为探究青藏高原东南部大气中多环芳烃(Polycyclic Aromatic Hydrocarbons,简称PAHs)的污染、源及输送特征,利用鲁朗地区(29.77°N,94.73°E)总悬浮颗粒物(Total Suspended Particles,简称TSP)和大气中的14种PAHs含量,结合同期...为探究青藏高原东南部大气中多环芳烃(Polycyclic Aromatic Hydrocarbons,简称PAHs)的污染、源及输送特征,利用鲁朗地区(29.77°N,94.73°E)总悬浮颗粒物(Total Suspended Particles,简称TSP)和大气中的14种PAHs含量,结合同期气象环境数据进行了综合分析。结果表明,该地区TSP中PAHs和气相的PAHs质量浓度变化范围分别为0.22~5.05 ng m^(-3)和0.83~63.75 ng m^(-3),平均值分别为2.13 ng m^(-3)和11.33 ng m^(-3)。薪柴和柴油的燃烧是污染的主要方式,汽油燃烧等其他排放为次要方式。PAHs来自本地污染和远距离传输(Long Range Transmission,简称LRT)共同的影响。本地污染在四季各个源地均不相同。冬春季本地污染大,源在东南及正南方,夏秋季受本地和外来输送共同作用,本地源在东南方且占比小,LRT占比大。LRT受西北气流、西风气流和西南气流三支气流影响,污染严重时西南气流占主导,西风气流次之,污染较轻时西风气流或西北气流占主导,西北气流所传输的污染最少。该研究结果加深了对藏东南区域PAHs变化、输送特征的认识,为该区域大气污染治理提供了理论依据。展开更多
BACKGROUND Extrahepatic cholangiocarcinoma sarcoma is extremely rare in clinical practice.These cells consist of both epithelial and mesenchymal cells.Patient-derived cell lines that maintain tumor characteristics are...BACKGROUND Extrahepatic cholangiocarcinoma sarcoma is extremely rare in clinical practice.These cells consist of both epithelial and mesenchymal cells.Patient-derived cell lines that maintain tumor characteristics are valuable tools for studying the molecular mechanisms associated with carcinosarcoma.However,cholangiocarcinoma sarcoma cell lines are not available in cell banks.AIM To establish and characterize a new extrahepatic cholangiocarcinoma sarcoma cell line,namely CBC2T-2.METHODS We conducted a short tandem repeat(STR)test to confirm the identity of the CBC2T-2 cell line.Furthermore,we assessed the migratory and invasive properties of the cells and performed clonogenicity assay to evaluate the ability of individual cells to form colonies.The tumorigenic potential of CBC2T-2 cells was tested in vivo using nonobese diabetic/severe combined immunodeficient(NOD/SCID)mice.The cells were injected subcutaneously and tumor formation was observed.In addition,immunohistochemical analysis was carried out to examine the expression of epithelial marker CK19 and mesenchymal marker vimentin in both CBC2T-2 cells and xenografts.The CBC2T-2 cell line was used to screen the potential therapeutic effects of various clinical agents in patients with cholangiocarcinoma sarcoma.Lastly,whole-exome sequencing was performed to identify genetic alterations and screen for somatic mutations in the CBC2T-2 cell line.RESULTS The STR test showed that there was no cross-contamination and the results were identical to those of the original tissue.The cells showed round or oval-shaped epithelioid cells and mesenchymal cells with spindle-shaped or elongated morphology.The cells exhibited a high proliferation ratio with a doubling time of 47.11 h.This cell line has migratory,invasive,and clonogenic abilities.The chromosomes in the CBC2T-2 cells were polyploidy,with numbers ranging from 69 to 79.The subcutaneous tumorigenic assay confirmed the in vivo tumorigenic ability of CBC2T-2 cells in NOD/SCID mice.CBC2T-2 cells and xenografts were positive for both the epithelial marker,CK19,and the mesenchymal marker,vimentin.These results suggest that CBC2T-2 cells may have both epithelial and mesenchymal characteristics.The cells were also used to screen clinical agents in patients with cholangiocarcinoma sarcoma,and a combination of paclitaxel and gemcitabine was found to be the most effective treatment option.CONCLUSION We established the first human cholangiocarcinoma sarcoma cell line,CBC2T-2,with stable biogenetic traits.This cell line,as a research model,has a high clinical value and would facilitate the understanding of the pathogenesis of cholangiocarcinoma sarcoma.展开更多
This paper, using a revised Penman-Monteith model, computed the terrestrial surface humidity index of the Loess Plateau （China） based on climatic factors of monthly mean temperature, maximum temperature, minimum tem...This paper, using a revised Penman-Monteith model, computed the terrestrial surface humidity index of the Loess Plateau （China） based on climatic factors of monthly mean temperature, maximum temperature, minimum temperature, relative humidity, precipitation, wind speed and sunshine duration observed on the plateau from 1961 to 2008. The temporal-spatial distribution, anomaly distribution and sub-regional temporal variations of the terrestrial surface dry and wet conditions were analyzed as well. The results showed a decreasing trend in the annual average surface humidity from the southeast to the northwest in the research anna. Over the period of 1961-2008, an aridification tendency appeared sharply in the central interior region of the Loess Plateau, and less sharply in the middle part of the region. The border region showed the weakest tendency ol; aridification. It is clear that aridification diffused in all directions from the interior region. The spatial anomaly distribution of the terrestrial surface dry and wet conditions on the Loess Plateau can be divided into three key areas： the southern, western and eastern regions. The terrestrial annual humidity index displayed a significantly descending trend and showed remarkable abrupt changes from wet to dry in the years 1967, 1977 and 1979. In the above mentioned three key areas for dry and wet conditions, the terrestrial annual humidity index exhibited a fluctuation period of 3-4 years, while in the southern region, a fluctuation period of 7-8 years existed at the same time.展开更多
BACKGROUND Different types of periampullary diverticulum(PAD) may differentially affect the success of endoscopic retrograde cholangiopancreatography(ERCP) cannulation,but the clinical significance of the two current ...BACKGROUND Different types of periampullary diverticulum(PAD) may differentially affect the success of endoscopic retrograde cholangiopancreatography(ERCP) cannulation,but the clinical significance of the two current PAD classifications for cannulation is limited.AIM To verify the clinical value of our newly proposed PAD classification.METHODS A new PAD classification(Li-Tanaka classification) was proposed at our center.All PAD patients with native papillae who underwent ERCP from January 2012 to December 2017 were classified according to three classification systems, and the effects of various types of PAD on ERCP cannulation were compared.RESULTS A total of 3564 patients with native papillae were enrolled, including 967(27.13%)PAD patients and 2597(72.87%) non-PAD patients. In the Li-Tanaka classification, type Ⅰ PAD patients exhibited the highest difficult cannulation rate(23.1%, P = 0.01), and type Ⅱ and Ⅳ patients had the highest cannulation success rates(99.4% in type Ⅱ and 99.3% in type Ⅳ, P < 0.001). In a multivariableadjusted logistic model, the overall successful cannulation rate in PAD patients was higher than that in non-PAD patients [odds ratio(OR) = 1.87, 95% confidence interval(CI): 1.04-3037, P = 0.037]. In addition, compared to the non-PAD group,the difficulty of cannulation in the type Ⅰ PAD group according to the Li-Tanaka classification was greater(OR = 2.04, 95%CI: 1.13-3.68, P = 0.004), and the successful cannulation rate was lower(OR = 0.27, 95%CI: 0.11-0.66, P < 0.001),while it was higher in the type Ⅱ PAD group(OR = 4.44, 95%CI: 1.61-12.29, P <0.01).CONCLUSION Among the three PAD classifications, the Li-Tanaka classification has an obvious clinical advantage for ERCP cannulation, and it is helpful for evaluating potentially difficult and successful cannulation cases among different types of PAD patients.展开更多
BACKGROUND A previous study showed that irrigation with 100 mL saline reduced residual common bile duct(CBD)stones,which potentially cause recurrent stones after endoscopic retrograde cholangiopancreatography.AIM To d...BACKGROUND A previous study showed that irrigation with 100 mL saline reduced residual common bile duct(CBD)stones,which potentially cause recurrent stones after endoscopic retrograde cholangiopancreatography.AIM To determine whether saline irrigation can improve CBD clearance after lithotripsy.METHODS This prospective self-controlled study enrolled patients receiving mechanical lithotripsy for large(>1.2 cm)CBD stones.After occlusion cholangiography confirmed CBD stone clearance,peroral cholangioscopy(POC)was performed to determine clearance scores based on the number of residual stones.The amounts of residual stones spotted via POC were graded on a 5-point scale(score 1,worst;score 5,best).Scores were documented after only stone removal(control)and after irrigation with 50 mL and 100 mL saline,respectively.The stone composition was analyzed using infrared spectroscopy.RESULTS Between October 2018 and January 2020,47 patients had CBD clearance scores of 2.4±1.1 without saline irrigation,3.5±0.7 with 50 mL irrigation,and 4.6±0.6 with 100 mL irrigation(P<0.001).Multivariate analysis showed that CBD diameter>15 mm[odds ratio(OR)=0.08,95%confidence interval(CI):0.01-0.49;P=0.007]and periampullary diverticula(PAD)(OR=6.51,95%CI:1.08-39.21;P=0.041)were independent risk factors for residual stones.Bilirubin pigment stones constituted the main residual stones found in patients with PAD(P=0.004).CONCLUSION Irrigation with 100 mL of saline may not clear all residual CBD stones after lithotripsy,especially in patients with PAD and/or a dilated(>15 mm)CBD.Pigment residual stones are soft and commonly found in patients with PAD.Additional saline irrigation may be required to remove retained stones.展开更多
BACKGROUND Uric acid is the end product of purine metabolism.Previous studies have found that serum uric acid(SUA)levels are associated with the total cancer risk.However,due to the dual effect of uric acid on cancer,...BACKGROUND Uric acid is the end product of purine metabolism.Previous studies have found that serum uric acid(SUA)levels are associated with the total cancer risk.However,due to the dual effect of uric acid on cancer,the relationship between the SUA levels and most specific-site cancer remains unclear.AIM To investigate the associations between the SUA levels and incidence of hepatobiliary-pancreatic cancer.METHODS In this prospective cohort study,444462 participants free of cancer from the UK Biobank were included.The SUA levels were measured at baseline,and the incidence of hepatobiliary-pancreatic cancer was determined by contacting the cancer registry.The hazard ratios(HRs)and 95%confidence intervals(CIs)between the SUA levels and hepatobiliary-pancreatic cancer were investigated using multiple adjusted Cox regression models adjusted for potential confounders.RESULTS In total,920 participants developed liver,gallbladder,biliary tract or pancreatic cancer during a median of 6.6 yrs of follow-up.We found that the HR of pancreatic cancer in the highest SUA group was 1.77(95%CI:1.29-2.42)compared with that in the lowest group.After stratifying by gender,we further found that SUA was associated with an increased risk of pancreatic cancer only among the females(highest quartile vs lowest quartile HR 2.04,95%CI:1.35-3.08).Among the males,the SUA levels were positively associated with the gallbladder cancer risk(highest quartile vs lowest quartile HR 3.09,95%CI:1.28-7.46),but a U-shaped association with the liver cancer risk was observed(P-nonlinear=0.03).CONCLUSION SUA is likely to have gender-specific effects on hepatobiliary-pancreatic cancer.High SUA levels are a risk factor for pancreatic cancer in females and gallbladder cancer in males.A U-shaped association with the liver cancer risk was identified.展开更多
BACKGROUND Chronic hepatitis B virus infection remains a major global public health problem.Peginterferon-alpha-2a(PEG-IFN)has direct antiviral and immunoregulatory effects,and it has become one of the first choice dr...BACKGROUND Chronic hepatitis B virus infection remains a major global public health problem.Peginterferon-alpha-2a(PEG-IFN)has direct antiviral and immunoregulatory effects,and it has become one of the first choice drugs for the treatment of chronic hepatitis B(CHB).Cytokines play an important role in immunity,and they directly inhibit viral replication and indirectly determine the predominant pattern of the host immune response.AIM To determine the correlation between cytokine/chemokine expression levels and response to PEG-IFN treatment in patients with CHB.METHODS Forty-six kinds of cytokines were analyzed before PEG-IFN therapy and at 24 wk during therapy in 26 CHB patients.RESULTS The monokine induced by INF-γ(CXCL9)and serum interferon-inducible protein 10(IP-10)levels at baseline were higher in virological responders than in nonvirological responders(NRs)and decreased during treatment,whereas the NRs did not exhibit significant changes.The macrophage inflammatory protein 1d(MIP-1d)levels at baseline and during treatment were significantly higher in the virological responders than in the NRs,while thymus and activation-regulated chemokine(TARC)levels at baseline and during treatment were significantly lower in the virological responders than in the NRs.The CXCL9,IP-10,MIP-1d,and TARC baseline levels exhibited the expected effects for interferon treatment.The area under the receiver operating characteristic curve values of CXCL9,IP-10,MIP-1d,and TARC for predicting virological responses were 0.787,0.799,0.787,and 0.77(P=0.01,0.013,0.01,and 0.021),respectively.CONCLUSION We found that cytokine levels before and during treatment may represent potential biomarkers to select CHB patients who can respond to PEG-IFN.Therefore,cytokines can be used as an indicator of antiviral drug selection before CHB treatment.展开更多
BACKGROUND Most of study regarding periampullary diverticulum(PAD)impact on endoscopic retrograde cholangiopancreatography(ERCP)therapy for choledocholithiasis based on data from one endoscopy center and lacked to com...BACKGROUND Most of study regarding periampullary diverticulum(PAD)impact on endoscopic retrograde cholangiopancreatography(ERCP)therapy for choledocholithiasis based on data from one endoscopy center and lacked to compare the clinical characteristic of choledocholithiasis with PAD from different geographical patients.AIM To compare the choledocholithiasis clinical characteristics between two regional endoscopy centers and analyze impacts of clinical characteristics on ERCP methods for choledocholithiasis patients with PAD.METHODS Patients seen in two endoscopy centers(The First Hospital of Lanzhou University,Lanzhou,Gansu Province,China,and Kyoto Second Red Cross Hospital,Kyoto,Japan)underwent ERCP treatment for the first time between January 2012 and December 2017.The characteristics of choledocholithiasis with PAD were compared between the two centers,and their ERCP procedures and therapeutic outcomes were analyzed.RESULTS A total of 829 out of 3608 patients in the Lanzhou center and 241 out of 1198 in the Kyoto center had choledocholithiasis with PAD.Lots of clinical characteristics were significantly different between the two centers.The common bile duct(CBD)diameter was wider,choledocholithiasis size was lager and multiple CBD stones were more in the Lanzhou center patients than those in the Kyoto center patients(14.8±5.2 mm vs 11.6±4.2 mm,12.2±6.5 mm vs 8.2±5.3 mm,45.3%vs 20.3%,P<0.001 for all).In addition,concomitant diseases,such as acute cholangitis,gallbladder stones,obstructive jaundice,cholecystectomy,and acute pancreatitis,were significantly different between the two centers(P=0.03 to<0.001).In the Lanzhou center,CBD diameter and choledocholithiasis size were lower,and multiple CBD stones and acute cholangitis were less in non-PAD patients than those in PAD patients(13.4±5.1 mm vs 14.8±5.2 mm,10.3±5.4 mm vs 12.2±6.5,39%vs 45.3%,13.9%vs 18.5%,P=0.002 to<0.001).But all these characteristics were not significantly different in the Kyoto center.The proportions of endoscopic sphincterotomy(EST),endoscopic balloon dilatation(EPBD),and EST+EPBD were 50.5%,1.7%,and 42.5%in the Lanzhou center and 90.0%,0.0%,and 0.4%in the Kyoto center,respectively.However,the overall post-ERCP complication rate was not significantly different between the two centers(8.9%in the Lanzhou and 5.8%in the Kyoto.P=0.12).In the Lanzhou center,the difficulty rate in removing CBD stones in PAD was higher than in non-PAD group(35.3%vs 26.0%,P<0.001).But the rate was no significant difference between the two groups in Kyoto center.The residual rates of choledocholithiasis were not significantly different between the two groups in both centers.Post-ERCP complications occurred in 8.9%of the PAD patients and 8.1%of the non-PAD patients in the Lanzhou Center,and it occurred in 5.8%in PAD patients and 10.0%in non-PAD patients in the Kyoto center,all P>0.05.CONCLUSION Many clinical characteristics of choledocholithiasis patients with PAD were significantly different between the Lanzhou and Kyoto centers.The patients had larger and multiple stones,wider CBD diameter,and more possibility of acute cholangitis and obstructive jaundice in the Lanzhou center than those in the Kyoto center.The ERCP procedures to manage native duodenal papilla were different depending on the different clinical characteristics while the overall post-ERCP complications were not significantly different between the two centers.The stone residual rate and post-ERCP complications were not significantly different between choledocholithiasis patients with PAD and without PAD in each center.展开更多
Background:Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography(ERCP),the benefits and safety of high-carbohydrate fluid diet(CFD)intake 2 h before ERCP remain unclear.This...Background:Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography(ERCP),the benefits and safety of high-carbohydrate fluid diet(CFD)intake 2 h before ERCP remain unclear.This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients’recovery.Methods:This prospective,multicenter,randomized controlled trial involved 15 tertiary ERCP centers.A total of 1330 patients were randomized into CFD group(n=665)and fasting group(n=665).The CFD group received 400 mL of maltodextrin orally 2 h before ERCP,while the control group abstained from food/water overnight(>6 h)before ERCP.All ERCP procedures were performed using deep sedation with intravenous propofol.The investigators were blinded but not the patients.The primary outcomes included postoperative fatigue and abdominal pain score,and the secondary outcomes included complications and changes in metabolic indicators.The outcomes were analyzed according to a modified intention-to-treat principle.Results:The post-ERCP fatigue scores were significantly lower at 4 h(4.1±2.6 vs.4.8±2.8,t=4.23,P<0.001)and 20 h(2.4±2.1 vs.3.4±2.4,t=7.94,P<0.001)in the CFD group,with least-squares mean differences of 0.48(95%confidence interval[CI]:0.26-0.71,P<0.001)and 0.76(95%CI:0.57-0.95,P<0.001),respectively.The 4-h pain scores(2.1±1.7 vs.2.2±1.7,t=2.60,P=0.009,with a least-squares mean difference of 0.21[95%CI:0.05-0.37])and positive urine ketone levels(7.7%[39/509]vs.15.4%[82/533],χ^(2)=15.13,P<0.001)were lower in the CFD group.The CFD group had significantly less cholangitis(2.1%[13/634]vs.4.0%[26/658],χ^(2)=3.99,P=0.046)but not pancreatitis(5.5%[35/634]vs.6.5%[43/658],χ^(2)=0.59,P=0.444).Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla(odds ratio[OR]:0.61,95%CI:0.39-0.95,P=0.028)in the multivariable models.Conclusion:Ingesting 400 mL of CFD 2 h before ERCP is safe,with a reduction in post-ERCP fatigue,abdominal pain,and cholangitis during recovery.Trail Registration:ClinicalTrials.gov,No.NCT03075280.展开更多
Cholangiocarcinoma(CCA)is a bile duct malignancy with a dismal prognosis.This study systematically investigated the role of the ribosomal protein S6(RPS6)gene,which is dependent in CCA.We found that RPS6 upregulation ...Cholangiocarcinoma(CCA)is a bile duct malignancy with a dismal prognosis.This study systematically investigated the role of the ribosomal protein S6(RPS6)gene,which is dependent in CCA.We found that RPS6 upregulation in CCA tissues was correlated with a poor prognosis.Functional investigations have shown that alterations in RPS6 expression,both gain-and loss-of function could affect the proliferation of CCA cells.In xenograft tumor models,RPS6 overexpression enhances tumorigenicity,whereas RPS6 silencing reduces it.Integration analysis using RNA-seq and proteomics elucidated downstream signaling pathways of RPS6 depletion by affecting the cell cycle,especially DNA replication.Immunoprecipitation followed by mass spectrometry has identified numerous spliceosome complex proteins associated with RPS6.Transcriptomic profiling revealed that RPS6 affects numerous alternative splicing(AS)events,and combined with RNA immunoprecipitation sequencing,revealed that minichromosome maintenance complex component 7(MCM7)binds to RPS6,which regulates its AS and increases oncogenic activity in CCA.Targeting RPS6 with vivo phosphorodiamidate morpholino oligomer(V-PMO)significantly inhibited the growth of CCA cells,patient-derived organoids,and subcutaneous xenograft tumor.Taken together,the data demonstrate that RPS6 is an oncogenic regulator in CCA and that RPS6-V-PMO could be repositioned as a promising strategy for treating CCA.展开更多
Fibrosis resulting from pathological repair secondary to recurrent or persistent tissue damage often leads to organ failure and mortality.Biliary fibrosis is a crucial but easily neglected pathological feature in hepa...Fibrosis resulting from pathological repair secondary to recurrent or persistent tissue damage often leads to organ failure and mortality.Biliary fibrosis is a crucial but easily neglected pathological feature in hepatobiliary disorders,which may promote the development and progression of benign and malignant biliary diseases through pathological healing mechanisms secondary to biliary tract injuries.Elucidating the etiology and pathogenesis of biliary fibrosis is beneficial to the prevention and treatment of biliary diseases.In this review,we emphasized the importance of biliary fibrosis in cholangiopathies and summarized the clinical manifestations,epidemiology,and aberrant cellular composition involving the biliary ductules,cholangiocytes,immune system,fibroblasts,and the microbiome.We also focused on pivotal signaling pathways and offered insights into ongoing clinical trials and proposing a strategic approach for managing biliary fibrosis-related cholangiopathies.This review will offer a comprehensive perspective on biliary fibrosis and provide an important reference for future mechanism research and innovative therapy to prevent or reverse fibrosis.展开更多
Water injection for oil displacement is one of the most effective ways to develop fractured-vuggy carbonate reservoirs.With the increase in the number of rounds of water injection,the development effect gradually fail...Water injection for oil displacement is one of the most effective ways to develop fractured-vuggy carbonate reservoirs.With the increase in the number of rounds of water injection,the development effect gradually fails.The emergence of high-pressure capacity expansion and water injection technology allows increased production from old wells.Although high-pressure capacity expansion and water injection technology has been implemented in practice for nearly 10 years in fractured-vuggy reservoirs,its mechanism remains unclear,and the water injection curve is not apparent.In the past,evaluating its effect could only be done by measuring the injection-production volume.In this study,we analyze the mechanism of high-pressure capacity expansion and water injection.We propose a fluid exchange index for high-pressure capacity expansion and water injection and establish a discrete model suitable for high-pressure capacity expansion and water injection curves in fractured-vuggy reservoirs.We propose the following mechanisms:replenishing energy,increasing energy,replacing energy,and releasing energy.The above mechanisms can be identified by the high-pressure capacity expansion and water injection curve of the well HA6X in the Halahatang Oilfield in the Tarim Basin.By solving the basic model,the relative errors of Reservoirs I and II are found to be 1.9%and 1.5%,respectively,and the application of field examples demonstrates that our proposed high-pressure capacity expansion and water injection indicator curve is reasonable and reliable.This research can provide theoretical support for high-pressure capacity expansion and water injection technology in fracture-vuggy carbonate reservoirs.展开更多
Background:Gallbladder cancer(GBC)was once considered a contraindication for laparoscopic surgery,but it is becoming more common to use laparoscopic surgery for GBC treatment.The aim of this study was to analyze the l...Background:Gallbladder cancer(GBC)was once considered a contraindication for laparoscopic surgery,but it is becoming more common to use laparoscopic surgery for GBC treatment.The aim of this study was to analyze the long-and short-term outcomes of patients with more advanced T-staged GBC treated with curative intent as defined by the National Comprehensive Cancer Network(NCCN)after laparoscopic resection(LR)versus open resection(OR).Methods:A multicenter database was used to select consecutive GBC patients treated with curative-intent resection as defined by the NCCN between 2016 and 2020.The patients were divided into the LR group and the OR group.Propensity score matching(PSM)was used to eliminate selection bias.The endpoints were overall survival(OS),progression-free survival(PFS),and short-term outcomes.Risk factors that were independently associated with OS and PFS were identified.Results:Of 626 GBC patients treated with curative-intent resection,after PSM,51 patients were in the LR group and 153 patients were in the OR group.The LR group had more patients who were suitable to receive adjuvant chemotherapy(AC),a longer operation time,more harvested lymph nodes,and a lower overall morbidity rate.The rates of OS and PFS were not significantly different between the two groups.AC was independently associated with better OS and PFS.Conclusions:The overall morbidity of GBC patients after LR was lower,but the long-term outcomes between LR and OR were not significantly different.The GBC patients treated with LR were more likely to receive AC,and the use of AC after curative-intent resection of GBC helped achieve better long-term survival outcomes.展开更多
文摘为探究青藏高原东南部大气中多环芳烃(Polycyclic Aromatic Hydrocarbons,简称PAHs)的污染、源及输送特征,利用鲁朗地区(29.77°N,94.73°E)总悬浮颗粒物(Total Suspended Particles,简称TSP)和大气中的14种PAHs含量,结合同期气象环境数据进行了综合分析。结果表明,该地区TSP中PAHs和气相的PAHs质量浓度变化范围分别为0.22~5.05 ng m^(-3)和0.83~63.75 ng m^(-3),平均值分别为2.13 ng m^(-3)和11.33 ng m^(-3)。薪柴和柴油的燃烧是污染的主要方式,汽油燃烧等其他排放为次要方式。PAHs来自本地污染和远距离传输(Long Range Transmission,简称LRT)共同的影响。本地污染在四季各个源地均不相同。冬春季本地污染大,源在东南及正南方,夏秋季受本地和外来输送共同作用,本地源在东南方且占比小,LRT占比大。LRT受西北气流、西风气流和西南气流三支气流影响,污染严重时西南气流占主导,西风气流次之,污染较轻时西风气流或西北气流占主导,西北气流所传输的污染最少。该研究结果加深了对藏东南区域PAHs变化、输送特征的认识,为该区域大气污染治理提供了理论依据。
基金the National Natural Science Foundation of China,No.82060551and Lanzhou Chengguan District Science and Technology Planning Project,No.2019JSCX0092.
文摘BACKGROUND Extrahepatic cholangiocarcinoma sarcoma is extremely rare in clinical practice.These cells consist of both epithelial and mesenchymal cells.Patient-derived cell lines that maintain tumor characteristics are valuable tools for studying the molecular mechanisms associated with carcinosarcoma.However,cholangiocarcinoma sarcoma cell lines are not available in cell banks.AIM To establish and characterize a new extrahepatic cholangiocarcinoma sarcoma cell line,namely CBC2T-2.METHODS We conducted a short tandem repeat(STR)test to confirm the identity of the CBC2T-2 cell line.Furthermore,we assessed the migratory and invasive properties of the cells and performed clonogenicity assay to evaluate the ability of individual cells to form colonies.The tumorigenic potential of CBC2T-2 cells was tested in vivo using nonobese diabetic/severe combined immunodeficient(NOD/SCID)mice.The cells were injected subcutaneously and tumor formation was observed.In addition,immunohistochemical analysis was carried out to examine the expression of epithelial marker CK19 and mesenchymal marker vimentin in both CBC2T-2 cells and xenografts.The CBC2T-2 cell line was used to screen the potential therapeutic effects of various clinical agents in patients with cholangiocarcinoma sarcoma.Lastly,whole-exome sequencing was performed to identify genetic alterations and screen for somatic mutations in the CBC2T-2 cell line.RESULTS The STR test showed that there was no cross-contamination and the results were identical to those of the original tissue.The cells showed round or oval-shaped epithelioid cells and mesenchymal cells with spindle-shaped or elongated morphology.The cells exhibited a high proliferation ratio with a doubling time of 47.11 h.This cell line has migratory,invasive,and clonogenic abilities.The chromosomes in the CBC2T-2 cells were polyploidy,with numbers ranging from 69 to 79.The subcutaneous tumorigenic assay confirmed the in vivo tumorigenic ability of CBC2T-2 cells in NOD/SCID mice.CBC2T-2 cells and xenografts were positive for both the epithelial marker,CK19,and the mesenchymal marker,vimentin.These results suggest that CBC2T-2 cells may have both epithelial and mesenchymal characteristics.The cells were also used to screen clinical agents in patients with cholangiocarcinoma sarcoma,and a combination of paclitaxel and gemcitabine was found to be the most effective treatment option.CONCLUSION We established the first human cholangiocarcinoma sarcoma cell line,CBC2T-2,with stable biogenetic traits.This cell line,as a research model,has a high clinical value and would facilitate the understanding of the pathogenesis of cholangiocarcinoma sarcoma.
基金supported by the National Basic Research Program of China (2012CB955903,2012CB955304)the Special Fund for Public Welfare Industry(GYHY201106029,GYHY200806021)+2 种基金the National Natural Science Foundation of China (40830957)the China Meteorological Administration Special Program for Climatic Change(280200S011C00)the Drought Meteorology Science Research Program (IAM201111)
文摘This paper, using a revised Penman-Monteith model, computed the terrestrial surface humidity index of the Loess Plateau （China） based on climatic factors of monthly mean temperature, maximum temperature, minimum temperature, relative humidity, precipitation, wind speed and sunshine duration observed on the plateau from 1961 to 2008. The temporal-spatial distribution, anomaly distribution and sub-regional temporal variations of the terrestrial surface dry and wet conditions were analyzed as well. The results showed a decreasing trend in the annual average surface humidity from the southeast to the northwest in the research anna. Over the period of 1961-2008, an aridification tendency appeared sharply in the central interior region of the Loess Plateau, and less sharply in the middle part of the region. The border region showed the weakest tendency ol; aridification. It is clear that aridification diffused in all directions from the interior region. The spatial anomaly distribution of the terrestrial surface dry and wet conditions on the Loess Plateau can be divided into three key areas： the southern, western and eastern regions. The terrestrial annual humidity index displayed a significantly descending trend and showed remarkable abrupt changes from wet to dry in the years 1967, 1977 and 1979. In the above mentioned three key areas for dry and wet conditions, the terrestrial annual humidity index exhibited a fluctuation period of 3-4 years, while in the southern region, a fluctuation period of 7-8 years existed at the same time.
基金Supported by the National Natural Science Foundation of China,NO.31570509.
文摘BACKGROUND Different types of periampullary diverticulum(PAD) may differentially affect the success of endoscopic retrograde cholangiopancreatography(ERCP) cannulation,but the clinical significance of the two current PAD classifications for cannulation is limited.AIM To verify the clinical value of our newly proposed PAD classification.METHODS A new PAD classification(Li-Tanaka classification) was proposed at our center.All PAD patients with native papillae who underwent ERCP from January 2012 to December 2017 were classified according to three classification systems, and the effects of various types of PAD on ERCP cannulation were compared.RESULTS A total of 3564 patients with native papillae were enrolled, including 967(27.13%)PAD patients and 2597(72.87%) non-PAD patients. In the Li-Tanaka classification, type Ⅰ PAD patients exhibited the highest difficult cannulation rate(23.1%, P = 0.01), and type Ⅱ and Ⅳ patients had the highest cannulation success rates(99.4% in type Ⅱ and 99.3% in type Ⅳ, P < 0.001). In a multivariableadjusted logistic model, the overall successful cannulation rate in PAD patients was higher than that in non-PAD patients [odds ratio(OR) = 1.87, 95% confidence interval(CI): 1.04-3037, P = 0.037]. In addition, compared to the non-PAD group,the difficulty of cannulation in the type Ⅰ PAD group according to the Li-Tanaka classification was greater(OR = 2.04, 95%CI: 1.13-3.68, P = 0.004), and the successful cannulation rate was lower(OR = 0.27, 95%CI: 0.11-0.66, P < 0.001),while it was higher in the type Ⅱ PAD group(OR = 4.44, 95%CI: 1.61-12.29, P <0.01).CONCLUSION Among the three PAD classifications, the Li-Tanaka classification has an obvious clinical advantage for ERCP cannulation, and it is helpful for evaluating potentially difficult and successful cannulation cases among different types of PAD patients.
基金Supported by National Natural Science Foundation of China,No.81872036 and No.82060551.
文摘BACKGROUND A previous study showed that irrigation with 100 mL saline reduced residual common bile duct(CBD)stones,which potentially cause recurrent stones after endoscopic retrograde cholangiopancreatography.AIM To determine whether saline irrigation can improve CBD clearance after lithotripsy.METHODS This prospective self-controlled study enrolled patients receiving mechanical lithotripsy for large(>1.2 cm)CBD stones.After occlusion cholangiography confirmed CBD stone clearance,peroral cholangioscopy(POC)was performed to determine clearance scores based on the number of residual stones.The amounts of residual stones spotted via POC were graded on a 5-point scale(score 1,worst;score 5,best).Scores were documented after only stone removal(control)and after irrigation with 50 mL and 100 mL saline,respectively.The stone composition was analyzed using infrared spectroscopy.RESULTS Between October 2018 and January 2020,47 patients had CBD clearance scores of 2.4±1.1 without saline irrigation,3.5±0.7 with 50 mL irrigation,and 4.6±0.6 with 100 mL irrigation(P<0.001).Multivariate analysis showed that CBD diameter>15 mm[odds ratio(OR)=0.08,95%confidence interval(CI):0.01-0.49;P=0.007]and periampullary diverticula(PAD)(OR=6.51,95%CI:1.08-39.21;P=0.041)were independent risk factors for residual stones.Bilirubin pigment stones constituted the main residual stones found in patients with PAD(P=0.004).CONCLUSION Irrigation with 100 mL of saline may not clear all residual CBD stones after lithotripsy,especially in patients with PAD and/or a dilated(>15 mm)CBD.Pigment residual stones are soft and commonly found in patients with PAD.Additional saline irrigation may be required to remove retained stones.
基金Supported by National Natural Science Foundation of China,No.81872036.
文摘BACKGROUND Uric acid is the end product of purine metabolism.Previous studies have found that serum uric acid(SUA)levels are associated with the total cancer risk.However,due to the dual effect of uric acid on cancer,the relationship between the SUA levels and most specific-site cancer remains unclear.AIM To investigate the associations between the SUA levels and incidence of hepatobiliary-pancreatic cancer.METHODS In this prospective cohort study,444462 participants free of cancer from the UK Biobank were included.The SUA levels were measured at baseline,and the incidence of hepatobiliary-pancreatic cancer was determined by contacting the cancer registry.The hazard ratios(HRs)and 95%confidence intervals(CIs)between the SUA levels and hepatobiliary-pancreatic cancer were investigated using multiple adjusted Cox regression models adjusted for potential confounders.RESULTS In total,920 participants developed liver,gallbladder,biliary tract or pancreatic cancer during a median of 6.6 yrs of follow-up.We found that the HR of pancreatic cancer in the highest SUA group was 1.77(95%CI:1.29-2.42)compared with that in the lowest group.After stratifying by gender,we further found that SUA was associated with an increased risk of pancreatic cancer only among the females(highest quartile vs lowest quartile HR 2.04,95%CI:1.35-3.08).Among the males,the SUA levels were positively associated with the gallbladder cancer risk(highest quartile vs lowest quartile HR 3.09,95%CI:1.28-7.46),but a U-shaped association with the liver cancer risk was observed(P-nonlinear=0.03).CONCLUSION SUA is likely to have gender-specific effects on hepatobiliary-pancreatic cancer.High SUA levels are a risk factor for pancreatic cancer in females and gallbladder cancer in males.A U-shaped association with the liver cancer risk was identified.
基金Supported by National Natural Science Foundation of China,No.81872036Talent Innovation and Entrepreneurship Plan of Chengguan District of Lanzhou City,No.2019RCCX0038Science and Technology Plan of Chengguan District of Lanzhou City,No.2019JSXC0092.
文摘BACKGROUND Chronic hepatitis B virus infection remains a major global public health problem.Peginterferon-alpha-2a(PEG-IFN)has direct antiviral and immunoregulatory effects,and it has become one of the first choice drugs for the treatment of chronic hepatitis B(CHB).Cytokines play an important role in immunity,and they directly inhibit viral replication and indirectly determine the predominant pattern of the host immune response.AIM To determine the correlation between cytokine/chemokine expression levels and response to PEG-IFN treatment in patients with CHB.METHODS Forty-six kinds of cytokines were analyzed before PEG-IFN therapy and at 24 wk during therapy in 26 CHB patients.RESULTS The monokine induced by INF-γ(CXCL9)and serum interferon-inducible protein 10(IP-10)levels at baseline were higher in virological responders than in nonvirological responders(NRs)and decreased during treatment,whereas the NRs did not exhibit significant changes.The macrophage inflammatory protein 1d(MIP-1d)levels at baseline and during treatment were significantly higher in the virological responders than in the NRs,while thymus and activation-regulated chemokine(TARC)levels at baseline and during treatment were significantly lower in the virological responders than in the NRs.The CXCL9,IP-10,MIP-1d,and TARC baseline levels exhibited the expected effects for interferon treatment.The area under the receiver operating characteristic curve values of CXCL9,IP-10,MIP-1d,and TARC for predicting virological responses were 0.787,0.799,0.787,and 0.77(P=0.01,0.013,0.01,and 0.021),respectively.CONCLUSION We found that cytokine levels before and during treatment may represent potential biomarkers to select CHB patients who can respond to PEG-IFN.Therefore,cytokines can be used as an indicator of antiviral drug selection before CHB treatment.
文摘BACKGROUND Most of study regarding periampullary diverticulum(PAD)impact on endoscopic retrograde cholangiopancreatography(ERCP)therapy for choledocholithiasis based on data from one endoscopy center and lacked to compare the clinical characteristic of choledocholithiasis with PAD from different geographical patients.AIM To compare the choledocholithiasis clinical characteristics between two regional endoscopy centers and analyze impacts of clinical characteristics on ERCP methods for choledocholithiasis patients with PAD.METHODS Patients seen in two endoscopy centers(The First Hospital of Lanzhou University,Lanzhou,Gansu Province,China,and Kyoto Second Red Cross Hospital,Kyoto,Japan)underwent ERCP treatment for the first time between January 2012 and December 2017.The characteristics of choledocholithiasis with PAD were compared between the two centers,and their ERCP procedures and therapeutic outcomes were analyzed.RESULTS A total of 829 out of 3608 patients in the Lanzhou center and 241 out of 1198 in the Kyoto center had choledocholithiasis with PAD.Lots of clinical characteristics were significantly different between the two centers.The common bile duct(CBD)diameter was wider,choledocholithiasis size was lager and multiple CBD stones were more in the Lanzhou center patients than those in the Kyoto center patients(14.8±5.2 mm vs 11.6±4.2 mm,12.2±6.5 mm vs 8.2±5.3 mm,45.3%vs 20.3%,P<0.001 for all).In addition,concomitant diseases,such as acute cholangitis,gallbladder stones,obstructive jaundice,cholecystectomy,and acute pancreatitis,were significantly different between the two centers(P=0.03 to<0.001).In the Lanzhou center,CBD diameter and choledocholithiasis size were lower,and multiple CBD stones and acute cholangitis were less in non-PAD patients than those in PAD patients(13.4±5.1 mm vs 14.8±5.2 mm,10.3±5.4 mm vs 12.2±6.5,39%vs 45.3%,13.9%vs 18.5%,P=0.002 to<0.001).But all these characteristics were not significantly different in the Kyoto center.The proportions of endoscopic sphincterotomy(EST),endoscopic balloon dilatation(EPBD),and EST+EPBD were 50.5%,1.7%,and 42.5%in the Lanzhou center and 90.0%,0.0%,and 0.4%in the Kyoto center,respectively.However,the overall post-ERCP complication rate was not significantly different between the two centers(8.9%in the Lanzhou and 5.8%in the Kyoto.P=0.12).In the Lanzhou center,the difficulty rate in removing CBD stones in PAD was higher than in non-PAD group(35.3%vs 26.0%,P<0.001).But the rate was no significant difference between the two groups in Kyoto center.The residual rates of choledocholithiasis were not significantly different between the two groups in both centers.Post-ERCP complications occurred in 8.9%of the PAD patients and 8.1%of the non-PAD patients in the Lanzhou Center,and it occurred in 5.8%in PAD patients and 10.0%in non-PAD patients in the Kyoto center,all P>0.05.CONCLUSION Many clinical characteristics of choledocholithiasis patients with PAD were significantly different between the Lanzhou and Kyoto centers.The patients had larger and multiple stones,wider CBD diameter,and more possibility of acute cholangitis and obstructive jaundice in the Lanzhou center than those in the Kyoto center.The ERCP procedures to manage native duodenal papilla were different depending on the different clinical characteristics while the overall post-ERCP complications were not significantly different between the two centers.The stone residual rate and post-ERCP complications were not significantly different between choledocholithiasis patients with PAD and without PAD in each center.
文摘Background:Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography(ERCP),the benefits and safety of high-carbohydrate fluid diet(CFD)intake 2 h before ERCP remain unclear.This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients’recovery.Methods:This prospective,multicenter,randomized controlled trial involved 15 tertiary ERCP centers.A total of 1330 patients were randomized into CFD group(n=665)and fasting group(n=665).The CFD group received 400 mL of maltodextrin orally 2 h before ERCP,while the control group abstained from food/water overnight(>6 h)before ERCP.All ERCP procedures were performed using deep sedation with intravenous propofol.The investigators were blinded but not the patients.The primary outcomes included postoperative fatigue and abdominal pain score,and the secondary outcomes included complications and changes in metabolic indicators.The outcomes were analyzed according to a modified intention-to-treat principle.Results:The post-ERCP fatigue scores were significantly lower at 4 h(4.1±2.6 vs.4.8±2.8,t=4.23,P<0.001)and 20 h(2.4±2.1 vs.3.4±2.4,t=7.94,P<0.001)in the CFD group,with least-squares mean differences of 0.48(95%confidence interval[CI]:0.26-0.71,P<0.001)and 0.76(95%CI:0.57-0.95,P<0.001),respectively.The 4-h pain scores(2.1±1.7 vs.2.2±1.7,t=2.60,P=0.009,with a least-squares mean difference of 0.21[95%CI:0.05-0.37])and positive urine ketone levels(7.7%[39/509]vs.15.4%[82/533],χ^(2)=15.13,P<0.001)were lower in the CFD group.The CFD group had significantly less cholangitis(2.1%[13/634]vs.4.0%[26/658],χ^(2)=3.99,P=0.046)but not pancreatitis(5.5%[35/634]vs.6.5%[43/658],χ^(2)=0.59,P=0.444).Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla(odds ratio[OR]:0.61,95%CI:0.39-0.95,P=0.028)in the multivariable models.Conclusion:Ingesting 400 mL of CFD 2 h before ERCP is safe,with a reduction in post-ERCP fatigue,abdominal pain,and cholangitis during recovery.Trail Registration:ClinicalTrials.gov,No.NCT03075280.
基金the National Key Research and Development Program of China(2022YFC2407405)National Natural Science Foundation of China(82060551,32160230)+2 种基金Natural Science foundation of Gansu Province(22JR5RA891,China)Gansu Provincial Health Industry Research Program(GSWSQH2021-001,China)Science and Technology Bureau Talent Innovation Program of Chengguan District(2019RCCX0038,China).
文摘Cholangiocarcinoma(CCA)is a bile duct malignancy with a dismal prognosis.This study systematically investigated the role of the ribosomal protein S6(RPS6)gene,which is dependent in CCA.We found that RPS6 upregulation in CCA tissues was correlated with a poor prognosis.Functional investigations have shown that alterations in RPS6 expression,both gain-and loss-of function could affect the proliferation of CCA cells.In xenograft tumor models,RPS6 overexpression enhances tumorigenicity,whereas RPS6 silencing reduces it.Integration analysis using RNA-seq and proteomics elucidated downstream signaling pathways of RPS6 depletion by affecting the cell cycle,especially DNA replication.Immunoprecipitation followed by mass spectrometry has identified numerous spliceosome complex proteins associated with RPS6.Transcriptomic profiling revealed that RPS6 affects numerous alternative splicing(AS)events,and combined with RNA immunoprecipitation sequencing,revealed that minichromosome maintenance complex component 7(MCM7)binds to RPS6,which regulates its AS and increases oncogenic activity in CCA.Targeting RPS6 with vivo phosphorodiamidate morpholino oligomer(V-PMO)significantly inhibited the growth of CCA cells,patient-derived organoids,and subcutaneous xenograft tumor.Taken together,the data demonstrate that RPS6 is an oncogenic regulator in CCA and that RPS6-V-PMO could be repositioned as a promising strategy for treating CCA.
基金supported by the National Key Research and Development Program of China (2022YFC2407405)the Joint Research Fund Major Project of Gansu Province (23JRRA1488)the Medical Innovation and Development Project of Lanzhou University (lzuyxcx-2022-157).
文摘Fibrosis resulting from pathological repair secondary to recurrent or persistent tissue damage often leads to organ failure and mortality.Biliary fibrosis is a crucial but easily neglected pathological feature in hepatobiliary disorders,which may promote the development and progression of benign and malignant biliary diseases through pathological healing mechanisms secondary to biliary tract injuries.Elucidating the etiology and pathogenesis of biliary fibrosis is beneficial to the prevention and treatment of biliary diseases.In this review,we emphasized the importance of biliary fibrosis in cholangiopathies and summarized the clinical manifestations,epidemiology,and aberrant cellular composition involving the biliary ductules,cholangiocytes,immune system,fibroblasts,and the microbiome.We also focused on pivotal signaling pathways and offered insights into ongoing clinical trials and proposing a strategic approach for managing biliary fibrosis-related cholangiopathies.This review will offer a comprehensive perspective on biliary fibrosis and provide an important reference for future mechanism research and innovative therapy to prevent or reverse fibrosis.
基金supported by the China Postdoctoral Science Foundation(No.M2019650965)Major R&D Plan of Sichuan Province(No.2020YFQ0034)the National Natural Science Fund Projects(Grant No.51804253).
文摘Water injection for oil displacement is one of the most effective ways to develop fractured-vuggy carbonate reservoirs.With the increase in the number of rounds of water injection,the development effect gradually fails.The emergence of high-pressure capacity expansion and water injection technology allows increased production from old wells.Although high-pressure capacity expansion and water injection technology has been implemented in practice for nearly 10 years in fractured-vuggy reservoirs,its mechanism remains unclear,and the water injection curve is not apparent.In the past,evaluating its effect could only be done by measuring the injection-production volume.In this study,we analyze the mechanism of high-pressure capacity expansion and water injection.We propose a fluid exchange index for high-pressure capacity expansion and water injection and establish a discrete model suitable for high-pressure capacity expansion and water injection curves in fractured-vuggy reservoirs.We propose the following mechanisms:replenishing energy,increasing energy,replacing energy,and releasing energy.The above mechanisms can be identified by the high-pressure capacity expansion and water injection curve of the well HA6X in the Halahatang Oilfield in the Tarim Basin.By solving the basic model,the relative errors of Reservoirs I and II are found to be 1.9%and 1.5%,respectively,and the application of field examples demonstrates that our proposed high-pressure capacity expansion and water injection indicator curve is reasonable and reliable.This research can provide theoretical support for high-pressure capacity expansion and water injection technology in fracture-vuggy carbonate reservoirs.
文摘Background:Gallbladder cancer(GBC)was once considered a contraindication for laparoscopic surgery,but it is becoming more common to use laparoscopic surgery for GBC treatment.The aim of this study was to analyze the long-and short-term outcomes of patients with more advanced T-staged GBC treated with curative intent as defined by the National Comprehensive Cancer Network(NCCN)after laparoscopic resection(LR)versus open resection(OR).Methods:A multicenter database was used to select consecutive GBC patients treated with curative-intent resection as defined by the NCCN between 2016 and 2020.The patients were divided into the LR group and the OR group.Propensity score matching(PSM)was used to eliminate selection bias.The endpoints were overall survival(OS),progression-free survival(PFS),and short-term outcomes.Risk factors that were independently associated with OS and PFS were identified.Results:Of 626 GBC patients treated with curative-intent resection,after PSM,51 patients were in the LR group and 153 patients were in the OR group.The LR group had more patients who were suitable to receive adjuvant chemotherapy(AC),a longer operation time,more harvested lymph nodes,and a lower overall morbidity rate.The rates of OS and PFS were not significantly different between the two groups.AC was independently associated with better OS and PFS.Conclusions:The overall morbidity of GBC patients after LR was lower,but the long-term outcomes between LR and OR were not significantly different.The GBC patients treated with LR were more likely to receive AC,and the use of AC after curative-intent resection of GBC helped achieve better long-term survival outcomes.
