Brain high-throughput multi-omics data reveal molecular heterogeneity in Alzheimer's disease.

Unbiased data-driven omic approaches are revealing the molecular heterogeneity of Alzheimer disease. Here, we used machine learning approaches to integrate high-throughput transcriptomic, proteomic, metabolomic, and lipidomic profiles with clinical and neuropathological data from multiple human AD cohorts. We discovered 4 unique multimodal molecular profiles, one of them showing signs of poor cognitive function, a faster pace of disease progression, shorter survival with the disease, severe neurodegeneration and astrogliosis, and reduced levels of metabolomic profiles. We found this molecular profile to be present in multiple affected cortical regions associated with higher Braak tau scores and significant dysregulation of synapse-related genes, endocytosis, phagosome, and mTOR signaling pathways altered in AD early and late stages. AD cross-omics data integration with transcriptomic data from an SNCA mouse model revealed an overlapping signature. Furthermore, we leveraged single-nuclei RNA-seq data to identify distinct cell-types that most likely mediate molecular profiles. Lastly, we identified that the multimodal clusters uncovered cerebrospinal fluid biomarkers poised to monitor AD progression and possibly cognition. Our cross-omics analyses provide novel critical molecular insights into AD.

Lactate dehydrogenase A (LDHA)-mediated lactate generation promotes pulmonary vascular remodeling in pulmonary hypertension.

BACKGROUND: High levels of lactate are positively associated with prognosis and mortality in pulmonary hypertension (PH). Lactate dehydrogenase A (LDHA) is a key enzyme for the production of lactate. This study is undertaken to investigate the role and molecular mechanisms of lactate and LDHA in PH. METHODS: Lactate levels were measured by a lactate assay kit. LDHA expression and localization were detected by western blot and Immunofluorescence. Proliferation and migration were determined by CCK8, western blot, EdU assay and scratch-wound assay. The right heart catheterization and right heart ultrasound were measured to evaluate cardiopulmonary function. RESULTS: In vitro, we found that lactate promoted proliferation and migration of pulmonary artery smooth muscle cells (PASMCs) in an LDHA-dependent manner. In vivo, we found that LDHA knockdown reduced lactate overaccumulation in the lungs of mice exposed to hypoxia. Furthermore, LDHA knockdown ameliorated hypoxia-induced vascular remodeling and right ventricular dysfunction. In addition, the activation of Akt signaling by hypoxia was suppressed by LDHA knockdown both in vivo and in vitro. The overexpression of Akt reversed the inhibitory effect of LDHA knockdown on proliferation in PASMCs under hypoxia. Finally, LDHA inhibitor attenuated vascular remodeling and right ventricular dysfunction in Sugen/hypoxia mouse PH model, Monocrotaline (MCT)-induced rat PH model and chronic hypoxia-induced mouse PH model. CONCLUSIONS: Thus, LDHA-mediated lactate production promotes pulmonary vascular remodeling in PH by activating Akt signaling pathway, suggesting the potential role of LDHA in regulating the metabolic reprogramming and vascular remodeling in PH.

Changes in the centre of rotation and the anterior bone loss of the vertebral body in Mobi-C artificial disc replacement segments after cervical hybrid surgery: a retrospective study.

OBJECTIVE: To examine the short-term efficacy and imaging results of using the Mobi-C in cervical hybrid surgery on 2-level cervical spondylolisthesis. To observe post-operative changes in the flexion-extension centre of rotation (FE-COR) and anterior bone loss (ABL) of the anterior cervical disc replacement (ACDR) segment. METHODS: Forty-two patients (20 males and 22 females, aged 42‒67 years) who underwent cervical hybrid surgery were retrospectively analysed. Their ACDR segment used Mobi-C, and the fusion segment used ROI-C, with a follow-up of 25‒42 months (31.1 ± 4.8 months). The modified Japanese Orthopaedic Association (mJOA) score, Neck Disability Index (NDI), and visual analogue scale (VAS) were used to assess clinical outcomes. Pre-operative, 6-month post-operative, and final follow-up radiographs were collected to compare total cervical spine curvature (C2-C7), curvature of the operated segments, range of motion (ROM) in the total cervical spine, operated segmental ROM, ACDR segmental ROM, and operated adjacent segmental ROM. The height of the superior articular process (HSAP), the orientation of zygapophyseal joint spaces (OZJS), and the length of the superior articular surface (LSAS) were measured. The FE-COR of the ACDR segment was measured using the mid-plumb line method. The translation distance of the Mobi-C was measured. The degree of disc degeneration in the adjacent segment, bony fusion of the ACDF segment, and ABL of the upper and lower vertebra of the ACDR segment were observed. RESULTS: In our group, all patients have shown improvements in their postoperative mJOA, NDI, and VAS scores. Overall cervical ROM and surgical segmental ROM decreased (P < 0.05). However, there was no significant decrease in ACDR segmental ROM and upper or lower adjacent segmental ROM compared with pre-operatively (P > 0.05). For FE-COR-X, only the last follow-up compared with pre-surgery showed statistical significance (46.74 ± 7.71% vs. 50.74 ± 6.92%, P < 0.05). For FE-COR-Y, the change was statistically significant at both 6 months post-operation and the final follow-up compared to pre-operation (45.37% ± 21.11% vs. 33.82% ± 10.87%, 45. 37% ± 21.11% vs. 27.48% ± 13.58%, P < 0.05). No significant difference in the Mobi-C translation distance was observed (P > 0.05). Moreover, the difference in HSAP was not statistically significant at each node (P > 0.05). The OZJS and LSAS were significantly different at the final follow-up compared to the pre-operative period (P < 0.05). All the ACDF segments were observed in a stable condition at the final follow-up. Furthermore, 9 of the adjacent segments showed imaging ASD (9/82, 10.98%), and all were present at the last follow-up, of which 6 were mild, and 3 were moderate. Twenty of the 42 Mobi-C segments had no significant ABL (grade 0) 6 months post-operatively (47.62%). Sixteen cases (38.10%) showed mild ABL (grade 1), and 6 cases (14.28%) showed moderate ABL (grade 2). No severe ABL occurred. CONCLUSION: The cervical hybrid surgery using Mobi-C artificial cervical discs can achieve satisfactory results. The Mobi-C segmental FE-COR-X shows a slow forward shift trend, and FE-COR-Y drops noticeably within 6 months post-surgery before stabilizing. It's common to see mild to moderate ABL after cervical hybrid surgery using Mobi-C, and significant progression is unlikely in the short term. Furthermore, changes in the FE-COR after hybrid surgery in the Mobi-C segment might not affect clinical outcomes.

Carnosol alleviates sepsis-induced pulmonary endothelial barrier dysfunction by targeting nuclear factor erythroid2-related factor 2/sirtuin-3 signaling pathway to attenuate oxidative damage.

Excessive reactive oxygen species production during acute lung injury (ALI) will aggravate the inflammatory process and endothelial barrier dysfunction. Carnosol is a natural phenolic diterpene with antioxidant and anti-inflammatory properties, but its role in treating sepsis-induced ALI remains unclear. This study aims to explore the protective effects and underlying mechanisms of carnosol in sepsis-induced ALI. C57BL/6 mouse were preconditioned with carnosol for 1 h, then the model of lipopolysaccharide (LPS)-induced sepsis was established. The degree of pulmonary edema, oxidative stress, and inflammation were detected. Endothelial barrier function was evaluated by apoptosis and cell junctions. In vitro, Mito Tracker Green probe, JC-1 staining, and MitoSOX staining were conducted to investigate the effect of carnosol on mitochondria. Finally, we investigated the role of nuclear factor-erythroid 2-related factor (Nrf2)/sirtuin-3 (SIRT3) in carnosol against ALI. Carnosol alleviated LPS-induced pulmonary oxidative stress and inflammation by inhibiting excess mitochondrial reactive oxygen species production and maintaining mitochondrial homeostasis. Furthermore, carnosol also attenuated LPS-induced endothelial cell barrier damage by reducing vascular endothelial cell apoptosis and restoring occludin, ZO-1, and vascular endothelial-Cadherin expression in vitro and in vivo. In addition, carnosol increased Nrf2 nuclear translocation to promote SIRT3 expression. The protective effects of carnosol on ALI were largely abolished by inhibition of Nrf2/SIRT3. Our study has provided the first evidence that the Nrf2/SIRT3 pathway is a protective target of the endothelial barrier in ALI, and carnosol can serve as a potential therapeutic candidate for ALI by utilizing its ability to target this pathway.

ß-aminoisobutyrics acid, a metabolite of BCAA, activates the AMPK/Nrf-2 pathway to prevent ferroptosis and ameliorates lung ischemia-reperfusion injury.

BACKGROUND: Lung ischemia-reperfusion (I/R) injury is a serious clinical problem without effective treatment. Enhancing branched-chain amino acids (BCAA) metabolism can protect against cardiac I/R injury, which may be related to bioactive molecules generated by BCAA metabolites. L-ß-aminoisobutyric acid (L-BAIBA), a metabolite of BCAA, has multi-organ protective effects, but whether it protects against lung I/R injury is unclear. METHODS: To assess the protective effect of L-BAIBA against lung I/R injury, an animal model was generated by clamping the hilum of the left lung, followed by releasing the clamp in C57BL/6 mice. Mice with lung I/R injury were pre-treated or post-treated with L-BAIBA (150 mg/kg/day), given by gavage or intraperitoneal injection. Lung injury was assessed by measuring lung edema and analyzing blood gases. Inflammation was assessed by measuring proinflammatory cytokines in bronchoalveolar lavage fluid (BALF), and neutrophil infiltration of the lung was measured by myeloperoxidase activity. Molecular biological methods, including western blot and immunofluorescence, were used to detect potential signaling mechanisms in A549 and BEAS-2B cells. RESULTS: We found that L-BAIBA can protect the lung from I/R injury by inhibiting ferroptosis, which depends on the up-regulation of the expressions of GPX4 and SLC7A11 in C57BL/6 mice. Additionally, we demonstrated that the Nrf-2 signaling pathway is key to the inhibitory effect of L-BAIBA on ferroptosis in A549 and BEAS-2B cells. L-BAIBA can induce the nuclear translocation of Nrf-2. Interfering with the expression of Nrf-2 eliminated the protective effect of L-BAIBA on ferroptosis. A screening of potential signaling pathways revealed that L-BAIBA can increase the phosphorylation of AMPK, and compound C can block the Nrf-2 nuclear translocation induced by L-BAIBA. The presence of compound C also blocked the protective effects of L-BAIBA on lung I/R injury in C57BL/6 mice. CONCLUSIONS: Our study showed that L-BAIBA protects against lung I/R injury via the AMPK/Nrf-2 signaling pathway, which could be a therapeutic target.

L-BAIBA upregulates the expression of GPX4 and SLC7A11 by activating the AMPK/Nrf-2/GPX4/SLC7A11 signaling pathway, thereby protecting against I/R-induced increase in ROS and ferroptosis in the lung.

Care Disruption During COVID-19: a National Survey of Hospital Leaders.

BACKGROUND: The COVID-19 pandemic caused massive disruption in usual care delivery patterns in hospitals across the USA, and highlighted long-standing inequities in health care delivery and outcomes. Its effect on hospital operations, and whether the magnitude of the effect differed for hospitals serving historically marginalized populations, is unknown. OBJECTIVE: To investigate the perspectives of hospital leaders on the effects of COVID-19 on their facilities' operations and patient outcomes. METHODS: A survey was administered via print and electronic means to hospital leaders at 588 randomly sampled acute-care hospitals participating in Medicare's Inpatient Prospective Payment System, fielded from November 2020 to June 2021. Summary statistics were tabulated, and responses were adjusted for sampling strategy and non-response. RESULTS: There were 203 responses to the survey (41.6%), with 20.7% of respondents representing safety-net hospitals and 19.7% representing high-minority hospitals. Over three-quarters of hospitals reported COVID testing shortages, about two-thirds reported staffing shortages, and 78.8% repurposed hospital spaces to intensive care units, with a slightly higher proportion of high-minority hospitals reporting these effects. About half of respondents felt that non-COVID inpatients received worsened quality or outcomes during peak COVID surges, and almost two-thirds reported worsened quality or outcomes for outpatient non-COVID patients as well, with few differences by hospital safety-net or minority status. Over 80% of hospitals participated in alternative payment models prior to COVID, and a third of these reported decreasing these efforts due to the pandemic, with no differences between safety-net and high-minority hospitals. CONCLUSIONS: COVID-19 significantly disrupted the operations of hospitals across the USA, with hospitals serving patients in poverty and racial and ethnic minorities reporting relatively similar care disruption as non-safety-net and lower-minority hospitals.

Identification of factors controlling heavy metals/metalloid distribution in agricultural soils using multi-source data.

Understanding the factors that controlling the agricultural soil heavy metals/metalloids distribution is vital for cropland soil remediation and management. For this objective, 227 agricultural soils were sampled in the Guanzhong Plain, China, to measure the concentration of five heavy metals (Pb, Cd, Ni, Zn, and Cu) and one metalloid (As) by X-ray fluorescence spectrometer, meanwhile, 24 possible influencing factors to agricultural soil heavy metals/metalloid distribution were collected and grouped into three categories. A sequential multivariate statistical analysis was carried out to provide insight into the controlling factors of soil heavy metals/metalloid distribution, then stepwise multiple linear regression (SMLR) and partial least squares regression (PLS) were used to predict heavy metals/metalloid concentrations in agricultural soil based on the result of soil heavy metals/metalloid controlling factors identification. The results demonstrated the types of soil and land use did not have a substantial effect on soil heavy metals/metalloid distribution, except Zn and Cu. The soil properties category played a major role in influencing the soil heavy metals/metalloid concentration. The concentrations of Mn and Fe, which are the main constitute elements of soil inorganic colloid, were the most significant factors, followed by the concentrations of P, K and Ca. Soil pH and soil organic matter (SOM) content, which are often considered as important factors for soil heavy metals/metalloid distribution, were not important in the present study. The SMLR was more effective than the PLS for predicting soil heavy metals/metalloid content. The results of this study enlighten that future soil heavy metals/metalloid contamination treatment in regions with high pH and low SOM content should concentrate on inorganic colloid particles, which have strong adsorption capacity for soil heavy metals/metalloid and are environmentally friendly. Moreover, the combination of successive multivariate statistical analysis and SMLR provide an effective tool to predict and monitor agricultural soil heavy metals/metalloid distribution, and facilitate the improvement of environmental and territorial management.

Metabolomic and lipidomic signatures in autosomal dominant and late-onset Alzheimer's disease brains.

INTRODUCTION: The identification of multiple genetic risk factors for Alzheimer's disease (AD) suggests that many pathways contribute to AD onset and progression. However, the metabolomic and lipidomic profiles in carriers of distinct genetic risk factors are not fully understood. The metabolome can provide a direct image of dysregulated pathways in the brain. METHODS: We interrogated metabolomic signatures in the AD brain, including carriers of pathogenic variants in APP, PSEN1, and PSEN2 (autosomal dominant AD; ADAD), APOE ɛ4, and TREM2 risk variant carriers, and sporadic AD (sAD). RESULTS: We identified 133 unique and shared metabolites associated with ADAD, TREM2, and sAD. We identified a signature of 16 metabolites significantly altered between groups and associated with AD duration. DISCUSSION: AD genetic variants show distinct metabolic perturbations. Investigation of these metabolites may provide greater insight into the etiology of AD and its impact on clinical presentation. HIGHLIGHTS: APP/PSEN1/PSEN2 and TREM2 variant carriers show distinct metabolic changes. A total of 133 metabolites were differentially abundant in AD genetic groups. ß-citrylglutamate is differentially abundant in autosomal dominant, TREM2, and sporadic AD. A 16-metabolite profile shows differences between Alzheimer's disease (AD) genetic groups. The identified metabolic profile is associated with duration of disease.

Special congenital dacryocystocele.

Congenital Dacryocystocele is a rare disease of the eye and nose, which originates from congenital obstruction of lacrimal duct system, but accounts for a low proportion in congenital obstruction of lacrimal duct system. We present a case of congenital dacryocystocele to analyze the clinical features and to explore the clinical treatment effect of special congenital dacryocyst protrusion.

Safety and immunogenicity of COVID-19 vaccination in patients with non-alcoholic fatty liver disease (CHESS2101): A multicenter study.

BACKGROUND & AIMS: The development of COVID-19 vaccines has progressed with encouraging safety and efficacy data. Concerns have been raised about SARS-CoV-2 vaccine responses in the large population of patients with non-alcoholic fatty liver disease (NAFLD). The study aimed to explore the safety and immunogenicity of COVID-19 vaccination in NAFLD. METHODS: This multicenter study included patients with NAFLD without a history of SARS-CoV-2 infection. All patients were vaccinated with 2 doses of inactivated vaccine against SARS-CoV-2. The primary safety outcome was the incidence of adverse reactions within 7 days after each injection and overall incidence of adverse reactions within 28 days, and the primary immunogenicity outcome was neutralizing antibody response at least 14 days after the whole-course vaccination. RESULTS: A total of 381 patients with pre-existing NAFLD were included from 11 designated centers in China. The median age was 39.0 years (IQR 33.0-48.0 years) and 179 (47.0%) were male. The median BMI was 26.1 kg/m2 (IQR 23.8-28.1 kg/m2). The number of adverse reactions within 7 days after each injection and adverse reactions within 28 days totaled 95 (24.9%) and 112 (29.4%), respectively. The most common adverse reactions were injection site pain in 70 (18.4%), followed by muscle pain in 21 (5.5%), and headache in 20 (5.2%). All adverse reactions were mild and self-limiting, and no grade 3 adverse reactions were recorded. Notably, neutralizing antibodies against SARS-CoV-2 were detected in 364 (95.5%) patients with NAFLD. The median neutralizing antibody titer was 32 (IQR 8-64), and the neutralizing antibody titers were maintained. CONCLUSIONS: The inactivated COVID-19 vaccine appears to be safe with good immunogenicity in patients with NAFLD. LAY SUMMARY: The development of vaccines against coronavirus disease 2019 (COVID-19) has progressed rapidly, with encouraging safety and efficacy data. This study now shows that the inactivated COVID-19 vaccine appears to be safe with good immunogenicity in the large population of patients with non-alcoholic fatty liver disease.

The TMEM106B FTLD-protective variant, rs1990621, is also associated with increased neuronal proportion.

Apart from amyloid ß deposition and tau neurofibrillary tangles, Alzheimer's disease (AD) is a neurodegenerative disorder characterized by neuronal loss and astrocytosis in the cerebral cortex. The goal of this study is to investigate genetic factors associated with the neuronal proportion in health and disease. To identify cell-autonomous genetic variants associated with neuronal proportion in cortical tissues, we inferred cellular population structure from bulk RNA-Seq derived from 1536 individuals. We identified the variant rs1990621 located in the TMEM106B gene region as significantly associated with neuronal proportion (p value = 6.40 × 10-07) and replicated this finding in an independent dataset (p value = 7.41 × 10-04) surpassing the genome-wide threshold in the meta-analysis (p value = 9.42 × 10-09). This variant is in high LD with the TMEM106B non-synonymous variant p.T185S (rs3173615; r2 = 0.98) which was previously identified as a protective variant for frontotemporal lobar degeneration (FTLD). We stratified the samples by disease status, and discovered that this variant modulates neuronal proportion not only in AD cases, but also several neurodegenerative diseases and in elderly cognitively healthy controls. Furthermore, we did not find a significant association in younger controls or schizophrenia patients, suggesting that this variant might increase neuronal survival or confer resilience to the neurodegenerative process. The single variant and gene-based analyses also identified an overall genetic association between neuronal proportion, AD and FTLD risk. These results suggest that common pathways are implicated in these neurodegenerative diseases, that implicate neuronal survival. In summary, we identified a protective variant in the TMEM106B gene that may have a neuronal protection effect against general aging, independent of disease status, which could help elucidate the relationship between aging and neuronal survival in the presence or absence of neurodegenerative disorders. Our findings suggest that TMEM106B could be a potential target for neuronal protection therapies to ameliorate cognitive and functional deficits.

Whole-lesion ADC histogram analysis and the spondyloarthritis research consortium of canada (SPARCC) MRI index in evaluating the disease activity of ankylosing spondylitis.

BACKGROUND: Conventional MRI is limited in quantitative evaluation of ankylosing spondylitis (AS) activity states. A comparison of the effectiveness of the whole-lesion apparent diffusion coefficient (ADC) histogram analysis with the Spondyloarthritis Research Consortium of Canada (SPARCC) MRI index in evaluating the disease activity of AS might aid in this assessment. PURPOSE: To compare the effectiveness of the whole-lesion ADC histogram analysis with the SPARCC MRI index in evaluating the disease activity states of AS. STUDY TYPE: Prospective. POPULATION: A total of 57 AS patients and 27 healthy matched volunteers were included. FIELD STRENGTH/SEQUENCE: 3.0T MR including a diffusion-weighted imaging (DWI) sequence (b = 0, 1000 s/mm2 ). STATISTICAL TESTS: One-way analysis of variance (ANOVA) and Scheffe's post-hoc was used to compare the parameters among different groups. A receiver operating characteristic (ROC) analysis and the Spearman rank correlation were performed to test the diagnostic performance of all parameters in distinguishing different disease activity states and determining the correlations between them. ASSESSMENT: AS disease activity states was evaluated according to the Ankylosing Spondylitis Disease Activity Score (ASDAS). Initial DWI images and corresponding ADC maps were imported into our in-house software. Regions of interest (ROIs) were drawn in all slices and the relevant parameters were derived simultaneously. The SPARCC MRI index scores were counted artificially based on T2 -PDW-SPAIR images. RESULTS: The ADCmean , ADC percentiles, and SPARCC MRI index of the active group were significantly higher than the inactive and control groups (all P < 0.001). The 90th percentile could differentiate the inactive from the control group and the low disease activity group from the inactive group (P = 0.011 and 0.006, respectively). The 50th percentile of the high disease activity group was significantly higher than the low group (P = 0.004), while the SPARCC MRI index of the very high disease activity group was higher than the high group (P < 0.001). DATA CONCLUSION: The whole-volume ADC histogram analysis was superior to the SPARCC MRI index in assessing AS activity states. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:114-126.

Diffusion kurtosis imaging in sacroiliitis to evaluate the activity of ankylosing spondylitis.

BACKGROUND: Conventional magnetic resonance (MR) imaging is limited in providing sufficient information on microstructure or in quantitatively evaluating certain inflammation processes. Functional MR sequences such as diffusion kurtosis imaging (DKI) might help to evaluate the sacroiliac joint in ankylosing spondylitis (AS) patients. PURPOSE: To explore the application of DKI in evaluating the disease activity of AS. STUDY TYPE: Prospective. POPULATION: Forty-four patients with a diagnosis of AS according to the Assessment in SpondyloArthritis International Society (ASAS) criteria. FIELD STRENGTH/SEQUENCE: 3.0T MRI including the DKI sequence (b = 0, 500, 1000, 1500, 2000 s/mm2 ). STATISTICAL TESTS: Two-independent-samples t-test and one-way analysis of variance (ANOVA) were used to compare the DKI parameters among different groups, and post-hoc Scheffe's method was adopted. Receiver operating characteristic (ROC) analysis and Spearman's rank correlation were performed to test the diagnostic performance of DKI parameters in distinguishing different activity grades and the correlation between them, respectively. ASSESSMENT: AS disease activity was evaluated according to the Ankylosing Spondylitis Disease Activity Score (ASDAS), and four disease activity states were chosen by consensus: inactive disease and moderate, high, and very high disease activity. The three cutoffs selected to separate these states were: 1.3, 2.1, and 3.5 units, respectively. RESULTS: The corrected ADC (D) and apparent diffusion coefficient (ADC) values of sacroiliac joints in the active group were significantly higher, while the the kurtosis of diffusion (K value) value was significantly lower than those of the inactive group (all P < 0.001). The D value performed best in distinguishing different activity grades (all P < 0.001). The D and ADC values correlated positively, while the K value correlated negatively, with activity grade significantly (r = 0.918, 0.798, and -0.765, respectively; all P < 0.001). DATA CONCLUSION: DKI of sacroiliac joints might be useful to evaluate the disease activity of AS. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:101-108.

Effects of early enteral nutrition on the gastrointestinal motility and intestinal mucosal barrier of patients with burn-induced invasive fungal infection.

OBJECTIVE: To evaluate the effects of early enteral nutrition on the gastrointestinal motility and intestinal mucosal barrier of patients with burn-induced invasive fungal infection. METHODS: A total of 120 patients with burn-induced invasive fungal infection were randomly divided into an early enteral nutrition (EN) group and a parenteral nutrition (PN) group (n=60). The patients were given nutritional support intervention for 14 days, and the expression levels of serum transferrin, albumin, total protein, endotoxin, D-lactic acid and inflammatory cytokines were detected on the 1st, 7th and 14th days respectively. RESULTS: As the treatment progressed, the levels of serum transferrin, albumin and total protein of the EN group were significantly higher than those of the PN group (P<0.05), while the levels of serum endotoxin and D-lactic acid of the form group were significantly lower (P<0.05). After treatment, the expression levels of IL-6 and TNF-α were decreased in the EN group, which were significantly different from those of the PN group (P<0.05). During treatment, the incidence rates of complications such as abdominal distension, diarrhea, sepsis, nausea, vomiting and gastric retention were similar. The mean healing time of wound surface was 9.34±0.78 days in the EN group and 12.46±2.19 days in the PN group, i.e. such time of the former was significantly shorter than that of the latter (P<0.05). CONCLUSION: Treating patients having burn-induced invasive fungal infection by early enteral nutrition support with arginine can safely alleviate malnutrition and stress reaction, strengthen cellular immune function and promote wound healing, thereby facilitating the recovery of gastrointestinal motility and the function of intestinal mucosal barrier.

Spinal cord injury without radiographic abnormality with diffuse idiopathic skeletal hyperostosis: A case report.

INTRODUCTION: Spinal cord injury without fracture dislocation (SCIWORA) is relatively rare, and spastic paralysis for more than 2 months with Diffuse diopathic skeletal hyperoseosis (DISH) is even rarer. CASE PRESENTATION: A 70-year-old male patient presented with quadriplegia for more than 2 months after a fall. He's incontinent of stool and urine. An MRI was performed and the diagnosis was "SCIWORA, DISH". After surgical treatment, there was a significant recovery of postoperative related symptoms. CLINICAL DISCUSSION: The timing of SCIWORA surgery remains controversial, with most studies suggesting that early surgery (within 24 h) is more effective. Anterior cervical discectomy and fusion (ACDF) is one of the main surgical procedures that directly and completely removes compression from the anterior aspect of the spinal cord. Patients with SCIWORA combined with DISH may have fractures due to low-energy injuries and should be treated aggressively with surgery to avoid secondary injury to the spinal cord. CONCLUSION: Adult SCIWORA patients should be aggressively treated surgically when vital signs are stable and relatively calm. To avoid secondary injury, titanium plates combined with self-stabilizing fusions provide reliable immediate stabilization and can be used as one of the internal fixation modalities.

Irisin-Encapsulated Mitochondria-Targeted Biomimetic Nanotherapeutics for Alleviating Acute Kidney Injury.

Acute kidney injury (AKI) is the sudden decrease in renal function that can be attributed to dysregulated reactive oxygen species (ROS) production and impaired mitochondrial function. Irisin, a type I membrane protein secreted by skeletal muscles in response to physical activity, has been reported to alleviate kidney damage through regulation of mitochondrial biogenesis and oxidative metabolism. In this study, a macrophage membrane-coated metal-organic framework (MCM@MOF) is developed as a nanocarrier for encapsulating irisin to overcome the inherent characteristics of irisin, including a short circulation time, limited kidney-targeting ability, and low membrane permeability. The engineered irisin-mediated biomimetic nanotherapeutics have extended circulation time and enhanced targeting capability toward injured kidneys due to the preservation of macrophage membrane proteins. The irisin-encapsulated biomimetic nanotherapeutics effectively mitigate acute ischemia-reperfusion injury by protecting mitochondrial function and modulating SOD2 levels in renal tubular epithelial cells. The present study provides novel insights to advance the development of irisin as a potential therapeutic approach for AKI.

Prognostic impact of tumor size in ureteral cancer following segmental ureterectomy.

OBJECTIVE: To evaluate the classification and prognostic effects of a 2 cm tumor size in patients with ureteral cancer (UC) undergoing segmental ureterectomy (SU). PATIENTS AND METHODS: A total of 75 patients with UC who underwent SU in our hospital between April 2013 and April 2023 were included in this study. The study population was grouped based on tumor size, which was defined as the maximum diameter of the pathological specimens, resulting in 30 patients (40.0%) with tumor size <2 cm and 45 patients (60.0%) with tumor size ≥2 cm. The clinicopathological variables, perioperative parameters, and oncological outcomes were compared between the 2 groups. The endpoints were recurrence-free survival (RFS), and cancer-specific survival (CSS). RESULTS: A tumor ≥2 cm was related to a higher positive rate of urine exfoliative cytology (P = 0.049) and fewer preoperative ureteroscopies (P = 0.033) than tumors <2 cm. After a follow-up of 6.3 to 128.7 months (median 40.2 months), 23 cases (30.7%) experienced recurrence and 11 patients (14.7%) succumbed to UC in the end. Compared to those with tumor size <2 cm, patients with tumor size ≥2 cm experienced more urothelial recurrence (P = 0.032). Kaplan-Meier analysis demonstrated that patients with tumor size ≥2 cm displayed inferior urothelial RFS than those with tumor size <2 cm (P = 0.026). Multivariate Cox analysis identified tumor size ≥2 cm, and pathological stage ≥T2 were significant prognostic factors of poor urothelial RFS (all P < 0.05). CONCLUSION: Tumor size ≥2 cm was associated with a high rate of urothelial recurrence and served as an independent prognostic factor of adverse urothelial RFS in SU-treated patients with UC. Patients are advised to select surgical treatments for UC following the EAU guidelines.

[Application of polyetheretherketone rod semi-rigid pedicle screw internal fixation in lumbar non-fusion surgery].

OBJECTIVE: To investigate the effect of Polyetheretherketone (PEEK) rod semi-rigid pedicle screw fixation system in lumbar spine non-fusion surgery. METHODS: A total of 74 patients with tow-level lumbar degenerative diseases who underwent surgery from March 2017 to December 2019 were divided into PEEK rod group and titanium rod group. In the PEEK rod group, there were 34 patients, including 13 males and 21 females, aged from 51 to 79 years old with an average of (62.4±6.8) years old;There were 1 patient of L1-L3 segments, 7 patients of L2-L4 segments, 20 patients of L3-L5 segments and 6 patients of L4-S1 segments. In the titanium rod group, there were 40 patients, including 17 males and 23 females, aged from 52 to 81 years old with an average of (65.2±7.3) years old;There were 3 patient of L1-L3 segments, 11 patients of L2-L4 segments, 19 patients of L3-L5 segments and 7 patients of L4-S1 segments. The general conditions of operation, such as operation time, intraoperative blood loss, postoperative drainage was recorded. The visual analogue scale (VAS) for low back pain and Oswestry disability index (ODI) were compared in preoperatively and postoperatively(3 months, 12 months and last follow-up) between two groups. The change of range of motion (ROM) was observed by flexion and extension x-ray of lumbar. RESULTS: All patients successfully completed the operation. The follow-up time ranged from 22 to 34 months with an average of(26.8±5.6) months. The operative time (142.2±44.7) min and intraoperative blood loss(166.5±67.4)ml in PEEK group were lower than those in titanium group [(160.7±57.3) min、(212.8±85.4) ml](P<0.05). There was no significant differences in postoperative drainage between the two groups (P>0.05). At the final follow-up visit, in PEEK group and titanium group VAS of low back pain[(0.8±0.4) points vs (1.0±0.5) points], VAS for leg pain [ (0.7±0.4) points vs (0.8±0.5) points] and ODI [(9.8±1.6)% vs (12.1±1.5)%] were compared with preoperative [ (5.8±1.1) points vs (6.0±1.1)points], [ (7.2±1.7) points vs (7.0±1.6) points], [(68.5±8.9)% vs(66.3±8.2)%] were significantly different(P<0.05). There was no significant difference in VAS scores between the two groups at each postoperative time point (P>0.05). At 3 months after surgery, there was no difference in ODI between the two groups (P>0.05). There were significant differences in ODI between PEEK group and titanium rod group at 12 months [(15.5±2.1)% vs (18.4±2.4)%] and at the last follow-up [(9.8±1.6)% vs (12.1±1.5)%] (P<0.05). The total range of motion (ROM) of lumbar decreased in both groups after surgery. At 12 months after surgery and the last follow-up, the PEEK group compared with the titanium rod group, the total range of motion of lumbar was statistically significant (P<0.05). The range of motion (ROM) of the fixed segments decreased in both groups after surgery. The ROM of the fixed segments in PEEK group decreased from (9.5±4.6)° to (4.1±1.9)° at the last follow-up (P<0.05), which in the titanium rod group was decreased from (9.8±4.3)°to (0.9±0.5)° at the last follow-up (P<0.05). The range of motion (ROM) of upper adjacent segment increased in both groups, there was statistical significance in the ROM of upper adjacent segment between the two groups at 12 months after surgery and the last follow-up, (P<0.05). There was no screw loosening and broken rods in both groups during the follow-up period. CONCLUSION: The PEEK rod semi-rigid pedicle screw internal fixation system used in lumbar non-fusion surgery can retain part of the mobility of the fixed segment, showing comparable short-term clinical efficacy to titanium rod fusion. PEEK rod semi-rigid pedicle screw internal fixation system is a feasible choice for the treatment of lumbar spine degenerative diseases, and its long-term efficacy needs further follow-up observation.