Objective:To investigate the neuropsychological and imaging features of patients with posterior cortical atrophy (PCA).Methods:Patients of PCA, dementia with Lewy bodies (DLB), typical Alzheimer′s disease (t-AD) who were diagnosed in the Department of Neurology, Huashan Hospital, Fudan University from September 27, 2019, to September 24, 2021 were enrolled, and the normal controls who visited the Outpatient and Physical Examination Centers of Huashan Hospital, Fudan University and Rizhao People′s Hospital at the same time were enrolled, too. Neuropsychological assessments, magnetic resonance imaging (MRI), and positron emission tomography (PET)/CT data of the 4-group subjects were collected. Variance analysis was used to compare the differences in neuropsychological performance among the 4 groups, and the imaging features of PCA patients were summarized.Results:Eleven PCA patients, 17 DLB patients, 31 t-AD patients, and 11 normal controls were included in the study. The cognitive function of patients in the PCA group [Mini-Mental State Examination (MMSE) score 13.52±1.81; Montreal Cognitive Assessment (MoCA) score 7.06±1.72] was significantly impaired compared to the normal control group (MMSE score 27.85±1.75, t=-6.561, P<0.001; MoCA score 23.60±1.59, t=-7.968, P<0.001]. However, there was no statistically significant difference compared to the DLB group and the t-AD group. Patients in the PCA group exhibited more severe impairments in attention, executive function, and language compared to the DLB group (Trail Making Test A score: 298.86±16.16 vs 110.07±18.62, t=9.980, P<0.001; Trail Making Test B score: 305.51±18.89 vs 230.34±23.59, t=2.865, P=0.024; Boston Naming Test score: 8.67±1.53 vs 15.66±1.56, t=-2.682, P=0.013) and the t-AD group (148.91±12.77, t=7.071, P<0.001; 200.78±19.34, t=3.789, P=0.004; 15.15±1.05, t=-2.544, P=0.016). Scores for visuospatial function [PCA group: 1(0, 1), normal control group: 3(3, 3), Z=-4.023, P<0.001] and visual perception [PCA group: 0(0, 1), normal control group: 35(34, 36), Z=-3.704, P<0.001] were significantly lower in the PCA group compared to the normal control group. The cranial MRI findings of PCA patients showed atrophy of the parietal and occipital lobes, with less obvious atrophy of the medial temporal lobe, which can be distinguished from t-AD. 18F-fluorodeoxyglucose PET/CT of the PCA patients showed a relative reduced glucose metabolism in the bilateral parietal lobe, occipital lobe and posterior cingulate gyrus, while the 18F-florbetapir PET/CT showed deposition of amyloid protein in the bilateral frontal lobe, parietal lobe, temporal lobe, and cingulate gyrus. Conclusions:PCA patients exhibit neuropsychological characteristics of visuospatial dysfunction, along with impairments in various cognitive domains such as memory, attention, and executive functions. The typical MRI feature is parietal occipital lobe atrophy, and the PET/CT findings are consistent with metabolic changes in AD.

Background::In vitro fertilization (IVF) has emerged as a transformative solution for infertility. However, achieving favorable live-birth outcomes remains challenging. Current clinical IVF practices in IVF involve the collection of heterogeneous embryo data through diverse methods, including static images and temporal videos. However, traditional embryo selection methods, primarily reliant on visual inspection of morphology, exhibit variability and are contingent on the experience of practitioners. Therefore, an automated system that can evaluate heterogeneous embryo data to predict the final outcomes of live births is highly desirable. Methods::We employed artificial intelligence (AI) for embryo morphological grading, blastocyst embryo selection, aneuploidy prediction, and final live-birth outcome prediction. We developed and validated the AI models using multitask learning for embryo morphological assessment, including pronucleus type on day 1 and the number of blastomeres, asymmetry, and fragmentation of blastomeres on day 3, using 19,201 embryo photographs from 8271 patients. A neural network was trained on embryo and clinical metadata to identify good-quality embryos for implantation on day 3 or day 5, and predict live-birth outcomes. Additionally, a 3D convolutional neural network was trained on 418 time-lapse videos of preimplantation genetic testing (PGT)-based ploidy outcomes for the prediction of aneuploidy and consequent live-birth outcomes.Results::These two approaches enabled us to automatically assess the implantation potential. By combining embryo and maternal metrics in an ensemble AI model, we evaluated live-birth outcomes in a prospective cohort that achieved higher accuracy than experienced embryologists (46.1% vs. 30.7% on day 3, 55.0% vs. 40.7% on day 5). Our results demonstrate the potential for AI-based selection of embryos based on characteristics beyond the observational abilities of human clinicians (area under the curve: 0.769, 95% confidence interval: 0.709–0.820). These findings could potentially provide a noninvasive, high-throughput, and low-cost screening tool to facilitate embryo selection and achieve better outcomes. Conclusions::Our study underscores the AI model’s ability to provide interpretable evidence for clinicians in assisted reproduction, highlighting its potential as a noninvasive, efficient, and cost-effective tool for improved embryo selection and enhanced IVF outcomes. The convergence of cutting-edge technology and reproductive medicine has opened new avenues for addressing infertility challenges and optimizing IVF success rates.

An animal biosafety level-3 laboratory(ABSL-3)is a high-level biosafety installation that can conduct experiments on animals infected with highly pathogenic microorganisms.In recent years,with the continuous characterization of emerging and re-emerging infectious diseases,high-level biosafety laboratories have played increasingly important roles in pathogenic mechanism and drug and vaccine research and development.The demand for ABSL-3 is increasing year by year.At the same time,there is also a growing demand for personnel who are competent in working in ABSL-3.The systematization,normalization,and standardization of pre-service training have become important to guarantee a reduction in the risks to personnel working in ABSL-3.Training of ABSL-3 staff needs to be carried out in specific simulated laboratories.Therefore,it is necessary to construct simulated ABSL-3 and establish scientific and effective operating standards and mechanisms.This paper comprehensively introduces the design,construction,operation,and functions of a simulated ABSL-3 installation.

Objective:To investigate and analysis of the occurrence and influencing factors of sarcopenia in elderly critically ill patients in the intensive care unit (ICU).Methods:A prospective cohort study was conducted. Elderly patients (aged ≥ 60 years) admitted to the ICU of Tianjin Medical University General Hospital from November 2023 to June 2024 were enrolled. Clinical records were collected, and conduct muscle mass and strength measurements, as well as upper arm circumference and calf circumference were measured. Appendicular skeletal muscle index (ASMI) of less than 7.0 kg/m 2 for males and less than 5.7 kg/m 2 for females was defined as reduced muscle mass, grip strength of less than 28 kg for males and less than 18 kg for females was defined as decreased muscle strength, patients meeting both low muscle mass and low muscle strength criteria were diagnosed with sarcopenia. According to the diagnostic criteria for sarcopenia, patients were divided into sarcopenia group and non-sarcopenia group. Multivariate Logistic regression analysis was applied to identify risk factors for sarcopenia in the elderly and to develop a predictive model for the occurrence of sarcopenia. The predictive value of various risk factors for sarcopenia in elderly critically ill patients were evaluated by receiver operator characteristic curve (ROC curve). The Kaplan-Meier curve for the length of ICU stay of two groups patients were drawn. Results:Finally, 540 elderly critically ill patients were included, including 43 patients with sarcopenia, and the incidence of sarcopenia was 8.0%. Univariate analysis showed that there were significantly differences in body mass index (BMI), number of hospitalizations in the past year, the length of ICU stay, ventilation mode, duration of mechanical ventilation, pre-admission exercise habits, nutritional support methods, upper arm circumference, calf circumference, and albumin infusion between the sarcopenia group and the non-sarcopenia group. Multivariate Logistic regression analysis showed that BMI [odds ratio ( OR) = 0.79, 95% confidence interval (95% CI) was 0.67-0.93, P = 0.004], calf circumference ( OR = 0.64, 95% CI was 0.54-0.76, P < 0.001), and duration of mechanical ventilation ( OR = 1.06, 95% CI was 1.01-1.12, P = 0.034) were associated with an increased risk of sarcopenia in elderly critically ill patients. The ROC curve results showed that the area under the curve (AUC) and 95% CI of BMI, calf circumference, and duration of mechanical ventilation for predicting sarcopenia in elderly critically ill patients were 0.828 (0.767-0.888), 0.889 (0.844-0.933), and 0.397 (0.299-0.496), respectively, with cut-off values of 22.95 kg/m 2, 28.25 cm, and 50.50 days, respectively. The Kaplan-Meier curve showed that the cumulative survival rate of patients with sarcopenia was significantly lower than that of the non-sarcopenia group (Log-Rank test: χ 2 = 5.619, P = 0.018). Conclusion:Lower BMI, smaller calf circumference, and longer duration of mechanical ventilation are associated with an increased risk of sarcopenia in critically ill elderly patients.

Objective:To explore the β-amyloid (Aβ) deposition pattern of subjects with the preclinical Alzheimer′s disease (AD), community-derived amnestic mild cognitive impairment (aMCI) and normal cognition (NC) from communities of Shanghai.Methods:According to the inclusion and exclusion criteria, 273 subjects (104 males, 169 females; age (64.2±7.6) years) were recruited from Shanghai community and memory clinics from December 2018 to July 2020. All subjects underwent MRI, 18F-AV45 PET imaging and neuropsychological scale tests and were grouped into AD, aMCI and NC groups based on clinical diagnosis. Differences in demographic information, the neuropsychological scale tests′ scores and positive rate of Aβ deposition among each group were analyzed by one-way analysis of variance or χ2 test. Aβ deposition patterns of AD and MCI groups were analyzed at voxel level, and the differences of Aβ deposition among different groups were compared. Results:Among 273 patients, the positive rates of Aβ deposition in AD, aMCI and NC groups were 84.4%(38/45), 36.4%(20/55) and 23.1%(40/173), respectively ( χ2=58.37, P<0.001). Among AD, aMCI, NC and NC (Aβ-) groups ( n=132), the education years of AD group was the lowest ((9.7±4.6) years; F=8.86, P<0.001). In addition, there were significant differences in the scores of several neuropsychological scale tests among AD, aMCI, NC groups and NC (Aβ-) group ( F values: 27.68-235.50, all P<0.001). Compared with subjects in NC(Aβ-) group, the Aβ depositions in the aMCI and AD groups were widely distributed in the whole cerebral cortex; and AD group had higher Aβ deposition in bilateral frontal, parietal, temporal, occipital lobe, cingulate gyrus and precuneus than aMCI group. Conclusions:The positive rate of Aβ deposition in the preclinical AD population from the Shanghai community is obtained. There are significant different Aβ deposition patterns in subjects at different stages of AD.

Objective:To evaluate the role of the autophagy in hydrogen-induced reduction of myocardial injury in septic mice.Methods:A total of 192 clean-grade healthy male C57BL/6J mice, aged 6-8 weeks, weighing 20-25 g, were divided into 6 groups ( n=32 each) using a random number table method: sham operation group (group Sham), sham operation plus hydrogen group (group Sham+ H 2), sepsis group (group S), sepsis plus hydrogen group (group S+ H 2), sepsis plus bafilomycin A1 group (group S+ BafA1) and sepsis plus hydrogen plus bafilomycin A1 group (group S+ H 2+ BafA1). Sepsis was produced by cecal ligation and puncture (CLP) after anesthesia. The mice inhaled 2% hydrogen for 1 h starting from 1 and 6 h after operation in group Sham+ H 2, group S+ H 2 and group S+ H 2+ BafA1. Bafilomycin A1 1 mg/kg was intraperitoneally injected at 1 h after operation in S+ BafA1 and S+ H 2+ BafA1 groups. Twenty mice in each group were selected to record the 7-day survival rates after operation. Then the mice were sacrificed at 24 h after operation to observe the pathological changes of myocardial tissues which were scored and detect the serum cardiac troponin I (cTnI) concentration (by enzyme-linked immunosorbent assay) and determine the level of microtubule-associated protein 1 light chain 3 B (LC3B) and P62 (by Western blot). LC3Ⅱ/LC3Ⅰratio was calculated. Results:Compared with group Sham, the 7-day survival rate after operation was significantly decreased, the serum cTnI concentrations and pathological scores of myocardial tissues were increased, the expression of P62 was up-regulated ( P<0.05), no significant change was found in LC3Ⅱ/LC3Ⅰratio ( P>0.05), and no significant change was found in the parameters mentioned above in group Sham+ H 2 ( P>0.05). Compared with group S, the 7-day survival rate after operation was significantly increased, the serum cTnI concentrations and pathological scores of myocardial tissues were decreased, LC3Ⅱ/LC3Ⅰratio was increased, and the expression of P62 was down-regulated in group S+ H 2, and LC3Ⅱ/LC3Ⅰratio was significantly decreased, and the expression of P62 was up-regulated in group S+ BafA1 ( P<0.05). Compared with group S+ H 2, the 7-day survival rate was significantly decreased, the serum cTnI concentrations and pathological scores of myocardial tissues were increased, LC3Ⅱ/LC3Ⅰratio was decreased, and the expression of P62 was up-regulated in group Sham+ H 2 ( P<0.05). Conclusions:The mechanism by which hydrogen alleviates myocardial damage may be related to promoting autophagy in septic mice.

Objective:To evaluate the relationship between B-cell lymphoma/adenovirus E1B19 kDa-interacting protein 3-like protein (BNIP3L)/adenovirus E1B-interacting protein and mitochondrial dysfunction in the hippocampus of mice with sepsis-associated encephalopathy (SAE).Methods:One hundred and eighty C57BL/6J mice, aged 6-8 weeks, weighing 20-25 g, were divided into 4 groups ( n=45 each) using a random number table method: control group (C group), sham operation group (Sham group), SAE group, and SAE+ BNIP3L agonist carfilzomib group (SC group). The sepsis model was developed by cecal ligation and puncture (CLP) in anesthetized animals. In SC group, carfilzomib 2 mg/kg was intraperitoneally injected at 2 h after CLP. Twenty mice in each group were selected, and the survival at 7 days after operation was recorded. Eight surviving mice in each group were selected at 1 week after CLP for Morris water maze test. The remaining mice were sacrificed at 24 h after surgery, and the hippocampal tissues were harvested for determination of the expression of BNIP3L (by immunofluorescence) and BNIP3L in mitochondrial protein (by Western blot) and for microscopic examination of the morphological structure of mitochondria. The mitochondrial ATP content was measured by fluorescein-fluorescence enzyme luminescence method, and the mitochondrial membrane potential (MMP) was measured by fluorescence spectrophotometry. Results:Compared with C and Sham groups, the survival rate was significantly decreased, the escape latency was prolonged, the time of staying at the original platform quadrant was shortened, and the number of crossing the original platform region was decreased, the expression of BNIP3L in the hippocampal mitochondria was down-regulated, the MMP and content of mitochondrial ATP were decreased ( P<0.05), the intensity of fluorescence of BNIP3L in the hippocampus was decreased, and the damage to mitochondrial ultrastructure was marked in SAE group. Compared with SAE group, the survival rate was significantly increased, the escape latency was shortened, the time of staying at the original platform quadrant was prolonged, and the number of crossing the original platform region was increased, the expression of BNIP3L in the hippocampal mitochondria was up-regulated, the MMP and content of mitochondrial ATP were increased ( P<0.05), the intensity of fluorescence of BNIP3L in the hippocampus was decreased, and the damage to mitochondrial ultrastructure was attenuated in SC group. Conclusions:BNIP3L-mediated mitochondrial dysfunction may be involved in the mechanism of SAE developed in mice.

Objective:To evaluate the effect of sleep fragmentation on postoperative cognitive dysfunction (POCD) and hippocampal glutaminergic metabolism in aged mice anesthetized with isoflurane.Methods:Forty healthy SPF-grade male C57BL/6J mice, aged 18 months, weighing 20-30 g, were divided into 4 groups ( n= 10 each) by the random number table method: normal control group (group C), sleep fragmentation group (group SF), isoflurane anesthesia/surgery group (group I/S), and sleep fragmentation plus isoflurane anesthesia/surgery group (group SF+ I/S). Group C did not received any treatment. Group SF received sleep fragmentation for 24 h. The right carotid artery exposure was performed under isoflurane anesthesia in group I/S. Group SF+ I/S received isoflurane anesthesia/right carotid artery exposure at 24 h after sleep fragmentation. The metabolic levels of glutamate (Glu), glutamine (Gln), Glu/Gln complex (Glx), and N-acetylaspartate (NAA) and their ratio to creatine (Cr) were measured by in vivo 9.4T hydrogen proton magnetic resonance spectroscopy at 2 h after anaesthesia. Y maze and Morris water maze tests were used to evaluate the cognitive function at 1-7 days after surgery. The mice were sacrificed after the behavioral testing, brain tissues were immediately obtained, and the number of Nissl bodies and density of dendritic spines in the hippocampal CA1 region were measured by Nissl staining and Golgi staining, respectively. Results:Compared with group C, the percentage of exploration time and shuttle times at the novel arm were significantly decreased, the number of crossing the original platform was decreased, the time of stay at the target quadrant was shortened, the ratios of Glu/Cr, Gln/Cr and Glx/Cr in the hippocampal CA1 region were increased, and the ratio of NAA/Cr was decreased, and the number of Nissl bodies and density of dendritic spines were decreased in SF, I/S and SF+ I/S groups ( P<0.05). Compared with group SF and group I/S, the percentage of exploration time and shuttle times at the novel arm were significantly decreased, the number of crossing the original platform was decreased, the time of stay at the target quadrant was shortened, the ratios of Glu/Cr and Glx/Cr in hippocampal CA1 region was increased, the ratio of NAA/Cr was decreased, and the number of Nissl bodies and density of dendritic spines were decreased in group SF+ I/S ( P<0.05). Conclusions:Sleep fragmentation exacerbates POCD in aged mice anesthetized with isoflurane, and the mechanism is related to nerve injury induced by abnormality in hippocampal glutaminergic metabolism excitability.

Objective:To evaluate the effect of gender on anesthetic potency of ciprofol for gastroscopy when combined with fentanyl.Methods:American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ patients, aged 18-50 yr, with body mass index of 18-25 kg/m 2, undergoing elective gastroscopy with intravenous anesthesia, were divided into 2 groups according to gender: male group (M group) and female group (F group). After fentanyl 1.5 μg/kg was intravenously injected, ciprofol was given by the Dixon′s up-and-down method, with the initial dose of 0.4 mg/kg followed by dose increment/decrement of 0.04 mg/kg. The ED 50 and 95% confidence interval of ciprofol for gastroscopy anesthesia were calculated by the probit regression analysis. Results:The ED 50 (95% confidence interval) of ciprofol for gastroscopy was 0.33 (0.32-0.34) mg/kg in F group and 0.27 (0.26-0.28) mg/kg in M patients when combined with fentanyl 1.5 μg/kg. There was no significant difference between the two groups ( P>0.05). Conclusions:There is no significant gender difference in the anesthetic potency of ciprofol for gastroscopy (ED 50: female 0.33 mg/kg, male 0.27 mg/kg) when combined with fentanyl (1.5 μg/kg).

Neuropathic pain is a chronic disease that severely afflicts the life and emotional status of patients, but currently available treatments are often ineffective. Novel therapeutic targets for the alleviation of neuropathic pain are urgently needed. Rhodojaponin VI, a grayanotoxin from Rhododendron molle, showed remarkable antinociceptive efficacy in models of neuropathic pain, but its biotargets and mechanisms are unknown. Given the reversible action of rhodojaponin VI and the narrow range over which its structure can be modified, we perforwmed thermal proteome profiling of the rat dorsal root ganglion to determine the protein target of rhodojaponin VI. N-Ethylmaleimide-sensitive fusion (NSF) was confirmed as the key target of rhodojaponin VI through biological and biophysical experiments. Functional validation showed for the first time that NSF facilitated trafficking of the Cav2.2 channel to induce an increase in Ca²⁺ current intensity, whereas rhodojaponin VI reversed the effects of NSF. In conclusion, rhodojaponin VI represents a unique class of analgesic natural products targeting Cav2.2 channels via NSF.