With the rapid development of medical big data and artificial intelligence,Clinical Prediction Models(CPMs)have become pivotal tools for disease prevention,diagnosis,and treatment.Current research predominantly focuses on the economic analysis of pharmacological or public health interventions,yet a comprehensive methodological framework for the economic evaluation of CPMs has been notably absent.The Guidelines for Economic Evaluation of Clinical Prediction Models(hereafter the Guidelines),jointly initiated by the Chinese Research Hospital Association and Peking University,Tsinghua University,and Capital Medical University,adheres to the WHO Handbook for Guideline Development and the Reporting Items for Practice Guidelines in Healthcare(RIGHT)standards.A multidisciplinary collaboration,including a steering committee,expert panel,secretariat,and external review group,was established to develop the guideline following evidence-based principles and procedures.Consensus recommendations were formulated through the Delphi method.It describes the background,objectives,target group,and the development methodology and process,ensuring the entire compilation process of the Guidelines is transparent and standardized.Through comprehensive evidence retrieval,systematic evidence appraisal,and a scientific approach to forming recommendations,the scientific rigor and validity of the Guidelines were further enhanced.

With the rapid development of medical big data and artificial intelligence,Clinical Prediction Models(CPMs)have become pivotal tools for disease prevention,diagnosis,and treatment.Current research predominantly focuses on the economic analysis of pharmacological or public health interventions,yet a comprehensive methodological framework for the economic evaluation of CPMs has been notably absent.The Guidelines for Economic Evaluation of Clinical Prediction Models(hereafter the Guidelines),jointly initiated by the Chinese Research Hospital Association and Peking University,Tsinghua University,and Capital Medical University,adheres to the WHO Handbook for Guideline Development and the Reporting Items for Practice Guidelines in Healthcare(RIGHT)standards.A multidisciplinary collaboration,including a steering committee,expert panel,secretariat,and external review group,was established to develop the guideline following evidence-based principles and procedures.Consensus recommendations were formulated through the Delphi method.It describes the background,objectives,target group,and the development methodology and process,ensuring the entire compilation process of the Guidelines is transparent and standardized.Through comprehensive evidence retrieval,systematic evidence appraisal,and a scientific approach to forming recommendations,the scientific rigor and validity of the Guidelines were further enhanced.

Objective:To analyze the clinical characteristics, distribution of common pathogenic bacteria and drug resistance in children with non-chronic osteomyelitis, to provide a basis for empirical antimicrobial drug selection.Methods:This study was a retrospective analysis cohort study. Clinical data, pathogenic bacteria and drug sensitivity test results of 289 children aged 0 to 18 years with non-chronic osteomyelitis who were hospitalized in the Pediatrics Hospital of Fudan University from January 2013 to June 2023 were collected retrospectively. Statistical analyses were performed using chi-square test.Results:Of the 289 children, 188(65.1%) were male, with a male to female ratio of 1.86∶1, and the age was 3.00(0.66, 8.00) years. The age less than six years amounted 65.1% (188/289). The incidence was the highest from December to February of the following year, reaching 32.5%(94/289). The clinical manifestations were fever in 193 cases (66.8%), fever with localized pain in 47 cases (16.3%), and fever with localized swelling and fever with localized swelling and pain in 39 cases (13.5%) each. Single bone involvement was observed in 242(83.7%) cases, including 88(36.4%) femur, 47(19.4%) tibia, and 37(15.3%) humerus. Of the 130 pathogen-positive cases, 102(78.5%) were Staphylococcus aureus (SA) including 45(44.1%) methicillin-resistant Staphylococcus aureus (MRSA), 10(7.7%) were Pseudomonas aeruginosa, and 3(2.3%) each were Klebsiella pneumoniae and Staphylococcus mansoni. The rate of MRSA detection in SA fluctuated each year from 2013 to 2023, with the highest in 2017, when eight out of 13 SA cases were MRSA. The resistance rates of all SA to vancomycin, linezolid, moxifloxacin, ciprofloxacin, gentamicin, rifampicin, ceflorin, tigecycline, ticlosporin, fosfomycin, daptomycin, furotoxin, quinupristin/dalfopristin were all zero, and the differences in resistance rates of methicillin-susceptible Staphylococcus aureus (MSSA) and MRSA to cefazolin, cefuroxime, benzoxiline, ampicillin/sulbactam, and clindamycin were all statistically significant ( χ2=68.91, 68.91, 82.00, 68.91 and 9.20, respectively, all P<0.05). Intravenous anti-infective treatment was administered for 24(35, 47) days in 289 children with osteomyelitis, for a total duration of 42.00(35.00, 47.00) days. After treatment, 287 cases (99.3%) were discharged with improvement, while two cases (0.7%) died. One death was due to phagocytosis syndrome and septic shock, and the other death was due to septic shock and multiple organ dysfunction. Conclusions:Non-chronic osteomyelitis in children is most common in male children under six years old, and the most common sites are femur, tibia and humerus. The main clinical manifestations are fever, localized swelling and pain. SA was the most common causative agent. No SA strain resistant to vancomycin, linezolid, moxifloxacin, ciprofloxacin, gentamicin, rifampicin, ceflorin, tigecycline, ticlosporin, fosfomycin, daptomycin, furotoxin, quinupristin/dalfopristin is found.

Objective:To investigate the association of blood lipids and body mass index (BMI) with hyperuricemia (HUA) in the elderly.Methods:It was a cross-sectional study. A total of 114 391 elderly individuals received health examinations at primary healthcare institutions in Wujin District from January to December in 2022. The health examination included questionnaire survey, physical examination and laboratory examination. The multivariate logistic regression and restricted cubic spline (RCS) plots were used to analyze the association and dose-response relationship of blood lipid and BMI with HUA. The mediating effect model was used to explore the mediation effect of BMI on the association between blood lipid and HUA.Results:Among the 112 415 subjects, 18 506 (16.46%) were checked with HUA. After adjusting for relevant confounders, total cholesterol (TC) ( OR=1.20, 95% CI: 1.16-1.23), triglyceride (TG) ( OR=1.46, 95% CI: 1.44-1.49), high density lipoprotein cholesterol (HDL-C) ( OR=0.74, 95% CI: 0.73-0.76), low density lipoprotein cholesterol (LDL-C) ( OR=1.14, 95% CI: 1.12-1.15) and BMI ( OR=1.42, 95% CI: 1.39-1.44) were all associated with HUA (all P0.05). The RCS analysis revealed that TG, HDL-C, and LDL-C each exhibited a nonlinear dose-response relationship with HUA, the inflection points was 3.00 mmol/L, 1.57 mmol/L and 2.50 mmol/L, respectively (all P-nonlinear0.001). The results of interaction showed that there were additive interaction between high TC( S=1.27 , 95% CI: 1.17-1.37), high TG( S=1.32 , 95% CI: 1.25-1.40), high LDL-C( S=1.23 , 95% CI: 1.14-1.34) and overweight/obesity with HUA (all P0.05). The results of mediation effect analysis showed that the mediation effect of BMI on the association between blood lipids (HDL-C, LDL-C, TG and TC) and HUA, from high to low, were as follows: 22.5% (95% CI: 20.8%-24.2%), 13.9% (95% CI: 12.0%-16.2%), 13.5% (95% CI: 12.7%-14.4%) and-3.9% (95% CI:-6.6%--1.8%). Conclusion:The blood lipid levels and BMI are positively correlated with HUA in the elderly.

Objective　To analyze and study the status quo and deficiencies in the construction of talent teams at all levels of CDCs in Hainan Province and put forward countermeasures to provide a reference basis for the high-quality development of talent team construction in all levels of CDCs in Hainan Province. Methods Using field surveys and data retrieval, spatial analysis was employed to compare the overall differences in human resource status of the provincial-level CDC and CDCs in five regional areas (East, West, South, North, and Central Hainan). The coordination between human resource allocation and development strategies was analyzed. A descriptive analysis mainly utilized CDC survey questionnaires and other research forms to explore the health human resources of the province's CDCs. Results The professional and technical personnel in the provincial CDCs comprise 1 431 individuals, accounting for 82.3% (1 431/1 739) of the total number of actual employees, which falls short of the Central Institutional Reform Commission's (CIRC) mandate that technical professionals comprise at least 85% of the total workforce (CIRC Document [2014] No. 2). Among Hainan's CDC personnel, 115 individuals are recognized as high-level talents within the Hainan Free Trade Port framework. These include one Class C talent, 22 Class D talents, and 93 Class E talents. Class A, B, and C-level talents are deficient. The majority of staff at both the provincial and regional CDCs hold bachelor's degrees. There is a significant proportion of staff with associate degrees or lower qualifications, coupled with a severe shortage of highly educated personnel. Postgraduates with master’s degrees or above account for 27.8% (65/233) in the provincial CDC, indicating low educational credentials among personnel in Hainan's CDCs. The central region, characterized by slower economic and social development, faces greater challenges in attracting and retaining high-level talent. There is a scarcity of public health professionals with interdisciplinary expertise. Some public health staff lack clinical knowledge, experience, and skills in disease treatment. Furthermore, there is a need to strengthen on-site emergency response capabilities for public health emergencies. The structural ratio of senior, intermediate, and junior professional and technical positions in the provincial CDC is 40%∶45%∶15%. The position settings are limited to ranking levels without distinction by professional category, leading to a bottleneck-type competition like crossing the "one log bridge" for technical position promotions. Conclusion　Hainan Province faces significant challenges in developing its public health workforce, both in technical expertise and management capacity. Especially under the context of the closure operation of the Hainan Free Trade Port, it is necessary to continuously strengthen top-level talent design to cultivate a favorable policy, system, and cultural environment, thereby promoting the sustained and healthy development of the province's public health career.

Objective:To investigate the association of blood lipids and body mass index (BMI) with hyperuricemia (HUA) in the elderly.Methods:It was a cross-sectional study. A total of 114 391 elderly individuals received health examinations at primary healthcare institutions in Wujin District from January to December in 2022. The health examination included questionnaire survey, physical examination and laboratory examination. The multivariate logistic regression and restricted cubic spline (RCS) plots were used to analyze the association and dose-response relationship of blood lipid and BMI with HUA. The mediating effect model was used to explore the mediation effect of BMI on the association between blood lipid and HUA.Results:Among the 112 415 subjects, 18 506 (16.46%) were checked with HUA. After adjusting for relevant confounders, total cholesterol (TC) ( OR=1.20, 95% CI: 1.16-1.23), triglyceride (TG) ( OR=1.46, 95% CI: 1.44-1.49), high density lipoprotein cholesterol (HDL-C) ( OR=0.74, 95% CI: 0.73-0.76), low density lipoprotein cholesterol (LDL-C) ( OR=1.14, 95% CI: 1.12-1.15) and BMI ( OR=1.42, 95% CI: 1.39-1.44) were all associated with HUA (all P0.05). The RCS analysis revealed that TG, HDL-C, and LDL-C each exhibited a nonlinear dose-response relationship with HUA, the inflection points was 3.00 mmol/L, 1.57 mmol/L and 2.50 mmol/L, respectively (all P-nonlinear0.001). The results of interaction showed that there were additive interaction between high TC( S=1.27 , 95% CI: 1.17-1.37), high TG( S=1.32 , 95% CI: 1.25-1.40), high LDL-C( S=1.23 , 95% CI: 1.14-1.34) and overweight/obesity with HUA (all P0.05). The results of mediation effect analysis showed that the mediation effect of BMI on the association between blood lipids (HDL-C, LDL-C, TG and TC) and HUA, from high to low, were as follows: 22.5% (95% CI: 20.8%-24.2%), 13.9% (95% CI: 12.0%-16.2%), 13.5% (95% CI: 12.7%-14.4%) and-3.9% (95% CI:-6.6%--1.8%). Conclusion:The blood lipid levels and BMI are positively correlated with HUA in the elderly.

Objective:To analyze the clinical characteristics, distribution of common pathogenic bacteria and drug resistance in children with non-chronic osteomyelitis, to provide a basis for empirical antimicrobial drug selection.Methods:This study was a retrospective analysis cohort study. Clinical data, pathogenic bacteria and drug sensitivity test results of 289 children aged 0 to 18 years with non-chronic osteomyelitis who were hospitalized in the Pediatrics Hospital of Fudan University from January 2013 to June 2023 were collected retrospectively. Statistical analyses were performed using chi-square test.Results:Of the 289 children, 188(65.1%) were male, with a male to female ratio of 1.86∶1, and the age was 3.00(0.66, 8.00) years. The age less than six years amounted 65.1% (188/289). The incidence was the highest from December to February of the following year, reaching 32.5%(94/289). The clinical manifestations were fever in 193 cases (66.8%), fever with localized pain in 47 cases (16.3%), and fever with localized swelling and fever with localized swelling and pain in 39 cases (13.5%) each. Single bone involvement was observed in 242(83.7%) cases, including 88(36.4%) femur, 47(19.4%) tibia, and 37(15.3%) humerus. Of the 130 pathogen-positive cases, 102(78.5%) were Staphylococcus aureus (SA) including 45(44.1%) methicillin-resistant Staphylococcus aureus (MRSA), 10(7.7%) were Pseudomonas aeruginosa, and 3(2.3%) each were Klebsiella pneumoniae and Staphylococcus mansoni. The rate of MRSA detection in SA fluctuated each year from 2013 to 2023, with the highest in 2017, when eight out of 13 SA cases were MRSA. The resistance rates of all SA to vancomycin, linezolid, moxifloxacin, ciprofloxacin, gentamicin, rifampicin, ceflorin, tigecycline, ticlosporin, fosfomycin, daptomycin, furotoxin, quinupristin/dalfopristin were all zero, and the differences in resistance rates of methicillin-susceptible Staphylococcus aureus (MSSA) and MRSA to cefazolin, cefuroxime, benzoxiline, ampicillin/sulbactam, and clindamycin were all statistically significant ( χ2=68.91, 68.91, 82.00, 68.91 and 9.20, respectively, all P<0.05). Intravenous anti-infective treatment was administered for 24(35, 47) days in 289 children with osteomyelitis, for a total duration of 42.00(35.00, 47.00) days. After treatment, 287 cases (99.3%) were discharged with improvement, while two cases (0.7%) died. One death was due to phagocytosis syndrome and septic shock, and the other death was due to septic shock and multiple organ dysfunction. Conclusions:Non-chronic osteomyelitis in children is most common in male children under six years old, and the most common sites are femur, tibia and humerus. The main clinical manifestations are fever, localized swelling and pain. SA was the most common causative agent. No SA strain resistant to vancomycin, linezolid, moxifloxacin, ciprofloxacin, gentamicin, rifampicin, ceflorin, tigecycline, ticlosporin, fosfomycin, daptomycin, furotoxin, quinupristin/dalfopristin is found.

Objective: Depression was common during coronavirus disease-2019 (COVID-19) pandemic, while the association of perceived stress with depression among vaccinated healthcare workers has not been investigated. This study aimed to address this issue. Methods: We included a total of 898 fully vaccinated healthcare workers during the outbreak of severe acute respiratory syndrome coronavirus 2 Delta variant in Nanjing, 2021. Depression was ascertained by Patient Health Questionnaire-9, with a cut-off score of ≥5 indicative of mild-to-severe depression. Perceived stress, resilience, and compassion fatigue were assessed by Perceived Stress Scale-10, Resilience Scale-25, and Professional Quality of Life Scale version-5, respectively. Logistic regression analyses were used to estimate the odds ratio (OR) and 95% confidence interval (CI), along with subgroup and mediation analyses. Results: The prevalence of mild-to-severe depression was 41.1% in vaccinated healthcare workers. The odd of mild-to-severe depression was increased with higher perceived stress. Compared with vaccinated healthcare workers with the lowest tertile of perceived stress, those with the highest tertile had increased odds of mild-to-severe depression by 120% (OR 2.20, 95% CI 1.46 to 3.31) after multivariable-adjustment. However, perceived stress was not associated with mild-to-severe depression in vaccinated healthcare workers with strong resilience, but was in those with weak resilience (pinteraction=0.004). Further analysis showed that compassion fatigue mediated the relationship between perceived stress and mild-to-severe depression, with a mediating effect of 49.7%. Conclusion Perceived stress was related to an increased odd of mild-to-severe depression in vaccinated healthcare workers during COVID-19 pandemic, and this relationship might be explained by compassion fatigue.

Liver fibrosis is a reversible pathological process caused by chronic liver damage and a major risk factor for hepatocellular carcinoma (HCC). Hepatic stellate cell (HSC) activation is considered the main target for liver fibrosis therapy. However, the efficiency of this strategy is limited due to the complex microenvironment of liver fibrosis, including excessive extracellular matrix (ECM) deposition and hypoxia-induced imbalanced ECM metabolism. Herein, nilotinib (NIL)-loaded hyaluronic acid (HA)-coated Ag@Pt nanotriangular nanozymes (APNH NTs) were developed to inhibit HSCs activation and remodel the microenvironment of liver fibrosis. APNH NTs efficiently eliminated intrahepatic reactive oxygen species (ROS) due to their inherent superoxide dismutase (SOD) and catalase (CAT) activities, thereby downregulating the expression of NADPH oxidase-4 (NOX-4) and inhibiting HSCs activation. Simultaneously, the oxygen produced by the APNH NTs further alleviated the hypoxic microenvironment. Importantly, the released NIL promoted collagen depletion by suppressing the expression of tissue inhibitor of metalloproteinase-1 (TIMP-1), thus synergistically remodeling the microenvironment of liver fibrosis. Notably, an in vivo study in CCl₄-induced mice revealed that APNH NTs exhibited significant antifibrogenic effects without obvious long-term toxicity. Taken together, the data from this work suggest that treatment with the synthesized APNH NTs provides an enlightening strategy for remodeling the microenvironment of liver fibrosis with boosted antifibrogenic activity.

BACKGROUND: Pulmonary microvascular endothelial cells (PMVECs) were not complex, and the endothelial barrier was destroyed in the pathogenesis progress of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Previous studies have demonstrated that hepatocyte growth factor (HGF), which was secreted by bone marrow mesenchymal stem cells, could decrease endothelial apoptosis. We investigated whether mTOR/STAT3 signaling acted in HGF protective effects against oxidative stress and mitochondria-dependent apoptosis in lipopolysaccharide (LPS)-induced endothelial barrier dysfunction and ALI mice. METHODS: In our current study, we introduced LPS-induced PMEVCs with HGF treatment. To investigate the effects of mammalian target of rapamycin (mTOR)/signal transducer and activator of transcription 3 (STAT3) pathway in endothelial oxidative stress and mitochondria-dependent apoptosis, mTOR inhibitor rapamycin and STAT3 inhibitor S3I-201 were, respectively, used to inhibit mTOR/STAT3 signaling. Moreover, lentivirus vector-mediated mTORC1 (Raptor) and mTORC2 (Rictor) gene knockdown modifications were introduced to evaluate mTORC1 and mTORC1 pathways. Calcium measurement, reactive oxygen species (ROS) production, mitochondrial membrane potential and protein, cell proliferation, apoptosis, and endothelial junction protein were detected to evaluate HGF effects. Moreover, we used the ALI mouse model to observe the mitochondria pathological changes with an electron microscope in vivo. RESULTS: Our study demonstrated that HGF protected the endothelium via the suppression of ROS production and intracellular calcium uptake, which lead to increased mitochondrial membrane potential (JC-1 and mitochondria tracker green detection) and specific proteins (complex I), raised anti-apoptosis Messenger Ribonucleic Acid level (B-cell lymphoma 2 and Bcl-xL), and increased endothelial junction proteins (VE-cadherin and occludin). Reversely, mTOR inhibitor rapamycin and STAT3 inhibitor S3I-201 could raise oxidative stress and mitochondria-dependent apoptosis even with HGF treatment in LPS-induced endothelial cells. Similarly, mTORC1 as well as mTORC2 have the same protective effects in mitochondria damage and apoptosis. In in vivo experiments of ALI mouse, HGF also increased mitochondria structural integrity via the mTOR/STAT3 pathway. CONCLUSION In all, these reveal that mTOR/STAT3 signaling mediates the HGF suppression effects to oxidative level, mitochondria-dependent apoptosis, and endothelial junction protein in ARDS, contributing to the pulmonary endothelial survival and barrier integrity.
Animals ; Apoptosis ; Calcium/metabolism* ; Endothelial Cells/metabolism* ; Endothelium/metabolism* ; Hepatocyte Growth Factor/metabolism* ; Lipopolysaccharides/pharmacology* ; Mammals/metabolism* ; Mechanistic Target of Rapamycin Complex 1/metabolism* ; Mechanistic Target of Rapamycin Complex 2/metabolism* ; Mice ; Mitochondria/metabolism* ; Oxidative Stress ; Reactive Oxygen Species/metabolism* ; Respiratory Distress Syndrome ; Sirolimus/pharmacology* ; TOR Serine-Threonine Kinases/metabolism*