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Liver regenerative medicine can use functional liver cells to repair or replace damaged liver tissue and it is expected to be rapidly developed as an alternative treatment to liver transplantation. However, regenerative medicine requires cells with stable proliferation ability and liver cell characteristics. Liver organoids are derived from adult stem cells or pluripotent stem cells. They can be proliferated in large quantities and cultured for a long time in vitro, meanwhile maintain genetic stability, and simulate the structural and functional characteristics of organs in the body, providing a new strategy for liver regeneration. This article reviews liver organoids and their research progress in liver regenerative medicine, and discusses their application potential and existing limitations.
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Objective:To investigate the application value of carbon nanoparticle tracer in lymph node dissection for Siewert type Ⅱ and Ⅲ adenocarcinoma of esophagogastric junction (AEG).Methods:The retrospective cohort study was conducted. The clinicopathological data of 147 patients with Siewert type Ⅱ and Ⅲ AEG who were admitted to Shengli Petroleum Central Hospital from June 2015 to July 2020 were collected. There were 109 males and 38 females, aged (65±9)years. All the patients underwent laparoscopic-assisted radical resection of AEG via esophageal hiatus. Of 147 patients, 61 cases not injected with carbon nanoparticle tracer preoperatively were allocated into control group and 86 cases injected with carbon nanoparticle tracer preoperatively were allocated into experimental group. Observation indicators: (1) surgical and postoperative situations; (2) influencing factors analysis of No.10 lymph nodes metastasis. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Count data were represented as absolute numbers or percentages, and comparison between groups was analyzed by the chi-square test. Univariate analysis was conducted by statistic methods based on data type, and multivariate analysis was conducted by the Logistic step-wise regression model. Results:(1) Surgical and postoperative situations. Patients of the experimental group and control group completed laparoscopic-assisted radical resection of AEG via esophageal hiatus successfully. There was no significant difference in the operation time, volume of intraoperative blood loss, the total number of lymph node dissection, the number of the first station, the second station and positive lymph nodes between the two groups ( P>0.05). For the experimental group, the black staining rate of lymph nodes was 57.937%(1 365/2 356), the black staining rate of the first station and second station lymph nodes was 77.989%(1 024/1 313) and 43.691%(232/531), the black staining rate of Siewert type Ⅱ and Ⅲ AEG patients was 56.855%(423/744) and 58.437%(942/1 612), respectively. The lymph node metastasis rate was 19.091%(815/4 269) of 147 patients, 18.573%(242/1 303)of Siewert type Ⅱ AEG patients and 19.319%(573/2 966) of Siewert type Ⅲ AEG patients. For Siewert type Ⅱ AEG patients, the metastasis rate of No.1, 2, 3, 4sa, 4sb, 7, 8a, 11p lymph nodes was more than 10%, the metastasis rate of No.4d, 5, 6, 9, 10, 11d, 12a lymph nodes was lower than 10%. For Siewert type Ⅲ AEG patients, the metastasis rate of No.1, 2, 3, 4sa, 4sb, 7, 8a, 10, 11p and lower mediastinal lymph nodes was more than 10%, the metastasis rate of No.4d, 5, 6, 9 11d, 12a and lower mediastinal lymph nodes was lower than 10%. There was no significant difference in the Clavien Dindo classification of postoperative complications between the two groups ( P>0.05). (2) Influencing factors analysis of No.10 lymph nodes metastasis. Results of multivariate analysis showed that tumor T staging and degree of tumor differention was an independent influencing factor for No.10 lymph nodes metastasis ( P<0.05). Conclusions:For Siewert type Ⅱ and Ⅲ AEG patients, the application of carbon nano-partide tracer can not increase the number of lymph node dissection. The second station lymph node dissection should be paid attention for Siewert type Ⅱ AEG. Tumor T staging and degree of tumor differentiation are independent influencing factors for No.10 lymph nodes metastasis.
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Renal fibrosis, the final pathological outcome of end-stage chronic kidney diseases, is associated with inflammation, oxidative stress, epithelial-mesenchymal transdifferentiation (EMT), and extracellular matrix deposition. It belongs to the categories of edema, ischuria, anuria and vomiting, and consumptive disease in traditional Chinese medicine (TCM), with the key pathogenesis of Qi deficiency and blood stasis and the primary treatment principle of replenishing Qi and activating blood. Astragali Radix-Salviae Miltiorrhizae Radix et Rhizoma mainly contains astragalosides, polysaccharides, calycosin, salvianolic acid, and tanshinone, with the effect of tonifying Qi and activating blood. Studies have shown that this herb pair and its active components can delay the progress of renal fibrosis by regulating multiple signaling pathways. With consideration to the pathogenesis of Qi deficiency and blood stasis, this article reviews the research progress in the mitigation of renal fibrosis by Astragali Radix-Salviae Miltiorrhizae Radix et Rhizoma from the aspects of protecting glomerular filtration barrier, inhibiting EMT and mesangial cell proliferation, improving renal hemodynamics, and protecting renal function. Furthermore, the mechanisms were summarized. Specifically, Astragali Radix-Salviae Miltiorrhizae Radix et Rhizoma and its effective components can improve mitochondrial function and fatty acid metabolism, alleviate endoplasmic reticulum stress and autophagy disorders, and inhibit immune inflammation and oxidative stress by regulating nuclear factor E2-related factor 2 (Nrf2)/PTEN-induced kinase 1 (Pink1), Nrf2/antioxidant response element (ARE), tumor necrosis factor-α (TNF-α)/nuclear transcription factor-κB (NF-κB), miR-21/Smad7/transforming growth factor beta (TGF-β), Wnt/β-catenin, long non-coding RNA-taurine up-regulated gene 1 (lncRNA-TUG1)/tumor necrosis factor receptor-associated factor 5 (TRAF5), Ras-related C3 botulinum toxin substrate 1 (Rac1)/cell division cycle protein 42 (CDC42), Ras homolog (Rho)/Rho-associated coiled-coil containing protein kinase (ROCK), phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt), Janus kinase (JAK)/signal transducer and activator of transcription (STAT), peroxisome proliferator-activated receptor α (PPARα)/peroxisome proliferator-activated receptor γ coactivator l alpha (PGC-1α), and p38 mitogen-activated protein kinase (p38 MAPK). This review aims to provide references for the relevant research, give play to the role of Astragali Radix-Salviae Miltiorrhizae Radix et Rhizoma, and provide guidance for the clinical treatment of renal fibrosis.
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Objective: To construct and verify a light-weighted convolutional neural network (CNN), and explore its application value for screening the early stage (subcategory 0/1 and stage Ⅰ of pneumoconiosis) of coal workers' pneumoconiosis (CWP) from digital chest radiography (DR) . Methods: A total of 1225 DR images of coal workers who were examined at an Occupational Disease Prevention and Control Institute in Anhui Province from October 2018 to March 2021 were retrospectively collected. All DR images were collectively diagnosed by 3 radiologists with diagnostic qualifications and gave diagnostic results. There were 692 DR images with small opacity profusion 0/- or 0/0 and 533 DR images with small opacity profusion 0/1 to stage Ⅲ of pneumoconiosis. The original chest radiographs were preprocessed differently to generate four datasets, namely 16-bit grayscale original image set (Origin16), 8-bit grayscale original image set (Origin 8), 16-bit grayscale histogram equalized image set (HE16) and 8-bit grayscale histogram equalized image set (HE8). The light-weighted CNN, ShuffleNet, was applied to train the generated prediction model on the four datasets separately. The performance of the four models for pneumoconiosis prediction was evaluated on a test set containing 130 DR images using measures such as the receiver operating characteristic (ROC) curve, accuracy, sensitivity, specificity, and Youden index. The Kappa consistency test was used to compare the agreement between the model predictions and the physician diagnosed pneumoconiosis results. Results: Origin16 model achieved the highest ROC area under the curve (AUC=0.958), accuracy (92.3%), specificity (92.9%), and Youden index (0.8452) for predicting pneumoconiosis, with a sensitivity of 91.7%. And the highest consistency between identification and physician diagnosis was observed for Origin16 model (Kappa value was 0.845, 95%CI: 0.753-0.937, P<0.001). HE16 model had the highest sensitivity (98.3%) . Conclusion: The light-weighted CNN ShuffleNet model can efficiently identify the early stages of CWP, and its application in the early screening of CWP can effectively improve physicians' work efficiency.
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Humans , Retrospective Studies , Anthracosis/diagnostic imaging , Pneumoconiosis/diagnostic imaging , Coal Mining , Neural Networks, Computer , CoalABSTRACT
ObjectiveIn this study, based on ultra-high performance liquid chromatography-mass spectrometry(UHPLC-MS/MS) and high-throughput transcriptome sequencing technology(RNA-seq), we investigated the mechanism of Yishen Huashi granules in regulating serum metabolites and renal messenger ribonucleic acid(mRNA) expression to improve diabetic kidney disease(DKD). MethodSD rats were randomly divided into normal group , model group and Yishen Huashi granules group, with 8 rats in each group. The rat model of DKD was established by intraperitoneal injection of streptozotocin. Yishen Huashi granules group was given 5.54 g·kg-1·d-1 of Yishen Huashi granules by gavage, and the normal group and the model group were given the same amount of normal saline for 6 weeks. During the experiment, the body weight and blood glucose of rats were monitored, and the rats were anesthetized 24 hours after the last administration, blood was collected from the inferior vena cava, serum was separated, and renal function, blood lipid, and inflammatory indicators were detected. Kidney tissue of rats was fixed in neutral paraformaldehyde, and stained with hematoxylin-eosin(HE), Masson and periodic acid-Schiff(PAS) to observe the renal pathological changes. UHPLC-MS/MS and RNA-seq were used to identify the changes of serum metabolism and the differences of renal mRNA expression, and real time fluorescence quantitative polymerase chain reaction(Real-time PCR) and Western blot were used to detect the differential mRNA and protein expression in renal tissue to explore the common expression mechanism. ResultCompared with the normal group, rats in the model group showed a decrease in body weight, a significant increase in blood glucose, urinary microalbumin to urinary creatinine ratio(UACR), blood urea nitrogen(BUN), cystatin-C(Cys-C), β2-microglobulin(β2-MG), interleukin-6(IL-6), triglyceride(TG) and total cholesterol(TC), and a significant decrease in total superoxide dismutase(T-SOD)(P<0.01). After the intervention of Yishen Huashi granules, all the indexes were improved to different degrees in rats(P<0.05, P<0.01). Compared with the normal group, the model group showed renal mesangial stromal hyperplasia, fibrous tissue hyperplasia and tubular vacuolar degeneration. Compared with the model group, the renal pathology of rats in Yishen Huashi granules group was improved to a certain extent. A total of 14 target metabolites and 96 target mRNAs were identified, the target metabolites were mainly enriched in 20 metabolic pathways, including sphingolipid metabolism, glycerophospholipid metabolism, and the biosynthesis of phenylalanine, tyrosine and tryptophan. The target mRNAs were enriched to obtain a total of 21 differential mRNAs involved in the TOP20 pathways closely related to glycolipid metabolism. A total of 6 pathways, glycerophospholipid metabolism, arachidonic acid metabolism, purine metabolism, primary bile acid biosynthesis, ascorbic acid and uronic acid metabolism, and galactose metabolism, were enriched by serum differential metabolites and renal differential mRNAs, among them, there were 7 differential metabolites such as phosphatidylethanolamine(PE) and 7 differential mRNAs such as recombinant adenylate cyclase 3(ADCY3). Seven differential metabolites had high predictive accuracy as verified by receiver operating characteristic(ROC) curve, and the results of Real-time PCR and Western blot were highly consistent with the sequencing results. ConclusionYishen Huashi granules can reduce UACR, BUN and other biochemical indexes, correct the disorder of glucose and lipid metabolism, and improve renal function of DKD rats. And its mechanism may be related to the regulation of the level of PE and other blood metabolites, and expression of Phospho1 and other mRNAs in the kidney, of which six pathways, including glycerophospholipid metabolism, may play an important role.
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Objective:To analyze the video electroencephalogram (VEEG) and clinical features of simultaneous or sequential onset of childhood absence epilepsy (CAE) and childhood benign epilepsy with centrotemporal spikes (BECTS).Methods:Seven patients with simultaneous or sequential onset of CAE and BECTS admitted to Neurology Center, Beijing Tiantan Hospital from January 2016 to July 2023 were chosen. The clinical features, VEEG, treatments and prognoses of these patients were retrospectively analyzed. PubMed database was searched for articles on simultaneous or sequential onset of CAE and BECTS from January 2002 to July 2023, and studies with 3 or more cases of simultaneous or sequential onset of CAE and BECTS were included. Clinical characteristics of these patients in various studies were compared.Results:(1) The mean onset age in these 7 patients was 6.28 years, ranged from 4 to 8 years. CAE was recorded in 2 patients without clinical manifestation of BECTS during the course of disease progression; simultaneous or sequential onset of CAE and BECTS was recorded in 5 patients. Of the 7 patients, 2 effectively accepted valproate sodium (VPA) monotherapy, and 5 required additional antiepileptic drugs. Although all patients had well-controlled seizures and no developmental delays, 3 had learning disabilities, 3 had attention deficit hyperactivity disorder (ADHD), and 2 had anxiety. Wechsler Intelligence Scale for Children-III (WAIS-III) showed that 1 patient had below average intelligence and 6 had average intelligence. VEEG of all 7 patients showed simultaneous or sequential absence seizures and centrotemporal spikes. (2) Four studies were included in PubMed database. Combined with our study, these 5 sutdies indicated significant differences in onset age in patients with simultaneous or sequential onset of CAE and BECTS ( P<0.05), but no significant differences in simultaneous VEEG manifestations occurred or not and disease comorbidities or not in CAE and BECTS patients ( P>0.05). Conclusion:Patients with simultaneous or sequential onset of CAE and BECTS have different onset age, good overall prognosis and good response to anti-epileptic drugs, and trend to have complicated cognitive impairment.
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BACKGROUND@#Sarcopenia is an age-related progressive skeletal muscle disorder involving the loss of muscle mass or strength and physiological function. Efficient and precise AI algorithms may play a significant role in the diagnosis of sarcopenia. In this study, we aimed to develop a machine learning model for sarcopenia diagnosis using clinical characteristics and laboratory indicators of aging cohorts.@*METHODS@#We developed models of sarcopenia using the baseline data from the West China Health and Aging Trend (WCHAT) study. For external validation, we used the Xiamen Aging Trend (XMAT) cohort. We compared the support vector machine (SVM), random forest (RF), eXtreme Gradient Boosting (XGB), and Wide and Deep (W&D) models. The area under the receiver operating curve (AUC) and accuracy (ACC) were used to evaluate the diagnostic efficiency of the models.@*RESULTS@#The WCHAT cohort, which included a total of 4057 participants for the training and testing datasets, and the XMAT cohort, which consisted of 553 participants for the external validation dataset, were enrolled in this study. Among the four models, W&D had the best performance (AUC = 0.916 ± 0.006, ACC = 0.882 ± 0.006), followed by SVM (AUC =0.907 ± 0.004, ACC = 0.877 ± 0.006), XGB (AUC = 0.877 ± 0.005, ACC = 0.868 ± 0.005), and RF (AUC = 0.843 ± 0.031, ACC = 0.836 ± 0.024) in the training dataset. Meanwhile, in the testing dataset, the diagnostic efficiency of the models from large to small was W&D (AUC = 0.881, ACC = 0.862), XGB (AUC = 0.858, ACC = 0.861), RF (AUC = 0.843, ACC = 0.836), and SVM (AUC = 0.829, ACC = 0.857). In the external validation dataset, the performance of W&D (AUC = 0.970, ACC = 0.911) was the best among the four models, followed by RF (AUC = 0.830, ACC = 0.769), SVM (AUC = 0.766, ACC = 0.738), and XGB (AUC = 0.722, ACC = 0.749).@*CONCLUSIONS@#The W&D model not only had excellent diagnostic performance for sarcopenia but also showed good economic efficiency and timeliness. It could be widely used in primary health care institutions or developing areas with an aging population.@*TRIAL REGISTRATION@#Chictr.org, ChiCTR 1800018895.
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Humans , Aged , Sarcopenia/diagnosis , Deep Learning , Aging , Algorithms , BiomarkersABSTRACT
Cholangiocarcinoma (CCA) is a highly malignant biliary tumor with strong invasion and poor prognosis and is insensitive to radiotherapy and chemotherapy. Tumor-associated macrophage (TAM) is an important component of the tumor microenvironment. CCA cells recruit TAM into tumor tissue by releasing cytokines and polarize them into M2 TAM, which promotes the progression of CCA through various mechanisms such as assisting immune escape, promoting tumor cell proliferation, regulating angiogenesis, promoting tumor metastasis, and mediating immune resistance. As an emerging target of tumor immunotherapy, TAM provides new ideas for targeted therapy for CCA. This article reviews the mechanisms of TAM in promoting the progression of CCA and immunotherapy targeting TAM in recent years.
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Background@#and Purpose To examine the clinical and safety outcomes after endovascular treatment (EVT) for acute basilar artery occlusion (BAO) with different anesthetic modalities. @*Methods@#This was a retrospective analysis using data from the Endovascular Treatment for Acute Basilar Artery Occlusion (ATTENTION) registry. Patients were divided into two groups defined by anesthetic modality performed during EVT: general anesthesia (GA) or non-general anesthesia (non-GA). The association between anesthetic management and clinical outcomes was evaluated in a propensity score matched (PSM) cohort and an inverse probability of treatment weighting (IPTW) cohort to adjust for imbalances between the two groups. @*Results@#Our analytic sample included 1,672 patients from 48 centers. The anesthetic modality was GA in 769 (46.0%) and non-GA in 903 (54.0%) patients. In our primary analysis with the PSM-based cohort, non-GA was comparable to GA concerning the primary outcome (adjusted common odds ratio [acOR], 1.01; 95% confidence interval [CI], 0.82 to 1.25; P=0.91). Mortality at 90 days was 38.4% in the GA group and 35.8% in the non-GA group (adjusted risk ratio, 0.95; 95% CI, 0.83 to 1.08; P=0.44). In our secondary analysis with the IPTW-based cohort, the anesthetic modality was significantly associated with the distribution of modified Rankin Scale at 90 days (acOR: 1.45 [95% CI: 1.20 to 1.75]). @*Conclusion@#In this nationally-representative observational study, acute ischemic stroke patients due to BAO undergoing EVT without GA had similar clinical and safety outcomes compared with patients treated with GA. These findings provide the basis for large-scale randomized controlled trials to test whether anesthetic management provides meaningful clinical effects for patients undergoing EVT.
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ObjectiveTo evaluate the lipid-lowering activity of Quansanqi tablets(QSQ), an innovative new drug of Panax notoginseng. MethodMice and golden hamsters were used to establish a hyperlipidemia model by injecting egg yolk milk and feeding high-fat diets. The levels of total cholesterol (TC),triglyceride (TG),low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were detected, and liver function indicators [alanine aminotransferase (ALT), aspartate amino-transferase (AST), and alkaline phosphatase (ALP)] of golden hamsters were detected. Hematoxylin-eosin (HE) staining was used to observe the degree of liver injury. In the experiments, a normal group, a model group, an atorvastatin calcium group, and low-, medium-, and high-dose QSQ groups (0.32, 0.64, 1.28 g·kg-1 for mice, and 0.16, 0.32, 0.64 g·kg-1 for golden hamsters) were set up. ResultCompared with the normal group, the acute hyperlipidemia model mice showed increased TC, TG, and LDL-C levels (P<0.01), and the hyperlipidemia model mice showed increased TC and LDL-C levels (P<0.01). Additionally, the hyperlipidemia model golden hamsters showed increased serum TC, TG, LDL-C, ALT, AST, and ALP levels (P<0.05, P<0.01). HE staining indicated the presence of fat accumulation in the liver, accompanied by inflammatory reactions. Compared with the model group, QSQ of various doses could reduce TC, TG, and LDL-C levels in acute hyperlipidemia model mice (P<0.05, P<0.01), and the high-dose QSQ could reduce TC and LDL-C levels (P<0.01) and increase HDL-C level (P<0.05) in hyperlipidemia model mice, as well as reduce TC, TG, and LDL-C levels in hyperlipidemia model golden hamsters (P<0.05, P<0.01), especially in the first two weeks. In addition, atorvastatin calcium could further increase ALT, AST, and ALP levels (P<0.05, P<0.01) and aggravate liver function damage, while low-dose QSQ could reduce ALT, AST, and ALP (P<0.05), and medium- and high-dose QSQ did not cause further liver function damage. ConclusionQSQ have a significant lipid-lowering effect on different hyperlipidemia model animals and can improve liver function and liver injury.
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Objective: Taxifolin is a natural flavonoid compound that can be isolated from onions, grapes, oranges and grapefruit. It also acts as a medicine food homology with extraordinary antioxidant and anti-inflammatory activity. This study aims to explain the protective effects and potential mechanisms of taxifolin against inflammatory reaction. Methods: Levels of interleukin (IL)-6, IL-1β and intracellular reactive oxygen species (ROS) were assessed in different time after the treatment of taxifolin in RAW264.7 cells induced by lipopolysaccharide (LPS). Subsequently, the mRNA and protein levels of inducible nitric oxide synthase (iNOS), vascular endothelial growth factor (VEGF), cyclooxygenase (COX)-2, tumor necrosis factor (TNF)-α and the phosphorylation expression levels of the MAPK signal pathway were also evaluated. A silico analysis was used to explain the binding situation for the investigation of taxifolin and MAPK signal pathway. And then MAPK inhibitors were used to reveal the expression level of iNOS, VEGF, COX-2 and TNF-α in RAW264.7 cells. Results: It was demonstrated that cell inflammatory damage induced by LPS was significantly alleviated after the treatment of taxifolin. Then, the mRNA and protein levels of iNOS, VEGF, COX-2 and TNF-α were reduced and the phosphorylation expression levels of the MAPK signal pathway were down-regulated remarkably as well. In silico analysis, taxifolin could form a relatively stable combination with MAPK signal pathway. MAPK inhibitors showed increasing or decreasing effect in the mRNA levels of iNOS, VEGF, COX-2 and TNF-α, which suggesting that taxifolin down-regulated iNOS, VEGF, COX-2 and TNF-α expressions were not entirely through the MAPK pathway. Conclusion: This finding demonstrated that taxifolin improved the inflammatory responses that partly involved in the phosphorylation expression level of MAPK signal pathway in RAW264.7 cells exposed to acute stress.
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Objective:To establish the patient derived xenograft (PDX) model of liver malignant tumor, analyze the related factors affecting the carcinogenesis of PDX model, and analyze the differences of biological characteristics between the primary tumor and PDX model.Methods:Fresh liver malignant tumor tissue samples were collected from the patients who received the surgery from the Tianjin First Central Hospital and the samples were inoculated subcutaneously into BALB/c-nu mice. The correlations between clinicopathological information and tumor formation rate were analyzed, and the pathological morphology and specific protein expression of PDX model and primary tumor were compared.Results:Thirty-three PDX models were successfully established from 63 cases of liver malignant tumors. The overall tumor formation rate was 52.4% (33/63), including 46.3% (25/54) of primary liver cancer and 88.9% (8/9) of liver metastasis. The main factors affecting the tumor formation rate were tumor pathological type, distant metastasis and TNM stage (all P<0.05). The pathological morphology and specific protein expression of PDX model and primary tumor were similar. Conclusion:The PDX model of liver malignant tumor was successfully constructed, and the tumor formation rate was high, and can maintain the biological characteristics of the primary tumor.
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OBJECTIVE@#To observe the effect of moxibustion at oppositely-located points "Mingmen" (GV 4) and "Shenque" (CV 8) on the motor function of the hind limbs and bladder function in rats with neurogenic bladder after suprasacral spinal cord injury (SCI), so as to explore the effect of this therapy on bladder tissue apoptosis mediated by endoplasmic reticulum stress pathway.@*METHODS@#Twenty-eight female Wistar rats were randomly divided into a sham-operation group (8 rats) and a model establishment group (20 rats). Using the modified Allen's method, the spinal cord of T10 segment was injured to establish a neurogenic bladder model in the model establishment group. Sixteen rats were modeled successfully and then divided into a model group (8 rats) and a moxibustion group (8 rats). In the moxibustion group, 2 h after consciousness regaining from modeling anesthesia, moxibustion was exerted at "Shenque" (CV 8) and "Mingmen" (GV 4), 2 cones at each acupoint in one intervention. The intervention was administered once every two days and 5-time intervention was required totally. After intervention, Basso, Beattie and Bresnahan locomotor rating scale (BBB) score for the motor function of the hind limbs, and the urodynamics indexes (maximum bladder capacity, urine leakage pressure and bladder compliance) were compared among groups. HE staining method was adopted to observe the morphological changes of bladder tissue. With Western blot method and real-time PCR assay, the protein and mRNA expressions of the endoplasmic reticulum stress-related genes (glucose- regulated protein 78 [GRP78], activating transcription factor 4 [ATF4] and cysteinyl aspartate specific proteinase-12 [Caspase-12]) were determined.@*RESULTS@#The transitional epithelial cells were arranged irregularly, the bladder wall was getting thinner, and the cellular vacuolar degeneration and neutrophil infiltration were found in the model group. Whereas, compared with the model group, in the moxibustion group, the arrangement of transitional epithelial cells was clear and continuous in layers, the cellular vacuolar degeneration was mild and the infiltration presented in a small amount of neutrophil granulocytes. Compared with the sham-operation group, in the model group, the BBB score was reduced (P<0.01), the maximum bladder capacity and bladder compliance were increased (P<0.01), and the protein expression levels of GRP78, ATF4 and Caspase-12, as well as mRNA expressions were all increased (P<0.01). In comparison with the model group, in the moxibustion group, BBB score was increased (P<0.01), the maximum bladder capacity and bladder compliance were decreased (P<0.01), and the protein and mRNA expression levels of GRP78, ATF4 and Caspase-12 were all decreased (P<0.01).@*CONCLUSION@#Moxibustion at the "oppositely-located points" improves the urination function, alleviate urine retention in neurogenic bladder rats after spinal cord injury. The underlying mechanism may be related to the down-regulation of the expressions of GRP78, ATF4 and Caspase-12 in the endoplasmic reticulum stress pathway of the bladder tissues, and thus to alleviate the apoptosis of bladder tissue.
Subject(s)
Animals , Female , Rats , Caspase 12/genetics , Electroacupuncture , Endoplasmic Reticulum Stress , Moxibustion , RNA, Messenger , Rats, Sprague-Dawley , Rats, Wistar , Spinal Cord , Spinal Cord Injuries/therapy , Urinary Bladder, Neurogenic/therapyABSTRACT
With the development and marketing of a variety of new anti-tumor drugs, it the patients with liver cancer were benefited but it also raised a series of new problems. How to develop individualized therapeutic plans for the patients with liver cancer has always been bothering the clinicians. Patient-derived xenograft model retains the histological characteristics, molecular diversity and microenficity of human-derived tumors, and it can help conduct in vitro experiments, which can solve the above problems to a certain extent. This article summarizes the research progress of the application of patient-derived xenograft models on the diagnosis and treatment of primary liver cancer.
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Objective:To examine the incidence of lymphatic leakage after pediatric liver transplantation and explore the diagnosis and treatment of lymphatic leakage.Methods:From January 1, 2016 to December 31, 2019, clinical data were analyzed retrospectively for 805 pediatric liver transplant recipients. Based upon the diagnosis of lymphatic leakage, they were divided into two groups of lymphatic leakage ( n=271) and lymphatic non-leakage ( n=534). Analyzing the incidence of lymphatic leakage after liver transplantation in children, evaluating the treatment plan, comparing survival rate and the incidence of postoperative complications between two groups. Results:The incidence of lymphatic leakage was 33.7%(271/805); the proportion of partial liver donors was 14.8% in lymphatic leakage group and 25.8% in lymphatic non-leakage group ( P<0.001). Other basic profiles of two groups were not statistically different. The median follow-up period was 32 months in lymphatic leakage group and 30.6 months in lymphatic non-leakage group. No significant inter-group difference existed in cumulative survival rate, vascular complications, bile leakage, acute cell rejection or intestinal obstruction. The area-under-curve (AUC) of ascites to serum triglyceride (TG) ratio for predicting lymphatic leakage was 0.741, optimal cut-off value 0.54, sensitivity 59.2% and specificity 80.1%. Conclusions:Lymphatic leakage is a common complication after liver transplantation in children. With no significant correlation with the morbidity or mortality, it prolongs postoperative hospital stay. The ratio of ascites to serum TG may be utilized as an effective reference index for diagnosing lymphatic leakage. And lymphatic leakage can be improved by taking a low-fat diet.
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Objective:To explore the clinicalfactors related to allograft fibrosis after pediatric liver transplantation.Methods:The clinical data were respectively analyzed for 94 pediatric recipients from January 2013 to December 2016 at Tianjin First Central Hospital.The Patients were assigned into fibrotic and non-fibrotic groups based upon the results of protocol liver biopsies. Univariate and multivariate Logistic regression analyses were performed for examining the risk factors of fibrosis after pediatric livertransplantation. Then Logistic regression model was established to obtain the predicted value of combined predictive factors.Thereceiver operating characteristic curve (ROC) was conducted to evaluate the predictive value of combined predictive factors.Results:A total number of 54(57.5%) patients occurred fibrosis among the 94 patients. There weresignificant differences in cold ischemia time (Z=2.094), warm ischemia time (Z=2.421), biliary stricture( χ2=4.560), drug-induced liver injury ( χ2=7.389), hepatic artery thrombosis and rejection ( χ2=6.955)between two groups ( P<0.05). Logistic regression analysis showed that cold ischemia time (OR=1.003, 95%CI: 1.000~1.007, P=0.044), biliary stricture(OR=6.451, 95%CI: 1.205~33.295), rejection(OR=2.735, 95%CI: 1.057~7.077)and drug-induced liver injury (OR=4.977, 95%CI: 1.207~20.522, P=0.026) were independent risk factors for fibrosis 5 years after liver transplantation. The area under the ROC curve was 0.786(95%CI: 0.691~0.881), for predicting patient outcome.If using 0.311as a cutoff Value, the sensitivity was 90.70%, and the specificity was 60.00%. However, through the ROC curve comparison, there was statistical significance between combined predictive factors and the other independent risk factors ( P>0.05). Conclusions:The incidence of fibrosis 5 years after pediatricliver transplantation is 57.5%. Prolonged cold ischemia time, biliarystricture, rejectionand drug-induced liver injury after liver transplantation are independent risk factors for fibrosis 5 years after pediatric liver transplantation.And the combined predictive factors have a high predictive value forallograftfibrosis.
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OBJECTIVES@#This study aimed to explore the changes in the expression of the characteristic transcription factor retinoid related orphan receptor γt (RORγt) and the cytokine interleukin-17 (IL-17) of T helper cell 17 (Th17) in the pressure side of the periodontal tissue of rats under different orthodontic forces. Their effects on the expression of osteoprotegerin (OPG) and the quantity of osteoclast (OC) were also explored. The role of Th17 cell in alveolar bone remodeling under different forces was preliminarily investigated.@*METHODS@#A total of 108 rats were chosen and randomly divided into three groups. Mesial forces of 0, 50, and 100 g were loaded on the maxillary first molar in the three groups. The rats were executed at 0, 1, 3, 5, 7, and 14 days. The expression of RORγt mRNA was quantified by real-time quantitative polymerase chain reaction. The expression of IL-17 protein was quantified by enzyme linked immunosorbent assay. The expression levels of RORγt and OPG proteins were quantified, and the quantity of OC was counted via immunohistochemistry.@*RESULTS@#The expression levels of RORγt and IL-17 and the quantity of OC increased first and then decreased in the 50 and 100 g groups, and the peak values of the two groups were on days 5 and 7, respectively. The expression levels in the 50 g group basically recovered to normal level on day 14, while that in the 100 g group remained at a high level. The expression levels in the 50 g group were higher than those in the 0 g group and lower than those in the 100 g group. The expression of OPG in the 50 g group decreased first, then increased, and finally decreased. It basically recovered to normal level on day 14. The expression of OPG in the 100 g group decreased first and then increased. It remained at a high level on day 14. The expression in the 50 g group was significantly higher than that in the 0 g group on day 7, while the expression in the 100 g group was significantly higher than that in the 0 g group on day 14.@*CONCLUSIONS@#RORγt, IL-17, and OPG were expressed regularly over time under different orthodontic forces, indicating that Th17 participated in the process of bone resorption on the pressure side of periodontal tissue by secreting IL-17.
Subject(s)
Animals , Rats , Bone Resorption , Cytokines , Interleukin-17 , Molar , Nuclear Receptor Subfamily 1, Group F, Member 3 , Osteoclasts , Osteoprotegerin , Th17 Cells , Tooth Movement TechniquesABSTRACT
OBJECTIVE@#To compare the clinical efficacy of cupping treatment combined with antibiotics and antibiotics alone for bacterial pneumonia in children.@*METHODS@#A total of 72 children with bacterial pneumonia were randomly divided into an observation group (36 cases, 1 case dropped off) and a control group (36 cases). The children in the control group were treated with intravenous drip of cefodizine sodium [80 mg/(kg•d)] for 7 days. Based on the treatment of the control group, the children in the observation group were treated with cupping treatment on the bladder meridian of the back on the first day and the fourth day of antibiotic treatment; each cupping treatment was given for 5-10 min; the treatment of observation group was given for 7 days. The days for complete fever reduction, TCM syndrome scores and Canadian acute respiratory illness flu scale (CARIFS) scores before and after treatment were observed, and the clinical efficacy was evaluated.@*RESULTS@#The days for complete fever reduction in the observation group were shorter than that in the control group (@*CONCLUSION@#Cupping treatment combined with antibiotics has similar efficacy with antibiotics alone for bacterial pneumonia in children, but shows better effect in shortening the duration of fever and improving pulmonary symptoms.
Subject(s)
Child , Humans , Anti-Bacterial Agents , Canada , Cough , Cupping Therapy , Pneumonia, Bacterial , Treatment OutcomeABSTRACT
BACKGROUND@#Circular RNA ciRS-7 has been reported to be involved in the progression of various cancers. However, ciRS-7 expression and its role in clear cell renal cell carcinoma (ccRCC) progression remains unclear. This study aimed to investigate the effect of ciRS-7 expression on ccRCC and the related signaling pathway.@*METHODS@#ciRS-7 expression was analyzed using quantitative reverse transcription polymerase chain reaction in 87 pairs of ccRCC and matched adjacent normal tissues. The role of ciRS-7 in ccRCC cell proliferation and invasion was determined using the cell counting kit-8 and invasion assays, respectively. Potential mechanisms underlying the role of ciRS-7 in promoting ccRCC progression were explored by Western blotting. The relationship between the expression of ciRS-7 and features of ccRCC was analyzed by the Chi-square test and progression-free survival was determined using a Kaplan-Meier plot.@*RESULTS@#ciRS-7 was overexpressed in ccRCC tissues compared with that in matched adjacent normal tissues. In addition, ciRS-7 up-regulation was closely associated with tumor diameter (P = 0.050), clinical stage (P = 0.009), and distant metastasis (P = 0.007). ciRS-7 knockdown in 786O and 769P cells markedly inhibited their proliferative and invasive abilities. In addition, ciRS-7 inhibition reduced phosphorylated epidermal growth factor receptor (p-EGFR) and phosphorylated serine/threonine kinase (p-Akt) levels.@*CONCLUSIONS@#ciRS-7 up-regulation could promote ccRCC cell proliferation and invasion, which may be related with the EGFR/Akt signaling pathway. ciRS-7 might be a potential ccRCC therapeutic target.
ABSTRACT
Objective:To explore the preventive efficacy of 2-week ganciclovir intravenous injection for CMV infection after pediatric liver transplantation(LT).Methods:Clinical data were retrospectively analyzed for 404 pediatric LT recipients from January 1, 2015 to December 31, 2017. According to whether or not ganciclovir was intravenously administered for preventing CMV infection, they were divided into two groups of prevention(235 cases)and non-prevention(169 cases). The preoperative, intraoperative and postoperative follow-up data of two groups were recorded. Survival rate, incidence of CMV infection and time of initial CMV infection were compared between two groups.Results:The median follow-up time of 404 pediatric liver transplantation recipients was 856 days and the incidence of CMV infection 39.1%. No inter-group statistical difference existed in such basic clinical data as gender, age, primary disease, preoperative PELD score, CHILD grade, operative duration, intraoperative blood loss, immunosuppressive regimen or rejection rate. The median follow-up time of two groups was 1014 and 731 days; The incidence of CMV infection 37.4%(88/235)and 41.4%(70/169); The average postoperative time of initial CMV infection 75.5 and 110.2 days; The rate of CMV re-infection after initial CMV infection 26.1%(23/88)and 18.6%(13/70)respectively. No significant inter-group differences existed( P>0.05). Conclusions:Early postoperative 2-week intravenous ganciclovir injection fails to reduce the incidence of CMV infection after pediatric LT, nor delay the occurrence time of CMV infection. It is not recommended as a preventive program for CMV infection after pediatric LT.