1.S100A9 as a promising therapeutic target for diabetic foot ulcers.
Renhui WAN ; Shuo FANG ; Xingxing ZHANG ; Weiyi ZHOU ; Xiaoyan BI ; Le YUAN ; Qian LV ; Yan SONG ; Wei TANG ; Yongquan SHI ; Tuo LI
Chinese Medical Journal 2025;138(8):973-981
BACKGROUND:
Diabetic foot is a complex condition with high incidence, recurrence, mortality, and disability rates. Current treatments for diabetic foot ulcers are often insufficient. This study was conducted to identify potential therapeutic targets for diabetic foot.
METHODS:
Datasets related to diabetic foot and diabetic skin were retrieved from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified using R software. Enrichment analysis was conducted to screen for critical gene functions and pathways. A protein interaction network was constructed to identify node genes corresponding to key proteins. The DEGs and node genes were overlapped to pinpoint target genes. Plasma and chronic ulcer samples from diabetic and non-diabetic individuals were collected. Western blotting, immunohistochemistry, and enzyme-linked immunosorbent assays were performed to verify the S100 calcium binding protein A9 (S100A9), inflammatory cytokine, and related pathway protein levels. Hematoxylin and eosin staining was used to measure epidermal layer thickness.
RESULTS:
In total, 283 common DEGs and 42 node genes in diabetic foot ulcers were identified. Forty-three genes were differentially expressed in the skin of diabetic and non-diabetic individuals. The overlapping of the most significant DEGs and node genes led to the identification of S100A9 as a target gene. The S100A9 level was significantly higher in diabetic than in non-diabetic plasma (178.40 ± 44.65 ng/mL vs. 40.84 ± 18.86 ng/mL) and in chronic ulcers, and the wound healing time correlated positively with the plasma S100A9 level. The levels of inflammatory cytokines (tumor necrosis factor-α, interleukin [IL]-1, and IL-6) and related pathway proteins (phospho-extracellular signal regulated kinase [ERK], phospho-p38, phospho-p65, and p-protein kinase B [Akt]) were also elevated. The epidermal layer was notably thinner in chronic diabetic ulcers than in non-diabetic skin (24.17 ± 25.60 μm vs. 412.00 ± 181.60 μm).
CONCLUSIONS
S100A9 was significantly upregulated in diabetic foot and was associated with prolonged wound healing. S100A9 may impair diabetic wound healing by disrupting local inflammatory responses and skin re-epithelialization.
Calgranulin B/therapeutic use*
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Diabetic Foot/metabolism*
;
Humans
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Datasets as Topic
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Computational Biology
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Mice, Inbred C57BL
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Animals
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Mice
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Protein Interaction Maps
;
Immunohistochemistry
2.Expert consensus on the diagnosis and treatment of cemental tear.
Ye LIANG ; Hongrui LIU ; Chengjia XIE ; Yang YU ; Jinlong SHAO ; Chunxu LV ; Wenyan KANG ; Fuhua YAN ; Yaping PAN ; Faming CHEN ; Yan XU ; Zuomin WANG ; Yao SUN ; Ang LI ; Lili CHEN ; Qingxian LUAN ; Chuanjiang ZHAO ; Zhengguo CAO ; Yi LIU ; Jiang SUN ; Zhongchen SONG ; Lei ZHAO ; Li LIN ; Peihui DING ; Weilian SUN ; Jun WANG ; Jiang LIN ; Guangxun ZHU ; Qi ZHANG ; Lijun LUO ; Jiayin DENG ; Yihuai PAN ; Jin ZHAO ; Aimei SONG ; Hongmei GUO ; Jin ZHANG ; Pingping CUI ; Song GE ; Rui ZHANG ; Xiuyun REN ; Shengbin HUANG ; Xi WEI ; Lihong QIU ; Jing DENG ; Keqing PAN ; Dandan MA ; Hongyu ZHAO ; Dong CHEN ; Liangjun ZHONG ; Gang DING ; Wu CHEN ; Quanchen XU ; Xiaoyu SUN ; Lingqian DU ; Ling LI ; Yijia WANG ; Xiaoyuan LI ; Qiang CHEN ; Hui WANG ; Zheng ZHANG ; Mengmeng LIU ; Chengfei ZHANG ; Xuedong ZHOU ; Shaohua GE
International Journal of Oral Science 2025;17(1):61-61
Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans
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Dental Cementum/injuries*
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Consensus
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Diagnosis, Differential
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Cone-Beam Computed Tomography
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Tooth Fractures/therapy*
3.Platelet RNA enables accurate detection of ovarian cancer: an intercontinental, biomarker identification study.
Yue GAO ; Chun-Jie LIU ; Hua-Yi LI ; Xiao-Ming XIONG ; Gui-Ling LI ; Sjors G J G IN 'T VELD ; Guang-Yao CAI ; Gui-Yan XIE ; Shao-Qing ZENG ; Yuan WU ; Jian-Hua CHI ; Jia-Hao LIU ; Qiong ZHANG ; Xiao-Fei JIAO ; Lin-Li SHI ; Wan-Rong LU ; Wei-Guo LV ; Xing-Sheng YANG ; Jurgen M J PIEK ; Cornelis D DE KROON ; C A R LOK ; Anna SUPERNAT ; Sylwia ŁAPIŃSKA-SZUMCZYK ; Anna ŁOJKOWSKA ; Anna J ŻACZEK ; Jacek JASSEM ; Bakhos A TANNOUS ; Nik SOL ; Edward POST ; Myron G BEST ; Bei-Hua KONG ; Xing XIE ; Ding MA ; Thomas WURDINGER ; An-Yuan GUO ; Qing-Lei GAO
Protein & Cell 2023;14(6):579-590
Platelets are reprogrammed by cancer via a process called education, which favors cancer development. The transcriptional profile of tumor-educated platelets (TEPs) is skewed and therefore practicable for cancer detection. This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n = 3; Netherlands, n = 5; Poland, n = 1) between September 2016 and May 2019. The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889-0.948), 0.923 (0.855-0.990), 0.918 (0.872-0.963), and 0.887 (0.813-0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889-0.955) in the combined validation cohort; 0.955 (0.912-0.997) in VC1; 0.939 (0.901-0.977) in VC2; 0.917 (0.824-1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, and early-stage ovarian cancer. However, these observations warrant prospective validations in a larger population before clinical utilities.
Humans
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Female
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Blood Platelets/pathology*
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Biomarkers, Tumor/genetics*
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Ovarian Neoplasms/pathology*
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China
4.Risk Prediction Model for Pulmonary Fungal Infections in Patients with Lung Cancer
Wei-wei DU ; Wen-tao JI ; Tian LUO ; Jian-ping LIANG ; Yan-hua LV
Journal of Sun Yat-sen University(Medical Sciences) 2023;44(6):1022-1029
ObjectiveTo investigate the risk factors for pulmonary fungal infection in lung cancer patients, construct and validate a risk prediction model using available clinical data to predict the risk of pulmonary fungal infections in patients with lung cancer. MethodsWe conducted a retrospective study and collected information of 390 lung cancer patients treated at Zhongshan People's Hospital from January 2021 to March 2023. Demographic and clinical characteristics of the patients with and without pulmonary fungal infections were used to construct column line graphs to predict the occurrence of pulmonary fungal infections. All enrolled patients were randomly assigned to training set and internal validation set in the ratio of 7:3. For the modelling group, LASSO regression was applied to screen variables and select predictors, and multivariate logistic regression with a training set was used to construct the Noe column line graph model. The judgment ability of the model was determined by calculating the area under the curve (AUC), and in addition, calibration analysis and decision curve analysis (DCA) were performed on the model. ResultsLASSO regression identified 14 potential predictive factors, and further logistic regression analysis showed that hepatic injury, surgery, anemia, hypoalbuminemia, illness course, invasive operation, hospital stay at least 2 weeks and glucocorticoid used for at least 2 weeks were independent predictors for the occurrence of pulmonary fungal infection in lung cancer patients. A predictive model was established based on these variables, with an AUC95%CI of 0.980 (0.973, 0.896) for the training set and an AUC95%CI of 0.956 (0.795, 1.000) for internal validation, indicating high discriminative ability. The calibration curves for both the training set and validation set were distributed along the 45°line, and the decision curve analysis (DCA) showed net benefit for threshold probabilities greater than 0.03. ConclusionsThe construction and validation of a predictive model for the risk of lung fungal infections in lung cancer patients will help clinical practitioners to identify high-risk groups and give timely intervention or adjust treatment decisions.
5.Development and validation of a score predicting mortality for older patients with mitral regurgitation.
De-Jing FENG ; Yun-Qing YE ; Zhe LI ; Bin ZHANG ; Qing-Rong LIU ; Wei-Wei WANG ; Zhen-Yan ZHAO ; Zheng ZHOU ; Qing-Hao ZHAO ; Zi-Kai YU ; Hai-Tong ZHANG ; Zhen-Ya DUAN ; Bin-Cheng WANG ; Jun-Xing LV ; Shuai GUO ; Run-Lin GAO ; Hai-Yan XU ; Yong-Jian WU
Journal of Geriatric Cardiology 2023;20(8):577-585
OBJECTIVE:
To develop and validate a user-friendly risk score for older mitral regurgitation (MR) patients, referred to as the Elder-MR score.
METHODS:
The China Senile Valvular Heart Disease (China-DVD) Cohort Study functioned as the development cohort, while the China Valvular Heart Disease (China-VHD) Study was employed for external validation. We included patients aged 60 years and above receiving medical treatment for moderate or severe MR (2274 patients in the development cohort and 1929 patients in the validation cohort). Candidate predictors were chosen using Cox's proportional hazards model and stepwise selection with Akaike's information criterion.
RESULTS:
Eight predictors were identified: age ≥ 75 years, body mass index < 20 kg/m2, NYHA class III/IV, secondary MR, anemia, estimated glomerular filtration rate < 60 mL/min per 1.73 m2, albumin < 35 g/L, and left ventricular ejection fraction < 60%. The model displayed satisfactory performance in predicting one-year mortality in both the development cohort (C-statistic = 0.73, 95% CI: 0.69-0.77, Brier score = 0.06) and the validation cohort (C-statistic = 0.73, 95% CI: 0.68-0.78, Brier score = 0.06). The Elder-MR score ranges from 0 to 15 points. At a one-year follow-up, each point increase in the Elder-MR score represents a 1.27-fold risk of death (HR = 1.27, 95% CI: 1.21-1.34, P < 0.001) in the development cohort and a 1.24-fold risk of death (HR = 1.24, 95% CI: 1.17-1.30, P < 0.001) in the validation cohort. Compared to EuroSCORE II, the Elder-MR score demonstrated superior predictive accuracy for one-year mortality in the validation cohort (C-statistic = 0.71 vs. 0.70, net reclassification improvement = 0.320, P < 0.01; integrated discrimination improvement = 0.029, P < 0.01).
CONCLUSIONS
The Elder-MR score may serve as an effective risk stratification tool to assist clinical decision-making in older MR patients.
6.Association of greenness exposure with waist circumference and central obesity in Chinese adults aged 65 years and over.
Li Hong YE ; Jin Hui ZHOU ; Yan Lin TIAN ; Si Xin LIU ; Jun Xin LIU ; Jia Ming YE ; Jia CUI ; Chen CHEN ; Jun WANG ; Bing WU ; Yi Qi QIU ; Yuan WEI ; Yi Dan QIU ; Xu Lin ZHENG ; Li QI ; Yue Bin LV ; Juan ZHANG
Chinese Journal of Preventive Medicine 2023;57():86-92
Objective: To examine the association of greenness exposure with waist circumference (WC) and central obesity in older adults in China. Methods: Based on the cross-sectional data from the Chinese Longitudinal Healthy Longevity Survey in 2017-2018, 14 056 participants aged 65 years and over were included. Demographic characteristics, lifestyle, WC, and other information were collected through a questionnaire and physical examination. Based on the satellite monitoring data of moderate-resolution imaging spectroradiometer (MODIS) provided by NASA, the annual mean of normalized difference vegetation index (NDVI) within a radius of 1 000 meters was obtained as the measurement value of greenness exposure. Multivariate linear regression model, multivariate logistic regression model, and restricted cubic splines (RCS) model were used to analyze the association and dose-response relationship between greenness exposure and WC and central obesity in older adults in China. Results: A total of 14 056 participants were enrolled with a median age of 84.0 years [IQR: 75.0-94.0 years]. About 45.0% (6 330) of them were male and 48.6% (5 853) were illiterate. There were 10 964 (78.0%) participants from rural. The mean of WC was (84.4±10.8) cm. Central obesity accounted for 60.2% (8 465), and the NDVI range was (-0.06, 0.78). After adjusting for confounding factors, the multivariate linear regression model showed that the change value of WC in the urban group [β (95%CI):-0.49 (-0.93, -0.06)] was smaller than that in the rural [-0.78 (-0.98, -0.58)] for every 0.1 unit increase in NDVI (Pinteraction=0.022). Compared with the Q1 group in NDVI, WC of Q2 and Q3 groups in rural decreased, and the β (95%CI) values were-1.74 (-2.5, -0.98) and-2.78 (-3.55, -2.00), respectively. The multivariate logistic regression model showed that after adjusting for confounding factors, the risk of central obesity decreased for urban and rural older adults with an increase of 0.1 unit in NDVI, and the OR (95%CI) values were 0.87 (0.80, 0.95) and 0.86 (0.82, 0.89), respectively (Pinteraction=0.284). Compared with the Q1 group in NDVI, the risk of central obesity in the Q2 and Q3 groups in rural was lower, and the OR (95%CI) values were 0.68 (0.58, 0.80) and 0.57 (0.49, 0.68), respectively. The results of the multivariate regression model with RCS showed that there was a non-linear association of NDVI with WC (Pnonlinear=0.006) and central obesity (Pnonlinear=0.025). Conclusion: Greenness exposure is negatively associated with WC and central obesity in older adults in China.
7.Exploring the common mechanism of Yindan Xinnaotong soft capsule in the treatment of stroke and coronary heart disease through HIF1α -MMP9-mediated HIF1α signaling pathway
Jie GAO ; Yi-feng DONG ; Si-meng WANG ; Ru-shang HE ; Ting-can JIANG ; Ming-jiang WU ; Hong-hua WU ; Xing LI ; Guan-wei FAN ; Yan ZHU ; Ming LV
Acta Pharmaceutica Sinica 2023;58(6):1401-1411
Coronary heart disease (CHD) and stroke are the most well-known cardiovascular diseases, which share many common pathological basis. Yindan Xinnaotong soft capsule (YDXNT) is a commonly used Chinese patent medicine in the treatment of stroke and CHD. However, its action of mechanism of co-treatment for stroke and CHD is still unclear. The aim of this study was to explore the common mechanism of YDXNT in co-treatment of CHD and stroke using network pharmacology, experimental verification and molecular docking. An integrated literature mining and databases of IPA, ETCM, HERB, Swiss Target Prediction, OMIM and GeneCards were used to screen and predict active ingredients and potential targets of YDXNT in co-treatment of CHD and stroke. The protein-protein interaction network, GO analysis and pathway analysis were analyzed by IPA software. The effect of YDXNT on core targets was verified by immunofluorescence. UPLC-QTOF/MS and molecular docking were used to screen and predict the main active constituents of YDXNT and their interactions with core targets. A total of 151 potential targets are predicted for YDXNT in co-treatment of CHD and stroke. Hypoxia-inducible factor-1
8.Relationship between treatment and prognosis in patients with late-onset severe pneumonia after allogeneic hematopoietic stem cell transplantation.
Le Qing CAO ; Jing Rui ZHOU ; Yu Hong CHEN ; Huan CHEN ; Wei HAN ; Yao CHEN ; Yuan Yuan ZHANG ; Chen Hua YAN ; Yi Fei CHENG ; Xiao Dong MO ; Hai Xia FU ; Ting Ting HAN ; Meng LV ; Jun KONG ; Yu Qian SUN ; Yu WANG ; Lan Ping XU ; Xiao Hui ZHANG ; Xiao Jun HUANG
Journal of Peking University(Health Sciences) 2022;54(5):1013-1020
OBJECTIVE:
To explore the relationship between drug treatment and outcomes in patients with late-onset severe pneumonia (LOSP) after allogeneic stem cell transplantation (allo-SCT).
METHODS:
We retrospectively analyzed the effects of the initiation time of treatment drugs, especially antiviral drugs and glucocorticoids on the clinical outcomes in 82 patients between January 2016 and August 2021 who developed LOSP after allo-SCT in Peking University People's Hospital. Univariate analysis was performed by Mann-Whitney U test and χ2 test, and multivariate analysis was performed by Logistic regression. When multiple groups (n>2) were involved in the χ2 test, Bonferroni correction was used for the level of significance test.
RESULTS:
Of all 82 patients in this study, the median onset time of LOSP was 220 d (93-813 d) after transplantation, and the 60-day survival rate was 58.5% (48/82). The median improvement time of the survival patients was 18 d (7-44 d), while the median death time of the died patients was 22 d (2-53 d). Multivariate analysis showed that the initiation time of antiviral drugs from the onset of LOSP (< 10 d vs. ≥10 d, P=0.012), and the initiation time of glucocorticoids from antiviral drugs (< 10 d vs. ≥10 d, P=0.027) were the factors affecting the final outcome of the patients with LOSP at the end of 60 d. According to the above results, LOSP patients were divided into four subgroups: group A (antiviral drugs < 10 d, glucocorticoids ≥10 d), group B (antiviral drugs < 10 d, glucocorticoids < 10 d), group C (antiviral drugs ≥10 d, glucocorticoids ≥10 d) and group D (antiviral drugs ≥10 d, glucocorticoids < 10 d), the 60-day survival rates were 91.7%, 56.8%, 50.0% and 21.4%, respectively.
CONCLUSION
Our study demonstrated that in patients who developed LOSP after allo-SCT, the initiation time of antiviral drugs and glucocorticoids were associated with the prognosis of LOSP, and the survival rate was highest in patients who received antiviral drugs early and glucocorticoids later. It suggested that for patients with LOSP of unknown etiology should be highly suspicious of the possibility of a secondary hyperimmune response to viral infection.
Antiviral Agents/therapeutic use*
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Glucocorticoids/therapeutic use*
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Hematopoietic Stem Cell Transplantation/methods*
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Humans
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Pneumonia/etiology*
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Prognosis
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Retrospective Studies
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Transplantation, Homologous/adverse effects*
9.Related factors of revision of distal femoral fractures treated with lateral locking plate.
Guo Jin HOU ; Fang ZHOU ; Yun TIAN ; Hong Quan JI ; Zhi Shan ZHANG ; Yan GUO ; Yang LV ; Zhong Wei YANG
Journal of Peking University(Health Sciences) 2022;54(6):1172-1177
OBJECTIVE:
To analyze the factors related to the need for revision surgery due to nonunion or internal fixation failure after the treatment of distal femoral fracture with lateral locking plate (LLP).
METHODS:
Retrospective analysis was made of the clinical data of 130 cases with distal femoral fracture treated in our hospital from March 2005 to March 2019. SPSS 17.0 software (univariate analysis and Logistic regression analysis) was used to analyze the general condition [gender, age, body mass index (BMI), comorbidities, smoking history], injury related factors (energy of injury, open or closed injury, AO/OTA classification of fracture, fracture area distribution), operation related factors (operation time, reduction quality, postoperative infection) and construct characteristics of internal fixation.
RESULTS:
Twelve of 130 patients who were included in the study underwent revisional surgery, with a revision rate 9.2%. Univariate analysis showed that there were significant differences in age, BMI, AO/OTA classification, fracture area distribution, operation time, reduction quality, length of plate/fracture area, length of plate/fracture area above condylar between the two groups (P < 0.05). Logistic regression analysis showed that AO/OTA classification (A3), supracondylar involved fracture, operation time, reduction quality and the length of the plate/fracture area above the condylar were the possible related factors (P < 0.05). Destruction of the medial support ability of the femur in comminuted type A3 fracture, supra-condylar cortex area fracture involvement, increase of the bending stress of the LLP due to poor fracture reduction quality, damage of the blood supply of fracture end due to long-time operation, and stress concentration caused by insufficient length of plate might be risk factors of revisional operation after the treatment of distal femoral fracture with LLP. For the patients who needed revision after LLP treatment, additional use of medial minimally invasive plate fixation and autologous bone transplantation, change to intramedullary nail fixation were commonly used clinical treatment strategies.
CONCLUSION
AO/OTA classification (A3), supracondylar involved fracture, long operation time, poor reduction quality and the length of the plate/fracture area above the condylar were the possible predictive factors of the revision in distal femoral fractures treated with lateral locking plate. The appropriate application of the locking plate and operation strategy are the key to reduce the revision rate in distal femoral fractures.
Humans
;
Femoral Fractures/etiology*
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Retrospective Studies
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Femoral Fractures, Distal
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Bone Plates/adverse effects*
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Fracture Fixation, Internal/adverse effects*
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Treatment Outcome
10.Annual financial expenditure in 24 domestic blood stations: a comparative analysis
Huixia ZHAO ; Pengkun WANG ; Hongjun CAI ; Lina HE ; Qizhong LIU ; Feng YAN ; Jianhua LI ; Jiankun MA ; Jianling ZHONG ; Chaochao LV ; Yu JIANG ; Qingpei LIU ; Li LI ; Jian ZHANG ; Weitao YANG ; Wei ZHANG ; Zhenxing WANG ; Peng WANG ; Wenjie HUANG ; Qingjie MA ; Youhua SHEN ; Zhibin TIAN ; Meihua LUN ; Mei YU
Chinese Journal of Blood Transfusion 2022;35(9):947-949
【Objective】 To study the annual financial expenditure in blood stations with different scales, and to establish the regression equation between blood collection units and total expenditure. 【Methods】 The annual total expenditure, the per capita cost of serving population, as well as the collection units of whole blood and apheresis platelet of 24 blood stations were collected. The financial expenditure required for collecting 10 000U blood was calculated.The statistical analysis was carried out with SPSS statistical software. 【Results】 From 2017 to 2020, the total annual financial expenditure of 24 blood stations showed an upward trend. The total expenditure among blood stations was different. The per capita cost of servicing population in the areas where the 24 blood stations were located had been increasing year by year. The 24 blood stations were divided into two grades according to the blood collection volume as 50 000 U, and the relationship equation between the blood collection volume and the annual total expenditure had been established. After testing, each equation was effective(P<0.05); There was no difference in the financial expenditure required for collecting 10 000U blood among blood stations with different scales. 【Conclusion】 From 2017 to 2020, the blood stations with an annual collection volume more than 50 000 U demonstrated a higher financial expenditure and the per capita cost of serving population than those <50 000 U. The blood collection volume of blood stations is significantly correlated with the annual total expenditure and the per capita cost of serving population.

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