ObjectiveTo investigate the mechanisms by which Huanglian Jiedutang （HLJDT） modulates microglial （MG） phenotypes through the sialic acid-binding Ig-like lectin 2 （SIGLEC2/CD22）/Src-homology-2-domain-containing protein tyrosine phosphatase-1 （SHP-1）/phosphorylated protein kinase B （p-Akt） signaling pathway， thereby promoting myelin repair and alleviating agitation-like behaviors in vascular dementia （VAD）. MethodsSixty C57BL/6J mice were randomly assigned to a sham （normal） group， model group， HLJDT low-， medium-， and high-dose groups （2.5， 5， and 10 g·kg^-1·d^-1）， and a risperidone group （2 mg·kg^-1·d^-1）， with 10 mice per group. VAD was induced by bilateral common carotid artery stenosis （BCAS）. From day 42， mice received drug interventions for 2 weeks. Agitation-like behaviors were assessed using the resident-intruder test. After behavioral testing， ventrolateral part of the ventromedial hypothalamus （VMHvl） tissues were collected. Western blot was used to measure protein levels of myelin oligodendrocyte glycoprotein （MOG）， myelin basic protein （MBP）， proteolipid protein （PLP）， inducible nitric oxide synthase （iNOS）， arginase-1 （Arg1）， CD86， CD206， and CD22， SHP-1， and p-Akt. Immunofluorescence was used to evaluate myelin-associated glycoprotein （MAG） intensity and the proportion of iNOS⁺/ionized calcium-binding adapter molecule 1 （Iba1）⁺ cells. ELISA was used to detect tumor necrosis factor-α （TNF-α）， interleukin （IL）-6， and IL-1β. ResultsCompared with the normal group， the model group exhibited markedly increased biting and aggressive behaviors and shortened attack latency （P<0.01）. MOG， MBP， and PLP protein levels and MAG fluorescence intensity were significantly reduced （P<0.05， P<0.01）. INOS and CD86 expression and TNF-α， IL-6， and IL-1β levels were significantly elevated （P<0.01）. CD22 and SHP-1 expression increased significantly （P<0.01）， whereas p-Akt expression decreased （P<0.01）. Compared with the model group， the medium- and high-dose HLJDT groups and the risperidone group showed markedly reduced biting and aggression （P<0.05， P<0.01） and prolonged attack latency （P<0.01）. MOG， MBP， and PLP levels and MAG fluorescence intensity were significantly increased （P<0.05， P<0.01）. INOS， CD86， TNF-α， IL-6， and IL-1β levels decreased significantly （P<0.05， P<0.01）. CD22 and SHP-1 expression decreased， while p-Akt expression increased significantly （P<0.05， P<0.01）. ConclusionHLJDT may modulate CD22/SHP-1/p-Akt signaling in the VMHvl， promote the shift of MG toward an anti-inflammatory and phagocytic phenotype， enhance myelin repair， and improve agitation-like behaviors in VAD mice.

ObjectiveTo investigate the ameliorative effects of quercetin on neuropsychiatric symptoms associated with vascular dementia （VaD） and to elucidate the molecular mechanism， specifically whether quercetin inhibits pro-inflammatory activation of microglia by modulation of the receptor-interacting serine/threonine-protein kinase 1 （RIPK1）/NOD-like receptor protein 3 （NLRP3）/Caspase-1 signaling pathway， thereby promoting myelin repair in the medial prefrontal cortex （mPFC）. MethodsA C57BL/6J mouse model of VaD with neuropsychiatric symptoms was established by bilateral common carotid artery stenosis （BCAS） combined with chronic restraint stress （CRS）. Mice were randomly divided into a sham group， a model group， low-dose， medium-dose， and high-dose quercetin groups （30， 60， 120 mg·kg^-1·d^-1）， and a fluoxetine group （10 mg·kg^-1·d^-1）. After intervention， depressive- and anxiety-like behaviors were assessed by the sucrose preference test （SPT）， forced swim test （FST）， open field test （OFT）， and elevated plus maze （EPM）. mPFC tissue was collected. Immunofluorescence （IF） was used to detect myelin basic protein （MBP） expression and microglial morphology. Western blot was used to measure the protein level of MBP， myelin oligodendrocyte glycoprotein （MOG）， myelin-associated glycoprotein （MAG）， inducible nitric oxide synthase （iNOS）， CD86， RIPK1， phosphorylated RIPK1 （Ser166）， NLRP3， and Caspase-1. Enzyme-linked immunosorbent assay （ELISA） was used to determine the level of tumor necrosis factor-alpha （TNF-α）， interleukin-6 （IL-6）， and interleukin-1β （IL-1β）. ResultsCompared with the sham group， the model group exhibited significant depressive- and anxiety-like behaviors （P<0.01）， significantly decreased protein expression of MBP， MOG， and MAG in the mPFC （P<0.01）， activated microglia （characterized by enlarged cell bodies， reduced protrusions， and upregulated iNOS and CD86 expressions， P<0.01）， and significantly elevated p-RIPK1/RIPK1 ratio， NLRP3， Caspase-1 protein expression， and level of TNF-α， IL-6， and IL-1β （P<0.01， P<0.05）. Compared with the model group， the quercetin treatment （especially at medium and high doses） significantly ameliorated these behavioral abnormalities （P<0.05， P<0.01）， increased the expression of MBP （protein and fluorescence intensity）， MOG， and MAG in the mPFC （P<0.05， P<0.01）， suppressed excessive microglial activation （characterized decreased cell bodies， increased protrusions， and downregulated iNOS and CD86 expressions， P<0.01）， and significantly reduced the p-RIPK1/RIPK1 ratio， NLRP3， Caspase-1 protein expression， and inflammatory cytokine levels （P<0.01）. ConclusionQuercetin effectively alleviates neuropsychiatric symptoms in VaD mice. Its mechanism may be associated with the inhibition of microglial inflammatory activation mediated by the RIPK1/NLRP3/Caspase-1 signaling pathway， thereby promoting myelin repair in the mPFC region.

Objective To analyze the risk factors for catheter-related thrombosis(CRT)in the upper arm infusion port(UAP)and to construct a machine-learning prediction model.Methods A total of 6028 patients,who received UAP implantation at Shanghai Renji Hospital of China from February 2014 to February 2023,were enrolled in this study.The patients were divided into training set(n=4 219)and validation set(n=1 809).Six machine-learning prediction models,including Least Absolute Shrinkage and Selection Operator(LASSO)regression,random forest,decision tree,neural network,XGBoost and logistic,were constructed,and the model having best performance was selected as the optimal model.SHapely Additive exPlanations(SHAP)analysis was used to explain the neural network model,and DALEXtra package was used to explain the continuous variables.Results The neural network model was chosen as the final model.The variables,in order of the degree of importance from high to low,included sex,the diameter of catheter,catheter tip confirmation method,the length of catheter,inpatient or outpatient status,history of central venous catheter implantation,the length of subcutaneous tunnel,age,body mass index(BMI),primary tip displacement,and left or right venous approach.The learning curve,i.e.the area under curve(AUC)of the receiver operating characteristic(ROC)curve,for the training set was＞0.6,and the Delong testing and Bootstrap Methods Test showed that the neural network model performed well(P＜0.05).The Kolmogorov-Smirnov plot(KS plot)value was 0.313 5,indicating that the model had the good ability of discrimination.The clinical impact curve(CIC)assessment revealed that the model had good clinical value.Conclusion The machine-learning prediction model of upper arm infusion port with CRT has been successfully constructed.For minimizing the risk of CRT,it is recommended to prioritize the use of 5 F diameter catheters,adopt left-sided venous approach and positioning the tip of the catheter based on anatomical measurements,besides,the catheter length should be not shorter than 36.56 cm,and the subcutaneous tunnel length should not be less than 5 cm.The basic features associated with higher CRT risk include age of 50-65 years,BMI being between 18.69 kg/m2 and 20.81 kg/m2 or between 23.68 kg/m2 and 23.94 kg/m2 and male.

Objective To study the role of photobiomodulation(PBM)in promoting the repair of spinal cord injury(SCI)by regulating microglial cells.Methods Forty-five C57BL/6J mice were randomly divided into the sham operation(Sham)group,surgery(SCI)group and the treatment(SCI+PBM)group,with 15 mice in each.After laminectomy of the T10 vertebral body in the three groups of mice,the SCI group and the SCI+PBM group were used to construct the model of spinal cord hemisection.The SCI+PBM group received immediate PBM treatment after spinal cord injury,while the other two groups did not.On the 1st,3rd,7th,14th,21st and 28th days(D1,D3,D7,D14,D21,D28)after the operation,the Basso Mouse Scale(BMS)was used to assess the recovery of the hind limb motor function of the mice.On the 28th day post operatively,immunofluorescence was used to detect the changes of neurons in the areas of injury in the three groups of mice.Quantitative real-time PCR and Western blotting experiments were used to detect the phenotypic changes of BV2 cells under the interventions of PBM with inflammatory stimulation.Western blotting experiments were conducted to detect the effects of PBM on the nuclear factor kappa-B(NF-κB)pathway.Results On the 28th day after the operation,the results of the mouse motor assessment showed that the BMS scores and related behaviors of the mice in the SCI+PBM group were better than those of the mice in the SCI group(P＜0.05),and the neurons in the SCI+PBM group far outnumbered those in the SCI group(P＜0.05).The results of quantitative real-time PCR and Western blotting experiments showed that on the 14th day after the operation,PBM promoted the activation of M2-type microglial cells in vivo but inhibited the activation of M1-type microglial cells.In vitro experiments confirmed that PBM could promote the polarization of BV2 cells towards M2-type microglial cells.In addition,PBM inhibited the activation of the NF-κB pathway in injured spinal cords and in activated BV2 cells.Conclusion PBM can promote the repair of spinal cord injury in SCI mice by promoting microglial cells through inhibiting the NF-κB pathway.

ObjectiveTo evaluate the quality of Lygodium japonicum (Thunb.) Sw. (L. japonicum, Hai Jin Sha) by comparing its components without stewed (W) and stewed (S) using ultra-high-performance liquid chromatography (UHPLC) and chemometric analysis. Additionally, network pharmacology was employed to investigate the possible mechanisms of action of L. japonicum in the urinary calculi (UC) treatment.MethodsA fingerprinting method was established to identify components through UHPLC-tandem mass spectrometry. Chemometric techniques were used to compare the L. japonicum extraction methods. Furthermore, various network pharmacological approaches were used to identify and analyze the potential targets of the identified components in relation to UC.ResultsThe W and S extracts were distributed into two distinct clusters. Significant differences in the levels of protocatechuic aldehyde, caffeic acid, and p-coumaric acid were observed between S and W. Network pharmacology analysis revealed that the primary targets of L. japonicum in the UC treatment were serum albumin and epidermal growth factor receptors, with potential active components including protocatechuic acid and caffeic acid.ConclusionThis study comprehensively examined the therapeutic components of L. japonicum before and after boiling, shedding light on its potential mechanisms of action in UC treatment. These findings offer valuable insights into the development and utilization of L. japonicum resources.

Objective:Screening factors that might influence rheumatoid arthritis (RA) complicating interstitial lung diseases (ILD) by constructing and validating a model for early diagnostic.Methods:The study subjects were composed of 712 RA patients in the Department of Rheumatology and Immunology of the Second Hospital of Shanxi Medical University during December 2019 to October 2022. Fifty-two variables such as their demographic data, clinical symptoms, and laboratory indexes were collected. Patients were categorized into RA-only group and RA-ILD group with or without the occurrence of ILD disease. After data preprocessing, subjects were randomly assigned to the modeling and validation groups in a 7:3 ratio.Univariate analysis comparing baseline characteristics of the two groups of patients. Feature selection was performed using LASSO and SVM-RFE regression algorithms.Screening indicators were analyzed by logistic regression and the results were used to develop a nomograms model for the early diagnosis of RA complicating interstitial lung disease; and the modeling group was evaluated for its performance for internal assessment of the model and internal validation using data from the validation group.Results:A total of 712 subjects participated in the study, of which 498 in the modeling group and 214 in the validation group. Univariate analysis showed that the differences between the two groups were statistically significant ( P<0.05) in 18 characteristic indexes, including male, gender, age, smoking history, drinking history, number of swollen joints, number of painful joints, use of prednisone, WBC, ESR, CRP, IL-2, IL-10, IL-17, TNF-α, INF-γ, AFA family, APF, and serum albumin. The LASSO algorithm identified 13 risk variables for RA-ILD, the SVM-RFE algorithm identified 12 variables for RA-ILD, and the intersecting risk variables were male, age, history of alcohol consumption, number of painful joints, prednisone acetate, IL-2, AFA family, TNF-α, serum albumin, and IL-10. The results of multifactorial logistic regression analysis confirmed that the differences between males [ OR(95% CI)=3.61(2.11, 6.18)], gender, age [ OR(95% CI)=1.05(1.03, 1.08)], number of painful joints [ OR(95% CI)=1.03(1.01, 1.06)], IL-2 [ OR(95% CI)=0.91 (0.84, 0.99)], and TNF-α[ OR (95% CI)=1.06 (1.02, 1.10)] were statistically significant ( P<0.05) and were independently influences on ILD complicated by RA. The modeling and validation groups that were used to construct early diagnostic Nomograms had high calibration curve accuracies, and the model had a high diagnostic power, which was mainly demonstrated by the receiver operating characteristic (ROC) area under the curve (AUC) and decision curve analysis(DCA), the model modeling group had an AUC of 0.76 (95% CI=0.71, 0.81), with net benefit rates of 3%~82% and 93%~99%, whereas the model validation group had an AUC of 0.71 (95% CI=0.64, 0.79), with net benefit rates of 5%~11%, 14%~60% and 85%~89%. Conclusion:Male, gender, age, number of painful joints, IL-2, and TNF-α are independent factors for RA complicated with ILD, and the Nomogram model constructed has good performance in early diagnosis of the disease.

Metabolic syndrome is a complex group of metabolic disorders with an increasing global incidence rate,posing a serious threat to human health.Sodium-glucose linked transporter 2(SGLT2)inhibitors are a new type of oral hypoglycemic drug.SGLT2 inhibitors not only lower blood glucose level in a non-insulin-dependent manner by inhibiting glucose reabsorption by renal proximal convoluted tubular epithelial cell to promote urinary glucose excretion,but also by improving islet β cell function,reducing inflammatory responses,and inhibiting oxidative stress.In addition,SGLT2 inhibitors can reduce body weight through osmotic diuresis and increase fat metabolism;reduce blood pressure by inhibiting excessive activation of sympathetic nervous system and by improving vascular function.They can also improve blood lipids by increasing degradation of triacylglycerol;reduce blood uric acid by promoting uric acid excretion in kidney and intestine,and by reducing uric acid synthesis.This article reviews the effects and mechanisms of SGLT2 inhibitors on multiple metabolic disorders in metabolic syndrome and explores their potential application in metabolic syndrome treatment.

ObjectiveThis study aims to investigate the effect of Huanglian Jiedutang on brain iron metabolism disorders， myelin damage， and aggressive behavior in vascular dementia （VaD） mice by regulating the F-box leucine-rich repeat protein 5 （FBXL5）/iron regulatory protein 2 （IRP2） pathway. MethodSixty C57BL/6J mice were randomly divided into six groups： sham operation group， model group， risperidone group （2 mg·kg^-1·d^-1）， and low-dose， medium-dose， and high-dose groups of Huanglian Jiedutang （0.25， 0.5， 1 g·kg^-1·d^-1）， with 10 mice in each group. The VaD model was established by bilateral carotid artery stenosis （BCAS）. Drug intervention was administered for two weeks starting from the seventh week. Behavioral assessments， including the touch escape and resident-intruder tests， were conducted in the ninth week. After the behavioral tests， ventromedial hypothalamus ventrolateral （VMHvl） tissue samples were collected. Western blot was used to detect the expression of myelin-associated glycoprotein （MAG）， myelin oligodendrocyte glycoprotein （MOG）， myelin basic protein （MBP）， 4-hydroxynonenal （4-HNE）， glutathione peroxidase 4 （GPX4）， transferrin receptor 1 （TFR1）， ferritin light chain （Ft-L）， ferroportin 1 （FPN1）， FBXL5， and IRP2. Immunofluorescence was used to measure MBP fluorescence intensity. Transmission electron microscopy was employed to observe ultrastructural changes in the myelin sheath. Perl's staining was used to detect tissue iron deposition. Malondialdehyde （MDA） and superoxide dismutase （SOD） levels were measured by enzyme linked immunosorbent assay （ELISA）. ResultCompared to the sham operation group， the model group exhibited a significant increase in biting， aggression， and irritability scores， along with a reduced latency of the attack （P<0.01）. The expression levels of MAG， MOG， and MBP， as well as the fluorescent density of MBP， were significantly decreased （P<0.01）. Disordered myelin ultrastructure， increased Ft-L and TFR1 expression， decreased FPN1 expression， and elevated iron deposition were observed （P<0.01）. Antioxidants GPX4 and SOD were reduced， while 4-HNE and lipid peroxidation product MDA were increased （P<0.01）. FBXL5 protein expression decreased， and IRP2 protein expression increased （P<0.01）. Compared with the model group， in the middle-dose and high-dose groups of Huanglian Jiedutang and the risperidone group， the number of bites， aggressive behaviors， and irritability scores were reduced （P<0.05， P<0.01）， while the latency of the attack increased （P<0.01）. In the middle-dose and high-dose groups of Huanglian Jiedutang， the expression levels of MAG， MOG， and MBP， as well as MBP immunofluorescence increased （P<0.01）. The ultrastructure was orderly arranged. Ft-L and TFR1 expression decreased； FPN1 expression increased， and iron deposition was reduced （P<0.01）. GPX4 and SOD expression levels increased， and 4-HNE and MDA expression levels decreased （P<0.01）. FBXL5 protein expression increased， and IRP2 protein expression decreased （P<0.01）. ConclusionHuanglian Jiedutang may alleviate brain iron metabolism disorders， myelin damage， and aggressive behavior in VaD mice by regulating FBXL5/IRP2 expression in the VMHvl region.

Objective:To establish the ultra-high performance liquid chromatography (UPLC) fingerprint and high performance liquid chromatography (HPLC) content determination method of Curcumae Radix standard decoction; To predict the quality markers of Curcumae Radix standard decoction combined with network pharmacology.Methods:UPLC method was used to establish the fingerprint of Curcumae Radix standard decoction, and the common peaks were determined. Combined with chemical pattern recognition techniques such as similarity analysis and clustering analysis, Curcumae Radix standard decoction from different producing areas was studied, and curcumol was used as an index to determine the content of 24 batches of Curcumae Radix standard decoction. At the same time, network pharmacology was used to predict potential of curcumol and (1S, 6β)-1β-Methyl-4-(1-methylethylidene)-7β-(3-oxobutyl) bicyclo [4.1.0] heptan-3-one.Results:A total of 24 batches of Curcumae Radix standard decoction from different habitats were compared and analyzed, and 10 common peaks were calibrated. The similarity of 24 batches of samples ranged from 0.982 to 0.999. Clustering analysis and principal component analysis divided them into three categories. Heat map analysis showed that peak 8 (curcumol) and peak 9 ((1S, 6β)-1β-Methyl-4-(1-methylethylidene)-7β-(3-oxobutyl) bicyclo [4.1.0] heptan-3-one) were the main components. The content of curcumol in 24 batches of Curcumae Radix standard decoction was 0.69-1.87 mg/g; curcumol and (1S, 6β)-1β-Methyl-4-(1-methylethylidene)-7β- (3-oxobutyl) bicyclo [4.1.0] heptan-3-one may regulate the neuroactive ligand-receptor interaction signaling pathway, calcium signaling, and excitation by regulating neuroactive ligand-receptor interaction signaling pathway, calcium signaling, and excitation. It was preliminarily predicted that curcumol and (1S, 6β)-1β-Methyl-4-(1-methylethylidene)-7β-(3-oxobutyl) bicyclo [4.1.0] heptan-3-one were potential quality markers of Curcumae Radix.Conclusion:Curcumol and (1S, 6β)-1β-Methyl-4-(1-methylethylidene)-7β-(3-oxobutyl) bicyclo [4.1.0] heptan-3-one are potential quality markers of Curcumae Radix standard decoction, and the established fingerprint can be used for the quality control of Curcumae Radix standard decoction.

Objective To evaluate the technical feasibility and safety of upper arm vein approach in the implantation of totally implantable venous access port(TIVAP)under the guidance of ultrasound combined with DSA.Methods The clinical data of 1 546 patients with malignant tumors,who received TIVAP implantation via upper arm vein access under the guidance of ultrasound combined with DSA at the Affiliated Renji Hospital,School of Medicine of Shanghai Jiao Tong University of China between January 2020 and January 2022,were retrospectively analyzed.The implantation success rate,single-puncturing success rate,operation time,and complications were compared between the PICC catheterization room and the DSA operating room.Results The technical success rate in the 1546 patients was 100％,with a single-puncturing success rate of 99.48％.In 766 patients the TIVAP implantation was performed in the PICC catheterization room(PICC group),and in 780 patients the TIVAP implantation was carried out in the DSA operating room(DSA group).The mean operation time in the DSA group was(20.1±1.3)min,which was obviously shorter than(25.4±1.9)min in the PICC group,and the incidence of primary catheter misplacement in the DSA group was 0％,which was remarkably lower than 0.78％in the PICC group(P＜0.05).No statistically significant differences in the incidences of complications,including infection,thrombosis,upper limb movement disorder,catheter occlusion,exposure of infusion port body,and overturn of infusion port body,existed between the two groups(P＞0.05).Conclusion Ultrasound-guided TIVAP via upper arm vein approach is a safe and effective infusion route for patients with malignancy receiving chemotherapy.The combination use of ultrasound guidance and intraoperative DSA guidance can reduce the operation time as well as the incidence of operation-related complications.