BACKGROUND:Prolyl hydroxylase domain 2(PHD2)inhibitors can regulate bone metabolism and relieve osteoporosis in ovariectomized rats.cpd17 is a small molecule oral PHD2 inhibitor newly developed by China Pharmaceutical University.It is effective in the treatment of renal anemia with few side effects,but its effect on bone formation and bone resorption is still unclear. OBJECTIVE:To investigate the effects of cpd17 on mouse osteogenic precursor cells. METHODS:Osteogenic precursor cells were treated with cpd17.Alkaline phosphatase activity and extracellular matrix mineralization were measured,and the expression levels of osteogenesis-and osteoclastogenesis-related markers,as well as PHD2 and hypoxia-inducible factor 1α,were detected.After inhibition of the hypoxia-inducible factor 1α pathway using LW6(a hypoxia-inducible factor 1α pathway inhibitor),alkaline phosphatase activity and extracellular matrix mineralization were detected again,as well as the expression levels of osteogenesis-and osteoclastogenesis-related markers,PHD2 and hypoxia-inducible factor 1α. RESULTS AND CONCLUSION:cpd17 significantly enhanced alkaline phosphatase activity and extracellular matrix mineralization,up-regulated the expression of osteogenesis-related markers,down-regulated the expression of osteoclastogenesis-related markers,up-regulated the expression of hypoxia-inducible factor 1α,down-regulate the expression of PHD2.However,cpd17's effects were significantly attenuated by LW6.To conclude,the PHD2 inhibitor cpd17 promotes osteogenic differentiation and inhibits osteoclastic differentiation through activation of the hypoxia-inducible factor 1α signaling pathway.

Objective:To investigate multi-system involvement in Kennedy′s disease and its association with disease progression.Methods:We retrospectively reviewed the clinical, laboratory, and electrophysiological data from 48 genetically confirmed patients with Kennedy′s disease at the Department of Neurology, First Medical Center of the Chinese PLA General Hospital, between February 2016 and February 2024. The disease progression rate was calculated based on the functional scores at baseline and follow-up. Correlation analyses and multiple linear regression models were employed to assess the relationships among clinical variables and to identify potential predictors of disease progression.Results:The age of muscle weakness onset ranged from 16 to 66 years (mean 42±11 years), with a diagnostic delay of 5.0 (3.0, 9.8) years. Lower limb weakness was the most common initial symptom in 72.9% (35/48) of patients, and 37.5% (18/48) exhibited non-motor manifestations prior to the onset of weakness. Core motor manifestations included bulbar weakness (89.6%, 43/48) and symmetric proximal limb weakness (83.3%, 40/48), frequently accompanied by gynecomastia (74.2%, 23/31) and sexual dysfunction (64.6%, 31/48). The median CAG repeat length was 43 (42, 46), which showed a significant negative correlation with the age at onset ( r=-0.406, P=0.004). Patients with CAG repeats > 43 had a higher prevalence of sexual dysfunction. Elevated serum muscle enzymes were observed in 97.9% (47/48), and abnormal sex hormone levels were detected in 81.2% (39/48). Sensory neuropathy was present in 68.1% (32/47), with CAG repeat length inversely correlating with compound muscle action potential (CMAP) amplitudes in the median ( β=-0.29; t=-2.27, P=0.029) and ulnar ( β=-0.22; t=-2.23, P=0.031) nerves. Low-frequency repetitive nerve stimulation (RNS) revealed a decrement in 43.3% (13/30) of patients, most commonly affecting the axillary and spinal accessory nerves. The disease progression rate was 1.3±0.3 (range: 0.5-2.0). Furthermore, serum creatine kinase-MB (CK-MB) levels were negatively correlated with disease progression rate ( r=-0.303, P=0.036). Conclusions:Kennedy′s disease presents with diverse initial manifestations and frequent multi-system involvement. Non-motor manifestations may precede muscle weakness, serving as valuable clues for early diagnosis. Widespread sex hormone abnormalities (particularly testosterone/luteinizing hormone dysregulation) support the role of androgen insensitivity in disease pathogenesis. Sensory neuropathies are frequent and not length-dependent. The presence of decremental responses on low-frequency RNS suggests neuromuscular junction dysfunction, which may underlie motor impairment in patients with Kennedy′s disease. Finally, serum CK-MB may serve as a potential biomarker for disease progression.

Objective To develop and test the reliability and validity of a Fear of Movement Assessment Scale for patients with peripherally inserted central catheters(PICC),and to make a preliminary application.The aim is to provide an effective tool for nurses to accurately assess the level of fear of movement in patients with PICC and to develop targeted interventions.Methods Based on the psychological imagination belief model,the initial version of the scale was formed through literature review,semi-structured interviews,expert correspondence and a pre-survey.From February to April 2024,211 patients with PICCs were recruited from a tertiary hospital in Wuhan by convenience sampling for project analysis and reliability and validity test.From May to July 2024,256 patients with PICCs from 3 tertiary hospitals in Wuhan were selected by convenience sampling method for further validating the structural validity of the scale and for preliminary application.Results A total of 203 valid questionnaires were collected in February to April 2024,228 valid questionnaires were collected in May to July 2024.The fear of movement assessment scale for patients included 4 dimensions,including the perception of risk,belief of fear,avoidance of movement,and dysfunction,with a total of 17 items.The Cronbach's α coefficient was 0.922;the split-half reliability was 0.867;the test-retest reliability was 0.958.The content validity index at the item level was 0.867～1.000,and the content validity index at the scale level was 0.951.Both exploratory factor analysis and parallel analysis extracted 4 factors.The cumulative variance contribution rate was 61.348％.Confirmatory factor analysis showed that the model fitted well.The preliminary application results showed that the score of fear of movement in patients with PICCs was 53.95±11.08,which was moderately high.Conclusion The Fear of Movement Assessment Scale for patients with PICCs has good measurement properties,and can be used to assess the degree of fear of movement in patients with PICCs.

Objective:To analyze the correlation between serum chitinase 1 (CHIT1), secreted crimp-associated protein 5 (SFRP5) and renal function in patients with diabetic kidney disease (DKD).Methods:Two hundred patients with DKD (observation group) and 180 patients with simple diabetes (control group) diagnosed and treated in Beijing Rehabilitation Hospital Affiliated to Capital Medical University from July 2022 to July 2024 were retrospectively selected. Oxidative stress indexes, glucose and lipid metabolism indexes, renal function indexes, CHIT1 and SFRP5 levels of the two groups were detected. Multivariate Logistic regression was used to analyze the risk factors of DKD in diabetic patients, and Pearson test was used to analyze the correlation between serum CHIT1 and SFRP5 levels and renal function indexes.Results:The levels of CHIT1 and SFRP5 in the observation group were higher than those in the control group : (1.25 ± 0.29) μg/L vs. (0.90 ± 0.22) μg/L, (10.91 ± 3.21) μg/L vs. (5.70 ± 1.17) μg/L, there were statistical differences ( P<0.05). The results of Multivariate Logistic regression analysis showed that fasting blood glucose, glycated hemoglobin, postprandial 2 h blood glucose, total cholesterol, low density lipoprotein cholesterol, triacylglycerol, high density lipoprotein cholesterol, steady-state model insulin resistance index, steady-state model islet beta cell function index, advanced oxidized protein products, malondialdehyde, superoxide dismutol, total antioxidant capacity, cystatin C (CysC), urea nitrogen (BUN), serum creatinine (SCr), isotype cysteine (Hcy), glomerular filtration rate (GFR), CHIT1 and SFRP5 were all risk factors for DKD ( P<0.05). Pearson test results showed that serum CHIT1 and SFRP5 levels in DKD patients were positively correlated with CysC, BUN, SCr and Hcy levels ( r = 0.669, 0.708, 0.558, 0.537 and 0.619, 0.559, 0.639, 0.555, P<0.01), and there were negative correlation with GFR level ( r = - 0.558, -0.363, P<0.01). Conclusions:Serum CHIT1 and SFRP5 levels in DKD patients are significantly increased, which are related to renal function indicators. Changes in serum CHIT1 and SFRP5 levels can reflect the degree of renal function injury and can be used as auxiliary clinical indicators for disease monitoring.

The clinical diagnosis and treatment of urinary tract infection has long faced the challenges of insufficient standardization of diagnosis and treatment pathways,irrational use of antimicrobial drugs and high recurrence rate.How to optimize the hierarchical diagnosis and treatment pathway of urinary tract infection,standardize the use of antimicrobial drugs,and reduce the recurrence rate have always been the focus of clinical attention.There is significant heterogeneity in the existing diagnostic criteria for urinary tract infection,which seriously affects the comparability and evidence integration of clinical and research studies.In order to solve the above problems,a consensus on global multidisciplinary diagnostic criteria for urinary tract infection has been formed by international multidisciplinary experts after three rounds of Delphi method.Breaking through the traditional classification framework,the consensus innovatively established a four-dimensional quantitative scoring system including local symptoms and signs,systemic inflammatory response,quantitative analysis of pyuria and urine culture results,and established a hierarchical standard for stepwise urinary tract diagnosis according to the scoring threshold.Based on the key citations related to the consensus,this paper interprets in detail the basis for the selection of core indicators and the establishment of thresholds for the diagnosis of urinary tract infection in the consensus,and focuses on the key issues and implementation paths of the consensus in localization practice.This consensus provides a unified standard for standardizing the clinical diagnosis and treatment of urinary tract infection,improving the homogeneity of clinical research through standardized diagnostic processes,and promoting the standardization of UTI drug research and development and the rational use of antibiotics and precision.

Objective:To analyze the correlation between serum chitinase 1 (CHIT1), secreted crimp-associated protein 5 (SFRP5) and renal function in patients with diabetic kidney disease (DKD).Methods:Two hundred patients with DKD (observation group) and 180 patients with simple diabetes (control group) diagnosed and treated in Beijing Rehabilitation Hospital Affiliated to Capital Medical University from July 2022 to July 2024 were retrospectively selected. Oxidative stress indexes, glucose and lipid metabolism indexes, renal function indexes, CHIT1 and SFRP5 levels of the two groups were detected. Multivariate Logistic regression was used to analyze the risk factors of DKD in diabetic patients, and Pearson test was used to analyze the correlation between serum CHIT1 and SFRP5 levels and renal function indexes.Results:The levels of CHIT1 and SFRP5 in the observation group were higher than those in the control group : (1.25 ± 0.29) μg/L vs. (0.90 ± 0.22) μg/L, (10.91 ± 3.21) μg/L vs. (5.70 ± 1.17) μg/L, there were statistical differences ( P<0.05). The results of Multivariate Logistic regression analysis showed that fasting blood glucose, glycated hemoglobin, postprandial 2 h blood glucose, total cholesterol, low density lipoprotein cholesterol, triacylglycerol, high density lipoprotein cholesterol, steady-state model insulin resistance index, steady-state model islet beta cell function index, advanced oxidized protein products, malondialdehyde, superoxide dismutol, total antioxidant capacity, cystatin C (CysC), urea nitrogen (BUN), serum creatinine (SCr), isotype cysteine (Hcy), glomerular filtration rate (GFR), CHIT1 and SFRP5 were all risk factors for DKD ( P<0.05). Pearson test results showed that serum CHIT1 and SFRP5 levels in DKD patients were positively correlated with CysC, BUN, SCr and Hcy levels ( r = 0.669, 0.708, 0.558, 0.537 and 0.619, 0.559, 0.639, 0.555, P<0.01), and there were negative correlation with GFR level ( r = - 0.558, -0.363, P<0.01). Conclusions:Serum CHIT1 and SFRP5 levels in DKD patients are significantly increased, which are related to renal function indicators. Changes in serum CHIT1 and SFRP5 levels can reflect the degree of renal function injury and can be used as auxiliary clinical indicators for disease monitoring.

The clinical diagnosis and treatment of urinary tract infection has long faced the challenges of insufficient standardization of diagnosis and treatment pathways,irrational use of antimicrobial drugs and high recurrence rate.How to optimize the hierarchical diagnosis and treatment pathway of urinary tract infection,standardize the use of antimicrobial drugs,and reduce the recurrence rate have always been the focus of clinical attention.There is significant heterogeneity in the existing diagnostic criteria for urinary tract infection,which seriously affects the comparability and evidence integration of clinical and research studies.In order to solve the above problems,a consensus on global multidisciplinary diagnostic criteria for urinary tract infection has been formed by international multidisciplinary experts after three rounds of Delphi method.Breaking through the traditional classification framework,the consensus innovatively established a four-dimensional quantitative scoring system including local symptoms and signs,systemic inflammatory response,quantitative analysis of pyuria and urine culture results,and established a hierarchical standard for stepwise urinary tract diagnosis according to the scoring threshold.Based on the key citations related to the consensus,this paper interprets in detail the basis for the selection of core indicators and the establishment of thresholds for the diagnosis of urinary tract infection in the consensus,and focuses on the key issues and implementation paths of the consensus in localization practice.This consensus provides a unified standard for standardizing the clinical diagnosis and treatment of urinary tract infection,improving the homogeneity of clinical research through standardized diagnostic processes,and promoting the standardization of UTI drug research and development and the rational use of antibiotics and precision.

Objective To develop and test the reliability and validity of a Fear of Movement Assessment Scale for patients with peripherally inserted central catheters(PICC),and to make a preliminary application.The aim is to provide an effective tool for nurses to accurately assess the level of fear of movement in patients with PICC and to develop targeted interventions.Methods Based on the psychological imagination belief model,the initial version of the scale was formed through literature review,semi-structured interviews,expert correspondence and a pre-survey.From February to April 2024,211 patients with PICCs were recruited from a tertiary hospital in Wuhan by convenience sampling for project analysis and reliability and validity test.From May to July 2024,256 patients with PICCs from 3 tertiary hospitals in Wuhan were selected by convenience sampling method for further validating the structural validity of the scale and for preliminary application.Results A total of 203 valid questionnaires were collected in February to April 2024,228 valid questionnaires were collected in May to July 2024.The fear of movement assessment scale for patients included 4 dimensions,including the perception of risk,belief of fear,avoidance of movement,and dysfunction,with a total of 17 items.The Cronbach's α coefficient was 0.922;the split-half reliability was 0.867;the test-retest reliability was 0.958.The content validity index at the item level was 0.867～1.000,and the content validity index at the scale level was 0.951.Both exploratory factor analysis and parallel analysis extracted 4 factors.The cumulative variance contribution rate was 61.348％.Confirmatory factor analysis showed that the model fitted well.The preliminary application results showed that the score of fear of movement in patients with PICCs was 53.95±11.08,which was moderately high.Conclusion The Fear of Movement Assessment Scale for patients with PICCs has good measurement properties,and can be used to assess the degree of fear of movement in patients with PICCs.

Objective:To investigate multi-system involvement in Kennedy′s disease and its association with disease progression.Methods:We retrospectively reviewed the clinical, laboratory, and electrophysiological data from 48 genetically confirmed patients with Kennedy′s disease at the Department of Neurology, First Medical Center of the Chinese PLA General Hospital, between February 2016 and February 2024. The disease progression rate was calculated based on the functional scores at baseline and follow-up. Correlation analyses and multiple linear regression models were employed to assess the relationships among clinical variables and to identify potential predictors of disease progression.Results:The age of muscle weakness onset ranged from 16 to 66 years (mean 42±11 years), with a diagnostic delay of 5.0 (3.0, 9.8) years. Lower limb weakness was the most common initial symptom in 72.9% (35/48) of patients, and 37.5% (18/48) exhibited non-motor manifestations prior to the onset of weakness. Core motor manifestations included bulbar weakness (89.6%, 43/48) and symmetric proximal limb weakness (83.3%, 40/48), frequently accompanied by gynecomastia (74.2%, 23/31) and sexual dysfunction (64.6%, 31/48). The median CAG repeat length was 43 (42, 46), which showed a significant negative correlation with the age at onset ( r=-0.406, P=0.004). Patients with CAG repeats > 43 had a higher prevalence of sexual dysfunction. Elevated serum muscle enzymes were observed in 97.9% (47/48), and abnormal sex hormone levels were detected in 81.2% (39/48). Sensory neuropathy was present in 68.1% (32/47), with CAG repeat length inversely correlating with compound muscle action potential (CMAP) amplitudes in the median ( β=-0.29; t=-2.27, P=0.029) and ulnar ( β=-0.22; t=-2.23, P=0.031) nerves. Low-frequency repetitive nerve stimulation (RNS) revealed a decrement in 43.3% (13/30) of patients, most commonly affecting the axillary and spinal accessory nerves. The disease progression rate was 1.3±0.3 (range: 0.5-2.0). Furthermore, serum creatine kinase-MB (CK-MB) levels were negatively correlated with disease progression rate ( r=-0.303, P=0.036). Conclusions:Kennedy′s disease presents with diverse initial manifestations and frequent multi-system involvement. Non-motor manifestations may precede muscle weakness, serving as valuable clues for early diagnosis. Widespread sex hormone abnormalities (particularly testosterone/luteinizing hormone dysregulation) support the role of androgen insensitivity in disease pathogenesis. Sensory neuropathies are frequent and not length-dependent. The presence of decremental responses on low-frequency RNS suggests neuromuscular junction dysfunction, which may underlie motor impairment in patients with Kennedy′s disease. Finally, serum CK-MB may serve as a potential biomarker for disease progression.

Objective To research the procedure for creating an animal model of mitral regurgitation by implanting a device through the apical artificial chordae tendineae, and to assess the stability and dependability of the device. Methods Twelve large white swines were employed in the experiments. Through a tiny hole in the apex of the heart, the artificial chordae tendineae of the mitral valve was inserted under the guidance of transcardiac ultrasonography. Before, immediately after, and one and three months after surgery, cardiac ultrasonography signs were noted. Results All models were successfully established. During the operation and the follow-up, no swines died. Immediately after surgery, the mitral valve experienced moderate regurgitation. Compared with preoperation, there was a variable increase in the amount of regurgitation and the values of heart diameters at a 3-month follow-up (P<0.05). Conclusion In off-pump, the technique of pulling the mitral valve leaflets with chordae tendineae implanted transapically under ultrasound guidance can stably and consistently create an animal model of mitral regurgitation.