Objective To explore the molecular mechanism of cerebroprotein hydrolysate-1(CH-1)in improving cognitive impairment of VD at animal level,and to determine the regulatory effect of CH-1 on Nrf2/ARE signaling pathway.Methods Thirty-six SD rats were randomly divided into sham operation group,VD group,low-and high-dose groups,with 9 rats in each group.VD model was established by bilateral common carotid artery ligation,and CH-1 was injected intraperitone-ally for 3 weeks.Morris water maze test and new object recognition test were performed to evalu-ate cognitive function.Hippocampal tissues was collected for immunohistochemistry/Western blot analysis.Results Compared with the sham operation group,the VD group exhibited significantly prolonged escape latency at 2-4 d of Morris water maze test,and up-regulated expression of ubiquitinated protein,LC3 Ⅱ/Ⅰ ratio,P65 and Beclin1 protein in the hippocampus,while down-regulated P62 expression(P＜0.05).Obviously shortened escape latency was observed in the high-dose group at 3-4 d and the low-dose group at 4 d than the VD group(P＜0.05).The resi-dence time in target quadrant,number of platform crossings,total exploration time of novel object recognition in the high-dose group and the total exploration time of novel object recognition in the low-dose group were significantly longer than those in VD group(P＜0.05).The expression levels of ubiquitinated,LC3 Ⅱ/Ⅰ ratio,P65 and Beclin1 were significantly lower in the low-dose group and high-dose group than the VD group(P＜0.05).The expression level of P62 protein in the VD group,low-and high-dose group were significantly increased in a dose-dependent manner(2.78±0.44,1.80±0.24 vs 3.67±0.34;2.37±0.26,1.53±0.09 vs 2.92±0.19;2.74±0.14,1.81±0.19 vs 3.93±0.50;2.28±0.17,1.72±0.17 vs 3.17±0.31,P＜0.05).Conclusion CH-1 can effectively improve the cognitive ability of VD rats and reduce the autophagy of hippocampal neurons.This therapeutic effect may be closely related to its enhancing activity of Nrf2/ARE signaling pathway.

Heart failure (HF) is the end-stage of all cardiac diseases, characterized by high prevalence, high mortality, and heavy social and economic burden. Early warning of HF exacerbation is of great value for outpatient management and reducing readmission rates. Currently, remote dynamic monitoring technology, which captures changes in hemodynamic and physiological parameters of HF patients, has become the primary method for early warning and is a hot research topic in clinical studies. This paper systematically reviews the progress in this field, which was categorized into invasive monitoring based on implanted devices, non-invasive monitoring based on wearable devices, and other monitoring technologies based on audio and video. Invasive monitoring primarily involves direct hemodynamic parameters such as left atrial pressure and pulmonary artery pressure, while non-invasive monitoring covers parameters such as thoracic impedance, electrocardiogram, respiration, and activity levels. These parameters exhibit characteristic changes in the early stages of HF exacerbation. Given the clinical heterogeneity of HF patients, multi-source information fusion analysis can significantly improve the prediction accuracy of early warning models. The results of this study suggest that, compared with invasive monitoring, non-invasive monitoring technology, with its advantages of good patient compliance, ease of operation, and cost-effectiveness, combined with AI-driven multimodal data analysis methods, shows significant clinical application potential in establishing an outpatient management system for HF.
Humans ; Heart Failure/physiopathology* ; Monitoring, Physiologic/methods* ; Wearable Electronic Devices ; Remote Sensing Technology ; Early Diagnosis ; Electrocardiography ; Hemodynamics

Objective To explore the molecular mechanism of cerebroprotein hydrolysate-1(CH-1)in improving cognitive impairment of VD at animal level,and to determine the regulatory effect of CH-1 on Nrf2/ARE signaling pathway.Methods Thirty-six SD rats were randomly divided into sham operation group,VD group,low-and high-dose groups,with 9 rats in each group.VD model was established by bilateral common carotid artery ligation,and CH-1 was injected intraperitone-ally for 3 weeks.Morris water maze test and new object recognition test were performed to evalu-ate cognitive function.Hippocampal tissues was collected for immunohistochemistry/Western blot analysis.Results Compared with the sham operation group,the VD group exhibited significantly prolonged escape latency at 2-4 d of Morris water maze test,and up-regulated expression of ubiquitinated protein,LC3 Ⅱ/Ⅰ ratio,P65 and Beclin1 protein in the hippocampus,while down-regulated P62 expression(P＜0.05).Obviously shortened escape latency was observed in the high-dose group at 3-4 d and the low-dose group at 4 d than the VD group(P＜0.05).The resi-dence time in target quadrant,number of platform crossings,total exploration time of novel object recognition in the high-dose group and the total exploration time of novel object recognition in the low-dose group were significantly longer than those in VD group(P＜0.05).The expression levels of ubiquitinated,LC3 Ⅱ/Ⅰ ratio,P65 and Beclin1 were significantly lower in the low-dose group and high-dose group than the VD group(P＜0.05).The expression level of P62 protein in the VD group,low-and high-dose group were significantly increased in a dose-dependent manner(2.78±0.44,1.80±0.24 vs 3.67±0.34;2.37±0.26,1.53±0.09 vs 2.92±0.19;2.74±0.14,1.81±0.19 vs 3.93±0.50;2.28±0.17,1.72±0.17 vs 3.17±0.31,P＜0.05).Conclusion CH-1 can effectively improve the cognitive ability of VD rats and reduce the autophagy of hippocampal neurons.This therapeutic effect may be closely related to its enhancing activity of Nrf2/ARE signaling pathway.

Background:The diversity and function of gut microbiota have been regarded as crucial factors affecting human health.With the advances in genetics and epidemiology,especially the application of Mendelian randomization analysis,a novel perspective has been provided for profoundly uncovering the causal relationship between gut microbiota and duodenal ulcer.Aims:To investigate the causal relationship between gut microbiota and duodenal ulcer through two-sample Mendelian randomization analysis.Methods:Genetic variation samples of the gut microbiota were screened from the MiBioGen database.Genetic loci related to duodenal ulcer were selected as instrumental variables from genome-wide association study.The inverse-variance weighted method,weighted median method,and MR-Egger regression analysis were used to assess the causal relationship between gut microbiota and duodenal ulcer.Tests for heterogeneity and horizontal pleiotropy were conducted to ensure the stability of the results.Results:Bacteroides(OR=0.998,95%CI:0.996-1.000,P=0.014),Prevotella_7(OR=0.999,95%CI:0.998-1.000,P=0.043)and Terrisporobacter(OR=0.998,95%CI:0.997-1.000,P=0.029)exhibited negative causal relationship with duodenal ulcer,while Bifidobacterium(OR=1.001,95%CI:1.000-1.003,P=0.046),Lachnoclostridium(OR=1.002,95%CI:1.001-1.004,P=0.007)and Olsenella(OR=1.001,95%CI:1.000-1.002,P=0.018)presented positive causal relationship with duodenal ulcer.The sensitivity analysis indicated that the influences of heterogeneity and horizontal pleiotropy on the causal relationship could be excluded.Conclusions:The two-sample Mendelian randomization analysis revealed that Bacteroides,Prevotella_7 and Terrisporobacter were protective factors for duodenal ulcer,while Bifidobacterium,Lachnoclostridium and Olsenella were risk factors.

Objective:To investigate the clinical value of neuroendoscopic resection in recurrent or residual sellar and clivus tumors and the prevention and treatment of operative complications.Methods:A retrospective study was performed. Clinical data of 49 patients with residual or recurrent sellar and clivus tumors after neuroendoscopic resection in Department of Neurosurgery, First Affiliated Hospital of Sun Yat-sen University from November 2021 to October 2023 were collected; 45 patients were with pituitary adenoma, 3 were with craniopharyngioma, and 1 patient was with clivus chordoma; their surgical efficacy and complications were summarized and analyzed.Results:Total resection was achieved in 29 patients (59.2%), subtotal resection in 12 (24.5%), and partial resection in 8 (16.3%). Two patients (4.1%) had intraoperative internal carotid artery rupture and were given emergency laminar stenting, discharging with good recovery, but one of them left with unilateral motor nerve palsy. During 1-24 months of follow-up, 97.2% patients (35/36) had headache relief and visual acuity improvement, and no patient had permanent diabetes insipidus or cerebrospinal fluid rhinorrhea. Residual tumors increased in 3 patients (6.1%); no tumor recurrence after total resection was noted.Conclusion:Endoscopic resection of recurrent or residual sellar and clivus tumors is safe and effective; attention should be paid to the internal carotid artery during the operation.

Metabolic heterogeneity plays a central role in sustaining uncontrolled cancer cell proliferation and shaping the tumor microenvironment(TME),which significantly compromises the clinical outcomes and responses to therapy in head and neck squamous cell carcinoma(HNSCC)patients.This highlights the urgent need to delineate the intrinsic heterogeneity and biological roles of metabolic vulnerabilities to advance precision oncology.The metabolic heterogeneity of malignant cells was identified using single-cell RNA sequencing(scRNA-seq)profiles and validated through bulk transcriptomes.Serine-glycine-one-carbon(SGOC)metabolism was screened out to be responsible for the aggressive malignant properties and poor prognosis in HNSCC patients.A 4-SGOC gene prognostic signature,constructed by LASSO-COX regression analysis,demonstrated good predictive performance for overall survival and therapeutic responses.Patients in the low-risk group exhibited greater infiltration of exhausted CD8+T cells,and demonstrated better clinical outcomes after receiving immunotherapy and chemotherapy.Conversely,high-risk patients exhibited characteristics of cold tumors,with enhanced IMPDH1-mediated purine biosynthesis,resulting in poor responses to current therapies.IMPDH1 emerged as a potential therapeutic metabolic target.Treatment with IMPDH inhibitors effectively suppressed HNSCC cell proliferation and metastasis and induced apoptosis in vitro and in vivo by triggering GTP-exhaustion nucleolar stress.Our findings underscore the metabolic vulnerabilities of HNSCC in facilitating accurate patient stratification and individualized precise metabolic-targeted treatment.

Metabolic heterogeneity plays a central role in sustaining uncontrolled cancer cell proliferation and shaping the tumor microenvironment(TME),which significantly compromises the clinical outcomes and responses to therapy in head and neck squamous cell carcinoma(HNSCC)patients.This highlights the urgent need to delineate the intrinsic heterogeneity and biological roles of metabolic vulnerabilities to advance precision oncology.The metabolic heterogeneity of malignant cells was identified using single-cell RNA sequencing(scRNA-seq)profiles and validated through bulk transcriptomes.Serine-glycine-one-carbon(SGOC)metabolism was screened out to be responsible for the aggressive malignant properties and poor prognosis in HNSCC patients.A 4-SGOC gene prognostic signature,constructed by LASSO-COX regression analysis,demonstrated good predictive performance for overall survival and therapeutic responses.Patients in the low-risk group exhibited greater infiltration of exhausted CD8+T cells,and demonstrated better clinical outcomes after receiving immunotherapy and chemotherapy.Conversely,high-risk patients exhibited characteristics of cold tumors,with enhanced IMPDH1-mediated purine biosynthesis,resulting in poor responses to current therapies.IMPDH1 emerged as a potential therapeutic metabolic target.Treatment with IMPDH inhibitors effectively suppressed HNSCC cell proliferation and metastasis and induced apoptosis in vitro and in vivo by triggering GTP-exhaustion nucleolar stress.Our findings underscore the metabolic vulnerabilities of HNSCC in facilitating accurate patient stratification and individualized precise metabolic-targeted treatment.

Background:The diversity and function of gut microbiota have been regarded as crucial factors affecting human health.With the advances in genetics and epidemiology,especially the application of Mendelian randomization analysis,a novel perspective has been provided for profoundly uncovering the causal relationship between gut microbiota and duodenal ulcer.Aims:To investigate the causal relationship between gut microbiota and duodenal ulcer through two-sample Mendelian randomization analysis.Methods:Genetic variation samples of the gut microbiota were screened from the MiBioGen database.Genetic loci related to duodenal ulcer were selected as instrumental variables from genome-wide association study.The inverse-variance weighted method,weighted median method,and MR-Egger regression analysis were used to assess the causal relationship between gut microbiota and duodenal ulcer.Tests for heterogeneity and horizontal pleiotropy were conducted to ensure the stability of the results.Results:Bacteroides(OR=0.998,95%CI:0.996-1.000,P=0.014),Prevotella_7(OR=0.999,95%CI:0.998-1.000,P=0.043)and Terrisporobacter(OR=0.998,95%CI:0.997-1.000,P=0.029)exhibited negative causal relationship with duodenal ulcer,while Bifidobacterium(OR=1.001,95%CI:1.000-1.003,P=0.046),Lachnoclostridium(OR=1.002,95%CI:1.001-1.004,P=0.007)and Olsenella(OR=1.001,95%CI:1.000-1.002,P=0.018)presented positive causal relationship with duodenal ulcer.The sensitivity analysis indicated that the influences of heterogeneity and horizontal pleiotropy on the causal relationship could be excluded.Conclusions:The two-sample Mendelian randomization analysis revealed that Bacteroides,Prevotella_7 and Terrisporobacter were protective factors for duodenal ulcer,while Bifidobacterium,Lachnoclostridium and Olsenella were risk factors.

Objective:To investigate the effect of LRRK2G2019S mutation on activation of microglia after iron deprivation and its mechanism.Methods:(1) Microglia were differentiated from human induced pluripotent stem cells (IPSC) with the help of hematopoietic progenitor cells (HPC) and identified by immunofluorescent staining, and α-synuclein (α-syn) A53T mutant protein was obtained by protein purification technology. (2) Microglia were divided into control group, α-syn group, α-syn+ deferoxamine (DFO) group; phosphate buffer solution (PBS), 1 μmol/L purified α-syn A53T mutant protein, 1 μmol/L purified α-syn A53T mutant protein+30 mmol/L DFO were given respectively for 24 h. Fe 2+ concentration was detected by colorimetry, Rab35 protein expression was detected by Western blotting, intracellular reactive oxygen species (ROS) level was detected by flow cytometry, and interleukin-6 ( IL-6), tumor necrosis factor-α ( TNF-α) and transforming growth factor-β ( TGF-β) mRNA expressions were detected by real time-PCR (RT-PCR); microglia culture supernatant (MCS) in the 3 groups were transfered to SH-SY5Y cells, and SH-SY5Y cell apoptosis was detected by flow cytometry. (3) Bidirectional DNA sequencing was used to detect leucine rich repeat kinase 2 ( LRRK2) gene mutations in microglia treated with 1 μmol/L purified α-syn A53T mutant protein. Microglia were divided into control group, α-syn group and α-syn+GSK3357679A group, and treated with corresponding drugs for 24 h, respectively (LRRK2 inhibitor GSK3357679A concentration: 10 nmol/L), and LRRK2 protein expression was detected by Western blotting; microglia were divided into control group, α-syn group, α-syn+GSK3357679A, and α-syn+GSK3357679A+DFO group, and treated with corresponding drugs for 24 h, Rab35 protein expression was detected by Western blotting, intracellular ROS level was detected by flow cytometry, and IL-6, TNF-α and TGF-β mRNA expressions were detected by RT-PCR. (4) Microglia were divided into control group, α-syn group, α-syn+rapamycin (RAPA) group, and treated with corresponding drugs for 24 h (concentration of autophagy inducer RAPA: 50 nmol/L); protein expressions of Rab35, P62 and microtubule-associated protein light chain 3 II (LC3II) were detected by Western blotting; intracellular ROS level was detected by flow cytometry, and IL-6, TNF-α and TGF-β mRNA expressions were detected by RT-PCR. (5) Microglia were divided into control group, α-syn group, and α-syn+Rab35 group, and treated with corresponding drugs for 24 h (concentration of Rab35 overexpressed plasmids: 1 μg/mL); Rab35, P62, and LC3II protein expressions were detected by Western blotting; ROS level was detected by flow cytometry, and IL-6, TNF-α and TGF-β mRNA expressions were detected by RT-PCR. Results:(1) Immunofluorescent staining showed negative neuronal nuclei (NeuN) expression and positive ionized calcium-binding adapter molecule 1 (Iba1) expression in microglia, and high LRRK2 expression; PcDNA3.1-SNCA-A53T expression plasmid was constructed and α-syn A53T mutant protein was purified. (2) The Fe 2+ concentration in α-syn group was significantly higher than that in control group, and the Fe 2+ concentration in α-syn+DFO group was significantly lower than that in α-syn group ( P<0.05); the Rab35 protein and TGF-β mRNA expressions in control group, α-syn group and α-syn+DFO group were decreased successively, while the IL-6 and TNF-α mRNA expressions were increased successively, with significant differences ( P<0.05); ROS level and SH-SY5Y cell apoptosis rate in control group, α-syn group, α-syn+DFO group were increased successively. (3) Bidirectional DNA sequencing showed that the LRRK2G2019S mutation in microglia was the most obvious after α-syn A53T mutant protein stimulation; compared with the control group, the α-syn group had significantly increased LRRK2 protein expression, while the α-syn+GSK3357679A group had significantly decreased LRRK2 protein expression compared with α-syn group ( P<0.05); compared with the control group, the α-syn group had significantly decreased Rab35 protein and TGF-β mRNA expressions, and statistically increased IL-6 and TNF-α mRNA expressions ( P<0.05); compared with α-syn group, the α-syn+GSK3357679A group had significantly increased Rab35 protein and TGF-β mRNA expressions, and statistically decreased IL-6 and TNF-α mRNA expressions ( P<0.05); compared with α-syn+GSK3357679A group, α-syn+GSK3357679A+DFO group had significantly increased IL-6 and TNF-α mRNA expressions, and significantly decreased Rab35 protein and TGF-β mRNA expressions ( P<0.05). The α-syn group had higher ROS level than the control group, the α-syn+GSK3357679A group had lower ROS level than the α-syn group, and the α-syn+GSK3357679A+DFO group had higher ROS level than the α-syn+GSK3357679A group. (4) Compared with the control group, the α-syn group had significantly decreased Rab35 and LC3II protein, and TGF-β mRNA expressions, and significantly increased P62 protein, IL-6 and TNF-α mRNA expressions ( P<0.05); compared with α-syn group, the α-syn+RAPA group had significantly increased Rab35 and LC3II protein, and TGF-β mRNA expressions, and significantly decreased P62 protein, and IL-6 and TNF-α mRNA expressions ( P<0.05); the α-syn group had higher ROS level than the control group and α-syn+RAPA group. (5) Compared with the control group, the α-syn group had significantly decreased Rab35 and LC3II protein, and TGF-β mRNA expressions, and statistically increased P62 protein, and IL-6 and TNF-α mRNA expressions ( P<0.05); compared with the α-syn group, the α-syn+Rab35 group had significantly increased Rab35 and LC3II protein, and TGF-β mRNA expressions, and significantly decreased P62 protein, and IL-6 and TNF-α mRNA expressions ( P<0.05). The α-syn group had higher ROS level than the control group and α-syn+Rab35 group. Conclusion:LRRK2G2019S can induce neuroinflammation by inhibiting Rab35-related autophagy under iron deprivation, and Rab35 is expected to be a key factor in intervening neuroinflammation.

Wearable monitoring, which has the advantages of continuous monitoring for a long time with low physiological and psychological load, represents a future development direction of monitoring technology. Based on wearable physiological monitoring technology, combined with Internet of Things (IoT) and artificial intelligence technology, this paper has developed an intelligent monitoring system, including wearable hardware, ward Internet of Things platform, continuous physiological data analysis algorithm and software. We explored the clinical value of continuous physiological data using this system through a lot of clinical practices. And four value points were given, namely, real-time monitoring, disease assessment, prediction and early warning, and rehabilitation training. Depending on the real clinical environment, we explored the mode of applying wearable technology in general ward monitoring, cardiopulmonary rehabilitation, and integrated monitoring inside and outside the hospital. The research results show that this monitoring system can be effectively used for monitoring of patients in hospital, evaluation and training of patients' cardiopulmonary function, and management of patients outside hospital.
Humans ; Artificial Intelligence ; Internet of Things ; Wearable Electronic Devices ; Monitoring, Physiologic/methods* ; Electrocardiography ; Internet