1.Guidelines for Selecting Animal Models in Preclinical Research of Intervertebral Disc Degeneration(2025 Edition)
Zhonghai LI ; Bin LI ; Jie ZHAO ; Cao YANG ; Yingjun LI
Laboratory Animal and Comparative Medicine 2025;45(5):524-541
Intervertebral disc herniation is a highly prevalent orthopedic disorder,and intervertebral disc degeneration(IDD),the key pathological basis,is a complex pathological process characterized by progressive degradation of extracellular matrix,structural failure,and loss of biomechanical function,which not only shows higher prevalence in the population,but is also the primary cause of chronic low back pain and dysfunction worldwide,causing a huge socioeconomic burden.Although constructing IDD animal models is important for exploring the pathological mechanisms and promoting translational research of this disease,the etiology and pathophysiological mechanisms of IDD have not been fully elucidated.There are significant differences between humans and common laboratory animals in spinal anatomy,biomechanics,and degenerative course,coupled with the diversity and lack of unified standards of existing IDD animal models.This guide systematically reviews IDD animal models of rodents,non-human primates,as well as different species such as rabbits,goats/sheep,pigs,and dogs,focusing on the modeling principles of three main types of models:inducible models(such as annulus fibrosus/nucleus pulposus/endplate injury and mechanical injury)are suitable for simulating acute injury and rapid screening of therapies due to their high controllability and short cycle;spontaneous models can better simulate the age-related natural degeneration process in humans;genetically modified models provide powerful tools for analyzing specific molecular pathways.The guideline deeply analyzes the key technical points,reproducibility,and clinical relevance of these models.It also compares their advantages,limitations,and applicable research scenarios to guide researchers to conduct"scientific question-driven"precise model selection.Meanwhile,to improve the depth and comparability of research results,this guideline proposes a multidimensional endpoint evaluation system for IDD animal model experiments covering imaging,histology,biochemistry/molecular biology,biomechanics,and pain-related behavior,with recommended observation time windows.It also clarifies the"3Rs(replacement,reduction,and refinement)"ethical principles and animal welfare requirements throughout the experiment.In addition,the guideline outlines future research directions such as integrating single-cell omics,multiscale mechanical analysis,and strengthening pain-related phenotype assessment.This guideline aims to provide researchers with a systematic and standardized methodological framework for the rational selection and application of IDD animal models under specific scientific questions and resource constraints,in order to reduce inter-study heterogeneity,enhance the translation efficiency of preclinical findings,promote high-quality development in the field,and ultimately provide a solid scientific foundation for developing innovative therapies to delay or even reverse IDD.
2.Guidelines for Selecting Animal Models in Preclinical Research of Intervertebral Disc Degeneration(2025 Edition)
Zhonghai LI ; Bin LI ; Jie ZHAO ; Cao YANG ; Yingjun LI
Laboratory Animal and Comparative Medicine 2025;45(5):524-541
Intervertebral disc herniation is a highly prevalent orthopedic disorder,and intervertebral disc degeneration(IDD),the key pathological basis,is a complex pathological process characterized by progressive degradation of extracellular matrix,structural failure,and loss of biomechanical function,which not only shows higher prevalence in the population,but is also the primary cause of chronic low back pain and dysfunction worldwide,causing a huge socioeconomic burden.Although constructing IDD animal models is important for exploring the pathological mechanisms and promoting translational research of this disease,the etiology and pathophysiological mechanisms of IDD have not been fully elucidated.There are significant differences between humans and common laboratory animals in spinal anatomy,biomechanics,and degenerative course,coupled with the diversity and lack of unified standards of existing IDD animal models.This guide systematically reviews IDD animal models of rodents,non-human primates,as well as different species such as rabbits,goats/sheep,pigs,and dogs,focusing on the modeling principles of three main types of models:inducible models(such as annulus fibrosus/nucleus pulposus/endplate injury and mechanical injury)are suitable for simulating acute injury and rapid screening of therapies due to their high controllability and short cycle;spontaneous models can better simulate the age-related natural degeneration process in humans;genetically modified models provide powerful tools for analyzing specific molecular pathways.The guideline deeply analyzes the key technical points,reproducibility,and clinical relevance of these models.It also compares their advantages,limitations,and applicable research scenarios to guide researchers to conduct"scientific question-driven"precise model selection.Meanwhile,to improve the depth and comparability of research results,this guideline proposes a multidimensional endpoint evaluation system for IDD animal model experiments covering imaging,histology,biochemistry/molecular biology,biomechanics,and pain-related behavior,with recommended observation time windows.It also clarifies the"3Rs(replacement,reduction,and refinement)"ethical principles and animal welfare requirements throughout the experiment.In addition,the guideline outlines future research directions such as integrating single-cell omics,multiscale mechanical analysis,and strengthening pain-related phenotype assessment.This guideline aims to provide researchers with a systematic and standardized methodological framework for the rational selection and application of IDD animal models under specific scientific questions and resource constraints,in order to reduce inter-study heterogeneity,enhance the translation efficiency of preclinical findings,promote high-quality development in the field,and ultimately provide a solid scientific foundation for developing innovative therapies to delay or even reverse IDD.
3.HIV screening for people visiting to a three-A hospital of Sichuan Province and epidemiological characteristics of emerging HIV infection patients complicated witn other infections from 2020 to 2024
Xiaoqin GOU ; Jing TANG ; Xing QI ; Sheng LIN ; Wenqing LIU ; Zhonghai HAN ; Wei LIAO ; Jingying ZHAO ; Huaguo WANG
Chinese Journal of Nosocomiology 2025;35(18):2760-2764
OBJECTIVE To investigate the result of human immunodeficiency virus(HIV)screening for the people visiting to a three-A hospital of Sichuan Province and analyze the prevalence of complications with hepatitis B virus(HBV)infection,hepatitis C virus(HCV)infection and Treponema pallidum(TP)infection in the emerging HIV infection patients.METHODS The result of HIV screening for the people who visited to Ziyang Central Hos-pital from Jan.1,2020 to Dec.31,2024 and the test results of HBV,HCV and TP for the emerging HIV infec-tion patients were collected and were summarized and statistically analyzed by SPSS.0 software.RESULTS Totally 289 891 case-times were tested for HIV,1529 cases were previously diagnosed with HIV,465 of whom were tested posi-tive for the first time,there was significant difference in the positive rate of test for the first time among the 5 years(x2=15.998,P=0.003).Totally 353 cases were confirmed positive among the 465 primary positive screening cases.Among the emerging HIV infection patients,the positive rate was higher in the male than in the female(x2=141.141,P<0.001),and the positive rate was high among the population aged more than 40 year old(x2=11.448,P<0.001),mi-grant workers(x2=270.110,P<0.001)and low education level population(x2=25.911,P<0.001).The detection rate of gp41 was up to 100.00%in strip type testing.The analysis of the ratio of relative light unit(RLU)to Cutoff val-ue(COI)in the initial screening experiment showed that when COI was greater than 50,all of the confirmed tests were positive,when COI ranged between 1 and 5,the false positive rate was 97.06%.The incidence of complica-tion with HBV infection in the emerging HIV infection patients was increased year by year(x2=20.355,P<0.001),and the incidence of complication with HCV infection was increased in recent two years(x2=10.690,P=0.030).CONCLUSIONS There is no obvious rise of positive rate of HIV screening among the people visiting to the hospital in recent 5 years.The sensitivity of the primary screening of clinical laboratory is high without posi-tive missing test.The positive rates of HBV and HCV are increased among the emerging HIV infection patients.
4.HIV screening for people visiting to a three-A hospital of Sichuan Province and epidemiological characteristics of emerging HIV infection patients complicated witn other infections from 2020 to 2024
Xiaoqin GOU ; Jing TANG ; Xing QI ; Sheng LIN ; Wenqing LIU ; Zhonghai HAN ; Wei LIAO ; Jingying ZHAO ; Huaguo WANG
Chinese Journal of Nosocomiology 2025;35(18):2760-2764
OBJECTIVE To investigate the result of human immunodeficiency virus(HIV)screening for the people visiting to a three-A hospital of Sichuan Province and analyze the prevalence of complications with hepatitis B virus(HBV)infection,hepatitis C virus(HCV)infection and Treponema pallidum(TP)infection in the emerging HIV infection patients.METHODS The result of HIV screening for the people who visited to Ziyang Central Hos-pital from Jan.1,2020 to Dec.31,2024 and the test results of HBV,HCV and TP for the emerging HIV infec-tion patients were collected and were summarized and statistically analyzed by SPSS.0 software.RESULTS Totally 289 891 case-times were tested for HIV,1529 cases were previously diagnosed with HIV,465 of whom were tested posi-tive for the first time,there was significant difference in the positive rate of test for the first time among the 5 years(x2=15.998,P=0.003).Totally 353 cases were confirmed positive among the 465 primary positive screening cases.Among the emerging HIV infection patients,the positive rate was higher in the male than in the female(x2=141.141,P<0.001),and the positive rate was high among the population aged more than 40 year old(x2=11.448,P<0.001),mi-grant workers(x2=270.110,P<0.001)and low education level population(x2=25.911,P<0.001).The detection rate of gp41 was up to 100.00%in strip type testing.The analysis of the ratio of relative light unit(RLU)to Cutoff val-ue(COI)in the initial screening experiment showed that when COI was greater than 50,all of the confirmed tests were positive,when COI ranged between 1 and 5,the false positive rate was 97.06%.The incidence of complica-tion with HBV infection in the emerging HIV infection patients was increased year by year(x2=20.355,P<0.001),and the incidence of complication with HCV infection was increased in recent two years(x2=10.690,P=0.030).CONCLUSIONS There is no obvious rise of positive rate of HIV screening among the people visiting to the hospital in recent 5 years.The sensitivity of the primary screening of clinical laboratory is high without posi-tive missing test.The positive rates of HBV and HCV are increased among the emerging HIV infection patients.
5.Expert consensus for the clinical application of autologous bone marrow enrichment technique for bone repair (version 2023)
Junchao XING ; Long BI ; Li CHEN ; Shiwu DONG ; Liangbin GAO ; Tianyong HOU ; Zhiyong HOU ; Wei HUANG ; Huiyong JIN ; Yan LI ; Zhonghai LI ; Peng LIU ; Ximing LIU ; Fei LUO ; Feng MA ; Jie SHEN ; Jinlin SONG ; Peifu TANG ; Xinbao WU ; Baoshan XU ; Jianzhong XU ; Yongqing XU ; Bin YAN ; Peng YANG ; Qing YE ; Guoyong YIN ; Tengbo YU ; Jiancheng ZENG ; Changqing ZHANG ; Yingze ZHANG ; Zehua ZHANG ; Feng ZHAO ; Yue ZHOU ; Yun ZHU ; Jun ZOU
Chinese Journal of Trauma 2023;39(1):10-22
Bone defects caused by different causes such as trauma, severe bone infection and other factors are common in clinic and difficult to treat. Usually, bone substitutes are required for repair. Current bone grafting materials used clinically include autologous bones, allogeneic bones, xenografts, and synthetic materials, etc. Other than autologous bones, the major hurdles of rest bone grafts have various degrees of poor biological activity and lack of active ingredients to provide osteogenic impetus. Bone marrow contains various components such as stem cells and bioactive factors, which are contributive to osteogenesis. In response, the technique of bone marrow enrichment, based on the efficient utilization of components within bone marrow, has been risen, aiming to extract osteogenic cells and factors from bone marrow of patients and incorporate them into 3D scaffolds for fabricating bone grafts with high osteoinductivity. However, the scientific guidance and application specification are lacked with regard to the clinical scope, approach, safety and effectiveness. In this context, under the organization of Chinese Orthopedic Association, the Expert consensus for the clinical application of autologous bone marrow enrichment technique for bone repair ( version 2023) is formulated based on the evidence-based medicine. The consensus covers the topics of the characteristics, range of application, safety and application notes of the technique of autologous bone marrow enrichment and proposes corresponding recommendations, hoping to provide better guidance for clinical practice of the technique.
6.Numerical Analysis on Micro-Element Streaming Potential of Articular Cartilage
Yutao MEN ; Zhonghai ZHAO ; Chunqiu ZHANG
Journal of Medical Biomechanics 2022;37(1):E033-E039
Objective To investigate the distribution of streaming potential generated by interstitial fluid flow in articular cartilage and obtain electrical characteristics of articular cartilage. Methods The governing equation of fluid and electrostatic theory were combined to establish a two-dimensional (2D) micro-element model of cartilage, and the steady streaming potential generated in microelement under certain pressure was calculated by finite element method. Results The streaming potential in micro-pore model of articular cartilage with the length of 5 μm was about 38.4 μV. The effect of external pressure and Zeta potential on streaming potential of articular cartilage model was significant and showed a linear increase relationship. The streaming potential decreased with the increase of ion number concentration, but the concentration had different effects on streaming potential of articular cartilage. When the ion number concentration was low, streaming potential was more dependent on ion number concentration. When ion number concentration was high, the effect of ion number concentration on streaming potential was very small. Conclusions The results of this study provide important theoretical basis for differentiation and proliferation of chondrocytes, prevention and treatment of articular cartilage diseases, development of tissue-engineered cartilage and repair of articular cartilage injury by means of electric current, electric field and electromagnetic field stimulation.
7.Effects of Collagen Fiber Bundle on Mechanical Properties of Articular Cartilage
Huchen GONG ; Yutao MEN ; Zhonghai ZHAO ; Chunqiu ZHANG
Journal of Medical Biomechanics 2020;35(6):E705-E711
Objective To study the effects of collagen fiber bundle on mechanical properties of articular cartilage, so as to provide references for clinicians to guide the rehabilitation of patients with early cartilage injury. Methods The two-dimensional (2D) numerical model of fiber-reinforced porous viscoelasticity was established, with consideration of the relationship of fiber distribution, elastic modulus, porosity and permeability with cartilage depth. The influences from local fracture of the fiber bundle, the progressive fracture from the surface and the fiber bundle size on mechanical properties of the cartilage were studied, and the maximum principle strain of cartilage matrix was obtained. Results The maximum principal strain of the matrix occurred at a position in middle layer of the cartilage, about upper 1/3 of the cartilage, which was not affected by fiber breakage mode and fiber bundle size. The strain of the cartilage with thicker fiber bundles decreased. Conclusions The middle layer of the cartilage was prone to mechanical damage. The thicker fiber bundle could reduce the maximum principal strain of the matrix. Once the fiber bundle broke, the maximum principal strain of the cartilage matrix with thicker fiber bundle became larger, leading to an easier evolution of the cartilage damage.
8. Systematic review and meta-analysis on the effect of resistance training on bone mineral density in postmenopausal women with osteoporosis
Chinese Journal of Tissue Engineering Research 2020;24(30):4914-4920
BACKGROUND: Resistance training has been shown to help improve bone mineral density in postmenopausal women with osteoporosis. However, it remains to be studied whether the exercise mode, training intensity, training time, and training frequency of resistance training, and the combination with different modes (such as aerobic exercise) is better. OBJECTIVE: To evaluate the effect of resistance training on bone mineral density in postmenopausal women with osteoporosis. METHODS: Randomized controlled trials related to resistance training intervention on bone mineral density in postmenopausal women with osteoporosis were collected. Subjects were divided into resistance training group and blank control group. PubMed, EMBASE, Web of Science, CNKI and Wanfang database were retrieved from inception to December 2019, and relevant references of included literatures were searched. Two researchers screened the literature according to inclusion and exclusion criteria and valid data were extracted for quality evaluation. The included literature data were meta-analyzed by RevMan5.3 software. RESULTS AND CONCLUSION: (1) Finally, 23 randomized controlled trials were included. The risk bias evaluation results of the included literatures showed that the overall literature quality was above medium. (2) The results of meta-analysis showed that compared with the blank control group, the resistance training group had significant effect on the improvement of bone mineral density of lumbar spine [SMD=0.02, 95%CI (0.01,0.03), P < 0.000 1], bone mineral density of total hip [SMD=0.25, 95%CI (0.06, 0.44), P=0.03], bone mineral density of femoral neck [SMD=0.28, 95%CI (0.12,0.04), P=0.000 5], and bone mineral density of greater trochanter [SMD=0.02, 95%CI (0.00, 0.03), P=0.02]. (3) Resistance training is beneficial to maintain the bone mineral density level of postmenopausal women with osteoporosis, and can be an important part of exercise therapy for postmenopausal women with osteoporosis.
9.RNA interferes with Id2 gene expression to inhibit proliferation and invasion of PC-3 prostate cancer stem cells
Yingying ZHANG ; Yinglei WANG ; Lin MENG ; Lin XIAO ; Zhonghai LI ; Zhankui ZHAO ; Houke WU
Chinese Journal of Tissue Engineering Research 2019;23(12):1342-1348
BACKGROUND: The Id2 gene is an endogenous negative regulator of basic helix-loop-helix factor, which is involved in the cell proliferation, differentiation and existence. Id2 also shows functional diversity in the progression and infiltration of different types of tumors OBJECTIVE: To observe the changes of proliferation and invasiveness of PC-3 human prostate cancer stem cells after shRNA-Id2 transfection. METHODS: PC-3 human prostate cancer stem cells in logarithmic growth phase were harvested to isolate tumor stem cell spheres by serum-free suspension culture. The expression of CD44+CD24-on the surface of tumor stem cells was detected by flow cytometry. The shRNA-Id2 expression vector was constructed and transfected into PC-3 human prostate cancer stem cells. Untransfected PC-3 human prostate cancer stem cells were used as control. At 48 hours after transfection, the expression of Id2 gene and protein in shRNA-Id2 transfected prostate cancer stem cells, NC-shRNA empty vector transfected prostate cancer stem cells and untransfected prostate cancer stem cells were detected by RT-PCR and western blot, respectively. The proliferation and invasion of shRNA-Id2 transfected prostate cancer stem cells and untransfected prostate cancer stem cells were detected by MTT assay and Transwell chamber, respectively. The expressions of E-cadherin, vimentin and Twist were detected by western blot and RT-PCR. RESULTS AND CONCLUSION: Tumor stem cell spheres were successfully isolated by the serum-free suspension culture. The expression rate of CD44+CD24-on the surface of the third-generation PC-3 human prostate cancer stem cells was (85.69±8.96) %, indicating that the cultured tumor stem cell spheres overexpressed the phenotype of tumor stem cells. At 48 hours after transfection, the expression of Id2 gene and protein was significantly lower in the shRNA-Id2 transfection group than the non-transfection group (P < 0.05) , indicating that the expression of Id2 was successfully interfered with the expression of PC-3 prostate cancer stem cells. The invasive ability of the cells in the shRNA-Id2 transfection group was significantly lower than that in the non-transfection group (P < 0.05). Western blot and RT-PCR detection showed that the expression of E-cadherin, an epithelial marker of PC-3 prostate cancer stem cells, in the shRNA-Id2 transfection group was significantly higher than that in non-transfection group (P < 0.05) , while the expression of vimentin, a marker of mesenchymal stem cells, and Twist, a transcription factor regulating cell-mesenchymal transformation, in the shRNA-Id2 transfection group was significantly lower than that in the non-transfection group (P < 0.05). These findings indicate that RNA interference with Id2 gene can inhibit the proliferation and invasion of PC-3 prostate cancer stem cells by regulating the expression of E-cadherin, vimentin and Twist.
10.Effects of different concentrations of irbesartan on the differentiation and mineralization of preosteoblasts
Xiaowei DING ; Yuan XU ; Ze MIN ; Yongzhu QIAN ; Zhidan HE ; Yang XU ; Qianqian LIU ; Zhonghai ZHAO
Chinese Journal of Tissue Engineering Research 2017;21(4):499-504
BACKGROUND:Angiotensin II receptor antagonists have been found to exerct a stronger protective effect on bone than angiotensin converting enzyme inhibitors. OBJECTIVE:To investigate the effect of different concentrations of irbesartan (angiotensin II receptor antagonist) on the differentiation and mineralization of mouse preosteoblasts. METHODS:Mouse preosteoblast cel lines MC3T3-E1 in logarithmic phase were selected and cultured in the osteogenic induction medium containing 0 (control group), 0.001, 0.01, 0.1 mmol/L irbesartan, respectively. Ten days later, the cel differentiation was observed by alkaline phosphatase staining. The mineralization was observed by alizarin red staining after 21 days of culture. mRNA expressions of osteocalcin, alkaline phosphatase and Runt-associated transcription factor 2 in osteoblasts were detected by real-time PCR at 1, 4, 7, 14 and 21 days of culture. RESULTS AND CONCLUSION:The activity of alkaline phosphatase in al the irbesartan groups (0, 0.001, 0.01, 0.1) was higher than that in the control group (P<0.05), which was the most obvious in 0.01 mmol/L. The number and area of calcium nodules in each irbesartan group were significantly higher than those in the control group (P<0.05), especial y in 0.01 mmol/L. Compared with the control group, 0.01 mmol/L irbesartan significantly upregulated the mRNA expressions of osteocalcin, alkaline phosphatase and Runt-associated transcription factor 2 (P<0.05). These results suggest that 0.01 mmol/L irbesartan significantly promotes the differentiation and mineralization of osteoblasts.

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