ObjectiveTo explore the possible mechanism of action of Bushen Huoxue Granules （补肾活血颗粒， BHG） in the treatment of Parkinson's disease （PD） through the Nrf2/NLRP3 inflammasome axis. MethodsA total of 84 male C57/BL 6 mice were randomly divided into blank group， model group， Madopar group， dimethyl fumarate group， and low-， medium， and high-dose BHG group， with 12 mice in each group. Except for the blank group， all groups were induced into PD models by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine （MPTP） at a concentration of 30 mg/ml for 7 consecutive days. The blank group received an equal volume of saline. After model establishment， the low-， medium， and high-dose BHG groups were treated with 1.5， 3， and 6 g/（kg·d） of the BHG by gavage， respectively. The Madopar group was given 0.113 g/（kg·d） of Madopar tablets by gavage， and the dimethyl fumarate group was given 50 mg/（kg·d） of dimethyl fumarate solution. The blank group and the model group were given 10 ml/（kg·d） of distilled water by gavage. Gavage was administered once daily for 14 days. Behavioral changes were evaluated using the open field test （total distance， central area distance， and average speed）， rotarod test （time on the rod）， and climbing pole test （climbing time）. Serum levels of interleukin-1β （IL-1β）， interleukin-18 （IL-18）， and myeloperoxidase （MPO） were measured by ELISA. Immunohistochemistry was used to detect tyrosine hydroxylase （TH） expression in the brain substantia nigra. Immunofluorescence was used to detect α-synuclein （α-syn） expression. Western Blot was used to detect Nrf2， NLRP3， Caspase-1， and α-syn protein levels in the brain substantia nigra. RT-PCR was used to detect mRNA expression levels of Nrf2， NLRP3， and Caspase-1 in the brain substantia nigra. ResultsCompared with the blank group， the model group showed decreased total distance， central area distance， and average speed， reduced time on the rotarod， prolonged climbing time， reduced TH expression， increased α-syn expression， decreased Nrf2 protein and mRNA expression， increased NLRP3 and Caspase-1 protein and mRNA expression， and elevated serum IL-1β， IL-18， and MPO levels （P＜0.05）. Compared with the model group， all drug interventions significantly improved the above indicators （P＜0.05）. There was no significant differences in all indicators between the high-dose BHG group and the Madopar group （P＞0.05）. Compared with the dimethyl fumarate group， the medium and high-dose BHG groups showed increased Nrf2 mRNA expression in the brain substantia nigra （P＜0.05）. Compared with the high-dose BHG group， the low-dose group showed decreased total distance， central area distance， and average speed， reduced serum IL-18 levels， decreased α-syn， Nrf2， NLRP3， and Caspase-1 protein levels， and lower Nrf2 mRNA expression （P＜0.05）. ConclusionThe mechanism by which BHG treat PD may involve activating the Nrf2/NLRP3 inflammasome axis in the brain substantia nigra， thereby reducing neuroinflammation and α-syn aggregation. The high-dose group showed the best effects.

ObjectiveTo investigate the possible mechanism of Bushen Huoxue Granule （补肾活血颗粒， BHG） in treating Parkinson's disease （PD） from the perspecitve of dopamine （DA） homeostasis. MethodsSeventy-two mice were randomly divided into blank group， model group， madopar group and BHG low-， medium- and high-dose groups， with 12 mice in each group. Except for the blank group， all mice were administered intraperitoneal injections of 1-methyl-4-phenyl-1，2，3，6-tetrahydropyridine （MPTP） for 7 consecutive days to induce a PD model. On the day following the injection， BHG low-， medium- and high-dose groups were administered BHG at doses of 1.25， 2.5， and 5.0 mg/（g·d） by oral gavage， respectively， while the madopar group received madopar tablets at dose of 0.093 8 mg/（g·d） by oral gavage. The blank group and the model group were given 0.2 ml/10 g of distilled water by gavage. All treatments were given once daily for 14 days. Open field test， pole climbing test and grip test were used to evaluate the behavior of mice in each group. Immunohistochemistry was used to detect the expression of tyrosine hydroxylase （TH） in striatum. Nissl staining was used to detect the activity of striatal neurons. The contents of DA and 3,4-dihydroxyphenylacetic acid （DOPAC） in striatum were detected by ultra performance liquid chromatography tandem mass spectrometry. The number and volume of synaptic vesicles were observed by transmission electron microscope. The expression of vesicular monoamine transporter 2 （VMAT2） in striatum was detected by immunofluorescence. Western Blot was used to detect the expression of extracellular signal-regulated kinase （ERK）， phosphorylated ERK （p-ERK）， cAMP response element-binding protein （CREB）， phosphorylated CREB （p-CREB） and VMAT2 in striatum. ResultsCompared to the blank group， mice in the model group showed a significant decline in total distance and average speed in the open field test， along with an increase in total resting time； in the pole test， both the time required for the mice to turn completely downward （T-turn） and the total time taken to reach the bottom of the pole （T-total） were prolonged； forelimb grip strength was reduced； in the striatum， the mean optical density of TH， the average fluorescence intensity of VMAT2 protein， and DA content all decreased， while the number of striatal neurons was reduced， and the DOPAC/DA ratio was elevated； the levels of p-ERK/ERK， p-CREB/CREB， and VMAT2 in the striatum significantly decreased （P＜0.01）； transmission electron microscopy revealed that both the number and volume of synaptic vesicles in striatal neurons were markedly reduced. Compared to the model group， mice in the madopar group and BHG low-， medium- and high-dose groups showed significant improvements in all the above indicators （P＜0.05 or P＜0.01）. Compared to madopar group， the BHG high-dose group exhibited increased DA content and elevated p-CREB/CREB ratio in the striatum （P＜0.05）. Compared to the BHG low-dose group， the BHG high-dose group showed increased total distance and mean velocity， decreased total resting time， T-turn， and T-total， as well as enhanced forelimb grip strength； moreover， the average fluorescence intensity of VMAT2 protein， DA content， p-ERK/ERK， p-CREB/CREB， and VMAT2 levels in the striatum were all significantly elevated （P＜0.05 or P＜0.01）. ConclusionBHG may restore DA homeostasis and alleviate the damage of dopaminergic neurons by regulating ERK/CREB/VMAT2 signaling pathway.

Alveolar soft part sarcoma(ASPS)is a rare malignant tumor characterized by a lack of specific clinical manifestations,often presenting as painless,progressively enlarging masses.Its occur-rence in the retroperitoneum is uncommon.Due to the large retroperitoneal space,the tumor typically does not cause significant symptoms in the early stages,leading to advanced disease or metastasis at presentation,and consequently,poor prognosis.This article reported the clinical diagnosis and treatment of a patient with retroperitoneal ASPS and elucidated the features of epidemiology,clinical manifesta-tions,diagnostic modalities,and treatment approaches of this disease in conjunction with the literature.

ObjectiveTo explore the possible mechanism of Bushen Huoxue Formula （补肾活血方， BHF） in the treatment of Parkinson's disease （PD） from the the perspective of intestinal flora. MethodsSeventy-two male C57/BL6J mice were randomly divided into blank group， model group， Madopar group and low-， medium- and high-dose BHF groups， with 12 mice in each group. The mice in the blank group were intraperitoneally injected with 10 ml/kg of normal saline， and those in the other groups were intraperitoneally injected with 30 mg/kg of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine （MPTP） at a concentration of 3 mg/ml to induce PD mice model， both once a day for 7 consecutive days. After successful modeling， the low-， medium-， and high-dose BHF groups were given 7.5， 15， and 30 g/（kg·d） of BHF by gavage， respectively， while the Madopar group was given 112.5 mg/（kg ·d） of Domedopar tablets by gavage， and the blank group and the model group were given 15 ml/（kg·d） of distilled water， all once a day for 14 consecutive days. The rod climbing test， rotating rod test， grip strength test and weight-bearing swimming test were used to evaluate the behavioral indicators of mice. Western blotting was used to measure the protein expression levels of Toll-like receptor （TLR）/nuclear factor kappa B （NF-κB） pathway inflammatory factors in the mouse ileum， including Toll-like receptor 2 （TLR2）， Toll-like receptor 4 （TLR4）， NF-κB， tumor necrosis factor α （TNF-α）， interleukin 6 （IL-6）， and interleukin 17 （IL- 17）. 16S rRNA high-throughput sequencing was used to analyze changes in mouse intestinal flora. ResultsCompared to those in the blank group， the mice in the model group had longer bottoming time when climbing the pole， reduced grip strength， shortened rotary pole duration and swimming duration， and increased protein expression levels of TLR2， TLR4， NF-κB， TNF-α， and IL-6 in the ileal tissue （P＜0.01）. Compared to the model group， the Madopar group and the low-， medium- and high-dose BHF groups had shortened bottoming time of the climbing pole and increased grip strength； the Madopar group and the high-dose BHF group had prolonged rotary pole duration， and reduced protein expressions of TLR2， TLR4， NF-κB， TNF-α， IL-6， and IL-17 levels； and only the high-dose BHF group had prolonged swimming duration （P＜0.05 or P＜0.01）. Compared to those in the low-dose BHF group， the bottoming time of the climbing pole were shorter in the moderate- and high-dose groups （P＜0.05 or P＜0.01）， and the grip strength increased while the protein expression levels of TLR2， TLR4 and IL-17 decreased in the high-dose group （P＜0.05 or P＜0.01）. The intestinal flora results showed significant differences between the blank group and the model group in the Dominance index， Pielou_e index， Shannon index， and Simpson index （P＜0.05 or P＜0.01）. Compared to those of the model group， the Shannon index， Chao1 index， and Observed_otus index of the Madopar group， as well as the Chao1 index， Observed_otus index， Dominance index， Pielou_e index， Shannon index， and Simpson index of the high-dose BHF group all showed significantly statistical differences （P＜0.05 or P＜0.01）. At the phylum level， the relative abundance categories of bacterial phyla with statistically significant differences in each group included Proteobacteria， Bacteroidetes， and Firmicutes （P＜0.05 or P＜0.01）. At the genus level， the relative abundance categories of bacterial genera with statistically significant diffe-rences among each group included Muribaculaceae， Akkermansia， and Helicobacter pylori （P＜0.05 or P＜0.01）. ConclusionThe possible mechanism of BHF in treating PD may be to reconstruct the disordered intestinal flora structure and improve the inflammatory response.

Objective To observe the value of enhanced CT radiomics combined with clinical indicators for predicting of extramural venous invasion(EMVI+)of colorectal cancer.Methods Data of 131 patients with colorectal cancer proved by surgery pathology were retrospectively analyzed.The patients were divided into training set(n=92,including 44 cases with EMVI+ and 48 with EMVI-)and test set(n=39,including 23 cases with EMVI+ and 16 with EMVI-)at the ratio of 7∶3.The best radiomics features were extracted based on preoperative portal-venous phase CT to construct a radiomics model.Univariate and multivariate logistic regression analysis were used to analyze the clinical,CT and pathological data of the training set,and the independent predictors of colorectal cancer EMVI were screened to build a clinical model.Finally a combined model was established based on radiomics and clinical model.Receiver operating characteristic curve was drawn,and the area under the curve(AUC)was calculated to evaluate the efficacy of each model for predicting EMVI+ in colorectal cancer.Calibration curve and decision curve analysis were used to evaluate the calibration degree and clinical practicability of the models.Results Four best radiomics features were selected to construct the radiomics model.Carbohydrate antigen(CA)19-9 and CA 72-4 were both independent predictors of EMVI+ for colorectal cancer(OR=1.033,1.285,both P＜0.05).The AUC of combined model(AUC=0.908)for predicting EMVI+ of colorectal cancer in training set was higher than that of radiomics and clinical models(AUC=0.825,0.770,P=0.017,0.003).In test set,the AUC of radiomics,clinical and combined models was 0.751,0.632 and 0.799,respectively,not being statistical different between each pair(all P＞0.05).The radiomics model and combined model both had good calibration degree.Taken ＞0.1 in training set and ＞0.12 in test set as the thresholds,the clinical net benefit of combined model was higher.Conclusion Enhanced CT radiomics combined with clinical indicators could effectively predict EMVI+of colorectal cancer.

Objective:To investigate alterations in functional connectivity network and brain function activity in childhood absence epilepsy (CAE) based on neuromagnetic signals by using multi-frequency magnetoencephalography.Methods:Twenty-five drug-naive children diagnosed with CAE from the Affiliated Brain Hospital of Nanjing Medical University and the Affiliated Children′s Hospital of Nanjing Medical University during October 2022 and March 2024 and 25 healthy controls matched for age and sex from community were recruited in this cross-sectional study. The interictal data, ictal data of CAE and healthy control children were collected using a CTF-275 channel magnetoencephalography system. Corrected amplitude envelope correlation was used to construct functional connectivity network, and network-based statistics were used to compare network differences between groups. Relative power spectral density was used to describe the distribution characteristics of whole-brain spectral power. Nonparametric permutation tests were conducted 1 000 times to compare spectral power differences between groups.Results:In terms of functional connectivity, significant increases in network activity were observed in the low-frequency bands (δ, θ) during interictal periods in children with CAE. A sub-network with significantly increased functional connectivity, including key nodes of the default mode network, was observed in the δ band. Compared with interictal periods, functional connectivity in the δ band decreased during absence seizures in children with CAE, while connectivity in the mid-to-high-frequency bands (α-γ2) increased. In terms of spectral power, children with CAE during interictal periods exhibited widespread magnetic source activation in the δ band, activation in parts of the parietal and occipital lobes in the θ band, and significantly decreased magnetic source intensity in most areas of the parietal, occipital, and temporal lobes in the α-γ2 band. Compared with interictal periods, children with CAE during absence seizures exhibited widespread magnetic source activation in the δ band, and significantly decreased activation in the θ-γ2 band. According to the magnetic source distribution map, during absence seizures, the frontal lobe replaced the parieto-occipital region in cortical activation in the α band.Conclusion:In the analysis of functional network and spectral power based on multi-frequency neuromagnetic signals, the network pattern and magnetic source activation of children with CAE during interictal periods were significantly different from those of healthy children, and there were characteristic changes in neuromagnetic signals during consciousness impairment caused by absence seizures in children with CAE.

Aim To establish the pharmacokinetic-pharmacodynamic(PK-PD) modeling to characterize the antipyretic effects of coptisine, an active component in coptis chinensis on rats.Methods Nine healthy male Sprague-Dawley(SD) rats were randomly divided into three groups, each with three.The rats in the first group were injected intravenously with lipopolysaccharide(LPS,100 μg·kg-1) alone.The second and third group rats were given coptisine high-dose(3.87 mg·kg-1) and coptisine low-dose(1.93 mg·kg-1) by tail vein injection at 30 min after LPS injection, respectively.Body temperature was measured at different time points, and blood samples from tail vein were collected simultaneously.The blood concentration of coptisine was determined by ultra performance liquid chromatography.Monolix software was used to model PK-PD of coptisine mean plasma concentration and temperature effects,by population computation with non-covariates.Besides.the model with advantage was selected by the fitting goodness.Results Coptisine could inhibit body temperature of endotoxin-induced fever in rats significantly.Two-compartment linear elimination model was used to describe the final PK model.Gaussian function, an input function of body temperature changes, which was used to depict PD model, the PK and PD models were connected by the Emax model.At last, the final model was fitted better;the fitting results indicated that the EC50 of antipyretic effect of coptisine was 89.7 μg·L-1, and the Emax was 1.88℃.Conclusions Coptisine has a powerful anti-pyretic effect on endotoxin-induced pyrexia of rats with high potency, Low in vivo distribution and quick clearance.

Objective To understand the correlation between psychological counseling behaviors of accompanying family members and anxiety and depression of inpatients with hepatocellular carcinoma. Methods Used self-designed questionnaires to investigate the behaviors of 45 accompanying family members psychological counseling for their relative hospitalized patients with hepatocellular carcinoma, at the same time, evaluated the anxiety and depression among those 45 hospitalized patients with hepatocellular carcinoma, then analyzed the correlation between the accompanying family members' psychological counseling behaviors and hepatocellular carcinoma in patients' anxiety and depression. Results Among the accompanying family members,53.3%(24/45) were the spouses of the patients. During the accompanying nursing time, there were 20.0%(9/45) accompanying families told to their relative patients less than 2 hours per day, and 80.0%(36/45) told to the patients over 2 hours per day. The proportion of anxiety and depression in the hospitalized patients with hepatocellular carcinoma was 28.9%(13/45) and 77.8% (34/45) respectively. Whether the relationship between the accompanying family members and the patients with hepatocellular carcinoma were spouse relationship was related to the incidence of depression in the patients (χ2=10.470, P=0.005), and whether the time accompanying family members spent in talking with the patients over 2 hours every day was correlative with the incidence of anxiety and depression in the patients (χ2=7.012, P =0.030 andχ2=6.438, P=0.040). The patients who accompanying families told to them less than 2 hours per day suffered a higher depression rate (8/9), and among the patients who accompanying families told to them over 2 hours per day, the lowest rate of anxiety (1/12) was found in the patients who accompanying families told to them around 4.1-6.0 hours per day. Conclusions The patients who are accompanied and cared by their spouses have lower depression rate and lesser depression extent. The accompanying families talk to the patients total 4.1-6.0 hours per day could most favorably reduce the incidence of anxiety and depression in the hospitalized patients with hepatocellular carcinoma.

Objective To investigate the clinical efficacy of bromhidrosis with botulinum toxin A by needle free injection.Methods A total of 40 patients with bromhidrosis were collected and divided into needle free group and needle group.A comparative study was carried out in those subjects.Patients in needle free group received needle free injection of botulinum toxin A by INJEX30;Needle group received traditional injection by 26 G needles.Results In needle free group,16 cases were cured,3 cases were effective,1 case was ineffective,no significant pain,hematomas or necrosis were found.In needle group,15 cases were cured,4 cases were effective,and 1 case was ineffective;localized hematoma occurred in 2 cases.And cases in group needle experienced pain more intensely than cases in needle free group.Conclusions The INJEX30 improves the security,comfort and therapy compliance of botulinum toxin A injection in the bromhidrosis patients,with similar efficacy with traditional injection.

ObjectiveTo study the inhibiting effects on the invasion and metastasis of melanoma by CXCR4 gene silence in nude mice.MethodsThe CXCR4 specific recombinant plasmid vector was constructed and transfected into the cultured MV3 cell line with lipofectamine.The models of subcutaneous melanoma in nude mice were established with MV3 cells.The nude mouse model of lung metastasis was established by injection of MV3 cells into the tail vein.The animals were sacrificed at 8weeks after the melanoma cells injection.CXCR4-shRNA plasmid vectors were discontinuously injected directly into the established tumor and vein.The changes of weight and size of the tumors and the mice body weight during the therapy were calculated respectively.Histological observation was performed to evaluate the presence and number of metastatic tumors.ResultsThe subcutaneous melanoma tumors in nude mice were established successfully.The growth of tumors in the CXCR4-shRNA injected nude mice was inhibitted obviously through tumor growth curve. There were significant differences between negative shRNA control nude mice and blank control nude mice (P＜0.01).Melanoma cells with CXCR4 shRNA permanent transfection had a much lower lung and brain and liver metastatic potential in nude mice than control cells and mock control cells in vivo.ConclusionsCXCR4 gene silencing mediated by shRNA significantly suppresses the growth of MV3 cell in vitro.Silencing of CXCR4 mediated by shRNA can also effectively decrease the metastatic potential of lung and liver and brain.