1.Construction and Preliminary Application of Animal Disease Model Digital Atlas Database Platform
Huiping LI ; Hongbin GAO ; Jinyin WEN ; Jinchun YANG
Laboratory Animal and Comparative Medicine 2025;45(3):300-308
Objective Domestic research institutions and researchers have established a wide variety of animal disease models and accumulated a wealth of specialized, distinctive, and targeted atlas data during the model development process. These atlas data are of great value for development and application. Therefore, it is necessary to develop a professional and complete digital atlas database platform for animal models, which can achieve the open sharing of animal model atlas data and the integration and optimization of atlas resources related to disease animal models held by relevant domestic institutions. Methods Based on the B/S architecture, the authors' institution built a digital atlas database of animal models, using Java as the main development language and Oracle database system along with related auxiliary tools. The database platform ran in a Linux environment and could be accessed by users through a web browser. At present, the data on this platform mainly came from the atlas resources submitted by animal model resource units within Guangdong Province. Results In August 2024, a digital atlas database platform for animal models was constructed based on the classification structure of three dimensions: systemic diseases, animal species, and resource units. This platform provided functions such as collection, management, retrieval, and viewing of atlas data. As of January 2025, four resource units had submitted 61 atlas data entries of animal models to the platform, totalling 610 data items. Conclusion The animal model digital atlas database platform has been constructed and put into preliminary use. Although the amount of data on the platform is still limited, it is capable of integrating and openly sharing animal model atlas data. It is believed that with the continuous enrichment of atlas data in the future, this platform is expected to provide important data support for the development of laboratory animal science and comparative medicine research, thereby promoting the efficient utilization of scientific research resources.
2.Construction and Preliminary Application of Animal Disease Model Digital Atlas Database Platform
Huiping LI ; Hongbin GAO ; Jinyin WEN ; Jinchun YANG
Laboratory Animal and Comparative Medicine 2025;45(3):300-308
Objective Domestic research institutions and researchers have established a wide variety of animal disease models and accumulated a wealth of specialized, distinctive, and targeted atlas data during the model development process. These atlas data are of great value for development and application. Therefore, it is necessary to develop a professional and complete digital atlas database platform for animal models, which can achieve the open sharing of animal model atlas data and the integration and optimization of atlas resources related to disease animal models held by relevant domestic institutions. Methods Based on the B/S architecture, the authors' institution built a digital atlas database of animal models, using Java as the main development language and Oracle database system along with related auxiliary tools. The database platform ran in a Linux environment and could be accessed by users through a web browser. At present, the data on this platform mainly came from the atlas resources submitted by animal model resource units within Guangdong Province. Results In August 2024, a digital atlas database platform for animal models was constructed based on the classification structure of three dimensions: systemic diseases, animal species, and resource units. This platform provided functions such as collection, management, retrieval, and viewing of atlas data. As of January 2025, four resource units had submitted 61 atlas data entries of animal models to the platform, totalling 610 data items. Conclusion The animal model digital atlas database platform has been constructed and put into preliminary use. Although the amount of data on the platform is still limited, it is capable of integrating and openly sharing animal model atlas data. It is believed that with the continuous enrichment of atlas data in the future, this platform is expected to provide important data support for the development of laboratory animal science and comparative medicine research, thereby promoting the efficient utilization of scientific research resources.
3.Mediating effects of metabolic related indicators on the association between childhood overweight/obesity and left ventricular hypertrophy
LI Huiping, YANG Lili, ZHAO Min, XI Bo
Chinese Journal of School Health 2024;45(1):41-45
Objective:
To examine the mediating effects of blood pressure, glucose, lipids, and serum uric acid on the association between childhood overweight/obesity and left ventricular hypertrophy (LVH), and to provide scientific evidence for the prevention and control of cardiovascular diseases during childhood.
Methods:
One public school in Huantai County, Zibo City was selected to conduct the baseline survey from November 2017 to January 2018 using a convenient cluster sampling method. A total of 1 400 children aged 6 to 11 were included in the study. According to the classification criteria based on body mass index (BMI), participants were divided into the non overweight/obese group ( n =787) and the overweight/obese group ( n =613). The mediating effects of metabolic variables on the association between childhood overweight/obesity and left ventricular hypertrophy (LVH) were analyzed using the "mediation" package in R software.
Results:
Children who were overweight/obese had higher levels of BMI- Z score (2.0±0.8), systolic blood pressure (SBP) (109.1±8.9 mmHg), diastolic blood pressure (DBP) (65.4±6.8 mmHg), fasting plasma glucose (FPG) (4.8±0.5 mmol/L), insulin (INS) (11.3±7.6 μU/mL), apolipoprotein B (ApoB) (0.7±0.2 g/L), lowdensity lipoprotein cholesterol (LDL-C) (2.4±0.7 mmol/L), total cholesterol (TC) (4.2±0.9 mmol/L), triglycerides (TG) (0.9±0.4 mmol/L), and serum uric acid (SUA) (321.2±91.4 μmol/L) compared to those who were non-overweight/obese [the corresponding values were (-0.2±0.7),(104.3±8.8) mmHg, (62.2±6.2) mmHg, (4.7±0.6) mmol/L, (6.1±4.2) μU/mL, (0.6±0.2) g/L, (2.2±0.6) mmol/L, (4.1±0.7) mmol/L, (0.7±0.2) mmol/L, and (278.6±74.7) μmol/L, respectively], whereas the levels of high density lipoprotein cholesterol (HDL-C) were lower in overweight/obese children (1.5±0.3 mmol/L) than in non-overweight/obese children (1.7±0.4 mmol/L). All differences were statistically significant ( t =53.66, 9.88, 9.19, 3.60, 16.32, 7.36, 5.11, 2.55, 11.08, 9.58, -10.31, P <0.05). After adjusting for potential covariates, overweight/obese children had 8.72 times increased risk of developing LVH compared to the non-overweight/obese children ( OR=8.72, 95%CI =5.45-14.66, P <0.01). Mediation analysis showed that INS, HDL-C, LDL-C, TG, ApoB, and SUA partially mediated the association between childhood overweight/obesity and LVH, and among these, INS and TG had relatively strong mediating effects, accounting for 28.05% and 13.71% of the total effects, respectively.
Conclusions
INS, HDL-C, LDL-C, TG, ApoB, and SUA are intermediate risk factors on the association between childhood overweight/obesity and LVH. Keeping metabolic indicators (especially INS and TG) at healthy levels is particularly important for reducing the burden of cardiovascular diseases in overweight/obese children.
4.Influencing factors of attention deficit hyperactivity disorder and the correlation between bone mineral density and physical growth in children
Yuxia ZHENG ; Huiping WANG ; Zuohua WANG ; Yanfei YANG ; Xia ZHANG
Chinese Journal of Child Health Care 2024;32(1):98-102
【Objective】 To analyze the contributing factors of attention deficit hyperactivity disorder (ADHD) in children and the correlation between bone mineral density and physical growth, in order to provide new clues for the prevention and early intervention of ADHD. 【Methods】 A total of 116 children with ADHD were included into the observation group from June 2020 to June 2022, while another 80 healthy children in the same period were included as the control group.Clinical data of the two groups were compared, and the factors influencing ADHD in children were analyzed using multivariate Logistic regression. Children with ADHD were further divided into boys group and girls group based on gender. Bone mineral density (BMD) and physical growth (height and body weight) of the two groups were measured, and the correlation between the two was analyzed. 【Results】 In the observation group, the proportion of boys, maternal bad behaviors during pregnancy, their educational level below high school, critical parenting, and parental stress index were significantly higher compared to the control group (χ2=14.430, 5.689, 5.630, 6.738, t=6.936, P<0.05). Additionally, family environment score was significantly lower than that in the control group (t=6.328, P<0.05). Logistic regression analysis revealed that factors including boys (OR=3.298, 95%CI: 1.759 - 6.184), maternal bad behaviors during pregnancy (OR=2.730, 95%CI: 1.169 - 6.375), maternal education level of senior high school or below (OR=2.032, 95%CI: 1.127 - 3.663), critical parenting (OR=2.349, 95%CI: 1.223 - 4.513), and parental stress index (OR=1.089, 95%CI: 1.055 - 1.124) were positively correlated with ADHD in children (P<0.05), while family environment score was negatively related to ADHD (OR=0.868, 95%CI: 0.820 - 0.919, P<0.05). There were no significant differences in BMD, height and body weight between boys and girls in ADHD group (P>0.05). Pearson correlation analysis indicated a positive correlation of BMD with height and body weight (r=0.409, 0.317, P<0.05). 【Conclusions】 The development of ADHD in children is associated with gender, maternal bad behavior during pregnancy, family parental style and so on. Bone mineral density is closely related to physical growth in children with ADHD, clinical interventions can be implemented to prevent or early intervene ADHD.
5.Accuracy of sacroiliac screw placement in robot-assisted navigation
Wenhui ZHANG ; Chunli WANG ; Lizhen FAN ; Yuping YANG ; Jinlong ZHANG ; Hui ZHANG ; Jie LIU ; Huiping TAI
Chinese Journal of Tissue Engineering Research 2024;28(24):3845-3849
BACKGROUND:Orthopedic robots have been widely used in clinical practice,and relevant reports have shown that they have many advantages such as minimal trauma and short surgical time.However,there is currently no clear report on how accurate they are. OBJECTIVE:To evaluate the accuracy of robot-assisted sacroiliac screw insertion. METHODS:A total of 131 patients with sacroiliac joint fracture and dislocation and sacral fracture admitted to the Department of Trauma Surgery,Gansu Provincial Hospital from January 2020 to April 2023 were retrospectively collected,including 131 S1 screws and 46 S2 screws,totaling 177 screws.They were divided into two groups based on whether robot-assisted navigation was performed.There were 63 cases of sacroiliac screws inserted under robot-assisted navigation(observation group),with 36 males and 27 females,aged 19-72 years,with a mean age of(45.3±17.6)years.Among them,39 cases were fixed with only S1 screws,while 24 cases were fixed with S1S2 screws,resulting in a total of 87 sacroiliac screws.Under C-arm fluoroscopy,68 cases of sacroiliac screws were inserted with bare hands(control group),including 41 males and 27 females,aged 23-67 years,with a mean age of(42.6±21.3)years.Among them,46 cases were fixed with simple S1 screws,while 22 cases were fixed with S1S2 screws,resulting in a total of 90 sacroiliac screws.A postoperative CT scan was performed to evaluate the number of S1 screws,S2 screws,total screw level,and calculate accuracy based on the method introduced by SMITH et al. RESULTS AND CONCLUSION:(1)In the observation group,62 S1 screws were accurately placed(62/63),with an accuracy rate of 98%.24 S2 screws were accurately placed(24/24),with an accuracy rate of 100%.The total number of screws accurately placed was 86(86/87),with an accuracy rate of 99%.(2)In the control group,58 S1 screws were accurately inserted(58/68),with an accuracy rate of 85%.19 S2 screws were accurately inserted(19/22),with an accuracy rate of 86%.The total number of screws accurately inserted was 77(77/90),with an accuracy rate of 86%.(3)There was a statistically significant difference in the accuracy of the S1 screw,S2 screw,and total screw between the two groups(P<0.05).It is suggested that the placement of sacroiliac screws under robot navigation has higher accuracy compared to manual placement under C-arm fluoroscopy,but still has a lower error rate in placement.
6.Efficacy,metabolic characteristics,safety and immunogenicity of AK-HER2 compared with reference trastuzumab in patients with metastatic HER2-positive breast cancer:a multicenter,randomized,double-blind phase Ⅲ equivalence trial
Yang LUO ; Tao SUN ; Zhimin SHAO ; Jiuwei CUI ; Yueyin PAN ; Qingyuan ZHANG ; Ying CHENG ; Huiping LI ; Yan YANG ; Changsheng YE ; Guohua YU ; Jingfen WANG ; Yunjiang LIU ; Xinlan LIU ; Yuhong ZHOU ; Yuju BAI ; Yuanting GU ; Xiaojia WANG ; Binghe XU ; Lihua SONG
China Oncology 2024;34(2):161-175
Background and purpose:For patients with human epidermal growth factor receptor 2(HER2)-positive metastatic breast cancer,trastuzumab treatment can prolong the overall survival and significantly improve the prognosis of patients.However,the reference original research trastuzumab(Herceptin?)is more expensive.Biosimilars have comparable efficacy and safety profiles while increasing patient access to treatment.This clinical trial aimed to evaluate the efficacy,pharmacokinetics,safety and immunogenicity of the trastuzumab biosimilar AK-HER2 compared to trastuzumab(Herceptin?)in patients with HER2-positive metastatic breast cancer.Methods:This multi-center,randomised,double-blind phase Ⅲ clinical trial was conducted in 43 subcenters in China.This study complied with the research protocol,the ethical principles stated in the Declaration of Helsinki and the quality management standards for drug clinical trials.It was approved by the hospital's medical ethics committee.The clinical trial registration agency is the State Food and Drug Administration(clinical trial approval number:2015L04224;clinical trial registration number:CTR20170516).Written informed consent was obtained from subjects before enrollment.Enrolled patients were randomly assigned to the AK-HER2 group and the control group,respectively receiving AK-HER2 or trastuzumab(initial loading dose 8 mg/kg,maintenance dose 6 mg/kg,every 3 weeks as a treatment cycle,total treatment time is 16 cycles)in combination with docetaxel(75 mg/m2,treatment duration is at least 9 cycles).The primary endpoint of this clinical trial was the objective response rate(ORR9)between the AK-HER2 group and the control group in the 9th cycle.Secondary efficacy endpoints included ORR16,disease control rate(DCR),clinical benefit rate(CBR),progression-free survival(PFS)and 1-year survival rate.In this study,100 subjects(AK-HER2 group to control group=1:1)were randomly selected for blood sample collection after the 6th cycle of medication,The collection time points were 45 minutes after infusion(the end of administration),4,8,24,72,120,168,336,and 504 hours after the end of administration.After collection,blood samples were analyzed by PK parameter set(PKPS).Other evaluation parameters included safety and immunogenicity assessment.Results:A total of 550 patients with HER2-positive metastatic breast cancer were enrolled in this clinical trial between Sep.2017 and Mar.2021.In the AK-HER2 group(n=237),129 subjects in the experimental group achieved complete response(CR)or partial response(PR),and the ORR9 was 54.4%.There were 134 subjects in the control group(n=241)who achieved CR or PR,and the ORR9 was 55.6%.The ORR9 ratio between the AK-HER2 group and the control group was 97.9%[90%confidence interval(CI):85.4%-112.2%,P=0.784],which was not statistically significant.In all secondary efficacy endpoints,no statistically significant differences were observed between the two groups.We conducted a mean ratio analysis of pharmacokinetics(PK)parameters between the AK-HER2 group and the control group,and the results suggested that the pharmacokinetic characteristics of the two drugs are similar.The incidence of treatment emergent adverse event(TEAE)leading to drug reduction or suspension during trastuzumab treatment was 3.6%(10 cases)in the AK-HER2 group and 8.1%(22 cases)in the control group.There was statistically significant difference between the two groups(P=0.027).The incidence rate was significantly lower in the AK-HER2 group than in the control group,and there was no statistically significant difference among the other groups.The differences in the positive rates of anti-drug antibodies(ADA)and neutralizing antibodies(NAB)between groups were of no statistical significance(P=0.385 and P=0.752).Conclusion:In patients with HER2-positive metastatic breast cancer,AK-HER2 was comparable to the trastuzumab(Herceptin?)in terms of drug efficacy,pharmacokinetics,safety and immunogenicity.
7.Gemcitabine long-term maintenance chemotherapy benefits patients with survival: a multicenter, real-world study of advanced breast cancer treatment in China
Jian YUE ; Guohong SONG ; Huiping LI ; Tao SUN ; Lihua SONG ; Zhongsheng TONG ; Lili ZHANG ; Zhenchuan SONG ; Quchang OUYANG ; Jin YANG ; Yueyin PAN ; Peng YUAN
Chinese Journal of Oncology 2024;46(3):249-255
Objective:This study collected a real-world data on survival and efficacy of gemcitabine-containing therapy in advanced breast cancer. Aimed to find the main reasons of affecting the duration of gemcitabine-base therapy in advanced breast cancer patients.Methods:Advanced breast cancer patients who received gemcitabine-base therapy from January 2017 to January 2019 were enrolled(10 hospitals). The clinicopathological data, the number of chemotherapy cycles and the reasons for treatment termination were collected and analyzed. To identify the reasons related with continuous treatment for advanced breast cancer and the factors which affect the survival and efficacy.Results:A total of 224 patients with advanced breast cancer were enrolled in this study, with a median age of 52 years (26-77 years), 55.4%(124/224) was postmenopausal. Luminal type were 83 cases, TNBC were 97 cases, and human epidermal growth factor receptor 2 (HER's-2) overexpression were 44. At the analysis, 224 patients who received the gemcitabine-based regimens were evaluated, included 5 complete reponse (CR), 77 partial response (PR), 112 stable disease (SD) and 27 progressive disease (PD). The objective response rate (ORR) was 36.6%(82/224). Seventy patients had serious adverse diseases, including leukopenia (9), neutrophilia (49), thrombocytopenia (15), and elevated transaminase (2). The median follow-up time was 41 months (26~61 months), and the median PFS was 5.6 months. The reasons of termination treatment were listed: disease progression were 90 patients; personal reasons were 51 patients; adverse drug reactions were 18 patients; completed treatment were 65 patients. It was found that progression-free survival (PFS) was significantly longer in patients receiving >6 cycles than that in patients with ≤6 cycles (8.2 months vs 5.4 months, HR=2.474, 95% CI: 1.730-3.538, P<0.001). Conclusions:Gemcitabine-based regimen is generally well tolerated in the Chinese population and has relatively ideal clinical efficacy in the real world. The median PFS is significantly prolonged when the number of treatment cycles are appropriately increased.
8.Gemcitabine long-term maintenance chemotherapy benefits patients with survival: a multicenter, real-world study of advanced breast cancer treatment in China
Jian YUE ; Guohong SONG ; Huiping LI ; Tao SUN ; Lihua SONG ; Zhongsheng TONG ; Lili ZHANG ; Zhenchuan SONG ; Quchang OUYANG ; Jin YANG ; Yueyin PAN ; Peng YUAN
Chinese Journal of Oncology 2024;46(3):249-255
Objective:This study collected a real-world data on survival and efficacy of gemcitabine-containing therapy in advanced breast cancer. Aimed to find the main reasons of affecting the duration of gemcitabine-base therapy in advanced breast cancer patients.Methods:Advanced breast cancer patients who received gemcitabine-base therapy from January 2017 to January 2019 were enrolled(10 hospitals). The clinicopathological data, the number of chemotherapy cycles and the reasons for treatment termination were collected and analyzed. To identify the reasons related with continuous treatment for advanced breast cancer and the factors which affect the survival and efficacy.Results:A total of 224 patients with advanced breast cancer were enrolled in this study, with a median age of 52 years (26-77 years), 55.4%(124/224) was postmenopausal. Luminal type were 83 cases, TNBC were 97 cases, and human epidermal growth factor receptor 2 (HER's-2) overexpression were 44. At the analysis, 224 patients who received the gemcitabine-based regimens were evaluated, included 5 complete reponse (CR), 77 partial response (PR), 112 stable disease (SD) and 27 progressive disease (PD). The objective response rate (ORR) was 36.6%(82/224). Seventy patients had serious adverse diseases, including leukopenia (9), neutrophilia (49), thrombocytopenia (15), and elevated transaminase (2). The median follow-up time was 41 months (26~61 months), and the median PFS was 5.6 months. The reasons of termination treatment were listed: disease progression were 90 patients; personal reasons were 51 patients; adverse drug reactions were 18 patients; completed treatment were 65 patients. It was found that progression-free survival (PFS) was significantly longer in patients receiving >6 cycles than that in patients with ≤6 cycles (8.2 months vs 5.4 months, HR=2.474, 95% CI: 1.730-3.538, P<0.001). Conclusions:Gemcitabine-based regimen is generally well tolerated in the Chinese population and has relatively ideal clinical efficacy in the real world. The median PFS is significantly prolonged when the number of treatment cycles are appropriately increased.
9.Preparation of copolymer 7-hydroxyethyl chrysin loaded PLGA nanoparticles and the in vitro release
Xiaojuan WANG ; Baole YANG ; Chuan MA ; Lei HE ; Linlin JING ; Qiong HUANG ; Huiping MA
Journal of Zhejiang University. Medical sciences 2024;53(1):116-125
Objective:To prepare 7-hydroxyethyl chrysin(7-HEC)loaded poly(lactic-co-glycolic acid)(PLGA)nanoparticles and to detect the in vitro release.Methods:The 7-HEC/PLGA nanoparticles were prepared by emulsification solvent volatilization method.The particle size,polydispersity index(PDI),encapsulation rate,drug loading and zeta potential were measured.The prescription was optimized by single factor investigation combined with Box-Behnken response surface method.Mannitol was used as protectant to prepare lyophilized powder,and the optimal formulation was characterized and studied for the in vitro release.Results:The optimal formulation of 7-HEC/PLGA nanoparticles was as follows:drug loading ratio of 2.12∶20,oil-water volume ratio of 1∶14.7,and 2.72%soybean phospholipid as emulsifier.With the optimal formulation,the average particle size of 7-HEC/PLGA nanoparticles was(240.28±0.96)nm,the PDI was 0.25±0.69,the encapsulation rate was(75.74±0.80)%,the drug loading capacity was(6.98±0.83)%,and the potentiostatic potential was(-18.17±0.17)mV.The cumulative in vitro release reached more than 50%within 48 h.Conclusions:The optimized formulation is stable and easy to operate.The prepared 7-HEC/PLGA nanoparticles have uniform particle size,high encapsulation rate and significantly higher dissolution rate than 7-HEC.
10.Pien Tze Huang alleviates LPS-stimulated liver Kupffer cell injury by regulating miR-155 expression
Luzhen QIU ; Zhaobin YANG ; Shaozhen HE ; Daofeng HUANG ; Xiaomei CHENG ; Huiping CHEN ; Hao XIA
Chinese Journal of Emergency Medicine 2024;33(4):536-541
Objective:To explore the mechanism by which Pien Tze Huang improves liver Kupffer cell damage induced by lipopolysaccharide (LPS) by regulating the expression of miR-155.Methods:LPS induced liver Kupffer cells to establish a cell injury model to simulate septic liver injury. RT-qPCR was used to detect the expression of miR-155 in damaged cells, and RT-qPCR, Western Blot, ELISA and flow cytometry were used to evaluate the inflammatory response and apoptosis of damaged cells. Then we treated LPS-induced Kupffer cells with Pien Tze Huang at different concentrations (0 mg/L, 5 mg/L, 10 mg/L and 15 mg/L), and detected the expression of miR-155 in the cells, the inflammatory response of the cells and Apoptosis rate. MiR-155 was silenced in the cell injury model, and RT-qPCR, Western Blot, ELISA and flow cytometry were used to evaluate the effect of miR-155 on inflammatory response and apoptosis of model cells. Overexpression of miR-155 in damaged cells treated with Pien Tze Huang was used to detect changes in cellular inflammatory response and apoptosis. Data are expressed in the form of mean ± standard deviation, and each group of data is analyzed using t test or one-way analysis of variance.Results:In the LPS-induced liver Kupffer cell injury model, the expression of miR-155 was significantly increased ( P<0.05), the expression levels of pro-inflammatory factors IL-6 and TNF-α were significantly increased, and the anti-inflammatory factor IL-10 was significantly increased. was inhibited ( P<0.05), and the cell apoptosis rate was significantly increased ( P<0.05). After Pien Tze Huang treatment, the expression of miR-155 in damaged liver cells was inhibited ( P<0.05), the levels of cellular inflammatory factors IL-6 and TNF-α were inhibited, and the expression of anti-inflammatory factor IL-10 was promoted ( P<0.05). Inhibit cell apoptosis ( P<0.05). Silencing miR-155 reduced the inflammatory response and apoptosis rate of cells ( P<0.05). Overexpression of miR-155 can reverse the effect of Pien Tze Huang on liver cell injury ( P<0.05). Conclusions:In the model of LPS-induced liver Kupffer cell injury, Pien Tze Huang can inhibite the inflammatory response and apoptosis of cells by inhibiting the expression of miR-155.


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