Objective:To analyze the clinical phenotypes and genetic characteristics of pediatric patients with neurofibromatosis type 1 (NF1).Methods:A cross-sectional study was adopted. Clinical and imaging data of 25 pediatric patients diagnosed as having NF1 in Department of Pediatric Neurology, Linyi People's Hospital Affiliated to Shandong Second Medical University from January 2024 to July 2025 were collected. Whole exome sequencing and Sanger sequencing were used to conduct genetic testing on the pediatric patients and his/her parents. Protein 3D modeling of the domestic and foreign unreported variations was conducted using SWISS-MODEL software.Results:Among the 25 pediatric patients with NF1, 14 were male (56%) and 11 were female (44%), with age ranging from 8 months to 18 years. All pediatric patients exhibited café-au-lait macules, and 7 (28%) presented with plexiform neurofibromas. Genetic test identified 4 types of NF1 variants: nonsense variant ( n=11, 44%), frameshift variant ( n=9, 36%), missense variant ( n=3, 12%), and splice-site variant ( n=2, 8%). Importantly, 5 novel NF1 variants were discovered, including c.3455T>A, c.3709dupG, c.2665_2684del, c.7092_7095delinsTA, and c.3260del. Three pediatric patients inherited NF1 variant from their parents, while the remaining 22 harbored de novo mutation. Conclusion:NF1 exhibits a broad clinical spectrum, primarily affecting the skin and nervous system; this study identifies 5 previously unreported variants, expanding the genetic profile of NF1.

Objective:To analyze the clinical phenotypes and genetic characteristics of pediatric patients with neurofibromatosis type 1 (NF1).Methods:A cross-sectional study was adopted. Clinical and imaging data of 25 pediatric patients diagnosed as having NF1 in Department of Pediatric Neurology, Linyi People's Hospital Affiliated to Shandong Second Medical University from January 2024 to July 2025 were collected. Whole exome sequencing and Sanger sequencing were used to conduct genetic testing on the pediatric patients and his/her parents. Protein 3D modeling of the domestic and foreign unreported variations was conducted using SWISS-MODEL software.Results:Among the 25 pediatric patients with NF1, 14 were male (56%) and 11 were female (44%), with age ranging from 8 months to 18 years. All pediatric patients exhibited café-au-lait macules, and 7 (28%) presented with plexiform neurofibromas. Genetic test identified 4 types of NF1 variants: nonsense variant ( n=11, 44%), frameshift variant ( n=9, 36%), missense variant ( n=3, 12%), and splice-site variant ( n=2, 8%). Importantly, 5 novel NF1 variants were discovered, including c.3455T>A, c.3709dupG, c.2665_2684del, c.7092_7095delinsTA, and c.3260del. Three pediatric patients inherited NF1 variant from their parents, while the remaining 22 harbored de novo mutation. Conclusion:NF1 exhibits a broad clinical spectrum, primarily affecting the skin and nervous system; this study identifies 5 previously unreported variants, expanding the genetic profile of NF1.

Objective:To develop a prediction tool for 6-year incident risk of frailty among Chinese older adults aged 65 years or above.Methods:Data from the Chinese Longitudinal Healthy Longevity Survey from 2002 to 2018 was used, including 13 676 older adults aged 65 years or above who were free of frailty at baseline. Key predictors of frailty were identified via the least absolute shrinkage and selection operator (LASSO) method, and were thereafter used to predict the incident frailty based on the Cox proportional hazards regression model. The model was internally validated by 2 000 Bootstrap resamples and evaluated for the performance of discrimination and calibration using the area under the receiver operating characteristic curve (AUC) and calibration curve, respectively. The net benefit of the developed prediction tool was evaluated by decision-curve analysis.Results:The M( Q1, Q3) age and follow-up time of the participants were 81.0 (71.0, 90.0) years and 6.0 (4.1, 9.2) years, respectively. A total of 4 126 older persons (30.2%) were recorded with frailty incidents during the follow-up, with the corresponding incidence density of 41.8/1 000 person-years. A total of 15 key predictors of frailty were selected by LASSO, namely, age, sex, race, education years, meat consumption, tea drinking, performing housework, raising domestic animals, playing cards or mahjong, and baseline status of visual function, activities of the daily living score, instrumental activities of the daily living score, hypertension, heart disease, and self-rated health. The prediction model was internally validated with an AUC of 0.802, with the max Youden's index of 0.467 at a risk threshold of 19.0%. The calibration curve showed high consistency between predicted probabilities and observed proportions of frailty events. The decision curve indicated that higher net benefits could be obtained via the prediction model than did strategies based on intervention in all or none participants for any risk threshold less than 59%, and the model-based net benefit was estimated to be 0.10 at a risk threshold of 19.0%. Conclusions:The herein developed 6-year incident risk prediction model of frailty, based on easily accessible questionnaires and physical examination variables, has good predictive performance. It has application potential in identifying populations at high risk of incident frailty.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Parkinson's disease (PD) is the most common neurodegenerative movement disease. It is featured by abnormal alpha-synuclein (α-syn) aggregation in dopaminergic neurons in the substantia nigra. Macroautophagy (autophagy) is an evolutionarily conserved cellular process for degradation of cellular contents, including protein aggregates, to maintain cellular homeostasis. Corynoxine B (Cory B), a natural alkaloid isolated from Uncaria rhynchophylla (Miq.) Jacks., has been reported to promote the clearance of α-syn in cell models by inducing autophagy. However, the molecular mechanism by which Cory B induces autophagy is not known, and the α-syn-lowering activity of Cory B has not been verified in animal models. Here, we report that Cory B enhanced the activity of Beclin 1/VPS34 complex and increased autophagy by promoting the interaction between Beclin 1 and HMGB1/2. Depletion of HMGB1/2 impaired Cory B-induced autophagy. We showed for the first time that, similar to HMGB1, HMGB2 is also required for autophagy and depletion of HMGB2 decreased autophagy levels and phosphatidylinositol 3-kinase III activity both under basal and stimulated conditions. By applying cellular thermal shift assay, surface plasmon resonance, and molecular docking, we confirmed that Cory B directly binds to HMGB1/2 near the C106 site. Furthermore, in vivo studies with a wild-type α-syn transgenic drosophila model of PD and an A53T α-syn transgenic mouse model of PD, Cory B enhanced autophagy, promoted α-syn clearance and improved behavioral abnormalities. Taken together, the results of this study reveal that Cory B enhances phosphatidylinositol 3-kinase III activity/autophagy by binding to HMGB1/2 and that this enhancement is neuroprotective against PD.

Background: Clinical dexamethasone (DEX) treatment or stress in bovines results in extensive physiological changes with prominent hyperglycemia and neutrophils dysfunction. Objectives: To elucidate the effects of DEX treatment in vivo on cellular energy status and the underlying mechanism in circulating neutrophils. Methods: We selected eight-month-old male bovines and injected DEX for 3 consecutive days (1 time/d). The levels of glucose, total protein (TP), total cholesterol (TC), and the proinflammatory cytokines interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α in blood were examined, and we then detected glycogen and adenosine triphosphate (ATP) content, phosphofructosekinase-1 (PFK1) and glucose-6-phosphate dehydrogenase (G6PDH) activity, glucose transporter (GLUT)1, GLUT4, sodium/glucose cotransporter (SGLT)1 and citrate synthase (CS) protein expression and autophagy levels in circulating neutrophils. Results: DEX injection markedly increased blood glucose, TP and TC levels, the Ca 2+ /P 5+ ratio and the neutrophil/lymphocyte ratio and significantly decreased blood IL-1β, IL-6 and TNF-α levels. Particularly in neutrophils, DEX injection inhibited p65-NFκB activation and elevated glycogen and ATP contents and SGLT1, GLUT1 and GR expression while inhibiting PFK1 activity, enhancing G6PDH activity and CS expression and lowering cell autophagy levels. Conclusions DEX induced neutrophils glucose uptake by enhancing SGLT1 and GLUT1 expression and the transformation of energy metabolism from glycolysis to pentose phosphate pathway (PPP)-tricarboxylic acid (TCA) cycle. This finding gives us a new perspective on deeper understanding of clinical anti-inflammatory effects of DEX on bovine.

Objective:To investigate the application values of bone marrow morphology, bone marrow immunohistochemistry, flow cytometry, fluorescence in situ hybridization (FISH) and cytogenetic testing in newly diagnosed multiple myeloma.Methods:A total of 280 patients with multiple myeloma who were newly diagnosed in Tianjin KingMed Diagnosis Center from September 2018 to August 2019 were collected. The bone marrow biopsy was carried out according to the routine method, and bone marrow morphology, bone marrow immunohistochemistry, flow cytometry immunophenotyping, FISH and cytogenetic testing were performed. The detection results of each method were compared.Results:In 280 patients, the bone marrow immunohistochemistry results showed that the median ratio of plasma cells was higher than those of bone marrow morphology (20 cases, 0.675 vs. 0.300) and flow cytometry (47 cases, 0.650 vs. 0.147), and the differences were statistically significant ( Z = -3.883, P < 0.01; Z = -5.947, P < 0.01). Flow cytometry results showed that the positive rates of CD38, CD138, κ, λ, CD56 and CD19 were 100.0% (280/280), 100.0% (280/280), 57.5% (161/280), 42.5% (119/280), 62.1% (174/280) and 19.3% (54/280); bone marrow immunohistochemistry results showed that the positive rates of CD38, CD138, κ, λ and CD56 were 98.9% (277/280), 98.2% (275/280), 57.5% (161/280), 42.5% (119/280) and 62.1% (174/280); there was no statistical difference between the two detection methods in the detection coincidence rate of the same detection index (all P > 0.05). Among patients who underwent FISH detection, the detection rate of gene abnormalities was 69.9% (93/133); the detection rate of abnormalities by direct fluorescence in situ hybridization (D-FISH) was 42.9% (57/133); the detection rate of abnormalities by CD138 immunomagnetic sorting myeloma cells (MACS)-FISH was 82.7% (110/133). Among patients who underwent G-band karyotyping, the detection rate of abnormal karyotype was 38.5% (85/221). FSIH, especially MACS-FISH, had a higher detection rate of cytogenetic abnormalities than G-band karyotyping, and the difference was statistically significant ( χ2 = 65.697, P < 0.05). Conclusion:The comprehensive application of bone marrow morphology, bone marrow immunohistochemistry, flow cytometry, FISH (especially MACS-FISH), cytogenetic testing and other detection methods is more helpful for the diagnosis of multiple myeloma, and may be useful for prognostic judgment.

In order to extract the pulse wave signal of blood volume effectively in the case of uneven light, a light-adaptive heart rate detection method based on webcam was proposed. In this method, adaptive gamma transform is applied to face image sequence to eliminate the influence of illumination. The pulse wave source signal was extracted from the forehead area and the blood volume pulse wave was obtained by wavelet filtering. The heart rate is estimated by Fourier transform analysis. The Bland-Altman analysis indicates that the method used in this paper is in good agreement with the measurement results of the electronic sphygmomanometer, and the adaptive gamma transformation used in this paper eliminates the influence of light interference, and the measurement error of heart rate is significantly reduced, which is completely able to meet the requirements of daily heart rate monitoring.
Algorithms ; Blood Volume ; Face ; Heart Rate ; Humans ; Internet ; Monitoring, Physiologic ; Video Recording

Objective To evaluate the risks of amputation and fracture induced by sodium glucose co-transporter 2 (SGLT2) inhibitors (canagliflozin,dapagliflozin,empagliflozin,and ertugliflozin).Methods Reports of amputation and fracture events induced by SGLT2 inhibitors and non-SGLT2 inhibitors received from January 1,2004 to June 30,2018 in the US Food and Drug Administration Adverse Event Reporting System (FAERS) database were collected.The relationship between the drugs mentioned above and the amputation and fracture events in all patients and especially in patients with diabetes mellitus,respectively,were analyzed by the method of reporting odds ratio (ROR).Results A total of 1 633 reports of SGLT2 inhibitors-induced amputation (27.66％ of 5 904 amputation event reports in the database during the study period) and 244 reports of SGLT2 inhibitors-induced fracture (0.21％ of 114 051 fracture event reports in the database during the study period) were retrieved from the database.These reports were related to canagliflozin,dapagliflozin,and empagliflozin,but not to ertugliflozin.And a total of 4 271 nonSGLT2 inhibitors-induced amputation event reports and 113 807 fracture event reports were retrieved from the database.Of the 1 633 reports of SGLT2 inhibitor-induced amputation,1 432 reports (87.69％) involved lower-limbs (led,foot,and toe) amputation,which had the highest proportion.The ROR values of all amputation events induced by overall SGLT2 inhibitors,canagliflozin,dapagliflozin,and empagliflozin in all patients were 92.70 (95％ CI:87.47-98.24),150.72 (95％ CI:141.98-160.00),6.84 (95％ CI:4.54-10.31),and 16.54 (95％ CI:12.98-21.07),respectively,and in patients with diabetes mellitus were 30.53 (95％ CI:27.81-33.51),49.68 (95％CI:45.19-54.62),2.73 (95％ CI:1.75-4.27),and 5.09 (95％ CI:3.80-6.83),respectively.The ROR values of lower-limb amputation events induced by overall SGLT2 inhibitors,canagliflozin,dapagliflozin,and empagliflozin in all patients were 103.49 (95％ CI:97.19-110.20),167.29 (95％ CI:156.82-178.45),8.38 (95％ CI:5.50-12.75),and 18.63 (95％CI:14.39-24.12),respectively,and in patients with diabetes mellitus were 30.92 (95％ CI:28.00-34.13),49.96 (95％ CI:45.18-55.24),2.95 (95％ CI:1.87-4.66) and 5.42 (95 ％ CI:4.00-7.34),respectively.The ROR values of fracture events induced by overall SGLT2 inhibitors were 0.49 (95％ CI:0.43-0.56) and 0.57 (95％ CI:0.49-0.67) in all patients and in patients with diabetes mellitus,respectively.Conclusions SGLT2 inhibitors could increase the risk of amputation in patients,especially the lower-limb amputation.The reports of amputation induced by canagliflozin had higher proportion than those induced by dapagliflozin or empagliflozin.No significant relationship between SGLT2 inhibitors and fracture was found.

Objective To evaluate the risk of acute kidney injury (AKI) induced by sodium glucose co-transporter 2 (SGLT2) inhibitors (canagliflozin,dapagliflozin,empagliflozin,and ertugliflozin).Methods Reports of AKI events induced by SGLT2 inhibitors and non-SGLT2 inhibitors received from January 1,2013 to September 30,2018 in the US Food and Drug Administration Adverse Event Reporting System (FAERS) database were collected.The relationship between the drugs mentioned above and the AKI events in all patients and especially in patients with diabetes mellitus,respectively,were analyzed by the method of reporting odds ratio (ROR).Results A total of 2 949 reports of SGLT2 inhibitors-induced AKI (2.50％ of 117 843 AKI event reports in the database during the study period),and 114 894 reports of non-SGLT2 inhibitors-induced AKI were retrieved from the database.The ROR values of AKI events induced by overall SGLT2 inhibitors,canagliflozin,dapagliflozin,and empagliflozin in all patients were 4.14 (95％ CI:3.98-4.30),5.58 (95％ CI:5.35-5.83),2.62 (95％ CI:2.35-2.92),and 1.96 (95％ CI:1.76-2.19),respectively,and in patients with diabetes mellitus were 2.84 (95 ％ CI:2.71-2.98),3.90 (95 ％ CI:3.69-4.12),1.70 (95％CI:1.48-1.94),and 1.30 (95％CI:1.15-1.48),respectively.Due to the short time to market,less than 3 reports of AKI events induced by ertugliflozin were reported,thus ROR analysis was not conducted for ertugliflozin.The analyses of combined medication showed that in all patients,the ROR value of AKI events induced by SGLT2 inhibitors was 8.05 (95％ CI:7.10-9.13) when SGLT2 inhibitors were combined with diuretics,which increased by 80.90％ compared with that when SGLT2 inhibitors were given alone and in patients with diabetes mellitus,it was 6.07 (95％ CI:5.27-7.00),which increased by 92.09％;in all patients,the ROR value of AKI events induced by SGLT2 inhibitors was 5.87 (95％CI:4.89-7.04) when SGLT2 inhibitors were combined with non-steroidal anti-inflammatory drugs (NSAID),which increased by 39.43％ compared with that when SGLT2 inhibitors were given alone and in patients with diabetes mellitus,it was 4.66 (95％ CI:3.79-5.74),which increased by 61.25％;in all patients,the ROR value of AKI events induced by SGLT2 inhibitors was 5.60 (95％ CI:5.12-6.14) when SGLT2 inhibitors were combined with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers,which increased by 25.56％ compared with that when SGLT2 inhibitors were given alone and in patients with diabetes mellitus,it was 4.05 (95％ CI:3.66-4.48),which increased by 27.36％.Conclusions SGLT2 inhibitors might increase the risk of AKI and this risk was mainly from canagliflozin,suggesting that dapagliflozin and empagliflozin were relatively safe to patients.The risk of AKI might increase when SGLT2 inhibitors were combined with diuretics or NSAID.