1.The Invariant Neural Representation of Neurons in Pigeon’s Ventrolateral Mesopallium to Stereoscopic Shadow Shapes
Xiao-Ke NIU ; Meng-Bo ZHANG ; Yan-Yan PENG ; Yong-Hao HAN ; Qing-Yu WANG ; Yi-Xin DENG ; Zhi-Hui LI
Progress in Biochemistry and Biophysics 2025;52(10):2614-2626
ObjectiveIn nature, objects cast shadows due to illumination, forming the basis for stereoscopic perception. Birds need to adapt to changes in lighting (meaning they can recognize stereoscopic shapes even when shadows look different) to accurately perceive different three-dimensional forms. However, how neurons in the key visual brain area in birds handle these lighting changes remains largely unreported. In this study, pigeons (Columba livia) were used as subjects to investigate how neurons in pigeon’s ventrolateral mesopallium (MVL) represent stereoscopic shapes consistently, regardless of changes in lighting. MethodsVisual cognitive training combined with neuronal recording was employed. Pigeons were first trained to discriminate different stereoscopic shapes (concave/convex). We then tested whether and how light luminance angle and surface appearance of the stereoscopic shapes affect their recognition accuracy, and further verify whether the results rely on specify luminance color. Simultaneously, neuronal firing activity of neurons was recorded with multiple electrode array implanted from the MVL during the presentation of difference shapes. The response was finally analyzed how selectively they responded to different stereoscopic shapes and whether their selectivity was affected by the changes of luminance condition (like lighting angle) or surface look. Support vector machine (SVM) models were trained on neuronal population responses recorded under one condition (light luminance angle of 45°) and used to decode responses under other conditions (light luminance angle of 135°, 225°, 315°) to verify the invariance of responses to different luminance conditions. ResultsBehavioral results from 6 pigeons consistently showed that the pigeons could reliably identify the core 3D shape (over 80% accuracy), and this ability wasn’t affected by changes in light angle or surface appearance. Statistical analysis of 88 recorded neurons from 6 pigeons revealed that 83% (73/88) showed strong selectivity for specific 3D shapes (selectivity index>0.3), and responses to convex shapes were consistently stronger than to concave shapes. These shape-selective responses remained stable across changes in light angle and surface appearance. Neural patterns were consistent under both blue and orange lighting. The decoding accuracy achieves above 70%, suggesting stable responses under different conditions (e.g., different lighting angles or surface appearance). ConclusionNeurons in the pigeon MVL maintain a consistent neural encoding pattern for different stereoscopic shapes, unaffected by illumination or surface appearance. This ensures stable object recognition by pigeons in changing visual environments. Our findings provide new physiological evidence for understanding how birds achieve stable perception (“invariant neural representations”) while coping with variations in the visual field.
2.Reasons and strategies of reoperation after oblique lateral interbody fusion
Zhong-You ZENG ; Deng-Wei HE ; Wen-Fei NI ; Ping-Quan CHEN ; Wei YU ; Yong-Xing SONG ; Hong-Fei WU ; Shi-Yang FAN ; Guo-Hao SONG ; Hai-Feng WANG ; Fei PEI
China Journal of Orthopaedics and Traumatology 2024;37(8):756-764
Objective To summarize the reasons and management strategies of reoperation after oblique lateral interbody fusion(OLIF),and put forward preventive measures.Methods From October 2015 to December 2019,23 patients who under-went reoperation after OLIF in four spine surgery centers were retrospectively analyzed.There were 9 males and 14 females with an average age of(61.89±8.80)years old ranging from 44 to 81 years old.The index diagnosis was degenerative lumbar intervertebral dics diseases in 3 cases,discogenie low back pain in 1 case,degenerative lumbar spondylolisthesis in 6 cases,lumbar spinal stenosis in 9 cases and degenerative lumbar spinal kyphoscoliosis in 4 cases.Sixteen patients were primarily treated with Stand-alone OLIF procedures and 7 cases were primarily treated with OLIF combined with posterior pedicle screw fixation.There were 17 cases of single fusion segment,2 of 2 fusion segments,4 of 3 fusion segments.All the cases underwent reoperation within 3 months after the initial surgery.The strategies of reoperation included supplementary posterior pedicle screw instrumentation in 16 cases;posterior laminectomy,cage adjustment and neurolysis in 2 cases,arthroplasty and neuroly-sis under endoscope in 1 case,posterior laminectomy and neurolysis in 1 case,pedicle screw adjustment in 1 case,exploration and decompression under percutaneous endoscopic in 1 case,interbody fusion cage and pedicle screw revision in 1 case.Visu-al analogue scale(VAS)and Oswestry disability index(ODI)index were used to evaluate and compare the recovery of low back pain and lumbar function before reoperation and at the last follow-up.During the follow-up process,the phenomenon of fusion cage settlement or re-displacement,as well as the condition of intervertebral fusion,were observed.The changes in in-tervertebral space height before the first operation,after the first operation,before the second operation,3 to 5 days after the second operation,6 months after the second operation,and at the latest follow-up were measured and compared.Results There was no skin necrosis and infection.All patients were followed up from 12 to 48 months with an average of(28.1±7.3)months.Nerve root injury symptoms were relieved within 3 to 6 months.No cage transverse shifting and no dislodgement,loosening or breakage of the instrumentation was observed in any patient during the follow-up period.Though the intervertebral disc height was obviously increased at the first postoperative,there was a rapid loss in the early stage,and still partially lost after reopera-tion.The VAS for back pain recovered from(6.20±1.69)points preoperatively to(1.60±0.71)points postoperatively(P<0.05).The ODI recovered from(40.60±7.01)%preoperatively to(9.14±2.66)%postoperatively(P<0.05).Conclusion There is a risk of reoperation due to failure after OLIF surgery.The reasons for reoperation include preoperative bone loss or osteoporosis the initial surgery was performed by Stand-alone,intraoperative endplate injury,significant subsidence of the fusion cage after surgery,postoperative fusion cage displacement,nerve damage,etc.As long as it is discovered in a timely manner and handled properly,further surgery after OLIF surgery can achieve better clinical results,but prevention still needs to be strengthened.
3.Antimicrobial resistance and genomic characteristics of multidrug resistant diarrheagenic Escherichia coli from human and food samples in Henan Province
Hao-Yu QI ; Yan-Fen LI ; Yu WANG ; Zheng-Yong QIU ; Ying CUI ; Ling-Ling WU ; Meng ZHANG ; Yong-Li LI
Chinese Journal of Zoonoses 2024;40(8):723-731
This study was aimed at investigating the antimicrobial susceptibility and genomic characteristics of multidrug resistant diarrheagenic Escherichia coli isolated from human and food samples in Henan Province from 2017 to 2022.A total of 101 strains of multidrug resistant diarrheagenic E.coli were subjected to antimicrobial susceptibility testing with the broth di-lution method.Whole genome sequencing was performed to analyze the antimicrobial resistance genes,multilocus sequence typ-ing,and plasmid types.The sequencing data were used to construct a phylogenetic tree based on core genome single-nucleotide polymorphisms(cgSNPs).The isolates showed the highest resistance to ampicillin(87.1%),followed by tetracycline(79.2%)and nalidixic acid(64.4%).The resistance rate to cefotaxime was 38.6%.All 101 strains were classified into 60 STs,among which ST10,ST1491,and ST38 were dominant.Moreover,23 distinct plasmid replicons were identified,among which IncFIB was dominant.Diverse antimicrobial resistance genes(including quinolone,aminoglycoside,β-lactamase,and tetracycline)were identified.Insertion sequences(IS26,IS903B,and ISECP 1)were identified in upstream and downstream analysis of the gene context of the extended-spectrum β-lactamase bla CTX-M-14 and bla CTX-M-55 genes.In conclusion,multidrug resistant diarrhea-genic Escherichia coli isolated from clinical and food samples in Henan Province showed high genetic diversity and high antimi-crobial resistance.The dissemination of blaCTX-M carried by the strains was shown to be associated with the insertion sequence(IS).
4.Ameliorative effects of Schisandrol A in Suhuang antitussive capsule on post-infectious cough
Nan WU ; Zi-Yu BAI ; Yong-Yu OU ; Tong-Lian DI ; Zi-Yao ZHAO ; Hong JIANG ; Zhi-Hao ZHANG ; Ning-Hua TAN
Chinese Traditional Patent Medicine 2024;46(8):2562-2571
AIM To investigate the ameliorative effects of Schisandrol A(Sol A)in Suhuang antitussive capsule on post-infectious cough(PIC).METHODS The in vivo mouse PIC model was established by intratracheal instillation of lipopolysaccharide(LPS)combined with cigarette smoke exposure.The mice were randomly divided into the control group,the model group,the Suhuang antitussive capsule group(14 g/kg),the montelukast sodium positive control group(3 mg/kg),and low and high dose Sol A groups(10,30 mg/kg).The in vitro PIC model was established by stimulating human bronchial epithelial cells(BEAS-2B)with LPS.The cells were divided into the control group,the model group,the Suhuang antitussive capsule group(10 μg/mL)and low and high dose Sol A groups(3,10 μmol/L).HE and Masson staining were used to detect the pathological changes of the lung and bronchial tissues.ELISA was used to detect the levels of IL-1β,IL-6,TNF-α,ROS,MDA,SOD and GSH in the lung tissues.RT-qPCR was used to detect the IL-1β,IL-6 and TNF-α mRNA expressions in BEAS-2B cells.And Western blot was applied to detect the protein expressions of p-PI3K,p-Akt,NOX4,SIRT1,p-ERK,Fibronectin,E-cadherin,Vimentin and α-SMA in mouse lung tissue and BEAS-2B cells.RESULTS Compared with the model group,the groups intervened with Sol A or Suhuang antitussive capsule displayed prolonged cough latency(P<0.01);reduced cough frequency(P<0.01);relieved pulmonary inflammatory cell infiltration and collagen deposition in PIC mice;decreased pulmonary levels of IL-1β,IL-6,TNF-α,ROS,MDA and protein expressions of Fibronectin,Vimentin,α-SMA,p-ERK,p-PI3K,p-Akt,and NOX4(P<0.05,P<0.01);increased pulmonary levels of SOD and GSH and protein expressions of E-cadherin and SIRT1(P<0.05,P<0.01);decreased ROS level,IL-1β,IL-6,TNF-α mRNA expressions and p-ERK,p-PI3K,p-Akt,NOX4 protein expressions in vitro(P<0.05,P<0.01);and increased SIRT1 protein expression in vitro as well(P<0.01).CONCLUSION Being the main antitussive component of Suhuang antitussive capsule upon the PIC model,Sol A inhibits the inflammation via SIRT1/ERK signaling pathway and relieve the oxidative stress via PI3K/Akt/NOX4 signaling pathway.
5.Ameliorative effects of praeruptorin A from Suhuang antitussive capsules on cough variant asthma
Zi-Yao ZHAO ; Hong JIANG ; Yong-Yu OU ; Xiao-Yuan CHEN ; Nan WU ; Zi-Yu BAI ; Zhi-Hao ZHANG ; Ning-Hua TAN
Chinese Traditional Patent Medicine 2024;46(9):2904-2914
AIM To explore the effects of praeruptorin A from Suhuang antitussive capsules on cough variant asthma(CVA).METHODS The rats were randomly divided into the normal group,the model group,the dexamethasone group(0.5 mg/kg),the Suhuang antitussive capsules group(7 g/kg)and the low,medium and high dose praeruptorin A groups(15,30 and 60 mg/kg).The rat model of CVA was established by intraperitoneal injection of sensitizer(1 mg/mL ovalbumin and 10 mg/mL aluminum hydroxide)and aerosol inhalation of 1%ovalbumin followed by the corresponding dosing of drugs by gavage initiated on the 14th day.Another 14 days later,the rats had their pathological pulmonary changes observed by HE,Masson and PAS stainings;their number of inflammatory cells in bronchoalveolar lavage fluid(BALF)detected by hematology analyzer;and their levels of IL-4,IL-5,IL-13 and MUC5AC in BALF detected by ELISA.The RAW264.7 cell inflammatory model induced by lipopolysaccharide(LPS)was treated with 4,8,16 μmol/L praeruptorin A or 0.25 mg/mL Suhuang antitussive capsules,respectively.And the cells had their NO level detected by Griess method,and their ROS expression observed using fluorescence microscopy.The detections of the pulmonary and cellular mRNA expressions of IL-6,IL-1β,COX-2,iNOS and PPAR-γ by RT-qPCR;and the protein expressions of p-P65,P65,p-IκBα,IκBα,NLRP3,caspase-1(p20)and IL-1β by Western blot were conducted in both the cells and the rats.RESULTS The in vivo result showed that praeruptorin A reduced the cough frequency(P<0.01);prolonged the cough latency(P<0.05,P<0.01);reduced the number of eosinophils and neutrophils in BALF(P<0.05,P<0.01);decreased the levels of IL-4,IL-5,IL-13 and MUC5AC in BALF and the pulmonary mRNA expressions of IL-6,IL-1β,COX-2 and iNOS(P<0.05,P<0.01);and decreased the phosphorylation of P65 and IκBα protein and NLRP3,caspase-1(p20)and IL-1β protein expressions(P<0.05,P<0.01)as well.The in vitro result showed that praeruptorin A inhibited the release of LPS-induced NO and reduce the ROS level(P<0.01);decreased the mRNA expressions of IL-1β,COX-2 and iNOS(P<0.05,P<0.01);increased PPAR-γ mRNA expression(P<0.05),and decreased the phosphorylation of P65 and IκBα protein and the expression of NLRP3 protein(P<0.05,P<0.01).CONCLUSION Praeruptorin A,one of the main antitussive components of Suhuang antitussive capsules,may improve CVA because of its anti-inflammatory and antitussive role by inhibiting the activation of NF-κB signaling pathway and reducing the expression of NLRP3 inflammatory corpuscles.
6.Analysis of surgical situations and prognosis of pancreaticoduodenectomy in Jiangsu province (a report of 2 886 cases)
Zipeng LU ; Xin GAO ; Hao CHENG ; Ning WANG ; Kai ZHANG ; Jie YIN ; Lingdi YIN ; Youting LIN ; Xinrui ZHU ; Dongzhi WANG ; Hongqin MA ; Tongtai LIU ; Yongzi XU ; Daojun ZHU ; Yabin YU ; Yang YANG ; Fei LIU ; Chao PAN ; Jincao TANG ; Minjie HU ; Zhiyuan HUA ; Fuming XUAN ; Leizhou XIA ; Dong QIAN ; Yong WANG ; Susu WANG ; Wentao GAO ; Yudong QIU ; Dongming ZHU ; Yi MIAO ; Kuirong JIANG
Chinese Journal of Digestive Surgery 2024;23(5):685-693
Objective:To investigate the surgical situations and perioperative outcome of pancreaticoduodenectomy in Jiangsu Province and the influencing factors for postoperative 90-day mortality.Methods:The retrospective case-control study was conducted. The clinicopathological data of 2 886 patients who underwent pancreaticoduodenectomy in 21 large tertiary hospitals of Jiangsu Quality Control Center for Pancreatic Diseases, including The First Affiliated Hospital of Nanjing Medical University, from March 2021 to December 2022 were collected. There were 1 732 males and 1 154 females, aged 65(57,71)years. Under the framework of the Jiangsu Provincial Pancreatic Disease Quality Control Project, the Jiangsu Quality Control Center for Pancreatic Diseases adopted a multi-center registration research method to establish a provincial electronic database for pancrea-ticoduodenectomy. Observation indicators: (1) clinical characteristics; (2) intraoperative and post-operative conditions; (3) influencing factors for 90-day mortality after pancreaticoduodenectomy. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(IQR), and comparison between groups was conducted using the Mann-Whitney U test. Count data were expressed as absolute numbers or constituent ratio, and comparison between groups was conducted using the chi-square test, continuity correction chi-square test and Fisher exact probability. Maximal Youden index method was used to determine the cutoff value of continuous variables. Univariate analysis was performed using the corresponding statistical methods based on data types. Multivariate analysis was performed using the Logistic multiple regression model. Results:(1) Clinical characteristics. Of the 2 886 patients who underwent pancreaticoduodenectomy, there were 1 175 and 1 711 cases in 2021 and 2022, respectively. Of the 21 hospitals, 8 hospitals had an average annual surgical volume of <36 cases for pancreaticoduodenectomy, 10 hospitals had an average annual surgical volume of 36-119 cases, and 3 hospitals had an average annual surgical volume of ≥120 cases. There were 2 584 cases performed pancreaticoduodenectomy in thirteen hospitals with an average annual surgical volume of ≥36 cases, accounting for 89.536%(2 584/2 886)of the total cases. There were 1 357 cases performed pancrea-ticoduodenectomy in three hospitals with an average annual surgical volume of ≥120 cases, accounting for 47.020%(1 357/2 886) of the total cases. (2) Intraoperative and postoperative conditions. Of the 2 886 patients, the surgical approach was open surgery in 2 397 cases, minimally invasive surgery in 488 cases, and it is unknown in 1 case. The pylorus was preserved in 871 cases, not preserved in 1 952 cases, and it is unknown in 63 cases. Combined organ resection was performed in 305 cases (including vascular resection in 209 cases), not combined organ resection in 2 579 cases, and it is unknown in 2 cases. The operation time of 2 885 patients was 290(115)minutes, the volume of intra-operative blood loss of 2 882 patients was 240(250)mL, and the intraoperative blood transfusion rate of 2 880 patients was 27.153%(782/2 880). Of the 2 886 patients, the invasive treatment rate was 11.342%(327/2 883), the unplanned Intensive Care Unit (ICU) treatment rate was 3.087%(89/2 883), the reoperation rate was 1.590%(45/2 830), the duration of postoperative hospital stay was 17(11)days, the hospitalization mortality rate was 0.798%(23/2 882), and the failure rate of rescue data in 2 083 cases with severe complications was 6.529%(19/291). There were 2 477 patients receiving postoperative 90-day follow-up, with the 90-day mortality of 2.705%(67/2477). The total incidence rate of complication in 2 886 patients was 58.997%(1 423/2 412). The incidence rate of severe complication was 13.970%(291/2 083). The comprehensive complication index was 8.7(22.6) in 2 078 patients. (3) Influencing factors for 90-day mortality after pancreaticoduodenectomy. Results of multivariate analysis showed that age ≥ 70 years, postoperative invasive treatment, and unplanned ICU treatment were independent risk factors for 90-day mortality after pancreaticoduodenectomy ( odds ratio=2.403, 2.609, 16.141, 95% confidence interval as 1.281-4.510, 1.298-5.244, 7.119-36.596, P<0.05). Average annual surgical volume ≥36 cases in the hospital was an independent protective factor for 90-day mortality after pancreaticoduodenectomy ( odds ratio=0.368, 95% confidence interval as 0.168-0.808, P<0.05). Conclusions:Pancreaticoduodenectomy in Jiangsu Province is highly con-centrated in some hospitals, with a high incidence of postoperative complications, and the risk of postoperative 90-day mortality is significant higher than that of hospitallization mortality. Age ≥ 70 years, postoperative invasive treatment, and unplanned ICU treatment are independent risk factors for 90-day motality after pancreaticoduodenectomy, and average annual surgical volume ≥36 cases in the hospital is an independent protective factor.
7.Design,numerical simulation and experimental study of novel oxygenator
Ming-Hao YUE ; Shi-Yao ZHANG ; Ji-Nian LI ; Hui-Chao LIU ; Zi-Hua SU ; Ya-Wei WANG ; Zeng-Sheng CHEN ; Shi-Hang LIN ; Jin-Yu LI ; Ya-Ke CHENG ; Yong-Fei HU ; Cun-Ding JIA ; Ming-Zhou XU
Chinese Medical Equipment Journal 2024;45(3):23-28
Objective To design a novel oxygenator to solve the existing problems of extracorporeal membrane oxygenation(ECMO)machine in high transmembrane pressure difference,low efficiency of blood oxygen exchange and susceptibility to thrombosis.Methods The main body of the oxygenator vascular access flow field was gifted with a flat cylindrical shape.The topology of the vascular access was modeled in three dimensions,and the whole flow field was cut into a blood inlet section,an inlet buffer,a heat exchange zone,a blood oxygen exchange zone,an outlet buffer and a blood outlet section.The oxygenator was compared with Quadrox oxygenator by means of ANSYS FLUENT-based simulation and prototype experiments.Results Simulation calculations showed the oxygenator designed was comparable to the clinically used ones in general,and gained advantages in transmembrane pressure difference,blood oxygen exchange and flow uniformity.Experimental results indicated that the oxygenator behaved better than Quadrox oxygenator in transmembrane pressure difference and blood oxygen exchange.Conclusion The oxygenator has advantages in transmem-brane pressure difference,temperature change,blood oxygen ex-change and low probability of thrombosis.[Chinese Medical Equipment Journal,2024,45(3):23-28]
8.Exploring Symptom Cluster Patterns in Adult Cancer Patients Undergoing Chemotherapy: A Systematic Review
Pan YANG ; Hui-juan MEI ; Hao-yu ZHAO ; Rong-rong WU ; Yong-qin GE ; Yin LU
Journal of Korean Academy of Nursing 2024;54(4):478-494
Purpose:
This systematic review aimed to scrutinize the progression of symptom cluster research in adult cancer patients who received primary or adjuvant chemotherapy between 2001 and 2023, providing a comprehensive understanding of clinical practice and future research.
Methods:
PubMed, Ovid MEDLINE, Excerpta Medica Database, Cumulative Index to Nursing and Allied Health Literature, Cochrane Library, and Web of Science databases were searched for theme words and free words related to symptom clusters, cancer, and chemotherapy. Eligible studies were published between January 1, 2001, and May 30, 2023; adults who were diagnosed with cancer and received primary or adjuvant chemotherapy were evaluated.
Results:
Twenty-eight studies were included in this review. The Memorial Symptom Assessment Scale emerged as the predominant instrument and exploratory factor analysis was the most frequently employed statistical method to identify symptom clusters. Psychological, gastrointestinal, and physical image symptom clusters were the most commonly delineated. Furthermore, the temporal stability of the symptom clusters showed varying dynamics, with psychological symptom clusters displaying relative consistency over time.
Conclusion
Interventions are needed for the most common and stable symptoms in patients with cancer undergoing chemotherapy. Future endeavors may necessitate more longitudinal studies to delve deeper into the temporal stability and dynamic variations of symptom clusters. Such investigations hold promise for advancing symptom cluster research, elucidating the underlying mechanisms, and fostering the development of targeted interventions, thereby enriching the symptom management paradigm in oncological care.
9.Exploring Symptom Cluster Patterns in Adult Cancer Patients Undergoing Chemotherapy: A Systematic Review
Pan YANG ; Hui-juan MEI ; Hao-yu ZHAO ; Rong-rong WU ; Yong-qin GE ; Yin LU
Journal of Korean Academy of Nursing 2024;54(4):478-494
Purpose:
This systematic review aimed to scrutinize the progression of symptom cluster research in adult cancer patients who received primary or adjuvant chemotherapy between 2001 and 2023, providing a comprehensive understanding of clinical practice and future research.
Methods:
PubMed, Ovid MEDLINE, Excerpta Medica Database, Cumulative Index to Nursing and Allied Health Literature, Cochrane Library, and Web of Science databases were searched for theme words and free words related to symptom clusters, cancer, and chemotherapy. Eligible studies were published between January 1, 2001, and May 30, 2023; adults who were diagnosed with cancer and received primary or adjuvant chemotherapy were evaluated.
Results:
Twenty-eight studies were included in this review. The Memorial Symptom Assessment Scale emerged as the predominant instrument and exploratory factor analysis was the most frequently employed statistical method to identify symptom clusters. Psychological, gastrointestinal, and physical image symptom clusters were the most commonly delineated. Furthermore, the temporal stability of the symptom clusters showed varying dynamics, with psychological symptom clusters displaying relative consistency over time.
Conclusion
Interventions are needed for the most common and stable symptoms in patients with cancer undergoing chemotherapy. Future endeavors may necessitate more longitudinal studies to delve deeper into the temporal stability and dynamic variations of symptom clusters. Such investigations hold promise for advancing symptom cluster research, elucidating the underlying mechanisms, and fostering the development of targeted interventions, thereby enriching the symptom management paradigm in oncological care.
10.Strategies and Recommendations for the Development of Clinical Machine Learning Predictive Models
Zhengyao HOU ; Jinqi LI ; Yong YANG ; Mengting LI ; Hao SHEN ; Huan CHANG ; Xinyu LIU ; Bo DENG ; Guangjie GAO ; Yalin WEN ; Shiyue LIANG ; Yanqiu YU ; Shundong LEI ; Xingwei WU
Herald of Medicine 2024;43(12):2048-2056
Objective To propose strategies for developing clinical predictive models,aiming to assist researchers in conducting standardized clinical prediction model studies.Methods Literature review was conducted to summarize the operational steps and content for developing clinical predictive models.Then,a methodological framework was summarized and refined through expert consultation.Results The 11-step methodological framework for developing clinical predictive models was obtained by synthesizing the experience of 456 clinical predictive modeling studies and expert consultation,and the details were analyzed and elaborated.Conclusions This study presents methodological strategies and recommendations for the development of clinical predictive models,intended to serve as a guide for researchers.

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