1.Ablation of macrophage transcriptional factor FoxO1 protects against ischemia-reperfusion injury-induced acute kidney injury.
Yao HE ; Xue YANG ; Chenyu ZHANG ; Min DENG ; Bin TU ; Qian LIU ; Jiaying CAI ; Ying ZHANG ; Li SU ; Zhiwen YANG ; Hongfeng XU ; Zhongyuan ZHENG ; Qun MA ; Xi WANG ; Xuejun LI ; Linlin LI ; Long ZHANG ; Yongzhuo HUANG ; Lu TIE
Acta Pharmaceutica Sinica B 2025;15(6):3107-3124
Acute kidney injury (AKI) has high morbidity and mortality, but effective clinical drugs and management are lacking. Previous studies have suggested that macrophages play a crucial role in the inflammatory response to AKI and may serve as potential therapeutic targets. Emerging evidence has highlighted the importance of forkhead box protein O1 (FoxO1) in mediating macrophage activation and polarization in various diseases, but the specific mechanisms by which FoxO1 regulates macrophages during AKI remain unclear. The present study aimed to investigate the role of FoxO1 in macrophages in the pathogenesis of AKI. We observed a significant upregulation of FoxO1 in kidney macrophages following ischemia-reperfusion (I/R) injury. Additionally, our findings demonstrated that the administration of FoxO1 inhibitor AS1842856-encapsulated liposome (AS-Lipo), mainly acting on macrophages, effectively mitigated renal injury induced by I/R injury in mice. By generating myeloid-specific FoxO1-knockout mice, we further observed that the deficiency of FoxO1 in myeloid cells protected against I/R injury-induced AKI. Furthermore, our study provided evidence of FoxO1's pivotal role in macrophage chemotaxis, inflammation, and migration. Moreover, the impact of FoxO1 on the regulation of macrophage migration was mediated through RhoA guanine nucleotide exchange factor 1 (ARHGEF1), indicating that ARHGEF1 may serve as a potential intermediary between FoxO1 and the activity of the RhoA pathway. Consequently, our findings propose that FoxO1 plays a crucial role as a mediator and biomarker in the context of AKI. Targeting macrophage FoxO1 pharmacologically could potentially offer a promising therapeutic approach for AKI.
2.Exploring the clinical application effects of two different sources of domestic oral restoration membrane in guided bone regeneration during dental implantation in diabetic patients
Jing LI ; Yan DONG ; Fu WANG ; Kehui XU ; Chenyu WANG ; Li CHEN ; Lina NIU
Chinese Journal of Stomatology 2025;60(2):116-122
Objective:To investigate the bone augmentation effects of domestic decellularized porcine small intestinal submucosa (PSIS) absorbable biomembrane and domestic bovine pericardium tissue (BPT) absorbable biomembrane in guided bone regeneration (GBR) for single-tooth implantation in diabetic patients.Methods:A prospective case-control study was conducted with 48 diabetic patients who received single-tooth implant restoration at the Department of Prosthodontics, School of Stomatology. The Fourth Military Medical University, between January 2023 and January 2024. Patients were randomly assigned to the study group (PSIS group) and the control group (BPT group) using a random number table, with 24 patients in each group. GBR was performed simultaneously with the implant surgery. Cone-beam CT was used to compare the buccal-side horizontal bone gain at 6 months post-operation between the two groups. Wound healing was evaluated at 1 and 4 weeks post-operation using wound healing scores.Results:At 6 months post-operation, the buccal-side horizontal bone gain at 2 mm below the implant abutment in the study group [69.1 (55.2, 82.4) mm] and the control group [71.4 (59.8, 77.0) mm] showed no statistically significant difference ( Z=-0.25, P=0.805). The wound healing scores at 1 and 4 weeks post-operation in the study group did not differ significantly from those in the control group at the same time points (1 week: Z=-0.49, P=0.627; 4 weeks: Z=-0.61, P=0.539). Conclusions:The use of two types of domestic absorbable collagen membranes for GBR in single-tooth implantation in diabetic patients showed comparable buccal-side horizontal bone gain effects at 6 months post-operation and similar clinical outcomes for wound healing at 1 and 4 weeks post-operation in both groups. The GBR effects of PSIS and BPT are similar.
3.Mechanism study of lncRNA SNHG1/miR-340-5p/PTX3 signaling pathway in osimertinib resistance of lung cancer
Lu ZHANG ; Wenli ZHAO ; Lingwen HE ; Chenyu XU
International Journal of Laboratory Medicine 2025;46(14):1758-1763
Objective To explore the mechanism of the long non-coding RNA(lncRNA)small nucleolar RNA host gene 1(SNHG1)/microRNA(miR)-340-5p/pentraxin 3(PTX3)signaling pathway in osimertinib resistance of lung cancer.Methods The expression levels of SNHG1,miR-340-5p and PTX3 in lung cancer tissues,adjacent tissues and osimertinib-sensitive and resistant cell lines were detected by real-time fluores-cence quantitative PCR.SNHG1 was knockdown using siRNA to detect its effects on cell proliferation,apopto-sis and osimertinib sensitivity.The dual-luciferase reporter assay verified the binding relationship between SNHG1 and miR-340-5p,as well as between miR-340-5p and PTX3.Western blotting was used to analyze the expression changes of PTX3 protein.Results SNHG1 was highly expressed in lung cancer tissues and osimer-tinib-resistant cells,while the expression of miR-340-5p was downregulated.SNHG1 inhibits the function of miR-340-5p by directly binding to it and releases the negative regulation of miR-340-5p on PTX3,resulting in the high expression of PTX3 in lung cancer drug-resistant cells.Knockdown of SNHG1 can increase the apop-tosis rate of drug-resistant cells,inhibit the ability of colony formation,and enhance the sensitivity of cells to osimertinib.The miR-340-5p inhibitor upregulated the expression of PTX3 in lung cancer sensitive cells.Con-clusion SNHG1 as competitive endogenous RNA inhibition of miR-340-5p,thus raising PTX3 expression,the drug resistance of lung cancer cells,SNHG1/miR-340-5p/PTX3 shaft may provide potential targets in the treatment of lung cancer drug resistance.
4.Improved prebiotic-based "shield" equipped probiotics for enhanced colon cancer therapy by polarizing M1 macrophages and regulating intestinal microbiota.
Yang WANG ; Xiaomin SU ; Yao LIU ; Lina HU ; Lin KANG ; Ce XU ; Zanya SUN ; Chenyu SUN ; Huishu GUO ; Shun SHEN
Acta Pharmaceutica Sinica B 2025;15(8):4225-4247
Probiotics play a crucial role in colon cancer treatment by metabolizing prebiotics to generate short-chain fatty acids (SCFAs). Colon cancer patients are frequently propositioned to supplement with probiotics to enhance the conversion and utilization of prebiotics. Nevertheless, the delivery and colonization of probiotics is hindered by the harsh conditions of gastrointestinal tract (GIT). Here, we devised a straightforward yet potent modified prebiotic-based "shield" (Gelatin-Inulin, GI), employing dietary inulin and natural polymer gelatin crosslinked via hydrogen bonding for enveloping Lactobacillus reuteri (Lr) to formulate synbiotic hydrogel capsules (Lr@Gl). The GI "shield" serves as a dynamic barrier, augmenting the resistance of Lr to gastric acid and facilitating its bioactivity and adherence in the GIT, synergizing with Lr to elicit an anti-tumor effect. Simultaneously, Lr@GI demonstrates anti-tumor effects by depleting glutathione to release reactive oxygen species, accompanied by the activation of NLRP3 (NOD-like receptor family pyrin domain containing 3), and the induction M1 macrophage polarization. Furthermore, Lr@GI can not only promote the recovery of intestinal barrier but also regulate intestinal flora, promoting the production of SCFAs and further exerting anti-tumor effect. Crucially, Lr@GI also potentiates the anti-tumor effect of 5-Fluorouracil. The construction and synergistic anti-tumor mechanism of synbiotic hydrogel capsules system provide valuable insights for gut microbial tumor therapy.
5.Perifornical UCN3 Neurons Regulate Overeating-Induced Weight Gain.
Shanshan LU ; Xinran ZHANG ; Wanqi CHEN ; Baofang ZHANG ; Haiyang JING ; Yunlong XU ; Fengling LI ; Chenyu JIANG ; Gaowei CHEN ; Xiaofei DENG ; Yingjie ZHU
Neuroscience Bulletin 2025;41(6):1103-1108
6.Antimicrobial resistance surveillance in the bacterial strains isolated from pediatric intensive care units in China:results from 2020 to 2022
Jing LIU ; Huiyuan YAN ; Gangfeng YAN ; Guoping LU ; Pan FU ; Chuanqing WANG ; Danqun JIN ; Wenjia TONG ; Chenyu ZHANG ; Jianli CHEN ; Yi LIN ; Jia LEI ; Yibing CHENG ; Qunqun ZHANG ; Kaijie GAO ; Yuanyuan CHEN ; Shufang XIAO ; Juan HE ; Li JIANG ; Huimin XU ; Yuxia LI ; Hanghai DING ; Hehe CHEN ; Yao ZHENG ; Qunying CHEN ; Ying WANG ; Hong REN ; Chenmei ZHANG ; Zhenjie CHEN ; Mingming ZHOU ; Yucai ZHANG ; Yiping ZHOU ; Zhenjiang BAI ; Saihu HUANG ; Lili HUANG ; Weiguo YANG ; Weike MA ; Qing MENG ; Pengwei ZHU ; Yong LI ; Yan XU ; Yi WANG ; Yanqiang DU ; Huijun CAI ; Bizhen ZHU ; Huixuan SHI ; Shaoxian HONG ; Yukun HUANG ; Meilian HUANG
Chinese Journal of Infection and Chemotherapy 2025;25(3):303-311
Objective This study aimed to investigate the antimicrobial resistance profiles of bacterial strains isolated from pediatric intensive care units(PICU)in China for better antimicrobial therapy.Methods Clinical isolates were collected from 17 institutions,including tertiary care children's hospitals and pediatric department of tertiary general hospitals in China from January 1,2020 to December 31,2022.Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems.Results were interpreted according to the breakpoints released by the Clinical and Laboratory Standards Institute(CLSI)in 2020.Results A total of 10 688 isolates were collected,including gram-positive organisms(39.2%)and gram-negative organisms(60.8%).The top three organisms were S.aureus(13.6%,1 453/10 688),A.baumannii(10.0%,1 067/10 688),and coagulase-negative Staphylococcus(9.9%,1 058/10 688).Multi-drug resistant organisms(MDROs)were very common in children.The prevalence of methicillin-resistant Staphylococcus aureus(MRSA),carbapenem-resistant Enterobacterales(CRE),carbapenem-resistant E.coli,carbapenem-resistant K.pneumoniae(CRKP),carbapenem-resistant A.baumannii(CRAB),and carbapenem-resistant P.aeruginosa(CRPA)was 41.1%,19.4%,8.8%,30.9%,67.4%,and 28.8%,respectively.Overall,more than 50%of Enterobacteriales isolates were resistant to cephalosporins,while nearly 25%of Enterobacteriales isolates were resistant to carbapenems.MDROs were highly resistant to commonly used antibiotics.More than 80%of CRE and CRAB strains were resistant to all beta-lactam antibiotics.CRE and CRAB showed low resistance rates to tigecycline and polymyxin.CRPA showed lower resistance rates to piperacillin,beta-lactamase inhibitor combinations than the resistance rates to third and fourth generation cephalosporins.All of the Staphylococcus and Enterococcus isolates were susceptible to vancomycin and tigecycline.None of PRSP strains isolated from meningitis and nonmeningitis samples were resistant to rifampicin,vancomycin,or linezolid.The prevalence of β-lactamase-negative ampicillin-resistant(BLNAR)strains was 43.3%in Haemophilus influenzae.Conclusions MDROs were prevalent in PICU.It is necessary to establish an effective multidisciplinary team(MDT)to control the antimicrobial resistance.
7.Exploring the clinical application effects of two different sources of domestic oral restoration membrane in guided bone regeneration during dental implantation in diabetic patients
Jing LI ; Yan DONG ; Fu WANG ; Kehui XU ; Chenyu WANG ; Li CHEN ; Lina NIU
Chinese Journal of Stomatology 2025;60(2):116-122
Objective:To investigate the bone augmentation effects of domestic decellularized porcine small intestinal submucosa (PSIS) absorbable biomembrane and domestic bovine pericardium tissue (BPT) absorbable biomembrane in guided bone regeneration (GBR) for single-tooth implantation in diabetic patients.Methods:A prospective case-control study was conducted with 48 diabetic patients who received single-tooth implant restoration at the Department of Prosthodontics, School of Stomatology. The Fourth Military Medical University, between January 2023 and January 2024. Patients were randomly assigned to the study group (PSIS group) and the control group (BPT group) using a random number table, with 24 patients in each group. GBR was performed simultaneously with the implant surgery. Cone-beam CT was used to compare the buccal-side horizontal bone gain at 6 months post-operation between the two groups. Wound healing was evaluated at 1 and 4 weeks post-operation using wound healing scores.Results:At 6 months post-operation, the buccal-side horizontal bone gain at 2 mm below the implant abutment in the study group [69.1 (55.2, 82.4) mm] and the control group [71.4 (59.8, 77.0) mm] showed no statistically significant difference ( Z=-0.25, P=0.805). The wound healing scores at 1 and 4 weeks post-operation in the study group did not differ significantly from those in the control group at the same time points (1 week: Z=-0.49, P=0.627; 4 weeks: Z=-0.61, P=0.539). Conclusions:The use of two types of domestic absorbable collagen membranes for GBR in single-tooth implantation in diabetic patients showed comparable buccal-side horizontal bone gain effects at 6 months post-operation and similar clinical outcomes for wound healing at 1 and 4 weeks post-operation in both groups. The GBR effects of PSIS and BPT are similar.
8.Antimicrobial resistance surveillance in the bacterial strains isolated from pediatric intensive care units in China:results from 2020 to 2022
Jing LIU ; Huiyuan YAN ; Gangfeng YAN ; Guoping LU ; Pan FU ; Chuanqing WANG ; Danqun JIN ; Wenjia TONG ; Chenyu ZHANG ; Jianli CHEN ; Yi LIN ; Jia LEI ; Yibing CHENG ; Qunqun ZHANG ; Kaijie GAO ; Yuanyuan CHEN ; Shufang XIAO ; Juan HE ; Li JIANG ; Huimin XU ; Yuxia LI ; Hanghai DING ; Hehe CHEN ; Yao ZHENG ; Qunying CHEN ; Ying WANG ; Hong REN ; Chenmei ZHANG ; Zhenjie CHEN ; Mingming ZHOU ; Yucai ZHANG ; Yiping ZHOU ; Zhenjiang BAI ; Saihu HUANG ; Lili HUANG ; Weiguo YANG ; Weike MA ; Qing MENG ; Pengwei ZHU ; Yong LI ; Yan XU ; Yi WANG ; Yanqiang DU ; Huijun CAI ; Bizhen ZHU ; Huixuan SHI ; Shaoxian HONG ; Yukun HUANG ; Meilian HUANG
Chinese Journal of Infection and Chemotherapy 2025;25(3):303-311
Objective This study aimed to investigate the antimicrobial resistance profiles of bacterial strains isolated from pediatric intensive care units(PICU)in China for better antimicrobial therapy.Methods Clinical isolates were collected from 17 institutions,including tertiary care children's hospitals and pediatric department of tertiary general hospitals in China from January 1,2020 to December 31,2022.Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems.Results were interpreted according to the breakpoints released by the Clinical and Laboratory Standards Institute(CLSI)in 2020.Results A total of 10 688 isolates were collected,including gram-positive organisms(39.2%)and gram-negative organisms(60.8%).The top three organisms were S.aureus(13.6%,1 453/10 688),A.baumannii(10.0%,1 067/10 688),and coagulase-negative Staphylococcus(9.9%,1 058/10 688).Multi-drug resistant organisms(MDROs)were very common in children.The prevalence of methicillin-resistant Staphylococcus aureus(MRSA),carbapenem-resistant Enterobacterales(CRE),carbapenem-resistant E.coli,carbapenem-resistant K.pneumoniae(CRKP),carbapenem-resistant A.baumannii(CRAB),and carbapenem-resistant P.aeruginosa(CRPA)was 41.1%,19.4%,8.8%,30.9%,67.4%,and 28.8%,respectively.Overall,more than 50%of Enterobacteriales isolates were resistant to cephalosporins,while nearly 25%of Enterobacteriales isolates were resistant to carbapenems.MDROs were highly resistant to commonly used antibiotics.More than 80%of CRE and CRAB strains were resistant to all beta-lactam antibiotics.CRE and CRAB showed low resistance rates to tigecycline and polymyxin.CRPA showed lower resistance rates to piperacillin,beta-lactamase inhibitor combinations than the resistance rates to third and fourth generation cephalosporins.All of the Staphylococcus and Enterococcus isolates were susceptible to vancomycin and tigecycline.None of PRSP strains isolated from meningitis and nonmeningitis samples were resistant to rifampicin,vancomycin,or linezolid.The prevalence of β-lactamase-negative ampicillin-resistant(BLNAR)strains was 43.3%in Haemophilus influenzae.Conclusions MDROs were prevalent in PICU.It is necessary to establish an effective multidisciplinary team(MDT)to control the antimicrobial resistance.
9.Clinical analysis of robotic bilateral modified radical neck dissection through the bilateral axillo-breast approach for thyroid carcinoma
Lanqing CHEN ; Xiaolei LI ; Dayong ZHUANG ; Peng ZHOU ; Tao YUE ; Jing XU ; Sijuan CHEN ; Chenyu LI ; Changxiu SHAO ; Qingqing HE
Chinese Journal of Endocrine Surgery 2024;18(1):21-25
Objective:To research the efficacy and safety of robotic thyroidectomy and bilateral modified radical neck dissection through bilateral axillo-breast approach (BABA) .Methods:We retrospectively analyzed the clinical data of 37 patients with thyroid cancer who received bilateral modified radical neck dissection through the BABA at the Department of Thyroid and Breast Surgery of the 960th Hospital of the People’s Liberation Army from Jan. 2014 to Jan. 2023. There were 24 females and 13 males, and the average age of the patients was (33,22±10.53) years old. The tumor diameter, number of lymph node dissection and metastasis in the central and lateral regions, average operation time, average hospital stay, complications, and aesthetic score were recorded. SPSS 25.0 software was used for statistical analysis, and the measurement data was calculated using mean ± standard deviation ( ± s), and the counting data was expressed in percentages and numbers. Results:A total of 37 thyroid cancer patients underwent robotic bilateral regional lymph node dissection. The 37 patients received total thyroidectomy, bilateral central compartment and cervical lateral regional lymph node dissection. All the pathological types were papillary carcinoma, with a maximal tumor diameter of (1.47±0.85) cm. The average number of central lymph nodes dissected was 19.46±8.84, and there were (10.24±5.95) metastases; The average number of lymph nodes removed from the bilateral cervical region was 38.92±14.21, and there were (7.92±5.84) metastases. The average operation time was (288.05±77.09) min, the average length of stay in the hospital was (10.76±3.92) days, and the average length of stay in the hospital following surgery was (8.03±2.08) days. These patients had no permanent hypoparathyroidism, permanent recurrent laryngeal nerve palsy, infection, accessory nerve injury and phrenic nerve injury after operation. Transient hypoparathyroidism occurred in 15 patients, transient recurrent laryngeal nerve palsy occurred in 1 patient, and chyle leak occurred in 2 patients. One month after surgery, the aesthetic score was 9.51±0.69.Two patients were found lymph node metastases during the (27.81±15.10) months of follow-up, and received robotic cervical lymph node dissection with BABA.Conclusion:For carefully chosen thyroid cancer patients with bilateral lateral cervical region lymph node metastases, robotic bilateral cervical lymph node regional dissection via BABA is safe and feasible, and good cosmetic results can be obtained.
10.The significance of detecting human cytomegalovirus UL95 antigenic epitope peptide in the diagnosis of SLE
Ya HU ; Chenyu XU ; Wei QIANG ; Huidi ZHANG ; Fangfang FENG
Chinese Journal of Laboratory Medicine 2024;47(9):1042-1051
Objective:To explore the clinical significance of the dominant B-cell epitope peptide of the human cytomegalovirus (HCMV) UL95 gene, as well as the correlation between the plasma UL95 specific antibody levels and clinical indicators in systemic lupus erythematosus (SLE) patients, in order to find auxiliary diagnostic indicators for SLE.Methods:A non-randomized control study was conducted to analyze the sequencial characteristics and polymorphisms of HCMV UL95 gene, and bioinformatics analysis and chemical synthesis were used to synthesize UL95 dominant B cell epitope short peptides, which were used as coating antigens. Enzyme-linked immunosorbent assay (ELISA) assay was used to detect the specific antibody levels of plasma UL95 of 97 SLE patients and 35 healthy controls (HC). Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic value of UL95 short peptide antibodies for SLE diagnosis. Pearson correlation test was used to analyze the correlation between UL95 specific antibody levels and clinical indicators in SLE patients.Results:The nucleotide sequence similarity of UL95 gene was 92.9%-100%, and the amino acid sequence similarity was 92.1%-100%, whose sequences were highly conserved and homologous. A comprehensive prediction of multiple parameters resulted in 6 possible dominant B cell epitopes, named (Bp1, Bp2, Bp3, Bp4, Bp5, Bp6) respectively. The ELISA results showed that the levels of plasma UL95 specific antibodies (0.35±0.12) in SLE patients were significantly higher than those of the HC group (0.28±0.10)( t=3.091, P=0.002). The area under the ROC curve for distinguishing SLE and HC was 0.703, with a sensitivity of 54.6% and a specificity of 88.6%. In addition, the UL95 specifific antibody levels ( OD value) in the middle-high activity subgroup (systemic lupus erythematosus disease activity index, SLEDAI≥4) were higher (0.36±0.10) than those in the low activity subgroup (SLEDAI<4)(0.30±0.07) ( t=?2.055, P=0.044). UL95 specific antibody levels were positively correlated with clinical indicators such as total immunoglobulin G (IgG) and total immunoglobulin M (IgM), while negatively correlated with complement component 3 (C3), complement component 4 (C4), and platelet count. Conclusions:The antibody level of UL95 is closely related to the activity of lupus disease. The Bp1 (10-21) peptide segment of UL95 has important significance for the auxiliary diagnosis of SLE and is expected to become a new reference indicator.

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