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 summarize the initial experience and evaluate the technical feasibility of the endoscopic transcanal transpromontorial approach（TTA） for vestibular schwannoma resection by analyzing long-term follow-up outcomes. Methods:A retrospective analysis was conducted on the perioperative and long-term follow-up data（mean follow-up time: 5 years） of patients who underwent endoscopic TTA for vestibular schwannoma resection in the Department of Otorhinolaryngology Head and Neck Surgery at Xiangya Hospital, Central South University, between January 2020 and December 2020. Long-term outcomes were systematically evaluated. Results:This study included two patients（one 41-year-old male and one 51-year-old female）. According to the AAO-HNS hearing classification system, preoperative hearing was Class C in one patient and Class D in the other. Preoperative imaging confirmed Koos stageⅠ tumors in both cases. Postoperative transient facial nerve paralysis（House-Brackmann Grade Ⅲ） recovered to Grade Ⅰ within 4 months. No complications such as cerebrospinal fluid leakage, intracranial infection, or intracranial hemorrhage occurred. No tumor recurrence was observed during the 5-year follow-up period. Conclusion:The endoscopic transcanal transpromontorial approach is minimally invasive, facilitates rapid recovery, and demonstrates satisfactory technical feasibility and safety when strict patient selection criteria（Koos stageⅠtumors with non-serviceable hearing） are applied.
Humans ; Neuroma, Acoustic/surgery* ; Male ; Adult ; Middle Aged ; Retrospective Studies ; Female ; Endoscopy/methods* ; Follow-Up Studies ; Treatment Outcome

Although a single nucleotide polymorphism for N-acetyltransferase 10 (NAT10) has been identified in patients with early-onset stroke, the role of NAT10 in ischemic injury and the related underlying mechanisms remains elusive. Here, we provide evidence that NAT10, the only known RNA N4-acetylcytidine (ac4C) modification "writer", is increased in the damaged cortex of patients with acute ischemic stroke and the peri-infarct cortex of mice subjected to photothrombotic (PT) stroke. Pharmacological inhibition of NAT10 with remodelin on Days 3-7 post-stroke or astrocytic depletion of NAT10 via targeted virus attenuates ischemia-induced infarction and improves functional recovery in PT mice. Mechanistically, NAT10 enhances ac4C acetylation of the inflammatory cytokine tissue inhibitor of metalloproteinase 1 (Timp1) mRNA transcript, which increases TIMP1 expression and results in the accumulation of microtubule-associated protein 1 light chain 3 (LC3) and progression of astrocyte autophagy. These findings demonstrate that NAT10 regulates astrocyte autophagy by targeting Timp1 ac4C after stroke. This study highlights the critical role of ac4C in the regulation of astrocyte autophagy and proposes a promising strategy to improve post-stroke outcomes via NAT10 inhibition.

Objective:To investigate and compare the clinical outcomes of the arterial pre-occlusion technique(APOT) and the traditional technique in the surgery of locally advanced pancreatic cancer with arterial involvement after conversion therapy.Methods:This is a retrospective cohort study. The clinical data of 145 patients with locally advanced pancreatic cancer with arterial involvement admitted to the Department of Hepato-Biliary-Pancreatic Surgery of the First Hospital Affiliated to Naval Medical University,from January 2020 to December 2022 were retrospectively analyzed. All patients completed neoadjuvant therapy for tumors, and the feasibility of radical surgical treatment was determined by a multidisciplinary collaborative team evaluation before surgery. According to whether the intraoperative artery was pre-occluded, 145 patients were divided into two groups, including 28 cases in the APOT group(16 males, 12 females, aged (59.0±9.4) years), and 117 cases in the routine surgery group(76 males, 41 females, aged (55.1±8.2) years). To ensure comparability of baseline data between the APOT group and the routine surgery group, a 1∶2 match was performed using the propensity score matching method, and the caliper value was 0.006 45. The t-test,the Mann-Whitney U test, χ2 test or Fisher′s exact test were used to compare the data between the two groups,respectively. Results:After matching the propensity score,there were 28 cases in the APOT group and 56 cases in the routine surgery group. There were no significant differences in gender,age,preoperative comorbidities,preoperative body mass index,surgical approaches,chemotherapy regimen,stereotactic body radiation therapy ratio,tumor markers,and type of invaded artery between the two groups (all P>0.05).The arterial occlusion time M(IQR) in the APOT group was 7.0(3.8)minutes(range:3 to 15 minutes),and no ischemic manifestations were observed in the distal target organs that blocked blood vessels after surgery. The operation time was (170.3±57.7)minutes in the APOT group and (235.0±80.2)minutes in the routine surgery group,and the difference was statistically significant ( t=-3.800, P<0.01). The APOT group also experienced less intraoperative blood loss(650(588)ml vs. 800(600)ml; U=1 026.500, P=0.021). No significant differences were found between the groups in combined vein resection and reconstruction,celiac trunk resection,early postoperative complications, readmission rates at 30 days,and postoperative length of stay(all P>0.05). Extra-arterial dissection was performed in all patients,with arterial resection and reconstruction in 3 cases: 2 cases in the APOT group(1 case involving the superior mesenteric artery and 1 case involving the common hepatic artery) and 1 case in the routine group(involving the common hepatic artery). Postoperative abdominal bleeding occurred in 4 cases,with 3 cases in the routine group,1 case in the routine group. The R0 resection rate was 85.7%(24/28) in the APOT group and 80.4%(45/56) in the routine group,without significant differences between the groups( P=0.763). The median overall survival time was 27.6 months for the APOT group and 22.5 months for the routine group,while the median disease-free survival was 11.7 months and 16.8 months,respectively,with no significant differences between the two groups( P=0.532, P=0.927). Conclusion:The arterial pre-occlusion technique can be used for extra-arterial dissection in patients with locally advanced pancreatic cancer involving the arteries,reducing surgery time and intraoperative blood loss.

Objective:To investigate and compare the clinical outcomes of the arterial pre-occlusion technique(APOT) and the traditional technique in the surgery of locally advanced pancreatic cancer with arterial involvement after conversion therapy.Methods:This is a retrospective cohort study. The clinical data of 145 patients with locally advanced pancreatic cancer with arterial involvement admitted to the Department of Hepato-Biliary-Pancreatic Surgery of the First Hospital Affiliated to Naval Medical University,from January 2020 to December 2022 were retrospectively analyzed. All patients completed neoadjuvant therapy for tumors, and the feasibility of radical surgical treatment was determined by a multidisciplinary collaborative team evaluation before surgery. According to whether the intraoperative artery was pre-occluded, 145 patients were divided into two groups, including 28 cases in the APOT group(16 males, 12 females, aged (59.0±9.4) years), and 117 cases in the routine surgery group(76 males, 41 females, aged (55.1±8.2) years). To ensure comparability of baseline data between the APOT group and the routine surgery group, a 1∶2 match was performed using the propensity score matching method, and the caliper value was 0.006 45. The t-test,the Mann-Whitney U test, χ2 test or Fisher′s exact test were used to compare the data between the two groups,respectively. Results:After matching the propensity score,there were 28 cases in the APOT group and 56 cases in the routine surgery group. There were no significant differences in gender,age,preoperative comorbidities,preoperative body mass index,surgical approaches,chemotherapy regimen,stereotactic body radiation therapy ratio,tumor markers,and type of invaded artery between the two groups (all P>0.05).The arterial occlusion time M(IQR) in the APOT group was 7.0(3.8)minutes(range:3 to 15 minutes),and no ischemic manifestations were observed in the distal target organs that blocked blood vessels after surgery. The operation time was (170.3±57.7)minutes in the APOT group and (235.0±80.2)minutes in the routine surgery group,and the difference was statistically significant ( t=-3.800, P<0.01). The APOT group also experienced less intraoperative blood loss(650(588)ml vs. 800(600)ml; U=1 026.500, P=0.021). No significant differences were found between the groups in combined vein resection and reconstruction,celiac trunk resection,early postoperative complications, readmission rates at 30 days,and postoperative length of stay(all P>0.05). Extra-arterial dissection was performed in all patients,with arterial resection and reconstruction in 3 cases: 2 cases in the APOT group(1 case involving the superior mesenteric artery and 1 case involving the common hepatic artery) and 1 case in the routine group(involving the common hepatic artery). Postoperative abdominal bleeding occurred in 4 cases,with 3 cases in the routine group,1 case in the routine group. The R0 resection rate was 85.7%(24/28) in the APOT group and 80.4%(45/56) in the routine group,without significant differences between the groups( P=0.763). The median overall survival time was 27.6 months for the APOT group and 22.5 months for the routine group,while the median disease-free survival was 11.7 months and 16.8 months,respectively,with no significant differences between the two groups( P=0.532, P=0.927). Conclusion:The arterial pre-occlusion technique can be used for extra-arterial dissection in patients with locally advanced pancreatic cancer involving the arteries,reducing surgery time and intraoperative blood loss.

Objective To conduct a detailed clinical phenotypic analysis and gene mutation detection on an au-tosomal dominant Van der Hoeve syndrome family,and to identify the pathogenic gene mutation sites of the family and the impact of the mutation on gene coding.Methods Clinical data including medical history,physical examina-tion and auxiliary examination were collected and peripheral blood samples were collected from the Van der Hoeve syndrome families.Exome sequencing and Sanger sequencing were performed on 22 family members.The data were analyzed using bioinformatics software.Results The family had a total of 5 generations,with each generation expe-riencing consecutive illnesses.Each generation of men and women could suffer from the disease,which conformed to the characteristics of autosomal dominant inheritance.The 12 patients in this family were all born with blue sclera and short stature.8 patients had a history of fractures and could heal normally.3 patients were considering hearing loss caused by Van der Hoeve syndrome.12 patients had a base deletion(c.1128delT)in exon 17 of the COL1A1 gene,causing a change in the amino acid coding after position 376 and ending the amino acid coding prematurely at position 539.10 asymptomatic individuals in this family didn't had this mutation.Conclusion The patient of this family was identified as Van der Hoeve syndrome caused by c.1128 delT mutation.

Objective:To investigate the clinical value of adjuvant therapy after conversion resection for pancreatic cancer.Methods:The retrospective cohort study was conducted. The clinicopathological data of 173 patients with pancreatic cancer who underwent surgical resection after neoadjuvant and/or induction therapy in The First Affiliated Hospital of Naval Medical University from January 2019 to December 2021 were collected. There were 107 males and 66 females, aged (59±9)years. Observation indicators: (1) comparison of clinicopathological data between patients with and without adjuvant therapy after conversion resection for pancreatic cancer; (2) analysis of influencing factors for prognosis of pancreatic cancer after conversion resection; (3) follow-up and prognosis; (4) survival benefit of adjuvant therapy in subgroup populations. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were expressed as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data was conducted using the non-parameter rank sum test. The Graphpad prism 8 software was used to draw survival curves, the Kaplan-Meier method was used to calculate survival time and survival rates, and the Log-Rank test was used for survival analysis. The COX proportional hazards regression model was used for univariate and multivariate analyses. Interaction analysis was used to determine the benefit of adjuvant therapy in subgroup populations. Results:(1) Comparison of clinicopathological data between patients with and without adjuvant therapy after conversion resection for pancreatic cancer. Of the 173 pancreatic cancer patients, there were 108 cases with adjuvant therapy after conversion resection and 65 cases without adjuvant therapy after conversion resection, respectively. Age and body mass index were (58±9)years and (23.2±2.8)kg/m 2 in patients with adjuvant therapy, versus (61±8)years and (22.2±2.8)kg/m 2 in patients without adjuvant therapy, showing significant differences in the above indicators between them ( t=-2.036, 2.200, P<0.05). (2) Analysis of influencing factors for prognosis of pancreatic cancer after conversion resection. Results of multivariate analysis showed that CA19-9 normalization, pathological N staging, degree of tumor differentiation and postoperative adjuvant therapy were independent factors influencing overall survival time in pancreatic cancer patients receiving conversion resection ( hazard ratio=1.598, 1.541, 2.004, 2.571, 95% confidence interval as 1.041-2.453, 1.021-2.327, 1.288-3.118, 1.721-3.843, P<0.05). (3) Follow-up and prognosis. All 173 patients were followed up for 24.5(5.0,52.0)months. The postoperative median overall survival time of 173 patients was 28.9(5.7,51.9)months, and the 1-, 2-, 3-year overall survival rates were 90%, 59%, 40%, respectively. Of 2019, 2020, 2021, the proportions of patients receiving adjuvant therapy after conversion resection were 62.8%(27/43), 57.7%(30/52) and 65.4%(51/78) respectively. The postoperative median overall survival time was 42.2(8.8,49.7)months in patients with adjuvant therapy after conversion resection, versus 20.4(5.7,51.9)months in patients without adjuvant therapy after conversion resection, showing a significant difference between them ( χ2=29.893, P<0.05). (4) Survival benefit of adjuvant therapy in subgroup populations. Results of interaction analysis showed that in subgroup populations with CA19-9 normalization, pathological stage N0, pathological stage N1-2, moderate to well differentiated tumors, adjuvant therapy after conversion resection can bring a better survival benefit for patients with pancreatic cancer ( adjustment hazard ratio=0.220, 0.300, 0.410, 0.340, 95% confidence interval as 0.120-0.400, 0.170-0.560, 0.240-0.690, 0.210-0.690). Conclusions:Postoperative adjuvant therapy is an independent factor influencing overall survival time in pancreatic cancer patients receiving conversion resection. Adjuvant therapy after conversion resection can bring additional survival benefits for pancreatic cancer, particularly for patients who respond favorably to neoadjuvant and/or induction therapy.

Objective: To investigate the influencing factors for mild cognitive impairment (MCI) among the elderly inpatients of the department of geriatrics, so as to provide the reference for early screening and prevention of MCI in the elderly population. Methods: Inpatients aged 60 years and older and admitted to the Department of Geriatrics at the First Affiliated Hospital of Xinjiang Medical University were selected as the study subjects. Demographic information, past medical history, activities of daily living (ADL), depressive symptoms were collected through questionnaire surveys. MCI was diagnosed with Montreal Cognitive Assessment in combination with medical history and physical examination. Factors affecting MCI were identified using a multivariable logistic regression model. Results: A total of 1 019 elderly patients were collected, including 472 males (46.32%) and 547 females (53.68%), and had a median age of 73.00 (interquartile range, 14.00) years. Among them, 746 patients had an educational level of junior high school or above, accounting for 73.21%, 446 patients had cerebrovascular disease, accounting for 43.77%, and 220 patients were diagnosed with MCI, with a detection rate of 21.59%. Multivariable logistic regression analysis showed that age (OR=1.354, 95%CI: 1.285-1.426), educational level (primary school, OR=0.345, 95%CI: 0.163-0.731; junior high school or above, OR=0.196, 95%CI: 0.096-0.402), ADL (moderate/severe dependence, OR=4.744, 95%CI: 2.044-11.012) and cerebrovascular disease (OR=2.335, 95%CI: 1.482-3.679) were the influencing factors for MCI among geriatric inpatients. Conclusions The MCI of the elderly inpatients of the department of geriatrics is related to age, educational level, ADL and cerebrovascular disease. Therefore, targeted health education and cognitive function training should be provided for elderly patients to prevent MCI.

ObjectiveTo observe the effect of Scutellariae Radix-Coptidis Rhizoma on plaque stability in atherosclerotic （AS） mice and to explore its possible mechanism of action based on the Toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor kappa B （NF-κB） signaling pathway. MethodTen normal C57BL/6J mice were used as the normal group， and the same strain of ApoE knockout （ApoE^-/-） mice were fed with a high-fat diet for 12 weeks to construct an atherosclerosis model. Mice were randomly divided into five groups， namely the model group， the atorvastatin group， and the Scutellariae Radix-Coptidis Rhizoma low-， medium-， and high-dose groups， with ten mice in each group. Then normal and model groups were given equal volume of saline gavage， and the low-， medium-， high-dose Scutellariae Radix-Coptidis Rhizoma groups were given 1.95， 3.9， 7.8 g·kg^-1 of the drug by gavage for 8 weeks， respectively. The general state of mice was observed. Hematoxylin-eosin staining was utilized to observe the pathology of aortic root plaques and calculate the percentage of plaque area. Masson staining and oil red O staining combined with immunohistochemistry of F4/80 and α-SMA were used to detect the plaque components of aortic root plaques and calculate the plaque vulnerability index. Enzyme-linked immunosorbent assay was adopted to detect the expression levels of serum tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6）. Western blot was applied to detect the protein expression levels of matrix metalloproteinase-2 （MMP-2）， matrix metalloproteinase-9 （MMP-9）， TLR4， MyD88， NF-κB p65， and phosphorylation （p） -NF-κB p65 in the aortic tissues of mice in each group. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） assay was employed to detect the expression levels of MMP-2， MMP-9， TLR4， and MyD88， NF-κB p65 mRNA. ResultCompared with the model group， the general state of the mice in each medication group was improved， and no obvious side effects were observed. Compared with the model group， the percentage of plaque area in the aortic root of AS mice was significantly reduced in the medium- and high-dose Scutellariae Radix-Coptidis Rhizoma groups （P<0.05）. The content of collagen fibers and smooth muscle cells in the plaques of the high-dose Scutellariae Radix-Coptidis Rhizoma group was significantly increased （P<0.01）， and the content of lipids and macrophages was significantly reduced （P<0.05）， the plaque vulnerability index of each dose group of Scutellariae Radix-Coptidis Rhizoma was significantly reduced， with significant reduction of the medium- and high-dose groups （P<0.01）. MMP-2 and MMP-9 protein and mRNA expression levels in aortic tissues were significantly reduced in medium- and high-dose Scutellariae Radix-Coptidis Rhizoma groups （P<0.05）. The serum levels of TNF-α and IL-6 were significantly reduced in AS mice in medium- and high-dose Scutellariae Radix-Coptidis Rhizoma groups （P<0.05）. In the medium- and high-dose Scutellariae Radix-Coptidis Rhizoma groups， the levels of TLR4， MyD88 protein， and mRNA expression in aortic tissues were significantly reduced （P<0.05）， and the level of NF-κB p65 phosphorylation in aortic tissues was significantly reduced （P<0.05）. ConclusionScutellariae Radix-Coptidis Rhizoma may play an anti-inflammatory and stabilizing role by inhibiting the TLR4/MyD88/NF-κB signaling pathway.

ObjectiveTo investigate the therapeutic effect of Scutellariae Radix-Coptidis Rhizoma （SRCR） on atherosclerosis （AS） in mice and the effect of SRCR on macrophage pyroptosis in plaques via NOD-like receptor thermal protein domain-associated protein 3 （NLRP3） inflammasomes. MethodApoE^-/- mice were fed with a high-fat diet for the modeling of AS and randomized into model， atorvastatin （5 mg·kg^-1）， and low-， medium-， and high-dose （1.95， 3.9， 7.8 g·kg^-1， respectively） SRCR groups. Normal C57BL/6J mice were selected as the control group. After 8 weeks of administration， hematoxylin-eosin staining was used to observe the pathological status of the aortic plaque. The lipid accumulation in aortic plaque was observed by oil red O staining. The serum levels of total cholesterol （TC）， triglyceride （TG）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） in mice were measured. Immunofluorescence double staining was employed to detect the co-localized expression of EGF-like module-containing mucin-like hormone receptor-like 1 （EMR1）/NLRP3 and EMR1/gasdermin D （GSDMD）. The serum levels of interleukin-1β （IL-1β） and interleukin-18 （IL-18） were determined by enzyme-linked immunosorbent assay （ELISA）. The protein levels of NLRP3， apoptosis-associated speck-like protein （ASC）， Caspase-1， cleaved Caspase-1， GSDMD， N-terminus of GSDMD （GSDMD-NT）， pro-IL-1β， IL-1β， and IL-18 were determined by Western blot， and the mRNA levels of NLRP3， ASC， Caspase-1， GSDMD， IL-1β， and IL-18 were determined by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultCompared with the control group， the model group showed obvious plaques， elevated serum levels of TG， TC， LDL-C， IL-1β， and IL-18 （P<0.01）， lowered serum level of HDL-C （P<0.01）， and up-regulated expression of NLRP3 inflammasomes and molecules related to pyroptosis in the aortic plaques （P<0.01）. Compared with the model group， SRCR， especially at the medium and high doses， alleviated the plaque pathology， reduced the lipid content in plaques （P<0.05， P<0.01）， recovered the serum lipid levels （P<0.05）， reduced the macrophage recruitment （P<0.01）， activation of NLRP3 inflammasomes， and pyroptosis in aortic root plaques （P<0.05）， lowered the serum IL-1β and IL-18 levels （P<0.01）， and down-regulated the protein levels of NLRP3， ASC， Caspase-1， cleaved Caspase-1， GSDMD， GSDMD-NT， pro-IL-1β， IL-1β， and IL-18 （P<0.05） and the mRNA levels of NLRP3， ASC， Caspase-1， GSDMD， IL-1β， and IL-18 in the aortic tissue （P<0.05）. ConclusionSRCR exerts a therapeutic effect on high-fat diet-induced AS in mice by inhibiting the activation NLRP3 inflammasomes and reducing the pyroptosis of macrophages in plaques.