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.Tobacco retailer outside middle schools in Wuhan City and its impact on smoking behavior among students
YAN Zhiwen, YAO Guang, PEI Hongbing, WU Changhan, WU Lin, ZUO Yuting, GUO Yan
Chinese Journal of School Health 2024;45(2):218-222
Objective:
To understand the distribution of tobacco retailer within 100 meters outside middle schools in Wuhan City and its impact on smoking behavior of middle school students, so as to provide basis and feasible suggestions for the development of tobacco control policy for adolescents.
Methods:
From February to May 2023, a multi stage stratified cluster random sampling method was used to select 20 middle schools from 4 districts in Wuhan City. To investigate the distribution of tobacco retailer within 100 metres outside the school and the sale of tobacco to minors. A total of 4 882 students were surveyed using the core questions of the 2021 Chinese Adolescent Tobacco Prevalence Questionnaire. Fisher exact probability test, Chi square test and Chi square trend test were used for statistical analysis.
Results:
Nearly 70.00% of middle schools had tobacco retailer within 100 metres, with an average of (1.10±0.97) per middle school. The awareness rate (100.00%) and labeling rate (87.50%) of licensed tobacco retailer were higher than those of non licensed tobacco retailer (33.33%, 16.67%) ( P <0.05). The rates of tried smoking, current smoking and buying cigarettes within 30 days were 7.13%, 1.99% and 2.54%, respectively. The rates of students who tried smoking ( 8.58 %), current smoking (2.29%) and buying cigarettes within 30 days (2.85%) in schools with tobacco retailer within 100 metres were higher than those in schools without tobacco retailer (3.79%, 1.28%, 1.83%)( χ 2=35.80, 5.37, 4.37 , P <0.05). And as the grade increased, the rates of tried smoking, current smoking and buying cigarettes among middle school students all showed an upward trend ( χ 2 trend =66.20, 36.10, 16.17, P <0.05).
Conclusions
Middle school students in Wuhan City have high tobacco availability. The findings suggest that school ban should be extended from 50 meters to 100 meters, and the regulatory authorities must strictly prohibit selling tobacco products to minors at tobacco retailer.
3.Consistency between modified 12+ X prostate biopsy and systematic biopsy under transrectal interventional ultrasound and Gleason score after prostate cancer surgery
Yuguang XU ; Yangbai LU ; Yingchu YANG ; Guangxin ZHOU ; Kun YANG ; Zhiwen ZHENG ; Yahui YAO ; Xiaozhen LIU
Journal of Chinese Physician 2023;25(8):1134-1138
Objective:To explore the consistency between modified 12+ X prostate biopsy under transrectal interventional ultrasound and postoperative Gleason score in prostate cancer patients.Methods:A retrospective study was conducted on 312 patients diagnosed with prostate cancer and underwent radical resection at Zhongshan People′s Hospital from January 2020 to December 2022. All patients underwent modified 12+ X prostate biopsy and prostate system biopsy under transrectal interventional ultrasound before surgery. Using the Gleason score of postoperative pathological specimens as the " gold standard", the detection rates of prostate cancer and clinically significant prostate cancer using modified 12+ X prostate biopsy and prostate system biopsy under transrectal interventional ultrasound were compared, and the consistency between the two methods alone or in combination and postoperative Gleason score was compared.Results:Among 312 patients, the positive detection rate of the improved 12+ X puncture biopsy combined with the system puncture biopsy was significantly higher than that of the individual detection (95.51% vs 80.77% vs 76.92%), with a statistically significant difference ( P<0.05). The improved 12+ X puncture biopsy combined with system puncture biopsy showed a clinically significant higher detection rate of prostate cancer in positive patients compared to the two tests alone (94.63% vs 77.78% vs 80.00%), with a statistically significant difference ( P<0.05). There was no statistically significant difference in the detection rate of clinically significant prostate cancer among patients who missed diagnosis, either alone or in combination with biopsy ( P>0.05). The upgrade rate of Gleason score after prostate improvement 12+ X puncture biopsy (25.00%) was significantly lower than that of prostate system puncture (44.17%), which was significantly higher than combined puncture biopsy (11.74%), with a statistically significant difference ( P<0.05). After 312 patients received combined puncture biopsy, urinary retention was found in 14 cases (4.49%), hematuria in 30 cases (9.62%), fever in 28 cases (8.97%), and blood in stool in 18 cases (5.77%). After symptomatic treatment, they basically improved within 3 days after puncture. Conclusions:The combination of modified 12+ X prostate biopsy with systematic biopsy under transrectal interventional ultrasound can improve the detection rate of prostate cancer, and has good consistency with the postoperative Gleason score of prostate cancer patients, which has good clinical application value.
4.Effects of biomimetic network membrane prepared by chitosan/gelatin/pectin on proliferation and mineralization of mesenehymal stem cells
Hong SUN ; Zhiwen YAN ; Shuofeng LI ; Yanjie XIONG ; Fan LIANG ; Ao LI ; Fanglian YAO ; Pengcheng CHE
Journal of Jilin University(Medicine Edition) 2019;45(1):17-22,后插1
Objective::To explore the effects of the biomimetic network membrane prepared by chitosan/gelatin/pectin on the proliferation and mineralization of mesenchymal stem cells (MSCs) , and to evaluate its feasibility of constructing tissue engineering bone.Methods:Chitosan, gelatin and pectin were made into a new biomimetic network membrane in a certain ratio by biomimetics.The experiment was divided into control group (MSCs+conventional medium) , material group (MSCs+network membrane+conventional medium) and material+OS group (MSCs+network membrane+OS medium) .The cell morphology was observed by inverted phase contrast microscope;the growth and secretion of extracellular matrix of the MSCs were observed under scanning electron microscope (SEM) .The proliferation of cells was determined by MTT assay (The MSCs were divided into negative control group and material group, and they were cultivated with blank medium and medium including materials) .The expression of calcium in MSCs was detected by Alizarin Red staining.Real-time polymerase chain reaction (RT-PCR) was used to determine the expression levels of osteocalcin (OC) mRNA and osteopontin (OPN) mRNA in the MSCs.Results:The network membrane was semitransparent thin film.The MSCs were short shuttle and clustered under inverted phase contrast microscope.After cultured for 7d, the MSCs were shuttle;after cultured for 14d, the number of MSCs was increased, with pseudo feet on the membrane;after cultured for21d, the MSCs clustered with a lot of neo-formed extracellular matrix.The MTT results showed that there was no significant difference in the proliferation level of MSCs between material group and negative control group (P>0.05) .The Alizarin Red staining results showed that the MSCs in the network membrane were dyed orange red.The RT-PCR results showed that the expression levels of OC mRNA in the MSCs in material group and material+OS group were lower on the 7th and 14th days, but on the 21th day, the expression levels were significantly increased and reached the peak;the expression level of OC mRNA in the MSCs in material group was significantly increased on the 7th day, and the expression level reached the peak on the 14th day, then fell slightly on the 21th day;compared with control group, the expression levels of OC mRNA and OPN mRNA in the cells in material group and material+OS group at different time points were significantly increased (P<0.01) , but there were no significant differences between material group and material+OS group (P>0.05) .Conclusion:Chitosan/gelatin/pectin biomimetic network membrane has good biocompatibility, and MSCs can grow and proliferate well on the membrane.The membrane can induce the MSCs to express mineralization-related genes and proteins without inducers.
5. Perioperative application of thoracic paravertebral nerve block combined with general anesthesia in elderly patients with non-small cell lung cancer
Tianhong WU ; Wei ZHU ; Xiangyang CHENG ; Zhiwen YAO
Journal of Chinese Physician 2019;21(11):1679-1683
Objective:
To investigate the effect of thoracic paravertebral nerve block combined with general anesthesia in the perioperative period of elderly patients with non-small cell lung cancer (NSCLC).
Methods:
50 elderly patients with NSCLC in our hospital from June 2015 to June 2018 were randomly divided into control group (
6.Quality evaluation and content analysis of arteriovenous fistula dysfunction monitoring guidelines
Yao LIU ; Yanming DING ; Jing LI ; Li SU ; Tianjiao LIU ; Zhenhui TAO ; Chongyan YU ; Liyun CAO ; Jun DENG ; Xia LIU ; Zhiwen WANG
Chinese Journal of Modern Nursing 2019;25(36):4719-4723
Objective To carry out quality assessment and content analysis on guidelines on arteriovenous fistula (AVF) dysfunction monitoring in hemodialysis patients so as to provide a reference for building the localized clinical practice plan. MethodsDocuments were retrieved in guideline websites, professional society websites and electronic databases at home and abroad by computer. Quality assessment was carried out with the appraisal of guidelines for research and AGREEⅡ and JBI quality assessment tool on consensuses, and the recommendations of included guidelines were summarized. ResultsTotals of 4 evidence-based guidelines and one consensus were included with three of them in the level A and one in the level B of overall quality evaluation. A total of 12 items in 7 aspects were extracted including policy-making, team building, monitoring technology, training of personnel, continuous quality improvement, risk assessment and health education. Intraclass correlation coefficients of 4 evidence-based guidelines ranged from 0.866 to 0.935. Conclusions The guidelines have high levels of overall quality, but applicability needs to be improved. The recommendations are in general accord with each other, which can provide a basis for building the localized clinical practice plan.
7. Myofibroma/myofibromatosis: a clinicopathologic analysis of 9 cases
Yao FU ; Wenyan GUAN ; Haiyan WU ; Hongyan WU ; Zhiwen FAN ; Qing YE ; Fanqing MENG
Chinese Journal of Pathology 2018;47(1):45-50
Objective:
To investigate the clinical and histological features, diagnosis and differential diagnosis of myofibroma/myofibromatosis.
Methods:
The clinical data and pathology features of nine cases of myofibroma/myofibromatosis were collected from August 2011 to November 2016 in Affiliated Drum Tower Hospital, Nanjing University Medical School and Children′s Hospital of Nanjing Medical University. Immunohistochemistry(IHC), PDGFRB molecular analysis and ETV6-NTRK3 gene fusion were performed and relevant literature reviewed.
Results:
There were 7 males and 2 females, with age ranging from 3 days to 18 years (mean 5 years). The tumors were located in head and neck (eight cases) and trunk (one case). Clinically, the tumors presented as freely movable nodules. Microscopically, they appeared biphasic with alternating light- and dark-staining areas. The light-staining area consisted mainly of plump myoid spindle cells with eosinophilic cytoplasm arranged in nodules, short fascicles, or whorls.The dark-staining area was composed of round or polygonal cells with slightly hyperchromatic nuclei or small spindle cells arranged around a distinct hemangiopericytoma-like vascular pattern. IHC showed the tumor cells in the light-staining area were strongly positive for vimentin and SMA, while cells in dark-staining area were strongly positive for vimentin, and weakly for SMA. Tumor cells were negative for desmin, S-100 protein, h-Caldesmon, CD34 and STAT6. Analysis of PDGFRB mutations was performed in seven cases. Two cases showed 12 exon point mutation c. 1681 c>T(p.R561C), one case showed 14 exon point mutation c. 1998C>G (p.N666K). ETV6-NTRK3 gene fusion was not detected by fluorescence in situ hybridization in four patients under three years old. All cases were followed for 6 to 68 months, with two recurrences.
Conclusions
Myofibroma/myofibromatosis is an uncommon benign myofibroblastic tumor of infancy and childhood. The tumor can appear biphasic, and may show PDGFRB point mutation which is of potential diagnostic value.
8.Study on the pharmacokinetics of clozapine and its metabolites in human blood
Yefei PAN ; Zhiwen WEI ; Xiaohui TAN ; Yao LIU ; Fu SHANLIN ; Ande MA ; Kemeng YUN
Chinese Journal of Forensic Medicine 2017;32(3):240-244
Objective To study the pharmacokinetics and detection window of clozapine and its metabolites in human blood, so as to provide experimental basis for forensic cases of identification of clozapine poisoning. Methods 29 Taiyuan Han people's elbow venous blood was collected after given oral administration of 12.5mg clozapine at different time point, in which clozapine and its metabolites were extracted with solid phase extraction (SPE) and determined by HPLC-MS-MS. The qualitative analysis was based on retention time and MRM ions. The quantitative analysis was based on an internal standard method and calibration curve. Using the 3p97 pharmacokinetic software, pharmacokinetic equation of clozapine in the blood were imitated from the C-T data, and pharmacokinetic parameters were calculated. Results The pharmacokinetics of clozapine met a two compartment open model with a first kinetics absorption. The Tmax of clozapine(CLP), demethylclozapine(DMCLP), N-oxidation-clozapine(NO-CLP) respectively were 2.96±1.32h, 8.65±3.00h, 9.31±26.38h; The Cmax of CLP, DMCLP, NO-CLP respectively were 34.68±9.32ng/mL, 11.16±4.15ng/mL, 9.62±13.88ng/mL;The t1/2 of CLP, DMCLP, NO-CLP respectively were 17.02±23.63h, 27.06±12.58h, 41.27±29.75h; The detection window of CLP, DMCLP, NO-CLP respectively were 81.72±26.19h, 93.21±29.40h and 19.93±14.62h. Conclusion The pharmacokinetics of clozapine in blood of Han people is consistent with two compartment open model with a first kinetics absorption. The pharmacokinetics model and parameters of clozapine can provide expirimental basis for forensic identification of clozapine poisoning cases.
9.Study on the toxicokinetics of cymermethrin and its metabolites in dog bile
Feng ZHENG ; Yanan SHEN ; Aiai FAN ; Juan JIA ; Zhiwen WEI ; Yao LIU ; Bin CONG ; Keming YUN
Chinese Journal of Forensic Medicine 2017;32(6):557-562
Objective To study the toxicokinetics of Cymermethrin and its metabolites in dog bile and provide evidence for forensic cases of identification of Cymermethrin poisoning. Methods 1/4LD50 doses of Cymermethrin were given to 6 male dogs by oral perfusion after the gallbladder fistula surgery on them,and their bile were collected at different time, in which Cymermethrin and its metabolites were extracted by Liquid-liquid extraction with dichloromethane and detected by HPLC-MS-MS. The qualitative analysis was based on retention time and MRM ions. The quantitative analysis was based on an internal standard method and calibration curve. Toxicokinetics equations of Cymermethrin and its metabolites in the bile were established from the c-t curves which were fitted by the WinNonlin toxicokinetics software meanwhie toxicokinetics parameters were obtained. Results The toxicokinetics of Cymermethrin met first-order dynamic equation. The Tmax of Cymermethrin(CYM), 3-phenoxybenzoic acid (3-PBA), 3-(2,2-Dichloroethenyl)-2,2-dimethyl-cyclopropanecarboxylate (DCVA) respectively were 1.52±0.30,1.29±0.04,0.93±0.41 h ; The Cmax of CYM, 3-PBA, DCVA respectively were 0.38±0.03,7.9±1.32,30.9±16.24 μg/mL ; The T1/2 of CYM, 3-PBA, DCVA respectively were3.93±0.71,1.36±0.11,4.49±2.81 h; Conclusion The toxicokinetics of Cymermethrin in dog bile met first-order dynamic equation ; The toxicokinetics model and parameters of Cymermethrin can provide evidence for forensic identification of Cymermethrin poisoning cases.
10.Study on the stability of carbofuran and its metabolites in blood preserved at different conditions
Aiai FAN ; Yanan SHEN ; Feng ZHENG ; Zhiwen WEI ; Yao LIU ; Shanlin FU ; Keming YUN
Chinese Journal of Forensic Medicine 2017;32(6):578-582,587
Objective Study on the stability of carbofuran and its metabolite carbofuran phenol in blood preserved at different conditions,in order to provide a scientific evidence for forensic identification of carbofuran poisoning death. Methods The dogs were given intragastric administration with 4LD50(13.5mg/kg) of carbofuran, the blood were collected and divided into five equally groups preserved at 20℃(NC2.5mg/mL), 20℃(1%NaF), 20℃, 4℃ and -20℃, respectively. The concentrations of carbofuran and carbofuran phenol in above samples were detected by GC-MS/MS with MRM at 0d、5d、7d、15d、40d、83d and 150d. Results The concentration of carbofuran in preserved blood were found to be significant decrease at 7d(P < 0.05), then a steady decline. In each condition, the concentration of carbofuran phenol in preserved blood showed an increasing trend firstly, then a declined tendency. The concentration of carbofuran and carbofuran phenol descending fast in blood at 20 ℃ (NC) and 20 ℃ (1%NaF).Conclusion Carbofuran and carbofuran phenol in preserved specimens are found to be decomposed. The decomposition is quick at 20℃ and slow at -20℃. Citrate sodium and sodium fluoride are not suit for anticoagulation and antiputrefactiva. Biological specimens used for forensic identification of the carbofuran poisoning should be stored at refriferated or freezed, and be analyzed as soon as possible.


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