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1.
Proc Natl Acad Sci U S A ; 121(28): e2322972121, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38968116

ABSTRACT

Rapid accumulation of repair factors at DNA double-strand breaks (DSBs) is essential for DSB repair. Several factors involved in DSB repair have been found undergoing liquid-liquid phase separation (LLPS) at DSB sites to facilitate DNA repair. RNF168, a RING-type E3 ubiquitin ligase, catalyzes H2A.X ubiquitination for recruiting DNA repair factors. Yet, whether RNF168 undergoes LLPS at DSB sites remains unclear. Here, we identified K63-linked polyubiquitin-triggered RNF168 condensation which further promoted RNF168-mediated DSB repair. RNF168 formed liquid-like condensates upon irradiation in the nucleus while purified RNF168 protein also condensed in vitro. An intrinsically disordered region containing amino acids 460-550 was identified as the essential domain for RNF168 condensation. Interestingly, LLPS of RNF168 was significantly enhanced by K63-linked polyubiquitin chains, and LLPS largely enhanced the RNF168-mediated H2A.X ubiquitination, suggesting a positive feedback loop to facilitate RNF168 rapid accumulation and its catalytic activity. Functionally, LLPS deficiency of RNF168 resulted in delayed recruitment of 53BP1 and BRCA1 and subsequent impairment in DSB repair. Taken together, our finding demonstrates the pivotal effect of LLPS in RNF168-mediated DSB repair.


Subject(s)
DNA Breaks, Double-Stranded , DNA Repair , Tumor Suppressor p53-Binding Protein 1 , Ubiquitin-Protein Ligases , Ubiquitination , Ubiquitin-Protein Ligases/metabolism , Ubiquitin-Protein Ligases/genetics , Humans , Tumor Suppressor p53-Binding Protein 1/metabolism , Tumor Suppressor p53-Binding Protein 1/genetics , Ubiquitin/metabolism , Histones/metabolism , Histones/genetics , Polyubiquitin/metabolism
2.
Journal of Clinical Hepatology ; (12): 284-291, 2024.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1007242

ABSTRACT

objectiveTo investigate the differences in clinical indices and lipid metabolism between the patients with nonalcoholic fatty liver disease (NAFLD) and healthy individuals in the overweight population. MethodsIn this study, body mass index (BMI)>23 kg/m2 was defined as overweight. A total of 62 overweight patients with NAFLD who were admitted to Putuo Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from August 2020 to April 2021 were enrolled as overweight NAFLD group, and 50 overweight individuals who underwent physical examination during the same period of time were enrolled as control group. Clinical information and blood biochemical parameters were recorded for all subjects. Ultra-performance liquid chromatography-tandem mass spectrometry was used to analyze serum lipidomic profile, and principal component analysis and orthogonal partial least squares-discriminant analysis were used to perform the multivariate statistical analysis of lipidomic data. The chi-square test was used for comparison of categorical data between two groups, and the independent-samples t test or the Wilcoxon rank-sum test was used for comparison of continuous data between two groups. ResultsThe overweight NAFLD group had a significantly higher BMI than the overweight control group (Z=-2.365, P=0.018). As for serological markers, compared with the overweight control group, the overweight NAFLD group had significantly higher levels of red blood cells, hemoglobin, hematocrit, uric acid, total protein, globulin, alkaline phosphatase, gamma-glutamyl transpeptidase, alanine aminotransferase, aspartate aminotransferase, cholinesterase, low-density lipoprotein, total cholesterol, triglyceride, apolipoprotein B, and blood glucose (all P<0.05). The lipidomic analysis showed that there was a significant difference in lipid metabolism between the two groups, and a total of 493 differentially expressed lipids were identified (VIP value>1, P<0.05), among which 143 lipids were significantly upregulated and 350 lipids were significantly downregulated in the overweight NAFLD group. The mean total fatty acid content in the overweight NAFLD group was 3.6 times that in the overweight control group. Compared with the overweight control group, the overweight NAFLD group had a significant reduction in the content of triglyceride with>3 unsaturated bonds (P<0.001) and a significant increase in the content of triglyceride with ≤3 unsaturated bonds (P<0.001). ConclusionCompared with healthy overweight individuals, overweight NAFLD patients tend to have significant abnormalities in some biochemical parameters and lipid metabolites, with significant increases in the content of fatty acid in blood and the types of saturated fat chains in triglycerides.

3.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1016538

ABSTRACT

ObjectiveTo describe the epidemic characteristics of COVID-19 after policy adjustment from “Category B notifiable disease with category A management” to “Category B notifiable disease with category B management”, and to explore the protective effect of previous infection with SARS-CoV-2 on common symptoms of reinfection. MethodsHealthcare workers infected with SARS-CoV-2 in a grade A tertiary hospital in Shanghai were included in the study from December 4, 2022 to January 11, 2023. Data on demographic characteristics, clinical symptoms, medical history, and COVID-19 vaccination history were collected. We determined the epidemiological curve and characteristics, and then compared the difference in the severity of clinical symptoms between primary and reinfection subjects. ResultsA total of 2 704 cases were included in the study, of which 45 had reinfection, 605 (22.4%)were males, 608 (22.5%)were doctors, 1 275 (47.2%) were nurses, and 2 351 (86.9%) received ≥3 doses of COVID-19 vaccination. The average age of these healthcare workers was (34.9±9.1) years old. The number of cases with mild/moderate illness, asymptomatic infection, fever, headache, dry cough, expectoration, and chest tightness were 2 704 (100.0%), 92 (3.4%), 2 385 (88.2%), 2 066 (76.4%), 1 642 (60.7%), 1 807 (66.8%), and 439 (16.2%), respectively. Reinfection was a protective factor for fever (OR=0.161, P<0.001), headache (OR=0.320, P<0.001), and peak body temperature (β=-0.446, P<0.001). ConclusionFollowing the COVID-19 policy adjustment as a category B notifiable disease, healthcare workers at a grade A tertiary hospital in Shanghai predominantly experiences mild to moderate COVID-19 symptoms. Reinfection results in milder clinical manifestations, with a lower proportion of being asymptomatic.

4.
IEEE Trans Neural Netw Learn Syst ; 34(3): 1278-1290, 2023 Mar.
Article in English | MEDLINE | ID: mdl-34460387

ABSTRACT

Long-term visual place recognition (VPR) is challenging as the environment is subject to drastic appearance changes across different temporal resolutions, such as time of the day, month, and season. A wide variety of existing methods address the problem by means of feature disentangling or image style transfer but ignore the structural information that often remains stable even under environmental condition changes. To overcome this limitation, this article presents a novel structure-aware feature disentanglement network (SFDNet) based on knowledge transfer and adversarial learning. Explicitly, probabilistic knowledge transfer (PKT) is employed to transfer knowledge obtained from the Canny edge detector to the structure encoder. An appearance teacher module is then designed to ensure that the learning of appearance encoder does not only rely on metric learning. The generated content features with structural information are used to measure the similarity of images. We finally evaluate the proposed approach and compare it to state-of-the-art place recognition methods using six datasets with extreme environmental changes. Experimental results demonstrate the effectiveness and improvements achieved using the proposed framework. Source code and some trained models will be available at http://www.tianshu.org.cn.

5.
Journal of Clinical Hepatology ; (12): 401-407, 2023.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-964804

ABSTRACT

The prevalence rate of nonalcoholic fatty liver disease (NAFLD) is increasing year by year, which poses a heavy burden on global public health. The pathogenesis of NAFLD is closely associated with the factors including obesity, insulin resistance, and diet, among which diet is the core and cornerstone of the prevention and treatment of NAFLD. In view of the fact that previous studies focused on the association of different dietary components, structures, and plans with NAFLD and seldom explored the impact of overall dietary behavior on NAFLD, this article reviews the effect of dietary behavior on NAFLD, in order to provide a reference for the prevention and treatment of NAFLD and the guidance on rational dietary behaviors and habits for patients.

6.
Nat Commun ; 13(1): 2638, 2022 05 12.
Article in English | MEDLINE | ID: mdl-35551189

ABSTRACT

The rapid recognition of DNA double-strand breaks (DSBs) by the MRE11/RAD50/NBS1 (MRN) complex is critical for the initiation of DNA damage response and DSB end resection. Here, we show that MRN complex interacting protein (MRNIP) forms liquid-like condensates to promote homologous recombination-mediated DSB repair. The intrinsically disordered region is essential for MRNIP condensate formation. Mechanically, the MRN complex is compartmentalized and concentrated into MRNIP condensates in the nucleus. After DSB formation, MRNIP condensates move to the damaged DNA rapidly to accelerate the binding of DSB by the concentrated MRN complex, therefore inducing the autophosphorylation of ATM and subsequent activation of DNA damage response signaling. Meanwhile, MRNIP condensates-enhanced MRN complex loading further promotes DSB end resection. In addition, data from xenograft models and clinical samples confirm a correlation between MRNIP and radioresistance. Together, these results reveal an important role of MRNIP phase separation in DSB response and the MRN complex-mediated DSB end resection.


Subject(s)
DNA Breaks, Double-Stranded , DNA-Binding Proteins , Acid Anhydride Hydrolases/metabolism , Cell Cycle Proteins/metabolism , DNA , DNA Repair , DNA Repair Enzymes/metabolism , DNA-Binding Proteins/metabolism , Humans , MRE11 Homologue Protein/metabolism , Recombinational DNA Repair
7.
Journal of Clinical Hepatology ; (12): 2084-2090, 2022.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-942664

ABSTRACT

Objective To investigate the clinical efficacy and safety of Danshu Capsule in the treatment of chronic cholecystitis and gallstones through a large-sample, multicenter, open-label real-world research. Methods A total of 9579 patients with chronic cholecystitis and/or gallstones who were treated in 329 hospitals of China from January 2017 to December 2019 were enrolled and divided into gallstones group with 1148 patients, chronic cholecystitis group with 5360 patients, and chronic cholecystitis+gallstones group with 3071 patients.All patients were treated with oral administration of Danshu Capsule at a frequency of 1-2 capsules/time, three times a day after meals, for 4 consecutive weeks.Abdominal pain, biliary dyspepsia, traditional Chinese medicine (TCM) syndromes, and imaging findings of the biliary system were recorded before and after treatment to evaluate the efficacy of medication, and adverse drug reactions were monitored to evaluate the safety of Danshu Capsule.The Wilcoxon signed-rank test was used for comparison of non-normally distributed continuous data before and after treatment, and the Wilcoxon rank-sum test was used for comparison between any two groups.The paired chi-square test was used for comparison of categorical data before and after treatment; the Kruskal-Wallis H method was used for comparison between multiple groups, and the Logistic regression analysis and the Nemenyi test was used for further comparison between two groups. Results After treatment with Danshu Capsule, all patients had significant reductions in the overall incidence rate of pain induced by lipid meal ( χ 2 =32.422, P < 0.001), the frequency, duration, and degree of pain ( Z =-1.985, -2.887, and-3.178, all P < 0.05), the symptom scores of abdominal distension, abdominal fullness, belching, and nausea (all P < 0.001), and the total symptom score of biliary dyspepsia ( Z =-4.128, P < 0.001);there were also significant reductions in the TCM syndrome scores of right upper quadrant pain, bitter taste, acid regurgitation, chest distress, abdominal distension, poor appetite, and heaviness of limbs (all P < 0.05) and a significant reduction in total TCM syndrome score ( Z =3.860, P < 0.001).Subgroup analysis showed that after treatment, the gallstones group, the chronic cholecystitis group, and the chronic cholecystitis+gallstones group had significant reductions in the degree, frequency, and duration of pain, the symptom score of biliary dyspepsia, and TCM syndrome score (all P < 0.05), as well as a significant reduction in the number of patients with pain induced by lipid meal ( P < 0.001).The chronic cholecystitis group had significantly greater reductions in the score of pain frequency, the score of pain duration, the score of pain degree compared with the other two groups (all P < 0.05).Ultrasound examination showed that after treatment, all patients had significant reductions in poor sound transmission of gallbladder, gallbladder wall thickness, incidence rate of gallbladder wall thickening or roughness, and the number and size of gallstones (all P < 0.05).Danshu Capsule showed an overall response rate of 74.75% in the treatment of gallbladder wall lesion and an overall response rate of 67.40% in the treatment of gallstones.A total of 84 patients reported adverse events, mainly gastrointestinal symptoms, and the overall incidence rate of adverse reactions was 0.87%. Conclusion Danshu Capsule can significantly alleviate the symptom of pain and improve the symptoms of biliary dyspepsia, TCM syndrome, and gallbladder imaging findings in patients with chronic cholecystitis and/or gallstones, with a low incidence rate of adverse reactions, and therefore, it is a safe and effective drug for the treatment of chronic cholecystitis and gallstones.

8.
Chinese Journal of Oncology ; (12): 93-98, 2022.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-935187

ABSTRACT

Objective: To estimate stomach cancer incidence and mortality in Henan, 2016 and analyze the trend of stomach cancer incidence and mortality from 2010 to 2016. Methods: Stomach cancer related data in 2016 was extracted from Henan cancer registration and follow-up system. All data were qualified in validity, reliability and completeness according to the Guideline on Cancer Registration in China and International Agency for Research on Cancer (IARC/IACR). The incidence and mortality of stomach cancer were estimated by areas, gender and age based on the quality data and the registered population data of Henan province in 2016. The epidemic trend of stomach cancer was also been evaluated based on the age-standardized incidence and mortality by Chinese population (ASR China) from 2010 to 2016. Results: In 2016, the estimated incident cases of stomach cancer were 44 311. The incidence was 41.07/100 000, ASR China was 30.17/100 000, ASR by world population (ASR world) was 30.36/100 000, and the cumulative incidence rate was 3.84%. The incidences of male and female were 55.65/100 000 and 25.35/100 000, respectively. Meanwhile, 32 927 people died of stomach cancer in Henan. The mortality was 30.52/100 000, ASR China was 21.45/100 000, ASR world was 21.54/100 000, and the cumulative mortality was 2.53%. From 2010 to 2016, both the ASR China for incidence and mortality of stomach cancer in Henan showed a steady downward trend. In rural, the ASR China for incidence and mortality decreased rapidly, while the stable trend was observed in urban. Nevertheless, the incidence and mortality of stomach cancer in rural were still higher than those in urban. Conclusions: The incidence and mortality of stomach cancer in Henan province showed steadily declining trend from 2010 to 2016, and the geographical distribution difference between rural and urban areas was gradually narrowing. However, the disease burden was still high in 2016.


Subject(s)
Female , Humans , Male , China/epidemiology , Incidence , Registries , Reproducibility of Results , Rural Population , Stomach Neoplasms/epidemiology , Urban Population
9.
Chinese Journal of Oncology ; (12): 86-92, 2022.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-935186

ABSTRACT

Objective: To estimate the incidence and mortality of esophageal cancer in 2016 and their changing trend during 2010-2016 according to the cancer registration data in Henan province. Methods: The data quality including completeness, validity, and reliability of local registries which submitted the cancer registration data of 2016 were assessed according to the criteria of Guideline on Cancer Registration in China and IARC/IACR. Esophageal cancer cases (ICD10: C15) were extracted from the database, and the incidence and mortality stratified by gender, age, and areas (urban/rural) were calculated, the incidence and mortality of provincial cancer were estimated combined with provincial population data. China's 2000 census population and Segi's population were used to calculate the age-standardized rate. Joinpoint model was used to estimate the changing trend of age standardized incidence and mortality along with the calendar year. Results: Approximately 40.10 thousand new esophageal cancer cases were diagnosed in Henan in 2016, accounting for 13.46% of all new cancer cases, and it ranked the third among cancer of all sites. The crude incidence of esophageal cancer was 37.21/100 000 with an age-standardized incidence rate by China standard population (ASIRC) of 26.74/100 000 and an age-standardized incidence rate by world standard population (ASIRW) of 27.12/100 000. The incidence of esophageal cancer in males was higher than that in females, with the ASIRC of 34.53/100 000 and 19.19/100 000, respectively. It was higher in rural areas than that in urban areas, with the ASIRC of 28.13/100 000 and 20.90/100 000, respectively. About 29.30 thousand deaths of esophageal cancer in Henan in 2016, accounting for 15.61% of all cancer deaths in Henan, which ranked the third among cancer of all sites. The crude mortality rate was 27.14/100 000 with an age-standardized mortality rate by China standard population (ASMRC) of 18.74/100 000 and an age-standardized mortality rate by world standard population (ASMRW) of 18.78/100 000. The mortality in males was higher than that in females, with the ASMRC of 24.78/100 000 and 13.12/100 000, respectively. It was also higher in rural areas than that in urban areas, with the ASMRC of 19.48/100 000 and 15.73/100 000, respectively. The ASIRC and ASMRC were declining with annual percent change (APC) of 3.12% (APC=-3.12%; 95%CI: -5.30%, -0.90%; P=0.015) and 2.47% (APC=-2.47%; 95%CI: -4.70%, -0.20%; P=0.039) during 2010-2016. However, the significant declining trend was only observed in rural areas in Henan, and the changing trend was same between males and females. Conclusions: The incidence and mortality of esophageal cancer are declining since 2010, however, the disease burden remains large in Henan. Therefore, comprehensive prevention and control efforts should be strengthened according to its epidemic characteristics and risk factors.


Subject(s)
Female , Humans , Male , China/epidemiology , Esophageal Neoplasms/epidemiology , Incidence , Registries , Reproducibility of Results , Rural Population , Urban Population
10.
Oncogene ; 40(7): 1375-1389, 2021 02.
Article in English | MEDLINE | ID: mdl-33420374

ABSTRACT

Arginine methylation is an important posttranslational modification catalyzed by protein arginine methyltransferases (PRMTs). However, the role of PRMTs in colorectal cancer (CRC) progression is not well understood. Here we report that non-POU domain-containing octamer-binding protein (NONO) is overexpressed in CRC tissue and is a potential marker for poor prognosis in CRC patients. NONO silencing resulted in decreased proliferation, migration, and invasion of CRC cells, whereas overexpression had the opposite effect. In a xenograft model, tumors derived from NONO-deficient CRC cells were smaller than those derived from wild-type (WT) cells, and PRMT1 inhibition blocked CRC xenograft progression. A mass spectrometry analysis indicated that NONO is a substrate of PRMT1. R251 of NONO was asymmetrically dimethylated by PRMT1 in vitro and in vivo. Compared to NONO WT cells, NONO R251K mutant-expressing CRC cells showed reduced proliferation, migration, and invasion, and PRMT1 knockdown or pharmacological inhibition abrogated the malignant phenotype associated with NONO asymmetric dimethylation in both KRAS WT and mutant CRC cells. Compared to adjacent normal tissue, PRMT1 was highly expressed in the CRC zone in clinical specimens, which was correlated with poor overall survival in patients with locally advanced CRC. These results demonstrate that PRMT1-mediated methylation of NONO at R251 promotes CRC growth and metastasis, and suggest that PRMT1 inhibition may be an effective therapeutic strategy for CRC treatment regardless of KRAS mutation status.


Subject(s)
Colorectal Neoplasms/genetics , DNA-Binding Proteins/genetics , Protein-Arginine N-Methyltransferases/genetics , Proto-Oncogene Proteins p21(ras)/genetics , RNA-Binding Proteins/genetics , Repressor Proteins/genetics , Animals , Arginine , Carcinogenesis/genetics , Cell Movement/genetics , Cell Proliferation/genetics , Colorectal Neoplasms/pathology , Gene Expression Regulation, Neoplastic , Heterografts , Humans , Methylation , Mice
11.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-880096

ABSTRACT

OBJECTIVE@#To investigate the relationship between acute myeloid leukemia (AML) patients ASXL2, ZBTB7A gene mutations and the prognosis.@*METHODS@#42 AML Patients treated in our hospital from January 2014 to January 2016 were selected and ASXL2 and ZBTB7A genes of their bone marrow samples were sequenced, the genetic characteristics and prognosis of core-binding factor-AML(CBF-AML) patients with ASXL2 and ZBTB7A mutations were analyzed.@*RESULTS@#ASXL2 (33.3%) and ZBTB7A (9.5%) mutations were found in t (8; 21) AML patients. Compared with wild-type, patients with ASXL2 mutations showed significantly higher white blood cell count at diagnosis [(9.49±1.85)×10@*CONCLUSION@#ASXL2 and ZBTB7A mutations are frequently found in t (8; 21) AML patients. The mutation of ASXL2 and ZBTB7A genes shows no significant effect on the prognosis of AML patients.


Subject(s)
Humans , Cell Line, Tumor , DNA-Binding Proteins/genetics , Leukemia, Myeloid, Acute/genetics , Mutation , Oncogene Proteins, Fusion/genetics , Prognosis , Repressor Proteins/genetics , Transcription Factors/genetics
12.
Journal of Clinical Hepatology ; (12): 2684-2688, 2021.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-905021

ABSTRACT

The prevalence rate of nonalcoholic fatty liver disease (NAFLD) is increasing year by year and it has become one of the most common chronic liver diseases in the world. Studies have shown that circular RNA (circRNA) is closely associated with NAFLD and is considered a potential diagnostic biomarker and therapeutic target for NAFLD. This article summarizes the regulatory role of circRNA in the pathogenesis of NAFLD and its value in diagnosis and treatment and points out that circRNA plays an important role in the development and progression of NAFLD and may have important clinical significance in the diagnosis and treatment of NAFLD.

13.
Molecules ; 25(24)2020 Dec 21.
Article in English | MEDLINE | ID: mdl-33371407

ABSTRACT

The identification of aroma composition and key odorants contributing to aroma characteristics of white tea is urgently needed, owing to white tea's charming flavors and significant health benefits. In this study, a total of 238 volatile components were identified in the three subtypes of white teas using headspace solid-phase microextraction (HS-SPME) combined with comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry (GC × GC-TOFMS). The multivariate statistical analysis demonstrated that the contents of 103 volatile compounds showed extremely significant differences, of which 44 compounds presented higher contents in Baihaoyinzhen and Baimudan, while the other 59 compounds exhibited higher contents in Shoumei. The sensory evaluation experiment carried out by gas chromatography-olfactometry/mass spectrometry (GC-O/MS) revealed 44 aroma-active compounds, of which 25 compounds were identified, including 9 alcohols, 6 aldehydes, 5 ketones, and 5 other compounds. These odorants mostly presented green, fresh, floral, fruity, or sweet odors. Multivariate analyses of chemical characterization and sensory evaluation results showed that high proportions of alcohols and aldehydes form the basis of green and fresh aroma characteristic of white teas, and phenylethyl alcohol, γ-Nonalactone, trans-ß-ionone, trans-linalool oxide (furanoid), α-ionone, and cis-3-hexenyl butyrate were considered as the key odorants accounting for the different aroma characteristics of the three subtypes of white tea. The results will contribute to in-depth understand chemical and sensory markers associated with different subtypes of white tea, and provide a solid foundation for tea aroma quality control and improvement.


Subject(s)
Flavoring Agents/chemistry , Odorants/analysis , Tea/chemistry , Acyclic Monoterpenes/chemistry , Aldehydes/chemistry , Cyclohexanols/chemistry , Fruit/chemistry , Gas Chromatography-Mass Spectrometry/methods , Norisoprenoids/chemistry , Solid Phase Microextraction/methods , Trityl Compounds/chemistry , Volatile Organic Compounds/chemistry
14.
Journal of Clinical Hepatology ; (12): 1880-1882, 2020.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-825049

ABSTRACT

The incidence rate of nonalcoholic fatty liver disease (NAFLD) is increasing year by year and NAFLD has become one of the most common liver diseases in the world. Metabolomics follows the research thoughts of genomics and proteomics and conducts a quantitative analysis of all metabolites in organisms to explore the association between metabolites and physiological and pathological changes, which provides a new way for studying the traditional Chinese medicine diagnosis and treatment of NAFLD. This article summarizes the research advances in metabolomics and traditional Chinese medicine syndromes in NAFLD, so as to provide new thoughts and methods for further exploration of NAFLD.

15.
Journal of Clinical Hepatology ; (12): 924-927, 2020.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-819199

ABSTRACT

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease around the world, and its incidence rate is increasing year by year. Oxidative stress is the second hit in the classic “two-hit” pathogenesis of NAFLD, which is currently recognized as one of the pathogeneses of NAFLD. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a group of positive regulators that protect hepatocytes against oxidative stress. It is a key factor for cellular anti-oxidative stress and a key transcription factor that antagonizes liver oxidative stress. It plays an important role in the development and progression of NAFLD and may be a potential treatment target for improving NAFLD. This article reviews the role of oxidative stress and the Nrf2 pathway in the pathogenesis of NAFLD.

16.
Acta Pharmaceutica Sinica ; (12): 967-970, 2020.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-821690

ABSTRACT

italic>Chaetomium globosum WQ, an endophyte derived from Imperata cylindrical, can produce abundant cytochalasan compounds through solid state fermentation. Based on previous research and guided by 1H NMR spectrum and TLC, a new cytochalasan compound was isolated from the ethyl acetate extract of a solid culture of C. globosum WQ using silica gel column chromatography, gel filtration over Sephadex LH-20 and HPLC. The new compound was characterized as 20-iso-chaetoglobosin E (1) by a combination of spectroscopic (HR-MS, 1D and 2D NMR) analyses.

17.
Journal of Clinical Hepatology ; (12): 2441-2445, 2020.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-829629

ABSTRACT

ObjectiveTo investigate the association between serum interleukin (IL) and liver pathological changes in patients with chronic hepatitis B (CHB). MethodsA total of 59 patients with CHB who were treated in Putuo District Central Hospital of Shanghai from February 2018 to February 2019 were enrolled as subjects, and liver biopsy was performed for all patients. According to the degree of liver inflammation, the patients were divided into mild inflammation (G1-G2) group and severe inflammation (G3-G4) group, and according to the degree of liver fibrosis, the patients were divided into mild fibrosis (S0-S2) group and severe fibrosis (S3-S4) group. Serum liver function parameters, blood lipids, interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-10 (IL-10) were measured for all patients. The independent samples t-test was used for comparison of normally distributed continuous data between two groups, and the Wilcoxon non-parametric test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between groups. A Spearman correlation analysis was also performed. ResultsThe degree of liver fibrosis increased with the increase in liver inflammation (rs=0.538, P<0.001). Compared with the mild inflammation group, the severe inflammation group had significantly higher serum levels of alanine aminotransferase [95.00 (45.00-16925) U/L vs 51.00 (29.00-88.00) U/L, Z=-2.625, P=0.009], aspartate aminotransferase [54.50 (34.75-84.50) U/L vs 38.00 (30.00-49.00) U/L, Z=-2.014, P=0.044], and gamma-glutamyl transpeptidase [91.00 (56.72-192.25) U/L vs 44.00 (24.00-100.00) U/L, Z=-2.400, P=0.016]. The severe fibrosis group had a significantly higher serum level of high-density lipoprotein than the mild fibrosis group [0.97 (0.32-1.08) mmol/L vs 1.23 (0.36-1.38) mmol/L, Z=-1.300, P=0.008]. The severe inflammation group had a significantly higher serum level of IL-2 receptor than the mild inflammation group [704.00(418.00-103800) U/ml vs 436.00(335.00-555.00) U/ml, Z=-3.405, P=0.001], and the severe fibrosis group had a significantly higher serum level of IL-2 receptor than the mild fibrosis group [735.00(523.00-890.50) U/ml vs 447.00 (351.50-624.50) U/ml, Z=-5.358, P=0.001]. ConclusionThe degree of liver inflammation is positively correlated with that of liver fibrosis, while the serum level of IL-2 receptor increases with the increase in the degrees of liver inflammation and fibrosis, indicating that IL-2 receptor can reflect the degrees of liver inflammation and fibrosis to some extent.

18.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-873252

ABSTRACT

Objective::To observe the efficacy of modified Qiju Dihuang pills in protecting renal function of patients with early renal impairment with syndrome of Yin deficiency and Yang hyperactivity caused by hypertension and its effect in resisting inflammation and oxidative stress, and improving endothelial function. Method::Randomly divided into control group (59 cases) and observation group (60 cases) by random number table. Patients in control got valsartan capsules, 80 mg/time, 1 time/day. And patients whose blood pressure can't be controlled were added with nifedipine tablets, 10 mg/time, 1 time/day. In addition to the therapy of control group, patients in observation group were added with modified Qiju Dihuang pills, 1 dose/day. The control group took Qiju Dihuang pills.The courses of treatment were 16 weeks. And levels of cystatin C (CysC), urinary N-acetyl-β-glucosaminidase (NAG), β2 microglobulin (β2-MG), urinary microalbumin to creatinine ratio (UACR) and emodynamics of kidney were detected. Blood pressure, systolic pressure (SBP), diastolic pressure (DBP) and blood pressure renal artery resistance index (RI) and pulsatility index (PI) were recorded, and Yin deficiency and Yang hyperactivity were scored. Levels of nitric oxide (NO), endothelin-1 (ET-1), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), adiponectin (ADPN) and nuclear factor-kappa B (NF-κB) were detected. Result::The total effective rate in observation group was 91.67%(55/60), which was higher than 76.27%(45/59) in control group (χ2=5.255, P<0.05). Levels of SBP and DBP were lower than those in control group (P<0.05). At the 16th week during the treatment, the compliance rate of blood pressure was 90.66%, which was higher than 84.13% in control group (χ2=127.65, P<0.01). And levels of CysC, β2-MG, NAG, UACR, RI, PI, ET-1, SOD, GSH-Px, IL-6, NF-κB and TNF-α were lower than those in control group (P<0.01), while levels of NO, SOD and GSH-Px were higher than those in control group (P<0.01). Conclusion::In addition to the therapy for controlling blood pressure with routine western medicine, modified Qiju Dihuang pills can reduce level of the blood pressure, and control blood pressure with the standard, with anti-inflammatory and anti-oxidative stress effects. It can also improve the vasomotor function and the flow of kidney, protect the kidney function, and reduce the degree of injury, so as to delay the process of kidney damage and improve the prognosis.

19.
Journal of Experimental Hematology ; (6): 1196-1200, 2019.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-775742

ABSTRACT

OBJECTIVE@#To explore the relation of circulating follicular helper T cell (c Tfh) changes with B cell dysfunction in MDS patients.@*METHODS@#20 patients diagnosed as MDS from Auguct 2015 to October 2017 were enrolled in MDS group, and 20 healthy valuntears matching in age and sex were enrolled in healthy control (HC) group. The perepheral blood in 2 groups were collected, the mononuclear cells (PBMC) from which were isolated by densily gradient contrifugation, at the same time, the serum left in isolation process was reserved for further study. The flow cytometry was used to detect the ratio of cTfh such as CD4CXCR5 T cells and its subset CD4CXCR5ICOS T cells, CD4CXCR5PD-1 T cells in PBMC, as well as the ratio of plasmablast CD19CD20CD38 B cells. The ELISA was used to detect the concentration of IgA, IgM and IgG. The differences in ratio of cTfh cells and plasmablast B cells, as well as the concentration of IgA, IgM and IgG between MDS and HC groups were compared, at the same time, the correlation of cTfh cell ratio with the plasmablast B cell ratio and the concentration of IgA, IgM and IgG in MDS patient was analyzed.@*RESULTS@#The ratio of CD4CXCR5T, CD4CXCR5ICOST cells and CD19CD20CD38B cells and the concentration of IgA, IgM and IgG decreased in MDS patients, while the ratio of CD4CXCR5PD-1T cells increased in MDS patients. The ratio of CD4CXCR5T cells, CD4CXCR5ICOST cells positively correlated with the ratio of CD19CD20CD38B cells, as well as with the concentration of IgA, IgM and IgG in MDS patients. However, the ratio of CD4CXCR5PD-1T cells negatively correlated with the ratio of CD19CD20CD38B cells, as well as with the concentration of IgA, IgM and IgG.@*CONCLUSION@#The ratio of circulating Tfh cells and their subsets showed significant changes, that correlate with B cell dysfunction in MDS patients.


Subject(s)
Humans , B-Lymphocytes , Interleukins , Leukocytes, Mononuclear , Myelodysplastic Syndromes , Plasma Cells , Receptors, CXCR5 , T-Lymphocytes, Helper-Inducer
20.
Practical Oncology Journal ; (6): 557-560, 2019.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-823804

ABSTRACT

Ovarian cancer(OC)is an aggressive and fatal cancer. A growing number of studies have shown that the tumor mi-croenvironment(TME)is involved in the promotion and development of ovarian cancer,immunosuppression and inflammatory response through various mechanisms. TME includes tumor blood vessels and lymphatic vessels,as well as cancer cells,mesenchymal cells,im-mune cells,and extracellular matrix(ECM). Based on recent literature reports,this paper reviews the commonly used three-dimen-sional(3D)cell culture model of ovarian tumor microenvironment,and summarizes many 3D models that do not contain primitive stro-mal cells,aiming to find new approaches for ovarian cancer treatment.

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