OBJECTIVE: To observe the effect of electroacupuncture at "Sishencong" (EX-HN1) and "Fengchi" (GB20) on hippocampal neuronal ferritinophagy mediated by the nuclear receptor coactivator 4 (NCOA4)/ferritin heavy chain 1 (FTH1) signaling pathway in vascular dementia (VD) rats, and to explore the potential mechanisms of electroacupuncture for VD. METHODS: A total of 60 male rats of SPF grade were randomly divided into a blank group (12 rats), a sham surgery group (12 rats) and a modeling group (36 rats). In the modeling group, the modified 4-vessel occlusion method was used to establish the VD model. The 24 successfully modeled rats were randomly divided into a model group and an electroacupuncture group, with 12 rats in each group. In the electroacupuncture group, electroacupuncture was applied at left and right "Sishencong" (EX-HN1), and bilateral "Fengchi" (GB20), with continuous wave, in frequency of 2 Hz and current intensity of 1 mA, 30 min a time, once daily for 21 consecutive days. The learning and memory abilities were assessed using the Morris water maze test before modeling, after modeling and after intervention, as well as the novel object recognition test after intervention. After intervention, the neuronal morphology in the hippocampus was observed by Nissl staining; the iron deposition was observed by Prussian blue staining; the reactive oxygen species (ROS) level was detected by dihydroethidium (DHE) fluorescence staining; the levels of iron, malondialdehyde (MDA) and superoxide dismutase (SOD) in the hippocampal tissue were measured by the colorimetric assay, TBA method, and WST-1 method, respectively; the positive expression of NCOA4, FTH1 and glutathione peroxidase 4 (GPX4) was detected by immunohistochemistry; the protein expression of NCOA4, FTH1, GPX4, and the ratio of microtubule-associated protein 1 light chain 3B (LC3B) Ⅱ/Ⅰ in the hippocampus were detected by Western blot. RESULTS: Compared with the sham surgery group, in the model group, the escape latency was prolonged, and the number of platform crossings reduced (P<0.01), the recognition index (RI) was decreased (P<0.01); the hippocampal neurons displayed a blurred laminar structure, disorganized cellular arrangement, and the number of Nissl bodies was decreased (P<0.01); the percentage of iron deposition area in the hippocampus was increased (P<0.01); in the hippocampus, the levels of ROS, iron, MDA, and the protein expression of NCOA4, as well as the LC3B Ⅱ/Ⅰ ratio were increased (P<0.01), the SOD level, and the protein expression of FTH1 and GPX4 were decreased (P<0.01). Compared with the model group, in the electroacupuncture group, the escape latency was shortened and the number of platform crossings was increased (P<0.01), the RI was increased (P<0.01); the hippocampal neurons exhibited more regular morphology, better-organized cellular structure, and the number of Nissl bodies was increased (P<0.05); the percentage of iron deposition area in the hippocampus reduced (P<0.01); in the hippocampus, the levels of ROS, iron, MDA, and the protein expression of NCOA4, as well as the LC3B Ⅱ/Ⅰ ratio were decreased (P<0.01, P<0.05), the SOD level, and the protein expression of FTH1 and GPX4 were increased (P<0.01). CONCLUSION Electroacupuncture at "Sishencong" (EX-HN1) and "Fengchi" (GB20) can improve learning and memory abilities in VD rats, and its mechanism may be associated with the regulation of the hippocampal NCOA4/FTH1 signaling pathway, inhibition of ferritinophagy, and alleviation of oxidative stress damage.
Animals ; Electroacupuncture ; Dementia, Vascular/genetics* ; Male ; Rats ; Signal Transduction ; Humans ; Memory ; Rats, Sprague-Dawley ; Nuclear Receptor Coactivators/genetics* ; Ferritins/genetics* ; Learning ; Hippocampus/metabolism* ; Acupuncture Points

OBJECTIVES: To construct a bone tumor classification model based on feature decoupling and fusion for processing modality loss and fusing multimodal information to improve classification accuracy. METHODS: A decoupling completion module was designed to extract local and global bone tumor image features from available modalities. These features were then decomposed into shared and modality-specific features, which were used to complete the missing modality features, thereby reducing completion bias caused by modality differences. To address the challenge of modality differences that hinder multimodal information fusion, a cross-attention-based fusion module was introduced to enhance the model's ability to learn cross-modal information and fully integrate specific features, thereby improving the accuracy of bone tumor classification. RESULTS: The experiment was conducted using a bone tumor dataset collected from the Third Affiliated Hospital of Southern Medical University for training and testing. Among the 7 available modality combinations, the proposed method achieved an average AUC, accuracy, and specificity of 0.766, 0.621, and 0.793, respectively, which represent improvements of 2.6%, 3.5%, and 1.7% over existing methods for handling missing modalities. The best performance was observed when all the modalities were available, resulting in an AUC of 0.837, which still reached 0.826 even with MRI alone. CONCLUSIONS The proposed method can effectively handle missing modalities and successfully integrate multimodal information, and show robust performance in bone tumor classification under various complex missing modality scenarios.
Humans ; Bone Neoplasms/diagnosis* ; Multimodal Imaging/methods* ; Magnetic Resonance Imaging ; Tomography, X-Ray Computed ; Image Processing, Computer-Assisted/methods* ; Algorithms

Objective:To observe any effect of family rehabilitation interventions based on digital health management on elderly type 2 diabetes mellitus (T2DM) patients with sarcopenia.Methods:One hundred elderly T2DM patients with sarcopenia who had been discharged from hospital after treatment were divided into an observation group and a control group, each of 50. Both groups continued the diet control and training begun during their hospitalization, but the observation group was additionally provided with family rehabilitation based on digital health management. Before and after 3 months, the glucose and lipid metabolism and sarcopenia of both groups were evaluated with related symptom indexes, and their levels of diabetes self-management were compared.Results:Significant improvement was observed in both groups, but the average glucose and lipid metabolism indexes and sarcopenia-related symptom indexes of the observation group were significantly better than the control group′s averages. Their diabetes self-management was also significantly superior.Conclusion:Family rehabilitation based on digital health management can significantly improve glucose and lipid metabolism and muscle mass in elderly T2DM patients with sarcopenia. Such intervention is worthy of promotion and application in clinical practice.

OBJECTIVE: To explore the mechanism of electroacupuncture (EA) at "Fengchi" (GB 20) and "Sishencong" (EX-HN 1) on learning and memory impairment in vascular dementia (VD) rats by observing the influences on the N-methyl-D-aspartate receptor (NMDAR)/cyclic adenosine monophosphate response element-binding protein (CREB)/brain-derived neurotrophic factor (BDNF) signaling pathway and the excitotoxicity induced by hippocampal calcium overload. METHODS: Thirty-two male SD rats of SPF grade were selected and randomized into a normal group (6 rats), a sham-operation group (6 rats) and an operation group (20 rats). VD model was established with the modified Pulsinelli's four-vessel occlusion (4-VO) method. Twelve rats after successfully modeled were assigned randomly into a model group and an EA group, 6 rats in each one. In the EA group, EA was delivered at bilateral "Fengchi" (GB 20) and "Sishencong" (EX-HN 1), with the continuous wave, the frequency of 2 Hz and the electric current of 1 mA. Stimulation intensity was adjusted depending on the slightly trembling of rat head. EA was given once daily, 30 min each time; and EA intervention was delivered for 21 days continuously. Using Morris water maze test, the learning and memory function was assessed. The neuronal morphology in the hippocampal CA1 was observed with HE staining; the level of glutamate (GLU) in serum and hippocampal tissue, as well as the activity of calcium pump (Ca²⁺-ATP) in the hippocampus were detected using colorimetric method. The protein expression of NMDAR, calmodulin-dependent protein kinase Ⅱ (CaMKⅡ), phosphorylated calmodulin-dependent protein kinase Ⅱ (p-CaMKⅡ), phosphorylated cyclic phosphoradenosine effector element binding proteins (p-CREB), CREB, and BDNF in the hippocampal CA1 was detected using immunohistochemistry. The protein expression of NMDAR, CREB, p-CREB and BDNF in the hippocampal tissue was detected using Western blot method. RESULTS: Compared to the sham-operation group, in the model group, the escape latency was prolonged and the platform crossing times of rats were reduced (P<0.01), the hippocampal neuron structure was damaged to different degrees, the structure in hippocampal CA1 was loosened, the arrangement disorganized, with clear grid-like structure; the neuronal morphology was irregular, pyknosis and even dissolution occurred, glial cells increased, blood capillary was dilated and the inflammatory cells were infiltrated and scattered. The level of GLU in the serum and hippocampal tissue and the protein expression of hippocampal NMDAR were elevated (P<0.01), the activity of Ca²⁺-ATP and the protein expression of CaMKⅡ, p-CaMKⅡ, CREB, p-CREB and BDNF were reduced (P<0.01, P<0.05); and the ratio of p-CaMKⅡ/CaMKⅡ and that of p-CREB/CREB were dropped (P<0.05). In comparison with the model group, in the EA group, the escape latency was shortened and the platform crossing times of rats rose (P<0.01), the arrangement was improved in the hippocampal CA1, the neuronal morphology was intact, the nucleoli were clear relatively and the pyknosis or dissolution were attenuated, the numbers of glial cells reduced relatively, the dilation of blood capillary was alleviated. The level of GLU in the serum and hippocampal tissue and the protein expression of NMDAR were reduced in the hippocampal tissue (P<0.01), the activity of Ca²⁺-ATP and the protein expression of CaMKⅡ, p-CaMKⅡ, CREB, p-CREB and BDNF were elevated (P<0.05, P<0.01); and the ratio of p-CaMKⅡ/CaMKⅡ and that of p-CREB/CREB increased (P<0.05). CONCLUSION EA at "Fengchi" (GB 20) and "Sishencong" (EX-HN 1) can attenuate learning and memory impairment in VD rats, which may be obtained by reducing GLU level in hippocampal tissue, inhibiting hippocampal excitotoxicity, mediating protein expression related to the NMDAR/CREB/BDNF signaling pathway, and maintaining neuronal survival and growth.
Electroacupuncture ; Male ; Animals ; Rats, Sprague-Dawley ; Learning ; Memory ; Signal Transduction ; Cyclic AMP Response Element-Binding Protein/metabolism* ; Memory Disorders/therapy* ; Brain-Derived Neurotrophic Factor/metabolism* ; Receptors, N-Methyl-D-Aspartate/metabolism* ; Dementia, Vascular/therapy*

BACKGROUND: Dual regimen dolutegravir (DTG) plus lamivudine (3TC) has demonstrated non-inferior efficacy compared to DTG-based three-drug regimens (3DRs), yet directly comparative data regarding the efficacy and safety of DTG + 3TC and bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) for therapy-naïve people with human immunodeficiency virus (HIV)-1 (PWH) are still limited. We aimed to assess the antiviral potency and safety profiles of DTG + 3TC vs. B/F/TAF based on antiretroviral therapy (ART)-naïve PWH in China. METHODS: This retrospective multicenter study enrolled PWH initiating ART with DTG + 3TC or B/F/TAF from 2020 to 2022 in Guangdong and Guangxi. We analyzed response rates based on target not detected (TND) status using intention-to-treat (ITT) analysis. Subgroups were formed based on baseline viral load (VL) (<100,000 vs . ≥100,000 copies/mL) and CD4 + cell count (<200 vs . ≥200 cell/µL). Median time to TND VL was assessed by Kaplan-Meier method. We also measured changes from baseline in CD4 + cell counts, CD4/CD8 ratio, lipid parameters, weight, creatinine (Cr), estimated glomerular filtration rate (eGFR), and drug-related adverse effects (DRAEs). RESULTS: We enrolled 280 participants, including 137 (48.9%) on DTG + 3TC and 143 (51.1%) on B/F/TAF. At week 48, 96.4% (132/137) on DTG+3TC and 100% (143/143) on B/F/TAF achieved TND ( P = 0.064). At week 12, TND responses were higher with B/F/TAF (78.3% [112/143]) than DTG+3TC (30.7% [42/137]) ( P <0.001). This trend held across subgroups. B/F/TAF achieved TND faster (12 weeks) than DTG+3TC (24 weeks) ( P <0.001). No differences were seen in CD4 + cell count and CD4/CD8 ratio, except in the high-VL subgroup, where B/F/TAF showed better recovery. DRAEs were significantly lower with B/F/TAF (4.9% [7/143]) than with DTG + 3TC (13.1% [18/137]) ( P = 0.016). Lipid parameters, body weight, and Cr increased in both groups over 48 weeks, with DTG+3TC showing a more favorable effect on triglycerides, high-density lipoprotein (HDL) cholesterol, and weight gain. CONCLUSIONS In this real-life study, B/F/TAF led to a faster viral decline and fewer DRAEs compared to DTG+3TC. No significant difference was observed in the TND rate at week 48, regardless of baseline VL and CD4 + cell count. CD4 + recovery was superior for B/F/TAF in participants with high VL. The DTG + 3TC regimen had less impact on metabolic changes than B/F/TAF.
Adult ; Humans ; Anti-HIV Agents/therapeutic use* ; China ; Emtricitabine/pharmacology* ; HIV Infections/drug therapy* ; HIV-1 ; Lamivudine/pharmacology* ; Lipids ; Retrospective Studies

Vascular dementia(VD)is caused by cerebrovascular diseases,either hemorrhage or ischemic damage in the brain,with ischemia being the most common.In recent years,increasing efforts have been made to study the etiology,pathogenesis,and prevention of VD.The establishment of appropriate animal models to study the mechanism of VD and explore the efficacy of VD treatments has become an important issue in this research field.On the basis of conventional method,such as bilateral occlusion of common carotid arteries(2VO)and four-vessel occlusion,researchers have modified these method to improve stability with better reflection of the clinical manifestations of VD.This review summarizes these modified method and discusses possible cellular and molecular mechanisms and their advantages and disadvantages.

OBJECTIVE To investigate the potential developmental toxicity and delayed toxicity of Fuganline oral liquid(FGLOL)after long-term administration in juvenile SD rats via a three-stage juve-nile animal study(JAS).METHODS Stage 1:according to the proposed clinical dose for infants within one year of age,FGLOL 3.88,11.64,38.75 g·kg-1 was orally administered to rats of postnatal day 4(PND4)rats for 18 days,and the drug was stopped for 3 weeks.Stage 2:according to the proposed clinical dose for children ages 1 to 6,FGLOL 3.88,11.64,38.75 g·kg-1 was orally administered to PND15 rats for 31 d,and the drug was discontinued for 3 weeks.Stage 3:according to the proposed clinical dose for children aged 7 to 12,FGLOL 29.06,58.13,116.25 g·kg-1 was orally administered to PND40 rats for 66 d,and the drug was stopped for 4 weeks.The effects of FGLOL on health status,food intake,body mass,growth and development,nerve reflex development,learning and memory ability,physical development(body length),bone development(bone mineral density),hematology and coagulation(white blood cells,red blood cells and platelet count),blood biochemistry(glutamate dehydrogenase,urea nitrogen and triglycerides)and histopathology were investigated in young rats.RESULTS In the three-stage JAS test,long-term administration of FGLOL did not cause rat death,and no toxicological effects were observed on body mass,growth and development,nerve reflex development,physical development,bone development,hematology and coagulation,blood biochemistry and histopathology of juvenile rats compared with the vehicle control group.CONCLUSION The no observed adverse effect level(NOAEL)of FGLOL is 38.75 g·kg-1 for the JAS test corresponding to humans between 1 and 6 years old,while the NOAEL of FGLOL is 116.25 g·kg-1 for the JAS test and repeated drug toxicity test corresponding to humans aged 7 to 12.

OBJECTIVE To investigate the effects of Qinxiang Qingjie oral liquid(QXQJ)on growth and development after repeated administration of 18 d to postnatal day 4(PND4)rats.METHODS The number and sex of PND2 pups were adjusted using the cross-breeding method.These pups were ran-domly divided into the normal control,QXQJ 3.45,10.35 and 28.05 g·kg-1 groups.PND4,juvenile rats were ig given QXQJ every day,while the normal control group was given pure water,once a day,for 18 d,before observation of 3 weeks was resumed.During the experiment,the general condition,body mass,growth and development,physique,bone,hematology and coagulation of the rats in each group were detected.RESULTS 18 d after continuous administration of QXQJ,there was no obvious effect on the food intake,growth and development,nerve reflex,spontaneous behavior,hematology,coagula-tion,blood biochemistry,immunity,growth hormone,histopathology and other examination indexes of juve-nile rats.From PND5,juvenile rats in the QXQJ 10.35 and 28.05 g·kg-1groups developed yellow-brown soft or loose stools and abdominal distention,but the symptoms generally recovered at PND22.The body mass,top-rump length,tail length and limb length of the juvenile rats in the 28.05 g·kg-1 group were signifi-cantly lower at PND7(P<0.05),but recovered one week after drug withdrawal.The bone mineral specific gravity and bone mineral density of the 28.05 g·kg-1 group were significantly lower than those of the normal control group at PND22(P<0.05),but there was no significant difference at PND42.CONCLU-SION QXQJ can cause such indigestion symptoms as yellow brown soft stool or loose stool and abdominal enlargement in unweaned juvenile rats,thus affecting the physical development indicators of rats,but the symptoms can recover after withdrawal of medication or withdrawal from milk.The no observed adverse effect level(NOAEL)of QXQJ administered to 4-day-old rats for 18 d is 3.45 g·kg-1.

Objective:To investigate the application of multiscale low-rank plus sparsity (MLRS) modeling in fast ultra-high-field intracranial 4D Flow imaging.Methods:Ten healthy volunteers, 5 males and 5 females, aged 23-35 (29±4) years old, recruited from October 2022 to January 2023 at Huashan Hospital of Fudan University, were prospectively collected. A MLRS model acceleration algorithm was proposed according to the characteristics of 4D Flow data based on the multiscale low-rank (MLR) model. Firstly, full sampling brain 4D Flow scans were performed on healthy volunteers using 7.0 T MR, and the acquired data were under-sampled with Gaussian distributions at different acceleration rates (R of 4, 8, 12, and 16, respectively). The root mean square error (RMSE) and peak signal-to-noise ratio (PSNR) of the compressed sensing algorithm (CS), low-rank plus sparse algorithm (L+S), MLR, and MLRS model were calculated at different acceleration rates, with fully sampled data as reference. And the comparison of models was performed using the paired-samples t-test or Wilcoxon signed rank test. Pearson′s test was used to assess the correlation between hemodynamic parameters of the 4 algorithms and the fully sampled reference values at different acceleration rates, and the correlation coefficients were compared using Wilcoxon signed rank test. Results:The RMSE under the same acceleration rates was MLRS, MLR, L+S, and CS models in ascending order, and the RMSE of the MLRS model was significantly lower than that of the MLR, L+S, and CS models ( P<0.05); the PSNR was MLRS, MLR, L+S, and CS models in descending order, and the PSNR of the MLRS model was significantly higher than that of the MLR, L+S, and CS model ( P<0.05). The correlation coefficients between the blood flow velocity measured by the MLRS model and the reference value were significantly higher than those of the MLR, L+S, and CS models for different acceleration rates ( P<0.05). Conclusion:The proposed MLRS algorithm is capable of accelerating ultra-high-field 4D Flow MR imaging of the brain while guaranteeing the image quality, and the MLRS model has higher reconstruction accuracy compared with conventional acceleration models at the same acceleration rate.

Objective To investigate the expression and clinical significance of TM9SF3 in lung adenocarcinoma (LUAD). Methods TCGA and GEPIA databases were used to screen the differentially-expressed TM9SF family molecules and analyze their effects on patient prognosis with LUAD. The expression and localization of TM9SF3 in LUAD patients were verified by a human proteomic mapping database, Western blot assay, and polymerase chain reaction assay. Herein, the GSEA was used for the signal pathway enrichment analysis of TM9SF3-related genes. Meanwhile, the TIMER database and CIBERSORT algorithm were used to analyze the correlation between differentially-expressed TM9SF3 and the degree of immune cell infiltration. Results The expression of TM9SF3 in LUAD was significantly increased and had a significant adverse effect on the prognosis of LUAD patients. In addition, immunoblotting and polymerase chain reaction confirmed that TM9SF3 was highly expressed in LUAD. Meanwhile, the genes related to TM9SF3 expression were mainly enriched in cell signaling pathways regulating immune cell activity. The expression of TM9SF3 was significantly correlated with the expression changes of six immune cells. Conclusion TM9SF3 is differentially expressed in LUAD and may be used as a potential prognostic marker for LUAD patients. TM9SF3 can also change the level of immune cell infiltration in LUAD patients and is expected to be a new potential target for LUAD immunotherapy.