Alzheimer's disease (AD) is characterized by cognitive and functional deterioration, with pathological features such as amyloid-beta (Aβ) aggregates in the extracellular spaces of parenchymal neurons and intracellular neurofibrillary tangles formed by the hyperphosphorylation of tau protein. Despite a thorough investigation, current treatments targeting the reduction of Aβ production, promotion of its clearance, and inhibition of tau protein phosphorylation and aggregation have not met clinical expectations, posing a substantial obstacle in the development of drugs for AD. Recently, artificial intelligence (AI), computational biology (CB), and systems biology (SB) have emerged as promising methodologies in AD research. Their capacity to analyze extensive and varied datasets facilitates the identification of intricate patterns, thereby enriching our comprehension of AD pathology. This paper provides a comprehensive examination of the utilization of AI, CB, and SB in the diagnosis of AD, including the use of imaging omics for early detection, drug discovery methods such as lecanemab, and complementary therapies like phototherapy. This review offers novel perspectives and potential avenues for further research in the realm of translational AD studies.

Magnetic stimulation has made significant strides in the treatment of psychiatric disorders. Nonetheless, current magnetic stimulation techniques lack the precision to accurately modulate specific nuclei and cannot realize deep brain magnetic stimulation. To address this, we utilized superparamagnetic iron oxide nanoparticles as mediators to achieve precise targeting and penetration. We investigated the effects of magnetic fields with varying frequencies on neuronal activity and compared the activation effects on neurons using a 10-Hz precise magneto-stimulation system (pMSS) with repetitive transcranial magnetic stimulation in mice. Oxytocin levels, dendritic morphology and density, and mouse behavior were measured before and after pMSS intervention. Our findings suggest that pMSS can activate oxytocinergic neurons, leading to upregulation of oxytocin secretion and neurite outgrowth. As a result, sociability was rapidly improved after a one-week pMSS treatment regimen. These results demonstrate a promising magneto-stimulation method for regulating neuronal activity in deep brain nuclei and provide a promising therapeutic approach for autism spectrum disorder.
Animals ; Autism Spectrum Disorder/physiopathology* ; Paraventricular Hypothalamic Nucleus/physiology* ; Disease Models, Animal ; Transcranial Magnetic Stimulation/methods* ; Male ; Social Behavior ; Mice ; Oxytocin/metabolism* ; Mice, Inbred C57BL ; Neurons/physiology*

Postoperative infection of internal fixation of closed fractures the lower limbs in adults represents a devastating complication, characterized by diagnostic challenges, prolonged treatment duration and high disability rates. Current management of these infections faces multiple challenges, such as difficulties in early accurate diagnosis, and various controversies about the treatment plan, leading to poor overall diagnosis and treatment results. To address these issues, based on evidence-based medicine and principles with emphasis on scientific rigor, clinical applicability and innovation, the Trauma Branch of the Chinese Medical Association, Orthopedic Branch of the Chinese Medical Doctor Association, Orthopedics Branch of the Chinese Medical Association, and Trauma Orthopedics and Polytrauma Group of the Resuscitation and Emergency Committee of the Chinese Medical Doctor Association have collaboratively organized a panel of relevant experts to develop the Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults ( version 2025). The guideline proposed 10 recommendations, aiming to provide a foundation for standardized diagnosis and treatment of postoperative infection in adults with closed lower limb fractures.

Objective:To evaluate the role of splenic sympathetic nerve-regulated infiltration and polarization of dorsal root ganglion (DRG) macrophages in diabetic neuropathic pain (DNP) in mice.Methods:Forty-eight specific pathogen-free male C57BL/6 mice, aged 6 weeks, weighing 20-22 g, were divided into 4 groups ( n=12 each) using a random number table method: control group (Con group), DNP group, DNP plus sham operation group (DNP+ Sham group), and diabetes mellitus induced by DNP plus splenic sympathetic denervation group (DNP+ SS group). In DNP+ SS group, the splenic sympathetic denervation procedures were performed using 6-hydroxydopamine solution, while a solvent of 0.2% ascorbic acid saline solution was used as a substitute for 6-hydroxydopamine solution in DNP+ Sham group. After a two-week recovery, the diabetes mellitus was induced by intraperitoneal injection of streptozotocin 120 mg/kg in mice at 8 weeks of age. The mechanical paw withdrawal threshold (MWT) were measured on day 1 before developing the model and on days 7, 14, 21 and 28 after developing the model. After the last behavioral testing, the DRG was taken after anesthesia for determination of the expression of the macrophage marker ionized calcium-binding adaptor molecule 1(Iba1), calcitonin gene-related peptide (CGRP), and tumor necrosis factor-α (TNF-α) (by immunofluorescence) and expression of M1 phenotype markers (CD16, TNF-α, inducible nitric oxide synthase [iNOS]) and M2 phenotype markers (interleukin-10 [IL-10], transforming growth factor-β1 [TGF-β1], and CD206) mRNA (using quantitative real-time polymerase chain reaction). Results:Compared with Con group, the MWT was significantly decreased on days 14, 21 and 28 after developing the model, the expression of CGRP and TNF-α in the DRG was up-regulated, the count of Iba1-positive cells was increased, the expression of CD16, TNF-α and iNOS mRNA was up-regulated ( P<0.05), and no significant change was found in the expression of IL-10, TGF-β1 and CD206 in DNP group ( P>0.05). Compared with DNP group and DNP+ Sham group, the MWT was significantly increased on days 14, 21 and 28 after developing the model, the expression of CGRP and TNF-α in the DRG was down-regulated, the count of Iba1-positive cells was decreased, the expression of CD16, TNF-α and iNOS mRNA was down-regulated, and the expression of IL-10, TGF-β1 and CD206 mRNA was up-regulated in DNP+ SS group ( P<0.05), and no significant change was found in the aforementioned parameters at each time point in DNP and DNP+ Sham groups ( P>0.05). Conclusions:Activation of splenic sympathetic nerve can promote the infiltration and polarization of DRG macrophages, thus participating in the process of diabetic neuropathic pain in mice.

Objective To explore the influencing factors of cognitive impairment in non-dialysis patients with chronic kidney disease(CKD).Methods A total of 60 hospitalized non-dialysis patients with CKD in the Department of Nephrology of Northern Jiangsu People's Hospital Affiliated to Yangzhou University from September 2022 to September 2023 were enrolled as research objects.According to the estimated glomerular filtration rate(eGFR),they were divided into stage 1 to 2 of CKD group[eGFR ≥60 mL/(min·1.73 m2)]with 23 cases,the stage 3 of CKD group[eGFR 30～＜60 mL/(min·1.73 m2)]with 20 cases,and stage 4 to 5 of CKD group[eGFR＜30 mL/(min·1.73 m2)]with 17 cases.The Montreal Cognitive Assessment Scale(MoCA)was used to evaluate the cognitive function of the patients.Basic data and common clinical laboratory in-dicators on hospital admission were collected to analyze the differences in cognitive function levels under different renal function statuses and to explore the influencing factors of cognitive impairment.Results The incidence rates of cognitive impairment in the stage 1 to 2 of CKD group,stage 3 of CKD group,and stage 4 to 5 of CKD group were 47.8％,85.0％,and 94.1％respectively,the median MoCA scored 26,24 and 20 respectively,with statistically significant between-group differ-ences(P＜0.05).Cognitive function was significantly negatively correlated with age(r=-0.634,P＜0.001),blood urea nitrogen(BUN)(r=-0.574,P＜0.001),serum creatinine(Cr)(r=-0.417,P＜0.001),cystatin C(Cys-C)(r=-0.327,P=0.011),serum β2-microglobulin(β2-MG)(r=-0.259,P=0.046),and N-terminal pro-brain natriuretic peptide(NT-proBNP)(r=-0.474,P＜0.001),and was significantly positively correlated with hemoglobin(HB)(r=0.401,P=0.001)and eGFR(r=0.485,P＜0.001).Multivariate Logistic regression analysis showed that age(P=0.006)and NT-proBNP(P=0.041)were influencing factors of cognitive im-pairment in non-dialysis patients with CKD.Receiver operating characteristic(ROC)curve analysis showed that the area under the curve(AUC),sensitivity,and specificity of age for prediction were 0.860,0.864 and 0.812 respectively,the AUC,sensitivity,and specificity of NT-proBNP for pre-diction were 0.808,0.795 and 0.875 respectively,and the combined prediction of age and NT-proBNP had an AUC,sensitivity,and specificity of 0.893,0.955,and 0.750,respectively.Conclusion As renal function deteriorates,the incidence rate and severity of cognitive impairment in non-dialysis patients with CKD tend to increase.Advanced age,renal function deterioration,high NT-proBNP level,and anemia are associated with the occurrence of cognitive impairment in non-di-alysis patients with CKD,among which age and NT-proBNP are influencing factors for cognitive im-pairment.

Objective:To explore the distribution and clearance of 99mTc labeled diethylenetriamine pentaacetic acid(99mTc-DTPA)in different brain regions of adult rats after administration through brain extracellular space(ECS)pathway.Methods:After the injection of a volume of 2 μL and radioactive activity of about 3.7 MBq(100 μCi)of 99mTc-DTPA into the caudate nucleus and thalamus of SD rats through stereotactic positioning of rat brain,the single photon emission computed tomography/computed tomography(SPECT/CT)for small animals was used for imaging at different time points,and the dyna-mic distribution and clearance of the tracer in the whole body were observed continuously.The SD rats were injected with 99mTc-DTPA into thalamus and caudate nucleus respectively for biological distribution in vivo.They were put to death 4 h later.Their blood and urine were collected.The brain,cerebellum,heart,liver,spleen,lung,and kidney were taken and weighed by γ counter to measure its radioactivity.Results:SPECT/CT imaging results showed that after 99mTc-DTPA was administered through brain ECS,the radioactivity was concentrated in the brain,kidney and bladder.The tracer administered to the left caudate nucleus was preferentially drained to the right cerebellum,while the tracer administered to the right caudate nucleus was preferentially drained to the left cerebellum.There was a phenomenon of"con-tralateral cerebellar dominant drainage"in the caudate nucleus.The thalamic area preferentially drained to the ipsilateral cerebellum after administration.Four hours after administration via ECS,high radioac-tive uptake appeared in urine,cerebellum and brain,followed by blood and kidney.The radioactive up-take values of heart,liver,spleen and lung were low,which were mainly excreted through urinary sys-tem.Conclusion:Intracerebral ECS administration is a promising method of administration,but there are significant differences in distribution and clearance in different brain regions.This study further ex-pands the content and significance of"ECS regions",and also provides an important theoretical founda-tion for the treatment of encephalopathy and the research of new drugs through brain ECS in the future.

Objective:To evaluate the role of splenic sympathetic nerve-regulated infiltration and polarization of dorsal root ganglion (DRG) macrophages in diabetic neuropathic pain (DNP) in mice.Methods:Forty-eight specific pathogen-free male C57BL/6 mice, aged 6 weeks, weighing 20-22 g, were divided into 4 groups ( n=12 each) using a random number table method: control group (Con group), DNP group, DNP plus sham operation group (DNP+ Sham group), and diabetes mellitus induced by DNP plus splenic sympathetic denervation group (DNP+ SS group). In DNP+ SS group, the splenic sympathetic denervation procedures were performed using 6-hydroxydopamine solution, while a solvent of 0.2% ascorbic acid saline solution was used as a substitute for 6-hydroxydopamine solution in DNP+ Sham group. After a two-week recovery, the diabetes mellitus was induced by intraperitoneal injection of streptozotocin 120 mg/kg in mice at 8 weeks of age. The mechanical paw withdrawal threshold (MWT) were measured on day 1 before developing the model and on days 7, 14, 21 and 28 after developing the model. After the last behavioral testing, the DRG was taken after anesthesia for determination of the expression of the macrophage marker ionized calcium-binding adaptor molecule 1(Iba1), calcitonin gene-related peptide (CGRP), and tumor necrosis factor-α (TNF-α) (by immunofluorescence) and expression of M1 phenotype markers (CD16, TNF-α, inducible nitric oxide synthase [iNOS]) and M2 phenotype markers (interleukin-10 [IL-10], transforming growth factor-β1 [TGF-β1], and CD206) mRNA (using quantitative real-time polymerase chain reaction). Results:Compared with Con group, the MWT was significantly decreased on days 14, 21 and 28 after developing the model, the expression of CGRP and TNF-α in the DRG was up-regulated, the count of Iba1-positive cells was increased, the expression of CD16, TNF-α and iNOS mRNA was up-regulated ( P<0.05), and no significant change was found in the expression of IL-10, TGF-β1 and CD206 in DNP group ( P>0.05). Compared with DNP group and DNP+ Sham group, the MWT was significantly increased on days 14, 21 and 28 after developing the model, the expression of CGRP and TNF-α in the DRG was down-regulated, the count of Iba1-positive cells was decreased, the expression of CD16, TNF-α and iNOS mRNA was down-regulated, and the expression of IL-10, TGF-β1 and CD206 mRNA was up-regulated in DNP+ SS group ( P<0.05), and no significant change was found in the aforementioned parameters at each time point in DNP and DNP+ Sham groups ( P>0.05). Conclusions:Activation of splenic sympathetic nerve can promote the infiltration and polarization of DRG macrophages, thus participating in the process of diabetic neuropathic pain in mice.

Objective:To explore the distribution and clearance of 99mTc labeled diethylenetriamine pentaacetic acid(99mTc-DTPA)in different brain regions of adult rats after administration through brain extracellular space(ECS)pathway.Methods:After the injection of a volume of 2 μL and radioactive activity of about 3.7 MBq(100 μCi)of 99mTc-DTPA into the caudate nucleus and thalamus of SD rats through stereotactic positioning of rat brain,the single photon emission computed tomography/computed tomography(SPECT/CT)for small animals was used for imaging at different time points,and the dyna-mic distribution and clearance of the tracer in the whole body were observed continuously.The SD rats were injected with 99mTc-DTPA into thalamus and caudate nucleus respectively for biological distribution in vivo.They were put to death 4 h later.Their blood and urine were collected.The brain,cerebellum,heart,liver,spleen,lung,and kidney were taken and weighed by γ counter to measure its radioactivity.Results:SPECT/CT imaging results showed that after 99mTc-DTPA was administered through brain ECS,the radioactivity was concentrated in the brain,kidney and bladder.The tracer administered to the left caudate nucleus was preferentially drained to the right cerebellum,while the tracer administered to the right caudate nucleus was preferentially drained to the left cerebellum.There was a phenomenon of"con-tralateral cerebellar dominant drainage"in the caudate nucleus.The thalamic area preferentially drained to the ipsilateral cerebellum after administration.Four hours after administration via ECS,high radioac-tive uptake appeared in urine,cerebellum and brain,followed by blood and kidney.The radioactive up-take values of heart,liver,spleen and lung were low,which were mainly excreted through urinary sys-tem.Conclusion:Intracerebral ECS administration is a promising method of administration,but there are significant differences in distribution and clearance in different brain regions.This study further ex-pands the content and significance of"ECS regions",and also provides an important theoretical founda-tion for the treatment of encephalopathy and the research of new drugs through brain ECS in the future.

Postoperative infection of internal fixation of closed fractures the lower limbs in adults represents a devastating complication, characterized by diagnostic challenges, prolonged treatment duration and high disability rates. Current management of these infections faces multiple challenges, such as difficulties in early accurate diagnosis, and various controversies about the treatment plan, leading to poor overall diagnosis and treatment results. To address these issues, based on evidence-based medicine and principles with emphasis on scientific rigor, clinical applicability and innovation, the Trauma Branch of the Chinese Medical Association, Orthopedic Branch of the Chinese Medical Doctor Association, Orthopedics Branch of the Chinese Medical Association, and Trauma Orthopedics and Polytrauma Group of the Resuscitation and Emergency Committee of the Chinese Medical Doctor Association have collaboratively organized a panel of relevant experts to develop the Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults ( version 2025). The guideline proposed 10 recommendations, aiming to provide a foundation for standardized diagnosis and treatment of postoperative infection in adults with closed lower limb fractures.

Objective To explore the value of artificial intelligence federated learning system based on chest X-ray films for pathogen diagnosis of community-acquired pneumonia(CAP)in children.Methods Totally 900 cases of CAP children from 2 hospitals were retrospectively enrolled,including bacterial,viral and mycoplasma CAP(each n=300),and chest posteroanterior X-ray films were collected.Meanwhile,chest posteroanterior X-ray films of 5856 children from the publicly available dataset GWCMCx were collected,including 4273 CAP images and 1583 healthy chest images.All above 6756 images were divided into training set(n=5359)and validation set(n=1397)at the ratio of 8∶2.Then a pathogen diagnosis model of children CAP was established based on attention mechanism.Binary and ternary diagnostic algorithms were designed,and federated deployment training was performed.The efficacy of this system for pathogen diagnosis of children CAP was analyzed and compared with DenseNet model.Results Based on all data,the accuracy of the obtained artificial intelligence federated learning system model for diagnosing children CAP was 97.00%,with the area under the curve(AUC)of 0.990.Based on hospital data,the AUC of this system using single imaging data and clinical-imaging data for pathogen diagnosis of children CAP was 0.858 and 0.836,respectively,both better than that of DenseNet model(0.740,both P＜0.05).Conclusion The artificial intelligence federated learning system based on chest X-ray films could be used for pathogen diagnosis of children CAP.