Deactivation of the Unfolded Protein Response Aggravated Renal AA Amyloidosis in HSF1 Deficiency Mice.

Systemic amyloid A (AA) amyloidosis, which is considered the second most common form of systemic amyloidosis usually takes place several years prior to the occurrence of chronic inflammation, generally involving the kidney. Activated HSF1, which alleviated unfolded protein response (UPR) or enhanced HSR, is the potential therapeutic target of many diseases. However, the effect of HSF1 on AA amyloidosis remains unclear. This study focused on evaluating effect of HSF1 on AA amyloidosis based on HSF1 knockout mice. As a result, aggravated amyloid deposits and renal dysfunction have been found in HSF1 knockout mice. In progressive AA amyloidosis, HSF1 deficiency enhances serum amyloid A production might to lead to severe AA amyloid deposition in mice, which may be related to deactivated unfolded protein response as well as enhanced inflammation. Thus, HSF1 plays a significant role on UPR related pathway impacting AA amyloid deposition, which can mitigate amyloidogenic proteins from aggregation pathologically and is the possible way for intervening with the pathology of systemic amyloid disorder. In conclusion, HSF1 could not only serve as a new target for AA amyloidosis treatment in the future, but HSF1 knockout mice also can be considered as a valuable novel animal model for renal AA amyloidosis.

Sodium Sulfite as a Novel Hypoxia Revulsant Involved in Hypoxic Regulation in Escherichia coli.

As a reducing salt, sodium sulfite could deprive oxygen in solution, which could mimic hypoxic stress in Caenorhabditis elegans. In this study, the wild-type Escherichia coli strain MG1655 was used to examine the inhibition of sodium sulfite-induced hypoxia by observing the bacterial growth curves. We also analyzed the growth curves of mutant strains (for arcA/B, soxR/S, fnr, and oxyR) related to E. coli hypoxic pathways to reveal roles of the related genes during hypoxia. The ultrastructure of hypoxia-inhibited bacteria were also observed using transmission electron microscopy. Sodium sulfite could maintain hypoxic condition of bacterial culture for 8 h with concentrations over 40 mmol/L. Complete ultrastructure of the bacteria indicated sodium sulfite did inhibit bacterial growth and division. Among the hypoxia genes, fnr and arcB played key roles in sodium sulfite-induced hypoxia. This study showed that sodium sulfite could be used as a novel hypoxia revulsant for bacterial cultures.

Neuroprotective Effect of a Multistrain Probiotic Mixture in SOD1G93A Mice by Reducing SOD1 Aggregation and Targeting the Microbiota-Gut-Brain Axis.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by the selective loss of motor neurons. A bidirectional communication system known as the "microbiota-gut-brain" axis has a regulatory function in neurodegenerative disorders. The impact of probiotics on ALS through the "microbiota-gut-brain" axis remains uncertain. A longitudinal investigation was conducted to examine the alterations in the structure of the ileum and colon in mutant superoxide dismutase 1 (SOD1G93A) transgenic mice models of ALS by using immunofluorescence and Western blotting. Subsequently, the mice were administered a multistrain probiotic mixture (LBE) or vehicle orally, starting from 60 days of age until the terminal stage of the disease. The effects of these agents on the behavior, gut microbiota, microbial metabolites, and pathological processes of the spinal and intestine of SOD1G93A mice were analyzed, with a focus on exploring potential protective mechanisms. SOD1G93A mice exhibit various structural abnormalities in the intestine. Oral administration of LBE improved the proinflammatory response, reduced aberrant superoxide dismutase 1 (SOD1) aggregation, and protected neuronal cells in the intestine and spinal cord of SOD1G93A mice. Furthermore, LBE treatment resulted in a change in intestinal microbiota, an increase in short-chain fatty acid levels, and an enhancement in autophagy flux. SOD1G93A mice exhibited various structural abnormalities in the intestine. LBE can improve the proinflammatory response, reduce aberrant SOD1 aggregation, and protect neuronal cells in the spinal cord and intestine of SOD1G93A mice. The positive effect of LBE can be attributed to increased short-chain fatty acids and enhanced autophagy flux.

Natural and anthropogenic impacts on mercury accumulation in Xiaohai Lagoon, South China over the last 1200 years.

Anthropogenic use and release of mercury (Hg) have profoundly affected the global Hg cycle since preindustrial times. However, it is often difficult to quantify the relative contributions of natural and anthropogenic factors to environmental Hg accumulation. Here, we have presented a 1200-year record of Hg deposition in a sediment core from the Xiaohai Lagoon (South China), in combination with multiple environmental indicators (e.g., geochemical elements, grain size and total organic carbon, etc.). Using principal component analysis (PCA) and stepwise regression analysis (SRA), we aimed to explore the latent processes governing the accumulation of Hg over time and to quantitatively assess the natural and anthropogenic impacts on Hg deposition over the last millennium in Xiaohai Lagoon. Our results have demonstrated that between ∼ 870 and âˆ¼ 1860 CE, natural factors were the main drivers controlling Hg concentrations in the lagoon. These were directly driven by higher soil erosion and increased inputs of fine-grained matter. However, from 1860 to 2013 CE, enhanced anthropogenic activities played a significant role in Hg accumulation in Xiaohai Lagoon. Anthropogenic Hg fluxes increased significantly from ∼ 1860 CE, peaked several times during the 1860s to the 1950s, accelerated from the late 1950s to the early 2000s, and then declined gradually owing to the stringent environmental protection strategies and efficient pollutant control technologies. Our results have suggested that the increased anthropogenic Hg inputs between the 1860s and mid-1970s were mostly attributed to wars, the "Westernization Movement", and global industrial activity, with a surge mainly after the 1980s dominated by industrial activities in China and numerous developing countries in Southeast Asia. This study has shown the natural and anthropogenic influences associated with mercury pollution through quantitative analysis and can deepen our understanding of the processes and mechanisms of mercury deposition in natural environments under the influence of human activities.

High-Valence Metal Doping Induced Lattice Expansion for M-FeNi LDH toward Enhanced Urea Oxidation Electrocatalytic Activities.

The precise design of low-cost, efficient, and definite electrocatalysts is the key to sustainable renewable energy. The urea oxidation reaction (UOR) offers a promising alternative to the oxygen evolution reaction for energy-saving hydrogen generation. In this study, by tuning the lattice expansion, a series of M-FeNi layered double hydroxides (M-FeNi LDHs, M: Mo, Mn, V) with excellent UOR performance are synthesized. The hydrolytic transformation of Fe-MIL-88A is assisted by urea, Ni2+ and high-valence metals, to form a hollow M-FeNi LDH. Owing to the large atomic radius of the high-valence metal, lattice expansion is induced, and the electronic structure of the FeNi-LDH is regulated. Doping with high-valence metal is more favorable for the formation of the high-valence active species, NiOOH, for the UOR. Moreover, the hollow spindle structure promoted mass transport. Thus, the optimal Mo-FeNi LDH showed outstanding UOR electrocatalytic activity, with 1.32 V at 10 mA cm-2 . Remarkably, the Pt/C||Mo-FeNi LDH catalyst required a cell voltage of 1.38 V at 10 mA·cm-2 in urea-assisted water electrolysis. This study suggests a new direction for constructing nanostructures and modulating electronic structures, which is expected to ultimately lead to the development of a class of auxiliary electrocatalysts.

RABGGTB plays a critical role in ALS pathogenesis.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with unknown causes, which mainly affects motor neurons in the anterior horn of the spinal cord, brain stem, and cerebral cortex, also known as motor neuron disease. An important pathological feature of ALS is the formation of aggregates of mutant SOD1 protein, CTF25 of TDP-43, or other abnormal proteins in motor neurons, which require autophagy for degradation. Protein prenylation is known to participate in membrane association and proper localization of proteins. RABGGTB is the ß subunit of GGTase II (one of the prenyltransferases) that can regulate autophagy via Rab7 geranylgeranylation. In this study, we overexpressed RABGGTB via lentiviral transfection in NSC34-hSOD1G93A and TDP-43 cells. Overexpression of RABGGTB improved ALS cell proliferation by facilitating autophagosome-lysosome fusion. Furthermore, the abnormal aggregation of SOD1 protein was reduced. This indicates that protein prenylation is important for the proliferation and autophagy of cells autophagy. Enhanced autophagy has been observed in two of the most widely used ALS cell models. These findings indicate the widespread applicability of prenylation in ALS. In summary, overexpression of RABGGTB improved the geranylgeranylation of the Rab7 protein and had a positive effect on cells. These findings provide insights into the development of a novel therapeutic strategy for ALS.

Rab Geranylgeranyltransferase Subunit Beta as a Potential Indicator to Assess the Progression of Amyotrophic Lateral Sclerosis.

BACKGROUND: Currently, there is no effective treatment for amyotrophic lateral sclerosis (ALS), a devastating neurodegenerative disorder. Many biomarkers have been proposed, but because ALS is a clinically heterogeneous disease with an unclear etiology, biomarker discovery for ALS has been challenging due to the lack of specificity of these biomarkers. In recent years, the role of autophagy in the development and treatment of ALS has become a research hotspot. In our previous studies, we found that the expression of RabGGTase (low RABGGTB expression and no change in RABGGTA) is lower in the lumbar and thoracic regions of spinal cord motoneurons in SOD1G93A mice compared with WT (wild-type) mice groups, and upregulation of RABGGTB promoted prenylation modification of Rab7, which promoted autophagy to protect neurons by degrading SOD1. Given that RabGGTase is associated with autophagy and autophagy is associated with inflammation, and based on the above findings, since peripheral blood mononuclear cells are readily available from patients with ALS, we proposed to investigate the expression of RabGGTase in peripheral inflammatory cells. METHODS: Information and venous blood were collected from 86 patients diagnosed with ALS between January 2021 and August 2023. Flow cytometry was used to detect the expression of RABGGTB in monocytes from peripheral blood samples collected from patients with ALS and healthy controls. Extracted peripheral blood mononuclear cells (PBMCs) were differentiated in vitro into macrophages, and then the expression of RABGGTB was detected by immunofluorescence. RABGGTB levels in patients with ALS were analyzed to determine their impact on disease progression. RESULTS: Using flow cytometry in monocytes and immunofluorescence in macrophages, we found that RABGGTB expression in the ALS group was significantly higher than in the control group. Age, sex, original location, disease course, C-reactive protein (CRP), and interleukin-6 (IL-6) did not correlate with the ALS functional rating scale-revised (ALSFRS-R), whereas the RABGGTB level was significantly correlated with the ALSFRS-R. In addition, multivariate analysis revealed a significant correlation between RABGGTB and ALSFRS-R score. Further analysis revealed a significant correlation between RABGGTB expression levels and disease progression levels (ΔFS). CONCLUSIONS: The RABGGTB level was significantly increased in patients with ALS compared with healthy controls. An elevated RABGGTB level in patients with ALS is associated with the rate of progression in ALS, suggesting that elevated RABGGTB levels in patients with ALS may serve as an indicator for tracking ALS progression.

Femoral neck fracture patients with ischaemic stroke choose hemiarthroplasty or constrained liner total hip arthroplasty? A retrospective comparative study of 199 cases.

Background: The objective of this study was to assess the long-term survival rate, complications, as well as the clinical and radiological outcomes of hemiarthroplasty and total hip arthroplasty using constrained polyethylene liners in patients with ischemic stroke. Methods: This study was a retrospective cohort study that included patients with ischemic stroke who underwent hip arthroplasty from March 2010 to September 2017. In the Constrained Acetabular Liners (CAL) group, patients received an uncemented acetabular shell with a constrained polyethylene liner. The Dual Mobility (DM) group underwent hemiarthroplasty (HA). Additionally, hip function, range of motion, quality of life, the incidence of clinical complications, and prosthesis stability were investigated. Results: 96 patients with unilateral femoral neck fractures who underwent hip replacement with CAL were included in the CAL group, while 103 patients who underwent hip replacement with a dual mobility head were included in the DM group. VAS, and SF-36 data were available for both CAL and DM groups. At the 1-year postoperative follow-up, the HHS in the CAL group was significantly lower than that in the DM group (80.83 ± 3.91 vs. 83.17 ± 4.15, P < 0.05). The VAS score in the CAL group peaked at the 1-year follow-up (2.07 ± 0.91 vs. 1.49 ± 0.85, P < 0.05). However, there were no significant differences between the two groups in terms of HSS, VAS, and SF-36 at the last follow-up after surgery. Operative time and the amount of bleeding in the DM group were significantly lower than those in the CAL group (105.30 ± 29.68 vs. 94.85 ± 31.07; 355.11 ± 123.95 vs. 302.22 ± 107.68, P < 0.05). Additionally, there was no significant difference in the mean leg length discrepancy between the two groups. Conclusion: The clinical, imaging, and postoperative complications of the CAL and DM groups were analyzed. The prognosis for DM appears to be more beneficial for early patient recovery, but a higher likelihood of recurrent dislocation is observed. CAL offers excellent stability for primary THA in high-risk patients; however, attention should be given to preventing aseptic loosening.

[Melatonin-Mediated Inhibitory Effect on Hyperimmune Status of Acquired Aplastic Anemia].

OBJECTIVE: To evaluate the expression level of melatonin and its effects on immune function in aplastic anemia (AA) patients. METHODS: The enzyme-linked immunosorbent assay (ELISA) was used to detect the plasma levels of melatonin in AA patients, and the correlation between melatonin levels and laboratory indexs was analyzed. The activation, proliferation, and apoptosis of T cells from AA patients were analyzed by flow cytometry with or without melatonin in vitro. RESULTS: The plasma levels of melatonin in AA patients were significantly lower compared with healthy controls (HC) (12.23 pg/ml vs 20.04 pg/ml, P < 0.01), while the plasma melatonin levels of AA patients in remission group after immunosuppressive therapy (IST) were significantly higher than those in non-remission group (29.16 pg/ml vs 11.73 pg/ml, P =0.04). Moreover, the melatonin levels were positively correlated with platelets (r =0.49), the absolute reticulocyte count (r =0.45), and the percentage of neutrophils (r =0.43). Meanwhile, there was a negative correlation between melatonin levels and the percentages of lymphocytes (r =-0.45). The expressions of CD25 and CD69 in both CD4+ and CD8+ T cells from AA patients were remarkably inhibited by melatonin in vitro (all P < 0.05). When cultured with melatonin, the proliferation rates of both CD4+ and CD8+ T cells from AA patients were markedly suppressed (P =0.01 andP < 0.01). CONCLUSION: The plasma levels of melatonin were decreased in AA patients, which might play an important role in the mechanism of immunological abnormalities. The hyperimmune status of AA patients could be partially ameliorated by melatonin in vitro.

[Deciphering Hypoplastic Myelodysplastic Syndrome and Aplastic Anemia via In-Depth Analysis of Lymphocyte Subsets].

OBJECTIVE: To explore the difference of lymphocyte subsets in peripheral blood (PB) between aplastic anemia (AA) and hypoplastic myelodysplastic syndrome (hypo-MDS) patients, meanwhile to compare the clinical parameters obtained from PB and bone marrow (BM). METHODS: The lymphocyte subsets in hypo-MDS (n=25) and AA (n=33) patients were investigated by flow cytometry. Meanwhile, the differences in PB cell counts, biochemical indicators, BM cell counts and abnormal chromosomes between the two groups were analyzed. RESULTS: The percentage of CD8+T cells in AA group was significantly higher than that in hypo-MDS group (P=0.001), while the percentage of CD4+ T cells and the CD4+/CD8+ ratio in AA group were obviously lower than those in hypo-MDS group (P=0.015 and 0.001, respectively). Furthermore, the proportion of CD4+ and CD8+ activated T (TA) cells, and memory Tregs in AA group was distinctly lower than those in hypo-MDS group (P=0.043, 0.015 and 0.024, respectively). Nevertheless, the percentage of CD8+ naive T (TN) cells in AA patients was remarkably higher (P=0.044). And hypo-MDS patients had declined lymphocyte counts (P=0.025), increased levels of total bilirubin (TBil), lactate dehydrogenase (LDH), vitamin B12 and proportion of BM blasts than AA patients (P=0.019, 0.023, 0.027 and 0.045, respectively). CONCLUSION: In this study it was confirmed that the percentages of CD4+ and CD8+ TA cells, memory Tregs and CD8+ TN cells were significantly different between AA and hypo-MDS patients, which provide an essential basis for the identification of these two diseases.

A new joint reconstruction technique in the treatment of giant cell tumors around the knee: Structural allograft and unicompartmental arthroplasty.

OBJECTIVE: The long-term prognosis of patients who underwent unicompartmental knee arthroplasty (UKA) with a structural allograft or hemiarticular allograft transplantation to treat giant cell tumors (GCTs) around the knee and the prosthesis survival rate were analyzed. METHODS: We retrospectively reviewed 73 patients who were diagnosed with GCTs around the knee and underwent surgery to restore joint function from 2000 to 2015. Patients were divided into two groups according to the surgical procedure used for functional knee reconstruction: hemiarticular allograft transplantation or structural allograft and UKA. The Knee Society Score (KSS) and Western Ontario and McMaster Universities Arthritis Index (WOMAC) were used to analyze postoperative knee function between the two groups. The Kellgren-Lawrence (K-L) classification system was used to evaluate the progression of osteoarthritis. The incidence of complications and the prosthesis survival rate were also investigated. RESULTS: Patients who underwent UKA to treat GCT demonstrated significantly improved knee function. The rate of an excellent or good KSS was significantly different between the two groups (p = 0.041 at the 1-year follow-up, p = 0.033 at the last follow-up). The proportion of severe cases according to WOMAC in the two groups was also different (p = 0.030 at the 1-year follow-up, p = 0.021 at the last follow-up). According to the K-L grade of unaffected compartments, UKA better prevented the progression of osteoarthritis (p = 0.034). CONCLUSIONS: Patients with GCTs around the knee could benefit from UKA. In addition to providing better knee function and range of motion, UKA could also slow the progression of osteoarthritis in the knee joint. This new surgical method could meet the needs of patients wishing to preserve joint integrity and favorable joint function.

The role of 3-dimensional preoperative planning for primary total hip arthroplasty based on artificial intelligence technology to different surgeons: A retrospective cohort study.

Preoperative planning with computed tomography (CT)-based 3-dimensiona (3D) templating has been achieved precise placement of hip components. This study investigated the role of the software (3-dimensional preoperative planning for primary total hip arthroplasty [THA] based on artificial intelligence technology, artificial intelligence hip [AIHIP]) for surgeons with different experience levels in primary THA. In this retrospective cohort study, we included patients, who had undergone THA with the help of the AIHIP, and matched to patients, who had undergone THA without the help of the AIHIP, by age and the doctor who operated on them. The subjects were divided into 4 groups, senior surgeon (Chief of Surgery) with AIHIP group, senior surgeon without AIHIP group, junior surgeon (Associate Chief of Surgery) with AIHIP group and junior surgeon without AIHIP group. The general data, imaging index, clinical outcomes and accuracy of stem size prediction and cup size prediction were retrospectively documented for all patients. There was a significant difference in discrepancy in leg length (P = .010), neck-shaft angle (P = .025) and femoral offset (P = .031) between the healthy side and the affected side, operation duration (P < .001), decrease in hemoglobin (Hb) per 24 hours (P = .046), intraoperative radiation exposure frequency (P < .050) and postoperative complications (overall P = .035) among the patients in junior surgeon group. No significant differences were found between senior surgeon groups with respect to discrepancy in leg length (P = .793), neck-shaft angle (P = .088)and femoral offset (P = .946) between the healthy side and the affected side, operation duration (P = .085), decrease in Hb per 24 hours (P = .952), intraoperative radiation exposure frequency (P = .094) and postoperative complications (overall P = .378). The stem sizes of 95% were accurately estimated to be within 1 stem size, and 97% of the cup size estimates were accurate to within 1 cup size in senior surgeon group with AIHIP. A total of 87% stem sizes were accurately estimated to be within 1 stem size, and 85% cup sizes were accurate to within 1 cup size in junior surgeon group with AIHIP. In conclusion, our study suggests that an AI-based preoperative 3D planning system for THA is a valuable adjunctive tool for junior doctor and should routinely be performed preoperatively.

Efficacy of Direct Anterior Approach Versus Posterior Lateral Approach for Total Hip Replacement in Patients with Parkinson's Disease.

BACKGROUND The present study was performed to evaluate the efficacy of direct anterior approach (DAA) versus posterolateral approach (PLA) for total hip arthroplasty (THA) in patients with Parkinson's disease (PD). The aim of the study was to compare the speed of recovery of hip function and postoperative complications between the 2 approaches. MATERIAL AND METHODS The study included 285 Parkinson's patients who underwent THA; 209 eligible patients were recruited for analysis as per the inclusion criteria and assigned into DAA group (n=90) and PLA group (n=119) according to the surgical approach. Postoperative Harris Hip Score (HHS), Western Ontario and McMaster University Osteoarthritis Index (WOMAC), and Forgotten joint score (FJS) were collected to assess hip function. RESULTS The DAA had a statistically lower incidence of postoperative complications than the PLA, particularly the rate of postoperative dislocation. Perioperative outcomes showed a longer operative time in the DAA than in the PLA group and more intraoperative blood loss in the DAA than in the PLA group. At 3 months postoperatively, the HHS and WOMAC scores in the DAA group showed significantly higher scores compared to the PLA group versus the DAA group. However, these differences disappeared at 6 months postoperatively and the FJS in the DAA group had a statistically higher score compared to the PLA group. CONCLUSIONS In patients with Parkinson's disease complicated with hip disease, the DAA approach exhibited a lower rate of dislocation than the PLA approach and had faster recovery of hip function.

Tri-Lock Bone Preservation Stem Versus Conventional Corail Stem in Primary Total Hip Arthroplasty via Direct Anterior Approach: A Short-Term, Retrospective, Comparative Study.

BACKGROUND he present study was performed to evaluate the clinical efficacy of Tri-Lock bone preservation stems vs conventional Corail stems in primary total hip arthroplasty via direct anterior approach. MATERIAL AND METHODS In this retrospective analysis, patients receiving THA via DAA in a single-center hospital from January 2019 to March 2020 were assessed for eligibility and assigned to either a Tri-Lock BPS group or a Corail group based on the use of prostheses. Outcome measures for the efficiency evaluation of the 2 prostheses included perioperative outcomes, imaging results, Harris Hip Score, Western Ontario and McMaster University Osteoarthritis Index, and visual analog scale scores at 3, 6, 12, and 24 months postoperatively. RESULTS A total of 204 patients were included, including 98 patients (98 hips) in the Tri-Lock BPS group and 106 patients (106 hips) in the Corail group. Patients receiving Tri-Lock BPS exhibited better pain relief than those with Coral stems. Tri-Lock BPS had a higher safety profile vs Corail stems by significantly reducing the risk of complications (P=0.004). A markedly increased HHS score (84.42±16.27 vs 78.61±12.78, P=0.002) and a lower WOMAC score (25.08±15.39 vs 32.14±11.56, P=0.001) at 3 months postoperatively were observed in patients with Tri-Lock BPS vs those with Corail stems, indicating better restoration of hip function using Tri-Lock BPS. CONCLUSIONS During total hip arthroplasty via DAA, Tri-Lock BPS causes a smaller surgical wound, reduces the operative time and intraoperative bleeding, and produces less soft-tissue damage vs Corail stems, providing great benefits in femoral prosthesis placement.

Protective effects of intrathecal injection of AAV9-RabGGTB-GFP+ in SOD1G93A mice.

Introduction: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that widely affects motor neurons of the CNS. About 20% of patients with ALS have familial ALS (fALS). One of the classic models of ALS are SOD1G93A mice. Misfolded SOD1 protein can be overexpressed in motor neurons, which results in progressive paralysis of the limbs of mice. There is still no effective treatment for ALS. In recent years, the treatment of ALS by regulating autophagy has become a research hotspot. Autophagy obstacles have been confirmed to be one of the early pathological events of ALS. Rab7 is a member of the Ras superfamily and plays a key role in the late stage of autophagy. In our previous studies, we found that prenoylation of Rab7 was inhibited in the ALS model. Prenylation is a post-translational modification in which farnesyl or geranylgeranyl groups are covalently linked to target proteins. Based on these findings, we proposed the novel idea that the regulation of RabGGTB (the ß-subunit of RabGGTase) mediated prenylation modification of Rab7, and that this can be used as a prevention and treatment of ALS associated with abnormal protein accumulation. Methods: In the present study, RabGGTB was overexpressed in mouse spinal cord motoneurons by using adeno-associated virus as vector. Then immunofluorescence quantitative analysis was used for pathological study. The body weight, footprint analysis, the accelerating rotarod test, and neurological deficits score were used to evaluate animal behavior. Results: Our results show that the protein level of RabGGTB was significantly increased in the lumbar and thoracic regions of spinal cord motoneurons of injected mice. Furthermore, the onset time and survival time of SOD1G93A mice injected with AAV9-RabGGTB-GFP+ were delayed compared with those of mice without overexpression. At the same time, we also observed a decrease in SOD1 misfolded and glial overactivation in the lumbar spinal cord of these SOD1G93A mice. Conclusion: The findings reported here show that RabGGTB plays a significant role in the pathogenesis of SOD1G93A mice and with great therapeutic potential for reducing abnormal aggregation of SOD1 in ALS.

The indications for core decompression surgery in patients with ARCO stage I-II osteonecrosis of the femoral head: a new, comprehensive prediction system.

BACKGROUND: Core decompression (CD) is considered the most popular treatment method for patients with Association Research Circulation Osseous (ARCO) stage I-II osteonecrosis of the femoral head (ONFH). However, the definitive indication for CD is currently not well established. METHODS: This was a retrospective cohort study. Patients who were diagnosed with ARCO stage I-II ONFH and who underwent CD were included. According to the prognosis, the patients were divided into two groups: collapse of the femoral head after CD and noncollapse of the femoral head. Independent risk factors for the failure of CD treatment were identified. Subsequently, a new scoring system that included all these risk factors was built to help estimate the individual risk of CD failure in patients who were planning to undergo CD. RESULTS: The study included 1537 hips after decompression surgery. The overall failure rate of CD surgery was 52.44%. Seven independent prognostic factors for failed CD surgery were identified, such as male sex (HR = 75.449; 95% confidence interval (CI), 42.863-132.807), Aetiology (Idiopathic HR = 2.762; 95% CI, 2.016-3.788, Steroid-induced HR = 2.543; 95% CI, 1.852-3.685), if the patient had a seated occupation (HR = 3.937; 95% CI, 2.712-5.716), age (HR = 1.045; 95% CI, 1.032-1.058), haemoglobin level (HR = 0.909; 95% CI, 0.897-0.922), disease duration (HR = 1.217; 95% CI, 1.169-1.267) and the combined necrosis angle (HR = 1.025; 95% CI, 1.022-1.028). The final scoring system included these seven risk factors, and the area under the curve of this scoring system was 0.935 (95% confidential interval = 0.922-0.948). CONCLUSION: This new scoring system might provide evidence-based medical proof for determining whether a patient with ARCO stage I - II ONFH might benefit from CD surgery. This scoring system is crucial for making clinical decisions. Consequently, this scoring system is recommended before CD surgery, which could help determine the potential prognosis of patients.

Risk factors affecting the incidence of postoperative periprosthetic femoral fracture in primary hip arthroplasty patients: a retrospective study.

The purpose of this study was to identify the characteristics and risk factors for postoperative periprosthetic femoral fracture (PFF). This was a retrospective cohort study of 108 patients with and 432 control patients without postoperative PFF. Demographic characteristics, surgery-related information (primary hip disease diagnosed, fixation, femoral stem, method of operation, and bone resorption of the proximal femur), and postoperative patient outcomes (hip function, treatment history, and patients' lifestyle behaviors) were recorded and compared between the groups. PFF characteristics, such as the classification, time, and cause, were also documented, and a Cox regression model was built to identify the independent risk factors for postoperative PFF in these patients. Six independent risk factors for postoperative PFF were identified, namely, advanced age (hazard ratio (HR) = 1.026, 95% confidence interval (CI) = 1.007-1.045), femoral neck fracture as the primary disease (HR = 4.536, 95% CI = 2.955-6.961), osteoporosis (HR = 2.043, 95% CI = 1.234-3.383), hemiarthroplasty (or HA, HR = 2.173, 95% CI = 1.327-3.558), bone resorption of the proximal femur (HR = 1.627, 95% CI = 1.090-2.430), and a standard- or long-stem femoral prosthesis (HR = 2.996, 95% CI = 1.480-6.067). The predictive values for a low risk (estimated incidence ≤ 50%), moderate risk (estimated incidence 51%-89%), and high risk (estimated incidence ≥ 90%) of PFF were ≤ 3.0 points, 3.0-10.0 points, and ≥ 10.0 points, respectively. Most patients with postoperative PFF had Vancouver type B fractures. Six independent risk factors for postoperative PFF were identified: advanced age, hip fracture as the primary disease, osteoporosis, HA, bone resorption of the proximal femur, and a long femoral stem.

The diagnostic value of blood metagenomic next-generation sequencing in patients with acute hematogenous osteomyelitis.

Aims: This study aims to evaluate the diagnostic value of blood metagenomic next-generation sequencing (mNGS) in detecting pathogens from patients clinically diagnosed as acute hematogenous osteomyelitis (AHO). Methods: This retrospective study enrolled 66 patients with AHO. The test results of mNGS and bacterial culture on different samples, including blood and puncture fluid samples, from patients with AHO were compared to explore the diagnostic value of blood mNGS. Besides, this study also explored the efficacy of blood mNGS in decision making for antibiotic administration and analyzed the factors associated with the positive result of blood mNGS. Results: The most common causative pathogens were Staphylococcus and Streptococcus. The sensitivity of blood mNGS (77.3%) was higher than that of blood culture (42.4%) (P<0.001), while the turnaround time of blood mNGS (2.1 ± 0.4 d) is much less than that of blood culture (6.0 ± 2.1 d) (P<0.001). Besides, the sensitivity of blood mNGS tests (77.3%) was slightly lower than that of puncture fluid mNGS (89.4%). Furthermore, detection comparison at pathogen level unravels that blood mNGS might be suitable for diagnosing AHO caused by common pathogens, while puncture fluid mNGS could be considered as preferred examination in diagnosing AHO caused by uncommon pathogens. Finally, three independent factors associated with the true positive result of blood mNGS in patients with AHO were identified, including Gram-positive pathogens (OR=24.4, 95% CI = 1.4-421.0 for Staphylococcus; OR=14.9, 95%CI= 1.6-136.1 for other Gram-positive bacteria), body temperature at sampling time (OR=8.2, 95% CI = 0.6-107.3 for body temperature of >38.5°C; OR=17.2, 95% CI = 2.0-149.1 for patients who were chilling), and no use of antibiotics before sampling (OR=8.9, 95% CI =1.4-59.0). Conclusion: This is the first report on evaluating and emphasizing the importance of blood mNGS in diagnosing AHO. Blood sample might be an alternative sample for puncture fluid for mNGS, and its extensive application in diagnosing AHO could be expected.

Creeping and erupting dynamics in a pure-quartic soliton fiber laser.

Pure-quartic solitons (PQSs) are gradually becoming a hotspot in recent years due to their potential advantage to achieve high energy. Meanwhile, the fundamental research of PQSs is still in the fancy stage, and exploring soliton dynamics can promote the development of PQSs. Herein, we comprehensively and numerically investigate the impact of saturation power, small-signal gain, and output coupler on PQS dynamics in passively mode-locked fiber lasers. The result indicates that altering the above parameters makes PQSs exhibit pulsating or creeping dynamics similar to traditional solitons. Moreover, introducing an intra-cavity filter combined with intra-cavity large fourth-order dispersion makes PQSs go through stationary, pulsating to erupting. That is, the intra-cavity filter changes PQS dynamics. These findings provide new insights into PQS dynamics in fiber lasers.

Influence of Inlet Boundary Conditions on the Prediction of Flow Field and Hemolysis in Blood Pumps Using Large-Eddy Simulation.

Inlet boundary conditions (BC) are one of the uncertainties which may influence the prediction of flow field and hemolysis in blood pumps. This study investigated the influence of inlet BC, including the length of inlet pipe, type of inlet BC (mass flow rate or experimental velocity profile) and turbulent intensity (no perturbation, 5%, 10%, 20%) on the prediction of flow field and hemolysis of a benchmark centrifugal blood pump (the FDA blood pump) and a commercial axial blood pump (Heartmate II), using large-eddy simulation. The results show that the influence of boundary conditions on integral pump performance metrics, including pressure head and hemolysis, is negligible. The influence on local flow structures, such as velocity distributions, mainly existed in the inlet. For the centrifugal FDA blood pump, the influence of type of inlet BC and inlet position on velocity distributions can also be observed at the diffuser. Overall, the effects of position of inlet and type of inlet BC need to be considered if local flow structures are the focus, while the influence of turbulent intensity is negligible and need not be accounted for during numerical simulations of blood pumps.