1.Effect of neferine on proliferation and invasion of human hepatocellular carcinoma cell line HepG2 and Bel-7402
Yajun ZHOU ; Jing SHI ; Geng TIAN ; Hanxin ZHOU ; Guoquan GAO
Chinese Pharmacological Bulletin 2016;32(11):1539-1542
Aim To investigate the effect of neferine on proliferation and invasion of human hepatocellular car-cinoma. Methods HepG2 and Bel-7402 cells were cultured in vitro with different concentrations of nefer-ine, then cell proliferation was observed by CCK-8 as-say; cell invasion was observed by transwell invasion assay; the protein expression of RhoA, RhoC and ROCK was detected by Western blot. Results CCK-8 results showed that neferine could significantly inhibit cell proliferation in a dose-dependent manner compared with the control group. Transwell invasion assay showed that cell invasion was significantly decreased with neferine 3 μmol · L-1 . Western blot results showed that RhoA, RhoC and ROCK protein expres-sion was decreased when neferine was co-incubated with hepatocellular carcinoma cells. Conclusion Nef-erine can inhibit proliferation and invasion of HepG2 and Bel-7402 cells, which is mediated mainly by the inhibition of RhoA, RhoC and ROCK protein expres-sion.
2.Features and diagnosis of computed tomography and magnetic resonance imaging on autoimmune pancreatitis
Zefeng WANG ; Haijun WANG ; Junjing ZHANG ; Yajun GENG ; Jianjun REN
Chinese Journal of Digestive Surgery 2017;16(1):95-101
Objective To summarize the features of computed tomography (CT) and magnetic resonance imaging (MRI) of autoimmune pancreatitis (AIP) and investigate the key points of diagnosis and identification.Methods The retrospective and descriptive study was conducted.The clinical data of 21 patients with AIP who were admitted to the Affiliated Hospital of Inner Mongolia Medical University between February 2012 and February 2015 were collected.All the patients underwent plain and enhanced scans of CT and MRI,and magnetic resonanced cholangio-pancreatography (MRCP),and then received hormone therapy.Eleven patients with pancreatic cancer and 11 normal subjects who were diagnosed by MRI in the same period were selected,and apparent diffusion coefficient (ADC) was calculated and compared.Observation indicators:(1) situation of imaging examination:① pancreatic manifestations:density,signal,atrophy,calcification and enlargement of pancreas,change of pancreatic duct,② manifestations out of pancreas:changes of biliary tract system and kidney,③ diffusion weighted imaging (DWI) and ADC:comparisons of ADC among AIP,pancreatic cancer and normal pancreas;(2) diagnosis;(3) treatment and follow-up.The follow-up using outpatient examination and telephone interview was performed to detect the clinical symptoms and signs up to February 2016.Measurement data with normal distribution were represented as (-x)-± s.Comparisons among groups were done using one-way ANOVA.Pairwise comparison was analyzed by Dunnett'T3 test.Results (1) Situation of imaging examination:Of 21 patients,17 received scan of CT and 11 received scan of MRI (7 combined with scan of CT).① Pancreatic manifestations:14 patients had diffuse enlargement of pancreas,with full edge and “sausage-like” change.Plain scan of CT showed uniform isodense shadow,and enhanced scan showed that reduced enhancement in arterial phase and gradually homogenous enhancement in portal vein phase and lag phase with no enhancement in edge of pancreas.Plain scan of MRI showed lesions were manifested as slight hypointensity on T1 weighted imaging (T1WI),slight hyperintensity on T2WI and hyperintensity on DWI.Enhanced scan of MRI showed delayed enhancement,edge of lesions was manifested as slight hypointensity on T1WI and T2WI,without enhancement.Atrophy and calcification of pancreas:3 patients had atrophy of pancreatic parenchyma in which scattered calcification were seen.Enlargement of pancreas:4 patients had localized enlargement of pancreas showing “false tumor-like” change,including 2 with localized enlargement in head of pancreas.Change of pancreatic duct:MRCP showed that diffuse stenosis,local stenosis and local dilatation of pancreatic ducts were respectively detected in 4,3 and 1 patients.② Manifestations out of pancreas:11 patients had changes of biliary tract system,showing intrahepatic bile duct and common bile duct dilation,partial stenosis and extensive bile duct wall thickening.Enhanced scan of MRI showed there was obvious enhancement of bile duct wall.MRCP of 4 patients showed that the beak-like stenosis was seen in the distal common bile duct.Three patients had kidney changes,enhanced scan of CT showed that kidney demonstrated patch-shape hypodense shadow in arterial phase and homogenous enhancement of patch-shape hypodense shadow in lag phase,and plain scan of MRI showed that kidney lesions demonstrated equal signal on T1WI fat suppression (FS) and patch-shape low signal on T2WI FS.Lesions had gradually homogenous enhancement in substance phase and lag phase.③ DWI and ADC:lesions in patients with AIP and pancreatic cancer demonstrated high signal on DWI (b =1 000 s/mm2) compared with adjacent tissues (no involvement in pancreas or normal pancreatic parenchyma),ADC of pancreas in patients with AIP,with pancreatic cancer and with normal population was (0.001 30 ± 0.000 35)mm2/s,(0.000 80 ± 0.000 14) mm2/s and (0.001 60-± 0.000 24) mm2/s,respectively,with a statistically significant difference (F =30.409,P < 0.05).There were statistically significant differences between patients with pancreatic cancer and patients with AIP or normal population (P < 0.05) and no statistically significant difference between patients with AIP and with normal population (P > 0.05).(2) Diagnosis:11 patients were diagnosed by CT examination,with a diagnostic accuracy of 11/17.Eight patients were diagnosed by MRI examination,with a diagnostic accuracy of 8/11.One patient was misdiagnosed as cancer of pancreatic head by CT and MRI examinations,and 1 was misdiagnosed as cancer in the distal common bile duct.(3) Treatment and follow-up:21 patients underwent regular hormone therapy,and 40 mg prednisolone was given orally a daily for 3-4 weeks and then gradually reduced to 5 mg up to complete relief of the symptoms.All the 21 patients were followed up for 12-45 months.Of 17 patients with abdominal pain and distension,symptoms of 7 patients disappeared and symptoms of 10 patients decreased or occasionally occurred.Of 10 patients associated with jaundice,symptoms of 7 and 2 patients disappeared and decreased,respectively,and symptoms of 1 patient subsided.Conclusion CT and MRI examinations of pancreas demonstrate “sausage-like” and “false tumor-like” changes,the non-neoplastic bile and pancreatic duct stenosis combined with IgG4 related diseases in other organs is an important imaging evidence for diagnosis and differential diagnosis of AIP.
3.Imaging features and diagnosis of hepatic cystic echinococcosis
Zefeng WANG ; Junjing ZHANG ; Yajun GENG ; Jianxiang NIU ; Jianjun REN
Chinese Journal of Digestive Surgery 2015;14(11):963-967
Objective To summarize the features of computed tomography (CT) and magnetic resonance imaging (MRi) of hepatic cystic echinococcosis, and investigate the key points of identification and diagnosis.Methods The clinical data of 58 patients with hepatic cystic echinococcosis who were admitted to the Affiliated Hospital of Inner Mongolia Medical University from August 2011 to August 2014 were retrospectively analyzed.Patients received plain and enhanced scan of CT and MRI.Hepatic cystic echinococcosis was divided into the 5 types according to the literatures, including unilocular echinococcasis in type Ⅰ, multivesicular hydatid cysts in type Ⅱ, anechoic content with detachment of laminated membrane from the cyst wall in type Ⅲ, calcification of lesions in type Ⅳ and mixed echinococcosis in type Ⅴ.Patients who were diagnosed as with definite or suspected hepatic cystic echinococcosis underwent surgery.The follow-up including observing the recurrence of hepatic cystic echinococcosis was performed by outpatient examination and telephone interview at postoperative month 3, 6, 12 for 1 year and then once every year up to August 2015, and was ended if there was no recurrence for more than 5 years.Results (1) The results of CT and MRI examinations: of the 58 patients, 54 received scan of CT and 21 received scan of MRI.Seventeen patients were detected in type Ⅰ with clear-boundary and low-density cystic lesions by CT examination;MRI examinations showed there were single or multiple, round or oval abnormal signal including low T1WI signal, high T2 WI signal and low T1 WI and T2WI signal of cyst wall.Thirteen patients were detected in type Ⅱ, CT examination showed the daughter cysts of multiple sizes were found in the mother cyst, arranged in honeycomb or wheel shape;MRI examination showed there were lower T1 WI signal in the daughter cyst and higher T2 WI signal in the daughter cyst compared with signal in the mother cyst, and low signal in the cyst wall of the daughter cyst and mother cyst.Six patients were detected in type Ⅲ with capsule in capsule sign and water snake sign by CT examination and ribbon sign by MRI examination.Thirteen patients were detected in type Ⅳ, CT examination showed there were irregular high-density calcified shadow with the performances for return sample or sample volume skins changes.Nine patients in type Ⅴ had more than 2 kinds of lesions.(2) Diagnosis: 4 patients were misdiagnosed by CT examination including 3 with preoperative diagnosis of hepatic cyst and 1 with preoperative diagnosis of metastatic carcinoma of liver, with an accurate rate of diagnosis of 92.6% (50/54).Two patients with preoperative diagnosis of hepatic cystic adenocarcinoma were misdiagnosed by MRI examination, with an accurate rate of diagnosis of 90.5% (19/21).(3) Treatment and follow-up: 58 patients underwent surgery, including 40 undergoing internal capsule removal with external capsule suturing (31 with open operation and 9 with laparoscopic operation), 10 undergoing partial hepatectomy and 8 undergoing external capsule enucleation.Of 58 patients, 3 were complicated with effusion of residual cavity, 2 with unclosed external capsule, 1 with bile leakage and then was cured after 4-8 week drainage.Fifty patients were followed up for 12.0-48.0 months with a median time of 27.1 months and a follow-up rate of 86.2% (50/58).During the follow-up, 1 patient undergoing internal capsule removal had recurrence at postoperative month 8 and was cured by CT-guided interventional therapy using absolute alcohol, and other patients had no recurrence.Conclusions There was a higher accuracy in CT and MRI examinations for hepatic cystic echinococcosis.Honeycomb and wheel shapes are characteristic findings of hepatic cystic echinococcosis in type Ⅱ.The characteristic performances of CT examination for hepatic cystic echinococcosis in type Ⅲ are capsule in capsuleand water snake signs, and characteristic performances of MRI examination is ribbon sign.The ring-like enhancement of edge by MRI examination is an essential of identification and diagnosis between hepatic cystic echinococcosis and hepatic cyst, and irregular calcification is a differential point between hepatic echinococcosis and hepatic tumor.
4.Clinical analysis of emergency ERCP for acute biliary-pancreatic diseases
Meng WANG ; Guangyi WANG ; Ping ZHANG ; Guoyue Lü ; Yajun GENG ; Qiushi FENG
Chinese Journal of General Surgery 2011;26(8):671-673
Objectiye To investigate the clinical application value of emergency therapeutic encoscopic retrograde cholangio-pancreatography (ERCP) on acute biliary-pancreatic diseases.Methods Duodenoscope was applied on the emergency treatment for 103 patients of acute biliary-pancreatic diseases from March 2007 to May 2010. According to patients' conditions, the examination of ERCP,endoscopic nasobiliary drainage (ENBD) and endoscopic sphincterotomy (EST) were carried out. The papilla sphincter was slivered by needle knife under the circumstances of the stone incarceration in the papilla,then calculus was removed by net basket. ENBD or endoscopic retrograde biliary drainage (ERBD)was placed according to the state of an illness. Statistical analysis was made by SPSS 13.0 software with a 2 × 2 table analysis, Comparison of ratio were determined with x2 test, a value less than 0. 05 was considered as significant. Results Of 103 cases, the success rate of endoscopic treatment was 97. 1% ( 100/103 ).Among 100 cases, 25cases (24. 3% ) were treated with ERCP and ENBD/ERBD; 12 cases (11.7%) were treated with ERCP, needle knife fenestration and ENBD; 67 cases (65. 1% ) were treated with ERCP,EST, calculus removal and ENBD; 8 cases (7. 8% ) were treated with ERCP, EST and ERBD. Of 100 cases one (1.0%) suffered from postoperative hemorrhage of duodenal papilla, which was cured by endoscopic hemostasis. Compared with selective cases those undergoing emergency ERCP often needed two stage procedures (P = 0. 010), but there are no statistical differences between two groups in success rate (P = 0. 122). Conclusions Emergency ERCP are safe and effective in acute biliary-pancreatic diseases.
5.Correlation between thyroid nodules and the components of metabolic syndrome
Xiaoyan WANG ; Yajun WANG ; Hua HAO ; Mao MA ; Hui GENG ; Jingsen SHI
Journal of Xi'an Jiaotong University(Medical Sciences) 2017;38(1):151-153
ABSTRACT:Objective To investigate the prevalence of thyroid nodules in Xi’an City by ultrasonography and study the correlation between thyroid nodules and the components of metabolic syndrome.Methods We recruited 4 527 subjects in this cross-sectional study and divided them into thyroid nodules (TN)group and non-thyroid nodules (NTN)group.The height,weight,blood pressure,blood sugar,lipid,and serum uric acid were measured and analyzed.The relationship between thyroid nodules and thyroid function was assessed in the subjects who received TT3,TT4,TSH,TGAB,and TPOAB tests.Results ① The prevalence of thyroid nodules was 31.8% and was significantly higher in the female patients (38.4% vs.27.1%,χ2=64.44,P<0.001).However,the prevalence of metabolic syndrome was 9.1% and was significantly higher in the male ones (11.4% vs.5.9%,χ2=40.39,P<0.001).② Compared with that in NTN group,TT3 in TN group was significantly increased (t=6.04,P<0.001), but the other indexes did not obviously change in the two groups (P>0.05).③ Age,systolic blood pressure,and TG,LDL-C and serum uric acid levels were remarkably higher in TN group than in NTN group (P<0.001 ). Conclusion The prevalence of thyroid nodules in Xi’an City is noticeably high.High systolic blood pressure level, dyslipidemia and elevated uric acid are associated with thyroid nodules.Therefore,screening and management of the individuals with aforementioned characteristics deserve more attention.
6.Clinical features and treatment of residual gallbladder lesions after cholecystectomy
Yajun GENG ; Shudong LI ; Xingkai MENG ; Chengwang YANG ; Zefeng WANG ; Tao HE ; Wanxiang WANG ; Zhenxia WANG ; Jianjun REN
Chinese Journal of Digestive Surgery 2017;16(4):375-379
Objective To investigate the clinical features and treatment of residual gallbladder lesions after cholecystectomy.Methods The retrospective cross-sectional study was conducted.The clinicopathological data of 83 patients with residual gallbladder lesions after cholecystectomy who were admitted to the Affiliated Hospital of Inner Mongolia Medical University between January 2009 and April 2016 were collected.Among the 83 patients,74 had residual gallbladder (41 combined with bile duct stones and 33 with simple residual gallbladder)and 9 had simple residual bile duct stones.Patients received laboratory and imaging examinations,and then selected suitable surgery according to residual lesions.Observation indicators included:(1) clinical features:medical history,clinical manifestation,features of laboratory and imaging examinations;(2) surgical and postoperative situations:surgical procedure,operation time,volume of intraoperative blood loss,time of drainagetube removal,postoperative complications and duration of postoperative hospital stay;(3) postoperative pathological examination;(4) follow-up situation.Follow-up using outpatient examination and telephone interview was performed to detect survival of patients and recurrence of lesions using abdomen color Doppler ultrasound up to October 2016.Measurement data with normal distribution were represented as ~ ±s.Results (1) Clinical features:① medical history:all the 83 patients had histories of cholecystectomy,including 57 with emergency operation and 26 with selective operation.② Clinical manifestation:initial clinical manifestation occurred at 1-324 months postoperatively,with an average time of 96 months.Of 83 patients,49 had right upper abdominal colic associated with right shoulder or back rediating pain,fever,nausea and vomiting,24 had jaundice as the main symptoms,8 had gradually worse conditions,with right upper quadrant abdominal pain,chills and fever associated with jaundice in the advanced stage and 2 had abdominal discomfort associated with incomplete intestinal obstruction.③ Laboratory examination:elevated alanine transaminase (ALT) and aspartate transaminase (AST) levels were detected in 48 patients,elevated total bilirubin (TBil) level in 28 patients and elevated serum and urinary amylase level in 4 patients,respectively.④ Imaging examination:of 83 patients,77 had positive results of magnetic resonanced eholangio-pancreatography (MRCP),43 had positive results of abdominal color Doppler ultrasound and 39 (4 combined with pancreatitis) had positive results of abdominal computed tomography (CT).(2) Surgical and postoperative situations:all the 83 patients underwent surgery.Of 74 patients with residual gallbladder,72 underwent residual gallbladder resection (of 41 combined with bile duct stones,35 undergoing residual gallbladder resection + bill duct exploration and removing the stone + T-tube drainage,6 initially undergoing endoscopic sphincterotomy for removing bile duct stones and then residual gallbladder resection and 31 undergoing simple residual gallbladder resection),1 combined with residual gallbladder cancer underwent residual gallbladder resection + common bile duct resection + hepatic duct-jejunum internal drainage and 1 combined with residual gallbladder cancer and common bile duct space-occupying lesion underwent palliative biliary-enterostomy.Nine patients with simple residual bile duct stones underwent endoscopic sphincterotomy for removing bile duct stones.Operation time,volume of intraoperative blood loss,time of drainage-tube removal and duration of postoperative hospital stay were (92±39)minutes,(63±12)mL,(5±4)days and (9±5)days in 74 patients with residual gallbladder,respectively.There was no severe postoperative complication.Operation time,volume of intraoperative blood loss and duration of postoperative hospital stay were (57±33)minutes,(25±9)mL and (5 ± 3) days in 9 patients with simple residual bile duct stones,respectively.No severe complication was occurred in 9 patients.(3) Postoperative pathological examination:the length of residual cystic duct in 74 patients with residual gallbladder was (2.8 ± 1.0) cm,combining with stones.Of 74 patients,simple hyperplasia of residual gallbladder were detected in 54 patients,dysplasia in 14 patients,tumor-like hyperplasia and benign tumor in 4 patients and adenocarcinoma in 2 patients.(4) Follow-up situation:all the 83 patients were followed up for 6-71 months,with a median time of 33 months.Eighty-one patients were healthy survival,without recurrence of lesions.One patient had recurrence of bile duct stones at 34 months postoperatively,and then was cured by choledochojejunostomy,without recurrence up to the end of follow-up.One patient with residual gallbladder cancer complicated with common bile duct space-occupying lesion died at 9 months postoperatively.Conclusions Patients have recurrent right upper abdominal colic associated with right shoulder or back rediating pain,fever and jaundice after cholecystectomy,and lesions of residual gallbladder or bile duct stones should be considered.Reoperation is safe and feasible for patients,with a good clinical outcome.
7.Gene expression profiling in porcine fetal thymus.
Yanjiong CHEN ; Shengbin LI ; Lin YE ; Jianing GENG ; Yajun DENG ; Songnian HU
Genomics, Proteomics & Bioinformatics 2003;1(2):171-172
To obtain an initial overview of gene diversity and expression pattern in porcine thymus, 11,712 ESTs (Expressed Sequence Tags) from 100-day-old porcine thymus (FTY) were sequenced and 7,071 cleaned ESTs were used for gene expression analysis. Clustered by the PHRAP program, 959 contigs and 3,074 singlets were obtained. Blast search showed that 806 contigs and 1,669 singlets (totally 5,442 ESTs) had homologues in GenBank and 1,629 ESTs were novel. According to the Gene Ontology classification, 36.99% ESTs were cataloged into the gene expression group, indicating that although the functional gene (18.78% in defense group) of thymus is expressed in a certain degree, the 100-day-old porcine thymus still exists in a developmental stage. Comparative analysis showed that the gene expression pattern of the 100-day-old porcine thymus is similar to that of the human infant thymus.
Animals
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Computational Biology
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Expressed Sequence Tags
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Fetus
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metabolism
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Gene Expression Profiling
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Genetic Variation
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Sequence Analysis, DNA
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Sus scrofa
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genetics
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metabolism
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Thymus Gland
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metabolism
8.Treatment of Murine Allergic Contact Dermatitis with CTLA4-Ig
Qian ZHOU ; Geng KOU ; Weizhu QIAN ; Hao WANG ; Yanjun LIU ; Xiaoyun WANG ; Shuichuan SONG ; Jun JIN ; Xiaodong LI ; Mengchao WU ; Yajun GUO ; Lieping CHEN
Chinese Journal of Dermatology 1995;0(04):-
Objective To study the effects of CTLA4-Ig on mu rine allergic contact dermatitis.Methods Mice were exposed to DNFB to induce allergic contact dermatitis and were i njected with CTLA4-Ig.Ear swelling was measured 24h after antigen challenge.Splenocytes from treated mice were assayed for their ability to prolif erate in response to DNFB or FITC stimulation in vitro.Results Profound inhibition of contact hypersensitivity response(CHS )was shown by 69.7%in mice treated with CTLA4-Ig compared with mice treate d with PBS control.CT-LA4-Ig-treated mice displayed DNFB-specific tolerance,but exhibited a vigorous immune response to FITC when re-sensitizing 14days after the fir st challenge.Adoptive transfer of l ymphocytes from CTLA4-Ig-treated mice could induce inhibition of CHS in recipien t mice.Conclusions CTLA4-Ig can inhibit CHS by blocking B7/CD28co-stimulatory pathway,which provides a new way to suppress typeⅣallergic reaction.[
9.URA3 affects artemisinic acid production by an engineered Saccharomyces cerevisiae in pilot-scale fermentation.
Weiwei GUO ; Limei AI ; Dong HU ; Yajun CHEN ; Mengxin GENG ; Linghui ZHENG ; Liping BAI
Chinese Journal of Biotechnology 2022;38(2):737-748
CRISPR/Cas9 has been widely used in engineering Saccharomyces cerevisiae for gene insertion, replacement and deletion due to its simplicity and high efficiency. The selectable markers of CRISPR/Cas9 systems are particularly useful for genome editing and Cas9-plasmids removing in yeast. In our previous research, GAL80 gene has been deleted by the plasmid pML104-mediated CRISPR/Cas9 system in an engineered yeast, in order to eliminate the requirement of galactose supplementation for induction. The maximum artemisinic acid production by engineered S. cerevisiae 1211-2 (740 mg/L) was comparable to that of the parental strain 1211 without galactose induction. Unfortunately, S. cerevisiae 1211-2 was inefficient in the utilization of the carbon source ethanol in the subsequent 50 L pilot fermentation experiment. The artemisinic acid yield in the engineered S. cerevisiae 1211-2 was only 20%-25% compared with that of S. cerevisiae 1211. The mutation of the selection marker URA3 was supposed to affect the growth and artemisinic acid production. A ura3 mutant was successfully restored by a recombinant plasmid pML104-KanMx4-u along with a 90 bp donor DNA, resulting in S. cerevisiae 1211-3. This mutant could grow normally in a fed-batch fermentor with mixed glucose and ethanol feeding, and the final artemisinic acid yield (> 20 g/L) was comparable to that of the parental strain S. cerevisiae 1211. In this study, an engineered yeast strain producing artemisinic acid without galactose induction was obtained. More importantly, it was the first report showing that the auxotrophic marker URA3 significantly affected artemisinic acid production in a pilot-scale fermentation with ethanol feeding, which provides a reference for the production of other natural products in yeast chassis.
Artemisinins
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Fermentation
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Saccharomyces cerevisiae/metabolism*
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Saccharomyces cerevisiae Proteins/metabolism*
10.Epidemiological characteristics, diagnosis, treatment and prognosis of gallbladder cancer in China: a report of 6 159 cases
Xuheng SUN ; Yijun WANG ; Wei ZHANG ; Yajun GENG ; Yongsheng LI ; Tai REN ; Maolan LI ; Xu'an WANG ; Xiangsong WU ; Wenguang WU ; Wei CHEN ; Tao CHEN ; Min HE ; Hui WANG ; Linhua YANG ; Lu ZOU ; Peng PU ; Mingjie YANG ; Zhaonan LIU ; Wenqi TAO ; Jiayi FENG ; Ziheng JIA ; Zhiyuan ZHENG ; Lijing ZHONG ; Yuanying QIAN ; Ping DONG ; Xuefeng WANG ; Jun GU ; Lianxin LIU ; Yeben QIAN ; Jianfeng GU ; Yong LIU ; Yunfu CUI ; Bei SUN ; Bing LI ; Chenghao SHAO ; Xiaoqing JIANG ; Qiang MA ; Jinfang ZHENG ; Changjun LIU ; Hong CAO ; Xiaoliang CHEN ; Qiyun LI ; Lin WANG ; Kunhua WANG ; Lei ZHANG ; Linhui ZHENG ; Chunfu ZHU ; Hongyu CAI ; Jingyu CAO ; Haihong ZHU ; Jun LIU ; Xueyi DANG ; Jiansheng LIU ; Xueli ZHANG ; Junming XU ; Zhewei FEI ; Xiaoping YANG ; Jiahua YANG ; Zaiyang ZHANG ; Xulin WANG ; Yi WANG ; Jihui HAO ; Qiyu ZHANG ; Huihan JIN ; Chang LIU ; Wei HAN ; Jun YAN ; Buqiang WU ; Chaoliu DAI ; Wencai LYU ; Zhiwei QUAN ; Shuyou PENG ; Wei GONG ; Yingbin LIU
Chinese Journal of Digestive Surgery 2022;21(1):114-128
Objective:To investigate the epidemiological characteristics, diagnosis, treat-ment and prognosis of gallbladder cancer in China from 2010 to 2017.Methods:The single disease retrospective registration cohort study was conducted. Based on the concept of the real world study, the clinicopathological data, from multicenter retrospective clinical data database of gallbladder cancer of Chinese Research Group of Gallbladder Cancer (CRGGC), of 6 159 patients with gallbladder cancer who were admitted to 42 hospitals from January 2010 to December 2017 were collected. Observation indicators: (1) case resources; (2) age and sex distribution; (3) diagnosis; (4) surgical treatment and prognosis; (5) multimodality therapy and prognosis. The follow-up data of the 42 hospitals were collected and analyzed by the CRGGC. The main outcome indicator was the overall survival time from date of operation for surgical patients or date of diagnosis for non-surgical patients to the end of outcome event or the last follow-up. Measurement data with normal distribu-tion were represented as Mean±SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(range), and com-parison between groups was conducted using the U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Univariate analysis was performed using the Logistic forced regression model, and variables with P<0.1 in the univariate analysis were included for multivariate analysis. Multivariate analysis was performed using the Logistic stepwise regression model. The life table method was used to calculate survival rates and the Kaplan-Meier method was used to draw survival curves. Log-rank test was used for survival analysis. Results:(1) Case resources: of the 42 hospitals, there were 35 class A of tertiary hospitals and 7 class B of tertiary hospitals, 16 hospitals with high admission of gallbladder cancer and 26 hospitals with low admission of gallbladder cancer, respectively. Geographical distribution of the 42 hospitals: there were 9 hospitals in central China, 5 hospitals in northeast China, 22 hospitals in eastern China and 6 hospitals in western China. Geographical distribution of the 6 159 patients: there were 2 154 cases(34.973%) from central China, 705 cases(11.447%) from northeast China, 1 969 cases(31.969%) from eastern China and 1 331 cases(21.611%) from western China. The total average number of cases undergoing diagnosis and treatment in hospitals of the 6 159 patients was 18.3±4.5 per year, in which the average number of cases undergoing diagnosis and treatment in hospitals of 4 974 patients(80.760%) from hospitals with high admission of gallbladder cancer was 38.8±8.9 per year and the average number of cases undergoing diagnosis and treatment in hospitals of 1 185 patients(19.240%) from hospitals with low admission of gallbladder cancer was 5.7±1.9 per year. (2) Age and sex distribution: the age of 6 159 patients diagnosed as gallbladder cancer was 64(56,71) years, in which the age of 2 247 male patients(36.483%) diagnosed as gallbladder cancer was 64(58,71)years and the age of 3 912 female patients(63.517%) diagnosed as gallbladder cancer was 63(55,71)years. The sex ratio of female to male was 1.74:1. Of 6 159 patients, 3 886 cases(63.095%) were diagnosed as gallbladder cancer at 56 to 75 years old. There was a significant difference on age at diagnosis between male and female patients ( Z=-3.99, P<0.001). (3) Diagnosis: of 6 159 patients, 2 503 cases(40.640%) were initially diagnosed as gallbladder cancer and 3 656 cases(59.360%) were initially diagnosed as non-gallbladder cancer. There were 2 110 patients(34.259%) not undergoing surgical treatment, of which 200 cases(9.479%) were initially diagnosed as gallbladder cancer and 1 910 cases(90.521%) were initially diagnosed as non-gallbladder cancer. There were 4 049 patients(65.741%) undergoing surgical treatment, of which 2 303 cases(56.878%) were initially diagnosed as gallbladder cancer and 1 746 cases(43.122%) were initial diagnosed as non-gallbladder cancer. Of the 1 746 patients who were initially diagnosed as non-gallbladder cancer, there were 774 cases(19.116%) diagnosed as gallbladder cancer during operation and 972 cases(24.006%) diagnosed as gallbladder cancer after operation. Of 6 159 patients, there were 2 521 cases(40.932%), 2 335 cases(37.912%) and 1 114 cases(18.087%) undergoing ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI) examination before initial diagnosis, respec-tively, and there were 3 259 cases(52.914%), 3 172 cases(51.502%) and 4 016 cases(65.205%) undergoing serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis, respectively. One patient may underwent multiple examinations. Results of univariate analysis showed that geographical distribution of hospitals (eastern China or western China), age ≥72 years, gallbladder cancer annual admission of hospitals, whether undergoing ultrasound, CT, MRI, serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis were related factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.45, 1.98, 0.69, 0.68, 2.43, 0.41, 1.63, 0.41, 0.39, 0.42, 95% confidence interval as 1.21-1.74, 1.64-2.40, 0.59-0.80, 0.60-0.78, 2.19-2.70, 0.37-0.45, 1.43-1.86, 0.37-0.45, 0.35-0.43, 0.38-0.47, P<0.05). Results of multivariate analysis showed that geographical distribution of hospitals (eastern China or western China), sex, age ≥72 years, gallbladder cancer annual admission of hospitals and cases undergoing ultrasound, CT, serum CA19-9 examination before initially diagnosis were indepen-dent influencing factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.36, 1.42, 0.89, 0.67, 1.85, 1.56, 1.57, 0.39, 95% confidence interval as 1.13-1.64, 1.16-1.73, 0.79-0.99, 0.57-0.78, 1.60-2.14, 1.38-1.77, 1.38-1.79, 0.35-0.43, P<0.05). (4) Surgical treatment and prognosis. Of the 4 049 patients undergoing surgical treatment, there were 2 447 cases(60.435%) with complete pathological staging data and follow-up data. Cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb were 85(3.474%), 201(8.214%), 71(2.902%), 890(36.371%), 382(15.611%), 33(1.348%) and 785(32.080%), respectively. The median follow-up time and median postoperative overall survival time of the 2 447 cases were 55.75 months (95% confidence interval as 52.78-58.35) and 23.46 months (95% confidence interval as 21.23-25.71), respectively. There was a significant difference in the overall survival between cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb ( χ2=512.47, P<0.001). Of the 4 049 patients undergoing surgical treatment, there were 2 988 cases(73.796%) with resectable tumor, 177 cases(4.371%) with unresectable tumor and 884 cases(21.833%) with tumor unassessable for resectabi-lity. Of the 2 988 cases with resectable tumor, there were 2 036 cases(68.139%) undergoing radical resection, 504 cases(16.867%) undergoing non-radical resection and 448 cases(14.994%) with operation unassessable for curative effect. Of the 2 447 cases with complete pathological staging data and follow-up data who underwent surgical treatment, there were 53 cases(2.166%) with unresectable tumor, 300 cases(12.260%) with resectable tumor and receiving non-radical resection, 1 441 cases(58.888%) with resectable tumor and receiving radical resection, 653 cases(26.686%) with resectable tumor and receiving operation unassessable for curative effect. There were 733 cases not undergoing surgical treatment with complete pathological staging data and follow-up data. There was a significant difference in the overall survival between cases not undergoing surgical treatment, cases undergoing surgical treatment for unresectable tumor, cases undergoing non-radical resection for resectable tumor and cases undergoing radical resection for resectable tumor ( χ2=121.04, P<0.001). (5) Multimodality therapy and prognosis: of 6 159 patients, there were 541 cases(8.784%) under-going postoperative adjuvant chemotherapy and advanced chemotherapy, 76 cases(1.234%) under-going radiotherapy. There were 1 170 advanced gallbladder cancer (pathological staging ≥stage Ⅲa) patients undergoing radical resection, including 126 cases(10.769%) with post-operative adjuvant chemotherapy and 1 044 cases(89.231%) without postoperative adjuvant chemo-therapy. There was no significant difference in the overall survival between cases with post-operative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.23, P=0.629). There were 658 patients with pathological staging as stage Ⅲa who underwent radical resection, including 66 cases(10.030%) with postoperative adjuvant chemotherapy and 592 cases(89.970%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.05, P=0.817). There were 512 patients with pathological staging ≥stage Ⅲb who underwent radical resection, including 60 cases(11.719%) with postoperative adjuvant chemotherapy and 452 cases(88.281%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemo-therapy and cases without post-operative adjuvant chemo-therapy ( χ2=1.50, P=0.220). Conclusions:There are more women than men with gallbladder cancer in China and more than half of patients are diagnosed at the age of 56 to 75 years. Cases undergoing ultrasound, CT, serum CA19-9 examination before initial diagnosis are independent influencing factors influencing initial diagnosis of gallbladder cancer patients. Preoperative resectability evaluation can improve the therapy strategy and patient prognosis. Adjuvant chemotherapy for gallbladder cancer is not standardized and in low proportion in China.