Objective:To construct fused cancer cell/neutrophil membrane-coated polydopamine nanoparticles chelated with manganese ions (Ⅱ) (PMNP@FMs) and explore the potential for targeted pancreatic cancer fluorescence imaging and MRI.Methods:Cancer cell membranes fused with neutrophil membranes were encapsulated on the surface of polydopamine nanoparticles chelated with manganese ions (Ⅱ) (PMNPs) to prepare PMNP@FMs. The morphology, structure, and MRI performance of the product were characterized. The cytotoxicity of PMNP@FMs towards human pancreatic cancer cells (PANC-1) and normal human pancreatic ductal epithelial cells (hTERT-HPNE) was evaluated using cell counting kit (CCK)-8, and in vivo toxicity was assessed in healthy mice. PANC-1 pancreatic cancer xenograft nude mouse models were established for in vivo fluorescence imaging and MRI. Data were analyzed using the independent-sample t test, repeated measures analysis of variance and the least significance difference method. Results:PMNP@FMs exhibited a core-shell structure with a diameter of (112.81±8.64) nm, negative surface charge, and good dispersibility. The T 1 relaxivity of PMNPs was 18.81±0.22, which was 4.1 times higher than that of gadopentetate dimeglumine (Gd-DTPA) (4.55±0.24; t=75.54, P<0.001). Co-culture of PMNPs and PMNP@FMs with hTERT-HPNE and PANC-1 cells for 24 h resulted in cell viability above 90% within the concentration range of 0-500 μg/ml. PMNP@FMs did not affect mouse survival and showed no apparent organ damage. In vivo fluorescence imaging and MRI revealed that PMNP@FMs accumulated highly in tumors and reached the peak 24 h post intravenous administration (relative MR signal: 1.35±0.01, fluorescence intensity: (1.20±0.25)×10 10), surpassing the peak observed in the control group (1.22±0.01, (3.87±0.50)×10 9;F values: 11.03-188.01, t values: 18.20, 5.64, all P<0.05), with hepatic metabolism being the primary route of clearance. Conclusion:PMNP@FMs demonstrate a potential for targeted pancreatic cancer fluorescence imaging and MRI, offering promising prospect for precise diagnosis of early-stage pancreatic cancer.

ObjectiveTo observe the clinical efficacy and safety of Modified Guomin Decoction （加味过敏煎， MGD） in patients with mild to moderate atopic dermatitis （AD） of the traditional Chinese medicine （TCM） pattern of heart fire and spleen deficiency， and to explore its possible mechanisms. MethodsIn this randomized， double-blind， placebo-controlled study， 72 patients with mild to moderate AD and the TCM pattern of heart fire and spleen deficiency were randomly divided into a treatment group and a control group， with 36 cases in each group. The treatment group received oral MGD granules combined with topical vitamin E emulsion， while the control group received oral placebo granules combined with topical vitamin E treatment. Both groups were treated twice daily for 4 weeks. Clinical efficacy， TCM syndrome scores， Visual Analogue Scale （VAS） for pruritus， Dermatology Life Quality Index （DLQI） scores， Scoring Atopic Dermatitis （SCORAD） and serum biomarkers， including interleukin-33 （IL-33）， interleukin-1β （IL-1β）， immunoglobulin E （IgE）， and tumor necrosis factor-α （TNF-α） were compared before and after treatment. Safety indexes was also assessed. ResultsThe total clinical effective rates were 77.78% （28/36） in the treatment group and 38.89% （14/36） in the control group， with cure rates of 19.44% （7/36） and 2.78% （1/36）， respectively. The treatment group showed significantly better clinical outcomes compared to the control group （P＜0.05）. The treatment group exhibited significant reductions in total TCM syndrome scores， including erythema， edema， papules， scaling， lichenification， pruritus， irritability， insomnia， abdominal distension， and fatigue scores， as well as reductions in VAS， DLQI， SCORAD， and serum IgE and IL-33 levels （P＜0.05 or P＜0.01）. Compared to the control group， the treatment group had significantly better improvements in all indicators except for insomnia （P＜0.05）. No adverse events occurred in either group. ConclusionMGD is effective and safe in treating mild to moderate AD patients with heart fire and spleen deficiency pattern. It significantly alleviates pruritus， improves TCM syndromes and quality of life， and enhances clinical efficacy， possibly through modulation of immune responses.

Objective To explore an epileptic seizure prediction method for patients with refractory epilepsy to improve the classification and prediction efficiency of epileptic electroencephalogram(EEG)signals.Methods The study used the long-term EEG database of patients with intractable epilepsy from Children's Hospital Boston(CHB-MIT).The EEG features of epileptic seizures and preictal periods were extracted from multiple dimensions such as EEG synchronization,complexity,and energy distribution,and then these features were input into the artificial neural network model for classification and identification,thereby achieving accurate prediction of epilepsy.The performance were optimized by adjusting the model parameters,and a comparative evaluation was conducted with existing deep learning models.Results The model proposed in this study showed an accuracy rate of 99.29％,a precision of 91.44％,a sensitivity of 96.46％,and a specificity of 99.46％.Compared with current epilepsy seizure prediction studies based on machine learning or deep learning frameworks,the model in this study improved its classification prediction capabilities and demonstrated higher prediction accuracy.Conclusion An effective prediction of epileptic seizures was achieved by manually extracting epileptic EEG features and constructing an artificial neural network model.The model demonstrated high accuracy and stability,providing reliable technique to support clinical treatment and prevention of epilepsy.

Objective To investigate the application of transvaginal ultrasound(TVS),multimo-dal magnetic resonance imaging(MRI)and 18F-fluorodeoxyglucose positron emission computed tomo-graphy/computed tomography(18F-FDG PET/CT)in diagnosis of endometrial carcinoma(EC).Methods A total of 157 patients with endometrial cancer in our hospital were selected.The results of EC staging by multimodal MRI and transvaginal ultrasound and positive 18F-FDG PET/CT were recor-ded,and their results were compared with pathological results.Results The results of TVS showed 87 cases in stage Ⅰ,6 cases were misdiagnosed and 12 cases were missed diagnosis.In 55 cases of stage Ⅱ,12 cases were misdiagnosed and 8 cases were missed.In 15 cases of stage Ⅲ,2 cases were misdiagnosed without missed diagnosis.The results of multimodal MRI showed that 86 cases were mis-diagnosed in stage Ⅰ,3 cases were misdiagnosed and 10 cases were missed.In 58 cases of stage Ⅱ,10 cases were misdiagnosed and 3 cases missed diagnosis.There were 13 cases of stage Ⅲ with no missed diagnosis or misdiagnosis.The results of 18F-FDG PET/CT were positive in 145 cases and missed in 12 cases.Based on the golden standard of postoperative pathological staging,the accuracy of TVS di-agnosis of EC patients in stage Ⅰ was 87.10％(81/93),stage Ⅱ was 84.31％(43/51),and stage Ⅲ was 100％(13/13).Based on the golden standard of postoperative pathological staging,the accuracy of mul-timodal MRI in the diagnosis of EC patients was 89.25％(83/93)in stage Ⅰ,94.12％(48/51)in stageⅡ,and 100％(13/13)in stage Ⅲ.According to the pathological staging,145 EC positive cases were de-tected by 18F-FDG PET/CT,the accuracy rate was 92.36％(145/157).Conclusion 18F-FDG PET/CT has a high diagnostic accuracy in EC patients,TVS and multimodal MRI have a high value in the preoperative staging diagnosis of EC,and are worthy of clinical promotion.

Objective To explore the effect and mechanism of quercetin on osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs).Methods BMSCs were divided into a blank control group(Control)and quercetin(Quercetin)low-dose group(4.8 mL/kg),medium-dose group(9.6 mL/kg),and high-dose group(19.2 mL/kg)intervened with drug-containing serum,while the positive control group was treated with osteogenic differentiation medium,respectively.The cell cycle was analysed by flow cytometry,cell proliferation was detected by MTT assay,cell activity was determined by Alkaline phosphatase(ALP)assay kit,and calcified nodule formation was observed by alizarin red staining.The expression of β-catenin and the key factors of osteogenic differentiation,runt-related transcription factor 2(RUNX2)and osteocalcin(OCN),were detected by qPCR and Western blot,respectively.Results Compared with the control group,quercetin-containing serum significantly promoted the proliferation of BMSCs(P=0.000205,P=0.000063)and enhanced the formation of calcium nodules,and increased osteogenic and ALP activity after osteogenic differentiation.The results of qPCR and Western blot showed that the quercetin group significantly up-regulated the mRNA and protein expression of β-catenin(P<0.0001),RUNX2(P<0.0001)and OCN(P<0.0001)during osteogenic differentiation.Conclusion Quercetin can effectively promote the osteogenic differentiation of BMSCs,and its mechanism is achieved by activating the Wnt/β-catenin signaling pathway and up-regulating the expression of the osteogenesis-related transcription factor RUNX2.

Objective:To construct fused cancer cell/neutrophil membrane-coated polydopamine nanoparticles chelated with manganese ions (Ⅱ) (PMNP@FMs) and explore the potential for targeted pancreatic cancer fluorescence imaging and MRI.Methods:Cancer cell membranes fused with neutrophil membranes were encapsulated on the surface of polydopamine nanoparticles chelated with manganese ions (Ⅱ) (PMNPs) to prepare PMNP@FMs. The morphology, structure, and MRI performance of the product were characterized. The cytotoxicity of PMNP@FMs towards human pancreatic cancer cells (PANC-1) and normal human pancreatic ductal epithelial cells (hTERT-HPNE) was evaluated using cell counting kit (CCK)-8, and in vivo toxicity was assessed in healthy mice. PANC-1 pancreatic cancer xenograft nude mouse models were established for in vivo fluorescence imaging and MRI. Data were analyzed using the independent-sample t test, repeated measures analysis of variance and the least significance difference method. Results:PMNP@FMs exhibited a core-shell structure with a diameter of (112.81±8.64) nm, negative surface charge, and good dispersibility. The T 1 relaxivity of PMNPs was 18.81±0.22, which was 4.1 times higher than that of gadopentetate dimeglumine (Gd-DTPA) (4.55±0.24; t=75.54, P<0.001). Co-culture of PMNPs and PMNP@FMs with hTERT-HPNE and PANC-1 cells for 24 h resulted in cell viability above 90% within the concentration range of 0-500 μg/ml. PMNP@FMs did not affect mouse survival and showed no apparent organ damage. In vivo fluorescence imaging and MRI revealed that PMNP@FMs accumulated highly in tumors and reached the peak 24 h post intravenous administration (relative MR signal: 1.35±0.01, fluorescence intensity: (1.20±0.25)×10 10), surpassing the peak observed in the control group (1.22±0.01, (3.87±0.50)×10 9;F values: 11.03-188.01, t values: 18.20, 5.64, all P<0.05), with hepatic metabolism being the primary route of clearance. Conclusion:PMNP@FMs demonstrate a potential for targeted pancreatic cancer fluorescence imaging and MRI, offering promising prospect for precise diagnosis of early-stage pancreatic cancer.

Objective To explore an epileptic seizure prediction method for patients with refractory epilepsy to improve the classification and prediction efficiency of epileptic electroencephalogram(EEG)signals.Methods The study used the long-term EEG database of patients with intractable epilepsy from Children's Hospital Boston(CHB-MIT).The EEG features of epileptic seizures and preictal periods were extracted from multiple dimensions such as EEG synchronization,complexity,and energy distribution,and then these features were input into the artificial neural network model for classification and identification,thereby achieving accurate prediction of epilepsy.The performance were optimized by adjusting the model parameters,and a comparative evaluation was conducted with existing deep learning models.Results The model proposed in this study showed an accuracy rate of 99.29％,a precision of 91.44％,a sensitivity of 96.46％,and a specificity of 99.46％.Compared with current epilepsy seizure prediction studies based on machine learning or deep learning frameworks,the model in this study improved its classification prediction capabilities and demonstrated higher prediction accuracy.Conclusion An effective prediction of epileptic seizures was achieved by manually extracting epileptic EEG features and constructing an artificial neural network model.The model demonstrated high accuracy and stability,providing reliable technique to support clinical treatment and prevention of epilepsy.

Objective To explore prescription and syndrome law of TCM in the treatment of non-alcoholic fatty liver disease(NAFLD);To provide reference for clinical medication.Methods The relevant literature on the treatment of NAFLD with TCM was retrieved from CNKI,VIP,Wanfang Data and CBM from the establishment of the databases to October 31,2023.Excel 2019,Lantern 5.0 and SPSS Modeler 18.0 software were used to analyze the latent structure model,association rules and frequency statistics of high-frequency drugs(≥3%)to explore the prescription and syndrome law of TCM in the treatment of NAFLD.Results A total of 453 prescriptions were included,involving 260 kinds of Chinese materia medica,with a cumulative frequency of 4 910 times.The high-frequency drugs were Crataegi Fructus,Salviea Miltiorrhizae Radix et Rhizoma,Alismatis Rhizoma,Bupleuri Radix,Poria and Atractylodis Macrocephalae Rhizoma,etc.The efficacy categories were mainly tonic medicine,diuretic dampness medicine,blood circulation-activating and stasis-resolving medicine,heat-clearing medicine and qi-regulating medicine.The latent structure model obtained 12 latent variables,24 latent classes,and 7 comprehensive clustering models.The commonly used prescriptions were Erchen Decoction,Yinchenhao Decoction,Danggui Shaoyao Powder,Sini Powder,Sijunzi Decoction,Weiling Decoction,Zhuyu Decoction and Dihuang Decoction categorized formula.Conclusion NAFLD is the syndrome of deficiency in root and excess in superficiality.Spleen deficiency is the root cause,phlegm,dampness,heat and blood stasis are the symptoms.In clinical practice,it is mainly based on tonifying qi and spleen,cooperating with the methods of resolving phlegm,eliminating dampness,clearing heat and activating blood circulation.

AIM:To investigate the mechanism by which resveratrol(Res)up-regulates the hypoxia-inducible factor-1α(HIF-1α)/BCL2-adenovirus E1B 19 kD-interacting protein 3(BNIP3)signaling pathway to induce autophagy,thereby alleviating cerebral ischemia-reperfusion injury(CIRI)in rats.METHODS:Totally 120 SD rats were randomly divided into 6 groups:sham group,CIRI group,Res group,Res+HIF-1α activator CoCl2 group,Res+HIF-1α inhibitor 2-methoxyestradiol(2ME2)group,and Res+autophagy inhibitor 3-methyladenine(3-MA)group.Twelve rats with failed surgical modeling were excluded,leaving 18 rats in each group.The rats in CIRI group,Res group,Res+CoCl2 group,Res+2ME2 group and Res+3-MA group were subjected to middle cerebral artery occlusion(MCAO)modeling using the su-ture method,with 2 h of ischemia followed by 24 h of reperfusion.The rats in sham group underwent MCAO modeling sur-gery without suture insertion.The Zea Longa modified scoring method was used to assess rat neurological behavior,TTC staining was used to measure rat cerebral infarct volume,and immunohistochemistry and immunoblotting were performed to detect the expression levels of HIF-1α,BNIP3,beclin-1 and mammalian target of rapamycin(mTOR)proteins in the rat cerebral cortex.RESULTS:Compared with CIRI group,the rats treated with Res showed significantly improved spon-taneous behavioral function and reduced cerebral infarct volume.The expression of HIF-1α,BNIP3 and beclin-1 proteins increased,while mTOR protein expression decreased in rat brain tissue.Compared with the Res group,rats treated with Res+CoCl2 showed further improvement in spontaneous behavioral function and further reduction in cerebral infarct vol-ume.The expression of HIF-1α,BNIP3 and beclin-1 proteins increased,while mTOR protein expression decreased in rat brain tissue.Rats in the Res+2ME2 and Res+3-MA groups exhibited weakened neurological function and increased cere-bral infarct volume,accompanied by decreased expression of HIF-1α,BNIP3 and beclin-1 proteins,and increased expres-sion of mTOR protein in rat brain tissue.CONCLUSION:Resveratrol may alleviate cerebral ischemia-reperfusion injury by upregulating the HIF-1α/BNIP3 pathway and subsequently activating autophagy.

Sepsis is a life-threatening organ dysfunction caused by host's dysfunctional response to infection, which is an important cause of health threat worldwide. Recent studies have found that the metabolic disorder of iron homeostasis is closely related to sepsis. The body has a highly accurate iron metabolism and regulation system to prevent iron deficiency or iron overload. The imbalance of intracellular iron homeostasis is now considered to be one of the important mechanisms of sepsis and may be a new target for clinical intervention.