Objective To explore the potential mechanism of Xinnao Maikang in improving ApoE-/-atherosclerosis mice based on PPARγ/LXRα/ABCA1 pathway.Methods Totally 50 ApoE-/-mice were randomly divided into model group,atorvastatin group,Xinnao Maikang high-,medium-and low-dosage groups,and fed with high-fat diet for 12 weeks to establish atherosclerosis model.Another 10 C57BL/6J mice were selected as normal group,and atorvastatin group was given atorvastatin calcium suspension by intragastric administration,Xinnao Maikang high-,medium-and low-dosage groups were given Xinnao Maikang Decoction 56,28,14 g/kg by intragastric administration,the normal group and model group were given equal volume of normal saline by intragastric administration for 8 weeks.Liver index of mice was detected,serum lipid level of mice was detected by automatic biochemical analyzer,TC and TG contents in liver tissue were detected by biochemical kit,morphology of aortic intima and liver tissue were observed by HE staining,lipid deposition in liver tissue was observed by oil red O staining,the expressions of PPARγ,LXRα,ABCA1,ABCG1 and SR-BⅠ in liver tissue were detected by Western blot.Results Compared with the normal group,the liver index in the model group significantly increased(P<0.05),the contents of serum TC,TG and LDL-C significantly increased(P<0.05),and the contents of HDL-C significantly decreased(P<0.05),the contents of TC and TG in liver tissue increased(P<0.05),the aortic wall was thickened,the number of subcutaneous foam cells increased,the arrangement of liver cells were disaffected,and a large number of fat vacuoles could be seen,the protein expressions of PPARγ,LXRα,ABCA1,ABCG1 and SR-BⅠ in liver tissue significantly decreased(P<0.01).Compared with the model group,the liver index of Xinnao Maikang high-,medium-and low-dosage groups and atorvastatin group significantly decreased(P<0.05),the serum contents of TC,TG and LDL-C significantly decreased(P<0.05),and the HDL-C contents significantly increased(P<0.05),the contents of TC and TG in liver tissue significantly decreased(P<0.05),the aortic wall thickened and the subcutaneous foam cells decreased,the liver cells were arranged neatly,and fat degeneration was reduced to varying degrees,the protein expressions of PPARγ,LXRα,ABCA1,ABCG1 and SR-BⅠ in liver tissue of Xinnao Maikang high-dosage group and atorvastatin group significantly increased(P<0.05,P<0.01).Conclusion Xinnao Maikang can decrease blood lipid level,reduce atherosclerotic plaque and reduce lipid deposition in liver of atherosclerotic mice,and its mechanism may be related to regulating PPARγ/LXRα/ABCA1 pathway,regulating lipid metabolism,promoting reverse cholesterol transport.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective To investigate the susceptibility of Cryptococcus neoformans strains to antifungal drugs and examine the relevant clinical manifestations and laboratory test results in a tertiary hospital in Shanghai during the period from 2019 to 2023.Methods The isolates were identified by MALDI-TOF and biochemical identification cards.The minimum inhibitory concentration(MIC)values of 5-fluorocytosine,amphotericin B,fluconazole,voriconazole,and itraconazole against C.neoformans strains were measured using broth microdilution method.The corresponding clinical data were reviewed and compared.Results Majority(78.7％)of the 75 strains of C.neoformans were isolated from cerebrospinal fluid(CSF).The prevalence of wild type(WT)strains was the lowest(36.0％)for itraconazole and the highest(94.7％)for voriconazole.Cryptococcus capsular antigen test was positive in 62 strains.The results of Cryptococcus capsular antigen test was consistent with fungal culture in 96.9％of the cases.Conclusions Most of the C.neoformans strains were isolated from CSF.The prevalence of non-WT C.neoformans strains was the highest for itraconazole.The prevalence of WT C.neoformans strains was the highest for voriconazole.

Objective To investigate the alterations of cerebral blood flow(CBF)in type 2 diabetic mellitus(T2DM) patients without cognitive impairment by using arterial spin labeling(ASL)technique.Methods A total of 23 T2DM patients without cognitive impairment and 23 healthy controls(HC)matched by age,sex,and education attainment were recruited.Their clinical data were collected,and neuropsychological tests and cerebral magnetic resonance imaging were performed.Then,the outcomes of clinical features,neuropsychological tests,and global and regional CBF were compared between the two groups.The significant regional zCBF(z-transformed relative CBF)values were extracted and correlated with clinical data and neuropsychological scores in T2DM patients,controlling age,sex,and education.Results No significant difference was found in whole brain CBF between the two groups(P=0.155),while significantly higher CBF was identified in the left superior temporal gyrus and left insula in the T2DM group(Gaussian random field correction,initial threshold P < 0.001,cluster level P < 0.05).No correlation was observed between the significant regional zCBF values and the clinical data or the neuropsychological scores in T2DM patients(all P>0.05).Conclusion Alterations in cerebral hemodynamics may precede cognitive function changes in T2DM,suggesting that the ASL technique is promising for early monitoring of cerebral hemodynamic changes associated with cognitive impairment in patients with T2DM.
Humans ; Diabetes Mellitus, Type 2/physiopathology* ; Cerebrovascular Circulation ; Middle Aged ; Male ; Female ; Magnetic Resonance Imaging ; Case-Control Studies ; Cognitive Dysfunction ; Neuropsychological Tests ; Aged

Objective To assess the clinical and safety outcomes of endovascular therapy(EVT)administered beyond 24 h after the onset of symptoms in patients with acute ischemic stroke(AIS)resulting from middle cerebral artery atherosclerotic occlusion.Methods We enrolled consecutive AIS patients with middle cerebral artery atherosclerotic occlusion who received EVT in our hospital between January 2020 and June 2023 and divided them into two groups based on the time from AIS onset to EVT:EVT≤24 h group and EVT＞24 h group.The National Institutes of Health Stroke Scale(NIHSS)scores after surgery,90-day functional independence(defined as mRS 0-2),symptomatic ICH(sICH),postoperative acute thrombosis,as well as mortality,were analyzed in the two groups of patients.Results A total of 161 patients were recruited,with 106 cases in the EVT≤24 h group and 55 cases in the EVT＞24 h group.The NIHSS scores declined after EVT in both groups(P＜0.01).The NIHSS scores after surgery were lower in the EVT≤24 h group(median:4.5 vs.7.0,P＜0.05).90-day functional independence(45.3％vs.30.9％,95％CI:0.93-3.68),sICH(5.7％vs.9.1％,95％CI:0.18-2.06),postoperative acute thrombosis(6.6％vs.3.6％,95％CI:0.37-9.34),and mortality(3.8％vs.1.8％,95％CI:0.23-19.42)did not differ significantly between the groups(P＞0.05).Conclusion Our findings support EVT feasibility in selected patients with middle cerebral artery atherosclerotic occlusion beyond 24 h.Prospective studies are warranted for confirmation.

This study was aimed at establishing a method of ultra-fast quantitative PCR for Brucella detection.We used an exogenous recombinant plasmid as the internal reference and targeted the T4SS secretion system,an important Brucella viru-lence factor,to design specific primers and probes.The sensitivity,specificity,and repeatability of this method were evaluated,and a standard curve was constructed.The coincidence rate of detection findings with this method versus quantitative PCR was determined.This method markedly decreased the detection time to only 10 minutes.The standard curve demonstrated a good linear relationship(Y=-3.410 7x+38.357,R2=0.998 5)with a low minimum detection limit of 10 copies/μL.The method exhibited good specificity and did not specifically amplify several common clinical bacteria other than Brucella.The de-tection of three concentrations of positive plasmids yielded coefficients of variation(CVs)of 0.20％to 0.91％,thus demonstra-ting the method's excellent repeatability.Furthermore,140 clinical samples were analyzed concurrently with the fluorescence PCR method,which yielded a 100％compliance rate and consistent results.Our findings indicated that the Brucella ultra-fast quantitative PCR was ultrafast;had high sensitivity,high specificity,and good specificity;and can be used for the clinical de-tection of Brucella and emergency investigation of epidemics.Therefore,this method is valuable for the early diagnosis of Bru-cella.

Objective To investigate the effect of quercetin on paraptosis induced by low-concentration hydrogen peroxide(H2O2)in human lens epithelial cells(LECs).Methods The human lens epithelial cell line SRA01/04 was cul-tured in vitro and randomly divided into the following groups:control group,H2O2 group(50 μmol·L-1 H2O2),and H2O2+Quercetin group(50 μmol·L-1 H2O2 and 20 μmol·L-1 quercetin).The area and number of endoplasmic reticulum vacuoles in the cells were observed using transmission electron microscopy and super-resolution laser confocal microscopy.Intracellular reactive oxygen species(ROS)levels were detected using the DCFH-DA fluorescent probe.Western blot was performed to detect the expression levels of the following proteins:insulin-like growth factor 1 receptor(IGF1R),phos-phorylated IGF1R(p-IGF1R),ALG-2-interacting protein X(ALIX),glucose-regulated protein 78(GRP78),extracellular signal-regulated kinase(ERK),phosphorylated ERK(p-ERK),P38,and phosphorylated P38(p-P38).Additionally,len-ses from 8-week-old Sprague-Dawley rats were subjected to ex vivo culture and divided into the normal group,the H2O2 treatment group(50 μmol·L-1 H2O2),and the combination treatment group(50 μmol·L-1 H2O2 and 20 μmol·L-1 quer-cetin).The degree of lens opacity was observed under a stereomicroscope,and the area of lens opacity was quantified.The ultrastructure of the endoplasmic reticulum in the rat LECs was observed by transmission electron microscopy.Western blot was used to detect the expression levels of the aforementioned proteins in the rat LECs.Results Compared with the control group,the H2O2 group exhibited significant increases in the area and number of endoplasmic reticulum vacuoles,ROS levels,and the relative protein expression levels of p-IGF1R,p-ERK,p-P38,and GRP78,while the relative expression of ALIX protein was decreased(all P＜0.001).Compared with the H2 O2 group,the H2O2+quercetin group showed signifi-cant reductions in the area and number of endoplasmic reticulum vacuoles,ROS levels,and the relative expression levels of p-IGF1R,p-ERK,p-P38,and GRP78,while the relative expression of ALIX protein was increased(all P＜0.01).In the ex vivo cultured rat lens model,compared with the normal group,the H2O2 group displayed a significant increase in lens opac-ity area,expanded endoplasmic reticulum area in LECs,elevated relative expression levels of p-IGF1R,p-ERK,p-P38,and GRP78 proteins,and decreased ALIX expression(all P＜0.000 1).In contrast,the combination treatment group showed significantly reduced lens opacity area,decreased endoplasmic reticulum area in LECs,lower relative expression of p-IGF1R,p-ERK,p-P38,and GRP78,and increased ALIX expression compared to the H2O2 group(all P＜0.01).Conclu-sion Quercetin inhibits activation of the IGF1R/MAPK signaling pathway and alleviates endoplasmic reticulum stress,thereby effectively attenuating paraptosis in lens epithelial cells.These findings provide a novel strategy for the prevention and treatment of early age-related cataract.

Objective To investigate the susceptibility of Cryptococcus neoformans strains to antifungal drugs and examine the relevant clinical manifestations and laboratory test results in a tertiary hospital in Shanghai during the period from 2019 to 2023.Methods The isolates were identified by MALDI-TOF and biochemical identification cards.The minimum inhibitory concentration(MIC)values of 5-fluorocytosine,amphotericin B,fluconazole,voriconazole,and itraconazole against C.neoformans strains were measured using broth microdilution method.The corresponding clinical data were reviewed and compared.Results Majority(78.7％)of the 75 strains of C.neoformans were isolated from cerebrospinal fluid(CSF).The prevalence of wild type(WT)strains was the lowest(36.0％)for itraconazole and the highest(94.7％)for voriconazole.Cryptococcus capsular antigen test was positive in 62 strains.The results of Cryptococcus capsular antigen test was consistent with fungal culture in 96.9％of the cases.Conclusions Most of the C.neoformans strains were isolated from CSF.The prevalence of non-WT C.neoformans strains was the highest for itraconazole.The prevalence of WT C.neoformans strains was the highest for voriconazole.

Objective To investigate the effect of quercetin on paraptosis induced by low-concentration hydrogen peroxide(H2O2)in human lens epithelial cells(LECs).Methods The human lens epithelial cell line SRA01/04 was cul-tured in vitro and randomly divided into the following groups:control group,H2O2 group(50 μmol·L-1 H2O2),and H2O2+Quercetin group(50 μmol·L-1 H2O2 and 20 μmol·L-1 quercetin).The area and number of endoplasmic reticulum vacuoles in the cells were observed using transmission electron microscopy and super-resolution laser confocal microscopy.Intracellular reactive oxygen species(ROS)levels were detected using the DCFH-DA fluorescent probe.Western blot was performed to detect the expression levels of the following proteins:insulin-like growth factor 1 receptor(IGF1R),phos-phorylated IGF1R(p-IGF1R),ALG-2-interacting protein X(ALIX),glucose-regulated protein 78(GRP78),extracellular signal-regulated kinase(ERK),phosphorylated ERK(p-ERK),P38,and phosphorylated P38(p-P38).Additionally,len-ses from 8-week-old Sprague-Dawley rats were subjected to ex vivo culture and divided into the normal group,the H2O2 treatment group(50 μmol·L-1 H2O2),and the combination treatment group(50 μmol·L-1 H2O2 and 20 μmol·L-1 quer-cetin).The degree of lens opacity was observed under a stereomicroscope,and the area of lens opacity was quantified.The ultrastructure of the endoplasmic reticulum in the rat LECs was observed by transmission electron microscopy.Western blot was used to detect the expression levels of the aforementioned proteins in the rat LECs.Results Compared with the control group,the H2O2 group exhibited significant increases in the area and number of endoplasmic reticulum vacuoles,ROS levels,and the relative protein expression levels of p-IGF1R,p-ERK,p-P38,and GRP78,while the relative expression of ALIX protein was decreased(all P＜0.001).Compared with the H2 O2 group,the H2O2+quercetin group showed signifi-cant reductions in the area and number of endoplasmic reticulum vacuoles,ROS levels,and the relative expression levels of p-IGF1R,p-ERK,p-P38,and GRP78,while the relative expression of ALIX protein was increased(all P＜0.01).In the ex vivo cultured rat lens model,compared with the normal group,the H2O2 group displayed a significant increase in lens opac-ity area,expanded endoplasmic reticulum area in LECs,elevated relative expression levels of p-IGF1R,p-ERK,p-P38,and GRP78 proteins,and decreased ALIX expression(all P＜0.000 1).In contrast,the combination treatment group showed significantly reduced lens opacity area,decreased endoplasmic reticulum area in LECs,lower relative expression of p-IGF1R,p-ERK,p-P38,and GRP78,and increased ALIX expression compared to the H2O2 group(all P＜0.01).Conclu-sion Quercetin inhibits activation of the IGF1R/MAPK signaling pathway and alleviates endoplasmic reticulum stress,thereby effectively attenuating paraptosis in lens epithelial cells.These findings provide a novel strategy for the prevention and treatment of early age-related cataract.

Objective To assess the clinical and safety outcomes of endovascular therapy(EVT)administered beyond 24 h after the onset of symptoms in patients with acute ischemic stroke(AIS)resulting from middle cerebral artery atherosclerotic occlusion.Methods We enrolled consecutive AIS patients with middle cerebral artery atherosclerotic occlusion who received EVT in our hospital between January 2020 and June 2023 and divided them into two groups based on the time from AIS onset to EVT:EVT≤24 h group and EVT＞24 h group.The National Institutes of Health Stroke Scale(NIHSS)scores after surgery,90-day functional independence(defined as mRS 0-2),symptomatic ICH(sICH),postoperative acute thrombosis,as well as mortality,were analyzed in the two groups of patients.Results A total of 161 patients were recruited,with 106 cases in the EVT≤24 h group and 55 cases in the EVT＞24 h group.The NIHSS scores declined after EVT in both groups(P＜0.01).The NIHSS scores after surgery were lower in the EVT≤24 h group(median:4.5 vs.7.0,P＜0.05).90-day functional independence(45.3％vs.30.9％,95％CI:0.93-3.68),sICH(5.7％vs.9.1％,95％CI:0.18-2.06),postoperative acute thrombosis(6.6％vs.3.6％,95％CI:0.37-9.34),and mortality(3.8％vs.1.8％,95％CI:0.23-19.42)did not differ significantly between the groups(P＞0.05).Conclusion Our findings support EVT feasibility in selected patients with middle cerebral artery atherosclerotic occlusion beyond 24 h.Prospective studies are warranted for confirmation.