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Objective To explore the predictive value of the model for end-stage liver disease (MELD) score, energy metabolism and serum thyroid hormone levels on the severity and prognosis of patients with liver failure and their correlation. Methods This study collected clinicopathological data from 60 liver failure patients, e.g., end-stage liver disease (MELD) score, energy metabolism, and serum thyroid hormone levels. The χ 2 test was performed to analyze the categorical variables, while the Mann-Whitney U test and independent sample t test were performed to assess the continuous variables between the two groups. Spearman correlation coefficient test was used to evaluate correlation of each index. The receiver operating characteristic (ROC) curve was used to analyze the optimal cut-off points of serum total triiodothyronine (TT3) and free triiodothyronine (FT3) levels in predicting prognosis of the patients. Results The rates of low TT3 and FT3 levels in liver failure patients were 78.2% and 69.1%, respectively, whereas the low TT3 rates were 95.2% and 67.6% and the low FT3 rates were 90.5% and 55.9% in survival and non-survival groups of patients, respectively (both P < 0.05). Moreover, the MELD score was significantly higher in the non-survival patients than in survival patients [26.0(21.0-29.0) vs 21.0 (19.0-24.0), Z =-3.396, P =0.001], while TT3 and FT3 levels were significantly lower in the non-survival patients than in the survival patients [0.69(0.62-0.73) vs 0.83(0.69-0.94) and 2.17(1.99-2.31) vs 2.54(2.12-2.86), respectively; Z =-2.884、-2.876, all P < 0.01]. The MELD score was negatively associated with serum TT3, FT3, and thyroid stimulating hormone (TSH) levels and the respiratory quotient (RQ) ( r =-0.487、-0.329、-0.422、-0.350, all P < 0.01), whereas the RQ was associated with serum TT3 and FT3 levels ( r =0.271、0.265, all P < 0.05). The optimal cutoff values in predicting the severity and survival of patients was 0.75 nmol/L and 2.37pmol/L with the sensitivity values of 67.6% and 64.7% and the specificity of 90.5% and 81.0%, respectively. Conclusion Abnormal thyroid hormone levels and low respiratory quotient could be used to predict the severity and prognosis of patients with liver failure.
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Traditional pig breeding has a long cycle and high cost, and there is an urgent need to use new technologies to revitalize the pig breeding industry. The recently emerged CRISPR/Cas9 genome editing technique shows great potential in pig genetic improvement, and has since become a research hotspot. Base editor is a new base editing technology developed based on the CRISPR/Cas9 system, which can achieve targeted mutation of a single base. CRISPR/Cas9 technology is easy to operate and simple to design, but it can lead to DNA double strand breaks, unstable gene structures, and random insertion and deletion of genes, which greatly restricts the application of this technique. Different from CRISPR/Cas9 technique, the single base editing technique does not produce double strand breaks. Therefore, it has higher accuracy and safety for genome editing, and is expected to advance the pig genetic breeding applications. This review summarized the working principle and shortcomings of CRISPR/Cas9 technique, the development and advantages of single base editing, the principles and application characteristics of different base editors and their applications in pig genetic improvement, with the aim to facilitate genome editing-assisted genetic breeding of pig.
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Animals , Swine/genetics , Gene Editing , CRISPR-Cas Systems/genetics , DNA Breaks, Double-StrandedABSTRACT
Objective To establish a new patient-derived xenograft (PDX) model of human liver cancer by inoculating the complex of human primary liver cancer cells and a novel microcarrier (microcarrier 6) into mice with normal immune function. Methods Primary liver cancer cells were isolated and extracted from the fresh human liver cancer tissue of five patients and were then co-cultured with microcarrier 6 to construct a three-dimensional tumor cell culture model in vitro . According to the type of graft, 75 male C57BL/6 mice were divided into cell control group, microcarrier control group, and experimental group (each sample corresponded to three groups, with 15 groups in total and 5 mice in each group). The liver cancer cell-microcarrier complex was implanted into the mice by subcutaneous inoculation, and tumor formation time, tumor formation rate, and histopathological manifestations were observed. The Fisher's exact test was used for comparison of categorical data between two groups. Results As for the liver cancer cells from the five patients, tumor formation was observed in the mice corresponding to three patients. In these three experiments, tumor formation was not observed in the control groups and was only observed in the experimental groups, and 12 of the 15 mice in the experimental groups had successful tumor formation, with a tumor formation rate as high as 80%, which was significantly different from that in the cell control groups and the microcarrier control groups (all P < 0.05). The tumor formation time was 5-7 days; the xenograft tumor grew rapidly, and HE staining showed nested or flaky cells with obvious heteromorphism, with the presence of pathological mitosis; immunohistochemical staining showed positive CK8/18, Hep, and Gpc-3, which was in accordance with the characteristics of human liver cancer cells. Conclusion This experiment successfully establishes a new PDX model of human liver cancer based on the complex of microcarrier 6 and human primary liver cancer cells in mice with normal immunity. This model can be used to better elucidate the mechanism of the development and progression of liver cancer in the body with normal immunity, and besides, it also provides a new animal model with higher value for the precise treatment of liver cancer.
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ObjectiveTo investigate the ability of Ganshuang granule (a liver-protecting drug widely used in clinical practice) extract to reduce N-acetyl-p-aminophenol (APAP)-induced hepatotoxicity and possible mechanisms. MethodsA total of five cell culture groups were set up in this experiment, i.e., normal control group, APAP injury group, and three injury protection groups treated with different concentrations of Ganshuang granule extract. Then 20 mmol/L APAP was added to the cell culture medium and incubated for 24 hours to establish an in vitro model of drug-induced liver injury, and the injury protection groups were treated with different concentrations of Ganshuang granule extract (0.2, 1, and 5 μg/ml) in advance for 8 hours of incubation before APAP were added for 24 hours. Related markers were measured, including the markers for hepatocellular injury ［alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH)］, the markers for mitochondrial injury ［mitochondrial membrane potential, and glutamate dehydrogenase (GDH)］, and antioxidant and oxidative stress markers ［glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), and reactive oxygen species (ROS)］. Related mechanism was discussed based on the experimental results. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups. ResultsGanshuang granule extract alleviated APAP-induced hepatotoxicity, improved cell viability (P＜0001), and reduced the levels of AST, ALT, and LDH in supernatant (P＜0.001, P＜0.001, and P＜0.05). Ganshuang granule extract inhibited APAP-induced hepatocellular oxidative stress, and compared with the APAP group, the Ganshuang granule extract groups had significant reductions in the oxidative stress indicators ROS and MDA (both P＜0.01). Ganshuang granule extract alleviated the loss of mitochondrial membrane potential induced by APAP (P＜0.05) and reduced the content of the mitochondrial injury marker GDH in supernatant (P＜0.001) in a dose-dependent manner. Ganshuang granule extract inhibited the expression of CYP2E1/1A2 (both P＜0.05) and increased the expression of phase Ⅱ enzymes in hepatocytes. Ganshuang granule extract induced the expression of Nrf2 and its downstream genes NQO-1 and GCLC (all P＜0.05). ConclusionGanshuang granule extract can prevent APAP-induced hepatocellular injury through two ways. The first way is that Ganshuang granule extract downregulates the expression of CYP2E1/1A2 and thus reduces the production of NAPQI, a toxic product of APAP; the second way is that Ganshuang granule extract upregulates the expression of the detoxification pathway, which can activate Nrf2 to increase the expression of antioxidant enzymes (SOD and GSH) and phase Ⅱ enzymes and thus accelerate the harmless metabolism of APAP.
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ObjectiveTo investigate the effect of intraperitoneal transplantation of human liver-derived stem cells in the prevention and treatment of alcoholic fatty liver disease in mice. Methods A total of 30 male C57BL/6 mice were randomly divided into blank control group (group N), model control group (group M), and stem cell transplantation group (group S). The mice in group N were fed a normal diet, and those in the other two groups were fed Lieber-DeCarli alcohol liquid diet; at the same time, the mice in group S were given intraperitoneal transplantation of human liver-derived stem cells twice a week. After six weeks of intervention, body weight and liver index were measured, and the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were also measured. The levels of TG and non-esterified fatty acid (NEFA) in the liver were measured, and liver pathological examination and oil red O staining of the liver were performed. One-way ANOVA was used for comparison of continuous data between multiple groups, and the SNK-q test was used for further comparison between two groups. Results There were significant differences in the serum levels of ALT, AST, TG, TC, and HDL-C and the content of TG and NEFA in the liver between the three groups (F=66.94, 7.15, 8.02, 18.64, 386, 2314 and 3049, all P＜0.05), Compared with group N, group M showed significant increases in levels of ALT, AST, and TG in serum and levels of TG and NEFA in liver tissue (all P＜0.05). Group S had significantly lower levels of ALT, AST, and TG in serum and levels of TG and NEFA in liver tissue than group M (all P＜0.05). Liver HE staining and oil red O staining showed that group S had a significantly lower degree of liver steatosis than group M. ConclusionIntraperitoneal transplantation of human liver-derived stem cells has a marked effect in the prevention and treatment of alcoholic fatty liver disease in mice.
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ObjectiveTo investigate the effect of intraperitoneal transplantation of human liver-derived stem cells in the prevention and treatment of alcoholic fatty liver disease in mice. Methods A total of 30 male C57BL/6 mice were randomly divided into blank control group (group N), model control group (group M), and stem cell transplantation group (group S). The mice in group N were fed a normal diet, and those in the other two groups were fed Lieber-DeCarli alcohol liquid diet; at the same time, the mice in group S were given intraperitoneal transplantation of human liver-derived stem cells twice a week. After six weeks of intervention, body weight and liver index were measured, and the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were also measured. The levels of TG and non-esterified fatty acid (NEFA) in the liver were measured, and liver pathological examination and oil red O staining of the liver were performed. One-way ANOVA was used for comparison of continuous data between multiple groups, and the SNK-q test was used for further comparison between two groups. Results There were significant differences in the serum levels of ALT, AST, TG, TC, and HDL-C and the content of TG and NEFA in the liver between the three groups (F=66.94, 7.15, 8.02, 18.64, 386, 2314 and 3049, all P＜0.05), Compared with group N, group M showed significant increases in levels of ALT, AST, and TG in serum and levels of TG and NEFA in liver tissue (all P＜0.05). Group S had significantly lower levels of ALT, AST, and TG in serum and levels of TG and NEFA in liver tissue than group M (all P＜0.05). Liver HE staining and oil red O staining showed that group S had a significantly lower degree of liver steatosis than group M. ConclusionIntraperitoneal transplantation of human liver-derived stem cells has a marked effect in the prevention and treatment of alcoholic fatty liver disease in mice.
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Objective@#To investigate the protective effect of intraperitoneal transplantation of human liver-derived stem cells at different times against concanavalin A (ConA)-induced acute liver injury in mice.@*Methods@#A total of 88 male C57BL/6 mice were randomly divided into normal control group (group C), ConA model group (group M), and human liver-derived stem cells (HYX1)+ConA group (group E); according to the interval between phosphate buffer/HYX1 injection and ConA injection, Groups M and E were further divided into 3-hour groups (M1 and E1 groups), 6-hour groups (M2 and E2 groups), 12-hour groups (M3 and E3 groups), 24-hour groups (M4 and E4 groups), and 48-hour groups (M5 and E5 groups). The levels of alanine aminotransferase (ALT), aspartate transaminase (AST), and total bilirubin (TBil) in peripheral blood were measured, liver tissue sections were used to observe pathological changes, and the Ishak score for liver inflammation was determined. The independent samples t-test was used for comparison between groups, and P < 0.05 was considered statistically significant.@*Results@#The levels of ALT, AST, and TBil in group C were (36.25±1.16) U/L, (120.20±5.77) U/L, and (2.20±0.23) μmol/L, respectively; the levels of ALT, AST, and TBil and Ishak score were (8 721.23±837.39) U/L, (8 110.31±290.10) U/L, (8.41±0.10) μmol/L, and (13.32±1.30), respectively, in group M1, (8 334.31±666.50) U/L, (7 560.20±760.34) U/L, (10.40±0.80) μmol/L, and (12.67±0.81), respectively, in group M2, (8 960.75±551.93) U/L, (8 535.62±675.14) U/L, (10.95±1.43) μmol/L, and (14.57±0.65), respectively, in group M3, (8 618.57±886.40) U/L, (11 440.54 ± 1 327.86) U/L, (13.30±1.86) μmol/L, and (13.21±1.06), respectively, in group M4, and (10 170.13±1 112.37) U/L, (11 470.56±1 108.40) U/L, (12.75±1.55) μmol/L, and (15.07±1.58), respectively, in group M5. The levels of ALT, AST, and TBil and Ishak score were (1 016.35±163.47) U/L, (952.30±103.91) U/L, (7.77±0.62) μmol/L, and (3.50±0.21), respectively, in group E1, (42.10±6.20) U/L, (126.72±13.33) U/L, (3.41±0.53) μmol/L, and (2.01±0.40), respectively, in group E2, (44.21±4.30) U/L, (216.71±35.88) U/L, (3.47±0.44) μmol/L, and (2.13±0.25), respectively, in group E3, (2 909.69±212.14) U/L, (2 988.43±333.70) U/L, (7.03±0.93) μmol/L, and (4.70±0.50), respectively, in group E4, and (7 874.26±799.60) U/L, (10 940.54±947.35) U/L, (10.53±1.09) μmol/L, and (8.60±0.83), respectively, in group E5. Groups M1-M5 had significantly higher levels of ALT, AST, and TBil than group C (all P < 0.01), and groups M1-M4 had significantly higher levels of AST and ALT than groups E1-E4 (all P < 0.01), while there were no significant differences in the levels of AST and ALT between groups M5 and E5 (both P > 0.05). The pathological sections of liver tissue showed that compared with group M, group E had significant reductions in the degree of necrosis and Ishak score (both P < 0.05).@*Conclusion@#Intraperitoneal transplantation of human liver-derived stem cells has a protective effect against ConA-induced acute liver injury in mice, and the injection at 6 and 12 hours in advance has the best protective effect.
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Objective:To establish a mouse model of gastric cancer by inoculating MKN45 cells into mice with normal immune function utilizing microcarrier technology. Methods:A total of 60 male C57BL/6 mice were randomly divided into three groups, namely, 2D, con-trol, and 3D groups, according to the coculture system of MKN45 and microcarrier. The mouse models of gastric carcinoma were estab-lished by hypodermic injection. The time of tumorigenesis, rate of tumor formation, and pathological features were observed in each group. Results:In the 3D group, the time of tumor formation was short, whereas the rate of tumor formation was high (80%). No de-tectable tumor formations were observed in the 2D and control groups. HE and immunohistochemical staining of the transplantation tumor model showed evident characteristics of human gastric cancer. Conclusion:A human gastric cancer model in normal immune mice was successfully established. The onset and development mechanism of gastric cancer could be more effectively investigated in mice with normal immune function through this model. Moreover, a more valuable and new animal model for the research and devel-opment of anticancer drug was established.
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Hedgehog (Hh) signaling pathway is closely associated with the development of various types of human tumors.Recent studies have reported that Hh pathway plays an important role in oncogenesis,metastasis and therapy of colorectal neoplasms.Currently, Hh signals have been detected highly expressed in colorectal cancer tissues and cells.Inhibition of this pathway can deeply restrain the invasion and metastasis of colorectal cancer cells.And it has become a hot topic that Hh pathway is used as a target in the treatment of colorectal cancer.
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ObjectiveTo investigate the clinical efficacy of combined traditional Chinese and western medicine for treatment of patients with deep venous thrombosis(DVT)in lower extremity.Methods A retrospective study was conducted. Forty patients with DVT admitted into Mindong Hospital Affiliated to Fujian Medical University were randomly divided into control and treatment groups, 20 cases in each group. Conventional therapy was given in both groups. The patients in control group were hypodermically injected with low molecular heparin 3.075 kU, and orally took warfarin sodium; the former injection was terminated on the 3rd day, and afterwards warfarin was solely administered. On the basis of the treatment in the control group, the patients in treatment group were additionally treated with Huoxue Tongmai decoction(ingredients: peach kernel 15 g, red paeonia 15 g, honeysuckle flower 15 g, rhizoma alismatis 12 g, semen coicis 30 g, semen plantaginis 9 g, suberect spatholobus stem 12 g, radix scrophulariae 9 g, pawpaw 12 g, radix achyranthis bidentatae 12 g), the formula could be modified in accordance with patients' symptoms and signs, and Jiangjun powder was applied at the lesion externally(ingredients of the powder: rhubarb 250 g, mirabilite 200 g, flour 100 g, vinegar 500 g were mixed to form a smooth paste), once a day, 30 days constituting a therapeutic course and totally 2 courses being taken. The perimeter of the affected limb, visual analogy score(VAS), revascularization rate, curative effect and adverse reaction were observed before and after treatment and compared between the two groups.Results The total effective rate in treatment group was higher than that in control group〔90.0%(18/20) vs. 70.0%(14/20),P<0.05〕. After treatment, the perimeter of the affected limb in both groups was significantly smaller than that before treatment, the decrease in treatment group being more marked〔the upper leg(cm):46.21±4.80 vs. 53.18±4.45, the lower leg(cm): 32.57±4.26 vs. 36.21±5.01, bothP<0.05〕. TheVAS scores were significantly decreased in both groups after treatment for 1 month, they reached the valley values after treatment for 2 months, the degree of descent being more significant in the treatment group(2.24±0.58 vs. 3.36±0.61,P<0.01). The revascularization rate of the treatment group after treatment was higher than that of the control group〔85.0%(17/20) vs. 70.0%(14/20),P<0.05〕.ConclusionThe combined treatment of traditional Chinese and western medicine was obviously superior to the sole western medicine for treatment of patients with DVT.
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Objective To study the expression of microtubule-associated protein-2 (MAP-2) in the CA3 region of the hippocampus and any effect of acupuncture combined with exercise training on the recovery of learning and memory after experimental cerebral infarction.Methods Eighty Wistar rats were randomly divided into a sham-operation group (n = 8 ) and an operation group (n = 72 ) subdivided randomly and equally into a model group, an exercisetraining group and an acupuncture plus exercise training group, with 24 rats in each group. After right middle cerebral artery occlusion or a mock operation, the expression of MAP-2 in the CA3 region of the hippocampus was detected with immunohistochemistry 1, 3 and 5 weeks after the operation. Learning and memory function was assessed at the 5th week post operation.Results MAP-2- positive fibers were arranged in an orderly way and distributed densely in the shamoperation group. After cerebral infarction, number of MAP-2 positive neurons and dendrite fibers decreased in the CA3 region of the affected side. A week after the operation, MAP-2 positive fibers had increased significantly in the acupuncture plus exercise group compared with the model group and the exercise group. At the 3rd and 5th week post operation, expression of MAP-2 and optical density had increased significantly compared with the model group and the exercise training group. At the 5th week post operation, Y maze discrimination and learning tests showed that learning and memory had improved significantly more in the acupuncture plus exercise training group compared with the model group and the exercise training group.Conclusions Exercise training combined with acupuncture can promote changes in dendritic plasticity and increase MAP-2 expression in the CA3 region after cerebral infarction. This may be correlated positively with the recovery of learning and memory after cerebral infarction, at least in rats.
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@#Objective To observe the therapeutical effect of inflatable shoulder harness on hemiplegia subluxation of shoulder joint.Methods 68 stroke patients with hemiplegia subluxation of shoulder joint were divided into two groups: the experiment group (n=34) and the control group (n=34). All the patients accepted routine rehabilitation for subluxation of shoulder joint, meanwhile, the experiment group wore inflatable shoulder harness. The interval between acromion and caput humeralis were measured according to the X-ray before and after treatment, as well as the Fugl-Meyer Assessment and Visual Analogue Scale (VAS) of shoulder pain. Results After 8 week of treatment, the rate of diaplasis or improvement was not different significantly between these groups (P<0.05). Compared to the control group, the incidence and VAS score of shoulder pain, and the score of Fugl-Meyer Assessment improved significantly after the treatment (P<0.05). Conclusion On the basis of routine rehabilitation, inflatable shoulder harness may reduce the incidence and grade of shoulder pain, improve motor function of hemiplegic upper limb further in hemiplegia subluxation of shoulder.
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@#Objective To investigate the effects of intensive training and on the activity of daily living (ADL) and motor function in cerebral infarction patients. Methods 52 cerebral infarction patients with early rehabilitation were divided into an experiment group (n=26) and a control group (n=26). All patients were treated with the conventional training. Meanwhile, the patients in the experimental group were also treated with intensive training. The Modified Barthels Index (MBI) and brief-style Fugl-Meyer assessment (FMA) were used to evaluate the ADL and motor function before and 1 month after treatment. Results The scores of MBI and FMA were significantly different between the two groups 1 month after treatment (P＜0.05). Conclusion Intensive training can improve the ADL and motor function more than conventional training in cerebral infarction patients.
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OBJECTIVE: How to promote the generation of neural stem cells (NSCs) and induce them differentiate into the goal cell type has been the focus of neuroscience. In this article, we review the adjustment of basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) to the proliferation and differentiation of NSCs. DATA SOURCES: A computer-based online search of Medline database was undertaken to identify the related articles published in English from January 1998 to March 2006 by using the keywords of "bFGF, EGF, nerve stem cells". At the same time, Chinese relevant articles were searched in China National Knowledge Infrastruction published between January 2000 and March 2006 with the same keywords in Chinese. STUDY SELECTION: The data were selected firstly to look over the citations of every literature. Inclusive criteria: Articles related to the effect of bFGF and EGF on the proliferation and differentiation of NSCs. Exclusive criteria: Duplicate research or Meta analysis. DATA EXTRACTION: A total of 78 related articles were collected, of which 32 accorded with the inclusive criteria and 46 with duplicate or old contents literatures were eliminated. Among the 32 literatures, 8 involved in the research status of NSCs, 10 about the effect of bFGF on the proliferation and differentiation of NSCs and the mechanism, 4 involved in the effect of EGF on the proliferation and differentiation of NSCs and the mechanism, respectively, 8 related to the effect of bFGF and EGF together, and 5 related to the comparison of the effect of bFGF and EGF. DATA SYNTHESIS: ①NSCs are self-renewed, and can differentiate into different stem cells and mature tissue cells in different microenvironment. Many cytokines in the microenvironment play essential roles in the differentiation direction of NSCs. ②bFGF has strong improvement effect on the proliferation of NSCs and can activate the potential regeneration capacity of neuronal precursor cell in distinct areas of central nervous system, proliferation and differentiation of cells present bFGF concentration dependent. ③EGF can improve the growth of NSCs, and promote them differentiate into neuron and glial cells; its effect of facilitating cell proliferation also presents concentration dependent. ④To elevate the efficacy of proliferation and differentiation of NSCs, allied application of bFGF and EGF is usual in NSCs culture. ⑤There is not a unified cognition to the effect difference of bFGF and EGF. CONCLUSION: bFGF and EGF have powerful effect to improve the proliferation and differentiation of NSCs; therefore, both of them are important neural somatomedin. Moreover, their effects present concentration dependent.
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@# Objective To observe the clinical effect of multidisciplinary rehabilitation on diabetic foot.Methods98 diabetic foot patients were divided into the routine treatment group (50 cases), treated only with conventional treatment, and the multidisciplinary rehabilitation group (48 cases) added with multidisciplinary rehabilitation besides conventional treatment.ResultsAfter one month treatment, blood flow parameters of the patients with 0 grade diabetic foot in the multidisciplinary rehabilitation group were markedly improved showed by color Doppler ultrasonograghy of lower limbs ( P<0.05); after two months treatment, the effect of the multidisciplinary rehabilitation group was better than that of the routine treatment group ( P<0.05).ConclusionThe multidisciplinary rehabilitation has obvious effect on diabetic foot and can improve disease recovery earlier.