OBJECTIVES: Non-small cell lung cancer (NSCLC) is associated with poor prognosis, with 30% of patients diagnosed at an advanced stage. Mutations in the EGFR and KRAS genes are important prognostic factors for NSCLC, and targeted therapies can significantly improve survival in these patients. Although tissue biopsy remains the gold standard for detecting gene mutations, it has limitations, including invasiveness, sampling errors due to tumor heterogeneity, and poor reproducibility. This study aims to develop machine learning models based on radiomic features to predict EGFR and KRAS gene mutation status in NSCLC patients, thereby providing a reference for precision oncology. METHODS: Imaging and mutation data from eligible NSCLC patients were obtained from the publicly available Lung-PET-CT-Dx dataset in The Cancer Imaging Archive (TCIA). A three-dimensional-convolutional neural network (3D-CNN) was used to extract imaging features from the regions of interest (ROI). The LightGBM algorithm was employed to build classification models for predicting EGFR and KRAS gene mutation status. Model performance was evaluated using 5-fold cross-validation, with receiver operator characteristic (ROC) curves, area under the curve (AUC), accuracy, sensitivity, and specificity used for validation. RESULTS: The models effectively predicted EGFR and KRAS mutations in NSCLC patients, achieving an AUC of 0.95 for EGFR mutations and 0.90 for KRAS. The models also demonstrated high accuracy (EGFR 89.66%; KRAS 87.10%), sensitivity (EGFR 93.33%; KRAS 87.50%), and specificity (EGFR 85.71%; KRAS 86.67%). CONCLUSIONS A radiogenomics-machine learning predictive model can serve as a non-invasive tool for anticipating EGFR and KRAS gene mutation status in NSCLC patients.
Humans ; Carcinoma, Non-Small-Cell Lung/diagnostic imaging* ; Lung Neoplasms/diagnostic imaging* ; Mutation ; Proto-Oncogene Proteins p21(ras)/genetics* ; ErbB Receptors/genetics* ; Machine Learning ; Positron Emission Tomography Computed Tomography ; Female ; Male ; Neural Networks, Computer ; Middle Aged ; Aged

As the brain's resident immune cells, microglia perform crucial functions such as phagocytosis, neuronal network maintenance, and injury restoration by adopting various phenotypes. Dynamic imaging of these phenotypes is essential for accessing brain diseases and therapeutic responses. Although numerous probes are available for imaging pro-inflammatory microglia, no PET tracers have been developed specifically to visualize anti-inflammatory microglia. In this study, we present an ¹⁸F-labeled PET tracer (QTFT) that targets the P2Y₁₂, a receptor highly expressed on anti-inflammatory microglia. [¹⁸F]QTFT exhibited high binding affinity to the P2Y₁₂ (14.43 nmol/L) and superior blood-brain barrier permeability compared to other candidates. Micro-PET imaging in IL-4-induced neuroinflammation models showed higher [¹⁸F]QTFT uptake in lesions compared to the contralateral normal brain tissues. Importantly, this specific uptake could be blocked by QTFT or a P2Y₁₂ antagonist. Furthermore, [¹⁸F]QTFT visualized brain lesions in mouse models of epilepsy, glioma, and aging by targeting the aberrantly expressed P2Y₁₂ in anti-inflammatory microglia. In a pilot clinical study, [¹⁸F]QTFT successfully located epileptic foci, showing enhanced radioactive signals in a patient with epilepsy. Collectively, these studies suggest that [¹⁸F]QTFT could serve as a valuable diagnostic tool for imaging various brain disorders by targeting P2Y₁₂ overexpressed in anti-inflammatory microglia.

Periodontal bone defects, primarily caused by periodontitis, are highly prevalent in clinical settings and manifest as bone fenestration, dehiscence, or attachment loss, presenting a significant challenge to oral health. In regenerative medicine, harnessing developmental principles for tissue repair offers promising therapeutic potential. Of particular interest is the condensation of progenitor cells, an essential event in organogenesis that has inspired clinically effective cell aggregation approaches in dental regeneration. However, the precise cellular coordination mechanisms during condensation and regeneration remain elusive. Here, taking the tooth as a model organ, we employed single-cell RNA sequencing to dissect the cellular composition and heterogeneity of human dental follicle and dental papilla, revealing a distinct Platelet-derived growth factor receptor alpha (PDGFRA) mesenchymal stem/stromal cell (MSC) population with remarkable odontogenic potential. Interestingly, a reciprocal paracrine interaction between PDGFRA⁺ dental follicle stem cells (DFSCs) and CD31⁺ Endomucin⁺ endothelial cells (ECs) was mediated by Vascular endothelial growth factor A (VEGFA) and Platelet-derived growth factor subunit BB (PDGFBB). This crosstalk not only maintains the functionality of PDGFRA⁺ DFSCs but also drives specialized angiogenesis. In vivo periodontal bone regeneration experiments further reveal that communication between PDGFRA⁺ DFSC aggregates and recipient ECs is essential for effective angiogenic-osteogenic coupling and rapid tissue repair. Collectively, our results unravel the importance of MSC-EC crosstalk mediated by the VEGFA and PDGFBB-PDGFRA reciprocal signaling in orchestrating angiogenesis and osteogenesis. These findings not only establish a framework for deciphering and promoting periodontal bone regeneration in potential clinical applications but also offer insights for future therapeutic strategies in dental or broader regenerative medicine.
Receptor, Platelet-Derived Growth Factor alpha/metabolism* ; Humans ; Neovascularization, Physiologic/physiology* ; Dental Sac/cytology* ; Single-Cell Analysis ; Transcriptome ; Mesenchymal Stem Cells/metabolism* ; Bone Regeneration ; Animals ; Dental Papilla/cytology* ; Periodontium/physiology* ; Stem Cells/metabolism* ; Regeneration ; Angiogenesis

Objective:To evaluate the diagnostic efficacy and practicality of the Jaundice color card (JCard) as a screening tool for neonatal jaundice.Methods:Following the standards for reporting of diagnostic accuracy studies (STARD) statement, a multicenter prospective study was conducted in 9 hospitals in China from October 2019 to September 2021. A total of 845 newborns who were admitted to the hospital or outpatient department for liver function testing due to their own diseases. The inclusion criteria were a gestational age of ≥35 weeks, a birth weight of ≥2 000 g, and an age of ≤28 days. The neonate′s parents used the JCard to measure jaundice at the neonate′s cheek. Within 2 hours of the JCard measurement, transcutaneous bilirubin (TcB) was measured with a JH20-1B device and total serum bilirubin (TSB) was detected. The Pearson′s correlation analysis, Bland-Altman plots and the receiver operating characteristic (ROC) curve were used for statistic analysis.Results:Out of the 854 newborns, 445 were male and 409 were female; 46 were born at 35-36 weeks of gestational age and 808 were born at ≥37 weeks of gestational age. Additionally, 432 cases were aged 0-3 days, 236 cases were aged 4-7 days, and 186 cases were aged 8-28 days. The TSB level was (227.4±89.6) μmol/L, with a range of 23.7-717.0 μmol/L. The JCard level was (221.4±77.0) μmol/L and the TcB level was (252.5±76.0) μmol/L. Both the JCard and TcB values showed good correlation ( r=0.77 and 0.80, respectively) and agreements (96.0% (820/854) and 95.2% (813/854) of samples fell within the 95% limits of agreement, respectively) with TSB. The JCard value of 12 had a sensitivity of 0.93 and specificity of 0.75 for identifying a TSB ≥205.2?μmol/L, and a sensitivity of 1.00 and specificity of 0.35 for identifying a TSB ≥342.0?μmol/L. The TcB value of 205.2?μmol/L had a sensitivity of 0.97 and specificity of 0.60 for identifying TSB levels of 205.2 μmol/L, and a sensitivity of 1.00 and specificity of 0.26 for identifying TSB levels of 342.0 μmol/L. The areas under the ROC curve (AUC) of JCard for identifying TSB levels of 153.9, 205.2, 256.5, and 342.0 μmol/L were 0.96, 0.92, 0.83, and 0.83, respectively. The AUC of TcB were 0.94, 0.91, 0.86, and 0.87, respectively. There were both no significant differences between the AUC of JCard and TcB in identifying TSB levels of 153.9 and 205.2 μmol/L (both P>0.05). However, the AUC of JCard were both lower than those of TcB in identifying TSB levels of 256.5 and 342.0 μmol/L (both P<0.05). Conclusions:JCard can be used to classify different levels of bilirubin, but its diagnostic efficacy decreases with increasing bilirubin levels. When TSB level are ≤205.2 μmol/L, its diagnostic efficacy is equivalent to that of the JH20-1B. To prevent the misdiagnosis of severe jaundice, it is recommended that parents use a low JCard score, such as 12, to identify severe hyperbilirubinemia (TSB ≥342.0 μmol/L).

Healthy lifestyles and good living habits are effective strategies and important approaches to prevent chronic non-communicable diseases. With the development of evidence-based medicine, the evidence translation system has made some achievements in clinical practice. There is, however, no comprehensive, professional and efficient system for translating lifestyle evidence globally. Therefore, the Health Lifestyle Evidence (HLSE) Group of Lanzhou University constructed the HLSE Evidence Translation System (https://hlse.cn/), with the aim of synthesizing, evaluating, translating, and applying lifestyle-related evidence resources. This paper aims to introduce the functional module design of the evidence translation system, the system development process and testing, introduce the interface design and function demonstration, and explain the significance of constructing the HLSE.

Objective To explore the role and efficacy of VEGF and HGF gene adenovirus vector in promoting angiogenesis in ischemic tissue.Methods 84 Kunming mice were randomly divided into sham group,control group,VEGF group,HGF group and VEGF+HGF group,and the left lower limb ischemia model was established.The blood supply of ischemic tissue was observed by rheometer,and the expression levels of VEGF and HGF in each group were detected by Western Blot and ELISA.Immunohistochemical staining was used to detect angiogenesis(CD31,SMA)in ischemic tissues.Safety was assessed by side effects during treatment in mice.Results After the successful modeling,the blood flow velocity of the left lower limb in each group decreased significantly.On the 7th day after operation,the blood flow of the left lower limb in each group was significantly better than that on the 0th day after operation(P<0.05),and the blood flow of the left lower limb in Ad-VEGF-HGF group was significantly better than that in other groups(P<0.05).On the 28th day after operation,the blood flow of the left lower limb in Ad-VEGF-HGF group gradually stabilized,the blood flow in Ad-VEGF-HGF group was significantly better than that in other groups,and both VEGF group and HGF group were significantly better than the control group(P<0.05).On the 7th,14th,and 28th days following surgery,HGF and VEGF protein levels in the Ad-HGF,Ad-VEGF,and Ad-VEGF-HGF groups were substantially greater than those in the control group(P<0.05).The expression level in the Ad-VEGF-HGF group peaked on the 14th day(all P<0.001)and subsequently declined to preoperative levels on the 28th day after operation.Conclusion Ad-VEGF-HGF gene injection can effectively boost VEGF and HGF protein expression and rapidly reach the relative peak level,encour-aging angiogenesis after lower limb ischemia,increasing blood flow,and improving lower limb circulation.

Objective:To analyze clinical characteristics of primary pancreatic lymphoma (PPL) patients.Methods:Clinical features of 22 patients diagnosed as PPL admitted to Peking Union Medical College Hospital from January 2002 to May 2023 were analyzed retrospectively.Results:The median age was 56.4±13.3 years. The median time from onset to diagnosis was 1.0 (1.0, 3.0) months. The main clinical manifestations were abdominal pain (15/22), weight loss (14/22) and jaundice (10/22). Elevated lactate dehydrogenase (LDH) was observed in 15/20 (75%) patients. Only 2 (2/9, 22.2%) patients had increased CA199 levels and 2 (2/9, 22.2%) patients had increased CEA levels. The maximum tumor diameter was 5.0 (3.8, 6.9) cm. Contrast-enhanced CT mostly showed low enhancement lesions. Major pancreatic duct dilatation were rare on CT scan (4/20). Fifteen patients were confirmed by pancreatic pathology, of which 8 were obtained by surgery, 4 were obtained by CT or ultrasound-guided percutaneous biopsy, and 3 were obtained by EUS-FNA. The main pathological type was diffuse large B-cell lymphoma (14/22). 19 patients received chemotherapy, and 6 patients died with a median follow-up of 5.0 (1.5, 35.5) months.Conclusions:PPL is rare and easy to be misdiagnosed. Elevated LDH levels, normal tumor markers, and non-dilatation of main pancreatic duct are important diagnostic clues. It is important to obtain pathology by EUS-FNA and other methods for definite diagnosis.

Objective To assess the value of cardiac magnetic resonance(CMR)imaging for predicting adverse left ventricular remodeling in patients with ST-segment elevation myocardial infarction(STEMI).Methods We retrospectively analyzed the clinical data and serial CMR(cine and LGE sequences)images of 86 STEMI patients within 1 week and 5 months after percutaneous coronary intervention(PCI),including 25 patients with adverse LV remodeling and 61 without adverse LV remodeling,defined as an increase of left ventricular end-systolic volume(LVESV)over 15%at the second CMR compared to the initial CMR.The CMR images were analyzed for LV volume,infarct characteristics,and global and infarct zone myocardial function.The independent predictors of adverse LV remodeling following STEMI were analyzed using univariate and multivariate Logistic regression methods.Results The initial CMR showed no significant differences in LV volume or LV ejection fraction(LVEF)between the two groups,but the infarct mass and microvascular obstructive(MVO)mass were significantly greater in adverse LV remodeling group(P<0.05).Myocardial injury and cardiac function of the patients recovered over time in both groups.At the second CMR,the patients with adverse LV remodeling showed a significantly lower LVEF,a larger left ventricular end-systolic volume index(LVESVI)and a greater extent of infarct mass(P<0.001)with lower global peak strains and strain rates in the radial,circumferential,and longitudinal directions(P<0.05),infarct zone peak strains in the 3 directions,and infarct zone peak radial and circumferential strain rates(P<0.05).The independent predictors for adverse LV remodeling following STEMI included the extent of infarct mass(AUC=0.793,95%CI:0.693-0.873;cut-off value:30.67%),radial diastolic peak strain rate(AUC=0.645,95%CI:0.534-0.745;cut-off value:0.58%),and RAAS inhibitor(AUC= 0.699,95%CI:0.590-0.793).Conclusion The extent of infarct mass,peak radial diastolic strain rate,and RAAS inhibitor are independent predictors of adverse LV remodeling following STEMI.

Healthy lifestyles and good living habits are effective strategies and important approaches to prevent chronic non-communicable diseases. With the development of evidence-based medicine, the evidence translation system has made some achievements in clinical practice. There is, however, no comprehensive, professional and efficient system for translating lifestyle evidence globally. Therefore, the Health Lifestyle Evidence (HLSE) Group of Lanzhou University constructed the HLSE Evidence Translation System (https://hlse.cn/), with the aim of synthesizing, evaluating, translating, and applying lifestyle-related evidence resources. This paper aims to introduce the functional module design of the evidence translation system, the system development process and testing, introduce the interface design and function demonstration, and explain the significance of constructing the HLSE.

Objective To assess the value of cardiac magnetic resonance(CMR)imaging for predicting adverse left ventricular remodeling in patients with ST-segment elevation myocardial infarction(STEMI).Methods We retrospectively analyzed the clinical data and serial CMR(cine and LGE sequences)images of 86 STEMI patients within 1 week and 5 months after percutaneous coronary intervention(PCI),including 25 patients with adverse LV remodeling and 61 without adverse LV remodeling,defined as an increase of left ventricular end-systolic volume(LVESV)over 15%at the second CMR compared to the initial CMR.The CMR images were analyzed for LV volume,infarct characteristics,and global and infarct zone myocardial function.The independent predictors of adverse LV remodeling following STEMI were analyzed using univariate and multivariate Logistic regression methods.Results The initial CMR showed no significant differences in LV volume or LV ejection fraction(LVEF)between the two groups,but the infarct mass and microvascular obstructive(MVO)mass were significantly greater in adverse LV remodeling group(P<0.05).Myocardial injury and cardiac function of the patients recovered over time in both groups.At the second CMR,the patients with adverse LV remodeling showed a significantly lower LVEF,a larger left ventricular end-systolic volume index(LVESVI)and a greater extent of infarct mass(P<0.001)with lower global peak strains and strain rates in the radial,circumferential,and longitudinal directions(P<0.05),infarct zone peak strains in the 3 directions,and infarct zone peak radial and circumferential strain rates(P<0.05).The independent predictors for adverse LV remodeling following STEMI included the extent of infarct mass(AUC=0.793,95%CI:0.693-0.873;cut-off value:30.67%),radial diastolic peak strain rate(AUC=0.645,95%CI:0.534-0.745;cut-off value:0.58%),and RAAS inhibitor(AUC= 0.699,95%CI:0.590-0.793).Conclusion The extent of infarct mass,peak radial diastolic strain rate,and RAAS inhibitor are independent predictors of adverse LV remodeling following STEMI.