1.Early imaging and circulating marker features of gallbladder carcinoma
Yongzhong ZHAO ; Yi XUE ; Liqun LI ; Mengsen HOU ; Xiaojun YANG
Basic & Clinical Medicine 2024;44(2):265-269
Gallbladder carcinoma(GBC)is one of the most common malignant tumors in the biliary system,which is difficult to diagnose in the early stage due to its high degree of malignancy,invasiveness and lack of specific clin-ical manifestations.In this paper,we summarize ultrasound,CT and other imaging manifestations in the early stage of GBC,and describe the role of protein markers and microRNA marker as biomarkers in the diagnosis of early GBC.The enhanced understanding of the relevant features might help to improve the accuracy of the diagnosis of early gallbladder carcinoma.
2.Comparative analysis of small shadow morphology between chest CT and DR images of patients with occupational pneumoconiosis
Zhongxue LI ; Xiazi ZHAO ; Yongzhong TANG ; Qianchang LI ; Shiwen HUANG ; Feifei LI ; Xiaoping LI ; Kunhai QIU
China Occupational Medicine 2024;51(3):303-307
Objective To compare the morphology differences in small shadows of occupational pneumoconiosis (hereinafter referred to as "pneumoconiosis") between computed tomography (CT) and digital radiography (DR) imaging. Methods A total of 1 010 pneumoconiosis patients were selected as the research subjects using a judgment sampling method. Chest DR imaging and CT imaging were performed on patients, and the differences in small shadow morphology between the two images were compared. Results In both DR and CT images of patients, circular small shadows identified as p, q, and r shapes accounted for 76.2%, 11.5%, and 1.3%, respectively, while irregular small shadows were identified in 1.8% of cases. There was medium high consistency between DR and CT in detecting these four types of small shadow morphology (Kappa=0.72, P<0.01). The detection rate of irregular small shadows (including interlobular septal thickening, ground-glass opacity, and/or centrilobular emphysema) by CT images was 54.0% (545/1 010), with 88.6% (483/545) of these cases also showing small circular shadows. Irregular small shadows in CT images were mostly identified as p small circular shadows in DR images, accounting for 88.8% (484/545). The results of DR and CT images for p/p, p/q, q/p, q/q, q/r, r/q and r/r in small circular shadows showed medium high consistency (Kappa =0.52, P<0.01). Conclusion The results of CT and DR imaging for pneumoconiosis with small shadow were of medium high consistency, with CT demonstrating advantages in detecting irregular small shadow morphology of pneumoconiosis. CT images can be used to describe the shape of circular small shadow as DR images, and irregular small shadow can be described as interlobular septal thickening, ground-glass opacity, and/or centrilobular emphysema.
3.Effect of transnasal humidified rapid insufflation ventilatory exchange on cerebral oxygen saturation during induction of general anesthesia in patients undergoing traumatic brain injury emergency surgery
Yue ZHAO ; Yang ZHANG ; Tianfeng HUANG ; Yinyin DING ; Yongzhong TAO ; Ju GAO
Chinese Critical Care Medicine 2024;36(4):404-409
Objective:To evaluate the effect of transnasal humidified rapid insufflation ventilatory exchange (THRIVE) on regional cerebral oxygen saturation (rScO 2) during induction of general anesthesia in patients undergoing traumatic brain injury (TBI) emergency surgery. Methods:A prospective randomized controlled trial was conducted. The TBI emergency general anesthesia patients who underwent intracranial hematoma removal surgery at the Northern Jiangsu People's Hospital from January to July in 2023 were enrolled. The patients were divided into a conventional mask ventilation group and a THRIVE group using a random number table method. The patients in the conventional mask ventilation group were anesthetized and induced to pre oxygenate without positive pressure ventilation in the front mask for 10 minutes, with an oxygen flow rate of 8 L/min and an fraction of inspired oxygen (FiO 2) of 1.00. After anesthesia induction for about 90 s, tracheal intubation was performed after the muscle relaxant took effect (patient's jaw muscle was relaxed). The patients in the THRIVE group were pre oxygenated with THRIVE for 10 minutes, with an oxygen flow rate of 30 L/min and a FiO 2 of 1.00. During anesthesia induction, the oxygen flow rate was increased to 50 L/min, and anesthesia induction medication was used. The lower jaw of patient was supported with both hands to maintain airway patency, and the patient's mouth was kept closed throughout the process. After the muscle relaxant took effect (the patient's jaw muscle was relaxed), tracheal intubation was performed. At the time of patient entering the operating room, 10 minutes of pre oxygenation, and immediately after successful intubation, rScO 2 was measured on the surgical and non-surgical sides. At the same time, ultrasound was used to measure the cross-sectional area (CSA) of the gastric antrum and arterial blood gas analysis was performed. The partial pressure of end-tidal carbon dioxide (P ETCO 2) during the first mechanical ventilation after successful tracheal intubation, the incidence of hypoxemia [pulse oxygen saturation (SpO 2) < 0.95] during tracheal intubation, as well as prognostic indicators such as the length of intensive care unit (ICU) stay, total length of hospital stay, and Glasgow outcome scale (GOS) score at discharge were recorded. Results:During the study period, a total of 70 TBI patients underwent emergency general anesthesia surgery, of which 2 patients died postoperatively, 2 patients were unable to cooperate with closed mouth breathing, and 3 patients had poor ultrasound image acquisition in the gastric antrum, all of whom were excluded. A total of 63 patients were ultimately enrolled, including 32 in the conventional mask ventilation group and 31 in the THRIVE group. There were no statistically significant differences in gender, age, body mass index (BMI), American Society of Anesthesiologists (ASA) classification, Glasgow coma scale (GCS) score, optic nerve sheath diameter (ONSD), baseline vital signs, fasting situation, anesthesia time, surgical time, and intraoperative blood loss between the patients in the two groups, indicating comparability. When entering the operating room, there was no statistically significant difference in rScO 2 on the surgical and non-surgical sides, and blood gas analysis indexes arterial partial pressure of oxygen (PaO 2) and arterial partial pressure of carbon dioxide (PaCO 2) between the patients in the two groups. When pre oxygenated for 10 minutes, both the surgical and non-surgical sides rScO 2 levels in the THRIVE group were significantly higher than those in the conventional mask ventilation group (surgical side: 0.709±0.036 vs. 0.636±0.028, non-surgical side: 0.791±0.016 vs. 0.712±0.027, both P < 0.01), and the PaO 2 was significantly increased [mmHg (1 mmHg≈0.133 kPa): 450.23±60.99 vs. 264.88±49.33, P < 0.01], PaCO 2 was significantly reduced (mmHg: 37.81±3.65 vs. 43.59±3.76, P < 0.01), and the advantage continues tilled immediately after successful intubation. There was no statistically significant difference in CSA at each time point of ultrasound examination between the two groups. Compared with the conventional mask ventilation group, the patients in the THRIVE group showed a significant decrease in P ETCO 2 during the first mechanical ventilation after successful tracheal intubation (mmHg: 43.10±2.66 vs. 49.22±3.31, P < 0.01), and the incidence of hypoxemia during tracheal intubation was also significantly reduced [0% (0/31) vs. 28.12% (9/32), P < 0.01]. In terms of prognostic indicators, there was no statistically significant difference in the length of ICU stay and total length of hospital stay between the patients in the conventional mask ventilation group and the THRIVE group [length of ICU stay (days): 10 (9, 10) vs. 10 (9, 11), total length of hospital stay (days): 28.00 (26.00, 28.75) vs. 28.00 (27.00, 29.00), both P > 0.05]. However, the proportion of patients in the THRIVE group with a good prognosis at discharge (GOS score > 3) was significantly higher than that in the conventional mask ventilation group [35.5% (11/31) vs. 12.5% (4/32), P < 0.05]. Conclusion:THRIVE can significantly increase rScO 2 during anesthesia induction in TBI emergency surgery patients and improve their neurological function prognosis.
4.Single base editing system mediates site-directed mutagenesis of genes GDF9 and FecB in Ouler Tibetan sheep.
Yifan ZHAO ; Yingbing ZHANG ; Ruiluan YU ; Ying WU ; Yongzhong CHEN ; Ruolin ZHAO ; Chengtu ZHANG ; Jianmin SU
Chinese Journal of Biotechnology 2023;39(1):204-216
In this study, a single base editing system was used to edit the FecB and GDF9 gene to achieve a targeted site mutation from A to G and from C to T in Ouler Tibetan sheep fibroblasts, and to test its editing efficiency. Firstly, we designed and synthesized sgRNA sequences targeting FecB and GDF9 genes of Ouler Tibetan sheep, followed by connection to epi-ABEmax and epi-BE4max plasmids to construct vectors and electrotransfer into Ouler Tibetan sheep fibroblasts. Finally, Sanger sequencing was performed to identify the target point mutation of FecB and GDF9 genes positive cells. T-A cloning was used to estimate the editing efficiency of the single base editing system. We obtained gRNA targeting FecB and GDF9 genes and constructed the vector aiming at mutating single base of FecB and GDF9 genes in Ouler Tibetan sheep. The editing efficiency for the target site of FecB gene was 39.13%, whereas the editing efficiency for the target sites (G260, G721 and G1184) of GDF9 gene were 10.52%, 26.67% and 8.00%, respectively. Achieving single base mutation in FecB and GDF9 genes may facilitate improving the reproduction traits of Ouler Tibetan sheep with multifetal lambs.
Animals
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Sheep/genetics*
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Gene Editing
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Tibet
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Mutation
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Phenotype
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Mutagenesis, Site-Directed
5.Impact of different diagnostic criteria for assessing mild micro-hepatic encephalopathy in liver cirrhosis: an analysis based on a prospective, multicenter, real-world study
Xiaoyan LI ; Shanghao LIU ; Chuan LIU ; Hongmei ZU ; Xiaoqing GUO ; Huiling XIANG ; Yan HUANG ; Zhaolan YAN ; Yajing LI ; Jia SUN ; Ruixin SONG ; Junqing YAN ; Qing YE ; Fei LIU ; Lei HUANG ; Fanping MENG ; Xiaoning ZHANG ; Shaoqi YANG ; Shengjuan HU ; Jigang RUAN ; Yiling LI ; Ningning WANG ; Huipeng CUI ; Yanmeng WANG ; Chuang LEI ; Qinghai WANG ; Hongling TIAN ; Zhangshu QU ; Min YUAN ; Ruichun SHI ; Xiaoting YANG ; Dan JIN ; Dan SU ; Yijun LIU ; Ying CHEN ; Yuxiang XIA ; Yongzhong LI ; Qiaohua YANG ; Huai LI ; Xuelan ZHAO ; Zemin TIAN ; Hongji YU ; Xiaojuan ZHANG ; Chenxi WU ; Zhijian WU ; Shengqiang LI ; Qian SHEN ; Xuemei LIU ; Jianping HU ; Manqun WU ; Tong DANG ; Jing WANG ; Xianmei MENG ; Haiying WANG ; Zhenyu JIANG ; Yayuan LIU ; Ying LIU ; Suxuan QU ; Hong TAO ; Dongmei YAN ; Jun LIU ; Wei FU ; Jie YU ; Fusheng WANG ; Xiaolong QI ; Junliang FU
Chinese Journal of Hepatology 2023;31(9):961-968
Objective:To compare the differences in the prevalence of mild micro-hepatic encephalopathy (MHE) among patients with cirrhosis by using the psychometric hepatic encephalopathy score (PHES) and the Stroop smartphone application (Encephal App) test.Methods:This prospective, multi-center, real-world study was initiated by the National Clinical Medical Research Center for Infectious Diseases and the Portal Hypertension Alliance and registered with International ClinicalTrials.gov (NCT05140837). 354 cases of cirrhosis were enrolled in 19 hospitals across the country. PHES (including digital connection tests A and B, digital symbol tests, trajectory drawing tests, and serial management tests) and the Stroop test were conducted in all of them. PHES was differentiated using standard diagnostic criteria established by the two studies in China and South Korea. The Stroop test was evaluated based on the criteria of the research and development team. The impact of different diagnostic standards or methods on the incidence of MHE in patients with cirrhosis was analyzed. Data between groups were differentiated using the t-test, Mann-Whitney U test, and χ2 test. A kappa test was used to compare the consistency between groups. Results:After PHES, the prevalence of MHE among 354 cases of cirrhosis was 78.53% and 15.25%, respectively, based on Chinese research standards and Korean research normal value standards. However, the prevalence of MHE was 56.78% based on the Stroop test, and the differences in pairwise comparisons among the three groups were statistically significant (kappa = -0.064, P < 0.001). Stratified analysis revealed that the MHE prevalence in three groups of patients with Child-Pugh classes A, B, and C was 74.14%, 83.33%, and 88.24%, respectively, according to the normal value standards of Chinese researchers, while the MHE prevalence rates in three groups of patients with Child-Pugh classes A, B, and C were 8.29%, 23.53%, and 38.24%, respectively, according to the normal value standards of Korean researchers. Furthermore, the prevalence rates of MHE in the three groups of patients with Child-Pugh grades A, B, and C were 52.68%, 58.82%, and 73.53%, respectively, according to the Stroop test standard. However, among the results of each diagnostic standard, the prevalence of MHE showed an increasing trend with an increasing Child-Pugh grade. Further comparison demonstrated that the scores obtained by the number connection test A and the number symbol test were consistent according to the normal value standards of the two studies in China and South Korea ( Z = -0.982, -1.702; P = 0.326, 0.089), while the other three sub-tests had significant differences ( P < 0.001). Conclusion:The prevalence rate of MHE in the cirrhotic population is high, but the prevalence of MHE obtained by using different diagnostic criteria or methods varies greatly. Therefore, in line with the current changes in demographics and disease spectrum, it is necessary to enroll a larger sample size of a healthy population as a control. Moreover, the establishment of more reliable diagnostic scoring criteria will serve as a basis for obtaining accurate MHE incidence and formulating diagnosis and treatment strategies in cirrhotic populations.
6.Relationships between serum lipids, CA153 level and breast cancer incidence and clinicopathological features of patients
Yixin ZHAO ; Yinan GUAN ; Yin ZHANG ; Xianbiao SHI ; Yongzhong YAO
Journal of International Oncology 2020;47(2):70-76
Objective:To explore the relationships between serum lipids, CA153 level and breast cancer incidence and clinicopathological features of patients.Methods:A total of 198 patients with breast cancer diagnosed and treated at Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School were enrolled as the case group, and 198 healthy women were selected with 1∶1 age pairing as controls. Five milliliters of fasting venous blood was collected to measure serum lipids levels in all subjects and CA153 levels in breast cancer patients. The difference of serum lipids levels between the two groups was compared. Logistic regression model was used to analyze the risk factors of breast cancer. For 165 breast cancer patients who did not receive neoadjuvant chemotherapy, independent sample t-test was used to compare serum lipids and CA153 levels in breast cancer patients with different pathological features, and Pearson correlation analysis was used to calculate the correlation between variables and CA153. Results:The triglyceride (TG) levels in the case group and the control group were (1.22±0.73) mmol/L and (1.06±0.52) mmol/L respectively, and the difference was statistically significant ( t=2.559, P=0.011); the total cholesterol (TC) levels were (4.47±0.86) mmol/L and (4.99±0.80) mmol/L respectively, and the difference was statistically significant ( t=-6.228, P<0.001); the high-density lipoprotein cholesterol (HDL-C) levels were (1.32±0.34) mmol/L and (1.53±0.38) mmol/L respectively, and the difference was statistically significant ( t=-5.913, P<0.001). Higher TC and HDL-C levels were independent protective factors for breast cancer ( OR=0.350, P<0.001; OR=0.531, P=0.013). The TC levels in lymph node positive and lymph node negative patients were (4.36±0.73) mmol/L and (4.67±0.83) mmol/L respectively, and the difference was statistically significant ( t=-2.518, P=0.013); low-density lipoprotein cholesterol (LDL-C) levels were (2.53±0.58) mmol/L and (2.77±0.70) mmol/L respectively, and the difference was statistically significant ( t=-2.312, P=0.022). The TC levels in patients with stage Ⅰ and stage Ⅱ/Ⅲ were (4.90±0.89) mmol/L and (4.46±0.76) mmol/L respectively, and the difference was statistically significant ( t=2.855, P=0.005); LDL-C levels were (2.95±0.71) mmol/L and (2.60±0.63) mmol/L respectively, and the difference was statistically significant ( t=2.705, P=0.008). The level of CA153 in triple-negative breast cancer patients [(14.94±7.45) U/ml] was significantly higher than that in non-triple-negative breast cancer patients [(11.96±5.96) U/ml], and the difference was statistically significant ( t=2.359, P=0.020). The level of CA153 was positively correlated with the level of TG ( r=0.167, P=0.032). Conclusion:Dyslipidemia is associated with an increased risk of breast cancer. The levels of serum lipids vary among patients with different lymph node status and tumor stages. CA153 level is positively correlated with TG level to some extent.
7.Survival prognosis and influencing factors of patients with primary liver cancer: a report of 3 106 cases
Haike LEI ; Xiaosheng LI ; Yulan ZHAO ; Mei HE ; Wei ZHANG ; Hong ZHOU ; Yongzhong WU
Chinese Journal of Digestive Surgery 2020;19(2):179-184
Objective:To investigate the survival prognosis of patients with primary liver cancer and its influencing factors.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 3 106 patients with primary liver cancer who had health insurance for special illness in the Chongqing Malignant Tumor Treatment System from January 2000 to August 2018 were collected. There were 2 559 males and 547 females, aged (60±13)years, with a range from 19 to 95 years. Observation indicators: (1) demographic characteristics; (2) clinical treatment and pathological examination; (3) follow-up and survival; (4) analysis of prognostic factors. Follow-up using telephone interview, outpatient or inpatient reexamination was preformed to detect survival of patients. Follow-up was done once every 3 months within the first year and once a year thereafter up to December 2018. Measurement data with normal distribution were represented as Mean± SD. Measurement data with skewed distribution were represent as M (range). Count data were expressed as absolute numbers or percentages. Survival analysis was done after excluding missing data of follow-up. The survival rate was calculated and survival curve was drawn by Kaplan-Meier method. The prognostic factors were analyzed after excluding missing data of follow-up, pathological type, and TNM staging. The log-rank test was used for univariate analysis, and COX proportional hazard model was used for multivariate analysis. Results:(1) Demographic characteristics: of the 3 106 patients with primary liver cancer, the number of males and females (gender), cases with age < 30 years, from 30 to 44 years, from 45 to 59 years, from 60 to 74 years, ≥75 years, cases of Han nationality or other ethnic groups, cases being married or other status (marital status), cases with occupation as enterprise unit staff and (or) workers, public institution personnel and (or) civil servants, freelancers and (or) self-employed entrepreneurs, unemployed, company staff, and other professionals were 2 559, 547, 35, 362, 1 131, 1 163, 415, 3 053, 53, 2 896, 210, 880, 342, 130, 101, 124, and 1 529, respectively. (2) Clinical treatment and pathological examination: of the 3 106 patients with primary liver cancer, cases with hospitalization time < 10 days, from 10 to 19 days, from 20 to 29 days, ≥30 days, cases without surgery or with surgery, cases with hepatocellular carcinoma, cholangiocarcinoma, hybrid type and other pathological types, cases of stage Ⅰ, Ⅱ, Ⅲ, Ⅳ of TNM staging were respectively 771, 1 312, 661, 362, 915, 2 191, 836, 63, 24, 29, 28, 90, 624. There were 2 183 out of 3 106 patients without pathological data and 2 335 without TNM staging data. (3) Follow-up and survival: of the 3 106 patients with primary liver cancer, 2 561 were followed up for 3.0-96.0 months, with a median follow-up time of 27.6 months. The 2 561 patients had survived for 1.0-96.0 months, with a median survival time of 24.7 months. The 1-, 3-, 5-year survival rates were 63.2%, 42.3%, 29.5%, respectively. (4) Analysis of prognostic factors: results of univariate analysis showed that age, marital status, occupation, hospitalization time, surgical treatment, pathological types, and TNM staging were related factors for prognosis of patients ( χ2=31.820, 6.752, 39.100, 120.889, 226.700, 10.452, 48.602, P<0.05). Results of multivariate analysis showed that being married, hospitalization time no less than 30 days, surgical treatment were independent protective factors for prognosis ( hazard ratio=1.463, 0.572, 0.575, 95% confidence interval: 1.044-2.049, 0.413-0.793, 0.438-0.755, P<0.05), stage Ⅲ and Ⅳ of TNM staging were independent risk factors for prognosis of patients ( hazard ratio=3.941, 5.036, 95% confidence interval: 1.687-9.211, 2.237-11.335, P<0.05). Conclusions:Patients with primary liver cancer have poor prognosis. Being married, hospitalization time no less than 30 days, and surgical treatment are independent protective factors for prognosis, stage Ⅲ and Ⅳ of TNM staging are independent risk factors for prognosis.
8.Prevalence and Molecular Characterization of Echinococcus granulosus Sensu Stricto in Northern Xinjiang, China
Baoping GUO ; Zhuangzhi ZHANG ; Xueting ZHENG ; Yongzhong GUO ; Gang GUO ; Li ZHAO ; Ren CAI ; Bingjie WANG ; Mei YANG ; Xi SHOU ; Wenbao ZHANG ; Bin JIA
The Korean Journal of Parasitology 2019;57(2):153-159
Echinococcus granulosus is an important zoonotic parasite globally causing cystic echinococcosis (CE) in humans and animals. In this study, prevalence of CE and variation of cox1 gene sequence were analyzed with isolates E. granulosus collected from different areas in northern Xinjiang, China. The survey showed that 3.5% of sheep and 4.1% of cattle were infected with CE. Fragment of cox1 was amplified from all the positive sheep and cattle samples by PCR. In addition, 26 positive samples across the 4 areas were included. The isolates were all E. granulosus sensu stricto (s.s.) containing 15 haplotypes (Hap1-15), and clustered into 2 genotypes, G1 (90.1%, 91/101) and G3 (9.9%, 10/101). Hap1 was the most common haplotype (48.5%, 49/101). Hap9 were found in humans samples, indicating that sheep and cattle reservoir human CE. It is indicate that E. granulosus may impact on control of CE in livestock and humans in the region.
Animals
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Cattle
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China
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Cross-Sectional Studies
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Echinococcosis
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Echinococcus granulosus
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Echinococcus
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Genotype
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Haplotypes
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Humans
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Livestock
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Parasites
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Polymerase Chain Reaction
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Prevalence
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Sheep
9. Study on the effects of total flavonoids from litchi nucleus on nuclear translocation of nuclear factor-kappa B and related protein expression in rat hepatic stellate cell
Guijin QIN ; Yongzhong ZHAO ; Yanxiu LIU ; Cai LI ; Jie CAO ; Qiuchen CHENG ; Xuhua XIAO ; Qing LU
Chinese Journal of Hepatology 2018;26(7):535-539
Objective:
The effect of total flavonoids of litchi (TFL) on nuclear translocation of nuclear factor-kappa B (NF- kappa B) in rat hepatic stellate cell line (HSC-T6) induced by transforming growth factor - beta 1 (TGF- beta 1) in vitro was studied to explore the mechanism of action of anti-hepatic fibrosis drugs.
Methods:
HSC-T6 was cultured in vitro, induced by TGFβ1 for 24 h, and then treated with TFL at 125, 250 and 500 μg/ml for 48 h. The effect of TFL on NF-κB nuclear translocation in HSC-T6 was observed by confocal laser microscopy. The effects of TFL on the expression of TLR4, p-IκB ɑ, p-NF-κB p65, NF-κB and Collagen I protein were detected by western blot. The expressions of TLR4 and p-NF-κB p65 were detected by immunofluorescence. Data were presented as mean±SEM. Homogeneity test of variance was performed and then followed by one-way analysis of variance (ANOVA). The multiple comparisons between groups were performed by LSD test.
10.Gut microbiota derived metabolites in cardiovascular health and disease.
Protein & Cell 2018;9(5):416-431
Trillions of microbes inhabit the human gut, not only providing nutrients and energy to the host from the ingested food, but also producing metabolic bioactive signaling molecules to maintain health and elicit disease, such as cardiovascular disease (CVD). CVD is the leading cause of mortality worldwide. In this review, we presented gut microbiota derived metabolites involved in cardiovascular health and disease, including trimethylamine-N-oxide (TMAO), uremic toxins, short chain fatty acids (SCFAs), phytoestrogens, anthocyanins, bile acids and lipopolysaccharide. These gut microbiota derived metabolites play critical roles in maintaining a healthy cardiovascular function, and if dysregulated, potentially causally linked to CVD. A better understanding of the function and dynamics of gut microbiota derived metabolites holds great promise toward mechanistic predicative CVD biomarker discoveries and precise interventions.
Cardiovascular Diseases
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metabolism
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microbiology
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pathology
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Gastrointestinal Microbiome
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Humans
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Metabolome

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