1.Development of a Core Outcome Set for Clinical Evaluation of Chronic Pulmonary Heart Disease Treated with Traditional Chinese Medicine Therapy
Baihan NIU ; Mingyan ZHANG ; Zhaochen JI ; Bo PANG ; Haiyin HU ; Junhua ZHANG
Journal of Traditional Chinese Medicine 2025;66(12):1227-1232
ObjectiveTo construct an outcome set for clinical evaluation of traditional Chinese medicine (TCM) for chronic pulmonary heart disease, and to provide consensus outcomes for the evaluation of the clinical effectiveness of TCM for chronic pulmonary heart disease. MethodsWe searched randomised controlled trials of TCM for chronic pulmonary heart disease on China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Service Platform (WF), VIP Chinese Science Journals Database (VIP), Chinese Biomedical Literature Service Database (SinoMed), PubMed, Cochrane Library, and Embase. We also searched Chinese Clinical Trial Registry Platform and the U.S. Clinical Trial Registry database to obtain the outcome indicators reported in the clinical research protocols of TCM for chronic pulmonary heart disease. The outcome indicators were also collected through semi-structured interviews of clinicians and patients. Then integrated the outcome indicators collected by the above methods to construct the indicator pool. Through two rounds of Delphi surveys and a consensus conference, the core outcome set for clinical evaluation of TCM for chronic pulmonary heart disease was determined. ResultsAfter screening, there were 1313 literature meeting the criteria, and 595 outcome indicators were extracted, then combined with the outcomes from semi-structured interviews which clinicians and patients concerned, finally an indicator item pool containing 369 outcome indicators were formed. After the initial screening of indicators in the pool by the steering committee, 58 indicators were established into the initial list of indicator entries. In the first round of Delphi survey, the expert coordination coefficient for the results was 0.401, and the Cronbach coefficient was 0.989. A total of 35 indicators that did not meet the criteria [<70% of the participants rated the outcome as 7~9 (critical) and the mean of the expert ratings <7] were deleted, and 23 were retained, with 7 new indicators added that were open to supplementation by the experts, resulting in a total of 30 indicators that were included in the second round of Delphi survey. In the second round of Delphi survey, the expert coordination coefficient was 0.303, and the Cronbach coefficient was 0.974, with a total of 7 indicators that did not meet the criteria being deleted, and 21 indicators being retained for the consensus conference. After the consensus meeting, the core outcome set for clinical evaluation of chronic pulmonary heart disease in two major categories, acute exacerbation stage and stable stage, was finally determined, in which there were four indicators in acute exacerbation stage: N-terminal B-type natriuretic peptide precursor (NT-proBNP), blood qi analysis, all-cause mortality rate, and complication rate; and there were eight indicators in the stable stage: pulmonary function index, six-minute walk test distance, New York cardiac function classification, all-cause mortality rate, re-hospitalisation rate, Chronic Obstructive Pulmonary Disease Assessment Test (CAT) score, Short Form 36 Health Survey (SF-36), and TCM syndrome score. ConclusionThe core outcome sets of TCM clinical evaluation in the acute exacerbation stage and stable stage are constructed, which is helpful to improve the practicability, comparability and transparency of TCM clinical research results in pulmonary heart disease.
2.Effect of high ligation of spermatic vein on leukocytes in expressed prostate secretion of patients with chronic prostatitis and varicocele.
Ji-Yang DING ; Peng ZHANG ; Chun-Hua NIU ; Hai-Yong LI ; Wen-Zhu XU ; Ying-Chen ZHANG ; Gang MA
National Journal of Andrology 2025;31(4):319-322
OBJECTIVE:
To investigate the effect of laparoscopic high ligation of spermatic cord vein in patients with chronic prostatitis and varicocele prostatitis.
METHODS:
A total of 90 varicocele patients were selected from January 2016 to December 2020, including 33 patients with chronic prostatitis. Changes of white blood cell count, National Institutes of Health chronic prostatitis symptom index (NIH-CPSI) score and serum testosterone level in the expressed prostate secretion (EPS) were observed before and after the operation of laparoscopic high ligation of spermatic vein.
RESULTS:
All patients were followed up three months after the surgery. There was no significant difference in the white blood cell counts in EPS, NIH-CPSI score, and serum testosterone level in patients with varicocele-only who underwent high ligation surgery after the operation. However, the white blood cell count in the EPS of patients with chronic prostatitis was lower than that before 3 months of operation ( [12.39±4.23]×109/L vs [21.36±5.05]×109/L). The NIH-CPSI score was significantly lower than that before operation ( [12.71±6.21] vs [26.76±8.43]). And the serum testosterone level was higher than that before operation ([4.34±1.77]ng/ml vs [2.36±1.05]ng/ml).
CONCLUSION
Laparoscopic high ligation of the spermatic vein in patients with chronic prostatitis and varicocele could effectively reduce the number of white blood cells in the EPS, boost the level of serum testosterone and improves symptoms of chronic prostatitis.
Male
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Humans
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Varicocele/surgery*
;
Prostatitis/blood*
;
Ligation
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Spermatic Cord/blood supply*
;
Testosterone/blood*
;
Chronic Disease
;
Prostate/metabolism*
;
Veins/surgery*
;
Leukocyte Count
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Leukocytes
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Laparoscopy
;
Adult
3.Ventral Hippocampal CA1 GADD45B Regulates Susceptibility to Social Stress by Influencing NMDA Receptor-Mediated Synaptic Plasticity.
Mengbing HUANG ; Jian BAO ; Xiaoqing TAO ; Yifan NIU ; Kaiwei LI ; Ji WANG ; Xiaokang GONG ; Rong YANG ; Yuran GUI ; Hongyan ZHOU ; Yiyuan XIA ; Youhua YANG ; Binlian SUN ; Wei LIU ; Xiji SHU
Neuroscience Bulletin 2025;41(3):406-420
Growth arrest DNA damage-inducible protein 45 β (GADD45B) has been reported to be a regulatory factor for active DNA demethylation and is implicated in the modulation of synaptic plasticity and chronic stress-related psychopathological processes. However, its precise role and mechanism of action in stress susceptibility remain elusive. In this study, we found a significant reduction in GADD45B expression specifically in the ventral, but not the dorsal hippocampal CA1 (dCA1) of stress-susceptible mice. Furthermore, we demonstrated that GADD45B negatively regulates susceptibility to social stress and NMDA receptor-dependent long-term potentiation (LTP) in the ventral hippocampal CA1 (vCA1). Importantly, through pharmacological inhibition using the NMDA receptor antagonist MK801, we provided further evidence supporting the hypothesis that GADD45B potentially modulates susceptibility to social stress by influencing NMDA receptor-mediated LTP. Collectively, these results suggested that modulation of NMDA receptor-mediated synaptic plasticity is a pivotal mechanism underlying the regulation of susceptibility to social stress by GADD45B.
Animals
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Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors*
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CA1 Region, Hippocampal/drug effects*
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Male
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Stress, Psychological/physiopathology*
;
Mice
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Neuronal Plasticity/drug effects*
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Long-Term Potentiation/drug effects*
;
Mice, Inbred C57BL
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Antigens, Differentiation/metabolism*
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Dizocilpine Maleate/pharmacology*
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Excitatory Amino Acid Antagonists/pharmacology*
;
GADD45 Proteins
4.Fluid shear promotes apoptosis of glomerular endothelial cells by activation of Piezo 1
Menglin LUO ; Feng ZHENG ; Xinyao JI ; Caihong QI ; Yuheng XIAO ; Changchun NIU
Basic & Clinical Medicine 2024;44(9):1236-1242
Objective To investigate the effect of fluid shear(FS)on apoptosis of glomerular epithelial cells(GECs)and the role of Piezo 1 protein in it.Methods GECs(glomerular epithelial cells)of SD rat were cul-tured.Fluid shear stimulation was simulated by a Flexcell-T5000 tensiometer.Apoptosis level was detected by flow cytometry.The expression of Piezo 1 proteins in GECs was detected by immunofluorescence staining.The activating of Piezo 1 channels by fluid shear was observed using Ca2+indicator(Cal-590 AM).The effect of Piezo 1 on apop-tosis in GECs was analyzed after modulating the function or expression of Piezo 1 protein using the chemical activa-tor Yoda1,the inhibitor GsMtx 4 was regulated by lentivirus Lv-shPiezo 1.Results Compared with the blank controlgroup,apoptosis increased in the fluid shear group(P<0.05).The rate of apoptosis increased with the enhancing of fluid shear strength;Piezo 1 was commonly expressed in GECs.Fluid shear activated Piezo 1 chan-nel and enhanced expression of Piezo 1.The agonist Yoda1 promoted the apoptosis of GECs GsMtx 4 inhibited the apoptosis induced by fluid shear.Lv-shPiezo 1 knocked down the expression of Piezo 1 in GECs and the apoptosis rate of GECs in the knockdown group was reduced as compared to that in the control group and Lv-Ctrl group(P<0.05).Conclusions Fluid shear may promote apoptosis of GECs by activation of Piezo 1 and by enhancing expression of Piezo 1.
5.HUVEC-Based OGD/R Injury Model to Study the Effect of Danggui-Chuanxiong Herb Pair Medicine on the Main Pharmacological Components on VEGF-PI3K-AKT/NF-κB Signaling Pathway
Qiuru JI ; Wenjuan NI ; Xiaoyan WANG ; Shuqi ZHANG ; Yali WU ; Lu NIU ; Kun LI ; Weixia LI ; Jinfa TANG
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(3):691-703
Objective To study the effects of Danggui-Chuanxiong herb pair medicine on vasoactive substances,adhesion factors,inflammatory factors,and VEGF-PI3K-AKT/NF-κB signaling pathways,in order to elucidate the mechanism of Danggui-Chuanxiong herb pair on the treatment of ischemic stroke(IS).Methods The oxygen glucose deprivation/reoxygenation(OGD/R)model of human umbilical vein endothelial cells(HUVEC)was constructed,and the cell viability was detected by cell proliferation kit(CCK-8 method)to explore the optimal modeling time of seven components;The release of lactate dehydrogenase(LDH)was detected by cytotoxicity kit;The expression of related cytokines was detected by enzyme-linked immunosorbent assay(ELISA);The mRNA expression of key proteins in the signaling pathway was detected by reverse transcription-polymerase chain reaction(RT-PCR).Results Reoxygenation after 6 h of oxygen-glucose deprivation of HUVEC is the best modeling time.High-dose chlorogenic acid group,ferulic acid group,senkyunolide H,low-dose and medium-dose butylidenephthalide group,medium-dose and high-dose senkyunolide A and ligustilide groups significantly decreased LDH leakage rate(P<0.05,P<0.01);The expression of IL-6 in the cells of the partial dose group of chlorogenic acid,caffeic acid,butenylphthalide,senkyunolide H and senkyunolide A was significantly increased,the expression of IL-1 in the cells of the partial dose group of chlorogenic acid,ferulic acid and senkyunolide A was significantly decreased,the expression of VEGF,ICAM-1 and VCAM-1 in the cells of the partial dose group of chlorogenic acid,ferulic acid and senkyunolide H was significantly decreased,the expression of NF-κB in the cells of the partial dose group of chlorogenic acid,ferulic acid,senkyunolide H and ligustilide was significantly decreased,the expression of PAI-1 in the cells of ferulic acid and senkyunolide H partial dose group decreased significantly(P<0.05,P<0.01);The mRNA relative expression levels of ERK,VEGF,NF-κB,VEGFR2 and MMP9 were significantly down-regulated in the cells of chlorogenic acid,ferulic acid,caffeic acid,butylidenephthalide and senkyunolide A partial dose group,while the mRNA relative expression levels of AKT were significantly up-regulated in the cells of senkyunolide H and senkyunolide A partial dose groups(P<0.05,P<0.01).Conclusion The medicinal components of Danggui-Chuanxiong herb pair may play a role in IS by inhibiting the mRNA expression of adhesion factor,inflammatory factor and key protein of VEGF-PI3K-AKT/NF-κB signaling pathway in HUVEC.
6.Prevalence of cataracts and the coverage rate of cataract surgery in Ningxia region
Jinjin ZHANG ; Lin CHEN ; Tian TIAN ; Haijun LIU ; Wei NIU ; Xue ZHANG ; Mengli JI ; Wenjuan ZHUANG
Chinese Journal of Experimental Ophthalmology 2024;42(3):279-284
Objective:To investigate the prevalence of cataracts, the surgical coverage, and postoperative visual acuity of adults in Ningxia.Methods:A cross-sectional study using multistage cluster random sampling was conducted.Ten survey sites in Ningxia were selected and the population aged 18 years and over was surveyed with questionnaire, height and weight measurements, visual acuity, intraocular pressure, fundus photography and slit-lamp examinations.Cataract prevalence and its influencing factors were analyzed.Cataract prevalence, surgical coverage and presenting visual acuity (PVA) and best corrected visual acuity (BCVA) after surgery were investigated in different age groups of the examined population.The study adhered to the Declaration of Helsinki and was approved by the Ethics Committee of the People's Hospital of Ningxia Hui Autonomous Region (No.[2023]-LL-010).Participants signed informed consent prior to the examination.Results:A total of 6 145 people should be examined, and 5 721 people were actually examined, with an examination rate of 93.10%.The study population consisted of 2 558 males, accounting for 44.71%, and 3 163 females, accounting for 55.28%, with ages ranging from 18 to 93 years old and an average age of (64.27±13.48) years.Among them, 1 180 patients diagnosed with cataract, with a cataract prevalence of 20.62%.The prevalence of cataract increased with age and decreased with education level, showing statistically significant differences ( χ2=1 091.32, 581.92; both at P<0.01).The prevalence of cataract was significantly higher among people with hypertension, diabetes mellitus, hyperlipidemia, and coronary heart disease than those without these diseases ( χ2=274.65, 118.15, 78.05, 182.71; all at P<0.01).Cataract surgery was performed in 245 cases in the cataract patient population, with a surgical coverage rate of 20.76%.Of the 245 cases, 229 cases were implanted with IOLs, with an implantation rate of 93.40%.The social burden rate of cataract blindness was 2.29%, and increased with age.Of the 339 eyes that underwent cataract surgery, 241 had a PVA≥0.3, accounting for 71.09%, and 272 had a BCVA≥0.3, accounting for 80.24%. Conclusions:In Ningxia, cataracts are still the main cause of vision impairment and blindness in the elderly, and the social burden rate of cataract blindness is high.Moreover, the coverage rate of cataract surgery is low, so both the coverage and quality of surgery need improvement.
7.Comparison of Clinical Characteristics of JAK2,CALR and Tri-Negative Driving Mutant Type in Patients with Essential Thrombocythemia
Yu-Meng LI ; Er-Peng YANG ; Zi-Qing WANG ; De-Hao WANG ; Ji-Cong NIU ; Yu-Jin LI ; Jing MING ; Ming-Qian SUN ; Zhuo CHEN ; Wei-Yi LIU ; Yan LYU ; Xiao-Mei HU
Journal of Experimental Hematology 2024;32(1):197-201
Objective:To investigate the relationship between mutated genes and clinical features in patients with essential thrombocythemia(ET).Methods:The clinical data of 69 patients with ET from October 2018 to March 2022 were retrospectively analyzed.According to driver mutation type,patients were divided into JAK2 group,CALR group and triple-negative group.The sex,age,cardiovascular risk factors,thrombosis,splenomegaly,routine blood test and coagulation status of patients in three groups were analyzed.Results:Among 69 ET patients,46 cases were associated with JAK2 mutation,14 cases with CALR mutation,8 cases with triple-negative mutation,and one with MPL gene mutation.There were no significant differences in age and sex among the three groups(P>0.05).The highest thrombotic rate was 26.09%(12/46)in JAK2 group,then 12.5%(1/8)in triple-negative group,while no thrombotic events occurred in CALR group.The incidence of splenomegaly was the highest in JAK2 group(34.78%),while no splenomegaly occurred in triple-negative group.The white blood cell(WBC)count in JAK2 group was(9.00±4.86)× 109/L,which was significantly higher than(6.03±2.32)× 109/L in CALR group(P<0.05).The hemoglobin(Hb)and hematocrit(HCT)in JAK2 group were(148.42±18.79)g/L and(0.44±0.06)%,respectively,which were both significantly higher than(131.00±15.17)g/L and(0.39±0.05)%in triple-negative group(P<0.05).The platelet(PLT)in JAK2 group was(584.17±175.77)× 109/L,which was significantly lower than(703.07±225.60)× 109/L in CALR group(P<0.05).The fibrinogen(Fg)in JAK2 and triple-negative group were(2.64±0.69)g/L and(3.05±0.77)g/L,respectively,which were both significantly higher than(2.24±0.47)g/L in CALR group(P<0.05,P<0.01).The activated partial thromboplastin time(APTT)in triple-negative group was(28.61±1.99)s,which was significantly decreased compared with(31.45±3.35)s in CALR group(P<0.05).Conclusions:There are differences in blood cell count and coagulation status among ET patients with different driver gene mutations.Among ET patients,JAK2 mutation is most common.Compared with CALR group,the thrombotic rate,WBC and Fg significantly increase in JAK2 group,while PLT decrease.Compared with triple-negative group,the incidence of splenomegaly and HCT significantly increase.Compared with CALR group,Fg significantly increases but APTT decreases in triple-negative group.
8.Clinical Features and Prognosis of Patients with Primary Extranodal Diffuse Large B-Cell Lymphoma
Si YI ; Xia LI ; Huan TAO ; Hong-Bing MA ; Jie JI ; Yu WU ; Ting NIU ; Yong-Qian JIA
Journal of Experimental Hematology 2024;32(6):1711-1718
Objective:To investigate the clinical features,gene mutation profile,efficacy and prognostic factors of primary extranodal diffuse large B-cell lymphoma(EN-DLBCL).Methods:A retrospective analysis was performed for 382 patients with primary EN-DLBCL with complete clinical data who were treated in West China Hospital from January 2013 to January 2023,and their clinical characteristics,gene mutation profile,efficacy and prognostic factors were analyzed.Results:The median age of the 382 patients with EN-DLBCL was 56 (18-89 )years old.The male-to-female ratio was 1.12∶1,and the most common primary sites were gastrointestinal tract (31.7%),Wechsler ring (19. 1%)and breast gland (7.1%).A total of 51 gene mutations were fund,and the most common frequencies of gene mutations were TP53 (32.5%),MYD88 (32.5%),and CD79B (30.0%).The median follow-up was 63 months,and the 5-year progression-free survival (PFS)rate was 74.5% and the 5-year overall survival (OS)rate was 89.6%. The adverse factors on PFS were as follows:>1 extranodal sites involvement (P<0.001),P53≥50%(P<0.001),hyper double expression(hDEL)of C-myc>50%/Bcl-2>70%(P<0.001).The adverse factors affecting the OS of patients were as follows:>1 extranodal sites involvement (P<0.001),P53≥50%(P<0.001),hDEL(P<0.001). Chemotherapy combined with local radiotherapy could improve PFS (P=0.041)and OS (P=0.003),while R-CHOP+X (molecule agents as BTKi、HDACi、Lenalidomide)failed to show a significant difference in PFS (P=0.075)and OS (P=0.767 ).Among the 40 patients who underwent next-generation sequencing at high risk,there was no significant in PFS (P=0.849)and OS (P=0.500)of patients with positive MYD88 and/or CD79B mutations (MCD subtype)treated with BTKi and patients with negative MYD88 and CD79B mutations.Conclusion:Primary EN-DLBCL can involve multiple organs or tissue sites.TP53,MYD88,and CD79B are the most common gene mutations.The efficacy of BTKi in patients with positive MCD subtypes at intermediate and high risk is not inferior to that in MCD-negative control patients.
9.Analysis of Genes Related to Platelet Activation in Essential Thrombocythemia Based on Transcriptomics
Yan SUN ; Er-Peng YANG ; Yu-Meng LI ; Ji-Cong NIU ; Pei ZHAO ; Wei-Yi LIU ; Zhuo CHEN ; Ming-Jing WANG ; Teng FAN ; Xiao-Mei HU
Journal of Experimental Hematology 2024;32(6):1814-1821
Objective:To analyze the genes related to platelet activation in essential thrombocythemia (ET)based on transcriptome sequencing technology (RNA-seq ),and to explore the potential targets related to ET thrombosis. Methods:Blood samples from ET patients and healthy individuals were collected for RNA-seq,and differentially expressed lncRNAs,miRNAs,and mRNAs were selected to construct a lncRNA-miRNA-mRNA regulatory network. Differential mRNAs in the regulatory network were enriched and analyzed using Gene Ontology (GO ) and Kyoto Encyclopedia of Genes and Genomes (KEGG).The real-time PCR method was applied to validate differential mRNAs on crucial signaling pathways.Results:A total of 32 lncRNAs (3 up-regulated,29 down-regulated),16 miRNAs (8 up-regulated,8 down-regulated),and 35 mRNAs (27 up-regulated,8 down-regulated)were identified as differentially expressed.Among them,5 lncRNAs,12 miRNAs,and 19 mRNAs constituted the regulatory network.KEGG enrichment analysis showed that the differential mRNAs were related to the platelet activation signaling pathway,and there were 6 differential mRNAs related to platelet activation,namely F2R,ITGA2B,ITGB1,ITGB3,PTGS1,and GP1 BB,which were all up-regulated in their expression.RT-PCR results showed that the expression of five mRNAs including F2R,ITGA2B,ITGB1,ITGB3,and GP1BB were upregulated in ET patients compared with healthy subjects,and consistent with RNA-seq results,while PTGS1 expression was not significantly different.Conclusion:Differential mRNAs in ET patients are related to the platelet activation pathway,and F2R,ITGA2B,ITGB1,ITGB3,and GP1BB mRNAs may serve as novel targets associated with platelet activation in ET.
10.Constructing a risk prediction model for failure after locking plate fixation for proximal humeral fractures in the elderly by combining the deltoid tuberosity index with preoperative factors
Daxing XU ; Muqiang JI ; Zesong TU ; Weipeng XU ; Weilong XU ; Wei NIU
Chinese Journal of Tissue Engineering Research 2024;28(21):3299-3305
BACKGROUND:Proximal humeral fracture in older adults is one of the three major osteoporotic fractures.Anatomic locking plate fixation is the first choice for most scholars to treat difficult-to-reduce and complex fracture types.However,the probability of reduction failure after the operation is high,which seriously affects patients'quality of life. OBJECTIVE:To investigate the correlation between deltoid tuberosity index and postoperative reduction failure of proximal humeral fractures in the elderly,analyze and filter preoperative independent risk factors for reduction failure of proximal humeral fractures in the elderly,and construct and verify the effectiveness of a clinical prediction model. METHODS:The clinical data of 153 elderly patients with proximal humeral fractures who met the diagnosis and inclusion criteria and received open reduction and locking plate surgery in Foshan Hospital of TCM from June 2012 to June 2021 were collected.The patients were divided into the reduction failure subgroup and the reduction maintenance subgroup.The independent risk factors were selected by multivariate Logistic regression analysis,and the nomogram was constructed by R language.After 1000 times of resampling by Bootstrap method,the Hosmer-Lemeshow goodness of fit correlation test,receiver operating characteristic curve,calibration curve,clinical decision,and influence curve were plotted to evaluate its goodness of fit,discrimination,calibration ability,and clinical application value.Fifty-five elderly patients with proximal humeral fractures from June 2013 to August 2021 were selected as the model's external validation group to evaluate the prediction model's stability and accuracy. RESULTS AND CONCLUSION:(1)Of the 153 patients in the training group,44 patients met reduction failure after internal plate fixation.The prevalence of postoperative reduction failure was 28.8%.Multivariate Logistic regression analysis identified that deltoid tuberosity index[OR=9.782,95%CI(3.798,25.194)],varus displacement[OR=4.209,95%CI(1.472,12.031)],and medial metaphyseal comminution[OR=4.278,95%CI(1.670,10.959)]were independent risk factors for postoperative reduction failure of proximal humeral fractures in older adults(P<0.05).(2)A nomogram based on independent risk factors was then constructed.The Hosmer-Lemeshow test results for the model of the training group showed that χ2=0.812(P=0.976)and area under curve=0.830[95%CI(0.762,0.898)].The calibration plot results showed that the model's predicted risk was in good agreement with the actual risk.The decision and clinical influence curves showed good clinical applicability.(3)In the validation group,the accuracy rate in practical applications was 86%,area under curve=0.902[95%CI(0.819,0.985)].(4)It is concluded that deltoid tuberosity index<1.44,medial metaphyseal comminution,and varus displacement were independent risk factors for reduction failure.(5)The internal and external validation of the risk prediction model demonstrated high discrimination,accuracy,and clinical applicability could be used to individually predict and screen the high-risk population of postoperative reduction failure of proximal humeral fractures in the elderly.The predicted number of patients at high risk is highly matched to the actual number of patients who occur when the model's threshold risk probability is above 65%,and clinicians should use targeted treatment.

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