Microbiome and mycobiome analyses in continuous positive airway pressure devices.

Objectives: Microorganisms are likely present in continuous positive airway pressure (CPAP) devices used daily. Considering the potential risk of infections among CPAP device users, here we aimed to compare the microbiomes in CPAP devices with those in nasal mucosal samples obtained from corresponding individuals using these devices. Methods: We conducted a prospective cohort study at tertiary medical institutes. Samples were collected from the tubes and filters of CPAP devices and the nasal mucosa of corresponding individuals using these devices. Microbiomes and mycobiomes were analyzed using 16S ribosomal RNA and internal transcribed spacer region sequencing. Results were compared according to the sampling site and usage duration for each patient. Results: Overall, 27 paired human nasal mucosa and CPAP samples were analyzed. Bacteria were present in 7 of 27 tubes (29.6%) and 22 of 27 filters (81.5%). Fungi were present in 2 of the 27 tubes (7.4%) and 16 of the 27 filters (59.3%). Actinobacteria and Firmicutes were the predominant phyla among all samples. Fungi were not detected in any of the nasal mucosal samples. However, Basidiomycota and Ascomycota were predominant in the CPAP filters and tube samples. No significant associations were identified among the results according to sampling site and usage duration. Conclusion: Bacteria or fungi can be detected to some extent in CPAP samples even if the CPAP usage period is short. The association between respiratory infections and these microbiomes or mycobiomes was not investigated. Further research might be required to determine the risk posed by CPAP devices as a microbial contamination source.

Daily habits, diseases, drugs and knee osteoarthritis: a two-sample Mendelian randomization analysis.

Background: The causal relationship between daily habits, diseases, drugs, and knee osteoarthritis (KOA) remains unclear. This study utilized a two-sample Mendelian randomization (MR) method to investigate the causal links between these factors and KOA, providing new insights for KOA prevention. Methods: SNPs strongly associated with exposure factors (daily habits, diseases, drugs) were extracted from publicly available genome-wide association study (GWAS) as instrumental variables (IVs). We then selected GWAS of KOA as the outcome, conducting a two-sample MR analysis. Results: Our findings revealed significant causal relationships between several factors and KOA. There was a notable association with time spent watching TV (OR = 4.038; 95% CI: 1.859-8.770; P = 4.192E-04), frequency of friend/family visits (OR = 0.415; 95% CI: 0.219-0.788; P = 7.174E-03), smoking history (OR = 0.781; 95% CI: 0.663-0.921; P = 3.235E-03), gastroesophageal reflux disease (GERD) (OR = 1.519; 95% CI: 1.244-1.856; P = 4.183E-05), hypercholesterolemia (OR = 0.498; 95% CI: 0.290-0.855; P = 0.011), hypothyroidism (OR = 1.048; 95% CI: 1.013-1.084; P = 6.645E-03), use of antithrombotic agents (OR = 0.892; 95% CI: 0.816-0.976; P = 0.013), statin medication (OR = 0.956; 95% CI: 0.916-0.998; P = 0.041), and thyroid preparations (OR = 1.042; 95% CI: 1.014-1.071; P = 2.974E-03) with KOA. Specifically, KOA was positively associated with longer time spent watching TV, GERD, hypothyroidism and thyroid preparations, however showed a negative correlation with more frequent visits from friends or family, smoking history, hypercholesterolemia, antithrombotic agents and statin medication. Sensitivity analysis indicated no significant pleiotropy in these studies (P > 0.05). Conclusion: This comprehensive study underscores the significance of modifying certain habits to mitigate the risk of KOA. Additionally, the elevated risk of KOA among individuals with GERD, hypothyroidism, and those using thyroid preparations warrants attention. These results would be beneficial for clinical research and nursing education.

BRD4 plays an antiaging role in the senescence of renal tubular epithelial cells.

Background: Age-related kidney failure is often induced by a decrease in the bioavailability of tubular epithelial cells in elderly chronic kidney disease (CKD) patients. BRD4, an epigenetic regulator and a member of the bromodomain and extraterminal (BET) protein family, acts as a super-enhancer (SE) organizing and regulating genes expression during embryogenesis and cancer development. But the physiological function of BRD4 in normal cells has been less studied. This study aimed to research certain biological roles of BRD4 in the process of normal cell aging and discuss the potential mechanisms. Methods: In this study, we investigated the biological functions of BRD4 proteins in the aging of renal tubular cells. At first, we used a D-galactose (D-gal) and BRD4 inhibitor (Abbv-075) to replicate kidney senescence in vivo. D-gal and Abbv-075 were then used to measure the aging-related changes, such as changes in cell cycle, ß-galactosidase activity, cell migration, and p16 protein expression in vitro. At last, we knocked down and over-expressed BRD4 to investigate the aging-related physiological phenomena in renal tubular cells. Results: In vitro, D-gal treatment induced noticeable aging-related changes such as inducing cell apoptosis and cell cycle arrest, increasing ß-galactosidase activity as well as up-regulating p16 protein expression in primary human tubular epithelial cells. In the aging mice model, D-gal significantly induced renal function impairment and attenuated BRD4 protein expression. At the same time, the BRD4 inhibitor (Abbv-075) was able to mimic D-gal-induced cell senescence. In vivo, Abbv-075 also decreased kidney function and up-regulated p21 protein expression. When we knocked down the expression of BRD4, the senescence-associated ß-galactosidase (SA-ß-gal) activity increased dramatically, cell migration was inhibited, and the proportion of cells in the G0/G1 phase increased. Additionally, the knockdown also promoted the expression of the senescence-related proteins p16. When the renal tubular cells were overexpressed with BRD4, cell aging-related indicators were reversed in the D-gal-induced cell aging model. Conclusions: BRD4 appears to have an active role in the aging of renal tubular cells in vivo and in vitro. The findings also suggest that BRD4 inhibitors have potential nephrotoxic effects for oncology treatment. BRD4 may be a potential therapeutic biomarker and drug target for aging-related kidney diseases, which warrants additional studies.

The Role of the Intestinal Flora and Its Derivatives in Neurocognitive Disorders: A Narrative Review from Surgical Perspective.

Perioperative neurocognitive dysfunction is a significant concern for population health, impacting postoperative recovery and increasing the financial burden on patients. With an increasing number of surgical procedures being performed, the prevention and management of perioperative neurocognitive dysfunction have garnered significant attention. While factors such as age, lifestyle, genetics, and education are known to influence the development of cognitive dysfunction, recent research has highlighted the role of the gut microbiota in neurological health. An increased abundance of pro-inflammatory gut microbiota can trigger and worsen neuroinflammation, neuronal cell damage, and impaired cellular autophagy. Moreover, the inflammation-promoting gut microbiota can disrupt immune function, impair neuroautophagy, and affect the production and circulation of extracellular vesicles and neurotransmitters. These factors collectively play a role in the onset and advancement of cognitive impairment. This narrative review delves into the molecular mechanisms through which gut microbiota and their derivatives contribute to cognitive impairment, focusing on the impact of anesthesia surgery, changes in gut microbial populations, and perioperative cognitive impairment associations. The study suggests that alterations in the abundance of various bacterial species and their metabolites pre- and post-surgery may be linked to postoperative cognitive impairment. Furthermore, the potential of probiotics or prebiotics in addressing cognitive impairment is discussed, offering a promising avenue for investigating the treatment of perioperative neurocognitive disorders.

Pilot-scale field studies on activated microbial remediation of petroleum-contaminated soil.

Soil contamination by petroleum, including crude oil from various sources, is increasingly becoming a pressing global environmental concern, necessitating the exploration of innovative and sustainable remediation strategies. The present field-scale study developed a simple, cost-effective microbial remediation process for treating petroleum-contaminated soil. The soil treatment involves adding microbial activators to stimulate indigenous petroleum-degrading microorganisms, thereby enhancing the total petroleum hydrocarbons (TPH) degradation rate. The formulated microbial activator provided a growth-enhancing complex of nitrogen and phosphorus, trace elements, growth factors, biosurfactants, and soil pH regulators. The field trials, involving two 500 m3 soil samples with the initial TPH content of 5.01% and 2.15%, were reduced to 0.41% and 0.02% in 50 days, respectively, reaching the national standard for cultivated land category II. The treatment period was notably shorter than the commonly used composting and bioaugmentation methods (typically from 8 to 12 weeks). The results indicated that the activator could stimulate the functional microorganisms in the soil and reduce the phytotoxicity of the contaminated soil. After 40 days of treatment, the germination rate of rye seeds increased from 20 to 90%, indicating that the microbial activator could be effectively used for rapid on-site remediation of oil-contaminated soils.

Re-assessing the diagnostic value of the enhancing "capsule" in hepatocellular carcinoma imaging.

Background/Aims: The enhancing "capsule" (EC) in hepatocellular carcinoma (HCC) diagnosis has received varying degrees of recognition across major guidelines. This study aimed to assess the diagnostic utility of EC in HCC detection. Methods: We retrospectively analyzed patients who underwent pre-surgical computed tomography (CT) and hepatobiliary agent-enhanced magnetic resonance imaging (HBA-MRI) between January 2016 and December 2019. A single hepatic tumor was confirmed based on the pathology of each patient. Three radiologists independently reviewed the images according to the Liver Imaging Reporting and Data System (LIRADS) v2018 criteria and reached a consensus. Interobserver agreement for EC before reaching a consensus was quantified using Fleiss κ statistics. The impact of EC on the LI-RADS classification was assessed by comparing the positive predictive values for HCC detection in the presence and absence of EC. Results: In total, 237 patients (median age, 60 years; 184 men) with 237 observations were included. The interobserver agreement for EC detection was notably low for CT (κ=0.169) and HBA-MRI (κ=0.138). The presence of EC did not significantly alter the positive predictive value for HCC detection in LI-RADS category 5 observations on CT (94.1% [80/85] vs. 94.6% [88/93], P=0.886) or HBA-MRI (95.7% [88/92] vs. 90.6% [77/85], P=0.178). Conclusions: The diagnostic value of EC in HCC diagnosis remains questionable, given its poor interobserver agreement and negligible impact on positive predictive values for HCC detection. This study challenges the emphasis on EC in certain diagnostic guidelines and suggests the need to re-evaluate its role in HCC imaging.

Erratum: Diagnostic Performance of Rectal CT for Staging Rectal Cancer: Comparison with Rectal MRI and Histopathology.

[This corrects the article on p. 1290 in vol. 84, PMID: 38107688.].

Approximate Bayesian computation and ecological niche models elucidate the demographic history and current fragmented population distribution of a Korean endemic shrub.

Climatic fluctuations and geological events since the LGM are believed to have significantly impacted the population size, distribution, and mobility of many species that we observe today. In this paper, we determined the processes driving the phylogeographic structure of the Korean endemic white forsythia by combining the use of genome-wide SNPs and predicting paleoclimatic habitats during the LGM (21 kya), Early Holocene (10 kya), Mid-Holocene (6 kya), and Late Holocene (3 kya). Using a maximum of 1897 SNPs retrieved from 124 samples across nine wild populations, five environmental predictors, and the species' natural occurrence records, we aimed to infer the species' demographic history and reconstruct its possible paleodistributions with the use of approximate Bayesian computation and ecological niche models, respectively. Under this integrated framework, we found strong evidence for patterns of range shift and expansion, and population divergence events from the onset of the Holocene, resulting in the formation of its five distinct genetic units. The most highly supported model inferred that after the split of an ancestral population into the southern group and a larger central metapopulation lineage, the latter gave rise to the eastern and northern clusters, before finally dividing into two sub-central groups. While the use of molecular data allowed us to identify and refine the (phylo)genetic relationships of the species' lineages and populations, the use of ecological data helped us infer a past LGM refugium and the directions of post-glacial range dynamics. The time frames of these demographic events were shown to be congruent with climatic and geological events that affected the central Korean Peninsula during these periods. These findings gave us a better understanding of the consequences of past spatiotemporal factors that may have resulted in the current fragmented population distribution of this endangered plant.

Diagnostic Performance of Rectal CT for Staging Rectal Cancer: Comparison with Rectal MRI and Histopathology.

Purpose: To compare the diagnostic performance of rectal CT with that of high-resolution rectal MRI and histopathology in assessing rectal cancer. Materials and Methods: Sixty-seven patients with rectal cancer who underwent rectal CT with rectal distension using sonographic gel and high-resolution MRI were enrolled in this study. The distance from the anal verge/anorectal junction, distance to the mesorectal fascia (MRF), extramural depth (EMD), extramesorectal lymph node (LN) involvement, extramural venous invasion (EMVI), and T/N stages in rectal CT/MRI were analyzed by two gastrointestinal radiologists. The CT findings of 20 patients who underwent radical surgery without concurrent chemoradiotherapy were compared using histopathology. Interclass correlations and kappa statistics were used. Results: The distance from the anal verge/anorectal junction showed an excellent intraclass correlation between CT and MRI for both reviewers. For EMD, the distance to the MRF, presence of LNs, extramesorectal LN metastasis, EMVI, T stage, and intermodality kappa or weighted kappa values between CT and MRI showed excellent agreement. Among the 20 patients who underwent radical surgery, T staging, circumferential resection margin involvement, EMVI, and LN metastasis on rectal CT showed acceptable concordance rates with histopathology. Conclusion: Dedicated rectal CT may be on par with rectal MRI in providing critical information to patients with rectal cancer.

Plastome phylogenomics and morphological traits analyses provide new insights into the phylogenetic position, species delimitation and speciation of Triplostegia (Caprifoliaceae).

BACKGROUND: The genus Triplostegia contains two recognized species, T. glandulifera and T. grandiflora, but its phylogenetic position and species delimitation remain controversial. In this study, we assembled plastid genomes and nuclear ribosomal DNA (nrDNA) cistrons sampled from 22 wild Triplostegia individuals, each from a separate population, and examined these with 11 recently published Triplostegia plastomes. Morphological traits were measured from herbarium specimens and wild material, and ecological niche models were constructed. RESULTS: Triplostegia is a monophyletic genus within the subfamily Dipsacoideae comprising three monophyletic species, T. glandulifera, T. grandiflora, and an unrecognized species Triplostegia sp. A, which occupies much higher altitude than the other two. The new species had previously been misidentified as T. glandulifera, but differs in taproot, leaf, and other characters. Triplotegia is an old genus, with stem age 39.96 Ma, and within it T. glandulifera diverged 7.94 Ma. Triplostegia grandiflora and sp. A diverged 1.05 Ma, perhaps in response to Quaternary climate fluctuations. Niche overlap between Triplostegia species was positively correlated with their phylogenetic relatedness. CONCLUSIONS: Our results provide new insights into the species delimitation of Triplostegia, and indicate that a taxonomic revision of Triplostegia is needed. We also identified that either rpoB-trnC or ycf1 could serve as a DNA barcode for Triplostegia.

Systemic antibiotics cause deterioration of emphysema associated with exaggerated inflammation and autophagy.

The interaction between the microbial environment and the host is important for immune homeostasis. Recent research suggests that microbiota dysbiosis can be involved in respiratory diseases. Emphysema is a chronic inflammatory disease, but it is unclear whether dysbiosis caused by antibiotics can affect disease progression. Here, we tried to elucidate the effect of systemic antibiotics on smoking-exposed emphysema models. In this study, the antibiotic mixture caused more alveolar destruction and airspace expansion in the smoking group than in the smoking only or control groups. This emphysema aggravation as a result of antibiotic exposure was associated with increased levels of inflammatory cells, IL-6, IFNγ and protein concentrations in bronchoalveolar lavage fluid. Proteomics analysis indicated that autophagy could be involved in antibiotic-associated emphysema aggravation, and increased protein levels of LC3B, atg3, and atg7 were identified by Western blotting. In microbiome and metabolome analyses, the composition of the gut microbiota was different with smoking and antibiotic exposure, and the levels of short-chain fatty acids (SCFAs), including acetate and propionate, were reduced by antibiotic exposure. SCFA administration restored emphysema development with reduced inflammatory cells, IL-6, and IFNγ and decreased LC3B, atg3, and atg7 levels. In conclusion, antibiotics can aggravate emphysema, and inflammation and autophagy may be associated with this aggravation. This study provides important insight into the systemic impact of microbial dysbiosis and the therapeutic potential of utilizing the gut microbiota in emphysema.

The complete chloroplast genome sequences of six Hylotelephium species: Comparative genomic analysis and phylogenetic relationships.

To evaluate the phylogenetic relationships between Hylotelephium and Orostachys, and to provide important information for further studies, we analyzed the complete chloroplast genomes of six Hylotelephium species and compared the sequences to those of published chloroplast genomes of congeneric species and species of the closely related genus, Orostachys. The total chloroplast genome length of nineteen species, including the six Hylotelephium species analyzed in this study and the thirteen Hylotelephium and Orostachys species analyzed in previous studies, ranged from 150,369 bp (O. minuta) to 151,739 bp (H. spectabile). Their overall GC contents were almost identical (37.7-37.8%). The chloroplast genomes of the nineteen species contained 113 unique genes comprising 79 protein-coding genes (PCGs), 30 transfer RNA genes (tRNAs), and four ribosomal RNA genes (rRNAs). Among the annotated genes, fourteen genes contained one intron, and two genes contained two introns. The chloroplast genomes of the nineteen Hylotelephium and Orostachys species had identical structures. Additionally, the large single copy (LSC), inverted repeat (IR), and small single copy (SSC) junction regions were conserved in the Hylotelephium and Orostachys species. The nucleotide diversity between the Hylotelephium chloroplast genomes was extremely low in all regions, and only one region showed a high Pi value (>0.03). In all nineteen chloroplast genomes, six regions had a high Pi value (>0.03). The phylogenetic analysis showed that the genus delimitation could not be clearly observed even in this study because Hylotelephium formed a paraphyly with subsect. Orostachys of the genus Orostachys. Additionally, the data supported the taxonomic position of Sedum taqeutii, which was treated as a synonym for H. viridescens in previous studies, as an independent taxon.

A highly selective C-rhamnosyltransferase from Viola tricolor and insights into its mechanisms.

C-Glycosides are important natural products with various bioactivities. In plant biosynthetic pathways, the C-glycosylation step is usually catalyzed by C-glycosyltransferases (CGTs), and most of them prefer to accept uridine 5'-diphosphate glucose (UDP-Glc) as sugar donor. No CGTs favoring UDP-rhamnose (UDP-Rha) as sugar donor has been reported, thus far. Herein, we report the first selective C-rhamnosyltransferase VtCGTc from the medicinal plant Viola tricolor. VtCGTc could efficiently catalyze C-rhamnosylation of 2-hydroxynaringenin 3-C-glucoside, and exhibited high selectivity towards UDP-Rha. Mechanisms for the sugar donor selectivity of VtCGTc were investigated by molecular dynamics (MD) simulations and molecular mechanics with generalized Born and surface area solvation (MM/GBSA) binding free energy calculations. Val144 played a vital role in recognizing UDP-Rha, and the V144T mutant could efficiently utilize UDP-Glc. This work provides a new and efficient approach to prepare flavonoid C-rhamnosides such as violanthin and iso-violanthin.

Design and Optimization of Composite Cathodes for Solid-State Batteries Using Hybrid Carbon Networks with Facile Electronic and Ionic Percolation Pathways.

Solid-state batteries (SSBs) have emerged as a promising alternative to conventional liquid electrolyte batteries due to their potential for higher energy density and improved safety. However, achieving high performance in SSBs is difficult because of inadequate contact and interfacial reactions that generate high interfacial resistance, as well as inadequate solid-solid contact between electrodes. These chronic issues are associated with inhomogeneous ion and electron transport networks owing to imperfect solid-solid interfacial contact. This study developed an optimal interfacial engineering strategy to facilitate an ion-electron transport network by designing an active material (NCM622) uniformly filled with a thin layer of a solid electrolyte (garnet-type Li6.25Ga0.25La3Zr2O12) and conductive additives. The optimal composite electrode architecture enhanced the high capacity, high rate capability, and long-term cycle stability, even at room temperature, owing to the percolating network for facile ionic conduction that assured a homogeneous reaction. In addition to mitigating the mechanical degradation of the cathode electrode, it also reduced the crosstalk effects on the anode-solid electrolyte interface. Effectively optimizing the selection and use of conductive additives in composite electrodes offers a promising approach to addressing key performance-limiting factors in SSBs, including interfacial resistance and solid-solid contact issues. This study underscores the critical importance of cathode architecture design for achieving high-performance SSBs by ensuring that the interfaces are intact with solid electrolytes at both the cathode and anode interfaces while promoting uniform reactions. This study provides valuable insights into the development of SSBs with improved performance, which could have significant implications for a wide range of applications.

Synovial cysts at the cervicothoracic junction: Illustrative series of three cases.

Background: Spinal synovial cysts are an uncommon pathology, estimated to affect 0.65-2.6% of the population. Cervical spinal synovial cysts are even rarer, accounting for only 2.6% of spinal synovial cysts. They are more commonly found in the lumbar spine. When they occur, they can compress the spinal cord or surrounding nerve roots resulting in neurological symptoms, particularly when they increase in size. Decompression and cyst resection are the most common treatment and typically result in resolution of symptoms. Methods: The authors present three cases of spinal synovial cysts occurring at the C7-T1 junction. They occurred in patients aged 47, 56, and 74, respectively, and presented with symptoms of pain and radiculopathy. Diagnosis was made with computed tomography (CT) scan and magnetic resonance imaging (MRI). The cysts were managed with laminectomy, resection, and fusion. Results: All patients reported full resolution of symptoms. There were no intra or postoperative complications. Conclusion: Cervical spinal synovial cysts are an uncommon cause of radiculopathy and pain in the upper extremities. They can be diagnosed through CT scans and MRI, and treatment with laminectomy, resection, and fusion results in excellent outcomes.

Contrasting range changes of terrestrial orchids under future climate change in China.

Climate change has impacted the distribution and abundance of numerous plant and animal species during the last century. Orchidaceae is one of the largest yet most threatened families of flowering plants. However, how the geographical distribution of orchids will respond to climate change is largely unknown. Habenaria and Calanthe are among the largest terrestrial orchid genera in China and around the world. In this paper, we modeled the potential distribution of eight Habenaria species and ten Calanthe species in China under the near-current period (1970-2000) and the future period (2081-2100) to test the following two hypotheses: 1) narrow-ranged species are more vulnerable to climate change than wide-ranged species; 2) niche overlap between species is positively correlated with their phylogenetic relatedness. Our results showed that most Habenaria species will expand their ranges, although the climatic space at the southern edge will be lost for most Habenaria species. In contrast, most Calanthe species will shrink their ranges dramatically. Contrasting range changes between Habenaria and Calanthe species may be explained by their differences in climate-adaptive traits such as underground storage organs and evergreen/deciduous habits. Habenaria species are predicted to generally shift northwards and to higher elevations in the future, while Calanthe species are predicted to shift westwards and to higher elevations. The mean niche overlap among Calanthe species was higher than that of Habenaria species. No significant relationship between niche overlap and phylogenetic distance was detected for both Habenaria and Calanthe species. Species range changes in the future was also not correlated with their near current range sizes for both Habenaria and Calanthe. The results of this study suggest that the current conservation status of both Habenaria and Calanthe species should be adjusted. Our study highlights the importance of considering climate-adaptive traits in understanding the responses of orchid taxa to future climate change.

Influence of Dental Titanium Implants with Different Surface Treatments Using Femtosecond and Nanosecond Lasers on Biofilm Formation.

This study aimed to evaluate the impact of different surface treatments (machined; sandblasted, large grit, and acid-etched (SLA); hydrophilic; and hydrophobic) on dental titanium (Ti) implant surface morphology, roughness, and biofilm formation. Four groups of Ti disks were prepared using distinct surface treatments, including femtosecond and nanosecond lasers for hydrophilic and hydrophobic treatments. Surface morphology, wettability, and roughness were assessed. Biofilm formation was evaluated by counting the colonies of Aggregatibacter actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg), and Prevotella intermedia (Pi) at 48 and 72 h. Statistical analysis was conducted to compare the groups using the Kruskal-Wallis H test and the Wilcoxon signed-rank test (α = 0.05). The analysis revealed that the hydrophobic group had the highest surface contact angle and roughness (p < 0.05), whereas the machined group had significantly higher bacterial counts across all biofilms (p < 0.05). At 48 h, the lowest bacterial counts were observed in the SLA group for Aa and the SLA and hydrophobic groups for Pg and Pi. At 72 h, low bacterial counts were observed in the SLA, hydrophilic, and hydrophobic groups. The results indicate that various surface treatments affect implant surface properties, with the hydrophobic surface using femtosecond laser treatment exerting a particularly inhibitory effect on initial biofilm growth (Pg and Pi).

Effectiveness of US Surveillance of Hepatocellular Carcinoma in Chronic Hepatitis B: US LI-RADS Visualization Score.

Background US is a standard surveillance tool of hepatocellular carcinoma (HCC), but its effectiveness varies depending on the degree of fibrosis or steatosis and the etiologies of liver disease. Purpose To evaluate the detection power of US and the occurrence of HCC according to the US Liver Imaging Reporting and Data System (LI-RADS) visualization score in chronic hepatitis B (CHB). Materials and Methods Consecutive patients with CHB undergoing regular US surveillance of HCC at a tertiary referral hospital were retrospectively included in this study. During the follow-up, all patients underwent regular HCC surveillance mainly with US and, in some cases, alternative CT or MRI. Outcomes of interest included cumulative incidence of HCC and false-negative rate of US in the optimal (LI-RADS visualization A) versus suboptimal groups (visualization B or C). Cox regression analysis was conducted to calculate the hazard ratio (HR) of HCC occurrence. Results A total of 2002 patients (median age, 54 years [IQR, 46-60 years]; 1192 men) were included: 972 and 1030 in the optimal and suboptimal groups, respectively. Causes of suboptimal visualization included parenchymal heterogeneity from advanced cirrhosis (n = 489), limited penetration from fatty liver (n = 200), and limited window from overlying organ shadow (n = 341). During a median follow-up of 75 months (IQR, 69-77 months), 163 patients developed HCC. Compared with the optimal group, the suboptimal group had a higher risk of HCC (2.38% per year vs 0.48% per year: hazard ratio, 4.93; 95% CI: 3.28, 7.41; P < .001) and higher odds of a false-negative rate of US (43.9% vs 16.7%: odds ratio, 3.90; 95% CI: 1.02, 15.00; P = .04). Conclusion Among patients with CHB, those with suboptimal US LI-RADS visualization of B or C had a higher risk of HCC and higher odds of false-negative rates of US for detecting HCC than those with optimal visualization of A. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Barr and Scoutt in this issue.

Classification of microvascular invasion of hepatocellular carcinoma: correlation with prognosis and magnetic resonance imaging.

BACKGROUND/AIMS: The microvascular invasion (MVI) of hepatocellular carcinoma (HCC) involves a wide histological spectrum, and it is unclear whether the degree of MVI correlates with patient prognosis or imaging findings. Here, we evaluate the prognostic value of MVI classification and analyze the radiologic features predictive of MVI. METHODS: Using a retrospective cohort of 506 patients with resected solitary HCCs, the histological and imaging features of MVI were reviewed and correlated with clinical data. RESULTS: MVI-positive HCCs invading ≥5 vessels or those with ≥50 invaded tumor cells were significantly associated with decreased overall survival (OS). The 5-year OS, recurrence-free survival (RFS), and beyond Milan criteria RFS rates were significantly poorer in patients with severe MVI compared with those with mild or no MVI. Severe MVI was a significant independent predictive factor for OS (odds ratio [OR], 2.962; p<0.001), RFS (OR, 1.638; p=0.002), and beyond Milan criteria RFS (OR, 2.797; p<0.001) on multivariable analysis. On MRI, non-smooth tumor margins (OR, 2.224; p=0.023) and satellite nodules (OR, 3.264; p<0.001) were independently associated with the severe-MVI group on multivariable analysis. Both non-smooth tumor margins and satellite nodules were associated with worse 5-year OS, RFS, and beyond Milan criteria RFS. CONCLUSION: Histologic risk classification of MVI according to the number of invaded microvessels and invading carcinoma cells was a valuable predictor of prognosis in HCC patients. Non-smooth tumor margin and satellite nodules were significantly associated with severe MVI and poor prognosis.

Isolation and Characterization of the Genes Involved in the Berberine Synthesis Pathway in Asian Blue Cohosh, Caulophyllum robustum.

Caulophyllum robustum, commonly named Asian blue cohosh, is a perennial herb in the family Berberidaceae. It has traditionally been used for folk medicine in China. We isolated berberine from the leaves, stem, roots, and fruits of C. robustum, and this is the first report on berberine in this species. Transcriptome analysis was conducted for the characterization of berberine biosynthesis genes in C. robustum, in which, all the genes for berberine biosynthesis were identified. From 40,094 transcripts, using gene ontology (GO) analysis, 26,750 transcripts were assigned their functions in the categories of biological process, molecular function, and cellular component. In the analysis of genes expressed in different tissues, the numbers of genes in the categories of intrinsic component of membrane and transferase activity were up-regulated in leaves versus stem. The berberine synthesis genes in C. robustum were characterized by phylogenetic analysis with corresponding genes from other berberine-producing species. The co-existence of genes from different plant families in the deepest branch subclade implies that the differentiation of berberine synthesis genes occurred early in the evolution of berberine-producing plants. Furthermore, the copy number increment of the berberine synthesis genes was detected at the species level.