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.

We report a case of spinocerebellar ataxia type 8(SCA8)presenting with multisystem atrophic phenotype.The patient was a 57-year-old male with a 4-year course of illness with dizziness and ataxia as the first symptoms,followed by autonomic dysfunction and rapid eye movement sleep disorder.Neurological examination reveals autonomic dysfunction,nystagmus,dysarthria,ataxia,brain stem and cerebellar symmetrical atrophy and"hot cross bun"sign on MRI.The diagnosis of SCA8 was confirmed by the genetic testing which showed an abnormally high number of CTA/CTG repeats in the two alleles of the ATXN8OS.The patient responded well to symptomatic treatment such as ataxia and autonomic dysfunction.SCA8 is a rare movement disorder with high clinical heterogeneity.This report suggests that SCA8 can also present with autonomic dysfunction,ataxia,pontine"hot cross bun"sign and other characteristics similar to multisystem atrophy phenotype.Thus,it is necessary for clinicians to avoid misdiagnosis or missing the diagnosis of SCA8 presenting with multiple system atrophy cerebral type in clinical work.

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.

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.

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 identify the differentially expressed long-chain non-coding RNA(lncRNA) and mRNA using ribonucleic acid sequencing(RNA-seq), and construct a competing endogenous RNA(ceRNA) regulatory network in mice with sepsis-associated encephalopathy.Methods:Ten clean-grade healthy male C57BL/6 mice, aged 6-8 weeks, weighing 20-25 g, were divided into 2 groups( n=5 each) using a random number table method: sham operation group(group Sham) and sepsis group(group Sepsis). Sepsis was induced by cecal ligation and puncture(CLP) in group Sepsis, while group Sham only underwent laparotomy without CLP. Morris water maze test and contextual fear conditioning test were performed to detect the cognitive function on 1 day before CLP and 3 days after CLP. Three mice were randomly sacrificed in group Sham, and 3 mice with the worst results in the cognitive function test were sacrificed in group Sepsis. The hippocampal tissues were obtained for RNA-seq via the BGISEQ-500 platform, and the differentially expressed mRNA and lncRNA were identified. The differentially expressed mRNAs and lncRNAs were visualized and analyzed by Dr. Tom platform provided by Shenzhen BGI Technology Service Co., Ltd., and the ceRNA regulatory network was constructed using the online visualization tool Cytoscape software. Results:Compared with group Sham, the escape latency was significantly prolonged, and the percentage of time of staying at the target quadrants and percentage of time spent freezing were decreased in group Sepsis( P<0.05). A total of 62 differentially expressed lncRNAs were obtained from RNA-seq, of which the expression of 45 lncRNAs was up-regulated and the expression of 17 lncRNAs was down-regulated.There were 282 differentially expressed mRNAs identified from RNA-seq, of which the expression of 173 mRNAs was up-regulated, and the expression of 109 mRNAs was down-regulated.Gene Ontology enrichment analysis revealed that the differentially expressed mRNAs were involved in biological processes such as memory, learning or memory, inflammatory responses, regulation of aging-related behavioral decline, and regulation of synaptic plasticity. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that differentially expressed mRNAs were enriched in IL-17 signaling pathway, TNF signaling pathway, NF-κB signaling pathway and etc. KDA analysis was performed on the differentially expressed mRNAs to identify the key driver genes, and the results showed that Ch25h, Il6ra, Lcn2, Sgk1, Nr4a3, Osm, Saa3, Ccl7, Sqle, Dhcr24 were the key SAE genes.A competing endogenous RNA regulatory network was successfully constructed based on 9 lncRNAs, 28 mRNAs and 134 miRNAs in the hippocampus of mice with SAE. Conclusions:The results of RNA-seq find that 10 mRNAs including Ch25h, Il6ra, Lcn2, Sgk1, Nr4a3, Osm, Saa3, Ccl7, Sqle, Dhcr24 and lncRNAs such as Rian, Gm35874 and Gm34347 are key genes regulating SAE in mice. Meanwhile, a ceRNA regulatory network based on lncRNA-miRNA-mRNA is successfully constructed in the hippocampus of mice with SAE.

Objective:To evaluate the effects of endothelial progenitor cell (EPC)-derived exosomes on neuronal injury induced by oxygen-glucose deprivation and restoration (OGD/R).Methods:HT22 neurons of mice were cultured and divided into 3 groups ( n=30 each) using a random number table method: control group (C group), OGD/R group and OGD/R plus EPC-derived exosome group (OGD/R+ EXO group). Cells in group C were cultured in normal atmosphere.In group OGD/R, the cells were exposed to 94%N 2-1%O 2-5%CO 2 for 6 h in glucose- and serum-free DMEM medium, followed by 24 h restoration of O 2 and glucose in the normal medium.In group OGD/R+ EXO, 20 μg/ml EPC-derived exosomes were added to the culture medium at 24 h before developing the model.EPCs were identified by immunofluorescence staining.Exosomes were identified by Western blot, transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). Cell viability was measured by CCK-8 assay, the levels of malondialdehyde (MDA) and superoxide dismutase (SOD) were determined by enzyme-linked immunosorbent assay.The neuronal apoptosis was detected by TUNEL staining, and the apoptosis rate was calculated.The expression of Bax, Bcl-2, caspase-3, and cleaved caspase-3 was determined by Western blot, and cleaved caspase-3/caspase-3 ratio was calculated. Results:The cultured cells were EPCs, and EPC-derived exosomes were successfully extracted.Compared with group C, the cell viability was significantly decreased, the content of MDA was increased, the activity of SOD was decreased, the apoptosis rate was increased, the expression of Bax was up-regulated, the expression of Bcl-2 was down-regulated, and the ratio of cleaved-caspase-3/caspase-3 was increased in group OGD/R and group OGD/R+ EXO ( P<0.05). Compared with group OGD/R, the cell viability was significantly increased, the content of MDA was decreased, the activity of SOD was increased, the apoptosis rate was decreased, the expression of Bax was down-regulated, the expression of Bcl-2 was up-regulated, and the ratio of cleaved-caspase-3/caspase-3 was decreased in group OGD/R+ EXO ( P<0.05). Conclusions:EPC-derived exosomes can reduce OGD/R-induced neuronal injury, which is related to inhibition of oxidative stress and neuronal apoptosis.

Spinocerebellar ataxia (SCA) is a group of highly heterogeneous autosomal dominant genetic disease, including many subtypes. SCA11 is a rare subtype of SCA, and is caused by mutant TTBK2 gene. A case of SCA11 was reported in this article. Whole exome sequencing showed that there was a c.1284dupA frameshift mutation in TTBK2 gene. Literature review found that only 6 pedigrees of SCA11 have been reported, but the mutation site of this case is a novel identified mutation that has not been reported in the Human Gene Mutation Database.

Remifentanil is widely used to control intraoperative pain. However, its analgesic effect is limited by the generation of postoperative hyperalgesia. In this study, we investigated whether the impairment of transmembrane protein 16C (TMEM16C)/Slack is required for α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic receptor (AMPAR) activation in remifentanil-induced postoperative hyperalgesia. Remifentanil anesthesia reduced the paw withdrawal threshold from 2 h to 48 h postoperatively, with a decrease in the expression of TMEM16C and Slack in the dorsal root ganglia (DRG) and spinal cord. Knockdown of TMEM16C in the DRG reduced the expression of Slack and elevated the basal peripheral sensitivity and AMPAR expression and function. Overexpression of TMEM16C in the DRG impaired remifentanil-induced ERK1/2 phosphorylation and behavioral hyperalgesia. AMPAR-mediated current and neuronal excitability were downregulated by TMEM16C overexpression in the spinal cord. Taken together, these findings suggest that TMEM16C/Slack regulation of excitatory synaptic plasticity via GluA1-containing AMPARs is critical in the pathogenesis of remifentanil-induced postoperative hyperalgesia in rats.

Objective:To explore the efficacy of precision hepatectomy in the treatment of single hepatocellular carcinoma with microvascular invasion (MVI) of and the risk factors of positive incisal margin after operation.Methods:The clinical data of 212 patients with single hepatocellular carcinoma with MVI treated in Affiliated Hospital of Panzhihua University from July 2016 to July 2019 were analyzed retrospectively. 152 patients were treated with precision hepatectomy and 60 patients with traditional hepatectomy. According to the pathological results of postoperative liver resection, the patients treated with precision hepatectomy were divided into two groups: negative group ( n=129) and positive group ( n=23). The operation-related indexes, postoperative complications and disease-free survival rate of precision hepatectomy and traditional hepatectomy were compared, and the general data of patients with negative and positive liver cutting edge were compared. multivariate analysis of the factors affecting the positive liver cutting edge after operation; to construct a line chart prediction model to predict the positive liver cutting edge after operation, and to evaluate its predictive efficiency. Normally distributed measurement data are represented by mean±standard deviation ( Mean± SD), independent t-test is used for comparison between groups; count data are represented by the number of cases and percentages, and χ2 test is used for comparison between groups. Results:The operative time, intraoperative blood loss, postoperative hospital stay, positive rate of surgical margin, total incidence of postoperative complications, AFP negative conversion rate 6 months after operation, and 1-year disease-free survival rate of precision hepatectomy were (328.62±38.74) min, (496.83±59.76) mL, (15.28±3.61) d, 15.13% (23/152), 3.95% (6/152), 81.58% (124/152), 67.11% (102/152), respectively. The mean values of traditional hepatectomy were (315.29±40.95) min, (681.46±58.27) mL, (23.87±4.65) d, 28.33% (17/60), 21.67% (13/60), 66.67% (40/60) and 46.67% (28/60), respectively, the difference was statistically significant ( P<0.05). Univariate analysis showed that the positive liver resection margin after precision liver resection was related to the maximum diameter of the tumor, vascular tumor thrombus, TNM staging, BCLC staging, liver cirrhosis, AFP 2 months after surgery, and the distance between the tumor and the resection margin ( OR=3.645, 5.248, 4.285, 4.462, 3.883, 3.964, 3.872; 95% CI: 2.875-4.415, 4.426-6.070, 3.271-5.299, 3.354-5.570, 3.062-4.704, 3.248-4.680, 2.987-4.757; P<0.05). Maximum tumor diameter >5 cm, vascular tumor thrombus, TNM stage Ⅲ, BCLC stage C, liver cirrhosis, postoperative AFP ≥20 μg Uniql, the distance between the tumor and the resection margin was <1 mm were the risk factors of positive incisal margin after precision hepatectomy in patients with single liver cancer with MVI( OR=6.685, 8.425, 7.758, 7.854, 7.124, 7.246, 6.926; 95% CI: 5.828-7.542, 7.6385-9.212, 6.926-8.590, 7.062-8.646, 6.583-7.665, 6.618-7.874, 6.028-7.824; P<0.05). The constructed line chart prediction model had better differentiation and higher accuracy. Conclusions:Precision hepatectomy in the treatment of single hepatocellular carcinoma with MVI has the advantages of less intraoperative bleeding, faster postoperative recovery, less postoperative complications, low positive rate of liver incisal margin and high disease-free survival rate. The construction of a risk prediction model with positive surgical margin provides a reference for improving the survival rate of patients in clinic.