Prognostic and Immunotherapeutic Predictive Value of CAD Gene in Hepatocellular Carcinoma: Integrated Bioinformatics and Experimental Analysis.

Hepatocellular carcinoma (HCC) is a common type of cancer that ranks first in cancer-associated death worldwide. Carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase (CAD) are the key components of the pyrimidine pathway, which promotes cancer development. However, the function of CAD in HCC needs to be clarified. In this study, the clinical and transcriptome data of 424 TCGA-derived HCC cases were analyzed. The results demonstrated that high CAD expression was associated with poor prognosis in HCC patients. The effect of CAD on HCC was then investigated comprehensively using GO annotation analysis, KEGG enrichment analysis, Gene Set Enrichment Analysis (GSEA), and CIBERSORT algorithm. The results showed that CAD expression was correlated with immune checkpoint inhibitors and immune cell infiltration. In addition, low CAD levels in HCC patients predicted increased sensitivity to anti-CTLA4 and PD1, while HCC patients with high CAD expression exhibited high sensitivity to chemotherapeutic and molecular-targeted agents, including gemcitabine, paclitaxel, and sorafenib. Finally, the results from clinical sample suggested that CAD expression increased remarkably in HCC compared with non-cancerous tissues. Loss of function experiments demonstrated that CAD knockdown could significantly inhibit HCC cell growth and migration both in vitro and in vivo. Collectively, the results indicated that CAD is a potential oncogene during HCC metastasis and progression. Therefore, CAD is recommended as a candidate marker and target for HCC prediction and treatment.

A new scoring system for predicting the outcome of hepatocellular carcinoma patients without microvascular invasion-a large-scale multicentre study.

BACKGROUND: The prognosis of HCC patients without MVI (so called M0) is highly heterogeneous and the need for adjuvant therapy is still controversial. METHODS: Patients with HCC with M0 who underwent liver resection (LR) or liver transplantation (LT) as an initial therapy were included. The Eastern Hepatobiliary Surgery Hospital (EHBH)-M0 score was developed from a retrospective cohort to form the training cohort. The classification which was developed using multivariate cox regression analysis was externally validated. RESULTS: The score was developed using the following factors: α-fetoprotein level, tumour diameter, liver cirrhosis, total bilirubin, albumin and aspartate aminotransferase. The score differentiated two groups of M0 patients (≤3, >3 points) with distinct long-term prognoses outcomes (median overall survival (OS), 98.0 vs. 46.0 months; p < 0.001). The predictive accuracy of the score was greater than the other commonly used staging systems for HCC. And for M0 patients with a higher score underwent LR. Adjuvant transcatheter arterial chemoembolization (TACE) was effective to prolong OS. CONCLUSIONS: The EHBH M0 scoring system was more accurate in predicting the prognosis of HCC patients with M0 after LR or LT. Adjuvant therapy is recommended for HCC patients who have a higher score.

An inferior vena cava-priority approach in laparoscopic isolated hepatic caudate lobectomy.

PURPOSE: Laparoscopic isolated caudate lobectomy is still a challenging operation for surgeons. The access route of the operation plays a vital role during laparoscopic caudate lobectomy. There are few references regarding this technique. Here, we introduce a preferred inferior vena cava (IVC) approach in laparoscopic caudate lobectomy. METHODS: Twenty-one consecutive patients with caudate hepatic tumours between June 2016 and December 2021 were included in this study. All of them received laparoscopic caudate lobectomy involving an IVC priority approach. The IVC priority approach refers to prioritizing the dissection of the IVC from the liver parenchyma before proceeding with the conventional left or right approach. It emphasizes the importance of the IVC dissection during process. Clinical data, intraoperative parameters and postoperative results were evaluated. Sixteen patients were performed pure IVC priority approach, while 5 patients underwent a combined approach. We subsequently compared the intraoperative and postoperative between the two groups. RESULTS: All 21 patients were treated with laparoscopic technology. The operative time was 190.95 ± 92.65 min. The average estimated blood loss was 251.43 ± 247.45 ml, and four patients needed blood transfusions during the perioperative period. The average duration of hospital stay was 8.43 ± 2.64 (range from 6.0 to 16.0) days. Patients who underwent the pure inferior vena cava (IVC) approach required a shorter hepatic pedicle clamping time (26 vs. 55 min, respectively; P < 0.001) and operation time (150 vs. 380 min, respectively; P = 0.002) than those who underwent the combined approach. Hospitalization (7.0 vs. 9.0 days, respectively; P = 0.006) was shorter in the pure IVC group than in the combined group. CONCLUSIONS: Laparoscopic caudate lobectomy with an IVC priority approach is safe and feasible for patients with caudate hepatic tumours.

Corynoxine promotes TFEB/TFE3-mediated autophagy and alleviates Aß pathology in Alzheimer's disease models.

Autophagy impairment is a key factor in Alzheimer's disease (AD) pathogenesis. TFEB (transcription factor EB) and TFE3 (transcription factor binding to IGHM enhancer 3) are nuclear transcription factors that regulate autophagy and lysosomal biogenesis. We previously showed that corynoxine (Cory), a Chinese medicine compound, protects neurons from Parkinson's disease (PD) by activating autophagy. In this study, we investigated the effect of Cory on AD models in vivo and in vitro. We found that Cory improved learning and memory function, increased neuronal autophagy and lysosomal biogenesis, and reduced pathogenic APP-CTFs levels in 5xFAD mice model. Cory activated TFEB/TFE3 by inhibiting AKT/mTOR signaling and stimulating lysosomal calcium release via transient receptor potential mucolipin 1 (TRPML1). Moreover, we demonstrated that TFEB/TFE3 knockdown abolished Cory-induced APP-CTFs degradation in N2aSwedAPP cells. Our findings suggest that Cory promotes TFEB/TFE3-mediated autophagy and alleviates Aß pathology in AD models.

PPARɑ Ligand Caudatin Improves Cognitive Functions and Mitigates Alzheimer's Disease Defects By Inducing Autophagy in Mice Models.

The autophagy-lysosomal pathway (ALP) is a major cellular machinery involved in the clearance of aggregated proteins in Alzheimer disease (AD). However, ALP is dramatically impaired during AD pathogenesis via accumulation of toxic amyloid beta (Aß) and phosphorylated-Tau (phospho-Tau) proteins in the brain. Therefore, activation of ALP may prevent the increased production of Aß and phospho-Tau in AD. Peroxisome proliferator-activated receptor alpha (PPARα), a transcription factor that can activate autophagy, and transcriptionally regulate transcription factor EB (TFEB) which is a key regulator of ALP. This suggests that targeting PPARα, to reduce ALP impairment, could be a viable strategy for AD therapy. In this study, we investigated the anti-AD activity of Caudatin, an active constituent of Cynanchum otophyllum (a traditional Chinese medicinal herb, Qing Yang Shen; QYS). We found that Caudatin can bind to PPARα as a ligand and augment the expression of ALP in microglial cells and in the brain of 3XTg-AD mice model. Moreover, Caudatin could activate PPARα and transcriptionally regulates TFEB-augmented lysosomal degradation of Aß and phosphor-Tau aggregates in AD cell models. Oral administration of Caudatin decreased AD pathogenesis and ameliorated the cognitive dysfunction in 3XTg-AD mouse model. Conclusively, Caudatin can be a potential AD therapeutic agent via activation of PPARα-dependent ALP.

Revisiting Fur Regulon Leads to a Comprehensive Understanding of Iron and Fur Regulation.

Iron is an essential element because it functions as a cofactor of many enzymes, but excess iron causes cell damage. Iron hemostasis in Escherichia coli was transcriptionally maintained by the ferric uptake regulator (Fur). Despite having been studied extensively, the comprehensive physiological roles and mechanisms of Fur-coordinated iron metabolism still remain obscure. In this work, by integrating a high-resolution transcriptomic study of the Fur wild-type and knockout Escherichia coli K-12 strains in the presence or absence of iron with high-throughput ChIP-seq assay and physiological studies, we revisited the regulatory roles of iron and Fur systematically and discovered several intriguing features of Fur regulation. The size of the Fur regulon was expanded greatly, and significant discrepancies were observed to exist between the regulations of Fur on the genes under its direct repression and activation. Fur showed stronger binding strength to the genes under its repression, and genes that were repressed by Fur were more sensitive to Fur and iron regulation as compared to the genes that were activated by Fur. Finally, we found that Fur linked iron metabolism to many essential processes, and the systemic regulations of Fur on carbon metabolism, respiration, and motility were further validated or discussed. These results highlight how Fur and Fur-controlled iron metabolism affect many cellular processes in a systematic way.

TNEA therapy promotes the autophagic degradation of NLRP3 inflammasome in a transgenic mouse model of Alzheimer's disease via TFEB/TFE3 activation.

BACKGROUND: The impairment in the autophagy-lysosomal pathway (ALP) and the activation of NLR family pyrin domain containing 3 (NLRP3) inflammasome represent two molecular events leading to neurodegeneration and neuroinflammation in Alzheimer's disease (AD), a devastating neurodegenerative disorder without a cure. Previously we demonstrated the cognitive-enhancing effect of a combined electroacupuncture (EA) therapy termed TNEA in a transgenic mouse model of AD, involving activation of transcription factor EB (TFEB), a master regulator of ALP. However, whether and how TNEA inhibits NLRP3 inflammasome via TFEB-mediated ALP in AD remains to be investigated. METHODS: 5xFAD mice overexpressing amyloid-ß (Aß) were treated with TNEA or EA on its composing acupoints (GB13 and GV24). The changes in the signaling pathways regulating NLRP3 inflammasome, the association of NLRP3 inflammasome with ALP, and the roles of TFEB/TFE3 in mice brains were determined by immunoblots, immunohistochemistry and AAV-mediated knockdown assays. RESULTS: TNEA inhibits the activation of NLRP3 inflammasome and the release of active interleukin 1ß (IL1B) in the hippocampi of 5xFAD mice. Mechanistically, TNEA promoted the autophagic degradation of inflammasome components via activating both TFEB and TFE3 by modulating kinases including AMPK and AKT. The composing acupoints in TNEA showed synergistic effects on regulating these molecular events and memory improvement. CONCLUSION: Our findings suggest that TNEA attenuates AD-associated memory impairment via promoting TFEB/TFE3-mediated autophagic clearance of Aß and NLRP3 inflammasome, and partially reveal the molecular basis of combined acupoints therapy originated from ancient wisdom.

Research progress on efflux pump inhibitors of Mycobacterium tuberculosis in recent years / 药学学报

Currently, the resistance of first-line anti-tuberculosis drugs has made the prevention and treatment of tuberculosis increasingly difficult, posing a serious threat to global public health. Several studies have shown that efflux pumps are one of the important causes for bacteria to develop multi-drug resistance and extremely-drug resistance, and efflux pump inhibitors can inhibit the efflux of antibacterial drugs, thereby reducing bacterial drug resistance. Numerous natural products and synthetic compounds have been reported to possess efflux pump inhibitory activity, but they have not been applied in clinical settings because of their toxicity, pharmacokinetic properties, etc. Therefore, we summarized the efflux pump inhibitory activity, antimicrobial activity, and structure-activity relationships of reported efflux pump inhibitors against Mycobacterium tuberculosis in recent years, providing references for the development of new efflux pump inhibitors with better activity and lower toxicity.

Research Progress on Mechanism of Acupuncture for Neurological and Other Diseases by Regulating Autophagy-Lysosomal Pathway / 中山大学学报(医学科学版)

As an important part of traditional Chinese medicine， the efficacy and scientificity of acupuncture have attracted more and more attention. In recent years， rigorous randomized controlled clinical trials have confirmed the efficacy of acupuncture on certain dominant diseases， and basic researches have partially revealed the mechanism of acupuncture for treating diseases. By analyzing published literatures and referring to relevant studies from our research team， this paper reviews the mechanisms of acupuncture for treating neurological and other diseases via regulating the autophagy-lysosomal pathway （ALP）. We found that acupuncture improved related pathologies in different disease models by up-regulating or down-regulating ALP， and there is a certain correlation between the distribution of acupoints and the one-way/two-way regulation of ALP； however， the current studies have some defects in experimental design and methodology， and the molecular mechanisms of acupuncture on ALP regulation remain to be further elucidated.

Efficacy and safety of transarterial chemoembolization plus antiangiogenic- targeted therapy and immune checkpoint inhibitors for unresectable hepatocellular carcinoma with portal vein tumor thrombus in the real world.

Purpose: This study aimed to assess the efficacy and safety of a triple therapy that comprises transarterial chemoembolization (TACE), antiangiogenic-targeted therapy, and programmed death-1 (PD-1) inhibitors in a real-world cohort of patients with unresectable hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). Methods: Consecutive patients treated with TACE combined with antiangiogenic therapy and PD-1 inhibitors at the Eastern Hepatobiliary Surgery Hospital between June 2019 and May 2021 were enrolled. The baseline characteristics and treatment course of the patients were recorded. The tumor response was evaluated based on the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and HCC-specific modified RECIST (mRECIST). The overall survival (OS) and progression-free survival (PFS) of the patients were analyzed using the Kaplan-Meier method. Adverse events (AEs) were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Results: As of the data cutoff on 30 August 2021, the median follow-up time was 10.0 (3.9-28.4) months. A total of 39 eligible patients were included. The objective response rate (ORR) and the disease control rate (DCR) were 35.9% and 74.4% according to the RECIST 1.1, and 48.7% and 84.6% according to mRECIST criteria, respectively. The median OS and PFS were 14.0 and 9.2 months, respectively. Moreover, 34 (87.2%) patients experienced at least one treatment-related AE and 8 (20.5%) patients experienced grade 3/4 treatment-related AEs. The most common treatment- and laboratory-related AEs were hypertension (46.2%) and decreased albumin (53.8%), respectively. No treatment-related mortality occurred during the study period. Conclusions: TACE combined with antiangiogenic-targeted therapy and immune checkpoint inhibitors may have promising anticancer activity in unresectable HCC patients with PVTT. AEs were manageable, with no unexpected overlapping toxicities.

Bromo-protopine, a novel protopine derivative, alleviates tau pathology by activating chaperone-mediated autophagy for Alzheimer's disease therapy.

Emerging evidence from Alzheimer's disease (AD) patients suggests that reducing tau pathology can restore cognitive and memory loss. To reduce tau pathology, it is critical to find brain-permeable tau-degrading small molecules that are safe and effective. HDAC6 inhibition has long been considered a safe and effective therapy for tau pathology. Recently, we identified protopine as a dibenzazecine alkaloid with anti-HDAC6 and anti-AD activities. In this study, we synthesized and tested novel protopine derivatives for their pharmacological action against AD. Among them, bromo-protopine (PRO-Br) demonstrated a two-fold increase in anti-HDAC6 activity and improved anti-tau activities compared to the parent compound in both in vitro and in vivo AD models. Furthermore, molecular docking results showed that PRO-Br binds to HDAC6, with a ∆G value of -8.4 kcal/mol and an IC50 value of 1.51 µM. In neuronal cell lines, PRO-Br reduced pathological tau by inducing chaperone-mediated autophagy (CMA). In 3xTg-AD and P301S tau mice models, PRO-Br specifically decreased the pathogenic hyperphosphorylated tau clumps and led to the restoration of memory functions. In addition, PRO-Br treatment promoted the clearance of pathogenic tau by enhancing the expression of molecular chaperones (HSC70) and lysosomal markers (LAMP2A) via CMA in AD models. Our data strongly suggest that administration of the brain-permeable protopine derivative PRO-Br, could be a viable anti-tau therapeutic strategy for AD.

[Effects of Chemical Fertilizer Reduction Combined with Straw Application on Diazotrophic Communities in a Double Rice Cropping System].

Based on a three-year field experiment, the effects of reduced chemical fertilizer combined with straw application on paddy yield, soil fertility properties, and community structure of diazotrophs in a double-rice cropping field three years after straw application were examined. Three treatments were applied:conventional fertilizer application (CF), chemical fertilizer reduction combined with a low straw application rate (CFLS, 3 t·hm-2), and a high straw application rate (CFHS, 6 t·hm-2). The results showed that CFLS and CFHS did not significantly reduce rice grain yield (P>0.05); significantly neutralized soil acidification; increased soil microbial biomass carbon and nitrogen, dissolved organic carbon, and organic carbon content (P<0.05); and significantly reduced soil redox potential, ammonium nitrogen, and nitrate nitrogen contents (P<0.05). This was more conducive to improve soil nitrogen use efficiency. Compared with those under the CF treatment, the natural nitrogen fixation functional communities of CFLS and CFHS increased the Shannon, PD, and Evenness indexes (P<0.05) due to the improvement of conditions such as the increase in soil carbon storage and the decrease in acidification degree. The relative abundance of microbial communities with nitrogen fixation, carbon fixation, and plant growth promotion functions such as Ferrigenium, Sulfurivermis, Methylomonas, Methylovulum, Ectothiorhodospira, and Nostoc increased significantly (P<0.05). In conclusion, the reduction in chemical fertilizer combined with 3 t·hm-2 and 6 t·hm-2 straw application was an effective measure to improve the community structure of soil diazotrophs and the potential of soil nitrogen fixation.

A Double Suspension Technique for Laparoscopic Isolated Caudate Lobectomy.

Background: Laparoscopic isolated caudate lobectomy is still a challenging procedure for hepatobiliary surgeons because of its deep location and narrow operating space. Hilar exposure and adequate operation space play an important role during laparoscopic caudate lobectomy. Very few references are available on this technique, and in this study, we present a new suspension technique to assist laparoscopic caudate lobectomy. Materials and Methods: The data of patients with caudate hepatic tumors who underwent laparoscopic isolated caudate lobectomy with or without the double suspension technique at the Eastern Hepatobiliary Surgery Hospital were retrospectively analyzed. Results: A total of 25 patients underwent laparoscopic isolated caudate lobectomy at Eastern Hepatobiliary Surgery Hospital between June 2016 and March 2022. Eight patients had perioperative complications, and no patient died within 30 days after surgery. There were no significant differences between the two groups in terms of conversion rate (8.3% versus 7.7%; P = .954), complication rate (25.0% versus 38.5%; P = .480), length of stay (8.0 [6.0-11.0] days versus 9.0 [6.0-19.0] days; P = .098), and postoperative liver function changes. Patients who underwent resection in the suspension group had shorter operation time (154.9 ± 44.3 minutes versus 224 ± 86.3 minutes; P = .018), inferior vena cava dissection time (30.1 ± 5.4 minutes versus 44.8 ± 7.4 minutes; P < .001), and less bleeding (125.0 [20-800.0] mL versus 350 [80-850.0] mL, P = .011). Conclusions: This double suspension technique is a safe and feasible method to assist laparoscopic caudate lobectomy. It provides clear exposure and adequate surgical space, thereby shortening the operation time and reducing intraoperative blood loss.

Fufang Zhenzhu Tiaozhi capsule ameliorates hyperuricemic nephropathy by inhibition of PI3K/AKT/NF-κB pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Excessive serum uric acid (SUA) causes hyperuricemic nephropathy (HN), characterized by inflammatory infiltration and tubulointerstitial fibrosis. Most recently, we demonstrated that Fufang Zhenzhu Tiaozhi (FTZ) capsule attenuated diabetic nephropathy through inhibition of renal inflammation and fibrosis. However, whether FTZ ameliorates HN is still unclear. AIM OF THE STUDY: To determine the protective roles and mechanism of FTZ in mouse renal injury and fibrosis under hyperuricemic condition. MATERIALS AND METHODS: HN mice, induced by potassium oxonate and hypoxanthine, were administrated with 600 and 1200 mg/kg FTZ (intragastrically) daily for three weeks. SUA levels, renal functions and histological changes were analyzed. Western blotting, quantitative real-time PCR (q-PCR) and RNA sequencing were used to identify the roles and underlying mechanism of FTZ in HN mice. RESULTS: We demonstrated that FTZ treatment mitigated renal injury in mice, as evidenced by the decrease in SUA, serum creatinine (SCr) and cystatin C (Cys C) levels, as well as improved renal histology. FTZ markedly attenuates inflammasome activation, collagen deposition and the imbalance of uric acid transporters. RNA-sequencing revealed a key mechanism involved in the protective effects on HN mice was related to PI3K/AKT/NF-κB pathway. Western blot also confirmed that FTZ diminished the phosphorylation of AKT and p65 in HN mice. CONCLUSIONS: FTZ prevents renal injury, inflammation and fibrosis in HN mice via promoting uric acid excretion and inhibiting PI3K/AKT/NF-κB signaling pathway.

How Does the COVID-19 Pandemic Affect Pediatric Patients with Intussusception Treated by Ultrasound-Guided Hydrostatic Enema Reduction?

BACKGROUND: The pandemic of COVID-19 has significantly influenced the epidemiology of intussusception. Nevertheless, the effects of the COVID-19 pandemic on the operation of ultrasound-guided hydrostatic enema reduction (USGHER) for intussusception have been largely unknown. METHODS: The data of pediatric patients with intussusception who were treated by USGHER from January to March of 2019 (Control Group), 2020 (Study Group 1), and 2021 (Study Group 2) in a large Chinese medical institution were retrospectively collected and analyzed. RESULTS: We enrolled 246 patients, including 90 cases in Control Group, 70 in Study Group 1, and 86 in Study Group 2 (p = 0.042). The time from the onset of symptoms to the hospital visit and the time from the hospital visit to performing the ultrasound in Study Group 1 was significantly longer than that in Control Group and Study Group 2 (p = 0.036, p = 0.031, respectively). The number of patients with bloody stool and the longest invaginated length of intussusception in Study Group 1 increased significantly compared with patients in the other two groups (p = 0.007, p = 0.042, respectively). Comparisons of neither the pressure of enema nor the time of duration when performing USGHER present statistical significance among the three groups (p = 0.091, p = 0.085, respectively). For all enrolled pediatric patients, there was no perforation case involved, and recurrence of intussusception occurred in few cases. CONCLUSIONS: Besides the negative impacts on the incidence of intussusception, the COVID-19 pandemic might have led to the diagnostic delay of intussusception and the deterioration of patients' clinical manifestations, but it did not significantly affect the operation of USGHER and patients' clinical outcome.

Association between BRAF expression in circulating tumor cells and the clinical feature of patients with multiple myeloma.

Multiple myeloma (MM) is the most common hematological malignancy with uncontrolled proliferation of monoclonal plasma cells. Despite treatment improvements, MM remains an incurable disease for most patients. Therefore, promising molecular markers are required for MM treatment decisions. In the present study, we explored the relationship between the BRAF expression in circulating tumor cells (CTCs) and the clinical features of patients with MM. The results showed that CTCs were associated with MM staging, and the expression of BRAF was associated with different CTCs. Moreover, the BRAF gene was correlated with patients' white blood cells, blood albumin levels, and Eastern Cooperative Oncology Group (ECOG) score. BRAF expression positively correlated with total CTCs, hybrid CTCs, and mesenchymal CTCs. Taken together, CTCs tightly correlated with the clinical stages and characteristics of MM. Our findings may provide a promising prognosis biomarker for MM treatment decisions.

Platelet Aggregation Before Aspirin Initiation in Pediatric Patients With Congenital Heart Disease at High Risk of Thrombosis.

Background: Aspirin following unfractionated heparin is the most common anticoagulation strategy for pediatric patients who experienced cardiac surgery at high risk of thrombosis. The platelet aggregation test is the golden method to evaluate the aspirin effect on platelet function. However, the platelet aggregation basal status before postoperative aspirin initiation and the related clinical influencing factors hasn't been investigated systemically in this population. Methods: In a prospective cohort of 247 children, arachidonic acid-induced platelet aggregation (PAG-AA) was measured by means of light transmission aggregometry (LTA) before the first dose of aspirin after cardiac surgical procedure and the perioperative variables were also collected. Distribution of this population's PAG-AA basal status was described. Univariate and multivariate logistic regression analysis were performed to identify the main influencing factors of PAG-AA. Results: The median time of aspirin administration was 2 (1-27) days after surgery and the corresponding median value of basal PAG-AA was 20.70% (1.28-86.49%), with 67.6% population under 55% and 47.8% population under 20%. Patients undergoing cardiopulmonary bypass (CPB) had a significantly lower basal PAG-AA than those without (30.63 ± 27.35 vs. 57.91 ± 27.58, p = 0.013). While patients whose test done within 3 days after CPB had a significantly lower PAG-AA than those out of 3 days (25.61 ± 25.59 vs. 48.59 ± 26.45, p = 0.001). Univariate analysis implied that the influencing factors of the basal PAG-AA including CPB use, test time point, cyanosis, and platelet count. Multivariate regression analysis indicated that only CPB use, test time point, and platelet count were the main independent influencing factors for the basal PAG-AA. Conclusion: The majority of children have impaired basal platelet aggregometry responses before postoperative aspirin initiation. The main influencing factors are CPB use, test time point, and platelet count. To establish the platelet aggregometry baseline prior to commencement of aspirin therapy, testing should be performed 3 days later following the procedure when effect of CPB is basically over.

Structure Characterization, Antioxidant and Immunomodulatory Activities of Polysaccharide from Pteridium aquilinum (L.) Kuhn.

Pteridium aquilinum (L.) Kuhn (Pteridaceae family) has been widely used as a food and medicine in China and Korea. Previous studies indicate that P. aquilinum contains a variety of bioactive chemical components such as flavonoids, phenols, terpenoids, saponins, polysaccharides, and so on. In the present study, a novel polysaccharide (named as PAP-3) with average molecular weight of 2.14 × 105 Da was obtained from P. aquilinum. The structure was studied through physicochemical and spectroscopic analysis. The results indicated that PAP-3 consists of arabinose, rhamnose, fucose, galactose, mannose, and xylose in a molar ratio of 1.58:1.00:3.26:4.57:4.81:3.33. The polysaccharide is mainly composed of (1→2)-linked xylose and (1→3,6)-linked mannose on the main chain, with (1→2)-linked xylose, (1→6)-linked mannose, and (1→6)- and (1→3,6)-linked galactose as side chains. Galactose, fucose, and xylose are located at the end of the side chains. The in vitro immunomodulatory and antioxidant activities were assayed. PAP-3 has strong free-radical scavenging activity on DPPH and ABTS radicals and significant immunomodulatory activity on RAW264.7 cells. These data provide useful information for further study on the polysaccharides of P. aquilinum and their applications in the food and medical industries.

Recurrence hazard rate in patients with hepatocellular carcinoma and bile duct tumor thrombus: a multicenter observational study.

BACKGROUND: Patients with hepatocellular carcinoma (HCC) bile duct tumor thrombus (BDTT) have a high rate of postoperative recurrence. We aimed to describe the patterns and kinetics of recurrence in BDTT patients and provide management options accordingly. METHODS: This retrospective study included 311 HCC patients with BDTT who underwent surgery from 2009 to 2017 at five centers in China. The hazard rate of recurrence was calculated using the hazard function. RESULTS: The hazard rate of intrahepatic recurrence was higher than that of extrahepatic recurrence (0.0588 vs. 0.0301), and both showed a decreasing trend, and the intrahepatic recurrence and extrahepatic recurrence risk decreased to a lower level after 40 and 20 months, respectively. Patients who underwent anatomic resection had a consistently lower hazard rate of recurrence than patients who underwent nonanatomic resection, whereas patients who received postoperative adjuvant transarterial chemoembolization (TACE) mainly had a lower hazard rate of recurrence in the first year than patients who did not. CONCLUSION: The follow-up of BDTT patients should be at least 40 months because of its high rate of recurrence, in parallel with the need for vigilance for extrahepatic recurrence within 20 months. Anatomic hepatectomy and adjuvant TACE are recommended to improve BDTT patient outcomes.