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

Immunotherapy has emerged as a revolutionary approach to treat immune-related diseases. Dendritic cells (DCs) play a pivotal role in orchestrating immune responses, making them an attractive target for immunotherapeutic interventions. Modulation of gene expression in DCs using genome editing techniques, such as the CRISPR-Cas system, is important for regulating DC functions. However, the precise delivery of CRISPR-based therapies to DCs has posed a significant challenge. While lipid nanoparticles (LNPs) have been extensively studied for gene editing in tumor cells, their potential application in DCs has remained relatively unexplored. This study investigates the important role of cholesterol in regulating the efficiency of BAMEA-O16B lipid-assisted nanoparticles (BLANs) as carriers of CRISPR/Cas9 for gene editing in DCs. Remarkably, BLANs with low cholesterol density exhibit exceptional mRNA uptake, improved endosomal escape, and efficient single-guide RNA release capabilities. Administration of BLAN_mCas9/gPD-L1 results in substantial PD-L1 gene knockout in conventional dendritic cells (cDCs), accompanied by heightened cDC1 activation, T cell stimulation, and significant suppression of tumor growth. The study underscores the pivotal role of cholesterol density within LNPs, revealing potent influence on gene editing efficacy within DCs. This strategy holds immense promise for the field of cancer immunotherapy, offering a novel avenue for treating immune-related diseases.

Objective To explore the establishment of a new model of informational drug treatment pathway management.Methods The orthopedic drug treatment pathways was developed through multidisciplinary diagnosis and treatment(MDT),and the pathway management was implemented with the help of an information systems to implement refined control rules.Cases before the implementation of the management pathway(January to May 2022)were selected as the control group,and cases after the implementation of the management pathway(June to December 2022)were selected as the improvement group to evaluate the management effectiveness.Results After establishing drug treatment pathways for 8 major types of surgeries,maintaining 990 medical prescriptions for recommended drugs in the HIS system,and 176 control rules in the MINDS system.There was a significant improvement in the orthopaedic department's indexes of antimicrobial drug use rate,antibacterial drug use intensity,average inpatient medication cost,and percentage of the amount of basic medication after applying a new model of drug treatment pathway management.According to the case analysis before and after the implementation of the pathway,the rational rate of using orthopedic antibiotics,analgesics,fluid replacement and volume expansion drugs,acid inhibiting and stomach protecting drugs,blood activating and swelling-reducing proprietary Chinese medicines were increased by 21.6%,12.7%,23.3%,32.1% and 27.1%,respectively.The average drug costs was reduced by 111.51 yuan,15.33 yuan,49.84 yuan,42.29 yuan and 14.23 yuan,respectively.Conclusion The management mode of drug treatment pathway based on MDT established by our hospital is practical and effective,and the relevant experience may provide valuable insights for pharmaceutical peers.

Nonalcoholic steatohepatitis (NASH) is a spectrum of chronic liver disease characterized by hepatic lipid metabolism disorder. Recent reports emphasized the contribution of triglyceride and diglyceride accumulation to NASH, while the other lipids associated with the NASH pathogenesis remained unexplored. The specific purpose of our study was to explore a novel pathogenesis and treatment strategy of NASH via profiling the metabolic characteristics of lipids. Herein, multi-omics techniques based on LC-Q-TOF/MS, LC-MS/MS and MS imaging were developed and used to screen the action targets related to NASH progress and treatment. A methionine and choline deficient (MCD) diet-induced mouse model of NASH was then constructed, and Schisandra lignans extract (SLE) was applied to alleviate hepatic damage by regulating the lipid metabolism-related enzymes CES2A and CYP4A14. Hepatic lipidomics indicated that MCD-diet led to aberrant accumulation of phosphatidylethanolamines (PEs), and SLE could significantly reduce the accumulation of intrahepatic PEs. Notably, exogenous PE (18:0/18:1) was proved to significantly aggravate the mitochondrial damage and hepatocyte apoptosis. Supplementing PE (18:0/18:1) also deteriorated the NASH progress by up regulating intrahepatic proinflammatory and fibrotic factors, while PE synthase inhibitor exerted a prominent hepatoprotective role. The current work provides new insights into the relationship between PE metabolism and the pathogenesis of NASH.

OBJECTIVE To establish the path-based management mode of 5-hydroxytryptamine-3 receptor antagonist （5- HT3RA） in chemotherapy patients， and to improve the rationality of medication in chemotherapy patients. METHODS 5-HT3RA standardized drug use control rules were formulated， with the help of medical intelligence and decision support （MINDS） system， path-based management was carried out for chemotherapy patients using 5-HT3RA in the form of whole-process information capture and prescription pre-review， and whole-process intervention was implemented on medication indications， usage and dosage， course of treatment， etc. The intervention effect was analyzed by comparing the changes in the use of 5-HT3RA without indication， unreasonable usage and dosage， repeated medication， unreasonable course of treatment， and per capita drug cost before and after the implementation of path-based management. RESULTS A total of 9 181 patients were included. After the implementation of path- based management， the proportion of unindicated drugs decreased by 0.48%， and the rate of unreasonable single dosage， unreasonable frequency， repeated medication， unreasonable treatment course （5-HT3RA still used 3 days after chemotherapy） decreased by 10.48%， 0.65%， 1.33% and 0.34%； per capita cost of 5-HT3RA decreased by 13.72 yuan； there were statistical significance （P＜0.05）. CONCLUSIONS 5-HT3RA path-based management mode effectively improves the rationality of medication and provides a new idea for rational clinical drug use.

Objective:To investigate the change of the detection rate of colorectal cancer (CRC), colorectal adenoma and advanced adenoma in adults under colonoscopy in Shihezi in the past ten years.Methods:Data of patients who completed colonoscopy in the First Affiliated Hospital of Shihezi University School of Medicine from January 1, 2010 to December 31, 2019 were investigated. The medical records were collected by consulting the electronic medical record system, including the age and sex of patients and the location, quantity, size and pathological type of lesions. The detection rates, including the overall detection rate in the past 10 years, those in the first 5 years (from 2010 to 2014) and the second 5 years (from 2015 to 2019) of colorectal adenomas, advanced colorectal adenomas and CRC, were studied.Results:A total of 50 645 cases were included, 14 931 cases were excluded by the exclusion criteria, and finally a total of 35 714 cases were included in the data analysis. The 10-year overall detection rates of colorectal adenoma, advanced colorectal adenoma and CRC were 17.65% (6 302/35 714), 4.45% (1 589/35 714) and 3.71% (1 324/35 714), respectively. The overall detection rates of colorectal adenoma and advanced colorectal adenoma in the second 5 years were higher respectively than those in the first 5 years [20.33% (4 565/22 457) VS 13.10% (1 737/13 257), 4.69% (1 053/22 457) VS 4.04% (536/13 257)]. The overall detection rate of CRC in the second 5 years [3.30% (741/22 457)] was lower than that in the first 5 years [4.40% (583/13 257)].Conclusion:Compared with 2010 to 2014, the detection rate of colorectal adenoma in Shihezi area in 2015 to 2019 increased significantly, the detection rate of advanced colorectal adenoma increased slightly, and the detection rate of CRC decreased slightly. Therefore, the detection and resection of colorectal adenoma by colonoscopy may be important in reducing the incidence of CRC.

Objective To investigate the clinical status of disease self-management ability in patients with chronic hepatitis B liver fibrosis and to analyze the effect of gratitude,social support and perceived stress on the ability.Methods Totally 236 patients with chronic hepatitis B liver fibrosis were selected from Guangzhou Red Cross Hospital by convenient sampling from January 2016 to June 2017 and investigated with the general information questionnaire,the Chronic Hepatitis B Self-Management Scale,the Gratitude Resentment and Appreciation Test (GRAT),the Social Support Rating Scale and the Perceived Stress Scale-Chinese (CPSS).PASW Statistics 18.0 and AMOS 18.0 were used to analyze the effects.Results The disease self-management score in patients with chronic hepatitis B liver fibrosis was (94.41 ± 16.78).According to correlation analysis,gratitude,social support and perceived stress were positively correlated with disease self-management (r=0.327,0.339;P ＜ 0.05);while perceived stress was negatively correlated with disease self-management (r=-0.574,P ＜ 0.05).The multiple linear regression analysis and model fitting showed that gratitude had direct effect on disease self-management (β=0.314);social support had direct influence (β=0.354) and indirect (β=0.199) effect on it;and perceived stress had direct (β=-0.567) and indirect (β=-0.058) on it.Conclusions The patients with chronic hepatitis B liver fibrosis show a relatively poor disease self-management ability.Clinical medical and nursing staff shall cultivate the patients' gratitude,mobilize their social support,reduce their perceived stress and improve their disease self-management ability.

OBJECTIVE:To improve the process efficiency of automatic dispensation machine before dispensing. METHODS:After building quality control circle(QCC)in the hospital inpatient,according to the steps of QCC,the key links and factors that affect process efficiency of automatic dispensation machine before dispensing were found out,corresponding countermeasures were developed based on causes,then it was evaluated by process time and other indexes in dispensing before and after the development of QCC. RESULTS:The 2 links(removing the drug packaging,manually counting and developing add-drug list)with the longest time before dispensing improved work efficiency by setting add-drug quantity and variety truly,timing checking dispensation medi-cine,timely counting dispensation medicine drug list,strengthening training and other methods,process time of automatic dispensa-tion machine before dispensing was shortened from 179.8 min(before)to 119.2 min(after)(shortened by 33.7%),target achieve-ment rate was 168.5%;and QCC staff showed positive growth in means, responsibility, team cohesion, and other aspects (increase rate were 15%-81%). CONCLUSIONS:QCC shows obvious effect on improving process efficiency of automatic dispen-sation machine before dispensing.

[Summary] To investigate the association between sleep disorder and ambulatory blood pressure rhythm in patients with type 2 diabetes. 418 patients with type 2 diabetes were divided into two groups according to Pittsburgh sleep quality index ( PSQI):patients without sleep disorder and patients with sleep disorder. Oral glucose tolerance test, insulin releasing test, and C-peptide releasing test were performed to investigate the differences in the β-cell function, the circadian rhythm of blood pressure, and blood pressure variation between the two groups after fasting and glucose-load. The correlation and regression analysis were performed between PSQI and other indicators. (1)The level of HbA1C , fasting plasma insulin, area under curve of insulin, fasting plasma C-peptide, area under curve of C-peptide, and homeostasis model assessment for insulin resistance ( HOMA-IR) were significantly higher in patients withsleepdisordercomparedtothoseinpatientswithoutsleepdisorder[(8.2±2.1)% vs(7.4±1.8)%,(13.42± 4.55vs11.86±4.52)mU/L,(8.51±0.54vs8.38±0.51)mU·L-1·min,(2.42±1.25vs1.79±0.73)ng/ml, (6.59±0.39vs6.49±0.43)μg·L-1·min,4.63±1.12vs3.86±0.97,allP<0.05]. Insulinsensitivityindex (ISI) was lower in patients with sleep disorder than that in patients without sleep disorder(-4. 26 ± 0. 78 vs-4. 05 ± 0.62,P<0.05). (2)Thelevelof24hmeansystolicanddiastolicbloodpressure,nocturalsystolicanddiastolicblood pressure, and systolic blood pressure during daytime and nighttime were significantly higher in patients with type 2 diabetes who were suffering from sleep disorder. The blood pressure variation was more marked in patients with sleep disorder. (3)Multiple stepwise regression analysis showed that PSQI score was positively related to area under curve of C-peptide, HOMA-IR, 24 h mean systolic blood pressure, and noctural systolic blood pressure (β=0. 242, 0. 293, 0. 352, 0. 413, all P<0. 05), and negatively related to ISI and decreasing ratio of noctural systolic blood pressure (β=-0. 124 and -0. 226, both P<0. 05). Sleep disorder may cause abnormal circadian rhythm of blood pressure through various mechanisms. Improving sleep disorder may help to ameliorate insulin resistance and restore normal circadian rhythm of blood pressure.

Through retrospective analysis of the clinical and laboratory data of 1 466 inpatients with type 2 diabetes mellitus(T2DM),we investigated the prevalence of chronic kidney disease (CKD) and analyzed the risk factors.The prevalence of CKD in hospitalized patients with T2DM was 52.25％.In the patients with CKD,protein urine was present in 93.47％ of the cases,27.93％ of them had glomerular filtration rate(eGFR) ≤60 ml · min-1 · 1.73 m-2,damage of renal tubular function was present in 24.28％,and abnormal renal imaging in 14.88％.Logistic regression showed that age,body mass index(BMI),duration of diabetes,systolic blood pressure,serum uric acid,low density lipoprotein-cholesterol (LDL-C),and smoking were independently associated with patients of T2 DM and CKD.The prevalence of CKD was increased with aging,diabetic course,BMI,and LDL-C.CKD is a common chronic complication in patients with T2DM,especially in patients with prolonged course,advanced age,and obesity.Much attention should be paid to early detection of CKD in patients with diabetes.In addition to detecting urinary protein and eGFR,renal tubular function and morphological examination should also be included.