1.Establishment and validation of a model for femoral head necrosis after internal fixation of femoral neck fracture using logistic regression and SHAP analysis
Long LIAO ; Zepeng ZHAO ; Zongyuan LI ; Qinglong YU ; Tao ZHANG ; Jinyuan TANG ; Nan YE ; Han XU ; Bo SHI
Chinese Journal of Tissue Engineering Research 2026;30(3):626-633
BACKGROUND:The most common complication of traumatic femoral neck fractures after internal fixation is femoral head necrosis.Currently,many studies have reported on the risk factors that affect the occurrence and development of postoperative femoral head necrosis,but there is still a lack of tools to predict the risk of femoral head necrosis after internal fixation of femoral neck fractures.OBJECTIVE:To develop a predictive model that estimates the risk of femoral head necrosis shortly after patients with femoral neck fractures receive cannulated screw internal fixation.METHODS:A retrospective analysis reviewed clinical records of 172 patients who underwent cannulated screw internal fixation for femoral neck fractures at Department of Orthopedics of Mianyang Central Hospital from January 2013 to June 2023.Patients were categorized into two groups based on the presence or absence of femoral head necrosis within one year post-operation:the necrosis group and the non-necrosis group.Univariate analysis,Lasso regression,and multivariate Logistic regression techniques were employed to identify the determinants of femoral head necrosis.A nomogram prediction model was constructed using R language's"rms"package,version 4.0.The receiver operating characteristic curve was used to evaluate the discriminatory ability of the model.The Hosmer-Lemeshow test was used to evaluate the goodness of fit of the model,and the decision curve analysis was used to determine its clinical application benefits.Internal validation of the study was conducted using the Bootstrap method,involving 1 000 repeated samplings.To delve deeper into the primary factors influencing femoral head necrosis post-internal fixation of the femoral neck,this paper employed the SHAP method for data set analysis.RESULTS AND CONCLUSION:(1)The risk factors leading to femoral head necrosis in the short term after cannulated screw fixation of femoral neck fractures include:smoking,diabetes,Garden classification,fracture line location,reduction quality,age,and operation time.(2)The prediction model demonstrated robust performance,evidenced by an area under the curve of 0.940(95%Confidence Interval:0.903 to 0.977),indicating a high level of prediction accuracy.The model achieved a sensitivity of 90.2%and a specificity of 87.6%,indicating that its diagnostic performance was stable.The Hosmer-Lemeshow goodness-of-fit test yielded a chi-square value of 6.593 with a P-value of 0.581,confirming that the model's predictions closely align with the observed outcomes.(3)The calibration curve of the model also performed well,and its overall trend was very close to the ideal curve,further proving the high accuracy of the model.(4)The internal validation was carried out by the Bootstrap method with 1 000 repeated samplings,and the area under the curve of the model internal validation was still as high as 0.939,proving that the model had good stability.(5)Through the decision curve,it is found that within the probability threshold range of 1%to 92%,the model can obtain the maximum net benefit value.(6)The SHAP analysis results show that among the risk factors analyzed in this study,the location of the fracture line serves as the most significant predictor of femoral head necrosis following internal fixation with cannulated screws in femoral neck fractures,and subcapital fractures are extremely prone to femoral head necrosis after surgery.(7)It is concluded that the validated prediction model demonstrates strong discriminative power and reliability,offering practical clinical utility.It serves as a useful reference tool for short-term risk assessment of femoral head necrosis following internal fixation of femoral neck fractures.
2.Establishment and validation of a model for femoral head necrosis after internal fixation of femoral neck fracture using logistic regression and SHAP analysis
Long LIAO ; Zepeng ZHAO ; Zongyuan LI ; Qinglong YU ; Tao ZHANG ; Jinyuan TANG ; Nan YE ; Han XU ; Bo SHI
Chinese Journal of Tissue Engineering Research 2026;30(3):626-633
BACKGROUND:The most common complication of traumatic femoral neck fractures after internal fixation is femoral head necrosis.Currently,many studies have reported on the risk factors that affect the occurrence and development of postoperative femoral head necrosis,but there is still a lack of tools to predict the risk of femoral head necrosis after internal fixation of femoral neck fractures.OBJECTIVE:To develop a predictive model that estimates the risk of femoral head necrosis shortly after patients with femoral neck fractures receive cannulated screw internal fixation.METHODS:A retrospective analysis reviewed clinical records of 172 patients who underwent cannulated screw internal fixation for femoral neck fractures at Department of Orthopedics of Mianyang Central Hospital from January 2013 to June 2023.Patients were categorized into two groups based on the presence or absence of femoral head necrosis within one year post-operation:the necrosis group and the non-necrosis group.Univariate analysis,Lasso regression,and multivariate Logistic regression techniques were employed to identify the determinants of femoral head necrosis.A nomogram prediction model was constructed using R language's"rms"package,version 4.0.The receiver operating characteristic curve was used to evaluate the discriminatory ability of the model.The Hosmer-Lemeshow test was used to evaluate the goodness of fit of the model,and the decision curve analysis was used to determine its clinical application benefits.Internal validation of the study was conducted using the Bootstrap method,involving 1 000 repeated samplings.To delve deeper into the primary factors influencing femoral head necrosis post-internal fixation of the femoral neck,this paper employed the SHAP method for data set analysis.RESULTS AND CONCLUSION:(1)The risk factors leading to femoral head necrosis in the short term after cannulated screw fixation of femoral neck fractures include:smoking,diabetes,Garden classification,fracture line location,reduction quality,age,and operation time.(2)The prediction model demonstrated robust performance,evidenced by an area under the curve of 0.940(95%Confidence Interval:0.903 to 0.977),indicating a high level of prediction accuracy.The model achieved a sensitivity of 90.2%and a specificity of 87.6%,indicating that its diagnostic performance was stable.The Hosmer-Lemeshow goodness-of-fit test yielded a chi-square value of 6.593 with a P-value of 0.581,confirming that the model's predictions closely align with the observed outcomes.(3)The calibration curve of the model also performed well,and its overall trend was very close to the ideal curve,further proving the high accuracy of the model.(4)The internal validation was carried out by the Bootstrap method with 1 000 repeated samplings,and the area under the curve of the model internal validation was still as high as 0.939,proving that the model had good stability.(5)Through the decision curve,it is found that within the probability threshold range of 1%to 92%,the model can obtain the maximum net benefit value.(6)The SHAP analysis results show that among the risk factors analyzed in this study,the location of the fracture line serves as the most significant predictor of femoral head necrosis following internal fixation with cannulated screws in femoral neck fractures,and subcapital fractures are extremely prone to femoral head necrosis after surgery.(7)It is concluded that the validated prediction model demonstrates strong discriminative power and reliability,offering practical clinical utility.It serves as a useful reference tool for short-term risk assessment of femoral head necrosis following internal fixation of femoral neck fractures.
3.Construction of A Conceptual Framework for the Integration of Traditional Chinese and Western Medicine in Evolutionary Syndrome Differentiation and Treatment Across Full-cycle of Parkinson's Disease
Yu WANG ; Jianing MEI ; Hongping ZHAO ; Yunzhe TANG ; Zijun WEI ; Qinliang TAO ; Xueyi HAN ; Jiyuan HU ; Yunyun ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):270-279
Parkinson's disease (PD) is a complex neurodegenerative disease involving multiple systems and neurotransmitters. Due to the high clinical heterogeneity of PD,it is urgent to establish a comprehensive and long-term traditional Chinese medicine (TCM) management model. In this paper,the conceptual framework of full-cycle management of PD is preliminarily constructed:based on the evolution of the pathophysiological mechanisms of protein deposition and neurotransmitter disorder in PD,the three-stage syndrome characteristics of the prodromal stage (predominant healthy Qi with subtle pathogenic factors),the early clinical stage (declining healthy Qi with growing pathogenic factors) and the middle and late stages (overwhelming pathogenic factors with deficient healthy Qi) are longitudinally described. Through the syndrome differentiation of visceral manifestations,the etiology and pathogenesis of PD motor and non-motor symptoms were comprehensively analyzed,while the matching treatment methods and prescriptions were inferred,and the modular scheme of the combining main symptoms,accompanying symptoms and secondary symptoms was proposed. The conceptual gap of TCM regarding motor complications ('variable syndrome') and PD-related hyperpyrexia syndrome ('critical syndrome') was explained. This framework reflects the characteristics of combination of disease and syndrome and overall constant motion,and provides new theories and research ideas for individualized and whole-process management of PD in TCM.
4.Construction of A Conceptual Framework for the Integration of Traditional Chinese and Western Medicine in Evolutionary Syndrome Differentiation and Treatment Across Full-cycle of Parkinson's Disease
Yu WANG ; Jianing MEI ; Hongping ZHAO ; Yunzhe TANG ; Zijun WEI ; Qinliang TAO ; Xueyi HAN ; Jiyuan HU ; Yunyun ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):270-279
Parkinson's disease (PD) is a complex neurodegenerative disease involving multiple systems and neurotransmitters. Due to the high clinical heterogeneity of PD,it is urgent to establish a comprehensive and long-term traditional Chinese medicine (TCM) management model. In this paper,the conceptual framework of full-cycle management of PD is preliminarily constructed:based on the evolution of the pathophysiological mechanisms of protein deposition and neurotransmitter disorder in PD,the three-stage syndrome characteristics of the prodromal stage (predominant healthy Qi with subtle pathogenic factors),the early clinical stage (declining healthy Qi with growing pathogenic factors) and the middle and late stages (overwhelming pathogenic factors with deficient healthy Qi) are longitudinally described. Through the syndrome differentiation of visceral manifestations,the etiology and pathogenesis of PD motor and non-motor symptoms were comprehensively analyzed,while the matching treatment methods and prescriptions were inferred,and the modular scheme of the combining main symptoms,accompanying symptoms and secondary symptoms was proposed. The conceptual gap of TCM regarding motor complications ('variable syndrome') and PD-related hyperpyrexia syndrome ('critical syndrome') was explained. This framework reflects the characteristics of combination of disease and syndrome and overall constant motion,and provides new theories and research ideas for individualized and whole-process management of PD in TCM.
5.Ionizing Radiation-induced Lens Injury: Epidemiology, Dose-effect Relationship, and Molecular Mechanisms
Cheng-Hao HU ; Shao-Han REN ; Hai-Tao ZHANG ; Jing-Ming ZHAN
Progress in Biochemistry and Biophysics 2026;53(3):688-696
The crystalline lens of the eye is recognized as one of the most radiosensitive tissues in the human body. While the International Commission on Radiological Protection (ICRP) has classified ionizing radiation (IR)-induced cataracts as a tissue reaction (deterministic effect) and subsequently reduced the occupational equivalent dose limit for the lens, significant uncertainties remain regarding the precise dose threshold and the complex biological pathways driving lens opacification. This review provides a comprehensive synthesis of current knowledge concerning radiation-induced lens damage, integrating epidemiological exposure characteristics with dose-response modeling and mechanistic molecular insights. First, we analyze exposure characteristics through four epidemiological dimensions: dose, time, space, and population. Clinical evidence suggests that radiation cataracts—particularly posterior subcapsular opacities—exhibit a distinct latency period that is inversely correlated with dose. We highlight that risk is not confined to acute high-dose scenarios (such as in atomic bomb survivors) but is increasingly relevant in chronic low-dose occupational settings (e.g., interventional radiology) and medical diagnostics (e.g., CT scans). Crucially, individual susceptibility is modified by genetic background, age, and environmental co-factors, complicating risk assessment. Second, we critically examine the dose-effect relationship. Although the ICRP suggests a threshold of 0.5 Gy, emerging data challenge the traditional threshold model, with some studies advocating for a linear non-threshold (LNT) relationship. We further discuss the critical roles of radiation quality and dose rate. High linear energy transfer (LET) radiation demonstrates a significantly higher relative biological effectiveness (RBE) for cataractogenesis compared to low-LET radiation. Paradoxically, and unlike many other tissues, the lens may exhibit an “inverse dose-rate effect,” where fractionated or protracted exposures potentially enhance biological damage—a finding that challenges classical radiobiological paradigms. Third, drawing upon the “cataractogenic load” hypothesis and the unique physiological constraints of the lens, this review elucidates the multidimensional molecular mechanisms driving radiation-induced opacification. Key mechanisms include four aspects. (1) DNA damage and repair: IR induces DNA double-strand breaks (DSBs) that, due to the lens’ limited repair capacity (modulated by genes such as ATM, Ptch1, and Ercc2), lead to the accumulation of damage. (2) Antioxidant defense system: dysfunction of the Nrf2/HO-1 antioxidant axis results in redox imbalances, triggering NF-κB-mediated inflammation and protein aggregation. (3) Cell proliferation and senescence: IR disrupts cell cycle regulation, causing a dichotomy of effects—driving premature senescence in some cell populations (evidenced by ATM nuclear foci) while inducing aberrant proliferation via growth factor upregulation (FGF2, TGFβ) in others. (4) Cell migration and adhesion: activation of the Wnt/β‑catenin pathway and alterations in the E-cadherin complex promote the abnormal migration of epithelial cells to the posterior capsule, a hallmark of radiation-induced cataracts. In conclusion, radiation-induced cataractogenesis is a multifactorial process in which genetic susceptibility and environmental stressors converge to overwhelm the lens’ homeostatic thresholds. Future research must prioritize longitudinal cohort studies to refine dose thresholds and employ multi-omics approaches to map the crosstalk between DNA damage responses and matrix remodeling. Establishing a robust mechanistic model is essential for developing targeted radioprotective strategies and optimizing radiation protection standards for occupational and medical safety.
6.Statistical analysis of vector monitoring in port areas of Shandong Province from 2017 to 2023
Huan-mei HAN ; Tao ZHANG ; Zhi-ping SU ; Rong-jun YAN ; Wei HUANG ; Wen-wen ZHANG
Acta Parasitologica et Medica Entomologica Sinica 2026;33(2):121-127
Objective To provide a scientific basis for vector prevention and control in port areas, vector monitoring has been conducted continuously to characterize the composition, density, and seasonal fluctuations of vectors across 21 port-areas of Shandong province from 2017 to 2023. Methods In accordance with the Regional Vector Monitoring Plan for Frontier Ports, vector surveillance of mosquitoes, flies, cockroaches, rodents, and other disease vectors was performed. Data were analyzed to describe vector community composition and identify seasonal fluctuations. Results A total of 601 rodents belonging to 1 family, 4 genera, and 4 species were captured. Three dominant rodent species inhabit port areas. In addition, 88 104 mosquitoes were captured and classified into 3 subfamilies, 4 genera, and 12 species; 38 959 flies were trapped and classified into 8 families,31 genera, and 51 species, including 9 dominant fly species in port-areas; and 54 672 captured cockroaches were classified into 2 families,4 genera, and 4 species, with Blattella germanica as the dominant species. Conclusions Significant vector community changes(P<0.005)have been identified after the epidemic. To improve the pertinence and efficacy of port health quarantine work, continuous and strong attention should be paid to vector compositions and population densities at Shandong ports.
7.Clinical characteristics of Mycoplasma pneumoniae pneumonia in 161 patients
Tao JI ; Guojing HAN ; Yuxiang SONG ; Heng ZHANG ; Yanning MA ; Hanpu GONG ; Jinxi YU ; Gang LIU ; Yifan ZHU ; Yongzhi ZHAI ; Haiyan ZHU
Chinese Journal of Nosocomiology 2025;35(10):1478-1482
OBJECTIVE To explore the clinical characteristics of Mycoplasma pneumoniae pneumonia(MPP)after COVID-19 epidemic so as to offer help for early clinical diagnosis and treatment.METHODS The clinical data that were collected from the MPP patients who were treated in the fever clinic of the First Medical Center of Chinese PLA General Hospital from Jul.2023 to Aug.2024 were retrospectively analyzed.The results of laboratory tests for the different age groups of patients complicated with other pathogens were statistically analyzed.RESULTS Of totally 161 MPP patients who were enrolled in the study,78(48.85%)were male,and 83(51.55%)were fe-male;the average age was(32.98±14.35)years old,and the patients aged between 20 and 40 years old accoun-ted for 43.48%(70 cases).The enrolled patients were divided into the simple MPP group with 92(57.14%)ca-ses and the MPP+mixed group with 69(42.86%)cases according to the result of etiological test of sputum;the patients of MPP+mixed group were divided into the MPP+bacteria group with 42(60.87%)cases,the MPP+fungi group with 10(14.49%)cases,and the MPP+viruses group with 17(24.64%)cases.There was significant difference in the age among the groups(P<0.05);there were no significant differences in the sex,white blood cell counts and percentage of mononuclear cells among the groups,the percentage of lymphocytes was highest in the simple MPP group,the levels of C-reactive protein(CRP)and interleukin-6(IL-6)were highest in the MPP+bacteria group,and there were significant differences(P<0.05).All of the patients were divided into three groups:the ≤20-year-old group the>20-40-year old group and the>40-year-old group.There were no sig-nificant differences in the white blood cell counts,percentage of lymphocytes,percentage of mononuclear cells and IL-6 level among the three groups,and the CRP level was highest in the>20-40-year old group(P=0.025).Ran-dom forest model analysis showed that the weight of CRP was highest(22.65%)among the clinical characteristics of the MPP patients,which played a key role in construction of model.As for other factors,the weight of age was 17.02%,the percentage of lymphocytes 15.34%,the white blood cells counts 14.86%,the percentage of mono-nuclear cells 14.39%,the IL-6 13.61%,the gender 2.13%.CONCLUSION MPP maintains common among the patients aged less than 40 years old after the COVID-19 epidemic,nearly half of the patients are complicated with the infections of other pathogens,and CRP is more helpful for the clinical diagnosis and treatment of the MPP in early stage.
8.Clinical characteristics and treatment of 34 patients with non-severe Chlamydia psittaci pneumonia
Tao JI ; Lili WANG ; Tingting XU ; Yuxiang SONG ; Heng ZHANG ; Hanpu GONG ; Jinxi YU ; Yan-ning MA ; Yifan ZHU ; Yongzhi ZHAI ; Guojing HAN
Chinese Journal of Nosocomiology 2025;35(14):2091-2094
OBJECTIVE To summarize the clinical characteristics and diagnosis and treatment experiences in dealing with non-severe Chlamydia psittaci pneumonia.METHODS The clinical data were collected from 34 patients who were diagnosed with non-severe C.psittaci pneumonia through quantitative polymerase chain reactiong(qPCR)for sputum in fever clinic of the First Medical Center of Chinese PLA General Hospital from Mar.2023 to Mar.2024 and were retrospectively analyzed.The clinical characteristics and treatment outcomes were evaluated.RESULTS The average age of the patients was(44.82±13.74)years old,the ratio of male to female was 1∶1.83;all of the patients had fever;major symptoms were cough(70.59%),pharyngodynia(44.12%),and flu-like symptoms(41.18%);82.35%of the patients had the history of contact with poultry.The C-reactive pro-tein(CRP)level,interleukin-6(IL-6),systemic inflammatory response index(SIRI)and aggregate index of sys-temic inflammation(AISI)were higher among the patients aged no less than 44 years old than among the patients less than 44 years old(P<0.05);the percentage of lymphocytes of the patients aged no less than 44 years old was lower than that of the patients aged less than 44 years old(P<0.05).As for the imaging findings,73.53%of the patients had consolidation shadows,26.47%had ground-glass opacities,and 32.35%involved both lungs.All of the patients received quinolones or tetracyclines for treatment of 7-14 days and all symptoms relieved.CT reexami-nated 1 month after the treatment showed that 55.88%of the cases had complete absorption of pulmonary infec-tious lesions,and 35.29%had partial absorption.CONCLUSIONS The patients with non-severe Chlamydia psitta-ci pneumonia are characterized by the history of contact with poultry,fever complicated with respiratory tract symptoms,rise of inflammatory markers(more significant among patients of advanced age)and lower lobe con-solidation shadow/ground-glass opacities.Early identification and standardized treatment may facilitate the favora-ble treatment outcomes.
9.Clinical value of evaluation of anatomical position of inferior mesenteric artery and vein as well as left colic artery in laparoscopic radical resection of colorectal
Bo ZHANG ; Tao WU ; Shuai ZHOU ; Ling DANG ; Jiaxing HE ; Ying YANG ; Zhuo HAN ; Longlong ZHENG ; Nan WANG
Chinese Journal of Digestive Surgery 2025;24(6):754-761
Objective:To investigate the clinical value of laparoscopic evaluation of anato-mical position of inferior mesenteric artery (IMA), inferior mesenteric vein (IMV) and left colic artery (LCA).Methods:The prospective one-arm study was conducted. The clinical data of 229 pati-ents who underwent laparoscopic left hemicolectomy for left colon or laparoscopic radical resection of rectal cancer in The Second Affiliated Hospital of Air Force Medical University from December 2022 to December 2023 were selected. The distance between the origin point of IMA and the origin point of the first branch (L1) as well as the distance from the origin point of LCA root to the junction of LCA and IMV (L2) were measured during the operation. IMA classification, the location relation-ship of LCA and IMV junction were recorded. Observation indicators: (1) situations of enrolled patients; (2) difference analysis between L1, L2 and clinical features; (3) distribution characteristics of the location relationship between LCA and IMV in different types of IMA. Mann-Whitney U test was used for comparison of measurement data with skewed distribution between groups, Kruskal-Wallis H test was used for comparison between multiple groups, and Dunn-Bonferroni test was used for pairwise comparison. Comparison of count data between groups was performed by chi-square test. Pearson or Spearman correlation analysis was conducted for correlation of continuous variables. Results:(1) Situations of enrolled patients. A total of 229 eligible patients were screened out, including 146 males and 83 females, aged 64(range, 55-71)years. The height of 229 patients was 168(range, 160-172)cm, the weight was 65.0(55.5,71.5)kg, the body surface area was (1.68±0.17)m 2, the tumor maximum diameter was 3.0(2.5,4.0)cm. The total number of lymph nodes dissected was 19(17,21), and the number of No.253 lymph node dissected was 4(3,5). The L1 was 3.50(1.20,8.00)cm, and the L2 was 2.20(0.50,7.30)cm. There were 58, 31, 32, 71, 22, 90, 26 and 212 patients with smoking, alcohol drinking, diabetes, hypertension, coronary heart disease, neoadjuvant chemo-therapy, neoadjuvant radiotherapy and preservation of the LCA, respectively. Among 229 patients, cases with BMI <18.5 kg/m 2, 18.5-23.9 kg/m 2 and >23.9 kg/m 2 were 11, 133 and 85, respectively. There were 153 cases in pathological stage Ⅰ-Ⅱ and 76 cases in stage Ⅲ. There were 168 cases of Dixon operation, 6 cases of Miles operation and 55 cases of sigmoid colon resection. There were 135 cases of IMA type 1, 44 cases of IMA type 2, 23 cases of IMA type 3, 2 cases of IMA type 4, and 25 cases of IMA type unable to judge. (2) Difference analysis between L1, L2 and clinical features.Correlation analysis showed negative correlation between the height, body surface area and L1 ( r=-0.17, -0.15, P<0.05). The L1 was 3.20(2.68,4.00)cm for male patients and 3.60(3.00,4.20)cm for female patients, respectively, showing a significant difference between the two groups ( Z=-2.37, P<0.05). The L1 of patients with IMA type 1, 2, and 3 was 3.20(2.80,4.00)cm, 3.85(3.00,4.48)cm, and 3.20(2.50,4.30)cm, respectively, showing a significant difference among them ( H=7.54, P<0.05). Further pairwise com-parison showed that there was a significant difference in L1 between patients with IMA type 2 and those with IMA type 1 ( P<0.05). The L2 of smokers and non-smokers were 2.50(1.95,3.20)cm and 2.20(1.60,2.80)cm, respectively, showing a significant difference between the two groups ( Z=-2.24, P<0.05). (3)Distribution characteristics of the location relationship between LCA and IMV in different types of IMA. There was no significant difference in LCA distribution between the anterior and posterior positions of IMV among the three IMA types (type 1, 2, 3) ( χ2=1.63, P>0.05). Conclusions:Patients with greater height have larger body surface area and shorter L1. L1 is significantly longer in female patients than in male patients. L1 is significantly longer in patients with IMA type 2 than in those with type 1. L2 is significantly longer in smokers than in non-smokers. There was no significant difference in the distribution location between LCA and IMV among patients of IMA type 1, 2 and 3.
10.Mechanism by which programmed cell death protein 1 influences osteoblast differentiation under high-glucose conditions
Wanli ZHANG ; Tao BAI ; Nianrong HAN ; AKRAM·OSMAN ; Yanlu LIU ; Yifei HUANG ; Wei HU
Chinese Journal of Tissue Engineering Research 2025;29(17):3521-3528
BACKGROUND:Programmed cell death protein 1 belongs to the immunoglobulin gene superfamily and can regulate the differentiation of osteoblasts and affect bone homeostasis.However,there are few studies on the regulatory role and mechanism of programmed cell death protein 1 in diabetic osteoporosis.OBJECTIVE:To investigate the regulatory role and mechanism of programmed cell death protein 1 on osteogenic differentiation of rat bone marrow mesenchymal stem cells under high-glucose environment.METHODS:(1)Animal experiment:A total of 12 Sprageu-Dawley rats were randomized into a control group(n=6)and a model group(n=6).The control group was fed routinely,whereas the model group was injected intraperitoneally with streptozotocin to establish a model of type 1 diabetes mellitus,and the high-fat feed was fed for 8 weeks to establish a model of type 1 diabetic osteoporosis.After 8 weeks of feeding,the femurs of rats in the two groups were taken and subjected to hematoxylin-eosin staining and micro-CT assay.The mRNA expression of programmed cell death protein 1 and programmed death ligand 1 was detected.(2)Cell experiment:Passage 3 rat bone marrow mesenchymal stem cells were randomly divided into four groups:normal control group,high-glucose model group cultured in low glucose medium,programmed cell death protein 1-silenced group transfected with programmed cell death protein 1 siRNA,and programmed cell death protein 1-silenced null group transfected with siRNA-NC.After 48 hours of transfection,the normal control group was cultured in a new low-glucose medium,and the other three groups were cultured in a high-glucose medium for another 48 hours of culture followed by osteogenic induction.After 21 days of osteogenic induction,alizarin red staining,and qRT-PCR(programmed cell death protein 1 and RUNX2 mRNA expression)and western blot(β-catenin,GSK-3β,p-GSK-3β and Axin2 protein expression)were performed.RESULTS AND CONCLUSION:In the animal experiment,hematoxylin-eosin staining and micro-CT assay showed successful modeling of type 1 diabetic osteoporosis in the model group.qRT-PCR assay showed that the mRNA expression of programmed cell death protein 1 and programmed cell death ligand 1 was higher in the model group than the control group(P<0.05).In the cell experiment,the results of alizarin red staining showed that the ability of mineralized nodule formation was lower in the high-glucose model group and the programmed cell death protein 1-silenced null group than in the control group and the programmed cell death protein 1-silenced group.Compared with the normal control group,the programmed cell death protein 1 mRNA expression and GSK3β and Axin2 protein expression were elevated in the high-glucose model group and the programmed cell death protein 1-silenced null group(P<0.05),and the RUNX2 mRNA expression and p-GSK3β and β-catenin protein expression were decreased(P<0.05).Compared with the high-glucose model group and the programmed cell death protein 1-silenced null group,programmed cell death protein 1 mRNA expression and GSK3β and Axin2 protein expression were decreased in the programmed cell death protein 1-silenced group(P<0.05),and RUNX2 mRNA expression and p-GSK3β and β-catenin protein expression were elevated(P<0.05).To conclude,programmed cell death protein 1 silencing can activate the Wnt/β-catenin and improve the osteogenic differentiation of rat bone marrow mesenchymal stem cells under high-glucose conditions.


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