A case study of a liver transplant-treated patient with glycogen storage disease type Ia presenting with multiple inflammatory hepatic adenomas: an analysis of clinicopathologic and genetic data.

BACKGROUND: Glycogen storage disease (GSD) is a disease caused by excessive deposition of glycogen in tissues due to genetic disorders in glycogen metabolism. Glycogen storage disease type I (GSD-I) is also known as VonGeirk disease and glucose-6-phosphatase deficiency. This disease is inherited in an autosomal recessive manner, and both sexes can be affected. The main symptoms include hypoglycaemia, hepatomegaly, acidosis, hyperlipidaemia, hyperuricaemia, hyperlactataemia, coagulopathy and developmental delay. CASE PRESENTATION: Here, we present the case of a 13-year-old female patient with GSD Ia complicated with multiple inflammatory hepatic adenomas. She presented to the hospital with hepatomegaly, hypoglycaemia, and epistaxis. By clinical manifestations and imaging and laboratory examinations, we suspected that the patient suffered from GSD I. Finally, the diagnosis was confirmed by liver pathology and whole-exome sequencing (WES). WES revealed a synonymous mutation, c.648 G > T (p.L216 = , NM_000151.4), in exon 5 and a frameshift mutation, c.262delG (p.Val88Phefs*14, NM_000151.4), in exon 2 of the G6PC gene. According to the pedigree analysis results of first-generation sequencing, heterozygous mutations of c.648 G > T and c.262delG were obtained from the patient's father and mother. Liver pathology revealed that the solid nodules were hepatocellular hyperplastic lesions, and immunohistochemical (IHC) results revealed positive expression of CD34 (incomplete vascularization), liver fatty acid binding protein (L-FABP) and C-reactive protein (CRP) in nodule hepatocytes and negative expression of ß-catenin and glutamine synthetase (GS). These findings suggest multiple inflammatory hepatocellular adenomas. PAS-stained peripheral hepatocytes that were mostly digested by PAS-D were strongly positive. This patient was finally diagnosed with GSD-Ia complicated with multiple inflammatory hepatic adenomas, briefly treated with nutritional therapy after diagnosis and then underwent living-donor liver allotransplantation. After 14 months of follow-up, the patient recovered well, liver function and blood glucose levels remained normal, and no complications occurred. CONCLUSION: The patient was diagnosed with GSD-Ia combined with multiple inflammatory hepatic adenomas and received liver transplant treatment. For childhood patients who present with hepatomegaly, growth retardation, and laboratory test abnormalities, including hypoglycaemia, hyperuricaemia, and hyperlipidaemia, a diagnosis of GSD should be considered. Gene sequencing and liver pathology play important roles in the diagnosis and typing of GSD.

Phenanthroline Derived N-Doped Carbon Dots as Robust Metal-Free Photocatalysts for PET-RAFT Polymerization and Polymerization-Induced Self-Assembly.

Metal-free organic photocatalysts for photo-mediated reversible deactivation radical polymerization (photo-RDRP) are witnessed to make increasing advancement in the precise synthesis of polymers. However, challenges still exist in the development of high-efficiency and environmentally sustainable carbon dots (CDs)-based organocatalysts. Herein, N-doped CDs derived from phenanthroline derivative (Aphen) are prepared as metal-free photocatalysts for photoinduced electron transfer reversible addition-fragmentation chain transfer (PET-RAFT) polymerization. The introduction of phenanthroline structure enhances the excited state lifetime of CDs and expands the conjugated length of their internal structure to enable the light-absorption to reach green light region, thereby enhancing photocatalytic activity. The as-designed CDs exhibit unprecedented photocatalytic capacity in photopolymerization even in large-volume reaction (100 mL) with high monomer conversion and narrow polymer dispersity (Mw/Mn < 1.20) under green light. The photocatalytic system is compatible with PET-RAFT polymerization of numerous monomers and the production of high molecular weight polyacrylate (Mn >250 000) with exquisite spatiotemporal control. Above results confirm the potential of CDs as photocatalyst, which has not been achieved with other CDs catalysts used in photo-RDRP. In addition, the construction of fluorescent polymer nanoparticles using CDs as both photocatalyst and phosphor through photoinitiated polymerization-induced self-assembly (Photo-PISA) technology is successfully demonstrated for the first time.

Integrating Hybrid Perovskite Nanocrystals into Metal-Organic Framework as Efficient S-Scheme Heterojunction Photocatalyst for Synergistically Boosting Controlled Radical Photopolymerization under 980 nm NIR Light.

S-scheme heterojunction photocatalyst MAPbI3@PCN-222 with light absorption extending to the NIR region is constructed by embedding organic-inorganic hybrid perovskite (MAPbI3) into porphyrinic Zr-MOF (PCN-222). Both in situ X-ray photoelectron spectroscopy, ultraviolet photoelectron spectral characterization, and photocatalytic polymerization experiment prove the formation of S-scheme heterojunction. MAPbI3@PCN-222 with a low dosage (90 ppm) displays an impressive photocatalytic ability for 980 nm light-mediated photoinduced electron/energy-transfer-reversible addition-fragmentation chain-transfer (PET-RAFT) polymerization in air. The well-defined controllable-molecular weight polymers including block copolymers and ultrahigh-molecular weight polymers can be achieved with narrow distributions (Mw/Mn < 1.20) via rapid photopolymerization. The industrial application potential of the photocatalyst also has been proved by scale-up synthesis of polymers with low polydispersity under NIR light-induced photopolymerization in a large-volume reaction system (200 mL) with high monomer conversion up to 99%. The penetration photopolymerization through the 5 mm polytetrafluoroethylene plate and excellent photocontrollable behavior illustrate the existence of long-term photogenerated electron transfer of heterojunction and abundant free radicals in photopolymerization. The photocatalyst still retains high catalytic activity after 10 cycles of photopolymerization in air. It is revealed for the first time that the special PET-RAFT polymerization pathway is initiated by the aldehyde-bearing α-aminoalkyl radical derived from the oxidization of triethanolamine (TEOA) by the heterojunction photocatalyst. This research offers a new insight into understanding the NIR-light-activated PET-RAFT polymerization mechanism in the presence of TEOA.

Two-Dimensional Cu-Porphyrin Metal-Organic Framework Nanosheet-Supported Flaky TiO2 as an Efficient Visible-Light-Driven Photocatalyst for Dye Degradation and Cr(VI) Reduction.

A series of 2D M(Cu, Zn, Co, and Mn)-TCPP MOFs/TiO2 binary nanocomposites (TCPP = tetrakis(4-carboxyphenyl)porphyrin) were constructed by solvothermal in situ loading of flaky TiO2 on the surface of 2D metal-organic frameworks (MOFs). The influence of different coordination metals on the catalytic activity was studied, and it was found that the 2D Cu-TCPP MOFs/TiO2 nanocomposite exhibited the best photo-Fenton performance. The superior property can be attributed to the high absorption coefficient and ultrathin two-dimensional structure of the 2D Cu-TCPP MOFs nanosheets. Meanwhile, the 2D Cu-TCPP MOFs/TiO2 II heterostructure can effectively promote the separation and transfer of photoformed carriers. Moreover, under visible irradiation, the optimized 2D Cu-TCPP MOFs/TiO2 composite can convert 99.9% of Cr(VI) to Cr(III) within 60 min with methanol as the hole scavenger at pH 3.14. Also, the photocatalytic performance of 2D Cu-TCPP MOFs/TiO2 was maintained after five reaction cycles. Furthermore, the proposed visible-light-driven photocatalysis mechanism of the 2D Cu-MOFs/TiO2 composite was reasonably derived according to experimental results. This study demonstrates the potential of building efficient TiO2-based visible light photocatalysts with 2D metal-porphyrin MOFs.

Clinical features, natural history and outcomes of pseudolymphoma of liver: A case-series and systematic review.

BACKGROUND: Pseudolymphoma is a rare, benign, nonspecific condition that forms a mass-like lesion characterized by the proliferation of non-neoplastic lymphocytes. Lacking of specific clinical symptoms, serological markers, and imaging features, the diagnosis is difficult. We reporte five cases of hepatic pseudolymphoma and provide a systematic review of existing literatures to improve our understanding of this rare liver disease. METHODS: We followed-up five cases of hepatic pseudolymphoma in West China Hospital from January 2002 to January 2022. We also summarized the cases of hepatic pseudolymphoma from January 1981 to December 2021 through the PubMed database and comprehensively analyzed the characteristics of the cases. RESULTS: The pathologic features of the five cases were characterized by benign lymphoid tissue hyperplasia, lymphoid follicle formation, and a polarized germinal center. Immunohistochemistry, in situ hybridization, and gene rearrangement revealed non-malignant lymphoma. Besides, a total of 116 cases have been reported in the PubMed database from 1981 to 2021. The incidence of hepatic pseudolymphoma is higher in middle-aged and elderly women and has been reported more frequently in Asia. All cases were pathologically diagnosed, among which 85.95% of the patients were treated by surgery. CONCLUSIONS: Hepatic pseudolymphoma is an extremely rare benign disease, mainly in middle-aged and elderly women. Without distinctive clinical and imaging characteristics, pathological diagnosis is the highly reliable method at present. Thus, in the absence of risk factors for a primary liver tumor or metastatic tumor in middle-aged and elderly women, the possibility of pseudolymphoma should be considered to avoid extensive treatments.

Expert Consensus on Pathological Diagnosis of Intrahepatic Cholangiocarcinoma (2022 version).

Intrahepatic cholangiocarcinoma (iCCA) can originate from the large bile duct group (segment bile ducts and area bile ducts), small bile duct group (septal bile ducts and interlobular bile ducts), and terminal bile duct group (bile ductules and canals of Hering) of the intrahepatic biliary tree, which can be histopathological corresponding to large duct type iCCA, small duct type iCCA and iCCA with ductal plate malformation pattern, and cholangiolocarcinoma, respectively. The challenge in pathological diagnosis of above subtypes of iCCA falls in the distinction of cellular morphologies, tissue structures, growth patterns, invasive behaviors, immunophenotypes, molecular mutations, and surgical prognoses. For these reasons, this expert consensus provides nine recommendations as a reference for standardizing and refining the diagnosis of pathological subtypes of iCCA, mainly based on the 5th edition of the World Health Organization Classification of Tumours of the Digestive System.

Case Report: A Novel Homozygous Variant Identified in a Chinese Patient With Benign Recurrent Intrahepatic Cholestasis-Type 1.

Benign recurrent intrahepatic cholestasis (BRIC) is a rare hereditary cholestatic liver disorder. Accurate diagnosis and timely interventions are important in determining outcomes. Besides clinical and pathologic diagnosis, genetic study of BRIC remains limited. Here, we report a young man enduring recurrent jaundice and severe pruritus for 15 years. The increased level of direct bilirubin was the main biochemical abnormality, and the work-up for common causes of jaundice were unremarkable. Liver biopsy showed extensive cholestasis of hepatocytes in zone 3. The novel homozygous variant including c.1817T > C and p.I606T was detected on his ATP8B1gene. The patient was finally diagnosed with BRIC-1. His symptoms were relieved, and liver function tests returned to normal after taking ursodeoxycholic acid. This case provides a different perspective to the methodology employed when dealing with cases of jaundice and helping diagnose rare diseases.

Congenital biliary atresia is correlated with disrupted cell junctions and polarity caused by Cdc42 insufficiency in the liver.

Rationale: Congenital biliary atresia (BA) is a destructive obliterative cholangiopathy of neonates that affects both intrahepatic and extrahepatic bile ducts. However, the cause of BA is largely unknown. Methods: We explored the cell junctions and polarity complexes in early biopsy BA livers by immunofluorescence staining and western blot. Cdc42, as a key cell junction and polarity regulator, was found dramatically decreased in BA livers. Therefore, in order to investigate the role of Cdc42 in BA development, we constructed liver-specific and tamoxifen induced cholangiocyte-specific Cdc42 deleted transgenic mice. We further evaluated the role of bile acid in aggravating biliary damage in Cdc42 insufficient mouse liver. Results: We found a dramatic defect in the assembly of cell junctions and polarity complexes in both cholangiocytes and hepatocytes in BA livers. This defect was characterized by the disordered location of cell junction proteins, including ZO1, ß-catenin, E-cadherin and claudin-3. Cdc42 and its active form, Cdc42-GTP, which serves as a small Rho GTPase to orchestrate the assembly of polarity complexes with Par6/Par3/αPKC, were substantially reduced in BA livers. Selective Cdc42 deficiency in fetal mouse cholangiocytes resulted in histological changes similar to those found in human BA livers, including obstruction in both the intra- and extrahepatic bile ducts, epithelial atrophy, and the disruption of cell junction and polarity complexes. A reduction in bile acids notably improved the histology and serological indices in Cdc42-mutant mice. Conclusion: Our results illustrate that BA is closely correlated with the impaired assembly of cell junction and polarity complexes in liver cells, which is likely caused by Cdc42 insufficiency and aggravated by bile acid corrosion.

Shear wave-based sound touch elastography in liver fibrosis assessment for patients with autoimmune liver diseases.

BACKGROUND: Shear wave-based ultrasonic elastography (USE) has been widely used for the assessment of liver fibrosis in patients with chronic liver diseases (CLD). However, diagnostic criteria and accuracy vary between different etiologies and specific elastography techniques. We aimed to evaluate the tissue stiffness measured by shear wave-based sound touch elastography (STE) in staging liver fibrosis in patients with autoimmune liver diseases (AILD). METHODS: One hundred and two AILD patients who had undergone STE liver stiffness measurements (LSMs) by using a Resona 7 ultrasound system were retrospectively studied. With the Scheuer liver fibrosis staging system as the reference, we investigated the diagnostic performance and cutoff values of STE measured liver stiffness in staging liver fibrosis through receiver operating characteristic (ROC) curve analysis. Moreover, comparisons of areas under the curve (AUCs) were made between LSMs and calculated biomarker scores, including the aspartate aminotransferase (AST)-to-platelet ratio index (APRI), and fibrosis-4 (FIB-4) index. RESULTS: Median LSMs increased with the advancing fibrosis stages with values of 6.89 kPa (1.51 m/s), 8.00 kPa (1.63 m/s), 9.60 kPa (1.79 m/s), 11.37 kPa (1.95 m/s) and 14.50 kPa (2.20 m/s), from stage 0 to stage 4 respectively. The cutoff values of STE for identifying significant fibrosis (≥ stage 2), severe fibrosis (≥ stage 3) and cirrhosis (stage 4) were 9.07 kPa (1.74 m/s), 9.97 kPa (1.82 m/s) and 10.48 kPa (1.87 m/s), respectively, with corresponding sensitivity of 79.1%, 93.3%, and 100%; specificity of 80.0%, 70.8% and 71.8%. The AUCs of LSMs in identifying fibrosis ≥ stage 2, ≥ stage 3 and stage 4 (0.82, 0.87, and 0.91, respectively) were significantly higher than that of APRI (0.67, 0.64, and 0.72, respectively) and FIB-4 (0.70, 0.68, and 0.75, respectively) (all P<0.05). CONCLUSIONS: LSM obtained by STE exhibited its good capability to evaluate liver fibrosis stages in patients with AILD. As a noninvasive modality for liver fibrosis staging, STE is superior to APRI and FIB-4 biomarker scores.

Brahma-Related Gene 1 Inhibition Prevents Liver Fibrosis and Cholangiocarcinoma by Attenuating Progenitor Expansion.

BACKGROUND AND AIMS: Intrahepatic cholangiocarcinoma (iCCA) is closely correlated with hepatic progenitor cell (HPC) expansion and liver fibrosis. Brahma-related gene 1 (Brg1), an enzymatic subunit of the switch/sucrose nonfermentable complex that is critical in stem cell maintenance and tumor promotion, is prominently up-regulated in both HPCs and iCCA; however, its role in this correlation remains undefined. APPROACH AND RESULTS: A retrospective cohort study indicated that high Brg1 expression suggests poor prognosis in patients with iCCA. In chronically injured livers induced by a 0.1% 3,5-diethoxycarbonyl-1,4-dihydrocollidine diet or bile duct ligation surgery, HPCs were dramatically activated, as indicated by their enhanced expression of Brg1 and a subset of stem cell markers; however, Brg1 ablation in HPCs strongly suppressed HPC expansion and liver fibrosis. Furthermore, in a chemically induced iCCA model, inhibition of Brg1 by a specific inhibitor or inducible gene ablation markedly improved histology and suppressed iCCA growth. Mechanistically, in addition to transcriptionally promoting both Wnt receptor genes and target genes, Brg1 was found to bind to the ß-catenin/transcription factor 4 transcription complex, suggesting a possible approach for regulation of Wnt/ß-catenin signaling. CONCLUSIONS: We have demonstrated the function of Brg1 in promoting HPC expansion, liver cirrhosis, and, ultimately, iCCA development in chronically injured livers, which is largely dependent on Wnt/ß-catenin signaling. Our data suggest that therapies targeting Brg1-expressing HPCs are promising for the treatment of liver cirrhosis and iCCA.

The Different Effects of Nucleotide and Nucleoside Analogues on the Prognosis of HBV-Related HCC After Curative Resection.

BACKGROUND: Postoperative oral antiviral treatment with nucleoside or nucleotide analogues can suppress viral replication and reduce tumour recurrence for patients with hepatitis b virus-related hepatocellular carcinoma (HBV-related HCC) after curative resection. However, the superior antiviral treatment is still unclear. We conducted this study to investigate the different effects of nucleotide and nucleoside analogues on the prognosis of HBV-related HCC after curative resection. METHODS: From February 2007 to February 2016, 487 consecutive patients with newly diagnosed HCC according to the Milan criteria who underwent R0 resection were enrolled according to the inclusion and exclusion criteria. According to their postoperative antiviral treatment, they were divided into the nucleotide group (NtA, n = 111) and the nucleoside group (NsA, n = 376). RESULTS: The baseline characteristics, serologic parameters, tumour characteristics, and operative data of the 2 groups were comparable. Nucleotide analogue use significantly decreased HCC recurrence (P = 0.028) and HCC-related death (P = 0.004), with hazard ratios (HRs) of 0.685 (95% CI, 0.484 to 0.971, P = 0.033) and 0.507 (95% CI, 0.310 to 0.830, P = 0.004), respectively, in multivariate Cox analyses. After the study patients were stratified according to three variables, we found that nucleotide analogue use was significantly associated with increased disease-free and overall survival among patients with cirrhosis, HBeAg-negative patients, and patients with positive HBV-DNA. CONCLUSIONS: In patients with HBV-related HCC, nucleotide analogues but not nucleoside analogues significantly reduced HCC recurrence and improved overall survival after R0 hepatic resection.

Mussel-inspired polydopamine-encapsulated carbon dots with dual emission for detection of 4-nitrophenol and Fe3.

Carbon dots (CDs) with excellent optical properties are widely used in biomedicine, fluorescence sensing, and light-emitting diodes (LEDs). However, it is still a challenge to prepare CDs that can stably emit red fluorescence in the water environment. In this study, polydopamine-encapsulated luminescent carbon dots (CDs@PDA) with an encapsulating structure were synthesized at room temperature from p-phenylenediamine-derived red-light CDs as the core and using mussel-inspired chemical properties of polydopamine (PDA). In the binary system of water:ethanol = 1: 3 (volume ratio), the as-prepared CDs@PDA had a dual emission of ultraviolet light (330 nm) and red light (640 nm) with the fluorescence quantum yields of 8.0 and 15.5%, respectively, at the same time under 285 nm light excitation. The as-prepared CDs@PDA could be directly used for fluorescence selective sensing of 4-nitrophenol (4-NP) and Fe3+ through simultaneously quenching of ultraviolet and red fluorescence based on the internal filtration effect mechanism with detection limits of 3.44 and 3.75 µM, respectively. This research showed that PDA-coated CDs can significantly improve the photoluminescence stability of CDs with new optical features. This means that the encapsulated structure of mussel chemistry is very helpful for expanding the application range of CDs in the water environment.

A standardized pathological proposal for evaluating microvascular invasion of hepatocellular carcinoma: a multicenter study by LCPGC.

BACKGROUND AND AIMS: Microvascular invasion (MVI) is a key pathological factor that severely affects the postoperative prognosis of patients with hepatocellular carcinoma (HCC). However, no MVI classification schemes based on standardized gross sampling protocols of HCC are available at present. METHODS: 119 HCC specimens were sampled at multiple sites (3-, 7-, and 13 points) for the optimum MVI detection rate. 16,144 resected HCCs were graded as M0, M1 or M2 by adopting three-tiered MVI grading (MVI-TTG) scheme based on the seven-point sampling protocol (SPSP). Survival analyses were performed on 2573 patients to explore the advantages of MVI-TTG. RESULTS: The MVI detection rate determined by SPSP was significantly higher than that determined by the 3-point sampling method (34.5% vs. 47.1%, p = 0.048), but was similar to that determined by the 13-point sampling method (47.1% vs. 51.3%, p = 0.517). Among 16,144 resected HCCs, the proportions of M0, M1 and M2 specimens according to SPSP were 53.4%, 26.2% and 20.4%, respectively. Postoperative survival analysis in 2573 HCC patients showed that the 3-year recurrence rates in M0, M1 and M2 MVI groups were 62.5%, 71.6% and 86.1%, respectively (p < 0.001), and the corresponding 3-year overall survival (OS) rates were 94.1%, 87.5% and 67.0%, respectively (p < 0.001). M1 grade was associated with early recurrence, while M2 grade was associated with both early and late recurrence. MVI-TTG had a larger area under the curve and net benefit rate than the two-tiered MVI grading scheme for predicting time to recurrence and OS. CONCLUSIONS: SPSP is a practical method to balance the efficacy of sampling numbers and MVI detection rates. MVI-TTG based on SPSP is a better prognostic predictor than the two-tiered MVI scheme. The combined use of SPSP and MVI-TTG is recommended for the routine pathological diagnosis of HCC.

Noninvasive assessment of liver fibrosis in chronic hepatitis B carriers with sound touch elastography: study of surgical pathology specimens.

PURPOSE: To evaluate the diagnostic performance of sound touch elastography (STE) for staging liver fibrosis in chronic hepatitis B (CHB) patients using pathological stage of surgical specimens as the reference standard. METHOD: 239 CHB patients were included. Liver stiffness measurements (LSMs) on STE and Supersonic shear imaging (SSI), gamma glutamyl transferase-to-platelet ratio (GPR), aspartate aminotransferase-to-platelet ratio index (APRI) and four-factor Fibrosis-4 (FIB-4) index were obtained. Areas under the receiver operating characteristic (ROC) curves (AUCs) for the diagnosis of fibrosis stage were calculated and compared. RESULTS: The LSMs obtained by STE and SSI significantly correlated with the fibrosis stages (r = 0.757; r = 0.758, respectively, both p < 0.001). No significant differences in AUCs were observed between STE and SSI in identifying fibrosis ≥stage 1 (0.92 vs. 0.94), ≥stage 2 (0.89 vs. 0.91), ≥stage 3 (0.90 vs. 0.91) or stage 4 (0.92 vs. 0.91). Both STE and SSI had significantly higher AUCs in identifying each fibrosis stage than the GPR (0.68, 0.77, 0.76 and 0.79), APRI (0.53, 0.66, 0.74 and 0.69) and FIB-4 (0.61, 0.77, 0.79 and 0.74). CONCLUSIONS: STE is an efficient tool for assessing liver fibrosis in CHB patients, with performance comparable to that of SSI and superior to that of biomarkers.

Enhanced SMARCD1, a subunit of the SWI/SNF complex, promotes liver cancer growth through the mTOR pathway.

The chromatin remodeling complex SWI/SNF regulates the accessibility of target genes to transcription factors and plays a critical role in the tumorigenesis of hepatocellular carcinoma (HCC). The SWI/SNF complex is assembled from approximately 15 subunits, and most of these subunits have distinct roles and are often aberrantly expressed in HCC. A comprehensive exploration of the expression and clinical significance of these subunits would be of great value. In the present study, we obtained the gene expression profile of each SWI/SNF subunit and the corresponding clinical information from The Cancer Genome Atlas (TCGA). We found that 14 out of the 15 SWI/SNF subunits were significantly increased in HCC tissues compared with paired normal liver tissues, and 11 subunits were significantly associated with overall survival (OS). We identified a four-gene prognostic signature including actin-like 6A (ACTL6A), AT-rich interaction domain 1A (ARID1A), SWI/SNF related, matrix associated, actin dependent regulator of chromatin subfamily C member 1 (SMARCC1) and SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily D, member 1 (SMARCD1) that could effectively predict OS in HCC patients. Among the genes, SMARCD1 has the most prognostic value. We further conducted in vitro and in vivo experiments and revealed that SMARCD1 promotes liver cancer growth by activating the mTOR signaling pathway. In conclusion, our study has revealed that the expression of SWI/SNF complex subunits, especially SMARCD1, is highly associated with HCC development and acts as a promising prognostic predictor.

A facile synthesis of multifunctional carbon dots as fluorescence 'turn on' and 'turn off' probes for selective detection of Al3+ and 2,4,6-trinitrophenol.

Carbon dots (CDs) have drawn increasing interests due to their unique optical properties and promising application in various fields. In this study, citric acid (CA) and 5-chloromethyl-8-hydroxyquinoline (LQ) were used to synthesize nitrogen-doped CDs as novel fluorescent probes using a one-step solvothermal route. The as-prepared CDs had strong blue-white fluorescence emission when excited at 405 nm wavelength with a quantum yield (QY) of 25%, behaving with high ion concentration stability. Water-soluble CDs with a 8-hydroxyquinoline structure on their surface could be used to detect Al3+ using a 'turn on' mechanism and trinitrophenol (TNP) using a 'turn off' mechanism with detection limits of 229 nM and 44.4 nM, respectively. Al3+ enhances the fluorescence of CDs by forming a coordination complex to generate a fluorescence synergistic role and limit CD nonradiative transition. TNP quenched the fluorescence with high selectivity and sensitivity, which was attributed to the inner filter effect and static quenching. These results indicated that these CDs with their unique 'turn on' and 'turn off' nature have potential application in the environmental protection field and in prevention of terrorist threats.

Size-controllable preparation and antibacterial mechanism of thermo-responsive copolymer-stabilized silver nanoparticles with high antimicrobial activity.

The emergence of bacterial resistance has become one of the top global concern, and silver nanoparticles (AgNPs) provide alternative strategies for the development of new antimicrobial agent. Herein, three small sizes (1.5-4.0 nm) of well-dispersed AgNPs were successfully synthesized using a thermo-sensitive P(NIPAM-co-MQ) copolymer with coordination ability as a stabilizer. The copolymer stabilized silver nanoparticles (AgNPs@P) displayed good thermo-sensitive characteristics and solution stability at pH = 6.5-8.0. AgNPs@P had high-efficiency and long-term antimicrobial properties for Gram-positive bacteria (S. aureus) and Gram-negative bacteria (E. coli). In particular, AgNPs@P3 with ultrasmall size (1.59 nm) exhibited better antimicrobial activity against both normal bacteria and antibiotic-resistant bacteria with a very low MIC value of 4.05 µg/mL. Moreover, AgNPs@P also showed an interesting temperature-dependent antibacterial activity mainly owing to the effect of thermo-sensitive copolymer on AgNPs. It was found that the antibacterial activity of the AgNPs@P also was affected by the proportion of copolymer, sizes of AgNPs, and experimental temperature. The antibacterial mechanism of AgNPs@P involved a variety of ways including destroying cell membranes, internalization of AgNPs and generation of ROS. Our research provides a new perspective for the preparation of effective nanosilver antimicrobial agents.

Concomitant systemic lupus erythematosus might have a negative impact on the biochemical responses to treatment in patients with primary biliary cholangitis.

BACKGROUND: Primary biliary cholangitis (PBC) is often overlapping with other autoimmune conditions, including systemic lupus erythematosus (SLE). Since the concomitant PBC and SLE are rare, the impacts of SLE on the response and prognosis in ursodeoxycholic acid (UDCA)-treated patients with PBC remain unclear. METHODS: A PBC database of 769 patients at West China hospital was used to identify 26 patients with concomitant PBC and SLE. The clinical and biochemical characteristics of these patients were collected and analyzed. Propensity score matching was used to compensate for the differences in age, total bilirubin, and alkaline phosphatase. The biochemical responses and prognoses were compared between the patients with and without concomitant SLE. RESULTS: The female-to-male ratio was 25:1 in the PBC patients with concomitant SLE. Compared with the group with PBC alone, the median hemoglobin and albumin values in the PBC-SLE group at the time of diagnosis of PBC were lower (both P < 0.05). After treatment, the group with PBC alone showed lower alanine aminotransferase and glutamyltransferase values and aspartate aminotransferase/platelet ratio indices at the final visit (all P < 0.05). The Kaplan-Meier estimate showed that the adverse event-free survival did not differ between the patients with and without concomitant SLE (P = 0.564). CONCLUSION: The results of this retrospective, single-center study suggested that the concomitant SLE status might have a negative impact on the biochemical responses to the treatment, while the effect of concomitant SLE on PBC progression remains to be further defined.Key Points• The prevalence of SLE in the PBC population being in a large PBC cohort was as low as 3.4%.• Compared with PBC-SLE group, the group with PBC alone showed lower alanine aminotransferase and glutamyltransferase values and aspartate aminotransferase/platelet ratio indices at the final visit, indicating that the concomitant SLE may have a negative impact on the biochemical responses to the treatment of PBC.

Ultrasonographic findings of intrahepatic lymphoepithelioma-like cholangiocarcinoma associated with Epstein-Barr virus: Two cases report.

RATIONALE: Epstein-Barr virus (EBV)-related lymphoepithelioma-like cholangiocarcinoma (LELCC) is an extremely rare primary liver tumor with nonspecific clinical manifestations. The clinicopathological features of EBV-associated LELCC have been reported in a few cases. But reports of the tumor's imaging characteristics, particularly ultrasonographic findings, are very rare. PATIENT CONCERNS: The first patient was a 64-year-old man with left upper quadrant pain and no nausea and dizziness for about 3 months. The second patient was a 40-year-old man, had an incidental finding of a hepatic tumor in a routine health checkup at a local hospital. DIAGNOSES: In the first patient, the abdominal ultrasound demonstrated a slightly heterogeneous hypoechoic nodule in segment 3 of the liver. The nodule was about 2.0 cm × 1.7 cm in size, with a clear margin and regular shape. Color Doppler flow imaging (CDFI) revealed no blood flow signals in this nodule. According to the clinical information and imaging features, it was difficult to determine the diagnosis of the nodule. In the second patient, gray-scale ultrasound revealed a slightly heterogeneous hypoechoic mass measuring 3.5 cm × 2.5 cm with well-defined margin and regular shape at the superior segment of the left hepatic lateral lobe. There was a blurrily hypoechoic halo around the mass. In contrast-enhanced ultrasound (CEUS), the mass was homogeneous hyperenhancement in the arterial phase. In the portal phase and late phase, the center enhancement of the mass washed out gradually, presenting hypoenhancement, Therefore, the tumor was diagnosed as malignancy. INTERVENTION: Finally, a laparoscopic left hepatic lateral lobectomy was performed in the first patient. The second patient underwent a left hepatectomy with cholecystectomy. OUTCOMES: The first patient has been alive without recurrence or distant metastases for 11 months since the surgery. The second patient received routine follow-up after surgery. Until now, he has been tumor-free for 32 months. LESSONS: We mainly focus on the ultrasound characteristics of EBV-associated LELCC, especially its enhancement patterns on CEUS, which may provide valuable information for diagnosis of the LELCC. When a liver tumor with typical CEUS patterns of malignancy is found in middle-aged adults with EBV positive, the possibility of EBV-related LELCC should be considered.

Mussel-Inspired Catechol-Formaldehyde Resin-Coated Fe3O4 Core-Shell Magnetic Nanospheres: An Effective Catalyst Support for Highly Active Palladium Nanoparticles.

Magnetic Fe3O4@catechol-formaldehyde resin (CFR) core-shell nanospheres were fabricated via a controllable hydrothermal method. The shell thickness of Fe3O4@CFR nanospheres can be effectively regulated in the range of 10-170 nm via adjusting reaction parameters. In particular, catechol groups on the surface of nanospheres also play a significant role in mussel-inspired chemistry to further combine with graphene oxide (GO) to wrap the Fe3O4@CFR spheres. The obtained Fe3O4@CFR and Fe3O4@CFR@GO nanospheres can be used as the effective catalyst supports of small Pd nanoparticles (PdNPs, <10 nm) formed via an in situ synthesis route. The as-fabricated nanohybrid catalysts of Fe3O4@CFR@PdNPs and Fe3O4@CFR@GO@PdNPs with excellent dispersibility and stability are reusable after magnetic separation from catalytic systems. In particular, a super active performance was demonstrated for the catalytic reduction of methylene blue dye with highest turnover frequency (5260 min-1) yet reported in the literature using a very low dosage of the Fe3O4@CFR@GO@PdNP catalyst. In addition, the Fe3O4@CFR@GO@PdNP catalyst also exhibits a highly catalytic efficiency for the Suzuki coupling reaction using pure water as a green solvent at room temperature.