1.Whole-transcriptome sequencing and bioinformatics analysis of calcified outer-layer tissue from cystic echinococcosis
Wang, S.B. ; Sun, H.H. ; Ma, Y.B. ; Dai, Y. ; Ren, Q. ; Liu, Y.Q. ; Shi, C.H. ; Tao, J. ; Li, J.
Tropical Biomedicine 2024;41(No.1):20-28
Echinococcosis is a common zoonotic disease in livestock; the type with the highest incidence is cystic
echinococcosis (CE). In clinical management, patients with CE of the liver in which the cyst wall is calcified
have been found to have better prognoses than those without calcification. In this study, we collected
calcified and uncalcified cyst wall tissue from patients with hepatic CE and observed significant changes
in the expression of 2336 messenger ribonucleic acids (mRNAs), 178 long noncoding RNAs (lncRNAs),
210 microRNAs (miRNAs), and 33 circular RNAs (circRNAs) using high-throughput sequencing (HTS).
Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of
differentially expressed RNAs (DERNAs: DEmRNAs, DElncRNAs, DEmiRNAs, and DEcircRNAs) were
performed to explore these RNAs’ potential biological functions and signaling pathways. Ultimately,
the results of hematoxylin and eosin (H&E) and terminal deoxynucleotidyl transferase deoxyuridine
triphosphate (dUTP) nick end labeling (TUNEL) staining confirmed the correlation between calcification
and apoptosis of the cyst wall. In summary, this study was an initial exploration of the molecular-biological
mechanism underlying spontaneous calcification of the hydatid cyst wall, and it provides a theoretical
basis for exploring new targets for drug treatment in CE.
5.Implantation of Adipose-Derived Mesenchymal Stromal Cells (ADSCs)-Lining Prosthetic Graft Promotes Vascular Regeneration in Monkeys and Pigs
Xiao ZUO ; Pengfei HAN ; Ding YUAN ; Ying XIAO ; Yushi HUANG ; Rui LI ; Xia JIANG ; Li FENG ; Yijun LI ; Yaya ZHANG ; Ping ZHU ; Hongge WANG ; Ning WANG ; Y. James KANG
Tissue Engineering and Regenerative Medicine 2024;21(4):641-651
BACKGROUND:
Current replacement procedures for stenosis or occluded arteries using prosthetic grafts have serious limitations in clinical applications, particularly, endothelialization of the luminal surface is a long-standing unresolved problem.METHOD: We produced a cell-based hybrid vascular graft using a bioink engulfing adipose-derived mesenchymal stromal cells (ADSCs) and a 3D bioprinting process lining the ADSCs on the luminal surface of GORE-Tex grafts. The hybrid graft was implanted as an interposition conduit to replace a 3-cm-long segment of the infrarenal abdominal aorta in Rhesus monkeys.
RESULTS:
Complete endothelium layer and smooth muscle layer were fully developed within 21 days post-implantation, along with normalized collagen deposition and crosslinking in the regenerated vasculature in all monkeys. The regenerated blood vessels showed normal functionality for the longest observation of more than 1650 days. The same procedure was also conducted in miniature pigs for the interposition replacement of a 10-cm-long right iliac artery and showed the same long-term effective and safe outcome.
CONCLUSION
This cell-based vascular graft is ready to undergo clinical trials for human patients.
6.Genetic and healthy lifestyle factors in relation to the incidence and prognosis of severe liver disease in the Chinese population.
Yuanjie PANG ; Jun LV ; Christiana KARTSONAKI ; Canqing YU ; Yu GUO ; Yiping CHEN ; Ling YANG ; Iona Y MILLWOOD ; Robin G WALTERS ; Silu LV ; Sushila BURGESS ; Sam SANSOME ; Junshi CHEN ; Zhengming CHEN ; Liming LI
Chinese Medical Journal 2023;136(16):1929-1936
BACKGROUND:
Severe liver disease (SLD), including cirrhosis and liver cancer, constitutes a major disease burden in China. We aimed to examine the association of genetic and healthy lifestyle factors with the incidence and prognosis of SLD.
METHODS:
The study population included 504,009 participants from the prospective China Kadoorie Biobank aged 30-79 years. The individuals were from 10 diverse areas in China without a history of cancer or liver disease at baseline. Cox regression was used to estimate adjusted hazard ratios (HRs) for incident SLD and death after SLD diagnosis associated with healthy lifestyle factors (smoking, alcohol, physical activity, and central adiposity). Additionally, the contribution of genetic risk for hepatitis B virus (HBV, assessed by genetic variants in major histocompatibility complex, class II, DP/DQ [ HLA - DP / DQ ] genes) was also estimated.
RESULTS:
Compared with those with 0-1 healthy lifestyle factor, participants with 2, 3, and 4 factors had 12% (HR 0.88 [95% confidence interval [CI] 0.85, 0.92]), 26% (HR 0.74 [95%CI: 0.69, 0.79]), and 44% (HR 0.56 [95%CI: 0.48, 0.65]) lower risks of SLD, respectively. Inverse associations were observed among participants with both low and high genetic risks (HR per 1-point increase 0.83 [95%CI: 0.74, 0.94] and 0.91 [95%CI: 0.82, 1.02], respectively; Pinteraction = 0.51), although with a non-significant trend among those with a high genetic risk. Inverse associations were also observed between healthy lifestyle factors and liver biomarkers regardless of the genetic risk. Despite the limited power, healthy lifestyle factors were associated with a lower risk of death after incident SLD among participants with a low genetic risk (HR 0.59 [95%CI: 0.37, 0.96]).
CONCLUSIONS
Lifestyle modification may be beneficial in terms of lowering the risk of SLD regardless of the genetic risk. Moreover, it is also important for improving the prognosis of SLD in individuals with a low genetic risk. Future studies are warranted to examine the impact of healthy lifestyles on SLD prognosis, particularly among individuals with a high genetic risk.
Humans
;
Prospective Studies
;
Incidence
;
East Asian People
;
Healthy Lifestyle
;
Risk Factors
;
Liver Neoplasms
;
Prognosis
;
China/epidemiology*
7.Clinical effects of robot-assisted esophageal hiatal hernia repair and laparoscopic esophageal hiatal hernia repair: a retrospective comparative study.
Maimaitiaili MAIMAITIMING ; Duolikun YASHENG ; Yierxiatijiang AINIWAER ; Y L LI ; Aikebaier AILI ; J WANG ; Ke LIMU
Chinese Journal of Surgery 2023;61(6):498-502
Objective: To analyze the short-term clinical effects of robot-assisted and laparoscopic repair of the hiatal hernia. Methods: The clinical data of 56 patients underwent minimally invasive hiatal hernia repair from January 2021 to January 2022 in the Department of Minimally Invasive Surgery, Hernias and Abdominal Wall Surgery, People's Hospital of Xinjiang Uygur Autonomous Region were retrospectively analyzed. There were 32 males and 24 females, aging (59.7±10.7) years (range: 28 to 75 years). All patients were divided into laparoscopy group (n=27) and robot group (n=29) according to surgical procedures. Perioperative conditions, hospital stay, and improvement in symptoms before and after surgery were compared between the two groups by the t test, Wilcoxon rank-sum test and χ2 test. Results: All surgical procedures were successfully completed, without conversion to laparotomy or change in operation mode. There were no serious complications related to the operation. The intraoperative blood loss of the robot group was less than that of the laparoscopic group (M (IQR)): (20 (110) ml vs. 40 (80) ml, Z=-4.098, P<0.01). The operation time ((111.7±33.6) minutes vs. (120.4±35.0) minutes, t=-0.943, P=0.350) and hospitalization time ((3.9±1.4) days vs. (4.7±1.9) days, t=-1.980, P=0.053) of the robot group and the laparoscopic group were similar. Follow-up for 12 months after the operation showed no postoperative complications and recurrence. The score of the health-related quality of life questionnaire for gastroesophageal reflux disease in the robot group decreased from 10.8±2.8 before the operation to 6.5±0.6 after the operation, and that in the laparoscopic group decreased from 10.6±2.1 before the operation to 6.3±0.6 after the operation. There was no difference in the influence of different surgical methods on the change in score (t=0.030,P=0.976). Conclusion: Compared with laparoscopic repair of the hiatal hernia, robot-assisted hiatal hernia repair has the advantages of less bleeding, rapid postoperative recovery and good short-term effect.
Male
;
Female
;
Humans
;
Hernia, Hiatal/complications*
;
Retrospective Studies
;
Robotics
;
Herniorrhaphy/methods*
;
Quality of Life
;
Laparoscopy/methods*
;
Recurrence
;
Fundoplication/methods*
8.Clinical and genetic characteristics of children with primary dilated cardiomyopathy.
Kui ZHENG ; Fei WU ; Mei-Na LOU ; Ying-Xue WANG ; Bo LI ; Jing-Xia HAO ; Yong-Li WANG ; Ying-Qian ZHANG ; Huan-Jun QI
Chinese Journal of Contemporary Pediatrics 2023;25(7):726-731
OBJECTIVES:
To study the genetic characteristics, clinical characteristics, and prognosis of children with primary dilated cardiomyopathy (DCM).
METHODS:
A retrospective analysis was performed on the medical data of 44 children who were diagnosed with DCM in Hebei Children's Hospital from July 2018 to February 2023. According to the genetic testing results, they were divided into two groups: gene mutation-positive group (n=17) and gene mutation-negative group (n=27). The two groups were compared in terms of clinical data at initial diagnosis and follow-up data.
RESULTS:
Among the 44 children with DCM, there were 21 boys (48%) and 23 girls (52%). Respiratory symptoms including cough and shortness of breath were the most common symptom at initial diagnosis (34%, 15/44). The detection rate of gene mutations was 39% (17/44). There were no significant differences between the two groups in clinical characteristics, proportion of children with cardiac function grade Ⅲ or Ⅳ, brain natriuretic peptide levels, left ventricular ejection fraction, and left ventricular fractional shortening at initial diagnosis (P>0.05). The median follow-up time was 23 months, and 9 children (20%) died, including 8 children from the gene mutation-positive group, among whom 3 had TTN gene mutation, 2 had LMNA gene mutation, 2 had TAZ gene mutation, and 1 had ATAD3A gene mutation. The gene mutation-positive group had a significantly higher mortality rate than the gene mutation-negative group (P<0.05).
CONCLUSIONS
There is no correlation between the severity of DCM at initial diagnosis and gene mutations in children. However, children with gene mutations may have a poorer prognosis.
Male
;
Female
;
Humans
;
Child
;
Stroke Volume
;
Retrospective Studies
;
Ventricular Function, Left
;
Phenotype
;
Cardiomyopathy, Dilated/diagnosis*
;
Mutation
;
ATPases Associated with Diverse Cellular Activities/genetics*
;
Membrane Proteins/genetics*
;
Mitochondrial Proteins/genetics*
9.Values of ATX in predicting disease progression in patients with PBC and PBC related HCC.
M Y ZHANG ; H XIE ; J ZHAO ; Q S LIANG ; L HAN ; X R ZHAI ; B S LI ; Z S ZOU ; Y SUN
Chinese Journal of Hepatology 2023;31(6):40-46
Objective: To clarify the values of autotaxin (ATX) in patients with primary biliary cholangitis (PBC) and PBC-related hepatocellular carcinoma (HCC). Methods: 179 patients with PBC were selected from prospective cohorts of autoimmune liver diseases at the time of first diagnosis of PBC in Department of Hepatology, the Fifth Medical Center of PLA General Hospital, from January 2016 to January 2018, all patients with PBC received UDCA therapy, primary endpoint was event of HCC, the follow-up period was censored at the date of HCC. The relationship between level of ATX and clinical features in patients with PBC and its potential value in predicting disease progression and PBC-related HCC were analyzed. Results: The ATX level in the peripheral blood of patients with PBC was significantly higher than that of alcoholic liver cirrhosis(ALC) (t = 3.278, P = 0.001) and healthy controls(HC) (t = 6.594, P < 0.001), however, when comparing PBC to non-PBC related HCC, no significant difference was found between the groups(t=-0.240, P = 0.811). Consistent with peripheral blood levels, histochemical staining indicated that ATX in the liver of patients with PBC was significantly higher than that of HC (Z=-3.633, P < 0.001) and ALC (Z=-3.283, P < 0.001), and the expression of ATX in PBC with advanced histological stage was significantly higher than PBC with early stage (Z=-2.018, P = 0.034). The baseline ATX level in PBC patients without developing to HCC during follow-up had significant difference to patients with developing to HCC (228.451 ± 124.093 ng/ml vs 301.583 ± 100.512 ng/ml, t = 2.339, P = 0.021). The result in multivariate logistic regression analysis showed that ATX were independent predictors of PBC related HCC(OR 1.245, 95%CI 1.097-1.413). The optimal critical value of peripheral blood ATX level at baseline for predicting HCC was 235.254 ng/ml, with the cut-off value of 0.714 in AUC of the ROC (95% CI was 0.597~ 0.857), sensitivity and specificity were 84.6% and 59.0%, respectively. Conclusion: ATX level was significantly higher in PBC patients over controls, and it's concentration was correlated with UDCA efficacy and fibrosis stage. ATX has potential values in predicting disease progression and PBC-related HCC.
10.Differences in clinicopathological features, gene mutations, and prognosis between primary gastric and intestinal gastrointestinal stromal tumors in 1061 patients.
Jia Xin LI ; Lin SUN ; Shuai ZHAO ; Bing SHAO ; Yu Hong GUO ; Shuai CHEN ; Han LIANG ; Y SUN
Chinese Journal of Gastrointestinal Surgery 2023;26(4):346-356
Objective: To analyze the clinicopathological features and gene mutations of primary gastrointestinal stromal tumors (GISTs) of the stomach and intestine and the prognosis of intermediate- and high-risk GISTs. Methods: This was a retrospective cohort study. Data of patients with GISTs admitted to Tianjin Medical University Cancer Institute and Hospital from January 2011 to December 2019 were collected retrospectively. Patients with primary gastric or intestinal disease who had undergone endoscopic or surgical resection of the primary lesion and were confirmed pathologically as GIST were included. Patients treated with targeted therapy preoperatively were excluded. The above criteria were met by 1061 patients with primary GISTs, 794 of whom had gastric GISTs and 267 intestinal GISTs. Genetic testing had been performed in 360 of these patients since implementation of Sanger sequencing in our hospital in October 2014. Gene mutations in KIT exons 9, 11, 13, and 17 and PDGFRA exons 12 and 18 were detected by Sanger sequencing. The factors investigated in this study included: (1) clinicopathological data, such as sex, age, primary tumor location, maximum tumor diameter, histological type, mitotic index (/5 mm2), and risk classification; (2) gene mutation; (3) follow-up, survival, and postoperative treatment; and (4) prognostic factors of progression-free survival (PFS) and overall survival (OS) for intermediate- and high-risk GIST. Results: (1) Clinicopathological features: The median ages of patients with primary gastric and intestinal GIST were 61 (8-85) years and 60 (26-80) years, respectively; The median maximum tumor diameters were 4.0 (0.3-32.0) cm and 6.0 (0.3-35.0) cm, respectively; The median mitotic indexes were 3 (0-113)/5 mm² and 3 (0-50)/5 mm², respectively; The median Ki-67 proliferation indexes were 5% (1%-80%) and 5% (1%-50%), respectively. The rates of positivity for CD117, DOG-1, and CD34 were 99.7% (792/794), 99.9% (731/732), 95.6% (753/788), and 100.0% (267/267), 100.0% (238/238), 61.5% (163/265), respectively. There were higher proportions of male patients (χ²=6.390, P=0.011), tumors of maximum diameter > 5.0 cm (χ²=33.593, P<0.001), high-risk (χ²=94.957, P<0.001), and CD34-negativity (χ²=203.138, P<0.001) among patients with intestinal GISTs than among those with gastric GISTs. (2) Gene mutations: Gene mutations were investigated in 286/360 patients (79.4%) with primary gastric GISTs and 74/360 (20.6%) with primary intestinal GISTs. Among the 286 patients with gastric primary GISTs, 79.4% (227/286), 8.4% (24/286), and 12.2% (35/286), had KIT mutations, PDGFRA mutations, and wild-type, respectively. Among the 74 patients with primary intestinal GISTs, 85.1% (63/74) had KIT mutations and 14.9% (11/74) were wild-type. The PDGFRA mutation rate was lower in patients with intestinal GISTs than in those with gastric GISTs[ 0% vs. 8.4%(24/286), χ²=6.770, P=0.034], whereas KIT exon 9 mutations occurred more often in those with intestinal GISTs [22.2% (14/63) vs. 1.8% (4/227), P<0.001]. There were no significant differences between gastric and intestinal GISTs in the rates of KIT exon 11 mutation type and KIT exon 11 deletion mutation type (both P>0.05). (3) Follow-up, survival, and postoperative treatment: After excluding 228 patients with synchronous and metachronous other malignant tumors, the remaining 833 patients were followed up for 6-124 (median 53) months with a follow-up rate of 88.6% (738/833). None of the patients with very low or low-risk gastric (n=239) or intestinal GISTs (n=56) had received targeted therapy postoperatively. Among 179 patients with moderate-risk GISTs, postoperative targeted therapy had been administered to 88/155 with gastric and 11/24 with intestinal GISTs. Among 264 patients with high-risk GISTs, postoperative targeted therapy had been administered to 106/153 with gastric and 62/111 with intestinal GISTs. The 3-, 5-, and 10-year PFS of patients with gastric or intestinal GISTs were 96.5%, 93.8%, and 87.6% and 85.7%, 80.1% and 63.3%, respectively (P<0.001). The 3-, 5-, and 10-year OS were 99.2%, 98.8%, 97.5% and 94.8%, 92.1%, 85.0%, respectively (P<0.001). (4) Analysis of predictors of intermediate- and high-risk GISTs: The 5-year PFS of patients with gastric and intestinal GISTs were 89.5% and 73.2%, respectively (P<0.001); The 5-year OS were 97.9% and 89.3%, respectively (P<0.001). Multivariate analysis showed that high risk (HR=2.918, 95%CI: 1.076-7.911, P=0.035) and Ki-67 proliferation index > 5% (HR=2.778, 95%CI: 1.389-5.558, P=0.004) were independent risk factors for PFS in patients with intermediate- and high-risk GISTs (both P<0.05). Intestinal GISTs (HR=3.485, 95%CI: 1.407-8.634, P=0.007) and high risk (HR=3.753,95%CI:1.079-13.056, P=0.038) were independent risk factors for OS in patients with intermediate- and high-risk GISTs (both P<0.05). Postoperative targeted therapy was independent protective factor for PFS and OS (HR=0.103, 95%CI: 0.049-0.213, P<0.001; HR=0.210, 95%CI:0.078-0.564,P=0.002). Conclusions: Primary intestinal GIST behaves more aggressively than gastric GISTs and more frequently progress after surgery. Moreover, CD34 negativity and KIT exon 9 mutations occur more frequently in patients with intestinal GISTs than in those with gastric GISTs.
Male
;
Humans
;
Gastrointestinal Stromal Tumors/surgery*
;
Retrospective Studies
;
Ki-67 Antigen
;
Stomach Neoplasms/pathology*
;
Prognosis
;
Mutation
;
Intestines/pathology*
;
Proto-Oncogene Proteins c-kit/genetics*
;
Receptor, Platelet-Derived Growth Factor alpha/genetics*


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