1.Clinical features of chronic hepatitis C patients with genotype 3 infection:A multicenter retrospective cohort study
Jingyi XIE ; Yujia JING ; Yishan LIU ; Manling BAI ; Zhangqian CHEN ; Qiang XU ; Hong DU ; Yuxiu MA ; Liting ZHANG ; Shanshan ZHU ; Xiaoqin GAO ; Xinggang BAI ; Guoying YU ; Jianqi LIAN ; Xiaozhong WANG ; Yongping ZHANG ; Jiuping WANG ; Fanpu JI ; Jianjun FU ; Ning GAO
Journal of Clinical Hepatology 2025;41(8):1533-1540
Objective To investigate the clinical features of chronic hepatitis C(CHC)patients with hepatitis C virus genotype 3(HCV GT3)infection and the risk factors for disease progression.Methods A multicenter retrospective cohort study was conducted among 1 002 CHC patients from 11 clinical centers in Northwest China from December 2017 to November 2023,and according to their genotype,they were divided into GT1,GT2,GT3,and GT6 groups.Clinical features were compared between the patients with different genotypes.The one-way analysis of variance was used for comparison of normally distributed continuous data between groups,and the Scheffe test was used for further comparison between two groups.The Kruskal-Wallis H test was used for comparison of data with skewed distribution between groups;the chi-square test or Fisher test was used for comparison of categorical data between groups.The multivariate logistic regression analysis was used to explore the influencing factors for the progression of CHC to liver cirrhosis.Results In terms of the genotype,there were 427 patients with GT1 infection,242 with GT2 infection,299 with GT3 infection(210 patients with GT3a infection,87 with GT3b infection,and 2 with unclassified genotype),and 34 with GT6 infection.The patients with GT3 infection had a significantly younger age than those with GT1 infection(51.3±0.5 years vs 53.2±0.6 years,P<0.05)or GT2 infection(51.3±0.5 years vs 53.7±0.8 years,P<0.05),and for the patients with liver cirrhosis,the patients with GT3 infection had a significantly younger age than those with GT1 infection(52.1±0.5 years vs 59.4±0.9 years,P<0.001)or GT2 infection(52.1±0.5 years vs 58.1±1.1 years,P<0.001).Among the patients with GT3 infection,male patients accounted for 77.9%and the patients with liver cirrhosis accounted for 46.2%,which were significantly higher than those among the patients with GT1,GT2 or GT6 infection(all P<0.001).At baseline,the patients with GT3 infection had significantly higher levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)than those with GT1 or GT2 infection,significantly higher aspartate aminotransferase-to-platelet ratio index(APRI)and fibrosis-4(FIB4)than those with GT1,GT2 or GT6 infection,a significantly lower platelet count(PLT)than those with GT2 or GT6 infection,a significantly higher level of alpha-fetoprotein than those with GT2 or GT6 infection,and a significantly lower level of albumin(Alb)than those with GT6 infection(all P<0.05).There were no significant differences between the patients with GT3a infection and those with GT3b infection in age,sex,the proportion of patients with liver cirrhosis,comorbidities,HCV RNA quantification,PLT,ALT,AST,alkaline phosphatase,Alb,APRI,and FIB-4(all P>0.05).The multivariate logistic regression analysis showed that PLT≤150×109/L(odds ratio[OR]=10.72,95%confidence interval[CI]:5.76-35.86,P<0.001)and Alb≤35 g/L(OR=3.74,95%CI:1.22-11.45,P=0.021)were risk factors for liver cirrhosis.Conclusion Most CHC patients with GT3 infection are male in Northwest China,and compared with the patients with other genotypes,such patients tend to have a younger age of onset and higher degrees of liver inflammation activity and fibrosis.Low PLT and a low level of Alb are risk factors for progression to liver cirrhosis in CHC patients with GT3 infection.
2.Effects of baicalin on ferroptosis of mouse fibroblasts under high glucose treatment and its mechanism
Zheng GONG ; Xiaowei ZHANG ; Xiaomei LI ; Zhimin YIN ; Limin BAI ; Jiaxi WANG ; Yujia HAN ; Shuangyi XU ; Lu YU ; Gang XU
Chinese Journal of Burns 2025;41(3):277-285
Objective:To investigate the effects of baicalin on ferroptosis of mouse fibroblasts (Fbs) under high glucose treatment and its mechanism, and to provide a basis for the treatment of diabetic wounds.Methods:The study was an experimental study. Mouse Fbs were collected and divided into control group with conventional culture, high glucose group treated with glucose at final molarity of 30.0 mmol/L, and low baicalin group and high baicalin group pretreated with baicalin at final molarties of 5 and 10 μmol/L respectively and then treated as that in high glucose group. After 48 h of culture, the cell survival rate was detected by the cell counting kit-8, the reactive oxygen species level in cells was detected by the fluorescent probe method, the levels of malondialdehyde, glutathione, and ferrous ion in cells were detected by colorimetry, and the protein expression levels of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) in cells and nuclear factor-erythroid 2-related factor 2 (Nrf2) in cytoplasm and nucleus were detected by Western blotting. Another batch of mouse Fbs were collected and divided into control group, high glucose group, high baicalin group, and high baicalin+ML385 group. The cells in the first three groups were treated as before, the cells in the last group were pretreated with baicalin and ML385 of Nrf2 inhibitor at final molarties of 10 μmol/L and then treated as that in high glucose group. After 48 h of culture, the protein expression levels of SLC7A11 and GPX4 in cells and the protein expression level of Nrf2 in cytoplasm and nucleus were detected as before. Except that the sample number in detecting SLC7A11 and GPX4 was 4, the sample number in detecting other indexes was 3.Results:After 48 h of culture, the cell survival rates in control group, high glucose group, low baicalin group, and high baicalin group were (100.0±10.7)%, (70.0±5.0)%, (80.9±3.2)%, and (91.4±1.9)%, respectively. Compared with those in control group, the cell survival rate, the glutathione level, and SLC7A11 and GPX4 protein expression levels in cells, and nuclear Nrf2 protein expression level were significantly decreased in high glucose group ( P<0.05), and the levels of reactive oxygen species, malondialdehyde, and ferrous ion in cells, and cytoplasmic Nrf2 protein expression level were significantly increased in high glucose group ( P<0.05). Compared with those in high glucose group, the cell survival rate, glutathione level, SLC7A11 and GPX4 protein expression levels in cells, and nuclear Nrf2 protein expression level in low baicalin group and high baicalin group were significantly increased ( P<0.05), the reactive oxygen species and ferrous ion levels in cells, and cytoplasmic Nrf2 protein expression level in low baicalin group and high baicalin group were significantly decreased ( P<0.05), and the malondialdehyde level in cells in high baicalin group was significantly decreased ( P<0.05). Compared with those in low baicalin group, the cell survival rate, glutathione level, SLC7A11 and GPX4 protein expression levels in cells, and nuclear Nrf2 protein expression level in high baicalin group were significantly increased ( P<0.05), and the reactive oxygen species, malondialdehyde, and ferrous ion levels in cells, and cytoplasmic Nrf2 protein expression level in high baicalin group were significantly decreased ( P<0.05). After 48 h of culture, compared with those in control group, the nuclear Nrf2 protein expression level and SLC7A11 and GPX4 protein expression levels in cells were significantly decreased ( P<0.05), and the cytoplasmic Nrf2 protein expression level was significantly increased in high glucose group ( P<0.05); compared with those in high glucose group, the cytoplasmic Nrf2 protein expression level was significantly decreased ( P<0.05), and the nuclear Nrf2 protein expression level and SLC7A11 and GPX4 protein expression levels in cells were significantly increased in high baicalin group ( P<0.05); compared with those in high baicalin group, the cytoplasmic Nrf2 protein expression level was significantly increased ( P<0.05), and the nuclear Nrf2 protein expression level and SLC7A11 and GPX4 protein expression levels in cells were significantly decreased in high baicalin+ML385 group ( P<0.05). Conclusions:Baicalin can inhibit the occurrence of ferroptosis in cells by activating the Nrf2 signaling pathway and up-regulating the expressions of proteins related to SLC7A11/GPX4 axis in Fbs in high glucose treatment, thus increasing the cell survival rate.
3.Clinical features of chronic hepatitis C patients with genotype 3 infection:A multicenter retrospective cohort study
Jingyi XIE ; Yujia JING ; Yishan LIU ; Manling BAI ; Zhangqian CHEN ; Qiang XU ; Hong DU ; Yuxiu MA ; Liting ZHANG ; Shanshan ZHU ; Xiaoqin GAO ; Xinggang BAI ; Guoying YU ; Jianqi LIAN ; Xiaozhong WANG ; Yongping ZHANG ; Jiuping WANG ; Fanpu JI ; Jianjun FU ; Ning GAO
Journal of Clinical Hepatology 2025;41(8):1533-1540
Objective To investigate the clinical features of chronic hepatitis C(CHC)patients with hepatitis C virus genotype 3(HCV GT3)infection and the risk factors for disease progression.Methods A multicenter retrospective cohort study was conducted among 1 002 CHC patients from 11 clinical centers in Northwest China from December 2017 to November 2023,and according to their genotype,they were divided into GT1,GT2,GT3,and GT6 groups.Clinical features were compared between the patients with different genotypes.The one-way analysis of variance was used for comparison of normally distributed continuous data between groups,and the Scheffe test was used for further comparison between two groups.The Kruskal-Wallis H test was used for comparison of data with skewed distribution between groups;the chi-square test or Fisher test was used for comparison of categorical data between groups.The multivariate logistic regression analysis was used to explore the influencing factors for the progression of CHC to liver cirrhosis.Results In terms of the genotype,there were 427 patients with GT1 infection,242 with GT2 infection,299 with GT3 infection(210 patients with GT3a infection,87 with GT3b infection,and 2 with unclassified genotype),and 34 with GT6 infection.The patients with GT3 infection had a significantly younger age than those with GT1 infection(51.3±0.5 years vs 53.2±0.6 years,P<0.05)or GT2 infection(51.3±0.5 years vs 53.7±0.8 years,P<0.05),and for the patients with liver cirrhosis,the patients with GT3 infection had a significantly younger age than those with GT1 infection(52.1±0.5 years vs 59.4±0.9 years,P<0.001)or GT2 infection(52.1±0.5 years vs 58.1±1.1 years,P<0.001).Among the patients with GT3 infection,male patients accounted for 77.9%and the patients with liver cirrhosis accounted for 46.2%,which were significantly higher than those among the patients with GT1,GT2 or GT6 infection(all P<0.001).At baseline,the patients with GT3 infection had significantly higher levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)than those with GT1 or GT2 infection,significantly higher aspartate aminotransferase-to-platelet ratio index(APRI)and fibrosis-4(FIB4)than those with GT1,GT2 or GT6 infection,a significantly lower platelet count(PLT)than those with GT2 or GT6 infection,a significantly higher level of alpha-fetoprotein than those with GT2 or GT6 infection,and a significantly lower level of albumin(Alb)than those with GT6 infection(all P<0.05).There were no significant differences between the patients with GT3a infection and those with GT3b infection in age,sex,the proportion of patients with liver cirrhosis,comorbidities,HCV RNA quantification,PLT,ALT,AST,alkaline phosphatase,Alb,APRI,and FIB-4(all P>0.05).The multivariate logistic regression analysis showed that PLT≤150×109/L(odds ratio[OR]=10.72,95%confidence interval[CI]:5.76-35.86,P<0.001)and Alb≤35 g/L(OR=3.74,95%CI:1.22-11.45,P=0.021)were risk factors for liver cirrhosis.Conclusion Most CHC patients with GT3 infection are male in Northwest China,and compared with the patients with other genotypes,such patients tend to have a younger age of onset and higher degrees of liver inflammation activity and fibrosis.Low PLT and a low level of Alb are risk factors for progression to liver cirrhosis in CHC patients with GT3 infection.
4.Effects of baicalin on ferroptosis of mouse fibroblasts under high glucose treatment and its mechanism
Zheng GONG ; Xiaowei ZHANG ; Xiaomei LI ; Zhimin YIN ; Limin BAI ; Jiaxi WANG ; Yujia HAN ; Shuangyi XU ; Lu YU ; Gang XU
Chinese Journal of Burns 2025;41(3):277-285
Objective:To investigate the effects of baicalin on ferroptosis of mouse fibroblasts (Fbs) under high glucose treatment and its mechanism, and to provide a basis for the treatment of diabetic wounds.Methods:The study was an experimental study. Mouse Fbs were collected and divided into control group with conventional culture, high glucose group treated with glucose at final molarity of 30.0 mmol/L, and low baicalin group and high baicalin group pretreated with baicalin at final molarties of 5 and 10 μmol/L respectively and then treated as that in high glucose group. After 48 h of culture, the cell survival rate was detected by the cell counting kit-8, the reactive oxygen species level in cells was detected by the fluorescent probe method, the levels of malondialdehyde, glutathione, and ferrous ion in cells were detected by colorimetry, and the protein expression levels of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) in cells and nuclear factor-erythroid 2-related factor 2 (Nrf2) in cytoplasm and nucleus were detected by Western blotting. Another batch of mouse Fbs were collected and divided into control group, high glucose group, high baicalin group, and high baicalin+ML385 group. The cells in the first three groups were treated as before, the cells in the last group were pretreated with baicalin and ML385 of Nrf2 inhibitor at final molarties of 10 μmol/L and then treated as that in high glucose group. After 48 h of culture, the protein expression levels of SLC7A11 and GPX4 in cells and the protein expression level of Nrf2 in cytoplasm and nucleus were detected as before. Except that the sample number in detecting SLC7A11 and GPX4 was 4, the sample number in detecting other indexes was 3.Results:After 48 h of culture, the cell survival rates in control group, high glucose group, low baicalin group, and high baicalin group were (100.0±10.7)%, (70.0±5.0)%, (80.9±3.2)%, and (91.4±1.9)%, respectively. Compared with those in control group, the cell survival rate, the glutathione level, and SLC7A11 and GPX4 protein expression levels in cells, and nuclear Nrf2 protein expression level were significantly decreased in high glucose group ( P<0.05), and the levels of reactive oxygen species, malondialdehyde, and ferrous ion in cells, and cytoplasmic Nrf2 protein expression level were significantly increased in high glucose group ( P<0.05). Compared with those in high glucose group, the cell survival rate, glutathione level, SLC7A11 and GPX4 protein expression levels in cells, and nuclear Nrf2 protein expression level in low baicalin group and high baicalin group were significantly increased ( P<0.05), the reactive oxygen species and ferrous ion levels in cells, and cytoplasmic Nrf2 protein expression level in low baicalin group and high baicalin group were significantly decreased ( P<0.05), and the malondialdehyde level in cells in high baicalin group was significantly decreased ( P<0.05). Compared with those in low baicalin group, the cell survival rate, glutathione level, SLC7A11 and GPX4 protein expression levels in cells, and nuclear Nrf2 protein expression level in high baicalin group were significantly increased ( P<0.05), and the reactive oxygen species, malondialdehyde, and ferrous ion levels in cells, and cytoplasmic Nrf2 protein expression level in high baicalin group were significantly decreased ( P<0.05). After 48 h of culture, compared with those in control group, the nuclear Nrf2 protein expression level and SLC7A11 and GPX4 protein expression levels in cells were significantly decreased ( P<0.05), and the cytoplasmic Nrf2 protein expression level was significantly increased in high glucose group ( P<0.05); compared with those in high glucose group, the cytoplasmic Nrf2 protein expression level was significantly decreased ( P<0.05), and the nuclear Nrf2 protein expression level and SLC7A11 and GPX4 protein expression levels in cells were significantly increased in high baicalin group ( P<0.05); compared with those in high baicalin group, the cytoplasmic Nrf2 protein expression level was significantly increased ( P<0.05), and the nuclear Nrf2 protein expression level and SLC7A11 and GPX4 protein expression levels in cells were significantly decreased in high baicalin+ML385 group ( P<0.05). Conclusions:Baicalin can inhibit the occurrence of ferroptosis in cells by activating the Nrf2 signaling pathway and up-regulating the expressions of proteins related to SLC7A11/GPX4 axis in Fbs in high glucose treatment, thus increasing the cell survival rate.
5.Bionic design,preparation and clinical translation of oral hard tissue restorative materials
Han ZHAO ; Yan WEI ; Xuehui ZHANG ; Xiaoping YANG ; Qing CAI ; Chengyun NING ; Mingming XU ; Wenwen LIU ; Ying HUANG ; Ying HE ; Yaru GUO ; Shengjie JIANG ; Yunyang BAI ; Yujia WU ; Yusi GUO ; Xiaona ZHENG ; Wenjing LI ; Xuliang DENG
Journal of Peking University(Health Sciences) 2024;56(1):4-8
Oral diseases concern almost every individual and are a serious health risk to the popula-tion.The restorative treatment of tooth and jaw defects is an important means to achieve oral function and support the appearance of the contour.Based on the principle of"learning from the nature",Deng Xu-liang's group of Peking University School and Hospital of Stomatology has proposed a new concept of"microstructural biomimetic design and tissue adaptation of tooth/jaw materials"to address the worldwide problems of difficulty in treating dentine hypersensitivity,poor prognosis of restoration of tooth defects,and vertical bone augmentation of alveolar bone after tooth loss.The group has broken through the bottle-neck of multi-stage biomimetic technology from the design of microscopic features to the enhancement of macroscopic effects,and invented key technologies such as crystalline/amorphous multi-level assembly,ion-transportation blocking,and multi-physical properties of the micro-environment reconstruction,etc.The group also pioneered the cationic-hydrogel desensitizer,digital stump and core integrated restora-tions,and developed new crown and bridge restorative materials,gradient functionalisation guided tissue regeneration membrane,and electrically responsive alveolar bone augmentation restorative membranes,etc.These products have established new clinical strategies for tooth/jaw defect repair and achieved inno-vative results.In conclusion,the research results of our group have strongly supported the theoretical im-provement of stomatology,developed the technical system of oral hard tissue restoration,innovated the clinical treatment strategy,and led the progress of the stomatology industry.
6.Value of serum Lp-PLA2 in the diagnostic grading and prognostic assessment of pneumonia-related acute respiratory distress syndrome
Yujia YANG ; Baojun DONG ; Jinhui QU ; Jin HUANG ; Xue BAI ; Hongwei YANG
Chinese Journal of Clinical Laboratory Science 2024;42(8):580-585
Objective To explore the value of lipoprotein-associated phospholipase A2(Lp-PLA2)in the diagnostic grading and prog-nostic assessment of pneumonia-associated acute respiratory distress syndrome(p-ARDS).Methods The study was a prospective ob-servational study.Fifty-seven patients with p-ARDS admitted to the ICU ward of Tianjin Hospital from January 2022 to August 2023 were included as the research subjects.Twenty-six pneumonia patients admitted to the general respiratory ward during the same period and 10 healthy individuals undergoing medical examinations were selected as the control group.Their serum samples were collected,and the samples from p-ARDS and pneumonia patients were obtained within 24 hours of admission.The levels of serum Lp-PLA2,in-terleukin 6(IL-6),and IL-8 were detected using the Luminex? multiplex test kit.The baseline data and laboratory test results,inclu-ding routine blood parameters,biochemical markers,C-reactive protein(CRP),procalcitonin(PCT),and D-dimer at admission,were collected from the patients with p-ARDS or pneumonia.The levels of serum Lp-PLA2 were compared by grouping based on clinical diagnosis,severity of ARDS,and clinical outcomes on day 28 after admission.The diagnostic and prognostic value of serum Lp-PLA2 in p-ARDS was evaluated by plotting the receiver operating characteristic(ROC)curve,Spearman correlation analysis,and Logistic regression analysis.Results The levels of serum Lp-PLA2 in the p-ARDS group([233.67±83.49]ng/mL)were significantly higher than that in the pneumonia group([150.86±39.48]ng/mL,P<0.05),while those in the pneumonia group were significantly higher than that in the healthy control group([150.86±39.48]ng/mL vs[92.07±12.89]ng/mL,P<0.05).The analysis results of the ROC curve showed that serum Lp-PLA2 had a better ability to distinguish p-ARDS from pneumonia than indicators such as IL-6,IL-8,CRP,and PCT,with an area under the ROC curve(AUCROC)of 0.781(95%CI:0.685-0.878).The diagnostic value of serum Lp-PLA2 combined with D-dimer was higher,with an AUCROC of 0.897(95%CI:0.832-0.963).Subgroup analysis found that as lung inju-ry worsened,the levels of serum Lp-PLA2 increased,and that serum Lp-PLA2 levels were negatively correlated with the PaO2/FiO2 ra-tio in p-ARDS patients(r=-0.549)and positively correlated with the sequential organ failure assessment(SOFA)scores at admission(r=0.412).The levels of serum Lp-PLA2 in the death group of p-ARDS were significantly higher than that in the survival group([314.5±43.1]ng/mL vs[174.9±48.9]ng/mL,P<0.001).Logistic regression analysis showed that after adjusting for the SOFA score,serum Lp-PLA2 was independently associated with the mortality risk on day 28 after admission(OR=1.099,95%CI:1.026-1.178,P=0.007).Similar results were obtained after adjusting for IL-8 or the PaO2/FiO2 ratio.Conclusion Serum Lp-PLA2 may be used as a biomarker to aid in the diagnostic grading and prognostic assessment of p-ARDS.
7.Protective effect of polysacchcride of Atractylodes macrocephala koidz.on lipopo-lysaccharide induced acute kidney injury in juvenile laying hen
Yujia WU ; Siyuan LIU ; Xu LIU ; Heping BAI ; Qian LI ; Xiaodan WANG
Chinese Journal of Veterinary Science 2024;44(12):2635-2643
To investigate the effect of the polysaccharide derived from Atractylodes macrocephala koidz.(PAMK)on lipopolysaccharide(LPS)-induced acute kidney injury in juvenile laying hens.A total of 100 one-day-old male Hy-Line brown laying hens were randomly divided into five groups:a control group(CON group),an LPS treatment group(LPS group),a PAMK low-dose group(LPS+PAMK 250 mg/L,group A),a PAMK medium-dose group(LPS+PAMK 500 mg/L,group B),and a PAMK high-dose group(LPS+PAMK 1 000 mg/L,group C).The PAMK-treated groups were fed with corresponding doses of PAMK mixed with water daily from 1-20 days of age.At the age of 14,16,18 and 20 days,the chickens in the LPS group and PAMK-treated groups were intraperitoneally injected with LPS,while the chickens in the blank control group were injec-ted with the same volume of normal saline.After feeding for 21 days,the kidneys were collected,and pathological changes in kidney tissue sections were observed using hematoxylin and eosin(HE)staining.Kidney weight and chick weight were measured to calculate the kidney coefficient.The levels of BUN,CRE,MDA,SOD,GSH-Px and T-AOC in kidney tissues were measured.The contents of TNF-α and IL-1β were determined by ELISA.The mRNA expression of inflammatory factor genes(IL-1β,TNF-α and NF-κB)and apoptosis-related factors(p53,Bcl-2,Bax and Caspase-3)in the kidneys was detected using quantitative real-time PCR.The results indicated that PAMK alleviated LPS-induced renal tissue injury.Compared to the LPS group,PAMK significantly re-duced the kidney coefficient and BUN concentration in the kidneys(P<0.05).Additionally,the levels of TNF-α and IL-1β,as well as the mRNA expression of TNF-α,IL-1β,and NF-κB in the PAMK group,were decreased compared to the LPS group.Furthermore,T-AOC,SOD and GSH-Px activities in the PAMK group were significantly increased(P<0.05),while MDA content was significantly decreased(P<0.01).Compared with the LPS group,the mRNA expression of Bax,Caspase-3 and p53 in the PAMK low-dose group and the PAMK medium-dose group decreased,while the mRNA expression of Bcl-2 increased.In conclusion,PAMK can inhibit the inflammatory response and oxidative stress response caused by LPS,and alleviate the apoptosis of kidney cells,and the treatment effect of PAMK in the middle dose group is the best,which provides a theoreti-cal basis for PAMK treatment of acute kidney injury in chickens.
8.Protective effect of polysacchcride of Atractylodes macrocephala koidz.on lipopo-lysaccharide induced acute kidney injury in juvenile laying hen
Yujia WU ; Siyuan LIU ; Xu LIU ; Heping BAI ; Qian LI ; Xiaodan WANG
Chinese Journal of Veterinary Science 2024;44(12):2635-2643
To investigate the effect of the polysaccharide derived from Atractylodes macrocephala koidz.(PAMK)on lipopolysaccharide(LPS)-induced acute kidney injury in juvenile laying hens.A total of 100 one-day-old male Hy-Line brown laying hens were randomly divided into five groups:a control group(CON group),an LPS treatment group(LPS group),a PAMK low-dose group(LPS+PAMK 250 mg/L,group A),a PAMK medium-dose group(LPS+PAMK 500 mg/L,group B),and a PAMK high-dose group(LPS+PAMK 1 000 mg/L,group C).The PAMK-treated groups were fed with corresponding doses of PAMK mixed with water daily from 1-20 days of age.At the age of 14,16,18 and 20 days,the chickens in the LPS group and PAMK-treated groups were intraperitoneally injected with LPS,while the chickens in the blank control group were injec-ted with the same volume of normal saline.After feeding for 21 days,the kidneys were collected,and pathological changes in kidney tissue sections were observed using hematoxylin and eosin(HE)staining.Kidney weight and chick weight were measured to calculate the kidney coefficient.The levels of BUN,CRE,MDA,SOD,GSH-Px and T-AOC in kidney tissues were measured.The contents of TNF-α and IL-1β were determined by ELISA.The mRNA expression of inflammatory factor genes(IL-1β,TNF-α and NF-κB)and apoptosis-related factors(p53,Bcl-2,Bax and Caspase-3)in the kidneys was detected using quantitative real-time PCR.The results indicated that PAMK alleviated LPS-induced renal tissue injury.Compared to the LPS group,PAMK significantly re-duced the kidney coefficient and BUN concentration in the kidneys(P<0.05).Additionally,the levels of TNF-α and IL-1β,as well as the mRNA expression of TNF-α,IL-1β,and NF-κB in the PAMK group,were decreased compared to the LPS group.Furthermore,T-AOC,SOD and GSH-Px activities in the PAMK group were significantly increased(P<0.05),while MDA content was significantly decreased(P<0.01).Compared with the LPS group,the mRNA expression of Bax,Caspase-3 and p53 in the PAMK low-dose group and the PAMK medium-dose group decreased,while the mRNA expression of Bcl-2 increased.In conclusion,PAMK can inhibit the inflammatory response and oxidative stress response caused by LPS,and alleviate the apoptosis of kidney cells,and the treatment effect of PAMK in the middle dose group is the best,which provides a theoreti-cal basis for PAMK treatment of acute kidney injury in chickens.
9.Biosynthesis of rumbrins and inspiration for discovery of HIV inhibitors.
Beifen ZHONG ; Jun WAN ; Changhui SHANG ; Jiajia WEN ; Yujia WANG ; Jian BAI ; Shan CEN ; Youcai HU
Acta Pharmaceutica Sinica B 2022;12(11):4193-4203
Investigation on how nature produces natural compounds with chemical and biological diversity at the genetic level offers inspiration for the discovery of new natural products and even their biological targets. The polyketide rumbrin ( 1) is a lipid peroxide production and calcium accumulation inhibitor, which contains a chlorinated pyrrole moiety that is a rare chemical feature in fungal natural products. Here, we identify the biosynthetic gene cluster (BGC) rum of 1 and its isomer 12E-rumbrin ( 2) from Auxarthron umbrinum DSM3193, and elucidate their biosynthetic pathway based on heterologous expression, chemical complementation, and isotopic labeling. We show that rumbrins are assembled by a highly reducing polyketide synthase (HRPKS) that uniquely incorporates a proline-derived pyrrolyl-CoA starer unit, and followed by methylation and chlorination. Sequent precursor-directed biosynthesis was able to yield a group of rumbrin analogues. Remarkably, inspired by the presence of a human immunodeficiency virus (HIV)-Nef-associated gene in the rum cluster, we predicted and pharmacologically demonstrated rumbrins as potent inhibitors of HIV at the nanomolar level. This work enriches the recognition of unconventional starter units of fungal PKSs and provides a new strategy for genome mining-guided drug discovery.
10.Heart Failure Is Associated with Increased Risk of Long-Term Venous Thromboembolism
Tianyu XU ; Yuli HUANG ; Zuheng LIU ; Yujia BAI ; Zhuang MA ; Xiaoyan CAI ; Yuhui ZHANG ; Jian ZHANG
Korean Circulation Journal 2021;51(9):766-780
Background and Objectives:
Venous thromboembolism (VTE), consisting of deep vein thrombosis (DVT) and pulmonary embolism (PE), is highly prevalent in in-hospital HF patients and contributes to worse prognoses. However, the risk of VTE in out-patients with HF in long-term period is controversial. This study aimed to evaluate the associations between HF and the risk of VTE in a long-term follow-up duration.
Methods:
We searched for studies investigating the risk of VTE, PE, and DVT in patients with HF before April 15, 2020, in PubMed, MEDLINE, and Embase databases. Cohort studies and post hoc analysis of RCTs were eligible for inclusion if they reported relative risk of VTE, DVT or PE in patients with HF in more than 3-month follow-up period.
Results:
We identified 31 studies that enrolled over 530,641 HF patients. Overall, patients with HF were associated with an increased risk of VTE (risk ratio [RR]=1.57, 95% confidence interval [CI]=1.34–1.84) and PE (RR=2.00, 95% CI=1.38–2.89). However, the risk of DVT was not significantly increased in HF patients (RR=1.33, 95% CI=0.67–2.63). Subgroup analysis showed that patients with chronic HF (RR=1.54, 95% CI=1.32–1.80) had a higher risk of VTE than those with acute HF (RR=0.95, 95% CI=0.68–1.32).
Conclusions
In conclusion, HF was an independent risk for VTE and PE but not DVT in a longterm follow-up period. Patients with chronic HF were prone to suffer from VTE than acute HF.

Result Analysis
Print
Save
E-mail