The burden of upper motor neuron involvement is correlated with the bilateral limb involvement interval in patients with amyotrophic lateral sclerosis: a retrospective observational study.

JOURNAL/nrgr/04.03/01300535-202505000-00032/figure1/v/2024-07-28T173839Z/r/image-tiff Amyotrophic lateral sclerosis is a rare neurodegenerative disease characterized by the involvement of both upper and lower motor neurons. Early bilateral limb involvement significantly affects patients' daily lives and may lead them to be confined to bed. However, the effect of upper and lower motor neuron impairment and other risk factors on bilateral limb involvement is unclear. To address this issue, we retrospectively collected data from 586 amyotrophic lateral sclerosis patients with limb onset diagnosed at Peking University Third Hospital between January 2020 and May 2022. A univariate analysis revealed no significant differences in the time intervals of spread in different directions between individuals with upper motor neuron-dominant amyotrophic lateral sclerosis and those with classic amyotrophic lateral sclerosis. We used causal directed acyclic graphs for risk factor determination and Cox proportional hazards models to investigate the association between the duration of bilateral limb involvement and clinical baseline characteristics in amyotrophic lateral sclerosis patients. Multiple factor analyses revealed that higher upper motor neuron scores (hazard ratio [HR] = 1.05, 95% confidence interval [CI] = 1.01-1.09, P = 0.018), onset in the left limb (HR = 0.72, 95% CI = 0.58-0.89, P = 0.002), and a horizontal pattern of progression (HR = 0.46, 95% CI = 0.37-0.58, P < 0.001) were risk factors for a shorter interval until bilateral limb involvement. The results demonstrated that a greater degree of upper motor neuron involvement might cause contralateral limb involvement to progress more quickly in limb-onset amyotrophic lateral sclerosis patients. These findings may improve the management of amyotrophic lateral sclerosis patients with limb onset and the prediction of patient prognosis.

Smell loss is associated with cognitive impairment in amyotrophic lateral sclerosis patients.

BACKGROUND: Smell loss significantly impacts the quality of life in patients. However, there is limited research on smell loss in individuals with amyotrophic lateral sclerosis (ALS), and the correlation between smell loss and cognitive impairment is unclear. This study aimed to investigate the correlation between smell loss and cognition impairment in ALS patients. METHODS: The study included 216 ALS patients. The Edinburgh Cognitive and Behavioural ALS Screen (ECAS) and smell identification test specifically for the Chinese population (CSIT) were administered to evaluate participants' cognitive and olfactory function, respectively. RESULTS: After covarying for age, sex, BMI, education level, degree of hunger, dietary bias, eagerness for food, stress, smoking status, alcohol consumption, and upper respiratory tract infection (URTI) or rhinitis, CSIT scores were significantly correlated with ECAS scores (r = 0.162, p = 0.028), especially the ALS-specific scores (r = 0.158, p = 0.031). Even after excluding patients with URTI or rhinitis, the results were similar. CSIT scores were significantly correlated with ECAS scores (r = 0.224, p = 0.011), especially the ALS-specific scores (r = 0.205, p = 0.019). CONCLUSION: In patients with ALS, smell loss is significantly correlated with cognitive impairment, particularly frontotemporal dysfunction. Cognitive dysfunction may lead to worse olfactory performance in ALS patients.

Validation of the Center for Neurologic Study Bulbar Function Scale-Chinese version in a population with amyotrophic lateral sclerosis.

OBJECTIVE: The Center for Neurologic Study Bulbar Function Scale (CNS-BFS) was specifically designed as a self-reported measure of bulbar function. The purpose of this research was to validate the Chinese translation of the CNS-BFSC as an effective measurement for the Chinese population with ALS. METHODS: A total of 111 ALS patients were included in this study. The CNS-BFSC score, three bulbar function items from the ALSFRS-R, and visual analog scale (VAS) score for speech, swallowing and salivation were assessed in the present study. Forty-six ALS patients were retested on the same scale 5-10 days after the first evaluation. RESULTS: The CNS-BFSC sialorrhea, speech and swallowing subscores were separately correlated with the VAS subscores (p < 0.001). The CNS-BFSC total score and sialorrhea and speech scores were significantly correlated with the ALSFRS-R bulbar subscore (p < 0.001). The CNS-BFSC total score and ALSFRS-R bulbar subscale score were highly predictive of a clinician diagnosis of impaired bulbar function (area under the receiver operating characteristic curve, 0.947 and 0.911, respectively; p < 0.001). A cutoff value for the CNS-BFSC total score was selected by maximizing Youden's index; this cutoff score was 33, with 86.4% sensitivity and 93.3% specificity. The CNS-BFSC total score and the sialorrhea, speech and swallowing subscores had good-retest reliability (p > 0.05). The Cronbach's α of the CNS-BFSC was 0.972. CONCLUSION: The Chinese version of the CNS-BFSC has acceptable efficacy and reliability for the assessment of bulbar dysfunction in ALS patients.

The integrity of the corticospinal tract and corpus callosum, and the risk of ALS: univariable and multivariable Mendelian randomization.

Studies suggest that amyotrophic lateral sclerosis (ALS) compromises the integrity of white matter fiber tracts, primarily affecting motor fibers. However, it remains uncertain whether the integrity of these fibers influences the risk of ALS. We performed bidirectional two-sample Mendelian randomization (MR) and multivariable MR analyses to evaluate the associative relationships between the integrity of fiber tracts [including the corticospinal tract (CST) and corpus callosum (CC)] and the risk of ALS. Genetic instrumental variables for specific fiber tracts were obtained from published genome-wide association studies (GWASs), including 33,292 European individuals from five diffusion magnetic resonance imaging (dMRI) datasets. Summary-level GWAS data for ALS were derived from 27,205 ALS patients and 110,881 controls. The MR results suggested that an increase in the first principal component (PC1) of fractional anisotropy (FA) in the genu of the CC (GCC) was correlated with an increased risk of ALS (PFDR = 0.001, odds ratio = 1.363, 95% confidence interval 1.178-1.577). Although other neuroimaging phenotypes [mean diffusivity in the CST, radial diffusivity (RD) in the CST, FA in the GCC, PC1 in the body of the CC (BCC), PC1 in the CST, and RD in the GCC] did not pass correction, they were also considered to have suggestive associations with the risk of ALS. No evidence revealed that ALS caused changes in the integrity of fiber tracts. In summary, the results of this study provide genetic support for the potential association between the integrity of specific fiber tracts and the risk of ALS. Greater fiber integrity in the GCC and BCC may be a risk factor for ALS, while greater fiber integrity in the CST may have a protective effect on ALS. This study provides insights into ALS development.

The positive impact of introducing public engagement as a self-directed learning strategy in undergraduate nervous system education.

Undergraduate medical education in China has shifted from educator-centered learning to self-directed learning (SDL) over the past few decades. Careful design of public engagement activities can enable SDL and empower medical students to pioneer public health and patient safety education. In this study, we aimed to innovate nervous system education by implementing a public engagement model that empowers students to learn about the nervous system by teaching the public. Our goal was to generate greater interest in the nervous system at the undergraduate stage, inspire students' enthusiasm to pursue a career in neurology, and ultimately, contribute to health promotion. During the nervous system module of the second year of the undergraduate curriculum, students were given the option to participate in the public engagement model. Participants were tasked with the creation of educational videos focusing on knowledge, attitudes, and behaviors associated with the prevention and management of neurological diseases and their complications. The videos were made accessible to the general public through the university's official channel at the end of the semester. A total of 117 students (67.24% of all students) chose to participate in the public engagement model. Female students and those with higher Grade Point Averages in the present semester were more likely to participate. The model received strong positive feedback from participants, as students found the public engagement task helpful in learning about the nervous system module as well as in enhancing their public engagement skills. Despite the time and effort consumption, participating in the public engagement task did not affect students' exam scores. The public engagement task is an innovative model in the nervous system curriculum and has the potential to be integrated into a broader range of undergraduate courses. It empowers medical students to pioneer public health and patient safety education.

Postural instability and lower extremity dysfunction in upper motor neuron-dominant amyotrophic lateral sclerosis.

Background: Upper motor neuron-dominant ALS (UMND ALS) is recognized to have early onset and good prognosis, but may have a rapid decline in motor function due to gait instability in the early stage. We investigated changes in lower extremity function in UMND ALS, particularly UMND ALS patients accompanied with postural instability or repeated falls (UMND ALS plus). Results: Among the 2,353 ALS patients reviewed, 211 (9.0%) had UMND ALS. UMND ALS had a longer diagnosis delay and restricted symptoms. Although UMND ALS patients had better lower extremity function and strength than matched classic ALS patients on first evaluation, there was no difference in the time of needing assistance or not being able to walk after disease onset. In contrast, UMND ALS plus has severe UMN symptoms and a more rapid decline in motor function. The lower extremity function was no better than that in the matched classic ALS. The prognosis of UMND ALS and UMND ALS plus were significantly better than those of overall ALS. Conclusion: UMND ALS has restricted symptoms but has a rapid decline in lower extremity function in the early stage of the disease. The motor function decline of UMND ALS plus is as fast as classic ALS. Whether these patients represent a distinct subgroup of ALS deserves further investigation.

Feedback of chain elongation microorganisms on iron-based conductive materials: Enhanced microbial functions and biotoxicity adaptation mechanisms.

Despite the increased research efforts aimed at understanding iron-based conductive materials (CMs) for facilitating chain elongation (CE) to produce medium chain fatty acids (MCFAs), the impact of these materials on microbial community functions and the adaptation mechanisms to their biotoxicity remain unclear. This study found that the supply of zero-valent iron (ZVI) and magnetite enhanced the MCFAs carbon-flow distribution by 26 % and 52 %, respectively. Metagenomic analysis revealed the upregulation of fatty acid metabolism, pyruvate metabolism and ABC transporters with ZVI and magnetite. The predominant functional microorganisms were Massilibacterium and Tidjanibacter with ZVI, and were Petrimonas and Candidatus_Microthrix with magnetite. Furthermore, it was demonstrated that CE microorganisms respond and adapt to the biotoxicity of iron-based CMs by adjusting Two-component system and Quorum sensing for the first time. In summary, this study provided a new deep-insight on the feedback mechanisms of CE microorganisms on iron-based CMs.

Silencing of the T-type voltage-gated calcium channel α1 subunit by fungus-mediated RNAi altered the structure of F-actin and caused defective behaviors in Ditylenchus destructor.

BACKGROUND: T-type calcium channels, characterized as low-voltage activated (LVA) calcium channels, play crucial physiological roles across a wide range of tissues, including both the neuronal and nonneuronal systems. Using in situ hybridization and RNA interference (RNAi) techniques in vitro, we previously identified the tissue distribution and physiological function of the T-type calcium channel α1 subunit (DdCα1G) in the plant-parasitic nematode Ditylenchus destructor. METHODS AND RESULTS: To further characterize the functional role of DdCα1G, we employed a combination of immunohistochemistry and fungus-mediated RNAi and found that DdCα1G was clearly distributed in stylet-related tissue, oesophageal gland-related tissue, secretory-excretory duct-related tissue and male spicule-related tissue. Silencing DdCα1G led to impairments in the locomotion, feeding, reproductive ability and protein secretion of nematodes. To confirm the defects in behavior, we used phalloidin staining to examine muscle changes in DdCα1G-RNAi nematodes. Our observations demonstrated that defective behaviors are associated with related muscular atrophy. CONCLUSION: Our findings provide a deeper understanding of the physiological functions of T-type calcium channels in plant-parasitic nematodes. The T-type calcium channel can be considered a promising target for sustainable nematode management practices.

Chinese Translation and Validation of the Center for Neurologic Study Lability Scale.

INTRODUCTION: Pseudobulbar palsy is a common symptom in patients with amyotrophic lateral sclerosis (ALS), but it is often underdiagnosed or misdiagnosed as other diseases. The Center for Neurologic Study Lability Scale (CNS-LS) is a self-report scale consisting of seven questions designed for evaluating pseudobulbar affect (PBA). The current study aimed to validate a Chinese version of the CNS-LS. METHODS: The Chinese version of the CNS-LS was obtained through a standardized forward-backward translation and cultural adaptation. A total of 105 patients with ALS were recruited from the ALS database of Peking University Third Hospital in Beijing, China, to complete the CNS-LS. The reliability of the Chinese version was determined by the test-retest method, and receiver operating characteristic (ROC) analysis was performed for criterion validity. RESULTS: Of 105 patients with ALS, 37 had symptoms of PBA and were diagnosed with that condition by neurologists. Forty-two patients completed the CNS-LS twice, and there was no statistically significant difference between the scores (Z = -0.896, p = 0.37). The Spearman correlation coefficient between the test and retest scores was 0.940 (p < 0.0005), and the Cronbach alpha coefficient was high (α = 0.905, n = 105). Scores of 12 or higher on the CNS-LS identified PBA with sensitivity of 0.919 and specificity of 0.882. The area under the ROC curve was 0.924. CONCLUSION: The Chinese version of the CNS-LS demonstrated good sensitivity and specificity in the group of patients with ALS enrolled in this study. The CNS-LS should be a useful instrument for clinical and research purposes for patients in this language group.

Assessing care dependence status and associated influencing factors among middle-aged hemiplegic stroke patients during the post-acute rehabilitation phase: A correlational study.

AIMS: To comprehensively examine the prevailing condition of care dependence among middle-aged individuals who have experienced hemiplegia subsequent to a stroke and were currently undergoing post-acute rehabilitation. Additionally, the study sought to analyse the determinants that impacted this phenomenon. DESIGN: A single-centre, cross-sectional study design. METHODS: During the period from January 2020 to October 2022, a cohort of 196 hemiplegic stroke patients, aged between 40 and 65, and within 6 months of their stroke onset, was selected from the cerebrovascular outpatient clinic at a tertiary hospital in Hangzhou. The demographic and disease-related data, care dependence level, mental state, nutrition and depression status were collected. Furthermore, all collected data were analysed by descriptive and correlative statistical methods. RESULTS: The care dependence level was 51.04 ± 9.42, with an incidence of care dependence of 78.1%. Multivariate regression analysis showed that age, history of falls, physical dysfunction, chronic comorbidities, depression, nutritional status and cognitive dysfunction were influencing factors for care dependence in the participants after a stroke. CONCLUSION: The incidence of care dependence among hemiplegic patients aged from 40 to 65 years old in the early stage after a stroke was high. Nursing staff should focus on these patients with a history of falling, physical dysfunction, comorbidity, depression status, nutritional status and cognitive dysfunction in clinical practice. RELEVANCE TO CLINICAL PRACTICE: The incidence of care dependence in middle-aged hemiplegic patients following a stroke is significantly increased. Some risk factors should be assessed, monitored, and controlled by nursing staff as early as possible in order to reduce the dependence levels in post-acute rehabilitation period and improve the quality of life of hemiplegia patients. REPORTING METHOD: Our study complies with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Checklist: cross-sectional studies (see Table S1). PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Application of non-mydriatic fundus photography-assisted telemedicine in diabetic retinopathy screening.

BACKGROUND: Early screening and accurate staging of diabetic retinopathy (DR) can reduce blindness risk in type 2 diabetes patients. DR's complex pathogenesis involves many factors, making ophthalmologist screening alone insufficient for prevention and treatment. Often, endocrinologists are the first to see diabetic patients and thus should screen for retinopathy for early intervention. AIM: To explore the efficacy of non-mydriatic fundus photography (NMFP)-enhanced telemedicine in assessing DR and its various stages. METHODS: This retrospective study incorporated findings from an analysis of 93 diabetic patients, examining both NMFP-assisted telemedicine and fundus fluorescein angiography (FFA). It focused on assessing the concordance in DR detection between these two methodologies. Additionally, receiver operating characteristic (ROC) curves were generated to determine the optimal sensitivity and specificity of NMFP-assisted telemedicine, using FFA outcomes as the standard benchmark. RESULTS: In the context of DR diagnosis and staging, the kappa coefficients for NMFP-assisted telemedicine and FFA were recorded at 0.775 and 0.689 respectively, indicating substantial intermethod agreement. Moreover, the NMFP-assisted telemedicine's predictive accuracy for positive FFA outcomes, as denoted by the area under the ROC curve, was remarkably high at 0.955, within a confidence interval of 0.914 to 0.995 and a statistically significant P-value of less than 0.001. This predictive model exhibited a specificity of 100%, a sensitivity of 90.9%, and a Youden index of 0.909. CONCLUSION: NMFP-assisted telemedicine represents a pragmatic, objective, and precise modality for fundus examination, particularly applicable in the context of endocrinology inpatient care and primary healthcare settings for diabetic patients. Its implementation in these scenarios is of paramount significance, enhancing the clinical accuracy in the diagnosis and therapeutic management of DR. This methodology not only streamlines patient evaluation but also contributes substantially to the optimization of clinical outcomes in DR management.

Purinergic P2X7 receptor involves in anti-retinal photodamage effects of berberine.

Berberine (BBR) is a Chinese herb with antioxidant and anti-inflammatory properties. In a previous study, we found that BBR had a protective effect against light-induced retinal degeneration in BALB/c mice. The purinergic P2X7 receptor (P2X7R) plays a key role in retinal degeneration via inducing oxidative stress, inflammatory changes, and cell death. The aim of this study was to investigate whether BBR can induce protective effects in light damage experiments and whether P2X7R can get involved in these effects. C57BL/6 J mice and P2X7 knockout (KO) mice on the C57BL/6 J background were used. We found that BBR preserved the outer nuclear layer (ONL) thickness and retinal ganglion cells following light stimulation. Furthermore, BBR significantly suppressed photoreceptor apoptosis, pro-apoptotic c-fos expression, pro-inflammatory responses of Mϋller cells, and inflammatory factors (TNF-α, IL-1ß). In addition, protein levels of P2X7R were downregulated in BBR-treated mice. Double immunofluorescence showed that BBR reduced overexpression of P2X7R in retinal ganglion cells and Mϋller cells. Furthermore, BBR combined with the P2X7R agonist BzATP blocked the effects of BBR on retinal morphology and photoreceptor apoptosis. However, in P2X7 KO mice, BBR had an additive effect resulting in thicker ONL and more photoreceptors. The data suggest that the P2X7 receptor is involved in retinal light damage, and BBR inhibits this process by reducing histological impairment, cell death, and inflammatory responses.

Clarifying the Functional Role of Serotonin in Meloidogyne graminicola Host Plant Parasitism by Immunolocalization and RNA Interference.

Serotonin (5-hydroxytryptamine) is an essential neurotransmitter involved in regulating various behaviors in plant-parasitic nematodes, including locomotion, egg laying, feeding, and mating. However, the functional role of serotonin in root-knot nematode invasion of host plants and the molecular mechanisms underlying feeding behavior remain poorly understood. In this study, we tested the effects of exogenous serotonin and the pharmacological compounds fluoxetine and methiothepin on the feeding behaviors of Meloidogyne graminicola. Our results suggested that M. graminicola possesses an endogenous serotonin signaling pathway and that serotonin plays a crucial role in modulating feeding behaviors in M. graminicola second-stage juveniles. We also identified and cloned the serotonin synthesis enzyme tryptophan hydroxylase (Mg-tph-1) in M. graminicola and investigated the role of endogenous serotonin by generating RNA interference nematodes in Mg-tph-1. Silencing Mg-tph-1 substantially reduced nematode invasion, development, and reproduction. According to the immunostaining results, we speculated that these serotonin immunoreactive cells near the nerve ring in M. graminicola are likely homologous to Caenorhabditis elegans ADFs, NSMs, and RIH serotonergic neurons. Furthermore, we investigated the impact of phytoserotonin on nematode invasion and development in rice by overexpressing OsTDC-3 or supplementing rice plants with tryptamine and found that an increase in phytoserotonin increases nematode pathogenicity. Overall, our study provides insights into the essential role of serotonin in M. graminicola host plant parasitism and proposes that the serotonergic signaling pathway could be a potential target for controlling plant-parasitic nematodes.

A neuroimaging biomarker for Individual Brain-Related Abnormalities In Neurodegeneration (IBRAIN): a cross-sectional study.

Background: Alzheimer's disease (AD) is a prevalent neurodegenerative disorder that poses a worldwide public health challenge. A neuroimaging biomarker would significantly improve early diagnosis and intervention, ultimately enhancing the quality of life for affected individuals and reducing the burden on healthcare systems. Methods: Cross-sectional and longitudinal data (10,099 participants with 13,380 scans) from 12 independent datasets were used in the present study (this study was performed between September 1, 2021 and February 15, 2023). The Individual Brain-Related Abnormalities In Neurodegeneration (IBRAIN) score was developed via integrated regional- and network-based measures under an ensemble machine learning model based on structural MRI data. We systematically assessed whether IBRAIN could be a neuroimaging biomarker for AD. Findings: IBRAIN accurately differentiated individuals with AD from NCs (AUC = 0.92) and other neurodegenerative diseases, including Frontotemporal dementia (FTD), Parkinson's disease (PD), Vascular dementia (VaD) and Amyotrophic Lateral Sclerosis (ALS) (AUC = 0.92). IBRAIN was significantly correlated to clinical measures and gene expression, enriched in immune process and protein metabolism. The IBRAIN score exhibited a significant ability to reveal the distinct progression of prodromal AD (i.e., Mild cognitive impairment, MCI) (Hazard Ratio (HR) = 6.52 [95% CI: 4.42∼9.62], p < 1 × 10-16), which offers similar powerful performance with Cerebrospinal Fluid (CSF) Aß (HR = 3.78 [95% CI: 2.63∼5.43], p = 2.13 × 10-14) and CSF Tau (HR = 3.77 [95% CI: 2.64∼5.39], p = 9.53 × 10-15) based on the COX and Log-rank test. Notably, the IBRAIN shows comparable sensitivity (beta = -0.70, p < 1 × 10-16) in capturing longitudinal changes in individuals with conversion to AD than CSF Aß (beta = -0.26, p = 4.40 × 10-9) and CSF Tau (beta = 0.12, p = 1.02 × 10-5). Interpretation: Our findings suggested that IBRAIN is a biologically relevant, specific, and sensitive neuroimaging biomarker that can serve as a clinical measure to uncover prodromal AD progression. It has strong potential for application in future clinical practice and treatment trials. Funding: Science and Technology Innovation 2030 Major Projects, the National Natural Science Foundation of China, Beijing Natural Science Funds, the Fundamental Research Funds for the CentralUniversity, and the Startup Funds for Talents at Beijing Normal University.

Comparison of short-term efficacy analysis of medium-rectal cancer surgery with robotic natural orifice specimen extraction and robotic transabdominal specimen extraction.

BACKGROUND: With the development of minimally invasive technology, the trauma caused by surgery get smaller, At the same time, the specimen extraction surgery through the natural orifice is more favored by experts domestically and abroad, robotic surgery has further promoted the development of specimen extraction surgery through the natural orifice. The aim of current study is to compare the short-term outcomes of robotic-assisted natural orifice specimen extraction (NOSES ) and transabdominal specimen extraction(TRSE ) in median rectal cancer surgery. METHODS: From January 2020 to January 2023, 87 patients who underwent the NOSES or TRSE at the First Affiliated Hospital of Nanchang University were included in the study, 4 patients were excluded due to liver metastasis. Of these, 50 patients were in the TRSE and 33 patients in the NOSES. Short-term efficacy was compared in the two groups. RESULTS: The NOSES group had less operation time (P < 0.001), faster recovery of gastrointestinal function (P < 0.001), shorter abdominal incisions (P < 0.001), lower pain scores(P < 0.001). lower Inflammatory indicators of the white blood cell count and C-reactive protein content at 1, 3, and 5 days after surgery (P < 0.001, P = 0.037). There were 9 complications in the NOSES group and 11 complications in the TRSE group(P = 0.583). However, there were no wound complications in the NOSES group. The number of postoperative hospital stays seems to be same in the two groups. And there was no significant difference in postoperative anus function (P = 0.591). CONCLUSIONS: This study shows that NOSES and TRSE can achieve similar radical treatment effects, NOSES is a feasible and safe way to take specimens for rectal cancer surgery in accordance with the indication for NOSES.

Puerarin prevents sepsis-associated encephalopathy by regulating the AKT1 pathway in microglia.

BACKGROUND: Previous studies have reported that puerarin possesses cardioprotective, vasodilatory, anti-inflammatory, anti-apoptotic, and hypoglycemic properties. However, the impact of puerarin on sepsis-associated encephalopathy (SAE) remains unexplored. In this study, we explored whether puerarin can modulate microglia-mediated neuroinflammation for the treatment of SAE and delved into the underlying mechanisms. METHODS: We established a murine model of SAE through intraperitoneal injection of lipopolysaccharide (LPS). The puerarin treatment group received pretreatment with puerarin. For in vitro experiments, BV2 cells were pre-incubated with puerarin for 2 h before LPS exposure. We employed network pharmacology, the Morris Water Maze (MWM) test, Novel Object Recognition (NOR) test, immunofluorescence staining, enzyme-linked immunosorbent assay (ELISA), Western blotting, and quantitative real-time PCR (qRT-PCR) to elucidate the molecular mechanism of underlying puerarin's effects in SAE treatment. RESULTS: Our findings demonstrate that puerarin significantly reduced the production of inflammatory cytokines (TNF-α and IL-6) in the peripheral blood of LPS-treated mice. Moreover, puerarin treatment markedly ameliorated sepsis-associated cognitive impairment. Puerarin also exhibited inhibitory effects on the release of TNF-α and IL-6 from microglia, thereby preventing hippocampal neuronal cell death. Network pharmacology analysis identified AKT1 as a potential therapeutic target for puerarin in SAE treatment. Subsequently, we validated these results in both in vitro and in vitro experiments. Our study conclusively demonstrated that puerarin reduced LPS-induced phosphorylation of AKT1, with the AKT activator SC79 reversing puerarin's anti-inflammatory effects through the activation of the AKT1 signaling pathway. CONCLUSION: Puerarin exerts an anti-neuroinflammatory effect against SAE by modulating the AKT1 pathway in microglia.

Stratifin Promotes Hepatocellular Carcinoma Progression by Modulating the Wnt/ß-Catenin Pathway.

Abnormal stratifin (SFN) expression is closely related to the progression of several human cancers, but the potential roles of SFN in hepatocellular carcinoma (HCC) remain largely unknown. In this study, we found that SFN was upregulated in HCC cell lines and tissues and was positively associated with tumor size, poor differentiation, Tumor Node Metastasis (TNM) stage, and vascular invasion. In addition, high expression levels of SFN were associated with poor overall survival and disease-free survival. Biologically, downregulation of SFN suppressed tumor cell proliferation, epithelial-mesenchymal transition (EMT), invasion, and migration in vitro and tumor growth in vivo. However, overexpression of SFN promoted cell proliferation, EMT, invasion, and migration in vitro and tumor growth in vivo. Mechanistically, overexpression of SFN activated the Wnt/ß-catenin pathway by promoting Glycogen synthase kinase-3 beta (GSK-3ß) phosphorylation, decreasing ß-catenin phosphorylation, promoting ß-catenin transport into the nucleus, and enhancing the expression of c-Myc, whereas depletion of SFN inhibited the Wnt/ß-catenin pathway. In addition, TOPFlash/FOPFlash reporter assays showed that overexpression or downregulation of SFN obviously increased or decreased, respectively, the activity of the Wnt/ß-catenin pathway. Our results indicated that SFN plays an important role in HCC, possibly providing a prognostic factor and therapeutic target for HCC.

Comparison of robotic-assisted and laparoscopic-assisted natural orifice specimen extraction surgery in short-terms outcomes of middle rectal cancer.

BACKGROUND: Surgery is becoming less invasive as technology advances. Natural orifice specimen extraction surgery (NOSES) ushered in a new era of minimally invasive techniques. At the same time, NOSES is gaining popularity in the world. With their distinct advantages, surgical robots have advanced the development of NOSES. The aim of current study was to compare the short-term outcomes between robotic-assisted NOSES and laparoscopic-assisted NOSES for the treatment of middle rectal cancer. METHODS: Patients with middle rectal cancer who underwent robotic-assisted or laparoscopic-assisted NOSES at the First Affiliated Hospital of Nanchang University between January 2020 and June 2022 had their clinicopathological data collected retrospectively. 46 patients were enrolled in the study: 23 in the robotic group and 23 in the laparoscopic group. Short-term outcomes and postoperative anal function in the two groups were compared. RESULTS: There was no significant difference in the clinicopathological data between the two groups. The robotic group had less intraoperative blood loss (p = 0.04), less postoperative abdominal drainage (p = 0.02), lower postoperative white blood cell counts (p = 0.024) and C-reactive protein levels (p = 0.017), and shorter catheter removal time when compared to the laparoscopic group (p = 0.003). Furthermore, there were no significant difference in mean operative time (159 ± 31 min vs 172 ± 41 min) between the robotic and laparoscopic groups (p = 0.235), but time to naked the rectum (86.4 ± 20.9 min vs. 103.8 ± 31.5 min p = 0.033) and time of digestive tract reconstruction (15.6 ± 3.88 min vs. 22.1 ± 2.81 min p < 0.01) in the robotic group were significantly shorter than laparoscopic group. The robotic group had lower postoperative Wexner scores than the laparoscopic group. CONCLUSIONS: This research reveals that combining a robotic surgical system and NOSES results in superior outcomes, with short-term outcomes preferable to laparoscopic-assisted NOSES.

Ephedra Herb extract ameliorates adriamycin-induced nephrotic syndrome in rats via the CAMKK2/AMPK/mTOR signaling pathway.

This study aimed to investigate the effect and mechanisms of Ephedra Herb (EH) extract on adriamycin-induced nephrotic syndrome (NS), providing an experimental basis for the clinical treatment of NS. Hematoxylin and eosin staining, creatinine, urea nitrogen, and kidn injury molecule-1 were used to evaluate the activities of EH extract on renal function. The levels of inflammatory factors and oxidative stress were detected by kits. The levels of reactive oxygen species, immune cells, and apoptosis were measured by flow cytometry. A network pharmacological approach was used to predict the potential targets and mechanisms of EH extract in the treatment of NS. The protein levels of apoptosis-related proteins and CAMKK2, p-CAMKK2, AMPK, p-AMPK, mTOR and p-mTOR in the kidneys were detected by Western blot. The effective material basis of EH extract was screened by MTT assay. The AMPK pathway inhibitor (compound C, CC) was added to investigate the effect of the potent material basis on adriamycin-induced cell injury. EH extract significantly improved renal injury and relieve inflammation, oxidative stress, and apoptosis in rats. Network pharmacology and Western blot results showed that the effect of EH extract on NS may be associated with the CAMKK2/AMPK/mTOR signaling pathway. Moreover, methylephedrine significantly ameliorated adriamycin-induced NRK-52e cell injury. Methylephedrine also significantly improved the phosphorylation of AMPK and mTOR, which were blocked by CC. In sum, EH extract may ameliorate renal injury via the CAMKK2/AMPK/mTOR signaling pathway. Moreover, methylephedrine may be one of the material bases of EH extract.

Husband-wife Relationship, Neonatal Health, Breast Milk Volume and Postpartum Depression: A Prospective Cohort Study.

Postpartum depression (PPD) is a major public health problem that has negative effects on mothers, infants, and society. This study was aimed at investigating the prevalence of PPD and elucidating the delivery factors implicated in PPD so as take more targeted measures for reducing the potential risk factors. A prospective cohort study was conducted. Following the criterion, 151 pregnant women were included in the study. The Edinburgh Postpartum Depression Scale (EPDS) and the general questionnaire were filled out 2-3 days after delivery. At weeks 2 and 6 postpartum, the EPDS was reassessed either online or via telephone. Also, electronic medical records based on relevant information during the delivery period were collected. Statistical significance was defined as p < 0.05. A high rate of PPD (31.13%) was reported. Univariate correlation analysis showed statistically significant differences in the husband-wife relationship (χ2 = 18.497, p < 0.001), neonatal health (χ2 = 14.710, p < 0.001), and breast milk volume (χ2 = 5.712, p = 0.017) between PPD and normal control groups. Adjusting for other covariates, multivariate logistic regression analysis showed that satisfactory conjugal relation could reduce the risk of PPD (OR, 0.053; p = 0.022); Neonatal health problems significantly increase the risk of PPD (OR, 6.497; p = 0.001); Adequate breast milk could alleviate the risk of PPD (OR, 0.351; P = 0.045). Data analysis suggests that marital discord and unhealthy new-born are independent risk factors; nevertheless, sufficient breast milk is a protective factor against PPD. Healthcare workers such as hospital and community doctors and social workers should pay attention to PPD. Furthermore, perinatal emotional support, health education, and EPDS assessment need to be incorporated into maternity care. Screening and personalized psychological counselling should be carried out for high-risk pregnant women with PPD.