Objective To explore the therapeutic effect of picroside Ⅱ(P Ⅱ)on diabetes nephropathy(DN)rats by regulating fatty acid synthase(Fas)/fatty acid synthase ligand(FasL)signaling pathway.Methods A DN rat model was constructed by combining high sugar and high-fat diet with streptozotocin(STZ)injection.DN rats were grouped into model group(DN group),low,medium and high dose picroside Ⅱ groups(P-L group,P-M group,P-H group),and high dose picroside Ⅱ+Fas recombinant protein group(P-H+rh-Fas group),with healthy rats as control group,and 18 rats in each group.Fasting blood glucose(FBG),body mass,24-hour urinary protein(24h UTP),and renal function(SCr,BUN)were measured in rats.Hematoxylin-eosin(HE)staining and Masson staining were applied to observe the pathological changes in renal tissue of rats;immunohistochemistry and Western blot were applied to detect the expression of RAGE,COL-Ⅳ and pathway proteins,respectively.Results Compared with the control group,rats in DN group showed thickening of the glomerular basement membrane,mesangial proliferation,tubular degeneration,dilation,atrophy,fatty degeneration,obvious collagen deposition,higher levels of FBG,24h UTP,SCr,BUN,TNF-α,IL-6 and IL-1β,body mass loss,and higher expression of RAGE,COL-Ⅳ,Fas and FasL(P＜0.05).Compared with the DN group,the glomerular and tubular lesions were reduced and collagen deposition was decreased in the P-L,P-M and P-H groups,furthermore,the FBG,24h UTP,SCr,BUN,TNF-α,IL-6,IL-1β levels were lower,body mass was higher,and the RAGE,COL-Ⅳ,Fas,FasL expression was lower(P＜0.05).Compared with the P-H group,the renal tissue lesions in the P-H+rh-Fas group worsened,the FBG,24 h UTP,SCr,BUN,TNF-α,IL-6,IL-1β levels were higher,body mass was lower,and the RAGE,COL-Ⅳ,Fas,FasL expression was higher(P＜0.05).Conclusion Picroside Ⅱ exerts therapeutic effects on DN rats by inhibiting the Fas/FasL signaling pathway.

INTRODUCTION: Lecanemab has shown promise in treating early Alzheimer's disease (AD), but its safety and efficacy in Chinese populations remain unexplored. This study aimed to evaluate the safety and 6-month clinical outcomes of lecanemab in Chinese patients with mild cognitive impairment (MCI) or mild AD. METHODS: In this single-arm, real-world study, participants with MCI due to AD or mild AD received biweekly intravenous lecanemab (10 mg/kg). The study was conducted at Hainan Branch, Ruijin Hospital Shanghai Jiao Tong University School of Medicine. Patient enrollment and baseline assessments commenced in November 2023. Safety assessments included monitoring for amyloid-related imaging abnormalities (ARIA) and other adverse events. Clinical and biomarker changes from baseline to 6 months were evaluated using cognitive scales (mini-mental state examination [MMSE], montreal cognitive assessment [MoCA], clinical dementia rating-sum of boxes [CDR-SB]), plasma biomarker analysis, and advanced neuroimaging. RESULTS: A total of 64 patients were enrolled in this ongoing real-world study. Safety analysis revealed predominantly mild adverse events, with infusion-related reactions (20.3%, 13/64) being the most common. Of these, 69.2% (9/13) occurred during the initial infusion and 84.6% (11/13) did not recur. ARIA-H (microhemorrhages/superficial siderosis) and ARIA-E (edema/effusion) were observed in 9.4% (6/64) and 3.1% (2/64) of participants, respectively, with only two symptomatic cases (one ARIA-E presenting with headache and one ARIA-H with visual disturbances). After 6 months of treatment, cognitive scores remained stable compared to baseline (MMSE: 22.33 ± 5.58 vs . 21.27 ± 4.30, P = 0.733; MoCA: 16.38 ± 6.67 vs . 15.90 ± 4.78, P = 0.785; CDR-SB: 2.30 ± 1.65 vs . 3.16 ± 1.72, P = 0.357), while significantly increasing plasma amyloid-β 42 (Aβ42) (+21.42%) and Aβ40 (+23.53%) levels compared to baseline. CONCLUSIONS: Lecanemab demonstrated a favorable safety profile in Chinese patients with early AD. Cognitive stability and biomarker changes over 6 months suggest potential efficacy, though high dropout rates and absence of a control group warrant cautious interpretation. These findings provide preliminary real-world evidence for lecanemab's use in China, supporting further investigation in larger controlled studies. REGISTRATION ClinicalTrials.gov , NCT07034222.
Humans ; Alzheimer Disease/drug therapy* ; Male ; Female ; Aged ; Middle Aged ; Cognitive Dysfunction/drug therapy* ; Aged, 80 and over ; Amyloid beta-Peptides/metabolism* ; Biomarkers ; East Asian People

Objective To explore the therapeutic effect of picroside Ⅱ(P Ⅱ)on diabetes nephropathy(DN)rats by regulating fatty acid synthase(Fas)/fatty acid synthase ligand(FasL)signaling pathway.Methods A DN rat model was constructed by combining high sugar and high-fat diet with streptozotocin(STZ)injection.DN rats were grouped into model group(DN group),low,medium and high dose picroside Ⅱ groups(P-L group,P-M group,P-H group),and high dose picroside Ⅱ+Fas recombinant protein group(P-H+rh-Fas group),with healthy rats as control group,and 18 rats in each group.Fasting blood glucose(FBG),body mass,24-hour urinary protein(24h UTP),and renal function(SCr,BUN)were measured in rats.Hematoxylin-eosin(HE)staining and Masson staining were applied to observe the pathological changes in renal tissue of rats;immunohistochemistry and Western blot were applied to detect the expression of RAGE,COL-Ⅳ and pathway proteins,respectively.Results Compared with the control group,rats in DN group showed thickening of the glomerular basement membrane,mesangial proliferation,tubular degeneration,dilation,atrophy,fatty degeneration,obvious collagen deposition,higher levels of FBG,24h UTP,SCr,BUN,TNF-α,IL-6 and IL-1β,body mass loss,and higher expression of RAGE,COL-Ⅳ,Fas and FasL(P＜0.05).Compared with the DN group,the glomerular and tubular lesions were reduced and collagen deposition was decreased in the P-L,P-M and P-H groups,furthermore,the FBG,24h UTP,SCr,BUN,TNF-α,IL-6,IL-1β levels were lower,body mass was higher,and the RAGE,COL-Ⅳ,Fas,FasL expression was lower(P＜0.05).Compared with the P-H group,the renal tissue lesions in the P-H+rh-Fas group worsened,the FBG,24 h UTP,SCr,BUN,TNF-α,IL-6,IL-1β levels were higher,body mass was lower,and the RAGE,COL-Ⅳ,Fas,FasL expression was higher(P＜0.05).Conclusion Picroside Ⅱ exerts therapeutic effects on DN rats by inhibiting the Fas/FasL signaling pathway.

Objective:To investigate the relationship between waist circumference trajectory and new-onset nonalcoholic fatty liver disease (NAFLD) in the non-obese population.Methods:The study cohort was composed of the ones who met the selection criteria in Kailuan study. Waist circumference trajectories of the participants in 2006-2007, 2008-2009 and 2010-2011 were determined by SAS Proc Traj program. Four groups with different waist circumference trajectories were generated, including low-, medium-, medium-high- and high-stability groups. All groups were followed up for their health conditions in 2012-2013, 2014-2015 and 2016-2017, respectively. Incidence rates of NAFLD during physical examination were compared among different waist circumference trajectory groups. Cox regression model was used to analyze the correlation between different waist circumference trajectory groups and new-onset NAFLD.Results:Finally, 12 477 observers were included in the statistical analysis, including 8 181 males and 4 296 females. There were 1 026 (8.2 %), 5 183 (41.5 %), 5 481 (44.0 %) and 787 cases (6.3 %) in the low, medium, medium-high and high stability-stability groups, respectively. There were 4 123 NAFLD cases occurred during the follow-up period. The cumulative incidence of NAFLD increased along with the increase of waist circumference trajectory (21 %, 43 %, 59 %, 72 %, respectively) ( P<0.01). The risks of NAFLD were 2.411 (95 %CI: 2.021-2.877), 4.050 (95 %CI: 3.402-4.820) and 5.489 (95 %CI: 4.506-6.686) times higher in medium-, medium-high- and high-stability group than that in the low-stability group ( P<0.01). After adjusting for age, sex and other confounding factors, the risks of NAFLD in the medium-, medium-high- and high-stability groups were 2.150 (95 %CI: 1.789-2.582), 3.176 (95 %CI: 2.623-3.846) and 3.732 (95 %CI: 2.987-4.662) times higher than that in the low-stability group. Conclusion:The risk of NAFLD in non-obese people increased along with the increase of waist circumference trajectory, which seemed to have played an independent risk factor for NAFLD.

Objective:To study the clinical efficacy of botulinum toxin type A injection in the treatment of upper facial dynamic wrinkles.Methods:A total of 35 patients with upper facial dynamic wrinkles treated in our hospital from February 2016 to October 2016 were selected as research objects.All the patients were treated with botulinum toxin type A.The excellence rate of 30min after treatment,3 d after treatment and 7 d after treatment were evaluated and compared.The facial wrinkles severity index of the patients were evaluated by the facial wrinkles scale (FWS),and the differences of the FWS index before treatment,4 weeks after treatment and 6 months after treatment were compared.The adverse reactions,like upper facial tension,fatigue and local injection of ecchymosis after treatment were observed and compared.Results:The excellence rate of the patients after treatment of 30 min,3 d and 7 d were gradually increased.The excellence rate of the patients after treatment of 3 d and 7 d were significantly higher than that of after treatment of 30 min,and the excellence rate of the patients after treatment of 7 d were significantly higher than that of after treatment of 3 d (P＜0.05).The FWS index of the patients after treatment of 4 weeks and 6 months were significantly lower than those of before treatment,and the FWS index of the patients after treatment of 4 weeks were significantly lower than that of 6 months after treatment(P＜0.05).After treatment,only 4 patients had slight discomfort and all of these symptoms were disappeared after 3-4 days,there was no effect on their normal work and life.Conclusion:Botulinum toxin type A injection has a remarkable clinical curative effect in the treatment of patients with upper facial dynamic wrinkles,can maintain tor a long time,and also has good safety,it is worthy clinical application.

Objective:To investigate the curative effect of botulinum toxin type A combined with plastic operation of pouches on patients with eye skin relaxation and its impact on patients' satisfaction,and to provide reference for clinical application.Methods:A total of 60 patients with eye skin relaxation,who were treated in Baoji Central Hospital from June 2015 to June 2016,were selected as subjects and divided into control group (n=28) and treatment group (n=32) according to the patients' choices.The patients of control group were treated with plastic operation of pouches,while the patients of treatment group were treated with botulinum toxin type A combined with plastic operation of pouches.The two groups were followed up for 6 months.The improvement of crow's feet,the relief of pouches and the improvement of eye skin gloss of the patients after operation were observed and recorded.The incidence of complications were also observed.At the end of the follow-up,the satisfaction degrees of the patients were investigated with the self-made questionnaire.Results:After treatment,the improvement rate(100％) of crow's feet of the treatment group was significantly higher than that(60.71％) of the control group;the improvement rate (96.88％) of pouches of the treatment group was significantly higher than that (32.14％) of the control group;the improvement rate (87.50％) of eye skin gloss of the treatment group was significantly higher than that (53.57％) of the control group,and the differences were statistically significant (all P＜0.05).After treatment,there was no significant difference in the incidence of incision swelling,small amount of secretions and small hematoma between the two groups (P＞0.05),the operation eye swelling and incision bruises outer canthus in the control group were more than those in the treatment group (P＜0.05).The total satisfaction rate [93.75％ (30/32)] of the treatment group was significantly higher than that[67.86％ (19/28)] of the control group,the difference was statistically significant (P＜0.05).Conclusion:Botulinum toxin type A combined with plastic operation of pouches in the treatment of eye skin relaxation has a better efficacy and safety,which can significantly reduce the incidence of operation eye swelling and incision bruises outer canthus,and improve patients' satisfaction rate.It is worthy of clinical application.

Objective To explore the application value of monoexponential, biexponential models multiple b values diffusion weighted imaging(DWI) in distinguishing pancreatic cancer from non-tumorous pancreas.Methods Subjects comprised 37 pancreatic cancers confirmed by clinical or surgery.Pancreas multiple b values DWI was performed using 3.0T scanner.Standard apparent diffusion coefficient (ADCstandard) was calculated using monoexponential diffusion model.Pure diffusion coefficient (ADCslow), pseudodiffusion coefficient (ADCfast) and perfusion fraction (f) were calculated using intravoxel incoherent motion(IVIM) diffusion model.Parameters of pancreatic cancers and non-tumorous pancreas were compared using independent samples t test.Results Mean ADCslow value of pancreatic cancer was higher than that of non-tumorous pancreas (0.611×10-3 mm2/s vs 0.521×10-3 mm2/s,P=0.037).Mean ADCfast and f values of pancreatic cancer were lower than that of non-tumorous pancreas (5.066×10-3 mm2/s vs 7.188×10-3 mm2/s,P=0.035;55.8% vs 64.0%,P=0.016;respectively).ADCslow of pancreatic cancer was positively correlated to ADCstandard (r=0.824,P=0.000).ADCfast of pancreatic cancer was negatively correlated to f(r=-0.558,P=0.000).Conclusion ADCslow, ADCfast and f derived from IVIM-DWI model can distinguish pancreatic cancer from non-tumorous pancreas.IVIM-DWI may be a promising and non-invasive tool for early diagnosing and differentiating pancreatic carcinoma from non-tumorous pancreas.

Objective To investigate the predicting value of intermedin (IMD) for the prognosis of elderly sepsis patients.Methods A retrospective analysis was conducted. Forty-one patients with sepsis, aged ≥65 years, and admitted to geriatrics intensive care unit of Aerospace Center Hospital from April 2015 to December 2016 were enrolled. Thirty healthy patients were studied as control during the same time. The expression of C-reactive protein (CRP), procalcitonin (PCT) and IMD were tested within 24 hours during hospitalization, and the acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ) score and prognosis was evaluated. According to APACHE Ⅱ score, patients were divided into 3 groups, 10-20 score, 21-30 score, and > 30 score group. And based on the prognosis, the patients were divided into death group and survival group. The differences of expression levels of CRP, PCT and IMD in each group were assessed. The relationship of IMD and infection index was analyzed by Pearson correlation. Receiver operating characteristic curve (ROC) was used to evaluate the prognostic value of CRP, PCT and IMD in patients with sepsis.Results Compared with the control group, the levels of CRP, PCT and IMD were significantly higher in the sepsis patients [CRP (mg/L): 114.71±40.08 vs. 4.03±2.68, PCT (μg/L): 1.338±0.812 vs. 0.007±0.001, IMD (ng/L):43.03±9.67 vs. 16.77±2.06, allP < 0.01]. With the increase of APACHE Ⅱ score, the levels of PCT and IMD were gradually increased. In APACHE Ⅱ 10-20 score, 21-30 score, > 30 score groups, PCT (μg/L) were 0.397±0.129, 1.164±0.326, and 1.999±0.888, respectively (F = 19.392,P = 0.000); IMD (ng/L) were 29.12±5.60, 40.48±4.40,52.75±4.73, respectively (F = 33.310,P = 0.000). There was no significant difference in CRP among APACHE Ⅱ score groups (F = 2.137,P = 0.132). The level of IMD was positively correlated with CRP and PCT (r1 = 0.351,P1 = 0.024;r2 = 0.617,P2 = 0.000), and there was no correlation with temperature and white blood cell count (r1 = 0.063,P1 = 0.697;r2 = 0.064,P2 = 0.692). The expression of PCT and IMD in the death groups were significantly higher than the survival group [PCT (μg/L): 1.547±0.883 vs. 1.043±0.608, IMD (ng/L): 47.44±8.23 vs. 36.80±8.13, bothP < 0.05], while CRP was not significantly different. The area under the ROC curve [AUC (95% confidence interval, 95%CI)] of IMD was larger than that of PCT and CRP [0.809 (0.675-0.943) vs. 0.680 (0.511-0.849), 0.664 (0.490-0.838)]; when cut-off value of IMD was 41.58 ng/L, the sensitivity was 75.0% and the specificity was 82.4%.Conclusions The levels of CRP, PCT and IMD were increased in elderly sepsis patients, and IMD and PCT can better reflect the severity of sepsis. IMD is more valuable in predicting the prognosis of sepsis patients.

Objective To investigate perfusion imaging and parameters of normal pancreas by dual-source CT and to evaluate the appropriate perfusion imaging scan.Methods Sixty-six subjects with normal pancreas underwent low-dose pancreatic perfusion and plain scan.CT images were sent to a separate workstation via a network.The blood flow (BF)and blood volume (BV)of pancreas head,body and tail were measured using the VPCT Body software and analyzed by one-way ANOVA.Then the time-density curve of pancreas was drawn,and the enhancement peak time and the corresponding CT value were also measured.Results The average BF values of pancreas head,body and tail were (1 1 6.09 ± 31.83)mL·100 g-1 ·min-1 ,(1 1 9.72±32.50)mL·100 g-1 ·min-1 , (1 14.65±31.42)mL·100 g-1 ·min-1 ,and the mean BV values were (29.83 ±1 9.07)mL/100 g,(30.39 ± 1 9.38)mL/100 g, (28.82±1 9.22)mL/100 g,respectively.The perfusion parameters in different pancreatic parts were not statistically different.The mean enhancement peak time was (27.92 s±4.52)s,(28.02±5.34)s in pancreas head,(27.40±4.36)s in pancreas body,(27.34±4.57)s in pancreas tail.On plain image,the average CT value of pancreas was (41.43±5.88)HU.However,on enhanced image,the mean CT value was (95.96±18.44)HU in normal pancreas [(96.73±19.71)HU in pancreas head,(98.45±17.52)HU in body,(92.69±18.1 7)HU in tail].Conclusion The perfusion parameters including blood flow and blood volume in pancreatic head,body and tail are identical. The mean enhancement peak time is (27.92±4.52)s,and the corresponding enhancement CT value is (95.96±18.44)HU.

Objective To assess the value of apparent diffusion coefficient (ADC)in clinic ,pathology and prognosis of rectal cancer. Methods The MRI and DWI findings of 109 patients with pathological proved rectal adenocarcinoma were retrospectively analyzed. DWI with b=0 s/mm2 and b= 1 000 s/mm2 were acquired.Mean tumor ADCs were measured and compared between subgroups stratified by histologic differentiation grades,T-stage,N-stage,mesorectal fascia status and presence of lymphangiovascular or peri-neral invasion.Results Mean tumor ADCs were significantly different when comparing groups stratified by histologic differentiation grades,T-stage,mesorectal fascia status and presence of lymphangiovascular invasion.Tukey’s post hoc test showed that the differences of mean ADCs between good-moderate differentiated group and moderate differentiated group(P =0.996),moderate-poor differentiated group and poor differentiated group(P =0.957)were not significant.The differences among other groups of differentia-tion grades differed significantly(P <0.05).In the T-stage groups,the mean ADCs of T1 stage tumor was significantly higher than that of T3 stage tumor(P <0.05).There were no significant differences among other T-stage groups(P >0.05).There were no sig-nificant differences among N0,N1 and N2 in N-stage groups(P >0.05).Conclusion ADC values can reflect pathologic and prognos-tic features of rectal cancer.