1.Effects of different concentrations of alcoholic beverage and doses of al-cohol on a rat model of alcoholic liver disease
Chen WANG ; Jianjiao ZUO ; Yanshan MA ; Yuntong ZHOU ; Zhiwei LI ; Linan ZHANG ; Yinghua XIE
Chinese Journal of Pathophysiology 2025;41(11):2272-2280
AIM:To establish a stable and efficient rat model of alcoholic liver disease(ALD),we investigat-ed the effects of different alcoholic beverage concentrations and alcohol dosing regimens.METHODS:(1)SPF-grade male SD rats were randomized into 5 groups(n=10):blank,ALD1,ALD2,ALD3,and ALD4.Except for the blank group,rats received intragastric administration of 56%alcohol(6 mL/kg twice daily with an 8-hour interval)for 4 weeks,along with free access to 0%,5%,10%,or 15%alcoholic beverage to evaluate concentration-dependent effects.(2)An-other cohort was divided into three groups(n=10):blank,ALD5,and ALD6.Rats(except blank)were gavaged with 56%alcohol twice daily for 9 weeks(8 mL/kg for ALD5;6 mL/kg in week 1,increasing by 0.5 mL/kg weekly for ALD6),with 10%alcoholic beverage available ad libitum to assess dose-dependent effects.Serum biochemical markers[alanine aminotransferase(ALT),aspartate aminotransferase(AST),total cholesterol(TC),triglycerides(TG),high-density li-poprotein cholesterol(HDL-C),and low-density lipoprotein cholesterol(LDL-C)]and inflammatory cytokines[interleu-kin-6(IL-6),IL-1β and tumor necrosis factor-α(TNF-α)]were analyzed after modeling,complemented by imaging(B-ultrasound,CT,and MRI).Success and survival rates were calculated.RESULTS:(1)ALD1~4 groups exhibited sig-nificantly elevated ALT,AST,TC,TG,LDL-C,IL-1β,IL-6 and TNF-α(P<0.05 or P<0.01)and reduced HDL-C and liver-to-spleen CT density ratio vs blank.ALD3(10%alcoholic beverage)showed the highest modeling success rate with low mortality.(2)ALD5 and ALD6 groups also had siginificant differin terms(P<0.01),with ALD6(gradually increas-ing dose)displaying more severe liver injury,higher success rate,and better survival.CONCLUSION:The optimal ALD model was induced by intragastric administration of 56%alcohol(6 mL/kg twice daily in week 1,increasing by 0.5 mL/kg weekly for 9 weeks)combined with 10%alcoholic beverage.This protocol offers a reliable approach for ALD re-search and drug development.
2.Deconstruction and measurement of the public welfare connotation of public hospitals based on the theory of equal rights and responsibilities
Ye MA ; Mingzhu JIANG ; Linan WANG ; Xiaohua YING
Chinese Journal of Hospital Administration 2025;41(4):268-275
This study started from the connotation of public welfare and, from the perspective of equal rights and responsibilities, interpreted the public welfare responsibilities and entitlements of hospitals. It developed corresponding quantitative measurement tools and constructed a Public Welfare Rights and Responsibilities Index. Public welfare responsibilities were reflected in the provision of equitable, accessible, appropriate, and reasonable basic medical and public health services. These responsibilities were quantified using the market price of basic medical services, the average cost per case-mix index unit, and public service expenditures. Entitlements were reflected in financial subsidies, tax exemptions, and land policy support. Based on this framework, the study applies the Public Welfare Rights and Responsibilities Index to evaluate 147 public hospitals in City S from 2019 to 2021. The results show that the overall level of public welfare among public hospitals in City S was relatively high (with an average index of 2.39), but showed a slight downward trend. Differences were observed across hospital grades and types, with secondary-level hospitals and general hospitals demonstrating relatively higher levels of public welfare. This study could provide a practical and quantifiable method for measuring hospital public welfare within an equal rights and responsibilities framework, offering a novel analytical tool and empirical evidence to support policy formulation and performance evaluation.
3.Effects of different concentrations of alcoholic beverage and doses of al-cohol on a rat model of alcoholic liver disease
Chen WANG ; Jianjiao ZUO ; Yanshan MA ; Yuntong ZHOU ; Zhiwei LI ; Linan ZHANG ; Yinghua XIE
Chinese Journal of Pathophysiology 2025;41(11):2272-2280
AIM:To establish a stable and efficient rat model of alcoholic liver disease(ALD),we investigat-ed the effects of different alcoholic beverage concentrations and alcohol dosing regimens.METHODS:(1)SPF-grade male SD rats were randomized into 5 groups(n=10):blank,ALD1,ALD2,ALD3,and ALD4.Except for the blank group,rats received intragastric administration of 56%alcohol(6 mL/kg twice daily with an 8-hour interval)for 4 weeks,along with free access to 0%,5%,10%,or 15%alcoholic beverage to evaluate concentration-dependent effects.(2)An-other cohort was divided into three groups(n=10):blank,ALD5,and ALD6.Rats(except blank)were gavaged with 56%alcohol twice daily for 9 weeks(8 mL/kg for ALD5;6 mL/kg in week 1,increasing by 0.5 mL/kg weekly for ALD6),with 10%alcoholic beverage available ad libitum to assess dose-dependent effects.Serum biochemical markers[alanine aminotransferase(ALT),aspartate aminotransferase(AST),total cholesterol(TC),triglycerides(TG),high-density li-poprotein cholesterol(HDL-C),and low-density lipoprotein cholesterol(LDL-C)]and inflammatory cytokines[interleu-kin-6(IL-6),IL-1β and tumor necrosis factor-α(TNF-α)]were analyzed after modeling,complemented by imaging(B-ultrasound,CT,and MRI).Success and survival rates were calculated.RESULTS:(1)ALD1~4 groups exhibited sig-nificantly elevated ALT,AST,TC,TG,LDL-C,IL-1β,IL-6 and TNF-α(P<0.05 or P<0.01)and reduced HDL-C and liver-to-spleen CT density ratio vs blank.ALD3(10%alcoholic beverage)showed the highest modeling success rate with low mortality.(2)ALD5 and ALD6 groups also had siginificant differin terms(P<0.01),with ALD6(gradually increas-ing dose)displaying more severe liver injury,higher success rate,and better survival.CONCLUSION:The optimal ALD model was induced by intragastric administration of 56%alcohol(6 mL/kg twice daily in week 1,increasing by 0.5 mL/kg weekly for 9 weeks)combined with 10%alcoholic beverage.This protocol offers a reliable approach for ALD re-search and drug development.
4.Deconstruction and measurement of the public welfare connotation of public hospitals based on the theory of equal rights and responsibilities
Ye MA ; Mingzhu JIANG ; Linan WANG ; Xiaohua YING
Chinese Journal of Hospital Administration 2025;41(4):268-275
This study started from the connotation of public welfare and, from the perspective of equal rights and responsibilities, interpreted the public welfare responsibilities and entitlements of hospitals. It developed corresponding quantitative measurement tools and constructed a Public Welfare Rights and Responsibilities Index. Public welfare responsibilities were reflected in the provision of equitable, accessible, appropriate, and reasonable basic medical and public health services. These responsibilities were quantified using the market price of basic medical services, the average cost per case-mix index unit, and public service expenditures. Entitlements were reflected in financial subsidies, tax exemptions, and land policy support. Based on this framework, the study applies the Public Welfare Rights and Responsibilities Index to evaluate 147 public hospitals in City S from 2019 to 2021. The results show that the overall level of public welfare among public hospitals in City S was relatively high (with an average index of 2.39), but showed a slight downward trend. Differences were observed across hospital grades and types, with secondary-level hospitals and general hospitals demonstrating relatively higher levels of public welfare. This study could provide a practical and quantifiable method for measuring hospital public welfare within an equal rights and responsibilities framework, offering a novel analytical tool and empirical evidence to support policy formulation and performance evaluation.
5.Detection and analysis of EBV DNA integration in NK/T cell lymphoma genome
Xin WANG ; Xudong ZHANG ; Qingjiang CHEN ; Guannan WANG ; Junxia HU ; Shaoxuan WU ; Mijing MA ; Meifeng YIN ; Wanqiu YANG ; Meng DONG ; Mengjie DING ; Mingzhi ZHANG ; Linan ZHU
Chinese Journal of Clinical Oncology 2018;45(23):1194-1200
To investigate the presence of integrated Epstein-Barr virus (EBV) DNA in the NK/T cell lymphoma (NKTCL) ge-nome and analyze the integration information in the genome of NKTCL cell lines. Methods: PCR and in situ hybridization were used to detect EBV infection in five EBV (+) NK/T samples and four EBV (-) NK/T samples provided by the biobanks of the First Affiliated Hospi-tal of Zhengzhou University. Whole-genome DNA of the samples was sequenced and subjected to bioinformatics analysis. Whole-ge-nome sequence alignment was used to identify the EBV integration sequence. BLAST analysis was used to compare EBV fasta files of the samples and EBV fasta library. CREST software was used to extract softclip reads, filter all paired reads, and enumerate their distri-bution on chromosomes. The integrated genomics viewer (IGV) was used to compare the distribution of reads in partial regions of chromosome. PCR was used to amplify the high-frequency integration region of the EBV DNA. The amplified fragments were sanger se-quenced. Results: EBV DNA and EBER expression were detected in five EBV (+) NK/T samples but not in the four EBV (-) NK/T samples. Sequencing depth, coverage depth, proportion of coverage, and proportion of alignment all met the requirements for subsequent re-search. Sequence alignment revealed that the captured sequences were viral sequences. Filtered reads were most numerous in EBV (+) NKTCL cell line SNK, YTS, and EBV (+) nasal NKTCL tissue. The reads were non-randomly enriched in chromosome 2. EBV DNA inte-gration in the 400 bp region of chr2:30234084-30234483 caused insertion or deletion in the chr2p23.1 site. Conclusions: EBV DNA is highly integrated in the chr2p23.1 site of EBV (+) NKTCL cells and may affect the expression of related genes.
6.Expression and clinical significance of PD-1/PD-Ls in EBV-positive T/NK lymphoprolif-erative disorders
Junxia HU ; Qingjiang CHEN ; Xudong ZHANG ; Wencai LI ; Guannan WANG ; Xin WANG ; Meng DONG ; Shaoxuan WU ; Mijing MA ; Meifeng YIN ; Wanqiu YANG ; Mengjie DING ; Mingzhi ZHANG ; Linan ZHU
Chinese Journal of Clinical Oncology 2018;45(24):1248-1253
Objective: To investigate the expression and clinical significance of programmed death-ligand 1 (PD-L1), programmed death-ligand 2 (PD-L2), and their receptor programmed cell death protein 1 (PD-1) in EBV-positive T/NK lymphoproliferative disease [Epstein-Barr virus-positive T/natural killer (NK)-cell lymphoproliferative disease, EBV(+)-T/NK-LPD]. Methods: The pathological paraffin-embedded tissues of 17 patients with EBV(+)-T/NK-LPD from the First Affiliated Hospital of Zhengzhou University from January 2013 to December 2017 were collected. These patients include 12 males and 5 females, aged 10-82 years old, the average age being 29 years, 4 people in gradeⅠ, 7 in gradeⅡ, 3 in gradeⅢ, and 3 people with hydroa vacciniforme-like lymphoproliferative disorders. Immunohistochemical SP method was used to detect the expression of PD-1, PD-L1, and PD-L2 in human EBV(+)-T/NK-LPD tissues. The relationship between PD-1, PD-L1, PD-L2 expression, and clinicopathological parameters, pathological grades and prognosis were analyzed by Fisher's exact probabilities and Spearman rank correlation. Result: After statistical analysis, the results showed that in 17 cases of tissue samples, there were 12 cases with positive PD-1 expression, 6 cases with positive PD-L1 expression and 5 cases with positive PD-L2 expression. There was no significant correlation between PD-1 and PD-L2 expression and prognosis (P>0.05). PD-L1 expression showed a positive correlation with prognosis (P<0.05). There was no significant correlation between the expression of PD-L1 and PD-L2 with age, sex, as well as LDH and Ki-67 levels (P>0.05). Moreover, there was no significant correlation of PD-1 and PD-L2 expression with pathological grade (r=0.141, r=-0.149, both P>0.05). However, there was a negative correlation between the PD-L1 expression and pathological grade (r=-0.563), and the correlation between the PD-L1 ex-pression and pathological grade was statistically significant (P<0.05). Conclusions: PD-1, PD-L1, and PD-L2 are abnormally expressed in the pathological tissues of EBV(+)-T/NK-LPD. Although there was no significant correlation between the expression of PD-1 and prognosis or pathological grade, it was significantly higher in EBV+T/NK-LPD. PD-1/PD-Ls associated signaling pathway is expected to be a potential new target for EBV(+)-T/NK-LPD immunotherapy.
7.Fluid solid interaction analysis of bioprosthetic heart valve.
Xuejie MA ; Yawei DU ; Linan ZHANG ; Zengtao HOU ; Xin YE
Chinese Journal of Medical Instrumentation 2014;38(5):325-328
This paper constructs numerical models of bioprosthetic heart valve and blood. The fluid solid interaction is carried out using penalty function method. The mechanical property of the bioprosthetic heart valve during cardiac cycle is simulated with ANSYS software. Results show that the Von Mises stress concentrates at the junction of attachment edge and coaptation edge. The open time of bioprosthetic heart valve is consistent with that of actural measurement. The peak velocity of blood is in the range of physiology. This model provides more realistic mechanical property of bioprosthetic heart valve during cardiac cycle compared to pure solid model, and facilitates design and optimization of bioprosthetic heart valve.
Bioprosthesis
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Heart Valve Prosthesis
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Heart Valves
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Humans
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Models, Cardiovascular
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Prosthesis Design
8.Establishment and identification of calpastatin transgenic mouse models
Tingqiao YE ; Shuangtao MA ; Dan LI ; Xi ZHENG ; Qiang WANG ; Linan SU ; Yan ZHANG ; Yun YANG ; Yongjian YANG
Acta Laboratorium Animalis Scientia Sinica 2014;(4):47-51
Objective To establish an animal model of calpastatin ( CAST) transgenic mice by inserting the full hu-man CAST into the genome of C57BL/6J mice.Methods Recombinant transgenic vector pRP .EX3d-EF1A-CAST-IRES-eGFP was constructed by Gateway technology .It was injected into the fertilized eggs from C 57BL/6J mice.The injected eggs were transplanted into the oviduct of pseudopregnant mice .Tail DNA PCR screening was performed to identify the positive founder mice.The expressions of CAST mRNA and protein in tissues of the transgenic mice were detected by RT -PCR and Western blotting.Results Ninty eggs were transplanted into the oviducts of 3 recipients.The transplantation success rate was 100%.23 viable offsprings were born from the recipients .Tail DNA PCR screening showed that two of the offsprings were positive transgenic mice .The positive rate of transgenic mice was 9%.RT-PCR assay revealed that CAST mRNA ex-pressions were present in the heart , liver, kidney, lung, spleen, brain and skeletal muscle of the transgenic mice .Addition-ally, the CAST protein expression was significantly increased in the transgenic mice .Conclusion CAST transgenic mice have been successfully established and provide a good animal model support for further studies on the CAST function .
9.Fluid Solid Interaction Analysis of Bioprosthetic Heart Valve
Xuejie MA ; Yawei DU ; Linan ZHANG ; Zengtao HOU ; Xin YE
Chinese Journal of Medical Instrumentation 2014;(5):325-328
This paper constructs numerical models of bioprosthetic heart valve and blood. Thefluid solid interaction is carried out using penalty function method. The mechanical property of the bioprosthetic heart valve during cardiac cycle is simulated with ANSYS software. Results show that the Von Mises stress concentrates at the junction of attachment edge and coaptation edge. The open time of bioprosthetic heart valve is consistent with that of actural measurement. The peak velocity of blood is in the range of physiology. This model provides more realistic mechanical property of bioprosthetic heart valve during cardiac cycle compared to pure solid model, and facilitates design and optimization of bioprosthetic heart valve.
10.Relationship between plasma fibrinogen and D-dimer in patients with ST-elevation myocardial infarction.
Yong LI ; Lufen GUO ; Linan MA ; Zhizhong LI ; Shuzheng LV
Clinical Medicine of China 2009;25(2):150-152
Objective To study the difference in fibrinogen and D-dimer between the patients with ST-ele-vation myocardial infarction (STEMI) and those with normal angiography of coronary artery.Methods 100 patients with STEMI who underwent PCI and 100 patients with normal coronary arteriograms as controls from Jan.2005 to Dec.2007 were studied.Plasma concentrations of fibrinogen and D-dimer were compared.Results There was no significant difference in gender, age, history of hypertension and diabetes and smoking between the two groups.Plas-ma concentration of fbfinogen(Fg) was higher in control group [(2.65±0.68 )g/L ] than STEMI group [(2.38±0.91)g/L] (P<0.05).The square root of plasma concentration of D-dimer was higher in STEMI group [(13.23±5.08) μg/L] than control group [(9.40±5.03)μg/L ] (P<0.01).The square root of the rate between D-dimer and fibrinogen was higher in STEMI group (9.11±4.13 ) than control group (5.92±3.35 ) (P<0.01).Conclusion The levels of fibrinogen in patients with STEMI are significantly lower than that of control group, and D-dimer is higher in the former group than in the latter group, suggesting that fresh thrombosis and secondary fibrinolysis exit in STEMI patients at the acute stage.

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