Na4Sn4(C2O4)3F6 and NaSnC2O4F·H2O: two tin(II) fluoride oxalates display large birefringence.

Birefringent materials play an important role in laser techniques as an essential part of optical devices. Therefore, the exploration of high-performance birefringent materials has been a central focus of researchers. Herein, two tin(II) fluoride oxalates Na4Sn4(C2O4)3F6 and NaSnC2O4F·H2O were gained by the combination of birefringence-active groups of Sn2+ with stereochemically active lone pairs and planar π-conjugated [C2O4]2- groups. These groups assemble into low-dimensional structures of 0D [C2O4F4]6- clusters and 1D [SnC2O4F]∞- chains in Na4Sn4(C2O4)3F6, and double [Sn2(C2O4)2F2]∞2- chains in NaSnC2O4F·H2O, which gives rise to the large birefringence of 0.160@546 nm and 0.189@546 nm, respectively. Detailed structure-property analysis and theoretical calculations indicate that strong optical anisotropy can be induced by the rational arrangement of the Sn2+-polyhedra and [C2O4]2- groups.

Prognosis and therapeutic benefits prediction based on NK cell marker genes through single-cell RNA-seq with integrated bulk RNA-seq analysis for hepatocellular carcinoma.

Tumor-infiltrating immune cells greatly participate in regulating tumorigenesis and metastasis of hepatocellular carcinoma (HCC). Natural killer cell, as an important role of innate immunity, plays an indispensable role in antitumor immunity and regulate tumor development. In this study, we firstly identified 251 NK cell marker genes of HCC based on single-cell RNA sequencing data. Subsequently, an NK cell marker genes-related prognostic signature (NKPS) was developed in the cancer genome atlas (TCGA) cohort for risk stratification and prognosis prediction. The predictive value of the NKPS in prognosis was well validated in different clinical subgroups and three external datasets (ICGC-LIHC cohort, GSE14520 cohort and Guilin cohort). Moreover, multivariate analysis revealed the independent prognostic value of NKPS for OS in HCC. Further functional analysis indicated the NKPS was associated with basic cellular processes, that may contribute to the development and progression of HCC. Thereafter, immune characteristics as well as the therapeutic benefits in NKPS risk score-defined subgroups were analyzed. Patients with low-risk score exhibited immune-active status, manifested as higher immune scores, more infiltration of CD8+ T cells and macrophage M1, and higher T-cell receptor (TCR) richness and diversity. Remarkably, the NKPS was negatively correlated with immunotherapy response-related signatures. In addition, the low-risk group exhibited significantly improved therapeutic benefits, either from immunotherapy or traditional chemotherapy and target therapy. Overall, the NKPS showed an excellent predictive value for prognosis and therapeutic responses for HCC, which might also provide novel insights into better HCC management strategies.

Radiomics model based on contrast-enhanced computed tomography to predict early recurrence in patients with hepatocellular carcinoma after radical resection.

BACKGROUND: Radical resection remains an effective strategy for patients with hepatocellular carcinoma (HCC). Unfortunately, the postoperative early recurrence (recurrence within 2 years) rate is still high. AIM: To develop a radiomics model based on preoperative contrast-enhanced computed tomography (CECT) to evaluate early recurrence in HCC patients with a single tumour. METHODS: We enrolled a total of 402 HCC patients from two centres who were diagnosed with a single tumour and underwent radical resection. First, the features from the portal venous and arterial phases of CECT were extracted based on the region of interest, and the early recurrence-related radiomics features were selected via the least absolute shrinkage and selection operator proportional hazards model (LASSO Cox) to determine radiomics scores for each patient. Then, the clinicopathologic data were combined to develop a model to predict early recurrence by Cox regression. Finally, we evaluated the prediction performance of this model by multiple methods. RESULTS: A total of 1915 radiomics features were extracted from CECT images, and 31 of them were used to determine the radiomics scores, which showed a significant difference between the early recurrence and nonearly recurrence groups. Univariate and multivariate Cox regression analyses showed that radiomics scores and serum alpha-fetoprotein were independent indicators, and they were used to develop a combined model to predict early recurrence. The area under the receiver operating characteristic curve values for the training and validation cohorts were 0.77 and 0.74, respectively, while the C-indices were 0.712 and 0.674, respectively. The calibration curves and decision curve analysis showed satisfactory accuracy and clinical utilities. Kaplan-Meier curves based on recurrence-free survival and overall survival showed significant differences. CONCLUSION: The preoperative radiomics model was shown to be effective for predicting early recurrence among HCC patients with a single tumour.

Hg3(SeO3)2(SO4): A UV Nonlinear Optical Mercury Selenite Sulfate Constructed by Neat [Hg6O8(SeO3)4]∞ Layers and SO4 Tetrahedra.

A novel mercury selenite sulfate named Hg3(SeO3)2(SO4) has been successfully synthesized under a mild hydrothermal method. Hg3(SeO3)2(SO4) crystallizes in a monoclinic space group P21 and features a unique three-dimensional (3D) frame structure formed by [Hg6O8(SeO3)4]∞ layers and SO4 tetrahedra, which enables it to exhibit a comprehensive performance of a moderate second-harmonic generation (SHG) response of approximately 1.3 times that of baseline KH2PO4 (KDP), a moderate birefringence (0.118@546 nm), and a wide band gap (4.70 eV), which indicates that it has potential for application as an ultraviolet (UV) nonlinear optical material. Detailed theoretical calculations show that the Hg2+-based polyhedra with large polarizability and deformability and the SeO3 groups with stereochemically active lone pair (SCALP) electrons are the main contributors to moderate optical properties.

Dominant neoantigen verification in hepatocellular carcinoma by a single-plasmid system coexpressing patient HLA and antigen.

BACKGROUND: Previous studies confirmed that most neoantigens predicted by algorithms do not work in clinical practice, and experimental validations remain indispensable for confirming immunogenic neoantigens. In this study, we identified the potential neoantigens with tetramer staining, and established the Co-HA system, a single-plasmid system coexpressing patient human leukocyte antigen (HLA) and antigen, to detect the immunogenicity of neoantigens and verify new dominant hepatocellular carcinoma (HCC) neoantigens. METHODS: First, we enrolled 14 patients with HCC for next-generation sequencing for variation calling and predicting potential neoantigens. Then, the Co-HA system was established. To test the feasibility of the system, we constructed target cells coexpressing HLA-A*11:01 and the reported KRAS G12D neoantigen as well as specific T-cell receptor (TCR)-T cells. The specific cytotoxicity generated by this neoantigen was shown using the Co-HA system. Moreover, potential HCC-dominant neoantigens were screened out by tetramer staining and validated by the Co-HA system using methods including flow cytometry, enzyme-linked immunospot assay and ELISA. Finally, antitumor test in mouse mode and TCR sequencing were performed to further evaluate the dominant neoantigen. RESULTS: First, 2875 somatic mutations in 14 patients with HCC were identified. The main base substitutions were C>T/G>A transitions, and the main mutational signatures were 4, 1 and 16. The high-frequency mutated genes included HMCN1, TTN and TP53. Then, 541 potential neoantigens were predicted. Importantly, 19 of the 23 potential neoantigens in tumor tissues also existed in portal vein tumor thrombi. Moreover, 37 predicted neoantigens restricted by HLA-A*11:01, HLA-A*24:02 or HLA-A*02:01 were performed by tetramer staining to screen out potential HCC-dominant neoantigens. HLA-A*24:02-restricted epitope 5'-FYAFSCYYDL-3' and HLA-A*02:01-restricted epitope 5'-WVWCMSPTI-3' demonstrated strong immunogenicity in HCC, as verified by the Co-HA system. Finally, the antitumor efficacy of 5'-FYAFSCYYDL-3'-specific T cells was verified in the B-NDG-B2mtm1Fcrntm1(mB2m) mouse and their specific TCRs were successfully identified. CONCLUSION: We found the dominant neoantigens with high immunogenicity in HCC, which were verified with the Co-HA system.

The predictive value of PD-L1 expression in patients with advanced hepatocellular carcinoma treated with PD-1/PD-L1 inhibitors: A systematic review and meta-analysis.

BACKGROUND AND AIM: Programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1) inhibitors have transformed the treatment landscape of advanced hepatocellular carcinoma (HCC), but consistent responses are not observed in all patients, and prognostic biomarkers to guide treatment decisions are lacking. We aimed to evaluate the predictive value of PD-L1 expression in advanced HCC patients treated with PD-1/PD-L1 inhibitors. METHODS: A comprehensive search of PubMed, Embase, Web of Science, and the Cochrane Library was conducted. Studies comparing the objective response rate (ORR) and/or disease control rate (DCR) based on the tumor PD-L1 status of HCC were included. RESULTS: Eleven studies with 1,330 HCC patients treated with PD-1/PD-L1 inhibitors were included. Pooled odds ratio (OR) analysis demonstrated a significantly improved ORR in PD-L1-positive patients compared with PD-L1-negative patients (OR, 1.86, 95% CI, 1.35-2.55). Similar results were observed in the anti-PD-1 treatment (p < 0.001) and anti-PD-1/PD-L1 monotherapy (p < 0.001) subgroups. The pooled ORRs in the PD-L1-positive and PD-L1-negative groups were 26% (95% CI, 20%-32%) and 18% (95% CI, 13%-22%), respectively. For DCR, the pooled OR analysis showed no significant difference between PD-L1-positive patients and PD-L1-negative patients (66% [95% CI, 55%-76%] vs. 69% [95% CI, 62%-76%]; OR, 0.92, 95% CI, 0.59-1.44). The results were consistent across the drug target and combination treatment subgroups. CONCLUSION: Positive PD-L1 expression is associated with a better ORR in advanced HCC patients treated with anti-PD-1/PD-L1-based therapies. This feature can help to identify HCC patients who will benefit most from PD-1/PD-L1 inhibitors.

Comparison of the Postoperative Analgesic Effects between Ultrasound-Guided Transmuscular Quadratus Lumborum Block and Thoracic Paravertebral Block in Laparoscopic Partial Nephrectomy Patients: A Randomized, Controlled, and Noninferiority Study.

Background: This prospective, randomized, double-blinded, noninferiority study aimed to compare the effects of analgesia and recovery between transmuscular quadratus lumborum block (TMQLB) and paravertebral block (PVB). Methods: Sixty-eight, American Society of Anesthesiologists level I-III patients, who underwent laparoscopic partial nephrectomy in Peking Union Medical College Hospital were randomly allocated to either TMQLB or PVB group (independent variable) in a 1 : 1 ratio. The TMQLB and PVB groups received corresponding regional anesthesia preoperatively with 0.4 ml/kg of 0.5% ropivacaine and follow-up at postoperative 4, 12, 24, and 48 hours. The participants and outcome assessors were blinded to group allocation. We hypothesized that the primary outcome, postoperative 48-hour cumulative morphine consumption, in the TMQLB group was not more than 50% of that in the PVB group. Secondary outcomes including pain numerical rating scales (NRS) and postoperative recovery data were dependent variables. Results: Thirty patients in each group completed the study. The postoperative 48-hour cumulative morphine consumption was 10.60 ± 5.28 mg in the TMQLB group and 6.40 ± 3.40 mg in the PVB group. The ratio (TMQLB versus PVB) of postoperative 48-hour morphine consumption was 1.29 (95% CI: 1.13-1.48), indicating a noninferior analgesic effect of TMQLB to PVB. The sensory block range was wider in the TMQLB group than in the PVB group (difference 2 dermatomes, 95% CI 1 to 4 dermatomes, P=0.004). The intraoperative analgesic dose was higher in the TMQLB group than in the PVB group (difference 32 µg, 95% CI: 3-62 µg, P=0.03). The postoperative pain NRS at rest and on movement, incidences of side effects, anesthesia-related satisfaction, and quality of recovery scores were similar between the two groups (all P > 0.05). Conclusions: The postoperative 48-hour analgesic effect of TMQLB was noninferior to that of PVB in laparoscopic partial nephrectomy. This trial is registered with NCT03975296.

Development and validation of a nomogram for evaluating the incident risk of carotid atherosclerosis in patients with type 2 diabetes.

Introduction: The purpose of this study was to evaluate the clinical characteristics of carotid atherosclerotic disease in patients with type 2 diabetes mellitus, investigate its risk factors, and develop and validate an easy-to-use nomogram. Methods: 1049 patients diagnosed with type 2 diabetes were enrolled and randomly assigned to the training and validation cohorts. Multivariate logistic regression analysis identified independent risk factors. A method combining least absolute shrinkage and selection operator with 10-fold cross-validation was used to screen for characteristic variables associated with carotid atherosclerosis. A nomogram was used to visually display the risk prediction model. Nomogram performance was evaluated using the C index, the area under the receiver operating characteristic curve, and calibration curves. Clinical utility was assessed by decision curve analysis. Results: Age, nonalcoholic fatty liver disease, and OGTT3H were independent risk factors associated with carotid atherosclerosis in patients with diabetes. Age, nonalcoholic fatty liver disease, smoke, HDL-C, and LDL-C were characteristic variables used to develop the nomogram. The area under the curve for the discriminative power of the nomogram was 0.763 for the training cohort and 0.717 for the validation cohort. The calibration curves showed that the predicted probability matched the actual likelihood. The results of the decision curve analysis indicated that the nomograms were clinically useful. Discussion: A new nomogram was developed and validated for assessing the incident risk of carotid atherosclerotic in patients with diabetes; this nomogram may act as a clinical tool to assist clinicians in making treatment recommendations.

A signature based on NKG2D ligands to predict the recurrence of hepatocellular carcinoma after radical resection.

INTRODUCTION: Due to the high recurrence, the HCC prognosis remains poor. Yet, the biomarkers for predicting the recurrence of high-risk patients are currently lacking. We aimed to develop a signature to predict the recurrence of HCC based on NKG2D ligands. METHODS: The multivariate Cox proportional hazards regression was used to select recurrence-related variables of NKG2D ligands in HCC patients from The Cancer Genome Atlas (TCGA). HCC patients from the OEP000321 dataset and Guilin cohort were used to validate the predictive signature. The mRNA expression of NKG2D ligands was measured by QRT-PCR. Immunohistochemistry analysis of HCC tissue microarray samples was used to identify the expression of NKG2D ligands. RESULTS: In this study, NKG2D ligands expression in the mRNA and protein level was both abnormally expressed in HCC and associated with recurrence-free survival (RFS). Then, the recurrence-related variables of NKG2D ligands in HCC were selected by the multivariate Cox proportional hazards regression. Among the eight NKG2D ligands, MICA (HR = 1.347; 95% CI = 1.012-1.793; p = 0.041), ULBP3 (HR = 0.453; 95% CI = 0.231-0.889; p = 0.021) and ULBP5 (HR = 3.617; 95% CI = 1.819-7.194; p < 0.001) were significantly correlated with RFS in the TCGA-LIHC cohort. Then, the signature was constructed by the three NKG2D ligands. The predictive effectiveness of this signature was also validated in the OEP000321 dataset and Guilin cohort. Further, HCC patients were classified into low-risk and high-risk subgroups by the predictive score. Compared with the low-risk group, the high-risk group had poor RFS in both training and validation cohorts. Importantly, compared with the low-risk patients with the G1-G2 stage, the levels of infiltrated NK-activated cells and NKG2D expression were both lower in the high-risk patients. CONCLUSIONS: The signature based on MICA, ULBP3, and ULBP5 could predict HCC recurrence.

Novel index for the prediction of significant liver fibrosis and cirrhosis in chronic hepatitis B patients in China.

BACKGROUND: Noninvasive, practical, and convenient means of detection for the prediction of liver fibrosis and cirrhosis in China are greatly needed. AIM: To develop a precise noninvasive test to stage liver fibrosis and cirrhosis. METHODS: With liver biopsy as the gold standard, we established a new index, [alkaline phosphatase (U/L) + gamma-glutamyl transpeptidase (U/L)/platelet (109/L) (AGPR)], to predict liver fibrosis and cirrhosis. In addition, we compared the area under the receiver operating characteristic curve (AUROC) of AGPR, gamma-glutamyl transpeptidase to platelet ratio, aspartate transaminase to platelet ratio index, and FIB-4 and evaluated the accuracy of these routine laboratory indices in predicting liver fibrosis and cirrhosis. RESULTS: Correlation analysis revealed a significant positive correlation between AGPR and liver fibrosis stage (P < 0.001). In the training cohort, the AUROC of AGPR was 0.83 (95%CI: 0.78-0.87) for predicting fibrosis (≥ F2), 0.84 (95%CI: 0.79-0.88) for predicting extensive fibrosis (≥ F3), and 0.87 (95%CI: 0.83-0.91) for predicting cirrhosis (F4). In the validation cohort, the AUROCs of AGPR to predict ≥ F2, ≥ F3 and F4 were 0.83 (95%CI: 0.77-0.88), 0.83 (95%CI: 0.77-0.89), and 0.84 (95%CI: 0.78-0.89), respectively. CONCLUSION: The AGPR index should become a new, simple, accurate, and noninvasive marker to predict liver fibrosis and cirrhosis in chronic hepatitis B patients.

Study on pecan seed germination influenced by seed endocarp.

Nondeep physiological dormancy exists in freshly harvested pecan (Carya illinoinensis) seed, and the endocarp inhibits the seed germination. New methods were tried to detect if "chemical dormancy" or "mechanical dormancy" was caused by the endocarp. The germination of freshly harvested pecan seed with the removal of different parts of the endocarp and the fracture pressure of the endocarp of pecan seed soaked in water at different temperatures were tested. The results showed that (1) there was no significant difference in germination rate between the pecan kernel keeping in touch and out of touch with the same part of the endocarp, (2) whether a part of endocarp was removed to expose the radicle, preventing endocarp from splitting by glue inhibited the radicle elongation significantly, (3) the fracture pressure of the endocarp decreased significantly over water uptake time, and (4) little difference in the fracture pressure of the endocarp between different soaking temperatures. In conclusion, it suggested that (1) the endocarp caused "mechanical dormancy" but "chemical dormancy," (2) the prevention of radicle elongation was due to the endocarp pressuring the cotyledon rather than the direct physical restriction on the radicle, and (3) the radicle elongation seemed to be able to respond to the suture split and the pressure on the cotyledon.

Sharp Enhancement of Birefringence in Antimony Oxalates Achieved by the Cation-Anion Synergetic Interaction Strategy.

Birefringent materials with large birefringence play an important role in in laser science and technology owing to their ability to modulate polarized light. However, the lack of systematic and effective synthesis strategies severely hinders the development of novel superior birefringent materials. Herein, the cation-anion synergetic interaction strategy was proposed to successfully synthesize two excellent UV birefringent materials, RbSb(C2O4)F2·H2O and [C(NH2)3]Sb(C2O4)F2·H2O. Both compounds feature unprecedented [Sb(C2O4)F2]∞- anionic chains composed of planar π-conjugated [C2O4]2- units and a distorted SbO4F2 complex with stereochemically active lone pairs, which induce a large optical anisotropy. Remarkably, further enhancement of birefringence in [C(NH2)3]Sb(C2O4)F2·H2O was achieved via cation-anion synergetic interactions between the [C(NH2)3]+ cationic groups and [Sb(C2O4)F2]∞- anionic chains. It exhibited a giant birefringence of 0.323@546 nm, twice larger than that of its analogue RbSb(C2O4)F2·H2O (0.162@546 nm). A detailed structural analysis and theoretical calculations revealed that the cation-anion synergetic interaction strategy is an effective strategy for the efficient exploration of superior birefringent materials, which will guide the further exploration of new structure-driven functional materials.

Functional Roles of Chemokine Receptor CCR2 and Its Ligands in Liver Disease.

Chemokines are a family of cytokines that orchestrate the migration and positioning of immune cells within tissues and are critical for the function of the immune system. CCR2 participates in liver pathology, including acute liver injury, chronic hepatitis, fibrosis/cirrhosis, and tumor progression, by mediating the recruitment of immune cells to inflammation and tumor sites. Although a variety of chemokines have been well studied in various diseases, there is no comprehensive review presenting the roles of all known chemokine ligands of CCR2 (CCL2, CCL7, CCL8, CCL12, CCL13, CCL16, and PSMP) in liver disease, and this review aims to fill this gap. The introduction of each chemokine includes its discovery, its corresponding chemotactic receptors, physiological functions and roles in inflammation and tumors, and its impact on different immune cell subgroups.

Preoperative Radiomics Analysis of Contrast-Enhanced CT for Microvascular Invasion and Prognosis Stratification in Hepatocellular Carcinoma.

Purpose: Microvascular invasion (MVI) impairs long-term prognosis of patients with hepatocellular carcinoma (HCC). We aimed to develop a novel nomogram to predict MVI and patients' prognosis based on radiomic features of contrast-enhanced CT (CECT). Patients and Methods: HCC patients who underwent curative resection were enrolled. The radiomic features were extracted from the region of tumor, and the optimal MVI-related radiomic features were selected and applied to construct radiomic signature (Rad-score). The prediction models were created according to the logistic regression and evaluated. Biomarkers were analyzed via q-PCR from randomly selected HCC patients. Correlations between biomarkers and radiomic signature were analyzed. Results: A total of 421 HCC patients were enrolled. A total of 1962 radiomic features were extracted from the region of tumor, and the 11 optimal MVI-related radiomic features showed a favor predictive ability with area under the curves (AUCs) of 0.796 and 0.810 in training and validation cohorts, respectively. Aspartate aminotransferase (AST), tumor number, alpha-fetoprotein (AFP) level, and radiomics signature were independent risk factors of MVI. The four factors were integrated into the novel nomogram, named as CRM, with AUCs of 0.767 in training cohort and 0.793 in validation cohort for predicting MVI, best among radiomics signature alone and clinical model. The nomogram was well-calibrated with favorable clinical value demonstrated by decision curve analysis and can divide patients into high- or low-risk subgroups of recurrence and mortality. In addition, gene BCAT1, DTGCU2, DOCK3 were analyzed via q-PCR and serum AFP were identified as having significant association with radiomics signature. Conclusion: The novel nomogram demonstrated good performance in preoperatively predicting the probability of MVI, which might guide clinical decision.

Comparison analysis of widely-targeted metabolomics revealed the variation of potential astringent ingredients and their dynamic accumulation in the seed coats of both Carya cathayensis and Carya illinoinensis.

Pecan and hickory nuts are two of consumers' favorite ones. Pecan seeds can be eaten fresh, while hickory ones must remove astringency before eating. Here, we reported that total phenols, flavonoids and condensed tannins of hickory seeds were reduced after de-astringent treatments. They gradually increased with development, showing higher levels in hickory seed coat at mid-late periods than that in pecan's. Widely-targeted metabonomics analysis of developing testa identified 424 kinds of components, including 101, 38, 58, 27 classes of flavonoids, tannins, phenolic acids, organic acids and others, showing 16 different changing trends. Notably, most kinds of flavonoids, hydrolysable tannins and phenolic acids at maturity were more than that of pecan's, while oligomeric condensed tannins were opposite. Gene expression analysis provided further explanations for their dynamic accumulation. These results unraveled potential astringent components in hickory testa and preliminary molecular mechanisms of their dynamic changes, offering theoretical basis for the targeted de-astringency.

Taxonomy and Phylogeny of Four New Species in Absidia (Cunninghamellaceae, Mucorales) From China.

Four new species within the genus Absidia, A. globospora, A. medulla, A. turgida, and A. zonata, are proposed based on a combination of morphological traits, physiological features, and molecular evidences. A. globospora is characterized by globose sporangiospores, a 1.0- to 3.5-µm-long papillary projection on columellae, and sympodial sporangiophores. A. medulla is characterized by cylindrical to oval sporangiospores, a 1.0- to 4.5-µm-long bacilliform projection on columellae, and spine-like rhizoids. A. turgida is characterized by variable sporangiospores, up to 9.5-µm-long clavate projections on columellae, and swollen top of the projection and inflated hyphae. A. zonata is characterized by cylindrical to oval sporangiospores, a 2.0- to 3.5-µm-long spinous projection on columellae, and as many as eight whorled sporangiophores. Phylogenetic analyses based on sequences of internal transcribed spacer rDNA and D1-D2 domains of LSU rDNA support the novelty of these four species within the Absidia. All new species are illustrated, and an identification key to all the known species of Absidia in China is included.

Predictive potential of Nomogram based on GMWG for patients with hepatocellular carcinoma after radical resection.

BACKGROUND: Since it's a challenging task to precisely predict the prognosis of patients with hepatocellular carcinoma (HCC). We developed a nomogram based on a novel indicator GMWG [(Geometric Mean of gamma-glutamyltranspeptidase (GGT) and white blood cell (WBC)] and explored its potential in the prognosis for HCC patients. METHODS: The patients enrolled in this study were randomly assigned to training and validation cohorts. And we performed the Least Absolute Shrinkage and Selection Operator proportional hazards model (LASSO Cox) model with clinical characteristics, serum indexes, and novel GMWG. Multivariate analysis was performed to build a nomogram. The performance of the nomogram was evaluated by C-index, the area under the receiver operating characteristic curve (AUC), and the calibration curve. Kaplan-Meier curves showed discrimination of the nomogram. Clinical utility was assessed by decision curve analysis (DCA). The discrimination ability of the nomogram was determined by the net reclassification index (NRI). RESULTS: The geometric mean of GGT and white WBC count (GMWG), neutrophil to lymphocyte ratio (NLR), and tumor size were significantly associated with the overall survival (OS). The variables above were used to develop the nomogram. The indexes of nomogram were 0.70 and 071 in the training or validation cohort, respectively. AUC of 1-, 3- and 5-year OS showed satisfactory accuracy as well. The calibration curve showed agreement between the ideal and predicted values. Kaplan-Meier curves based on the overall survival (OS) and disease-free survival (DFS) showed significant differences between nomogram predictive low and high groups. DCA showed clinical utilities while NRI showed discrimination ability in both training or validation cohort. CONCLUSIONS: GMWG might be a potential prognostic indicator for patients with HCC. The nomogram containing GMWG also showed satisfaction prediction capacity.

Transcriptome Reveals Roles of Lignin-Modifying Enzymes and Abscisic Acid in the Symbiosis of Mycena and Gastrodia elata.

Gastrodia elata is a well-known medicinal and heterotrophic orchid. Its germination, limited by the impermeability of seed coat lignin and inhibition by abscisic acid (ABA), is triggered by symbiosis with fungi such as Mycena spp. However, the molecular mechanisms of lignin degradation by Mycena and ABA biosynthesis and signaling in G. elata remain unclear. In order to gain insights into these two processes, this study analyzed the transcriptomes of these organisms during their dynamic symbiosis. Among the 25 lignin-modifying enzyme genes in Mycena, two ligninolytic class II peroxidases and two laccases were significantly upregulated, most likely enabling Mycena hyphae to break through the lignin seed coats of G. elata. Genes related to reduced virulence and loss of pathogenicity in Mycena accounted for more than half of annotated genes, presumably contributing to symbiosis. After coculture, upregulated genes outnumbered downregulated genes in G. elata seeds, suggesting slightly increased biological activity, while Mycena hyphae had fewer upregulated than downregulated genes, indicating decreased biological activity. ABA biosynthesis in G. elata was reduced by the downregulated expression of 9-cis-epoxycarotenoid dioxygenase (NCED-2), and ABA signaling was blocked by the downregulated expression of a receptor protein (PYL12-like). This is the first report to describe the role of NCED-2 and PYL12-like in breaking G. elata seed dormancy by reducing the synthesis and blocking the signaling of the germination inhibitor ABA. This study provides a theoretical basis for screening germination fungi to identify effective symbionts and for reducing ABA inhibition of G. elata seed germination.

Comparison of Postoperative Pain Management Outcomes in the United States and China.

To compare pain management outcomes in postoperative patients from an American hospital and a Chinese hospital. A convenience sample of 244 patients in the United States and 268 patients in China with similar surgical sites completed the American Pain Society Patient Outcome Questionnaire-Revised (APS-POQ-R) and the Pain Management Index (PMI) was calculated on their first postoperative day. Patients in the United States reported a higher score on the "perception of pain management" subscale of the APS-POQ-R and a higher proportion of adequate treatment as measured by the PMI (85.2% vs. 39.0%, p < .001). Patient education and degrees of pain relief predicted patient satisfaction with pain management (item in APS-POQ-R) in patients from both countries. A higher level of compliance with pain management guidelines has contributed to a higher level of perception in patients in the United States. Establishing procedure-specific protocols and clinical pathways may improve pain management outcomes for Chinese patients.

Longdan Xiegan Tang attenuates liver injury and hepatic insulin resistance by regulating the angiotensin-converting enzyme 2/Ang (1-7)/Mas axis-mediated anti-inflammatory pathway in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: The ancient Chinese herbal formula Longdan Xiegan Tang (LXT, also called Gentiana Longdancao Decoction to Drain the Liver) treats insulin resistance- and inflammation-associated liver injuries in clinical practice. AIM OF THE STUDY: To investigate the molecular mechanisms underlying LXT-elicited improvement of the liver injuries. MATERIALS AND METHODS: Male rats were co-treated with olanzapine (5 mg/kg) and LXT extract (50 and 500 mg/kg) for eight weeks. Blood parameters were determined enzymatically or by ELISA. Gene/protein expression was analyzed by Real-Time PCR, Western blot and/or immunohistochemistry. RESULTS: LXT attenuated olanzapine-induced liver injury manifested by hyperactivities of plasma alanine aminotransferase and aspartate aminostransferase, hyperbilirubinemia and hypoalbuminemia. Furthermore, LXT improved hepatic insulin resistance that was indicated by hyperinsulinemia, the increased HOMA-IR index, and hepatic over-phosphorylation of Ser307 in insulin receptor substrate (IRS)1, Ser731 in IRS2, Tyr607 in phosphoinositide 3-kinase p85α and Ser473 in AKT at baseline. Mechanistically, LXT inhibited olanzapine-triggered hepatic over-phosphorylation of both IκB kinase (IKK)α/ß and nuclear factor (NF)κB p65 proteins, and mRNA overexpression of tumor necrosis factor α, interleukin 6, interleukin 1ß and CD68. More importantly, LXT restored the decreases in angiotensin-converting enzyme 2 (ACE2) protein level, and its downstream targets Ang (1-7) content and Mas receptor expression. CONCLUSIONS: The present results demonstrate that LXT attenuates liver injury and hepatic insulin resistance by regulating the ACE2/Ang (1-7)/Mas axis-mediated anti-inflammatory pathway in rats. Our findings provide a better understanding of LXT for treatment of insulin resistance- and inflammation-associated liver injuries.