-CS chains under acidic conditions. The UCNPs(DOX)@CS-RBS nanospheres exhibit great therapeutic efficacy, which is attributable to the combination of NO and DOX releases based on NO dose-dependent mechanisms. This study highlights the controllable release of NO and DOX from the same nanocarriers and the synergistic therapeutic effect on tumors, which could give new insights into improving cancer nanotherapeutics. STATEMENT OF SIGNIFICANCE: In this paper, core-shell structured UCNPs(DOX)@CS-RBS nanospheres have been designed and synthesized via a step-by-step procedure. The stimuli-responsive UCNPs(DOX)@CS-RBS nanospheres act as nanocarriers for controllable drug delivery towards cancer therapy. The encapsulated UCNPs can efficiently absorb NIR photons and convert them into visible light to trigger NO release. Meanwhile, the entrapped DOX can be released from the swollen nanospheres caused by stretched oleoyl-CS chains at lowered pH typical of intracellular environment. Synergistic cancer therapy will be achieved through the combination of NO and DOX releases based on NO dose-dependent mechanisms. This study provides new drug nanocarriers with high antitumor efficacy for synergistic cancer therapy.

Dynamic covalent linked triblock copolymer micelles for glutathione-mediated intracellular drug delivery.

Redox-responsive linkages dispersed in the backbones of the synthetic polymers, while young in the current spectrum of the biomedical application, are rapidly extending into their niche. In the present work, triblock copolymer PEG-PLA-PEG synthesized and characterized by 1H -NMR and SEC can self-assemble into redox-responsive micelles in aqueous media with nanosized 33nm and 47nm. And the copolymers PEG2000-PLA3000-PEG2000 and PEG2000-PLA5000-PEG2000 present lower CMC with 0.034 and 0.022mg/mL, and higher DLC of 4.28% and 5.14% respectively, compared with that of diblock copolymer. Moreover, drug release from the micelles can be triggered and significantly accelerated in reductive environment. The low cytotoxicity of redox-responsive micelles was confirmed by MTT assay against NIH 3T3 cells. All of these results demonstrated that these polymeric micelles self-assembled from double-disulfide tethered block copolymers are promising carriers for the redox-responsive intracellular delivery of hydrophobic anticancer drugs.

Chitosan-based core-shell nanomaterials for pH-triggered release of anticancer drug and near-infrared bioimaging.

As a naturally-abundant biopolymer, chitosan (CS) exhibit pH-sensitive structural transformation within a narrow pH range. Integrating hydrophobic groups to CS molecules gives modified CS polymers with more adjustable pH responsiveness. In this paper, near-infrared (NIR) photoluminescent Ag2S QDs capped by long-chain carboxylic acid were synthesized and then conjugated with CS via esterification reaction. The anticancer drug doxorubicin (DOX) has an affinity for the hydrophobic oleoyl groups and was entrapped by them to produce Ag2S(DOX)@CS nanospheres. A variety of experiments were performed to characterize the nanospheres. In vitro and in vivo experiments showed that the nanospheres can release DOX at lowered pH in tumor cells and have high antitumor efficacy. In addition, the strong NIR signal derived from the encapsulated Ag2S QDs makes real-time monitoring of the nanosphere distribution in a body possible. This study provides a new CS-based nanocomposite drug carrier for efficient cancer therapy.

Synthesis and evaluations of an acid-cleavable, fluorescently labeled nucleotide as a reversible terminator for DNA sequencing.

An acid-cleavable linker based on a dimethylketal moiety was synthesized and used to connect a nucleotide with a fluorophore to produce a 3'-OH unblocked nucleotide analogue as an excellent reversible terminator for DNA sequencing by synthesis.

Design and synthesis of fluorescence-labeled nucleotide with a cleavable azo linker for DNA sequencing.

A cleavable azo linker was synthesized and reacted with 5-(6)-carboxytetramethyl rhodamine succinimidyl ester, followed by further reactions with di(N-succinimidyl) carbonate and 5-(3-amino-1-propynyl)-2'-deoxyuridine 5'-triphosphate [dUTP(AP3)] to obtain the terminal product dUTP-azo linker-TAMRA as a potential reversible terminator for DNA sequencing by synthesis with no need for 3'-OH blocking.

Facile assembly of oppositely charged silver sulfide nanoparticles into photoluminescent mesoporous nanospheres.

Inorganic mesoporous materials have been attracting increasing attention during the past decade. In the present work, photoluminescent Ag2S nanospheres with mesoporous structures were prepared by assembling Ag2S nanoparticles with opposite charges in aqueous phase. Without structure-directing templates, mesoporous Ag2S with well-ordered face-centered cubic superlattice structures and high specific surface area was obtained. The mesoporous Ag2S nanospheres had the same crystal phase as their precursors Ag2S nanoparticles. Different from their near-infrared emitting precursors, the mesoporous Ag2S nanospheres exhibited cyan emission under ultraviolet excitation. The large number of sulfur-related defects existing in the mesostructures is most likely responsible for the photoluminescence. This work provides new insights into fabricating photoluminescent mesostructured materials via scale-up strategy.

Redox-responsive micelles self-assembled from dynamic covalent block copolymers for intracellular drug delivery.

Redox-responsive micelles self-assembled from dynamic covalent block copolymers with double disulfide linkage in the backbone have been developed successfully. The amphiphilic block copolymers PEG-PLA associated with complementary H-bonding sequences can self-assemble into spherical micelles in aqueous media with sizes from 34 nm to 107 nm with different molar mass of PEG and PLA. Moreover, in vitro drug release analyses indicate that reductive environment can result in triggered drug release profiles. The glutathione (GSH) mediated intracellular drug delivery was investigated against HeLa human cervical carcinoma cell line. Flow cytometry and fluorescence microscopy measurements demonstrated that the micelles exhibited faster drug release in glutathione monoester (GSH-OEt) pretreated HeLa cells than that in the nonpretreated cells. Cytotoxicity assay of DOX-loaded micelles indicated the higher cellular proliferation inhibition against 10 mM of GSH-OEt pretreated HeLa cells than that of the nonpretreated ones. These reduction-responsive, biodegradable and biocompatibility micelles could provide a favorable platform to construct excellent drug delivery systems for cancer therapy.

A new strategy for synthesizing AgInS2 quantum dots emitting brightly in near-infrared window for in vivo imaging.

A new strategy for fabricating water-dispersible AgInS2 quantum dots (QDs) with bright near-infrared (NIR) emission is demonstrated. A type of multidentate polymer (MDP) was synthesized and utilized as a compact capping ligand for the AgInS2 QDs. Using silver nitrate, indium acetate and sulfur-hydrazine hydrate complex as the precursors, MDP-capping AgInS2 QDs were synthesized in aqueous solution at room temperature. Characterization indicates that the MDP-capping AgInS2 QDs are highly photoluminescent in NIR window and possess good photostability. Also, the QDs are stable in different media and have low cytotoxicity. Nude mice photoluminescence imaging shows that the MDP-capping AgInS2 QDs can be well applied to in vivo imaging. These readily prepared NIR fluorescent nanocrystals have huge potential for biomedical applications.

Design and synthesis of new acid cleavable linkers for DNA sequencing by synthesis.

A new kind of acid sensitive tetrahydrofuranyl (THF) linker was synthesized and then reacted with 5-(6)-carboxytetramethylrhodaminesuccinimidyl ester (5(6)-TAMRA, SE), followed by di(N-succinimidyl) carbonate (DSC) and modified 2'-deoxyuridine triphosphate (dUTP); the final product, as a reversible terminator for DNA sequencing by synthesis (DNA SBS), was given obtained and confirmed by 1H-NMR, 31P-NMR, and HRMS with purity of up to 99%. The synthesized dye-labeled terminator incorporated into DNA strand successfully, and the fluorophore was cleaved completely under acidic conditions. The preliminary results encourage us to explore more acid-sensitive linkers for DNA SBS to increase the cleavage efficiency under weakly acidic conditions.

Oral absorbable fat-soluble vitamin formulation in pediatric patients with cholestasis.

OBJECTIVE: Fat-soluble vitamin (FSV) deficiencies are common complications in pediatric patients with chronic cholestasis. The aim of the present study was to evaluate the status of FSV deficiencies in patients under present practice and to test the effect of an oral, absorbable, fat-soluble vitamin formulation (OAFSV) in these patients. METHODS: We recruited a total of 23 pediatric patients receiving conventional FSV supplementation in a single medical center, with diagnosis of biliary atresia (10), progressive familial intrahepatic cholestasis (9), Alagille syndrome (2), and other conditions (2). Ten patients switched to OAFSV and continued for 3 months. Plasma levels of vitamins A, D, and E and an international normalized ratio (INR) for prothrombin time (PT), a surrogate marker for vitamin K deficiency, were measured. RESULTS: The proportion of patients with FSV A, D, E, and K deficiencies under conventional supplementation was 73.9%, 81.8%, 91.3%, and 20.0%, respectively. In patients with total bilirubin levels ≥3.0  mg/dL, the proportion of at least 1 FSV deficiency was 100%; and the deficiency rates of vitamin A, D, E, and K were 78.6%, 100.0%, 100.0% and 21.4%, respectively. Of the 10 patients receiving standard daily dose of OAFSV for 3 months, no adverse events or overdose effects were found. The rates of vitamin A, D, and E deficiency in the patients receiving OAFSV decreased from 80.0%, 100%, and 100%, respectively, to 70.0%, 60.0%, and 60.0% after 3 months of oral supplementation. CONCLUSIONS: High rates of FSV deficiency were found in pediatric patients with chronic cholestasis under present follow-up. OAFSV supplementation is safe and potentially effective in pediatric patients with cholestasis.

Synthesis and 188Re radiolabelling of dendrimer polyamide amine (PAMAM) folic acid conjugate.

Folic acid receptors (FR) are usually over expressed in many cancer cells and are considered as potential targeted therapy agent. Generation of five polyamido amine (PAMAM) dendrimer folic acid conjugate was synthesised and radiolabelled with (188)Re, furthermore the in vitro/in vivo stability was evaluated accordingly. The labelling yield of the conjugate G5-FA-DTPA-(188)Re was 67.1% and its radiochemical purity exceeded 95%. The conjugate also showed high in vitro stability and potential value for further structure modifications and evaluations.