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

This study aims to explore the protective effect of Chaihu Jia Longgu Muli Decoction on rats with heart failure after myocardial infarction, and to clarify its possible mechanisms, providing a new basis for basic research on the mechanism of classic Chinese medicinal formula-mediated inflammatory response in preventing and treating heart failure induced by apoptosis after myocardial infarction. A heart failure model after myocardial infarction was established in rats by coronary artery ligation. The rats were divided into sham group, model group, and low, medium, and high-dose groups of Chaihu Jia Longgu Muli Decoction, with 10 rats in each group. The low-dose, medium-dose, and high-dose groups of Chaihu Jia Longgu Muli Decoction were given 6.3, 12.6, and 25.2 g·kg~(-1) doses by gavage, respectively. The sham group and model group were given an equal volume of distilled water by gavage once daily for four consecutive weeks. Cardiac function was assessed using color Doppler echocardiography. Myocardial pathology was detected by hematoxylin-eosin(HE) staining, apoptosis was measured by TUNEL assay, and mitophagy was observed by transmission electron microscopy. The levels of tumor necrosis factor-α(TNF-α), interleukin(IL)-1β, and N-terminal pro-B-type natriuretic peptide(NT-proBNP) in serum were detected by enzyme-linked immunosorbent assay(ELISA). The expression of apoptosis-related proteins B-cell lymphoma 2(Bcl-2), Bcl-2-associated X protein(Bax), and cleaved caspase-3 was detected by Western blot. Additionally, the expression of phosphorylated nuclear transcription factor-κB(NF-κB) p65(p-NF-κB p65)(upstream) and nuclear factor kappa B inhibitor alpha(IκBα)(downstream) in the NF-κB signaling pathway was assessed by Western blot. The results showed that compared with the sham group, left ventricular ejection fraction(LVEF) and left ventricular short axis shortening(LVFS) in the model group were significantly reduced, while left ventricular end diastolic diameter(LVEDD) and left ventricular end systolic diameter(LVESD) increased significantly. Myocardial tissue damage was severe, with widened intercellular spaces and disorganized cell arrangement. The apoptosis rate was increased, and mitochondria were enlarged with increased vacuoles. Levels of TNF-α, IL-1β, and NT-proBNP were elevated, indicating an obvious inflammatory response. The expression of pro-apoptotic factors Bax and cleaved caspase-3 increased, while the anti-apoptotic factor Bcl-2 decreased. The expression of p-NF-κB p65 was upregulated, and the expression of IκBα was downregulated. In contrast, the Chaihu Jia Longgu Muli Decoction groups showed significantly improved of LVEF, LVFS and decreased LVEDD, LVESD compared to the model group. Myocardial tissue damage was alleviated, and intercellular spaces were reduced. The apoptosis rate decreased, mitochondrial volume decreased, and the levels of TNF-α, IL-1β, and NT-proBNP were lower. The expression of pro-apoptotic factors Bax and cleaved caspase-3 decreased, while the expression of the anti-apoptotic factor Bcl-2 increased. Additionally, the expression of p-NF-κB p65 decreased, while IκBα expression increased. In summary, this experimental study shows that Chaihu Jia Longgu Muli Decoction can reduce the inflammatory response and apoptosis rate in rats with heart failure after myocardial infarction, which may be related to the regulation of the IκBα/NF-κB signaling pathway.
Animals ; Apoptosis/drug effects* ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; Myocardial Infarction/physiopathology* ; Male ; NF-kappa B/genetics* ; Heart Failure/etiology* ; Rats, Sprague-Dawley ; Signal Transduction/drug effects* ; NF-KappaB Inhibitor alpha/genetics* ; Humans ; Tumor Necrosis Factor-alpha/genetics*

Objective:To discuss the promotive effect of nerve growth factor(NGF),which is highly expressed in the adipose-derived stem cell(ADSC)-induced Schwann-like cells(SCLCs),on the growth of dorsal root ganglion(DRG)cell processes in the rats,and to clarify its mechanism.Methods:The ADSCs were extracted from the epididymal adipose tissue of the SD rats,and their multidirectional differentiation potential was identified through osteogenic,adipogenic,and chondrogenic induction.The ADSCs were induced to differentiate into the SCLCs,and the expression levels of glial fibrillary acidic protein(GFAP)and S100 calcium-binding protein β(S100β)protein in the ADSCs and SCLCs were detected by immunofluorescence staining and Western blotting methods.The DRG cells were isolated and cultured,and immunofluorescence staining was used to detect the βⅢ-tubulin expression in the DRG cells for identification.The SCLCs were co-cultured with the DRG cells(co-culture group),the single-culture DRG cells were regared as DRG group and toluidine blue staining was used to observe and measure the length of DRG cell processes under the optical microscope in co-culture group and DRG group.Small interfering RNA(siRNA)transfection was used to knock down NGF,and plasmid transfection was used to over-express NGF.Real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the NGF mRNA expression levels in the cells in various groups;enzyme-linked immunosorbent assay(ELISA)method was used to detect the NGF protein levels in the cell supernatants.The transfected SCLCs were co-cultured with DRG cells and divided into control group,siNC/vector group,NGF knockdown group(si-NGF group),and NGF over-expression group(oe-NGF group).The lengths of DRG cell processes in various groups were observed.Results:The primary ADSCs adhered within 24 h after seeding,with a small number of lipid droplets remaining.After 3 d of culture,the cells were mostly short spindle-shaped,fusiform,or polygonal,growing rapidly in a vortex pattern.After passaging,the cells exhibited a uniform morphology,appearing as long spindles arranged in a fish-school pattern.After 14 d of adipogenic induction,the cell morphology changed from spindle-shaped to flat-round,with translucent lipid droplets forming in the cytoplasm,which were stained red by Oil Red O.After 28 d of osteogenic induction,the cells appeared sand-like with blurred morphology,and calcified nodules were observed,which were stained red by Alizarin Red and deposited in the extracellular matrix.After 28 d of chondrogenic induction in a 3D culture system,millet-sized chondrogenic spheres formed.Frozen sections of the spheres were stained with Alcian Blue,and acidic mucopolysaccharides in the cartilage tissue were stained blue under the microscope.Under the fluorescence microscope,the third-passage purified ADSCs showed positive expression of CD29[fluorescein isothiocy anate(FITC)-labeled green fluorescence]and CD44(Cy3-labeled red fluorescence).The immunofluorescence staining results showed that GFAP was labeled with FITC(green fluorescence),and S100β was labeled with Cy3(red fluorescence).The Western blotting results showed that compared with ADSCs,the expression levels of S100β and GFAP proteins in the SCLCs were increased(P<0.05).The primary DRG cells began to adhere 6 h after conventional culture,and after 3 d,the cell bodies appeared round and bright,with two linear processes extending from them.Under fluorescence microscope,the cells positively expressed the neuron-specific marker βⅢ-tubulin,confirming that the isolated cells were DRG cells.Compared with the ADSCs,the NGF protein expression level in the SCLCs was increased(P<0.05).Compared with DRG group,the length of DRG cell processes in co-culture group was the highest when DRG cells and SCLCs were co-cultured at a 1∶2 ratio(P<0.05).The RT-qPCR results showed that compared with si-NC group,the expression levels of NGF mRNA in the cell supernatant in si-NGF-1,si-NGF-2,and si-NGF-3 groups were significantly decreased(P<0.05),with si-NGF-1 showing the highest knockdown efficiency,which was selected for subsequent experiments.The ELISA results showed that compared with si-NC group,the NGF levels in the cell supernatant of si-NGF-1,si-NGF-2,and si-NGF-3 groups were decreased(P<0.05).Compared with Vector group,the expression level of NGF mRNA and NGF protein level in the supernatant in oe-NGF group were increased(P<0.05).Compared with control group and siNC/vector group,the length of DRG cell processes in si-NGF group was decreased(P<0.05),while the length of DRG cell processes in oe-NGF group was increased(P<0.05).Conclusion:ADSCs can be directionally differentiated into SCLCs,and the differentiated cells highly express NGF.Knockdown or overexpression of NGF can affect the growth of DRG cell processes.

Objective Currently, there is no commercially available quantitative detection kit for the main Felis domestic allergen (Fel d 1) in China. To establish a rapid detection method for Fel d 1, this study aims to prepare monoclonal antibodies against Fel d 1 protein. Methods The codon preference of Escherichia coli was utilized to optimize and synthesize the Fel d 1 gene. The prokaryotic expression plasmid pET-28a-Fel d 1 was constructed and used to express and purify the recombinant Fel d 1 protein. Subsequently, the recombinant protein was immunized into BALB/c mice and monoclonal antibodies (mAbs) were prepared by the hybridoma technique. An indirect ELISA was established using the recombinant Fel d 1 as the coating antigen, and hybridoma cell lines were screened for positive clones. The specificity and antigenic epitopes of the mAbs were confirmed by Western blot analysis. Finally, the selected hybridoma cells were injected into the peritoneal cavities of BALB/c mice for large-scale monoclonal antibody production. Results The recombinant plasmid pET-28a-Fel d 1 was successfully constructed, and soluble Fel d 1 protein was obtained after optimizing the expression conditions. Western blot and antibody titer assays confirmed the successful isolation of two hybridoma cell lines, 7D11 and 5H4, which stably secreted mAbs specific to Fel d 1. Antibody characterization revealed that the 5H4 mAb was of the IgG2a subtype and could recognize the amino acid region 105-163 of Fel d 1, while the 7D11 mAb was the IgG1 subtype and could recognize the amino acid region 1-59. Conclusion The high-purity recombinant Fel d 1 protein produced in this study provides a promising alternative for clinical immunotherapy of cat allergies. Furthermore, the monoclonal antibody prepared in this experiment lays a material foundation for the in-depth study of the biological function of Fel d 1 and the development of ELISA detection.
Animals ; Antibodies, Monoclonal/biosynthesis* ; Mice, Inbred BALB C ; Cats ; Mice ; Allergens/genetics* ; Glycoproteins/genetics* ; Enzyme-Linked Immunosorbent Assay ; Hybridomas/immunology* ; Recombinant Proteins/genetics* ; Female ; Antibody Specificity

The liver performs multiple life-sustaining functions. Hepatic diseases, including hepatitis, cirrhosis, and hepatoma, pose significant health and economic burdens globally. Along with the advances in nanotechnology, mesoporous silica nanoparticles (MSNs) exhibiting diversiform size and shape, distinct morphological properties, and favorable physico-chemical features have become an ideal choice for drug delivery systems and inspire alternative thinking for the management of hepatic diseases. Initially, we introduce the physiological structure of the liver and highlight its intrinsic cell types and correlative functions. Next, we detail the synthesis methods and physicochemical properties of MSNs and their capacity for controlled drug loading and release. Particularly, we discuss the interactions between liver and MSNs with respect to the passive targeting mechanisms of MSNs within the liver by adjusting their particle size, pore diameter, surface charge, hydrophobicity/hydrophilicity, and surface functionalization. Subsequently, we emphasize the role of MSNs in regulating liver pathophysiology, exploring their value in addressing liver pathological states, such as tumors and inflammation, combined with multi-functional designs and intelligent modes to enhance drug targeting and minimize side effects. Lastly, we put forward the problems, challenges, opportunities, as well as clinical translational issues faced by MSNs in the management of liver diseases.

BackgroundCognitive function is closely related to an individual's quality of life and social functioning， with approximately 20%~35% of patients with depressive disorder experiencing some degree of cognitive impairment even after clinical symptom remission. Existing evidence suggests that tACS can improve specific cognitive domains， such as memory function， while its effects on other cognitive dimensions， such as executive functioning， attention， and information processing speed， remain unclear. ObjectiveTo explore the effects of tACS on the multidimensional cognitive functions and emotional problems of patients with depressive disorder， thus to provide references for the treatment of depressive disorder. MethodsForty-nine patients with depressive disorder who were hospitalized in the Fourth People's Hospital of Wuhu from November 2022 to October 2024 and met the diagnostic criteria for depressive disorder outlined in the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5）， were selected as study participants. Subjects were randomly divided into study group （n=23） and control group （n=26） based on Microsoft Excel. Both groups received sertraline treatment. The initial dose was 50 mg/day， which gradually titrated upward based on individual variability， drug tolerance， and therapeutic response， with a maintenance dose ranging from 100 to 200 mg/day. In addition， the study group underwent tACS therapy for 4 weeks， with 5 sessions per week， each lasting 20 minutes. The control group received sham stimulation， in which the stimulus was interrupted after the first 30 seconds. At baseline， the 4^th week， and the 12^th week of treatment， patients were assessed using the Hamilton Depression Scale-17 item （HAMD-17）， Hamilton Anxiety Scale （HAMA）， and MATRICS Consensus Cognitive Battery （MCCB）. ResultsRepeated measures analysis of variance indicated that both the time effect and the time×group interaction effect for HAMD-17 scores were statistically significant between the two groups （F=260.437， 25.309， P<0.01）. At week 12 of treatment， the HAMD-17 score in the study group was lower than that in the control group （t=4.236， P<0.01）. For HAMA scores， the time effect， group effect， and time×group interaction effect were all statistically significant between the two groups （F=248.082， 4.506， 9.500， P<0.05 or 0.01）. At weeks 4 and 12， study group reported lower HAMA scores compared with control group （t=4.580， 2.608， P<0.05 or 0.01）. Regarding the MCCB scores for attention/vigilance， verbal learning， and overall composite， the time effect， group effect， and time×group interaction effect were all statistically significant between the two groups （F=70.331， 27.882， 51.679， 5.560， 10.948， 7.860， 8.490， 3.874， 5.025， P<0.05 or 0.01）. After intervention， the study group showed significantly higher MCCB scores for attention/vigilance， verbal learning， and overall composite at both week 4 （t=-2.149， -3.530， -2.740， P<0.05） and week 12 （t=-3.534， -3.576， -3.838， P<0.01） when compared to the control group. ConclusionThe combined tACS and sertraline therapy may demonstrate superior efficacy to pharmacotherapy alone in the short term for improving attention/vigilance， verbal learning， overall cognitive function， and anxiety symptoms in patients with depressive disorders. Based on the 12-week outcomes， the combined tACS and sertraline therapy not only sustaine its previously observed advantages in improving cognitive domains and anxiety symptoms， but also demonstrate potentially superior efficacy over monotherapy in alleviating depressive symptoms. ［Fund by Clinical Medical Research Transformation Special Project of Anhui Province （number， 202204295107020065）］

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

Objective:To systematically investigate the association and regulatory mechanism between genetic variants in the binding region of pancreatic and duodenal homeobox 1 (PDX1) and pancreatic cancer susceptibility in the Chinese population.Methods:Chromatin immunoprecipitation sequencing (ChIP-seq) was performed using the human pancreatic cancer cell line BxPC-3 to identify and annotate genetic variants within the PDX1 binding region. A two-center case-control study was conducted, and logistic regression models were employed to analyze the association between PDX1-related variants and pancreatic cancer susceptibility. Functional experiments were performed to elucidate the molecular mechanisms of these genetic variants.Results:ChIP-seq analysis identified 1 608 PDX1 binding regions. SNPs within these regions were significantly enriched in susceptible areas of pancreatic cancer ( P<0.001). The common variant rs154659, located within the most significant PDX1 binding peak, was further investigated. The multivariate logistic regression model showed that compared with individuals with TT genotype, individuals with CC genotype had a reduced risk of pancreatic cancer by 29.2% ( OR=0.708, 95% CI: 0.589-0.850). Functional studies demonstrated that the rs154659[C] allele displayed higher relative luciferase activity than the rs154659[T] allele. Knockdown of PDX1 significantly attenuated the relative luciferase differences between the two alleles. Conclusion:Genetic variants in the PDX1 binding region are associated with pancreatic cancer risk. The rs154659 modulates pancreatic cancer susceptibility by specifically altering PDX1 binding activity.

Objective:To investigate the association between blood selenium levels and sex hormones in Chinese men aged 18-79 years.Methods:Data were derived from the China National Human Biomonitoring survey conducted in 2017-2018, with a final sample size of 5 414 men. General demographic characteristics, behavioral habits, and dietary frequency were collected through questionnaires and physical examinations. Fasting blood samples were collected to measure blood lead, serum testosterone, and estradiol levels. Complex sampling linear regression models were used to analyze the associations between blood selenium levels and testosterone, estradiol, and the testosterone/estradiol ratio, adjusting for confounding factors including age, education level, marital status, smoking status, alcohol consumption, seafood intake, soy product intake, protein supplement intake, BMI, and diabetes status.Results:The mean age of the 5 414 participants was (46.85±27.91) years; 4 774 (91.65%) were of Han ethnicity and 4 505 (86.68%) were married. The median ( Q1, Q3) blood selenium concentration in men was 97.80 (80.64, 116.99) μg/L. After adjusting for confounding factors, the complex sampling linear regression model revealed negative associations between blood selenium levels and both testosterone levels and the testosterone/estradiol ratio, with a significant linear trend ( Ptrend<0.05). Compared with the Q1 group, the β (95% CI) values for testosterone in the Q2, Q3, and Q4 groups were -0.02 (-0.06 to 0.02), -0.03 (-0.08 to 0.01), and -0.06 (-0.09 to -0.02), respectively. Similarly, the β (95% CI) values for the testosterone/estradiol ratio in the Q2, Q3, and Q4 groups were -0.01 (-0.03 to 0.02), -0.01 (-0.04 to 0.04), and -0.03 (-0.06 to -0.01), respectively. Subgroup analysis indicated stronger associations between blood selenium levels and testosterone/estradiol levels in non-smoking and obese men (BMI≥28 kg/m2). Conclusion:Blood selenium levels are negatively associated with testosterone levels and the testosterone/estradiol ratio in Chinese adult males.

Objective:To investigate the impact of peripheral blood prolymphocyte percentage on the prognosis of patients with chronic lymphocytic leukemia (CLL) .Methods:This study included 300 patients diagnosed with CLL at the Department of Hematology of Jiangsu Provincial People’s Hospital from October 2011 to December 2020. The association between prolymphocyte percentage and other parameters was analyzed, and the optimal cutoff prolymphocyte percentage was determined by X-tile analysis. Further survival analysis and prognostic model construction were used to validate the predictive value of prolymphocyte percentage.Results:Of the 300 eligible patients with CLL who were enrolled, 50 received Bruton tyrosine kinase inhibitors (BTKi) as first-line treatment. The group with higher prolymphocyte percentage comprised more patients in the advanced stages ( P=0.010) and had higher β 2-microglobulin ( P<0.001), unmutated immunoglobulin heavy-chain variable region gene ( P<0.001), and TP53 aberration ( P=0.004). The optimal cutoff percentage of prolymphocytes was 1%. Patients with a prolymphocyte percentage >1% had significantly shorter treatment-free survival (TFS) ( P<0.001) and overall survival time ( P=0.007) than patients with a prolymphocyte percentage ≤1%. On multivariate analysis, prolymphocyte percentage >1% tended to have an independent prognostic value for TFS [ HR=1.405 (95% CI 0.971~2.032), P=0.071]. Compared with the nomogram of CLL international prognostic index (CLL-IPI) alone, the nomogram of CLL-IPI combined with prolymphocyte percentage showed better discrimination (area under the curve: 0.778 vs. 0.637; P=0.006). In addition, patients with a prolymphocyte percentage >1% were more likely to progress after BTKi treatment ( P=0.038) . Conclusion:Peripheral blood prolymphocyte percentage was associated with various clinical and biological parameters and prognosis among patients with treatment-naive CLL.