1.Parabacteroides distasonis promotes liver regeneration by increasing β-hydroxybutyric acid (BHB) production and BHB-driven STAT3 signals.
Manlan GUO ; Xiaowen JIANG ; Hui OUYANG ; Xianglong ZHANG ; Shuaishuai ZHANG ; Peng WANG ; Guofang BI ; Ting WU ; Wenhong ZHOU ; Fengting LIANG ; Xiao YANG ; Shicheng FAN ; Jian-Hong FANG ; Peng CHEN ; Huichang BI
Acta Pharmaceutica Sinica B 2025;15(3):1430-1446
The liver regenerative capacity is crucial for patients with end-stage liver disease following partial hepatectomy (PHx). The specific bacteria and mechanisms regulating liver regeneration post-PHx remain unclear. This study demonstrated dynamic changes in the abundance of Parabacteroides distasonis (P. distasonis) post-PHx, correlating with hepatocyte proliferation. Treatment with live P. distasonis significantly promoted hepatocyte proliferation and liver regeneration after PHx. Targeted metabolomics revealed a significant positive correlation between P. distasonis and β-hydroxybutyric acid (BHB), as well as hyodeoxycholic acid and 3-hydroxyphenylacetic acid in the gut after PHx. Notably, treatment with BHB, but not hyodeoxycholic acid or 3-hydroxyphenylacetic acid, significantly promoted hepatocyte proliferation and liver regeneration in mice after PHx. Moreover, STAT3 inhibitor Stattic attenuated the promotive effects of BHB on cell proliferation and liver regeneration both in vitro and in vivo. Mechanistically, P. distasonis upregulated the expression of fatty acid oxidation-related proteins, and increased BHB levels in the liver, and then BHB activated the STAT3 signaling pathway to promote liver regeneration. This study, for the first time, identifies the involvement of P. distasonis and its associated metabolite BHB in promoting liver regeneration after PHx, providing new insights for considering P. distasonis and BHB as potential strategies for promoting hepatic regeneration.
2.Erratum: Publisher erratum to "Fenofibrate-promoted hepatomegaly and liver regeneration are PPARα-dependent and partially related to the YAP pathway" Acta Pharmaceutica Sinica B 14 (2024) 2992-3008.
Shicheng FAN ; Yue GAO ; Pengfei ZHAO ; Guomin XIE ; Yanying ZHOU ; Xiao YANG ; Xuan LI ; Shuaishuai ZHANG ; Frank J GONZALEZ ; Aijuan QU ; Min HUANG ; Huichang BI
Acta Pharmaceutica Sinica B 2025;15(6):3354-3354
[This corrects the article DOI: 10.1016/j.apsb.2024.03.030.].
3.Early prediction of growth patterns after pediatric kidney transplantation based on height-related single-nucleotide polymorphisms
Yi FENG ; Yonghua FENG ; Mingyao HU ; Hongen XU ; Zhigang WANG ; Shicheng XU ; Yongchuang YAN ; Chenghao FENG ; Zhou LI ; Guiwen FENG ; Wenjun SHANG
Chinese Medical Journal 2024;137(10):1199-1206
Background::Growth retardation is a common complication of chronic kidney disease in children, which can be partially relieved after renal transplantation. This study aimed to develop and validate a predictive model for growth patterns of children with end-stage renal disease (ESRD) after kidney transplantation using machine learning algorithms based on genomic and clinical variables.Methods::A retrospective cohort of 110 children who received kidney transplants between May 2013 and September 2021 at the First Affiliated Hospital of Zhengzhou University were recruited for whole-exome sequencing (WES), and another 39 children who underwent transplant from October 2021 to March 2022 were enrolled for external validation. Based on previous studies, we comprehensively collected 729 height-related single-nucleotide polymorphisms (SNPs) in exon regions. Seven machine learning algorithms and 10-fold cross-validation analysis were employed for model construction.Results::The 110 children were divided into two groups according to change in height-for-age Z-score. After univariate analysis, age and 19 SNPs were incorporated into the model and validated. The random forest model showed the best prediction efficacy with an accuracy of 0.8125 and an area under curve (AUC) of 0.924, and also performed well in the external validation cohort (accuracy, 0.7949; AUC, 0.796). Conclusions::A model with good performance for predicting post-transplant growth patterns in children based on SNPs and clinical variables was constructed and validated using machine learning algorithms. The model is expected to guide clinicians in the management of children after renal transplantation, including the use of growth hormone, glucocorticoid withdrawal, and nutritional supplementation, to alleviate growth retardation in children with ESRD.
4.Strontium-containing mesoporous bioactive glass nanoparticles loaded with bisphosphonates ameliorate bone loss in ovariectomized mice
Zhi ZHOU ; Zhijie CHEN ; Shicheng HUO ; Zhanchun LI
Chinese Journal of Tissue Engineering Research 2024;28(17):2653-2658
BACKGROUND:Inhibition of osteoclast activity by bisphosphonates slows the progression of osteoporosis.However,serious complications of bisphosphonates,such as osteonecrosis of the jaw and atypical femur fracture,limit the clinical application of bisphosphonates.Effective alternative therapies need to be sought to improve existing clinical dilemmas. OBJECTIVE:To prepare strontium-containing mesoporous bioactive glass nanoparticles loaded with bisphosphonates(BPS@Sr-MBG)and analyze its activity against bone loss. METHODS:Strontium-containing mesoporous bioactive glass nanoparticles(Sr-MBG)were prepared by sol-gel method and added to alendronate saturated solution for the preparation of BPS@Sr-MBG.(1)Cell experiment:Mouse bone marrow macrophages were inoculated in 96-well plates and supplemented with ɑ-MEM complete culture medium containing macrophage colony stimulating factor and activator-ligand of nuclear factor κB receptor for osteoclast induced differentiation experiment.Meanwhile,they were cultured in three groups.The blank group was added with PBS.The control group was added with bisphosphonate,and the experimental group was added with BPS@Sr-MBG.After 5 days of culture,the differentiation of osteoclasts was observed by F-actin ring staining.(2)Animal experiments:Twenty-four female C57/BL mice were randomly divided into four groups with six mice in each group.Except sham operation group,ovariectomy group,BPS group and BPS@Sr-MBG group were used to construct osteoporosis model.One week after model establishment,mice in BPS group and BPS@Sr-MBG group were intraperitoneally injected with bisphosphonate solution and BPS@Sr-MBG solution,respectively.Mice in the sham operation group and ovariectomy group were intraperitoneally injected with PBS once a week.After 8 weeks of continuous injection,mouse femurs were taken for Micro-CT scanning and hematoxylin-eosin staining. RESULTS AND CONCLUSION:(1)Cell experiment:F-actin ring-formation staining demonstrated that compared with blank group,the area proportion and number of osteoclasts in the control group were decreased(P<0.01).Compared with the control group,the area proportion of osteoclasts and the number of osteoclasts in the experimental group were decreased(P<0.01).(2)Animal experiments:Micro-CT scanning results of femur showed that compared with the sham operation group,bone density,trabecular bone volume fraction,trabecular thickness and trabecular number of mice in the ovariectomy group were decreased(P<0.05,P<0.01),while trabecular distance and structural model index were increased(P<0.01).Compared with the ovariectomy group,the above bone parameters in the BPS group and BPS@Sr-MBG group were significantly improved(P<0.01),and the improvement in the BPS@Sr-MBG group was more obvious.The Micro-CT scanning results were further confirmed by hematoxylin-eosin staining of the femur.(3)The results show that BPS@Sr-MBG can exert anti-osteoporosis activity through anti-osteoclastic effect and promoting bone formation.
5.Impact of ERCC1 C8092A gene polymorphism on the efficacy of platinum-based chemotherapy for lung cancer
LI Yixuan ; WANG Yiwei ; FU Yihui ; MENG Chong ; KUANG Shicheng ; LYU Pengfei ; ZHOU jing ; XU Qiongjun ; HUANG Hairong ; XIAO Sha
China Tropical Medicine 2024;24(1):65-
Objective To explore the relationship between the polymorphism of excision repair cross-complementation group 1 (ERCC1) C8092A locus and the efficacy and prognosis of platinum-based chemotherapy for lung cancer (LC), and to provide a theoretical basis for precision treatment of LC. Methods From January 2014 to October 2017, 120 patients from two tertiary hospitals in Haikou City, and with pathologically confirmed lung cancer treated with platinum-based chemotherapy were selected as the research objects. After informed consent was obtained, peripheral blood samples were collected for DNA extraction, and the genotype of ERCC1 C8092A locus was detected by mass spectrometry. WHO's Response Evaluation Criteria in Solid Tumours (RECIST) was used to judge patients' chemotherapy efficacy and patients' survival status was obtained by telephone follow-up and other means. Results Among the 120 LC patients, the genotype frequencies of ERCC1 C8092A locus were 67 cases of CC wildtype (55.8%), 45 cases of CA heterozygous type (37.5%), and 8 cases of AA rare mutation type (6.7%), which conformed to Hardy-Weinberg equilibrium (χ2=0.140, P>0.05). The total effective rate of chemotherapy was 32.5%, with the highest effective rate in patients with the CA genotype (42.2%) at the ERCC1 C8092A locus and the lowest in patients with the CC genotype (25.4%). The overall one-year survival rate was 68.3% and the three-year survival rate was 35.8%. The patients with ERCC1 C8092A AA genotype had the lowest survival rate, with a one-year survival rate of 50.0% and three-year survival rate of only 25.0%. However, there were no statistical differences in the overall survival rate among the three genotypes of carriers of ERCC1 C8092A (χ2=0.328, P=0.849). Conclusions The polymorphism of ERCC1 C8092A locus is associated with the efficacy of platinum-based chemotherapy for LC, and patients with CA genotype have the highest efficacy. The one-year and three-year survival rates of patients with CC genotype are significantly higher than those of CA and AA genotypes.
6.Panax notoginseng extracts regulate inflammatory response of immune-stressed broilers through IL-6,CASP3 and STAT3
Lin DU ; Pingrui YANG ; Hanlin ZHOU ; Lijuan QIU ; Weidong HU ; Liting CAO ; Shicheng BI
Chinese Journal of Veterinary Science 2024;44(8):1755-1764
This study aims to observe the effect of Panax notoginseng extracts on inflammatory re-sponse in immunosuppressed broilers and to investigate the mechanism through network pharma-cology and molecular docking combined with in vivo animal tests.Based on the TCMSP database and GeneCard and other disease databases,we searched for targets related to Panax notoginseng and broiler inflammation,screened key compounds and targets by applying Cytoscape 3.7.1 and String databases,respectively,and constructed a network relationship diagram of traditional Chi-nese medicine(TCM)-key components-targets,and carried out GO functional enrichment and KEGG pathway enrichment analyses by using the DAVID platform.The GO functional enrichment analysis and KEGG pathway enrichment analysis were carried out by the DAVID platform,visual-ized by the Chiplot online website,and finally,the core clustered proteins were analyzed by Pymol software to obtain the core targets,and molecular docking technology was used to predict the de-gree of matching between the active ingredients and the core targets as well as the animal experi-ments to further explore the pharmacological mechanism of Panax notoginseng extracts.Sixty 1-day-old red-feathered broilers were randomly divided into three groups(LPS group,CON group,and PN group),and the test period was 35 days.The LPS and PN groups were injected intraperito-neally with 250 μg/kg body weight of LPS,and the CON group was injected with an equal amount of sterile physiological saline on the 12,14,33,and 35 d.The LPS and PN groups were injected with 250 μg/kg body weight of LPS,and the CON group was injected with an equal amount of sterile physiological saline.The effect of Panax notoginseng extract on inflammatory cytokines in serum was detected by ELISA,and the hormone content in serum was also detected in each group,and fluorescence quantitative PCR was used to detect the effect of each group on the mRNA ex-pression levels of STAT3,IL-6,and CASP3.The results showed that the serum levels of IFN-γ,IL-6,iNOS,TNF-α,and TNF-β were significantly increased(P<0.05),while the level of IL-10 was significantly decreased(P<0.05)after LPS tapping at weeks 2 and 5.The serum levels of IFN-y,IL-6,iNOS,TNF-α,and TNF-β were significantly decreased(P<0.05)and IL-10 was sig-nificantly increased(P<0.05)by the addition of Panax ginseng extracts to the basal diet com-pared with the LPS group.Panax notoginseng extracts significantly decreased the serum levels of adrenocorticotropic hormone(ACTH)and corticosterone(CORT)(P<0.05)and increased the levels of growth hormone(GH)(P<0.05).A total of 8 active ingredients and 123 potential tar-gets for broiler inflammation were predicted by network pharmacology.The protective mechanism of Panax notoginseng against broiler inflammation may be related to the C-type lectin receptor(CLR)signaling pathway,Toll-like receptor(TLR)signaling pathway,MAPK signaling pathway,NOD-like receptor(NLR)signaling pathway,and FoxO signaling pathway.According to the pre-diction,the alleviation of inflammatory response in broiler chickens by Panax notoginseng may be related to the action on 12 key targets.Fluorescence quantitative PCR showed that Panax notogin-seng extract down-regulated the mRNA expression of IL-6 and CASP3(P<0.05)and up-regula-ted that of STAT3(P<0.05),and molecular docking results also showed that the active ingredi-ents in Panax notoginseng extracts could exert anti-inflammatory effects through IL-6 and CASP3.The results suggested that Panax quinquefolium extracts might alleviate the inflammatory response of immune-stressed broilers through multi-components,multi-targets,and multi-path-ways,and this study helps propose new therapeutic strategies and provides a theoretical basis for the development of feed additives based on Penthorum chinense Pursh extract.
7.Expert consensus on recombinant B subunit/inactivated whole-cell cholera vaccine in preventing infectious diarrhea of enterotoxigenic Escherichia coli
Chai JI ; Yu HU ; Mingyan LI ; Yan LIU ; Yuyang XU ; Hua YU ; Jianyong SHEN ; Jingan LOU ; Wei ZHOU ; Jie HU ; Zhiying YIN ; Jingjiao WEI ; Junfen LIN ; Zhenyu SHEN ; Ziping MIAO ; Baodong LI ; Jiabing WU ; Xiaoyuan LI ; Hongmei XU ; Jianming OU ; Qi LI ; Jun XIANG ; Chen DONG ; Haihua YI ; Changjun BAO ; Shicheng GUO ; Shaohong YAN ; Lili LIU ; Zengqiang KOU ; Shaoying CHANG ; Shaobai ZHANG ; Xiang GUO ; Xiaoping ZHU ; Ying ZHANG ; Bangmao WANG ; Shuguang CAO ; Peisheng WANG ; Zhixian ZHAO ; Da WANG ; Enfu CHEN
Chinese Journal of Clinical Infectious Diseases 2023;16(6):420-426
Enterotoxigenic Escherichia coli(ETEC)infection can induce watery diarrhea,leading to dehydration,electrolyte disturbance,and even death in severe cases. Recombinant B subunit/inactivated whole-cell cholera(rBS/WC)vaccine is effective in preventing ETEC infectious diarrhea. On the basis of the latest evidence on etiology and epidemiology of ETEC,as well as the effectiveness,safety,and health economics of rBS/WC vaccine,National Clinical Research Center for Child Health(The Children’s Hospital,Zhejiang University School of Medicine)and Zhejiang Provincial Center for Disease Control and Prevention invited experts to develop expert consensus on rBS/WC vaccine in prevention of ETEC infectious diarrhea. It aims to provide the clinicians and vaccination professionals with guidelines on using rBS/WC vaccine to reduce the incidence of ETEC infectious diarrhea.
8.LncRNA C21orF96 promotes the invasion and metastasis of gastric cancer by regulating the expression of miR-875-5p and USF2 genes
Shicheng ZHOU ; Qinhui SUN ; Hongxia ZHANG ; Guodong LIAN ; Hongjun LIU ; Leping LI ; Xiaobo GUO
Chinese Journal of General Surgery 2020;35(1):57-60
Objective To verify that lncRNA-C21orF96 regulates the expression of miRNA-875-5p and USF2 genes and promotes the invasion and metastasis of gastric cancer.Methods RT-PCR was used to measure the expression of lncRNA-C21orF96 related miRNA in gastric cancer cells.pcDNA3.1 plasmid was used to over-express lncRNA-C21orF96 in KATO-Ⅲ and siRNA was used to knockdown the expression of lncRNA-C21orF96 in SGC-7901,and RT-PCR was used to measure the expression of miRNA-875-5p and USF2 genes;By overexpressing lncRNA-C21orF96 in MKN45,transwell was used to observe changes of cells invasion and migration.Results LncRNA-C21orF96 showed a significant inverse relationship with miR-875-5p,(SGC-7901:21.19 ±1.09 vs.3.28 ±0.06,P<0.01;SNU-16:24.76 ±2.09 vs.8.16 ±0.07,P < 0.01).In KATO-Ⅲ over-expressing lncRNA-C21 orF96,miR-875-5p expression decreased significantly while USF2 expression increased (P <0.01);In SGC-7901 with lncRNA-C21orF96 knockdown,miR-875-5p expression increased significantly while USF2 expression decreased (P < 0.05).The number of cells passing through the artificial basement membrane in the experimental group was significantly different from that in the control group (migration:216.19 ± 2.30 vs.89.19 ± 4.60,P<0.001;invasion:146.18 ±5.3 vs.59.18 ± 2.60,P < 0.001).Conclusions The overexpression of lncRNA-C21orF96 significantly reduces the expression of miR-875-5p and promotes the expression of USF2,hence promoting the invasion and metastasis of gastric cancer.
9. Prevalence and risk factors of diabetic peripheral neuropathy in Chinese communities
Li QIN ; Jingya NIU ; Jinyi ZHOU ; Qingjun ZHANG ; Fang ZHOU ; Ning ZHANG ; Zhengyuan ZHOU ; Hongyan SHENG ; Shicheng REN ; Jian SU ; Cihua ZHU ; Hongyan LYU ; Wenjuan WANG
Chinese Journal of Epidemiology 2019;40(12):1578-1584
Objective:
To investigate the prevalence and risk factors of diabetic peripheral neuropathy in type 2 diabetic patients under community management programs.
Methods:
A cross-sectional study was conducted on T2DM patients in eight communities in Wuhan and Changshu cities. Data would included questionnaire, body measurement, blood testing and clinical examination. The criterion of diabetic peripheral neuropathy was under the combination of symptoms with five physical examinations. Binary logistic regression model was used to analyze the influential factors.
Results:
The overall prevalence of peripheral neuropathy was 71.2
10. Manifestations of chest CT imaging in AIDS patients complicated with pulmonary cryptococcosis
Fangfei WEI ; Liping DENG ; Yong XIONG ; Jun ZHOU ; Shicheng GAO ; Yongxi ZHANG ; Xi′en GUI
Chinese Journal of General Practitioners 2019;18(9):856-860
Objective:
To analysis the manifestations of chest CT imaging in acquired immunodeficiency syndrome (AIDS) patients complicated with pulmonary cryptococcosis.
Methods:
The clinical data of 72 AIDS patients complicated with pulmonary cryptococcosis were analyzed retrospectively. There were 3 cases (4.2%) diagnosed with pulmonary cryptococcosis by biopsy, including 1 case of pulmonary cryptococcosis and 2 cases of disseminated cryptococcosis; 69 cases (95.8%) with pulmonary manifestations and clinically diagnosed with pulmonary cryptococcosis, including 43 cases of cryptococcal meningitis and 26 cases of disseminated cryptococcosis. The imaging features of chest CT, in terms of the morphology, size, number, distribution, internal features and margins of the lesions were analyzed.
Results:
The chest CT findings were solid nodules or mass in 49 cases (68.1%), patchy shadows in 40 cases (55.6%), cavitary nodules or mass in 10 cases (13.9%), mediastinal and hilar lymph node enlargement in 17 cases (23.6%) and pleural effusion in 10 cases (13.9%).
Conclusion
The chest CT findings of AIDS patients complicated with pulmonary cryptococcosis mainly are multiple solid nodules or masses, patchy shadows and solitary cavitary pulmonary nodules or mass. For early diagnosis and treatment, cryptococcus screening should be performed in HIV-infected patients with pulmonary nodules or mass on chest CT.

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