19 cinnamamide/ester-triazole compounds were designed, synthesized and evaluated for their anti-Alzheimer's disease (AD) activity. Among them, compound 4f displayed excellent anti-β-amyloid protein (Aβ)-mediated cytotoxicity (EC₅₀ = 2.03 ± 2.45 μmol·L^-1) in APPswe cells and acetylcholinesterase inhibiton (IC₅₀ = 4.88 ± 4.70 μmol·L^-1). Further study indicated that, at dosages of (1, 5 and 25 mg·kg^-1), compound 4f was effective in improving spatial learning and memory deficits in Aβ_1-42-impaired mice, which was achieved by promoting the nonamyloidogenic signaling and inhibiting the amyloidogenic pathway, along with the suppression of Aβ-induced Tau phosphorylation. All animal experiments in this study were approved by the Experimental Animal Care and Use Committee of the Institute of Medicinal Biotechnology (IMB-20220908D701). In conclusion, compound 4f holds promise as a lead candidate for AD treatment, and the present study lays the foundation for its subsequent development.

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 investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective To retrieve and extract the best evidence for preventing intracranial infections related to ex-ternal cerebrospinal fluid(CSF)drainage,and provide evidence-based support for reducing the incidence of intracra-nial infection caused by external CSF drainage.Methods Evidence-based care issues were determined according to PIPOST,and the best evidence on intracranial infection related to external CSF drainage tube was retrieved from top to bottom.The literature retrieval period was 2013-2023.Quality control of the literatures,as well as extraction and summary of the evidence were carried out by 2 trained graduate students.Results A total of 17 literatures were included in the analysis,including 3 guidelines,5 expert consensus,8 systematic reviews,and 1 randomized con-trolled trial.Management strategies from 3 dimensions(pre-catheterization,in-catheterization and post-catheteriza-tion)were obtained,including 20 pieces of evidence for preventing intracranial infection,such as preparation for ex-ternal CSF drainage tube,precautions during catheterization,and post-catheterization disposal.Conclusion There are differences in the management of external CSF drainage tube in clinical practice.It is necessary to develop uni-fied,standardized,and rational bundle strategies to prevent intracranial infection,so as to reduce the incidence of catheter-related intracranial infection.

Objective:To study the correlation between adverse clinical outcomes and early postnatal weight loss(representing the results of fluid management) during hospitalization in extremely premature infants(EPIs).Methods:From January 2019 to March 2023, EPIs (gestational age (GA)<28 weeks) admitted to neonatal intensive care unit(NICU) of our hospital were retrospectively analyzed. According to weight loss (WL) within the first 3 d after birth, the infants were assigned into no-WL group, WL<6% group, WL 6%-10% group and WL>10% group. The following items were compared among the four groups: fluid intake within the first 7 d after birth, the incidences of hemodynamically significant patent ductus arteriosus (hsPDA), PDA requiring surgical ligation, duration of invasive mechanical ventilation, ≥stage II necrotizing enterocolitis(NEC), grade 3-4 intraventricular hemorrhage(IVH), moderate bronchopulmonary dysplasia (BPD), severe BPD, mortality rates and total length of hospital stay.Results:A total of 119 EPIs were enrolled, including 41 in no-WL group, 22 in WL<6% group, 31 in WL 6%-10% group and 25 in WL>10% group. Among the four groups, no significant differences existed in fluid intake on d1 and d5-d7 after birth ( P>0.05). WL 6%-10% and >10% groups had significantly lower fluid intake during d2-d4 than no-WL group ( P<0.05).On d4, WL 6%-10% and >10% groups had lower fluid intake than WL <6% and no-WL groups( P<0.05).WL 6%-10% and >10% groups showed lower incidences of hsPDA than no-WL group ( P<0.05).WL>10% group had lower incidences of ≥stage II NEC, moderate BPD, shorter duration of invasive mechanical ventilation and total hospital stay than no-WL group( P<0.05). No significant differences existed in the incidences of PDA requiring surgical ligation, grade 3-4 IVH, severe BPD and mortality rates among the four groups ( P>0.05). Conclusions:For EPIs, a certain degree of WL within the first 3 d after birth is beneficial to reduce the incidences of hsPDA, NEC, moderate BPD, duration of invasive mechanical ventilation and total hospital stay. Focusing on body weight is helpful for a more optimal fluid management strategy in the early postnatal period.

Objective To study the bioequivalence of two glipizide tablets in healthy Chinese subjects.Methods Randomized,open,single-administration,two-period,self-cross-over trial design was used in the study.There were 28 Chinese healthy subjects in the fasted state and 28 in the fed state,complete repeat cross single dose oral glipizide tablets test preparation or reference preparation 5 mg.The plasma concentration of glipizide was determined by liquid chromatography/tandem mass spectrometry at different time points after administration.The non-compartmental model was used to calculate the pharmacokinetic parameters and evaluate the bioequivalence of the two formulations.Results The main pharmacokinetic parameters of glipizide in the fasted state were as follows:Cmax were(551.60±91.26)and(518.10±105.10)ng·mL-1;AUC0-t were(3 074.33±861.91)and(3 026.77±934.25)h·ng·mL-1;AUC0-∞ were(3 204.85±990.78)and(3 166.35±1 107.36)h ng·mL-1.The parameters of glipizide in the fed state were as follows:Cmax were(517.30±98.97)and(472.80±114.48)ng·mL-1;AUC0-t were(3 001.12±830.87)and(2 932.79±736.35)h·ng·mL-1;AUC0-∞ were(3 067.00±918.84)and(2 997.44±819.14)h·ng·mL-1.The 90％confidence interval of the Cmax,AUC0-t and AUC0-∞ of the test formulation and the reference formulation were from 80.00％to 125.00％.The incidence of adverse events in fasted group and fed group was no serious adverse events.Conclusion The two glipizide tablets were bioequivalent under fasted and fed conditions,and good security.

Currently,the research or publications related to the clinical comprehensive evaluation of Chinese patent medicine are increasing,which attracts the broad attention of all circles. According to the completed clinical evaluation report on Chinese patent medicine,there are still practical problems and technical difficulties such as unclear responsibility of the evaluation organization,unclear evaluation subject,miscellaneous evaluation objects,and incomplete and nonstandard evaluation process. In terms of evaluation standards and specifications,there are different types of specifications or guidelines with different emphases issued by different academic groups or relevant institutions. The professional guideline is required to guide the standardized and efficient clinical comprehensive evaluation of Chinese patent medicine and further improve the authority and quality of evaluation. In combination with the characteristics of Chinese patent medicine and the latest research achievement at home and abroad,the detailed specifications were formulated from six aspects including design,theme selection,content and index,outcome,application and appraisal,and quality control. The guideline was developed based on the guideline development requirements of China Assoication of Chinese medicine. After several rounds of expert consensus and public consultation,the current version of the guideline has been developed.
Medicine, Chinese Traditional ; Nonprescription Drugs ; Consensus ; China ; Reference Standards ; Drugs, Chinese Herbal

Objective:To investigate the efficacy of different conversion therapies for colorectal cancer with unresectable simultaneous liver metastasis.Methods:A total of 170 patients of colorectal cancer complicated with liver metastasis who were admitted to the First Affiliated Hospital of Nanchang University from Jan 2015 to Dec 2020 were included in the study. Patients were divided into an initial resectable group (42 cases) and an initial non-resectable group (128 cases).Results:There were no significant differences in OS and PFS between patients with CRLM (colorectal cancer with liver metastasis) who were resected initially and those successfully underwent transformation therapy ( P>0.05). The median OS was 36 months in the group with successful transformation, while it was 21 months in the group with simple primary tumor resection and no liver metastasis resection ( P=0.014), HR=0.48 (0.27-0.86). The median PFS was 28 months in the successful conversion group, while it was 10 months in the primary tumor resection only and no liver metastasis resection ( P=0.005), HR=0.43 (0.24-0.77). The OS difference between the group with simple primary tumor resection and no resected liver metastasis and the group with neither primary tumor nor liver metastasis resection was statistically significant: (21 months vs.13 months), HR=0.52 (0.32-0.86) ( P=0.01), while the PFS between the two groups was not statistically significant, ( P>0.05). Conclusions:Chemotherapy combined with targeted therapy has the best effect among the conversion therapies, and can improve the resection rate and survival rate of patients undergoing R 0 surgery. Resection of the primary lesion alone can also prolong the patient's survival.

Objective:To investigate the association between ureaplasma urealyticum (UU) colonization in the respiratory tract and bronchopulmonary dysplasia (BPD) in extremely preterm or extremely low birth weight infants.Methods:This was a retrospective study involving preterm infants with gestational age <28 weeks or birth weight <1 000 g who was hospitalized in the Neonatal Intensive Care Unit (NICU) of Chengdu Women's and Children's Central Hospital from June 2019 to March 2022. Respiratory tract secretion was collected for UU DNA detection within 24 h after admission. All the participants were divided into the UU-positive or negative groups based on the detection results. Clinical characteristics of the two groups were analyzed using Mann-Whitney U, t-, or Chi-square tests (Fisher exact test). Results:A total of 82 infants were enrolled, including 31 cases (37.8%) in the UU-positive group and 51 patients (62.2%) in the negative group. Among the 30 cases treated with azithromycin in the positive group, 27 (90.0%, 27/30) turned negative after two courses of treatment. The rates of premature rupture of membranes [51.6% (16/31) vs 17.6% (9/51), χ2=10.50] and prenatal antibiotic exposure [71.0% (22/31) vs 47.1% (24/51), χ2=4.47] in the UU-positive group were both higher than those in the UU-negative group (both P<0.05). Multivariate logistic regression analysis showed that premature rupture of membranes ( OR=5.893, 95% CI: 2.016-17.228) and gestational age ( OR=0.663, 95% CI: 0.441-0.999) were independent risk factors for UU colonization (both P<0.05). UU-positive group had a longer duration of oxygen use [ M ( P25- P75), 1 756 h (1 385-2 088 h) vs 1 357 h (1 128-1 656 h), Z=2.98], a longer length of hospital stay [81 d (70-105 d) vs 68 d (59-84 d), Z=3.05], and higher hospitalization costs [(201 574±70 326) yuan vs (161 288±53 412) yuan, t=－2.74] compared to the UU negative group (all P<0.05). The incidence of BPD [74.2% (23/31) vs 47.1% (24/51), χ2=5.80] and retinopathy of prematurity [93.4% (29/31) vs 74.5% (38/51), χ2=4.68] in the UU positive group was higher than those in the UU-negative group (both P<0.05). No significant correlation was found between UU colonization and the severity of BPD ( P>0.05). Conclusion:UU colonization may increase the incidence of BPD, but there was no clear correlation with the severity of BPD.

To evaluate the effectiveness of intervention plans developed by the evidence base multi-discipline critical strategies (EBPCS) on temperature and clinical outcomes in very preterm infants (VPIs) born at<32 weeks. Clinical data were collected from VPIs born in the delivery room/operating room of Chengdu Women's and Children's Central Hospital from May 1, 2021, to May 31, 2022, who required immediate temperature management and were transferred to the neonatal intensive care unit (NICU) of the hospital. The study population was randomly divided into a control group and an intervention group based on the random number table method, with 108 cases in each group. The control group implemented the conventional temperature management recommended by domestic guidelines, while the intervention group adopted EBPCS interventions compared to the control group. The differences in body temperature and clinical outcomes between the two groups were compared after the implementation of different temperature management strategies. A total of 216 VPIs were included. The intervention group had a lower incidence of hypothermia (30.55% vs. 87.03%, P<0.001), higher mean body temperature admitted to the NICU [(36.56±0.31) ℃ vs. (35.77±0.53) ℃, P<0.001], a lower dose of pulmonary surfactant [(115.94±36.96) mg/kg vs. (151.41±54.68) mg/kg, P=0.014], shorter duration of mechanical ventilation [(5.77±1.26) days vs. (14.19±4.63) days, P=0.006], and lower incidence of intraventricular haemorrhage (12.04% vs. 23.15%, P=0.032). The implementation of temperature intervention strategies developed by the EBPCS for VPIs after birth could prevent and reduce the incidence of hypothermia and improve clinical outcomes.
Child ; Female ; Humans ; Infant ; Infant, Newborn ; Fever ; Hypothermia/prevention & control* ; Infant, Premature ; Infant, Very Low Birth Weight ; Temperature