The effect of celastrol in combination with 5-fluorouracil on proliferation and apoptosis of gastric cancer cell lines

Background:Despite the availability of chemotherapy drugs such as 5-fluorouracil(5-FU),the treatment of some cancers such as gastric cancer remains challenging due to drug resistance and side effects.This study aimed to investigate the effect of celastrol in combination with the chemotherapy drug 5-FU on proliferation and induction of apoptosis in human gastric cancer cell lines(AGS and EPG85-257).Materials and Methods:In this in vitro study,AGS and EPG85-257 cells were treated with different concentrations of celastrol,5-FU,and their combination.Cell proliferation was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide(MTT)assay.The synergistic effect of 5-FU and celastrol was studied using Compusyn software.The DNA content at different phases of the cell cycle and apoptosis rate was measured usingflow cytometry.Results:Co-treatment with low concentrations(10%inhibitory concentration(IC10))of celastrol and 5-FU significantly reduced IC50(p<0.05)so that 48 h after treatment,IC50 was calculated at 3.77 and 6.9μM for celastrol,20.7 and 11.6μM for 5-FU,and 5.03 and 4.57μM for their combination for AGS and EPG85-257 cells,respectively.The mean percentage of apoptosis for AGS cells treated with celastrol,5-FU,and their combination was obtained 23.9,41.2,and 61.9,and for EPG85-257 cells 5.65,46.9,and 55.7,respectively.In addition,the 5-FU and celastrol-5-FU combination induced cell cycle arrest in the synthesis phase.Conclusions:Although celastrol could decrease the concentration of 5-fluorouracil that sufficed to suppress gastric cancer cells,additional studies are required to arrive at conclusive evidence on the anticancer effects of celastrol.

A Rapid Parameter of Enzyme-Treated Cellulosic Material Revealed by Reducing Sugar Release

This study was conducted to evaluate the effectiveness of enzymes in purifying and reducing the degree of polymerization of cellulose for the production of dissolving pulp.Our goal was to determine the contributions of xylanase(X)and endoglucanase(EG)in the treatment of pulp,specifically by quantifying the formation of soluble and insoluble reducing sugars using the dinitrosalycilic acid(DNS)test.Predominantly,the release of soluble reducing sugars(RSSol)was enhanced after xylanase treatment,while endoglucanase(EG)treatment led to changes in insoluble reducing sugars(RSIns).The maximum synergism was observed for RSIns when a high ratio of endoglucanase to xylanase(320EG:5X/g pulp)was used.The relative contribution of endoglucanase to RSins was determined to be 15.6%of the total reducing sugar.The viscosity of pulps treated with xylanase decreased only by 7%,whereas endoglucanase treatment significantly reduced viscosity by 45%.Modifications in the particle size were observed after pulp treatment with the combination of endoglucanase and xylanase.In summary,the DNS test is a rapid and effective method for evaluating the efficiency of enzyme treatments on pulps.The measurement of RSIns correlates with changes in pulp viscosity to different extents,providing valuable insights into the effectiveness of enzyme treatments.

Enhancing potassium-ion storage of Bi_(2)S_(3) through external–internal dual synergism: Ti_(3)C_(2)T_(x) compositing and Cu^(2+) doping

Potassium-ion batteries(PIBs)offer a cost-effective and resource-abundant solution for large-scale energy storage.However,the progress of PIBs is impeded by the lack of high-capacity,long-life,and fast-kinetics anode electrode materials.Here,we propose a dual synergic optimization strategy to enhance the K^(+)storage stability and reaction kinetics of Bi_(2)S_(3) through two-dimensional compositing and cation doping.Externally,Bi_(2)S_(3) nanoparticles are loaded onto the surface of three-dimensional interconnected Ti_(3)C_(2)T_(x) nanosheets to stabilize the electrode structure.Internally,Cu^(2+)doping acts as active sites to accelerate K^(+)storage kinetics.Various theoretical simulations and ex situ techniques are used to elucidate the external–internal dual synergism.During discharge,Ti_(3)C_(2)T_(x) and Cu^(2+)collaboratively facilitate K+intercalation.Subsequently,Cu^(2+)doping primarily promotes the fracture of Bi2S3 bonds,facilitating a conversion reaction.Throughout cycling,the Ti_(3)C_(2)T_(x) composite structure and Cu^(2+)doping sustain functionality.The resulting Cu^(2+)-doped Bi2S3 anchored on Ti_(3)C_(2)T_(x)(C-BT)shows excellent rate capability(600 mAh g^(-1) at 0.1 A g^(–1);105 mAh g^(-1) at 5.0 A g^(-1))and cycling performance(91 mAh g^(-1) at 5.0 A g^(-1) after 1000 cycles)in half cells and a high energy density(179 Wh kg–1)in full cells.

The efficacy study of trinity permeation synergism on anti-aging

Background:More and more consumers are paying attention to skin rejuvenation.However,there is a lack of a non-invasive and efficient solution.Objective:To evaluate the efficacy of a trinity permeation synergism(TPS),which consists of a firming essence,an atomizer and a photoelectric penetrator,for facial anti-aging efficacy.Material and methods:In this work,in vitro cell experiments and human efficacy study were used to evaluate the firming and anti-wrinkle effects.Cell experiments were used to verify the effect of the firming essence on the cell proliferation,migration,and anti-inflammation in keratinocytes(HaCaT),and on the gene expression levels of type I and type III collagen(Col-1 and Col-3)and type I matrix metalloproteinase(MMP-1)in human skin fibroblasts(HSF).After in vitro test,60 women aged 35–60 years were enrolled in the randomized test,of which 30 subjects were randomly selected to be the experimental group and treated with the TPS system,while the left 30 subjects were treated with the firming essence only considered as control.After 28 days,skin elasticity,skin redness value,and skin wrinkles were measured to evaluate the efficacy of the TPS system.Results:Cell experiments showed that the firming essence can significantly improve the proliferation and the migration of HaCaT cells.It also promoted the expression level of Col-1 and Col-3 gene,and inhibited the expression level of MMP-1 gene in HSF cells.After confirming the efficacy of firming essence,the efficacy benefit of the TPS was further studied.The 28-day tests show that combined use firming essence with atomizer and penetrator can significantly increase skin elasticity,reduce skin hemoglobin value and skin wrinkles on Day 28.Moreover,all the mentioned improvements are significantly better than that in the control group.Conclusion:Through efficient delivery in the whole process,TPS boosts the efficacy of active components in the firming essence.TPS offers an efficient,non-invasive,and convenient way for enhanced facial rejuvenation efficacy.

Compositional engineering of HKUST-1/sulfidized NiMn-LDH on functionalized MWCNTs as remarkable bifunctional electrocatalysts for water splitting

Water-splitting reactions such as the hydrogen evolution reaction(HER)and the oxygen evolution reaction(OER)typically require expensive noble metal-based electrocatalysts.This has motivated researchers to develop novel,cost-effective electrocatalytic systems.In this study,a new multicomponent nanocomposite was assembled by combining functionalized multiwalled carbon nanotubes,a Cu-based metal–organic framework(MOF)(HKUST-1 or HK),and a sulfidized NiMn-layered double hydroxide(NiMn-S).The resulting nanocomposite,abbreviated as MW/HK/NiMn-S,features a unique architecture,high porosity,numerous electroactive Cu/Ni/Mn sites,fast charge transfer,excellent structural stability,and conductivity.At a current density of 10 mA cm-2,this dual-function electrocatalyst shows remarkable performance,with ultralow overpotential values of 163 mV(OER)or 73 mV(HER),as well as low Tafel slopes(57 and 75 mV dec-1,respectively).Additionally,its high turnover frequency values(4.43 s-1 for OER;3.96 s-1 for HER)are significantly superior to those of standard noble metal-based Pt/C and IrO2 systems.The synergistic effect of the nanocomposite's different components is responsible for its enhanced electrocatalytic performance.A density functional theory study revealed that the multi-interface and multicomponent heterostructure contribute to increased electrical conductivity and decreased energy barrier,resulting in superior electrocatalytic HER/OER activity.This study presents a novel vision for designing advanced electrocatalysts with superior performance in water splitting.Various composites have been utilized in water-splitting applications.This study investigates the use of the MW/HK/NiMn-S electrocatalyst for water splitting for the first time to indicate the synergistic effect between carbon-based materials along with layered double hydroxide compounds and porous compounds of MOF.The unique features of each component in this composite can be an interesting topic in the field of water splitting.

Gradient carbonyl-iron/carbon-fiber reinforced composite metamaterial for ultra-broadband electromagnetic wave absorption by multi-scale integrated design

The demand of high-end electromagnetic wave absorbing materials puts forward higher requirements on comprehensive performances of small thickness,lightweight,broadband,and strong absorption.Herein,a novel multi-layer stepped metamaterial absorber with gradient electromagnetic properties is proposed.The complex permittivity and permeability of each layer are tailored via the proportion of carbonyliron and carbon-fiber dispersing into the epoxy resin.The proposed metamaterial is further optimized via adjusting the electromagnetic parameters and geometric sizes of each layer.Comparing with the four-layer composite with gradient electromagnetic properties which could only realize reflection loss(RL)of less than−6 dB in 2.0-40 GHz,the optimized stepped metamaterial with the same thickness and electromagnetic properties realizes less than−10 dB in the relevant frequency range.Additionally,the RL of less than−15 dB is achieved in the frequency range of 11.2-21.4 GHz and 28.5-40 GHz.The multiple electromagnetic wave absorption mechanism is discussed based on the experimental and simulation results,which is believed to be attributed to the synergy effect induced by multi-scale structures of the metamaterial.Therefore,combining multi-layer structures and periodic stepped structures into a novel gradient absorbing metamaterial would give new insights into designing microwave absorption devices for broadband electromagnetic protections.

Cytotoxic synergism of Clostridioides difficile toxin B with proinflammatory cytokines in subjects with inflammatory bowel diseases

Clostridioides difficile(C.difficile)is progressively colonizing humans and animals living with humans.During this process,hypervirulent strains and mutated toxin A and B of C.difficile(TcdA and TcdB)are originating and developing.While in healthy subjects colonization by C.difficile becomes a risk after the use of antibiotics that alter the microbiome,other categories of people are more susceptible to infection and at risk of relapse,such as those with inflammatory bowel disease(IBD).Recent in vitro studies suggest that this increased susceptibility could be due to the strong cytotoxic synergism between TcdB and proinflammatory cytokines the tumor necrosis factor-alpha and interferon-gamma(CKs).Therefore,in subjects with IBD the presence of an inflammatory state in the colon could be the driver that increases the susceptibility to C.difficile infection and its progression and relapses.TcdB is internalized in the cell via three receptors:chondroitin sulphate proteoglycan 4;poliovirus receptor-like 3;and Wnt receptor frizzled family.Chondroitin sulphate proteoglycan 4 and Wnt receptor frizzled family are involved in cell death by apoptosis or necrosis depending on the concentration of TcdB and cell types,while poliovirus receptor-like 3 induces only necrosis.It is possible that cytokines could also induce a greater expression of receptors for TcdB that are more involved in necrosis than in apoptosis.Therefore,in subjects with IBD there are the conditions:(1)For greater susceptibility to C.difficile infection,such as the inflammatory state,and abnormalities of the microbiome and of the immune system;(2)for the enhancement of the cytotoxic activity of TcdB+Cks;and(3)for a greater expression of TcdB receptors stimulated by cytokines that induce cell death by necrosis rather than apoptosis.The only therapeutic approach currently possible in IBD patients is monitoring of C.difficile colonization for interventions aimed at reducing tumor necrosis factor-alpha and interferon-gamma levels when the infection begins.The future perspective is to generate bacteriophages against C.difficile for targeted therapy.

Optimal Synergic Deep Learning for COVID-19 Classification Using Chest X-Ray Images

A chest radiology scan can significantly aid the early diagnosis and management of COVID-19 since the virus attacks the lungs.Chest X-ray(CXR)gained much interest after the COVID-19 outbreak thanks to its rapid imaging time,widespread availability,low cost,and portability.In radiological investigations,computer-aided diagnostic tools are implemented to reduce intra-and inter-observer variability.Using lately industrialized Artificial Intelligence(AI)algorithms and radiological techniques to diagnose and classify disease is advantageous.The current study develops an automatic identification and classification model for CXR pictures using Gaussian Fil-tering based Optimized Synergic Deep Learning using Remora Optimization Algorithm(GF-OSDL-ROA).This method is inclusive of preprocessing and classification based on optimization.The data is preprocessed using Gaussian filtering(GF)to remove any extraneous noise from the image’s edges.Then,the OSDL model is applied to classify the CXRs under different severity levels based on CXR data.The learning rate of OSDL is optimized with the help of ROA for COVID-19 diagnosis showing the novelty of the work.OSDL model,applied in this study,was validated using the COVID-19 dataset.The experiments were conducted upon the proposed OSDL model,which achieved a classification accuracy of 99.83%,while the current Convolutional Neural Network achieved less classification accuracy,i.e.,98.14%.

Compatibility mechanism of Chinese medicine formula:state of the art and perspectives

Traditional Chinese medicine(TCM)has been practiced in China and surrounding countries for thousands of years and has gradually attracted the attention of Western countries.After reasonable compatibility,TCMs could play the key role of enhancing efficacy and reducing toxicity,which has significant therapeutic advantages in the treatment of complex diseases in clinical practice.While the TCM compatibility is not the simple addition of drugs.Under the appropriate dosage ratio,multiple TCMs can play a synergistic role to realize the overall regulation of TCM treatment.Therefore,it is of critical essential to study the compatibility of TCM formula to promote TCM modernization,new drug development and clinical application.Recently,under the guidance of TCM theory,many researches on the composition,pharmacodynamic activity and pharmacokinetic properties of TCM formula have emerged by integrating new technologies and new methods,revealing the scientific connotation of the compatibility of TCM formula from different perspectives and levels.This paper introduces the research progress of compatibility rules from different levels of compatibility,compatibility for synergistic enhancement and detoxification,and application of cutting-edge technology,with representative cases,in order to provide ideas and references for further study on TCM compatibility.

Tribocorrosion behaviors of Ti-6Al-4V and Monel K500 alloys sliding against 316 stainless steel in artificial seawater

The tribocorrosion behaviors of Ti-6Al-4V and Monel K500 alloys sliding against 316 stainless steel were investigated using a ring-on-block test rig in both artificial seawater and distilled water. It is found that friction coefficients are in general larger in distilled water compared with seawater. The wear losses of Ti-6Al-4V and Monel K500 alloys are larger in seawater compared with distilled water. The mechanical action can destroy the passive film and increase the corrosion rate. The synergism effect between corrosion and wear occurs. The synergism action between corrosion and wear is related to the corrosion rate and with the increase of corrosion rate, the synergism becomes more important. 316 stainless steel suffers severe wear sliding against Monel K500 alloy compared with sliding against Ti-6Al-4V alloy in both distilled water and seawater.

Effect of wear conditions on tribological properties of electrolessly-deposited Ni-P-Gr-SiC hybrid composite coating

The friction and wear properties of the electrolessly-deposited Ni-P-Gr-SiC composites were investigated. The effects of graphite content, load and rotation speed on the friction coefficient and wear resistance of the composite coatings were mainly investigated. The worn surface and cross section of the coatings were characterized by scanning electron microscopy and energy-dispersive X-ray analysis. The results show that the composite coatings reveal good antifriction and wear resistance due to the synergic effect of graphite and SiC particles. The formation of graphite-rich mechanically mixed layer （GRMML） on the surface of Ni-P-Gr-SiC coating contributes to the good tribological behavior of the wear counterparts and SiC particles play a load bearing role in protecting GRMML from shearing easily.

Analgesic Effects of Tetrodotoxin Combined with Acetylsalicylic Acid on Acetic Acid-induced Abdominal Constriction and Formalin Test in Mice

Aim To study the effects of tetrodotoxin （TTX） combined with acetylsalicylic acid （ASA） on nociceptive stimulus in mice. Methods To assess the antinociceptive effects of TTX, ASA or TTX plus ASA, the acetic acid-induced abdominal constriction test and formalin pain test were used. Results TTX （0.5 - 4.0 μg· kg^-1 ） or ASA （25 - 200 mg· kg^-1 ） im produced a significant inhibition of acetic acid-induced abdominal constriction. The median inhibitory doses （ID508） were 2.1 μg· kg^-1 for TTX（ and 64 mg· kg^-1 for ASA. TTX and ASA also showed a dose-dependent inhibition of the second phase response in the formalin pain model, the ID508, being 2.3μg·kg^-1 and 74.2 mg· kg^-1, respectively. The ihteraction between TTX and ASA was synergistic, as evidenced by the fact that （1） when ASA alone compared with the combination of TTX （0.79 μg · kg^-1 or 0.39μg· kg^-1 ） and ASA, the ID508, of ASA reduced from 64.0 mg· kg^-1 to 5.8 mg· kg^-1 or 12.6 mg· kg^-1, and from 74.2 mg· kg^-1 to 7.4 mg· kg^-1 or 13.0 mg· kg^-1 on tile two models of nociceptive tests, respectively; and that （2） synergism in the analgesic effects was shown by isobiolographic analysis. Conclusion TTX, ASA and the combination of the two drags produce analgesic effects in acetic acid-induced abdominal constriction test and formalin-induced pain test. The interactions between TTX and ASA may be useful in developing novel analgesic agents.

Potato Y Potyvirus Helper Component Proteinase Enhances Long-distance Movement of Potato X Potexvirus

To mutagenize two conserved CCCT and PTK motifs in the central domain of Chinese strain of potato Y potyvirus (PVY-C) helper component proteinase (HC-Pro), four mutants of HC-Pro gene were obtained by PCR and site-directed mutagenesis, and then were inserted into the constitutive expression vector pBin438. Leaves from tobacco (Nicotiana tabacum L. cv. K326) were transformed with these four plant expression plasmids by Agrobacterium-mediated transformation, respectively. Southern and Western blotting analyses showed that these four mutants were integrated into tobacco genomic DNA and could express the corresponding proteins in most of die transgenic plants. The challenge of transgenic plants with potato X potexvirus (PVX) revealed that the expression products of PVY-C HC-Pro mutants in transgenic plants greatly abolished functions of HC-Pro in enhancing the accumulation and pathogenicity of PVX, indicating that CCCT and PTK motifs of HC-Pro were required for PVX/PVY synergism. Meanwhile, the results demonstrated that PVY-C HC-Pro had a function in accelerating the long-distance movement of PVX in these transgenic plants for the first time.

Remediation of in-situ Leach Mining Contaminated Soil by Amendment-plant Synergism

This study aimed to remediate in-situ leach mining contaminated soil by amendment-plant synergism. The results showed that plant species exhibited ex-tremely significant effects on the concentration of nitrate nitrogen; to be specific, the concentration of nitrate nitrogen in soil planted with wheat was reduced from 692.19 mg/kg to lower than 100 mg/kg; when the mass ratio of amendment to soil reached 3：50 and the amendment particle size was 1-2 mm, the concentration of nitrate ni-trogen in soil planted with wheat was reduced to 43 mg/kg. The amendment type exhibited extremely significant effects on the concentration of ammonium nitrogen; to be specific, when the mass ratio of amendment to soil reached 10：50, the concen-tration of ammonium nitrogen in soil added with 2-3 mm zeolite was reduced from 23 593.75 to 3 300 mg/kg on day 15. Amendments and plants mainly exhibited desorption performance for sulfate radical in soil, and the amendment type extreme-ly significantly affected the concentration of sulfate radical; to be specific, the con-centration of sulfate radical in soil added with limestone increased from 370 mg/kg to 900 mg/kg on day 7.

Screening on Synergist of Bacillus thuringiensis Wettable Powder

[Objective] This study aimed to screen the best synergistic material for Bt wettable powder and evaluate their synergistic effect. [Method] The synergism of six different kinds of additives for Bacillus thuringiensis wettable powder （Bt WP） on the 2^nd instar larvae of Plutella xylostella was tested by method of leaf dipping in labora- tory. [Result] The mixtures of Bt with 0.1% ZnCl2, 0.5% ZnCl2, 1.0% ZnCl2, 1.0% MgCI2, 0.5% boric acid, 1.0% boric acid, 0.5% citric acid or 1.0% citric acid all ex- hibited synergistic effect, in which the synergistic effect of mixture containing 0.5% boric acid was the highest, with 17.2 synergistic ratio; followed by the mixture containing 1.0% ZnCl2, with 15.6 synergistic ratio. Moreover, addition of 0.5% boric acid could shorten the median lethal time of Bt wettable powder by about 10 h. After the mixtures of Bt with 0.5% boracic acid or 1.0% ZnCl2 was stored for 15 d at room temperature, toxicities of the two mixtures did not change significantly. [Conclusion] Boracic acid as the synergist of Bt wettable powder could not only increase insecti- cidal effect of Bt, but also accelerate its insecticidal rate. So, boracic acid could improve the disadvantages of Bt wettable powder such as poor insecticidal effect and slow insecticidal speed in a certain degree.

Fuzzy multiple attribute decision-making model for synergic knowledge innovation in supply chain

The procedure of supply chain development is the process of continuously congregating knowledge and transforming knowledge.First,the precondition of synergic knowledge innovation in the supply chain is narrated.Then the characteristics of synergic knowledge innovation in the supply chain are analyzed,including complexity,accumulating and evolving process,and the cooperation of members and network integration.Due to the characteristics of multi-factors and uncertainties of the supply chain system,the fuzzy multi-attribution group decision-making model is introduced to solve the involved problem of synergic knowledge innovation in the supply chain.After elaborating on steps of using the fuzzy multiple attribute decision-making(MADM)model,the procedure of decision making for synergic knowledge innovation in the supply chain is explained from an example in the application of a fuzzy MADM model.The fuzzy MADM model,which amalgamates intuition and resolution decision-making can effectively improve the rationality of decision-making for synergic knowledge innovation in the supply chain.

Goals and Key Technology of Fertilizer-pesticide "Double Reduction" and Synergism for Greenhouse Strawberry

In order to develop green good, reduce the use of chemical fertilizer and pesticide, realize ＂double reduction＂ and synergism, improve safety and quality of products, protect the ecological environment and promote the healthy and steady development of strawberry industry, the goals and key technology of fertilizer-pesticide ＂double reduction＂ and synergism for greenhouse strawberry are summed up in this paper targeting at the current situation of strawberry production and combined with the new technology achievements at home and abroad. The key technology includes six items： healthy seedling cultivating technique, soil improvement and continuous cropping obstacle treatment technique, agricultural ecological prevention tech- nique, physicochemical trap of pest control technique, biological control technique and low residual risk chemical control technique.

脉冲MIG焊Synergic控制法的由来与发展

<正> 在本世纪40年代初,MIG焊就在美国研制成功,但在以后的20年时间里,基本上没有得到应用和发展,直到60年代初,欧洲一些先进国家的焊接界把它视为焊接工艺上的一项重大突破,并预言在60年代末有可能取代所有的MMA焊接工艺。可是这种愿望并未实现。因为当时MIG焊的设备价格比MMA焊接设备昂贵得多;氩气价格也很贵;而且这种工艺的好坏和设备性能有非常密切的关系。

Study on Controlling Tobacco Root-knot Nematode by Fertilizer and Pesticide Synergy

Synergism between pesticide and fertilizer in controlling root-knot nematode was investigated by field randomized block test. The results showed that the best control efficiency was shared by 0.5% abamectin and 25% mixed pesticide （abamectin and carbosulfan）, 24.1% and 28.0%, respectively. The positive effect was found by synergism between pesticide and fertiUzer in controlling reot-knot nematode. The economic benefit and agricultural benefit were gained by controlling root-knot nematodes. The results suggested that the agricultural and ecological benefit could be gained through the integration of agricultural practice and chemical technology in controlling root-knot nematode.

Hepatitis B virus infection, diabetes mellitus, and their synergism for cholangiocarcinoma development: A casecontrol study in Korea

AIM: To identify possible risk factors and their synergism for cholangiocarcinoma development.METHODS: A hospital-based, case-control study in which we included 276 cholangiocarcinoma patients [193 extrahepatic cholangiocarcinoma(ECC) and 83 intrahepatic cholangiocarcinoma(ICC)], diagnosed at a training hospital in Korea between 2007 and 2013, and 552 healthy controls matched 2:1 for age, sex, and date of diagnosis. Risk factors for cholangiocarcinoma and possible synergism between those factors were evaluated using conditional logistic regression and synergism index, respectively.RESULTS:There was an association between cholangiocarcinoma and hepatitis B virus(HBV) infection, diabetes mellitus(DM), cholecystolithiasis, choledocholithiasis, and hepatolithiasis, with the adjusted odds ratios(AORs) of 4.1, 2.6, 1.7, 12.4, and 39.9, respectively. Synergistic interaction on the additive model was investigated between HBV infection and DM(AOR = 12.2; 95%CI: 1.9-80.1). In the subgroup analyses, cholecystolithiasis, choledocholithiasis, hepatolithiasis, and DM were significant risk factors for ECC(AOR = 2.0, 18.1, 14.9, and 2.0, respectively), whereas choledocholithiasis, hepatolithiasis, HBV infection, and DM were risk factors for ICC(AOR = 8.6, 157.4, 5.3 and 4.9, respectively). Synergistic interaction was also observed between HBV infection and DM(OR = 22.7; 95%CI: 2.4-214.1). However, there was no synergistic interaction between other significant risk factors for cholangiocarcinoma.CONCLUSION: In this Korean study, HBV infection and DM were found to exert independent and synergistic effects on the risk for cholangiocarcinoma, including ICC. Exploring the underlying mechanismsfor such synergy may lead to the development of cholangiocarcinoma prevention strategies in high-risk individuals.