Epidermal ET-1 signal induces activation of resting hair follicles by upregulating the PI3K/AKT pathway in the dermis.

The prevalence of alopecia has increased recently. Hair loss is often accompanied by the resting phase of hair follicles (HFs). Dermal papilla (DP) plays a crucial role in HF development, growth, and regeneration. Activating DP can revive resting HFs. Augmenting WNT/ß-catenin signaling stimulates HF growth. However, the factors responsible for activating resting HFs effectively are unclear. In this study, we investigated epidermal cytokines that can activate resting HFs effectively. We overexpressed ß-catenin in both in vivo and in vitro models to observe its effects on resting HFs. Then, we screened potential epidermal cytokines from GEO DATASETs and assessed their functions using mice models and skin-derived precursors (SKPs). Finally, we explored the molecular mechanism underlying the action of the identified cytokine. The results showed that activation of WNT/ß-catenin in the epidermis prompted telogen-anagen transition. Keratinocytes infected with Ctnnb1-overexpressing lentivirus enhanced SKP expansion. Subsequently, we identified endothelin 1 (ET-1) expressed higher in hair-growing epidermis and induced the proliferation of DP cells and activates telogen-phase HFs in vivo. Moreover, ET-1 promotes the proliferation and stemness of SKPs. Western blot analysis and in vivo experiments revealed that ET-1 induces the transition from telogen-to-anagen phase by upregulating the PI3K/AKT pathway. These findings highlight the potential of ET-1 as a promising cytokine for HF activation and the treatment of hair loss.

Efficacy and Toxicity of Palliative Chemotherapy in Elderly Patients With Advanced Pancreatic Cancer.

OBJECTIVES: We aimed to compare the efficacy and toxicity of palliative chemotherapy in elderly patients with pancreatic ductal adenocarcinoma (PDAC) with those in younger patients. METHODS: A total of 60 patients with locally advanced or metastatic PDAC who received FOLFIRINOX or nab-paclitaxel plus gemcitabine at our institution from January 2014 to December 2021 were analyzed. Patients 70 years or older were classified into an elderly group. RESULTS: The elderly group included 16 patients (26.7%). In the elderly group, nab-paclitaxel plus gemcitabine was used more than FOLFIRINOX compared with the young group (75.0% and 25.0% vs 34.1% and 64.9%, respectively; P = 0.008). The overall survival was not significantly different between the 2 groups (15.6 vs 13.4 months, P = 0.259). However, the elderly group showed better progression-free survival (11.4 vs 7.4 months, P = 0.034). The incidence of adverse events including neutropenia (75.0% vs 81.8%, P = 0.716), thrombocytopenia (25.0% vs 31.3%, P = 0.743), and anemia (50.0% vs 43.2%, P = 0.771) was not different between the 2 groups. Peripheral neuropathy was more common in the elderly group (18.3% vs 2.3%, P = 0.054), though not statistically significant. CONCLUSION: The efficacy and toxicity of chemotherapy in elderly patients with advanced PDAC were comparable with those in younger patients.

Enhanced linear and symmetric synaptic weight update characteristics in a Pt/p-LiCoOx/p-NiO/Pt memristor through interface energy barrier modulation by Li ion redistribution.

Artificial synaptic devices have been extensively investigated for neuromorphic computing systems, which require synaptic behaviors mimicking the biological ones. In particular, a highly linear and symmetric weight update with a conductance (or resistance) change for potentiation and depression operation is one of the essential requirements for energy-efficient neuromorphic computing; however, it is not sufficiently met. In this study, a memristor with a Pt/p-LiCoOx/p-NiO/Pt structure is investigated, where a low interface energy barrier between the Pt electrode and the NiO layer makes for a more linear and symmetric conductance change. In addition, the use of voltage-driven Li+ ion redistribution in the NiO layer facilitates the analog conductance change at a low voltage. Besides the linear and symmetric potentiation and depression weight updates, the memristor exhibits various synaptic characteristics such as the dependence of weight update on the pulse amplitude and number, paired pulse facilitation, and short-term and long-term plasticity. The conductance modulation is thought to be induced by a tunable interface energy barrier at the NiO layer and Pt bottom electrode, as a result of Li+ ion diffusion in NiO supplied from the LiCoOx layer and their redistribution. Thanks to the use of Li+ ion redistribution, the conductance change could be achieved at a voltage <4 V within the time of µs range. These results verify the potential of artificial synapses with the Pt/LiCoOx/NiO/Pt memristor operated by voltage-driven Li+ ion redistribution under the low interface energy barrier conditions, realizing a highly linear and symmetric weight update at a low voltage with a high speed for energy-efficient neuromorphic computing systems.

Optimization and evaluation of Atrina pectinata polysaccharides recovered by subcritical water extraction: A promising path to natural products.

In this study, the recovery of Atrina pectinata posterior adductor polysaccharides (APP-PS) using subcritical water extraction (SWE) was optimized by response surface methodology (RSM) and the physicochemical and biological properties of the recovered APP-PS were evaluated. The optimal extraction conditions, which resulted in a maximum yield of 55.58 ± 1.12 %, were temperature, 152.08 °C; extraction time, 10 min; solid-liquid ratio, 30 g/600 mL. The obtained APP-PS was found to be 88.05 ± 0.17 % total sugar. Fourier transform infrared (FT-IR) and Nuclear magnetic resonance (NMR) analyses confirmed the presence of the α-coordination of D-glucan in the polymer sample. The analysis of monosaccharide composition, along with thermogravimetric analysis, revealed the typical structure of the sample, composed of glucose alone. Total phenolic contents of APP-PS were measured as 5.47 ± 0.01 mg Gallic acid/g of dry sample and total flavonoids contents were determined to be 0.78 ± 0.06 mg Quercetin/g of dry sample. For biological activities, ABTS+, DPPH and FRAP antioxidant activities were measured to be 20.00 ± 0.71, 2.35 ± 0.05 and 4.02 ± 0.07 µg Trolox equivalent/100 g of dry sample, respectively. Additionally ACE inhibitory was confirmed to be 87.02 ± 0.47 %. These results showed that SWE is an effective method to recover biofunctional materials from marine organisms.

Double-guidewire technique for selective biliary cannulation does not increase the rate of post-endoscopic retrograde cholangiopancreatography pancreatitis in patients with naïve papilla.

BACKGROUND/AIMS: This study aimed to compare the safety of the double-guidewire technique (DGT) with that of the conventional single-guidewire technique (SGT) in real-world situations. METHODS: A total of 240 patients with naïve papilla who underwent endoscopic retrograde cholangiopancreatography (ERCP) at Daegu Catholic University Medical Center between January 2021 and December 2021 were included. The primary outcome was the rate of post-ERCP pancreatitis (PEP) in the SGT and DGT groups. RESULTS: A total of 163 patients (67.9%) belonged to the SGT group, and 77 (32.1%) belonged to the DGT group. The rates of successful biliary cannulation were 95.7% and 83.1% in the SGT and DGT groups, respectively (p=0.002). In the study group, PEP occurred in 14 patients (5.8%). The PEP rates were not significantly different between the SGT and DGT groups (4.3% vs. 9.1%, p=0.150). In the multivariate analysis, the age of <50 years (odds ratio [OR], 9.305; 95% confidence interval [CI], 1.367-63.358; p=0.023) and hyperlipidemia (OR, 7.384; 95% CI, 1.103-49.424; p=0.039) were significant risk factors for PEP in the DGT group. CONCLUSION: DGT did not increase the PEP rate in patients with naïve papilla. In addition, the age of <50 years and hyperlipidemia were significant risk factors for PEP in the DGT group.

Construction of High Energy Nanoscale Lead Azide Composite with Improved Flame Sensibility from Intercalated Hydroxide.

It is of great significance to develop efficient methods for preparing high-content modified nanoscale lead azide (LA) composites used in microinitiating devices. In this work, a structurally controllable salicylate-intercalated lead hydroxide with a nanoscale mesoporous structure is designed. Using it as a precursor, carbon-based lead azide (LA/C) and salicylate-based lead azide (LA/SA) are fabricated by the gas-solid azidation of the framework (GAF) method within 3 h, greatly reducing the preparation time of nano-LA composites. The characterizations of the composites demonstrate that the Pb in the precursors is transformed into nanoscale LA attached to the salicylate radical or its carbonized skeleton. Due to the unique embedded nanostructures and excellent electrical and thermal conductivity of salicylate-derived carbon materials, LA/C exhibits excellent electrostatic safety (E50 = 0.25 J) and flame sensitivity (H50 = 28 cm). The adjustable organic-inorganic ratio of intercalated hydroxides allows the LA content in LA/C to reach as high as 92.5%, enabling 6.50 mg of LA/C to successfully detonate secondary explosive CL-20 in a microinitiating device, demonstrating an amazing detonation ability superior to other reported LA complexes. The research provides a new perspective for the development of nanoscale LA composites with high LA content and appropriate sensitivity.

PTEN/AKT and Wnt/ß-catenin signaling pathways regulate the proliferation of Lgr5+ cells in liver cancer.

The progression and spread of tumors are believed to be primarily caused by cancer stem cells (CSCs). Nevertheless, the task of focusing on CSCs for cancer treatment continues to be difficult. Lgr5, a G-protein-coupled receptor containing leucine-rich repeats, is highly expressed in different types of cancer and serves as a distinctive marker for cancer stem cells (CSCs). In this study, we employed the Cre-loxP system and Lgr5 tracking mice of male to selectively remove PTEN and ß-catenin in Lgr5+ cells of DEN-induced liver cancer and monitor the behavior of Lgr5+ cells. The tracking data revealed that the activation of PTEN-mediated AKT signaling in Lgr5 led to a significant rise in the quantity of Lgr5+ cells, whereas the inhibition of Wnt/ß-catenin signaling decreased the number of cells in DEN-induced liver cancer. Therefore, we have shown that the growth of Lgr5+ cells can be controlled by the PTEN/AKT and Wnt/ß-catenin pathways, offering a potential treatment option for fighting against liver cancer.

Enhanced Thermal Decomposition and Safety of Spherical CL-20@MOF-199 Composites via Micro-Nanostructured Self-Assembly Regulation.

The characteristics of high burning rate, high energy output, and low pressure exponent have always been the focus of development in the field of composite solid rocket propellants. In this paper, a metal-organic framework (MOF-199) compound is introduced to prepare micro-nanospherical CL-20@MOF-199 composites via the spray-drying self-assembly technique to reach the above goals. MOF-199, which acts as an attractive combustion catalyst and a safety regulator, is uniformly coated on the surface of CL-20 with close interface contact between particles, effectively accelerating the thermal decomposition of CL-20 and ensuring safety performance. The average noncovalent interaction (aNCI) analysis illustrates that there are strong C-H···O hydrogen bonds and van der Waals interaction between CL-20 and MOF-199 molecules, greatly enhancing the effect of interparticle assembly. The effects of different contents of MOF-199 on the thermal, safety, and energy properties of CL-20 were discussed. The thermal analysis demonstrates that MOF-199 has a significant thermal catalytic effect on CL-20, with an advanced peak temperature of thermal decomposition of 14.2 °C and a reduced activation energy barrier of 34.2 kJ·mol-1, mainly benefitting from more exposed catalytic active sites and close interface contact. In addition, CL-20@MOF-199 composites exhibit decreased mechanical sensitivity (IS: 21-40 cm, FS: 80-240 N) and excellent energy performance. This work clearly demonstrates that MOF-199 is both a superior combustion catalyst and a good safety buffer for CL-20, and it opens new potential for further applications of CL-20 in composite solid propellants.

A novel porcine model of CLN3 Batten disease recapitulates clinical phenotypes.

Mouse models of CLN3 Batten disease, a rare lysosomal storage disorder with no cure, have improved our understanding of CLN3 biology and therapeutics through their ease of use and a consistent display of cellular pathology. However, the translatability of murine models is limited by disparities in anatomy, body size, life span and inconsistent subtle behavior deficits that can be difficult to detect in CLN3 mutant mouse models, thereby limiting their use in preclinical studies. Here, we present a longitudinal characterization of a novel miniswine model of CLN3 disease that recapitulates the most common human pathogenic variant, an exon 7-8 deletion (CLN3Δex7/8). Progressive pathology and neuron loss is observed in various regions of the CLN3Δex7/8 miniswine brain and retina. Additionally, mutant miniswine present with retinal degeneration and motor abnormalities, similar to deficits seen in humans diagnosed with the disease. Taken together, the CLN3Δex7/8 miniswine model shows consistent and progressive Batten disease pathology, and behavioral impairment mirroring clinical presentation, demonstrating its value in studying the role of CLN3 and safety/efficacy of novel disease-modifying therapeutics.

Exploring Bioactive Compounds in Brown Seaweeds Using Subcritical Water: A Comprehensive Analysis.

In this study, we characterized the bioactive properties of three important brown seaweed species, Sargassum thunbergii, Undaria pinnatifida, and Saccharina japonica, by subcritical water extraction (SWE), as these species are well known for their beneficial health effects. Their physiochemical properties, including potential antioxidant, antihypertensive, and α-glucosidase inhibitory activity, and the antibacterial activity of the hydroysates were also analyzed. The highest total phlorotannin, total sugar content, and reducing sugar content in the S. thunbergii hydrolysates were 38.82 ± 0.17 mg PGE/g, 116.66 ± 0.19 mg glucose/g dry sample, and 53.27 ± 1.57 mg glucose/g dry sample, respectively. The highest ABTS+ and DPPH antioxidant activities were obtained in the S. japonica hydrolysates (124.77 ± 2.47 and 46.35 ± 0.01 mg Trolox equivalent/g, respectively) and the highest FRAP activity was obtained in the S. thunbergii hydrolysates (34.47 ± 0.49 mg Trolox equivalent/g seaweed). In addition, the seaweed extracts showed antihypertensive (≤59.77 ± 0.14%) and α-glucosidase inhibitory activity (≤68.05 ± 1.15%), as well as activity against foodborne pathogens. The present findings provide evidence of the biological activity of brown seaweed extracts for potential application in the food, pharmaceutical, and cosmetic sectors.

Linear and symmetric synaptic weight update characteristics by controlling filament geometry in oxide/suboxide HfOx bilayer memristive device for neuromorphic computing.

Memristive devices have been explored as electronic synaptic devices to mimic biological synapses for developing hardware-based neuromorphic computing systems. However, typical oxide memristive devices suffered from abrupt switching between high and low resistance states, which limits access to achieve various conductance states for analog synaptic devices. Here, we proposed an oxide/suboxide hafnium oxide bilayer memristive device by altering oxygen stoichiometry to demonstrate analog filamentary switching behavior. The bilayer device with Ti/HfO2/HfO2-x(oxygen-deficient)/Pt structure exhibited analog conductance states under a low voltage operation through controlling filament geometry as well as superior retention and endurance characteristics thanks to the robust nature of filament. A narrow cycle-to-cycle and device-to-device distribution were also demonstrated by the filament confinement in a limited region. The different concentrations of oxygen vacancies at each layer played a significant role in switching phenomena, as confirmed through X-ray photoelectron spectroscopy analysis. The analog weight update characteristics were found to strongly depend on the various conditions of voltage pulse parameters including its amplitude, width, and interval time. In particular, linear and symmetric weight updates for accurate learning and pattern recognition could be achieved by adopting incremental step pulse programming (ISPP) operation scheme which rendered a high-resolution dynamic range with linear and symmetry weight updates as a consequence of precisely controlled filament geometry. A two-layer perceptron neural network simulation with HfO2/HfO2-x synapses provided an 80% recognition accuracy for handwritten digits. The development of oxide/suboxide hafnium oxide memristive devices has the capacity to drive forward the development of efficient neuromorphic computing systems.

Radical Hydrocarboxylation of Unactivated Alkenes via Photocatalytic Formate Activation.

Herein we disclose a strategy to promote the hydrocarboxylation of unactivated alkenes using photochemical activation of formate salts. We illustrate that an alternative initiation mechanism circumvents the limitations of prior approaches and enables hydrocarboxylation of this challenging substrate class. Specifically, we found that accessing the requisite thiyl radical initiator without an exogenous chromophore eliminates major byproducts that have plagued attempts to exploit similar reactivity for unactivated alkene substrates. This redox-neutral method is technically simple to execute and effective across a broad range of alkene substrates. Feedstock alkenes, such as ethylene, are hydrocarboxylated at ambient temperature and pressure. A series of radical cyclization experiments indicate how the reactivity described in this report can be diverted by more complex radical processes.

Development of fish gelatin/carrageenan/zein bio-nanocomposite active-films incorporated with turmeric essential oil and their application in chicken meat preservation.

Gelatin/carrageenan (Ge/Car) active packaging films incorporated with turmeric essential oil (TEO) encapsulated in zein nanoparticles (ZNP) were developed. The efficacy of these active packaging films and their antimicrobial properties were also investigated to ensure their practical application. Three different types of nanocomposite films (Ge/Car, Ge/Car/TEO, and Ge/Car/ZNP) were prepared. The characterization of the films was elucidated using Fourier transform infrared (FTIR), X-ray diffraction analyses (XRD), and scanning electron microscope (SEM). Physicochemical and mechanical properties of the films were enhanced, owing to the application of TEO-containing nanocomposites. Supercritical-CO2 extracted TEO showed excellent biological activities, alongside GC-MS analysis identified that TEO contained 33 bioactive compounds where the major constituent was Zingiberene. ZNP proved an excellent carrier of TEO. The nanocomposite film sustainably released TEO, improving the shelf life of the chicken meat by reducing bacterial colonies from 3.08 log CFU/g to 2.81 log CFU/g after 14 days incubation against Salmonella enterica compared with 6.66 log CFU/g observed in the control film. The overall results of this study suggest that the nanocomposite active film is an excellent candidate for food packaging to ensure a better world.

Risk Factors for Emergency Department Presentations after the Initiation of Opioid Analgesics in Non-Cancer Patients in Korea: A Nationwide Study.

Background and Objectives: Opioid use in Korea is lower than in other developed countries. However, recent studies have reported an increase in opioid prescriptions and the number of chronic opioid users. The current status of adverse events (AEs) associated with opioid analgesics in Korea is unclear. This nested case-control study aimed to evaluate the influence of opioid analgesic use patterns on all emergency department (ED) visits and opioid-related ED visits after opioid analgesic initiation using the national claims database. Materials and Methods: Adult non-cancer patients who initiated non-injectable opioid analgesics (NIOA) between January 2017 and June 2018 were included. We defined the case group as patients who visited the ED within six months of opioid initiation, and the control group was selected in a 1:1 ratio using an exact matching method. Results: A total of 97,735 patients (13.58%) visited the ED within six months of NIOA initiation. Nearly 32% of cases were linked to opioid-related AEs. The most frequent AEs were falls and fractures (61.27%). After adjusting for covariates, opioid initiation at the ED was associated with all-cause or opioid-related ED visits (adjusted odds ratio (aOR) = 3.19, 95% confidence interval (CI) = 3.09-3.29; aOR = 3.82, 95% CI = 3.62-4.04, respectively). Chronic NIOA use was associated with all-cause and opioid-related ED visits (aOR = 1.32, 95% CI = 1.23-1.40; aOR = 1.56, 95% CI = 1.39-1.76, respectively). Conclusion: This study found that 13% of non-cancer patients visited the ED within six months of NIOA initiation. In addition, the NIOA use pattern was significantly associated with all-cause and opioid-related ED visits.

Venous Thromboembolism in Patients with Advanced Pancreatic Cancer Receiving Palliative Chemotherapy: Incidence and Effect on Prognosis.

Background/Aims: This study evaluated the incidence of venous thromboembolism (VTE) in patients with advanced pancreatic ductal adenocarcinoma (PDAC) at the authors' institution and analyzed the risk factors associated with VTE and the overall survival (OS). Methods: One hundred and seventy patients with locally advanced or metastatic PDAC who received palliative chemotherapy at Daegu Catholic University Medical Center from January 2011 to December 2020 were included. Results: During a median follow-up period of 341 days, 24 patients (14.1%) developed VTE. Cumulative incidence values of VTE were 4.7% (95% confidence interval [CI], 2.39-9.22) at 90 days, 9.9% (95% CI, 6.14-15.59) at 180 days, and 16.9% (95% CI, 11.50-24.36) at 360 days. Multivariate analysis showed that a carbohydrate antigen 19-9 (CA 19-9) level over 1,000 U/mL (hazard ratio [HR], 2.666; 95% CI, 1.112-6.389; p=0.028) and a history of alcohol consumption (HR, 0.327; 95% CI, 0.109-0.981; p=0.046) were significant factors associated with VTE. Patients with VTE showed a shorter median survival (347 days vs. 556 days; p=0.041) than those without VTE. Multivariate analysis revealed VTE (HR, 1.850; 95% CI, 1.049-3.263; p=0.033) and CA 19-9 level over 1,000 U/mL (HR, 1.843; 95% CI, 1.113-3.052; p=0.017) to be significant risk factors associated with OS. Conclusions: The cumulative incidence of VTE in patients with advanced PDAC was 16.9% at 360 days. While a history of alcohol consumption was a protective factor, a high CA19-9 level was a risk factor for VTE. In addition, the occurrence of VTE was associated with poor prognosis.

Distinct bulge stem cell populations maintain the pilosebaceous unit in a ß-catenin-dependent manner.

The pilosebaceous unit (PSU) is composed of multiple compartments and the self-renewal of PSU depends on distinct hair follicle stem cell (HFSC) populations. However, the differential roles of the HFSCs in sebaceous gland (SG) renewal have not been completely understood. Here, we performed multiple lineage tracing analysis to unveil the contribution of different HFSC populations to PSU regeneration during the hair cycle and wound healing. Our results indicated that the upper bulge stem cells contributed extensively to the SG replenishment during hair cycling, while HFSCs in the lower bugle did not. During skin wound healing, all HFSC populations participated in the SG replenishment. Moreover, ß-catenin activation promoted the contribution of HFSCs to SG replenishment, whereas ß-catenin deletion substantially repressed the event. Thus, our findings indicated that HFSCs contributed to SG replenishment in a ß-catenin-dependent manner.

Analysis of Medication Errors Reported by Community Pharmacists in the Republic of Korea: A Cross-Sectional Study.

Background and objectives: We aimed to describe medication-related incidents or medication errors (MEs) reported by community pharmacists and analyze the prevalent medications involved. Materials and Methods: We extracted ME reports from databases comprising patient safety incidents reported to the Korean Pharmaceutical Association between January 2013 and June 2021. Medications were analyzed according to the second (therapeutic subgroup) and fifth (chemical substance) levels of the Anatomical Therapeutic Chemical classification. Results: A total of 9046 MEs were identified, most of which were near miss reports (88.3%). Among the errors that reached the patients (521 cases), harmful incidents accounted for 76.8%. Most MEs occurred during prescription (89.5%), while harmful MEs occurred mainly during dispensing (73.3%). In the prescription step, wrong drugs (44.8%), dosing errors (27.0%), and wrong durations (14.0%) were common. Anti-inflammatory and anti-rheumatic products (M01), drugs for acid-related disorders (A02), and antihistamines for systemic use (R06) were the most frequently reported medication classes involved. Harmful incidents were most common for dosing errors (31.0%) and wrong drugs (26.8%) and were common with warfarin, levothyroxine, and glimepiride. Conclusions: The MEs reported by community pharmacists were mainly prescribing errors, most of which were rectified before reaching patients. The prevalent medications involved in harmful errors include anti-diabetic, anti-thrombotic, and anti-inflammatory agents.

The effect and therapeutic compliance of adjuvant therapy in patients with cholangiocarcinoma after R0 resection: a retrospective study.

BACKGRUOUND: This study aimed to compare clinical outcomes between surveillance and adjuvant therapy (AT) groups after R0 resection for cholangiocarcinoma (CCA). METHODS: A total of 154 patients who underwent R0 resection for CCA at the Daegu Catholic University Medical Center between January 2010 and December 2019 were included. Overall survival (OS) and progression-free survival (PFS) were analyzed. RESULTS: The median follow-up duration was 899 days. There were 109 patients in the AT group and 45 patients in the surveillance group. The patients in the AT group were younger (67 years vs. 74 years, p<0.001) and included more males (64.2% vs. 46.7%, p=0.044). The proportion of patients with stage III CCA was larger in the AT group than in the surveillance group (13.8% vs. 2.2%, p=0.005). In addition, AT did not improve OS (5-year OS rate, 69.3% in the AT group vs. 64.2% in the surveillance group, p=0.806) or PFS (5-year PFS rate, 42.6% in the AT group vs. 48.9% in the surveillance group, p=0.113). In multivariate analysis using the Cox proportional hazards model, stage III CCA (hazard ratio [HR], 10.81; 95% confidence interval [CI], 2.92-40.00; p<0.001) was a significant predictor of OS. American Society of Anesthesiologists classification II (HR, 0.50; 95% CI, 0.31-0.81; p=0.005), and American Joint Committee on Cancer stages II (HR, 3.14; 95% CI, 1.25-7.89; p=0.015) and III (HR, 8.08; 95% CI, 2.80-23.32; p<0.001) were independent predictors of PFS. CONCLUSION: AT after R0 resection for CCA did not improve OS or PFS.