Kaempferol mitigates sepsis-induced acute lung injury by modulating the SphK1/S1P/S1PR1/MLC2 signaling pathway to restore the integrity of the pulmonary endothelial cell barrier.

Sepsis-induced acute lung injury (SALI) is the common complication of sepsis, resulting in high incidence and mortality rates. The primary pathogenesis of SALI is the interplay between acute inflammation and endothelial barrier damage. Studies have shown that kaempferol (KPF) has anti-sepsis properties. Sphingosine kinase 1 (SphK1)/sphingosine-1-phosphate (S1P) signaling pathway's significance in acute lung damage and S1P receptor 1 (S1PR1) agonists potential in myosin light chain 2 (MLC2) phosphorylation are documented. Whether KPF can regulate the SphK1/S1P/S1PR1/MLC2 signaling pathway to protect the lung endothelial barrier remains unclear. This study investigates the KPF's therapeutic effects and molecular mechanisms in repairing endothelial cell barrier damage in both LPS-induced sepsis mice and human umbilical vein endothelial cells (HUVECs). KPF significantly reduced lung tissue damage and showed anti-inflammatory effects by decreasing IL-6 and TNF-α synthesis in the sepsis mice model. Further, KPF administration can reduce the high permeability of the LPS-induced endothelial cell barrier and alleviate lung endothelial cell barrier injury. Mechanistic studies showed that KPF pretreatment can suppress MLC2 hyperphosphorylation and decrease SphK1, S1P, and S1PR1 levels. The SphK1/S1P/S1PR1/MLC2 signaling pathway controls the downstream proteins linked to endothelial barrier damage, and the Western blot (WB) showed that KPF raised the protein levels. These proteins include zonula occludens (ZO)-1, vascular endothelial (VE)-cadherin and Occludin. The present work revealed that in mice exhibiting sepsis triggered by LPS, KPF strengthened the endothelial barrier and reduced the inflammatory response. The SphK1/S1P/S1PR1/MLC2 pathway's modulation is the mechanism underlying this impact.

Deep learning model based on contrast-enhanced MRI for predicting post-surgical survival in patients with hepatocellular carcinoma.

Objective: To develop a deep learning model based on contrast-enhanced magnetic resonance imaging (MRI) data to predict post-surgical overall survival (OS) in patients with hepatocellular carcinoma (HCC). Methods: This bi-center retrospective study included 564 surgically resected patients with HCC and divided them into training (326), testing (143), and external validation (95) cohorts. This study used a three-dimensional convolutional neural network (3D-CNN) ResNet to learn features from the pretreatment MR images (T1WIpre, late arterial phase, and portal venous phase) and got the deep learning score (DL score). Three cox regression models were established separately using the DL score (3D-CNN model), clinical features (clinical model), and a combination of above (combined model). The concordance index (C-index) was used to evaluate model performance. Results: We trained a 3D-CNN model to get DL score from samples. The C-index of the 3D-CNN model in predicting 5-year OS for the training, testing, and external validation cohorts were 0.746, 0.714, and 0.698, respectively, and were higher than those of the clinical model, which were 0.675, 0.674, and 0.631, respectively (P = 0.009, P = 0.204, and P = 0.092, respectively). The C-index of the combined model for testing and external validation cohorts was 0.750 and 0.723, respectively, significantly higher than the clinical model (P = 0.017, P = 0.016) and the 3D-CNN model (P = 0.029, P = 0.036). Conclusions: The combined model integrating the DL score and clinical factors showed a higher predictive value than the clinical and 3D-CNN models and may be more useful in guiding clinical treatment decisions to improve the prognosis of patients with HCC.

PVDF-HFP@Nafion-based quasisolid polymer electrolyte for high migration number in working rechargeable Na-O2 batteries.

Rechargeable sodium-oxygen (Na-O2) battery is deemed as a promising high-energy storage device due to the abundant sodium resources and high theoretical energy density (1,108 Wh kg-1). A series of quasisolid electrolytes are constantly being designed to restrain the dendrites growth, the volatile and leaking risks of liquid electrolytes due to the open system of Na-O2 batteries. However, the ticklish problem about low operating current density for quasisolid electrolytes still hasn't been conquered. Herein, we report a rechargeable Na-O2 battery with polyvinylidene fluoride-hexafluoropropylene recombination Nafion (PVDF-HFP@Nafion) based quasisolid polymer electrolyte (QPE) and MXene-based Na anode with gradient sodiophilic structure (M-GSS/Na). QPE displays good flame resistance, locking liquid and hydrophobic properties. The introduction of Nafion can lead to a high Na+ migration number (tNa+ = 0.68) by blocking the motion of anion and promote the formation of NaF-rich solid electrolyte interphase, resulting in excellent cycling stability at relatively high current density under quasisolid environment. In the meantime, the M-GSS/Na anode exhibits excellent dendrite inhibition ability and cycling stability. Therefore, with the synergistic effect of QPE and M-GSS/Na, constructed Na-O2 batteries run more stably and exhibit a low potential gap (0.166 V) after an initial 80 cycles at 1,000 mA g-1 and 1,000 mAh g-1. This work provides the reference basis for building quasisolid state Na-O2 batteries with long-term cycling stability.

Atox1 regulates macrophage polarization in intestinal inflammation via ROS-NLRP3 inflammasome pathway.

BACKGROUND: Inflammation and oxidative stress play an important role in the pathophysiology of inflammatory bowel disease (IBD). This study aimed to explore the effects of copper chaperone Antioxidant-1 (Atox1) on macrophages in a mouse model of intestinal inflammation. METHODS: A mouse model of TNBS-induced colitis was established and verified using the disease activity index. Atox1 conditional knockout mice were applied. The proportion of macrophages in colonic lamina propria mononuclear cells and ROS production were analyzed using flow cytometry. Inflammatory cytokines were measured using ELISA. Expression of macrophage M1/M2 polarization markers, p47phox, NLRP3, and Caspase-1 p20 was measured using quantitative RT-PCR and Western blotting. RESULTS: Atox1 expression was up-regulated in colon tissues of TNBS-induced colitis mice. Macrophages isolated from TNBS-induced colitis mice showed M1 polarization and nuclear translocation of Atox1. Inhibiting copper chaperone activity decreased p47phox, ROS production, and M1 polarization induced by CuCl2 in macrophages. TNBS induced up-regulation of inflammatory cytokines, M1 polarization markers, and p47phox expression in mice, an effect which was preempted by Atox1 knockout. Inflammatory cytokines and expression of M1 polarization markers, p47phox, NLRP3, Caspase-1 p20 were also increased in macrophages isolated from TNBS-induced colitis mice. These changes were alleviated in mice with Atox1 knockout. The effects of Atox1 on macrophage polarization were mediated via the ROS-NLRP3 inflammasome pathway. CONCLUSION: Atox1 plays a pro-inflammatory role, promotes M1 polarization of macrophages, and increases the concentrations of pro-inflammatory cytokines in intestinal tissue by regulating the ROS-NLRP3 inflammasome pathway. Atox1 is a potential therapeutic target in IBD.

A multi-organization epigenetic age prediction based on a channel attention perceptron networks.

DNA methylation indicates the individual's aging, so-called Epigenetic clocks, which will improve the research and diagnosis of aging diseases by investigating the correlation between methylation loci and human aging. Although this discovery has inspired many researchers to develop traditional computational methods to quantify the correlation and predict the chronological age, the performance bottleneck delayed access to the practical application. Since artificial intelligence technology brought great opportunities in research, we proposed a perceptron model integrating a channel attention mechanism named PerSEClock. The model was trained on 24,516 CpG loci that can utilize the samples from all types of methylation identification platforms and tested on 15 independent datasets against seven methylation-based age prediction methods. PerSEClock demonstrated the ability to assign varying weights to different CpG loci. This feature allows the model to enhance the weight of age-related loci while reducing the weight of irrelevant loci. The method is free to use for academics at www.dnamclock.com/#/original.

Surface Coordination Modulated Morphological Anisotropic Engineering of Iron-Benzoquinone Frameworks for Lithium-Ion Batteries.

Morphological anisotropic engineering is powerful to synthesize metal-organic frameworks (MOF) with versatile physicochemical properties for diverse applications ranging from gas storage/separation to electrocatalysis and batteries, etc. Herein, we developed a carbon substrate guided strategy for facet-anisotropic growth of Fe-THBQ (tetrahydroxy-1,4-benzoquinone) frameworks, which is built with cubic Fe octamer bridged by two parallel THBQ ligands along three orthogonal axes, extending to a three-dimensional (3D) framework with pcu-e network topology. The electronegative O-containing functional groups on carbon surfaces compete with THBQ linkers to interact with the unsaturated coordinated Fe cations on the {111} facets and selectively inhibit crystal growth along the <111> direction. The morphology of Fe-THBQ evolves from thermodynamically favored truncated cube to cuboctahedron depending on the O-containing functional groups on carbon substrate. The Fe-THBQ with varied morphologies exhibits facet-dependent performances for lithium storage. This work will shed lights on morphology modulation of MOFs for promising applications.

The efficacy of bracing in the treatment of progressive early-onset scoliosis.

Serial casting as one of the applications to treat early-onset scoliosis has been reported efficiently to improve deformity, but no report has focused on the efficacy of braces in the treatment of congenital early-onset scoliosis and comparison with progressive idiopathic early-onset scoliosis. Patients with progressive EOS treated with braces in our institution with a minimum of 4 years follow-up were reviewed. Two groups according to the etiological diagnosis were analyzed and compared: the congenital scoliosis (CS) group and idiopathic scoliosis (IS) group. The success cases and the failure cases were also compared. 27 patients with an average main Cobb angle of 38.19° (20-55) underwent initial bracing at an average age of 55.7 months (24-108), the average follow-up time was 76.19 months (49-117). In IS group the main Cobb angle was corrected to 18.69 ± 12.06° (48.61%) following the first bracing; the final Cobb angle was 23.08 ± 22.15°(38.76%) after brace removal. In CS group the main Cobb angle was corrected to 33.93 ± 10.31°(17.1%) following the first bracing and 37.93 ± 14.74°(3.53%) after brace removal. Both coronal chest width and T1-T12 height increased dramatically from pre-bracing to the last follow-up. Patients diagnosed as IS tended to have a better result in main Cobb angle correction than that of CS (P = 0.049). By the time of last follow-up, 8 patients had undergone surgery, and the operation time was postponed by 68.88 ± 26.43 months. For patients with progressive early-onset scoliosis, bracing is an efficient nonsurgical alternative to casting, and some of them can be cured; if not, eventual surgical intervention can be delayed for a period of time without restrictions on the thoracic cavity.

Discovery of novel ocotillol derivatives modulating glucocorticoid receptor/NF-κB signaling for the treatment of sepsis.

Glucocorticoids (GCs) have been used in the treatment of sepsis because of their potent anti-inflammatory effects. However, their clinical efficacy against sepsis remains controversial because of glucocorticoid receptor (GR) downregulation and side effects. Herein, we designed and synthesized 30 ocotillol derivatives and evaluated their anti-inflammatory activities. Ocotillol 24(R/S) differential isomers were stereoselective in their pharmacological action. Specifically, 24(S) derivatives had better anti-inflammatory activity than their corresponding 24(R) derivatives. Compound 20 most effectively inhibited NO release (85.97% reduction), and it exerted dose-dependent inhibitory effects on interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) levels. Mechanistic studies revealed that compound 20 reduces the degradation of GR mRNA and GR protein. Meanwhile, compound 20 inhibited the activation of nuclear factor-κB (NF-κB) signaling, thereby inhibiting the nuclear translocation of p65 and attenuating the inflammatory response. In vivo studies revealed that compound 20 attenuated hepatic, pulmonary, and renal pathology damage in mice with sepsis and suppressed the production of inflammatory mediators. These results indicated that compound 20 is a promising lead compound for designing and developing anti-sepsis drugs.

Euphorbia helioscopia L. exhibits promising therapeutic effects on hemangioendothelioma and melanoma through angiogenesis inhibition.

BACKGROUND: Euphorbia helioscopia L (EHL), a widely used medicinal plant in traditional Chinese medicine, has shown promising effects on certain cancers. However, previous studies on EHL did not elucidate the underlying molecular mechanisms. Herein, for the first time, we present the strong therapeutic potential of EHL extracts on malignant hemangioendothelioma, a rare type of vascular tumor. PURPOSE: To investigate the potential anti-tumor mechanism of extracts of EHL on hemangioendothelioma and melanoma. METHODS: The dried stems and leaves of EHL were extracted with Ethyl Acetate and n-Butyl alcohol, yielding two crude extracts Ethyl Acetate fraction (EA) and n-Butyl alcohol fraction (Bu). EA and Bu were prepared to assess the potential mechanism by assays for cell proliferation, cell cycle, apoptosis, colony formation, tube formation, cellular metabolic activity, reactive oxygen species (ROS), N-Acetylcysteine (NAC) antagonism, RNA expression and western blot. To further confirm the anti-tumor effect of EHL in vivo, we established hemangioendothelioma and melanoma tumor-bearing mouse model using node mice and administered with EA and Bu, tracked alterations in tumor volume and survival rate. Furthermore, tissue samples were obtained for histological, protein, and genetic investigations. RESULTS: We demonstrate that the injection of EA and Bu, significantly inhibits tumor growth and prolongs the lifespan of tumor-bearing mice. Bu treatment exhibited a remarkable 33 % healing effect on the primary hemangioendothelioma tumor, bringing the survival rate to a level comparable to that of healthy mice. Mechanically, both EA and Bu impair respiratory chain complexes, leading to mitochondrial dysfunction and accumulation of reactive oxygen species (ROS), resulting in DNA damage, cell apoptosis, and finally blocked angiogenesis. While EA demonstrates robust inhibitory effects on cancer cell growth and a broader impact on metabolism in vitro, the in vivo effect of Bu surpasses that of EA in terms of strength. EA and Bu also exhibit potent anti-tumor effects on a primary melanoma model by inhibiting angiogenesis. Importantly, when compared to other compounds used in the treatment of hemangioendothelioma, EA and Bu demonstrate more profound anti-tumor effects. CONCLUSION: For the first time, our findings reveal that EHL extracts, especially the high polarity compounds, exhibit potent anti-tumor effects by targeting cellular metabolism, specifically through the inhibition of mitochondria-related metabolic activities. This leads to the accumulation of ROS and effectively suppresses abnormal angiogenesis.

Shock wave assisted intracellular delivery of antibiotics against bone infection with Staphylococcus aureus via P2X7 receptors.

Background: Treatment of chronic osteomyelitis (bone infection) remains a clinical challenge; in particular, it requires enhanced delivery of antibiotic drugs for the treatment of intracellular Staphylococcus aureus (S. aureus), which prevents infection recurrence and resistance. Previous studies have found that noninvasive shock waves used to treat musculoskeletal diseases can alter cell permeability, however, it is unclear whether shock waves alter cell membrane permeability in chronic osteomyelitis. Furthermore, it remains unknown whether such changes in permeability promote the entry of antibiotics into osteoblasts to exert antibacterial effects. Methods: In our study, trypan blue staining was used to determine the shock wave parameters that had no obvious damage to the osteoblast model; the effect of shocks waves on the cell membrane permeability of osteoblast model was detected by BODIPY®FL vancomycin; high performance liquid chromatography-mass spectrometry (HLPC-MS) was used to detect the effect of shock wave on the entry of antibiotics into the osteoblast model; plate colony counting method was used to detect the clearance effect of shock wave assisted antibiotics on S. aureus in the osteoblast model. To explore the mechanism, the effect of different pulses of shock waves on S. aureus was examined by plate colony counting method, besides, P2X7 receptor in osteoblast was detected by immunofluorescence and the extracellular ATP levels was detected. Furthermore, the effect of P2X7 receptor antagonists KN-62 or A740003 on the intracellular antibacterial activity of shock-assisted antibiotics was observed. Then, we used S. aureus to establish a rat model of chronic tibial osteomyelitis and investigated the efficacy and safety of shock-wave assisted antibiotics in the treatment of chronic osteomyelitis in rats. Results: The viability of the osteoblast models of intracellular S. aureus infection was not significantly affected by the application of up to 400 shock wave pulses at 0.21 mJ/mm2. Surprisingly, the delivery of BODIPY®FL vancomycin to osteoblast model cells was markedly enhanced by this shock wave treatment. Furthermore, the shock wave therapy increased the delivery of hydrophilic antibiotics (vancomycin and cefuroxime sodium), but not lipophilic antibiotics (rifampicin and levofloxacin), which improved the intracellular antibacterial effect. Afterwards, we discovered that shock wave treatment increased the extracellular concentration of ATP (the P2X7 receptor activator)， while KN-62 or A740003, a P2X7 receptor inhibitor, decreased intracellular antibacterial activity. We then found that 0.1 mL of 1 × 1011 CFU/mL ATCC25923 S. aureus was suitable for modeling chronic osteomyelitis in rats. Besides, the shock wave-assisted vancomycin treatment with the strongest antibacterial and osteogenic effects among the tested treatments was confirmed in vivo by imaging examination, microbiological cultures, and histopathology, with favorable safety. Conclusions: Our results suggest that shock waves can promote the entry of antibiotics into osteoblasts for antibacteria by changing the cell membrane permeability in a P2X7 receptor-dependent manner. Besides, considering antibacterial and osteogenic efficiency and a high degree of safety in rat osteomyelitis model, shock wave-assisted vancomycin treatment may thus represent a possible adjuvant therapy for chronic osteomyelitis.

PKM2 interacts with and phosphorylates PHB2 to sustain mitochondrial quality control against septic cerebral-cardiac injury.

Sepsis induces profound disruptions in cellular homeostasis, particularly impacting mitochondrial function in cardiovascular and cerebrovascular systems. This study elucidates the regulatory role of the Pyruvate Kinase M2 (PKM2)- Prohibitin 2 (PHB2) axis in mitochondrial quality control during septic challenges and its protective effects against myocardial and cerebral injuries. Employing LPS-induced mouse models, we demonstrate a significant downregulation of PKM2 and PHB2 in both heart and brain tissues post-sepsis, with corresponding impairments in mitochondrial dynamics, including fission, fusion, and mitophagy. Overexpression of PKM2 and PHB2 not only restores mitochondrial function, as evidenced by normalized ATP production and membrane potential but also confers resistance to oxidative stress by mitigating reactive oxygen species generation. These cellular mechanisms translate into substantial in vivo benefits, with transgenic mice overexpressing PKM2 or PHB2 displaying remarkable resistance to sepsis-induced cardiomyocyte and neuronal apoptosis, and organ dysfunction. Our findings highlight the PKM2-PHB2 interaction as a novel therapeutic target for sepsis, providing a foundation for future research into mitochondrial-based interventions to treat this condition. The study's insights into the molecular underpinnings of sepsis-induced organ failure pave the way for potential clinical applications in the management of sepsis and related pathologies.

Autoimmune nodopathy with anti-contactin 1 antibody characterized by cerebellar dysarthria: a case report and literature review.

Background: Autoimmune nodopathy (AN) has emerged as a novel diagnostic category that is pathologically different from classic chronic inflammatory demyelinating polyneuropathy. Clinical manifestations of AN include sensory or motor neuropathies, sensory ataxia, tremor, and cranial nerve involvement. AN with a serum-positive contactin-1 (CNTN1) antibody usually results in peripheral nerve demyelination. In this study, we reported a rare case of AN with CNTN1 antibodies characterized by the presence of CNTN1 antibodies in both serum and cerebrospinal fluid, which is associated with cerebellar dysarthria. Methods: A 25-year-old man was admitted to our hospital due to progressive dysarthria with limb tremors. The patient was initially diagnosed with peripheral neuropathy at a local hospital. Three years after onset, he was admitted to our hospital due to dysarthria, apparent limb tremor, and limb weakness. At that time, he was diagnosed with spinocerebellar ataxia. Eight years post-onset, during his second admission, his condition had notably deteriorated. His dysarthria had evolved to typical distinctive cerebellar characteristics, such as tremor, loud voice, stress, and interrupted articulation. Additionally, he experienced further progression in limb weakness and developed muscle atrophy in the distal limbs. Magnetic resonance imaging (MRI), nerve conduction studies (NCS), and autoimmune antibody tests were performed. Results: The results of the NCS suggested severe demyelination and even axonal damage to the peripheral nerves. MRI scans revealed diffuse thickening of bilateral cervical nerve roots, lumbosacral nerve roots, cauda equina nerve, and multiple intercostal nerve root sheath cysts. Furthermore, anti-CNTN1 antibody titers were 1:10 in the cerebrospinal fluid (CSF) and 1:100 in the serum. After one round of rituximab treatment, the patient showed significant improvement in limb weakness and dysarthria, and the CSF antibodies turned negative. Conclusion: Apart from peripheral neuropathies, cerebellar dysarthria (central nervous system involvement) should not be ignored in AN patients with CNTN1 antibodies.

Proteomic alterations associated with the formation of monocyte extracellular trap induced by Candida albicans hyphae.

Background: The interaction between the host and Candida albicans is dynamic and intricate. We performed proteomic analysis to explore monocyte-C. albicans hyphae interaction. Materials & methods: Primary human monocytes were stimulated by heat-killed C. albicans hyphae and their proteins were profiled by tandem liquid chromatography with mass spectrometry (LC-MS/MS). Results: Based on the protein database of different species for analysis, we found that stimulation of monocytes by hyphae was accompanied by upregulation of histones and activation of extracellular traps (ETs) formation pathway. Meanwhile, monocyte ETs (MoETs) were evoked by synthesis or alteration of C. albicans cell wall proteins expression during the morphological switch to hyphal. Conclusion: MoETs formation is linked to cell wall proteins of C. albicans hyphae.

Accelerated 3D MR neurography of the brachial plexus using deep learning-constrained compressed sensing.

OBJECTIVES: To explore the use of deep learning-constrained compressed sensing (DLCS) in improving image quality and acquisition time for 3D MRI of the brachial plexus. METHODS: Fifty-four participants who underwent contrast-enhanced imaging and forty-one participants who underwent unenhanced imaging were included. Sensitivity encoding with an acceleration of 2 × 2 (SENSE4x), CS with an acceleration of 4 (CS4x), and DLCS with acceleration of 4 (DLCS4x) and 8 (DLCS8x) were used for MRI of the brachial plexus. Apparent signal-to-noise ratios (aSNRs), apparent contrast-to-noise ratios (aCNRs), and qualitative scores on a 4-point scale were evaluated and compared by ANOVA and the Friedman test. Interobserver agreement was evaluated by calculating the intraclass correlation coefficients. RESULTS: DLCS4x achieved higher aSNR and aCNR than SENSE4x, CS4x, and DLCS8x (all p < 0.05). For the root segment of the brachial plexus, no statistically significant differences in the qualitative scores were found among the four sequences. For the trunk segment, DLCS4x had higher scores than SENSE4x (p = 0.04) in the contrast-enhanced group and had higher scores than SENSE4x and DLCS8x in the unenhanced group (all p < 0.05). For the divisions, cords, and branches, DLCS4x had higher scores than SENSE4x, CS4x, and DLCS8x (all p ≤ 0.01). No overt difference was found among SENSE4x, CS4x, and DLCS8x in any segment of the brachial plexus (all p > 0.05). CONCLUSIONS: In three-dimensional MRI for the brachial plexus, DLCS4x can improve image quality compared with SENSE4x and CS4x, and DLCS8x can maintain the image quality compared to SENSE4x and CS4x. CLINICAL RELEVANCE STATEMENT: Deep learning-constrained compressed sensing can improve the image quality or accelerate acquisition of 3D MRI of the brachial plexus, which should be benefit in evaluating the brachial plexus and its branches in clinical practice. KEY POINTS: •Deep learning-constrained compressed sensing showed higher aSNR, aCNR, and qualitative scores for the brachial plexus than SENSE and CS at the same acceleration factor with similar scanning time. •Deep learning-constrained compressed sensing at acceleration factor of 8 had comparable aSNR, aCNR, and qualitative scores to SENSE4x and CS4x with approximately half the examination time. •Deep learning-constrained compressed sensing may be helpful in clinical practice for improving image quality and acquisition time in three-dimensional MRI of the brachial plexus.

Effect of robot-assisted gait training on motor dysfunction in Parkinson's patients:A systematic review and meta-analysis.

BACKGROUND: Robot-assisted gait training (RAGT) has been reported to treat motor dysfunction in patients with Parkinson's disease (PD) in the last few years. However, the benefits of RAGT for treating motor dysfunction in PD are still unclear. OBJECTIVES: To investigate the efficacy of RAGT for motor dysfunction in PD patients. METHODS: We searched PubMed, Web of Science, Cochrane Library, Embase, CNKI, Wanfang, Chinese Biomedical Literature Database (CBM), and Chinese VIP Database for randomized controlled trials investigating RAGT to improve motor dysfunction in PD from the databases' inception dates until September 1, 2022. The following outcome indexes were employed to evaluate motor dysfunction: the Berg Balance Scale (BBS), Activities-specific Balance Confidence Scale (ABC), 10-Meter Walk Test gait speed (10-MWT), gait speed, stride length, cadence Unified Parkinson Disease Rating Scale Part III (UPDRS III), 6-Minute Walk Test (6MWT), and the Timed Up and Go test (TUG). The meta-analysis was performed using the proper randomeffect model or fixed-effect model to evaluate the difference in efficacy between the RAGT and the control groups. The Cochrane Risk of Bias Tool was used for the included studies and Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) was used to interpret the certainty of the results. RESULTS: The results consisted of 17 studies comprising a total of 670 participants. Six hundred and seven PD patients with motor dysfunction were included: 335 in the RAGT group and 335 in the control group. This meta-analysis results established that when compared with the control group, robot-assisted gait training improved the BBS results of PD patients (MD: 2.80, 95%CI: 2.11-3.49, P< 0.00001), ABC score (MD: 7.30, 95%CI: 5.08-9.52, P< 0.00001), 10-MWT (MD: 0.06, 95%CI: 0.03-0.10, P= 0.0009), gait speed (MD: 3.67, 95%CI: 2.58-4.76, P< 0.00001), stride length (MD: 5.53, 95%CI: 3.64-7.42, P< 0.00001), cadence (MD: 4.52, 95%CI: 0.94-8.10, P= 0.01), UPDRS III (MD: -2.16, 95%CI: -2.48--1.83, P< 0.00001), 6MWT (MD: 13.87, 95%CI: 11.92-15.82, P< 0.00001). However, RAGT did not significantly improve the TUG test result of patients with PD (MD =-0.56, 95% CI: -1.12-0.00, P= 0.05). No safety concerns or adverse reactions among robot-assisted gait training patients were observed. CONCLUSION: Even though RAGT can improve balance function, walking function, and gait performance and has demonstrated positive results in several studies, there is currently insufficient compelling evidence to suggest that it can improve all aspects of lower motor function.

A machine learning model for identifying systemic lupus erythematosus through laboratory information system and electronic medical record.

OBJECTIVES: Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease. Its diagnosis poses significant challenges especially at early stages and in atypical cases. The aim of this study was to develop a machine learning model based on common laboratory tests that can aid SLE diagnosis. METHODS: A standard protocol was developed to collect data of SLE and control immune diseases. A 10-fold cross-validation was performed in the modeling dataset (n=862), and an external dataset (n=198) was used for model validation. Machine learning algorithms were applied to construct a diagnostic model. Performance was evaluated based on area under the curve (AUC) values, F1-score, negative predictive value, positive predictive value, accuracy, sensitivity, and specificity. RESULTS: The optimal model was based on a random forest algorithm with 10 clinical features. Thrombin time, prothrombin activity, and uric acid contributed most to the diagnostic model. The SLE diagnostic model showed sufficient predictive accuracy, with AUC values of 0.8286 in the validation dataset. CONCLUSIONS: Our diagnostic model based on 10 common laboratory tests identified the patients with SLE with high accuracy. An online version of the model can potentially be applied in clinical settings for the differential diagnosis of SLE.

KLHDC7B as a novel diagnostic biomarker in urine exosomal mRNA promotes bladder urothelial carcinoma cell proliferation and migration, inhibits apoptosis.

Bladder cancer is a common kind of urinary system cancer, in which bladder urothelial carcinoma (BLCA) comprises approximately 90% of all bladder cancer types. In our previous study, we discovered KLHDC7B in urine exosomal messenger RNA (mRNA) as a prospective molecular marker for bladder cancer detection. To systematically study the role and mechanism of KLHDC7B in BLCA, we focused on the most common type of BLCA in this study. First, we used RNA sequencing to discover that KLHDC7B was considerably increased in BLCA patients' urine exosomes compared to healthy controls. Then, we validated this result in an independent cohort and identified it as an effective tool for diagnosing and distinguishing high-grade and low-grade BLCA. Finally, we studied the role and mechanism of KLHDC7B in BLCA at the cellular level, providing a functional basis for its expression as a novel laboratory diagnostic biomarker for BLCA exosomal mRNA, which has important theoretical and clinical significance.

Safety and effects of a home-based Tai Chi exercise rehabilitation program in patients with chronic heart failure: study protocol for a randomized controlled trial.

Introduction: Chronic heart failure (CHF), as the final stage of the progression of many cardiovascular disorders, is one of the main causes of hospitalization and death in the elderly and has a substantial impact on patients' quality of life (QOL). Exercise-based cardiac rehabilitation (CR) has been shown to considerably enhance QOL and prognosis. Given the barriers to center-based CR faced by most developing countries in the form of expensive instruments, the development of home-based CR is necessary. Tai Chi, as an instrument-free exercise, has been shown to be successful in treating elderly CHF individuals. Fu Yang, as one of the academic concept of Traditional Chinese Medicine (TCM), believes that the fundamental pathogenesis of CHF is the gradual decline of Yang, and emphasizes the restoration of Yang physiological function in the treatment process. Therefore, we develope a home-based Tai Chi exercise rehabilitation program called Fu Yang Tai Chi (FYTC) for elderly CHF patients by combining the Fu Yang Theory of TCM with the CR theory. The objective of this study is to evaluate the effectiveness, acceptability, and safety of the program. Methods and analysis: We suggest conducting a parallel randomized controlled clinical trial with open label. Eighty CHF elderly participants will be randomly assigned in a 1:1 ratio to the FYTC rehabilitation program group or the moderate-intensity aerobic walking control group. Eligible participants will engage in either three sessions weekly of FYTC or walking exercise for 12 weeks. The primary outcome is the relative change in 6 min walk distance (6MWD). The secondary outcomes are the plasma levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP), QOL, left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDd), self-rating anxiety scale (SAS) and depression scale (SDS), exercise skills, and noninvasive hemodynamic monitoring. Throughout the trial, adverse events will be recorded for safety evaluation. Researchers who are blinded to the treatment allocation will analyze the data. Ethics and dissemination: This research was authorized by the Guang'anmen Hospital Ethics Committee of the Chinese Academy of Medical Sciences (2022-141-KY). Our findings will be shared online and in academic conferences as well as in peer-reviewed journals. Trial registration number: ChiCTR2200063511.

Integration of Single-Cell Transcriptomics Data Reveal Differences in Cell Composition and Communication in Acne.

Purpose: Acne is a kind of hair follicle sebaceous inflammatory disease, which has a high incidence rate among adolescents. Comparative data on cells which beneficial for precise treatment of acne patients. Patients and Methods: After integrating and removing the batch effect of single-cell transcriptomics data of acne patients and health skin, the dimensionality reduction clustering was performed and the change in characteristics of each cell group were analyzed. Further, cell communication differences between gender were analyzed by use Cellchat software. Results: 70,189 cells were analyzed, and 11 cell groups were identified. The proportion of basal cells and macrophages in skin of acne patients are relatively high than that of skin in healthy people. The results of cell communication showed that the communication intensity of acne patients was significantly higher than that of healthy skin, and the endothelial cells showed a strong ability to receive signals. From the perspective of gender differences, the proportion of macrophages in male patients were higher than that in female patients, and there were a large number of basal cells in the lesion area of female patients. There are also have some specific immune response ligand-receptor regulatory signals in male patients. Conclusion: There are significant differences in skin cell composition and cell communication patterns between acne patients and healthy people, especially reflected in gender differences. Basal cells, macrophages and endothelial cells can serve as key targets for acne treatment. The treatment methods for men and women should be more personalized.

Case report: Whole-exome sequencing for a hereditary elliptocytosis case with an unexpectedly low HbA1c.

Objectives: Hereditary elliptocytosis is a group of erythroid hereditary diseases characterized by elliptically shaped erythrocytes in peripheral blood. It is mainly inherited through autosomal dominant inheritance. This study aimed to conduct a genetic etiology analysis in a case with a clinical diagnosis of hereditary elliptocytosis and an unexpectedly low HbA1c. Methods: Whole-exome sequencing was performed to find the possible pathogenic mutations. At the same time, bioinformatics software was used to predict the mutation function. Sanger sequencing was performed to verify the suspected pathogenic mutations. Results: Whole-exome sequencing results showed that the proband with mild anemia had a heterozygous c.2303G>A (p.G768D) missense mutation in the 13th exon of the SPTB gene. The Sanger sequencing confirmed this heterozygous mutation. This mutation was extremely rare in the population, and multiple software's predictions were harmful. Conservative analysis revealed that this site was highly conserved in various species. Conclusion: The c.2303G>A mutation of the SPTB gene is the suspected cause of hereditary elliptocytosis in the patient. Our data show that microscopic examination of red blood cells on blood smears is an important means of diagnosing hereditary elliptocytosis. Whole-exome sequencing is an effective tool to determine the genetic etiology of erythrocyte membrane diseases, which can promote accurate diagnosis and genetic counseling.