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Background: Opening wedge high tibial osteotomy (OWHTO) is an effective surgical treatment for knee osteoarthritis. This study aimed to explore the feasibility and accuracy of a novel 3D-printed patient-specific instrument (PSI) based on "H-point" for medial OWHTO in a prospective cadaver study. Methods: Twenty-six fresh-frozen lower limbs were collected and randomly divided into two groups: PSI group treated with 3D virtual preoperative planning and a novel 3D-printed PSI; control group with the standard technique. 3D models were reversely reconstructed for preoperative surgical planning, guide plate design, and simulated osteotomy. Anatomic features of "H-point," surgical time, fluoroscopic dose, correction accuracy including tibiofemoral angle (FTA) and posterior tibial slope (TS) angle were measured. Results: First, H-point was always described as a bony bulge in the posteromedial to the proximal tibia and had a relatively constant relationship with the osteotomy site. Second, the absolute correction error of mFTA and TS were significantly smaller in the PSI group. The effective rate of TS in the PSI group was more concentrated with absolute correction error within 1° and within 2° for 53.3% and 93.3%, compared to 9.1% and 45.5% in the control group. The total operation time, positioning osteotomy time, distraction correction time and fluoroscopy dose in the PSI group were significantly less than those in the control group. Conclusions: The novel 3D-printed PSI based on H-point is feasibility and accuracy with advantages in terms of TS, surgery time and radiation dose for OWHTO. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) is a neurodegenerative disease characterized by a progressive decline in cognitive ability. Exosomes derived from bone-marrow mesenchymal stem cells (BMSC-exos) are extracellular vesicles that can execute the function of bone-marrow mesenchymal stem cells (BMSCs). Given the versatile therapeutic potential of BMSC and BMSC-exos, especially their neuroprotective effect, the aim of this study was to investigate the potential effect of BMSC-exos on AD-like behavioral dysfunction in mice and explore the possible molecular mechanism.Methods: BMSC-exos were extracted from the supernatant of cultured mouse BMSCs, which were isolated from the femur and tibia of adult C57BL/6 mice, purified and sorted via flow cytometry, and cultured in vitro. BMSC-exos were identified via transmission electron microscopy, and typical marker proteins of exosomes were also detected via Western blot. A sporadic AD mouse model was established by intracerebroventricular injection of streptozotocin (STZ). Six weeks later, BMSC-exos were administered via lateral ventricle injection or caudal vein injection lasting five consecutive days, and the control mice were intracerebroventricularly administered an equal volume of solvent. Behavioral performance was observed via the open field test (OFT), elevated plus maze test (EPM), novel object recognition test (NOR), Y maze test (Y-maze), and tail suspension test (TST). The mRNA and protein expression levels of IL-1β, IL-6, and TNF-α in the hippocampus were measured via quantitative polymerase chain reaction (qPCR) and Western blot, respectively. Moreover, the protein expression of Aβ1-42, BACE, IL-1β, IL-6, TNF-α, GFAP, p-Tau (Ser396), Tau5, synaptotagmin-1 (Syt-1), synapsin-1, and brain-derived neurotrophic factor (BDNF) in the hippocampus was detected using Western blot, and the expression of GFAP, IBA1, Aβ1-42 and DCX in the hippocampus was measured via immunofluorescence staining.Results: Lateral ventricle administration, but not caudal vein injection of BMSC-exos improved AD-like behaviors in the STZ-injected mouse model, as indicated by the increased number of rearing, increased frequency to the central area, and increased duration and distance traveled in the central area in the OFT, and improved preference index of the novel object in the NOR. Moreover, the hyperactivation of microglia and astrocytes in the hippocampus of the model mice was inhibited after treatment with BMSC-exos via lateral ventricle administration, accompanied by the reduced expression of IL-1β, IL-6, TNF-α, Aβ1-42, and p-Tau and upregulated protein expression of synapse-related proteins and BDNF. Furthermore, the results of the Pearson test showed that the preference index of the novel object in the NOR was positively correlated with the hippocampal expression of BDNF, but negatively correlated with the expression of GFAP, IBA1, and IL-1β. Apart from a positive correlation between the hippocampal expression of BDNF and Syt-1, BDNF abundance was found to be negatively correlated with markers of glial activation and the expression of the inflammatory cytokines, Aβ1-42, and p-Tau, which are characteristic neuropathological features of AD.Conclusions: Lateral ventricle administration, but not caudal vein injection of BMSC-exos, can improve AD-like behavioral performance in STZ-injected mice, the mechanism of which might be involved in the regulation of glial activation and its associated neuroinflammation and BDNF-related neuropathological changes in the hippocampus. [ABSTRACT FROM AUTHOR]

Background: Patients who underwent knee joint arthroplasty were at risk of venous thromboembolic events (VTEs), however, less studies were conducted to demonstrate the epidemiology and risk factors of deep venous thrombosis (DVT) following unicompartmental knee arthroplasty (UKA). Objective of this study was to explore the incidence and prognostic factors of DVT after UKA. Methods: Patients who underwent primary UKA from December 2018 to June 2022 were recruited in this study. Demographic characteristics, operation related variables and laboratory index were extracted and analyzed. Receiver operating characteristic analysis was performed to detect the optimum cut-off value for variables of interest. Univariate and multivariate logistic analysis were performed to identify risk factors of DVT. Results: 351 UKAs with a mean age of 65.4 ± 7.1 years were reviewed. After 12.9 ± 11.2 months follow-up, 35 DVTs were confirmed which indicating an incidence of 9.9%. The results showed that occupation (agricultural laborer) (P = 0.008), disease duration > 8.5 years (P = 0.035), operation time > 169 min (P = 0.003), intraoperative blood loss > 102 ml (P < 0.001), BMI > 26.8 kg/m 2 (P = 0.001), preoperative D-dimer > 0.29 mg/L (P = 0.001), prothrombin time < 10.7 s (P = 0.033) and INR < 0.98 (P = 0.032) between DVT and Non-DVT group were significantly different. Multivariate logistic regression analysis showed intraoperative blood loss > 102 ml (OR, 3.707; P, 0.001), BMI > 26.8 kg/m 2 (OR, 4.664; P, 0.004) and D-dimer > 0.29 mg/L (OR, 2.882; P, 0.009) were independent risk factors of DVT after UKA. Conclusion: The incidence of DVT in the present study was 9.9%, extensive intraoperative blood loss, advanced BMI and high level of D-dimer would increase the risk of lower extremity thrombosis by 2–4 times. [ABSTRACT FROM AUTHOR]

Background: Chikungunya virus (CHIKV) has reemerged as a major public health concern, causing chikungunya fever with increasing cases and neurological complications. Methods: In the present study, we investigated a low-passage human isolate of the East/ Central/South African (ECSA) lineage of CHIKV strain LK(EH)CH6708, which exhibited a mix of small and large viral plaques. The small and large plaque variants were isolated and designated as CHIKV-SP and CHIKV-BP, respectively. CHIKV-SP and CHIKV-BP were characterized in vitro and in vivo to compare their virus production and virulence. Additionally, whole viral genome analysis and reverse genetics were employed to identify genomic virulence factors. Results: CHIKV-SP demonstrated lower virus production in mammalian cells and attenuated virulence in a murine model. On the other hand, CHIKV-BP induced higher pro-inflammatory cytokine levels, compromised the integrity of the blood–brain barrier, and led to astrocyte infection in mouse brains. Furthermore, the CHIKV-SP variant had limited transmission potential in Aedesalbopictus mosquitoes, likely due to restricted dissemination. Whole viral genome analysis revealed multiple genetic mutations in the CHIKV-SP variant, including a Glycine (G) to Arginine (R) mutation at position 55 in the viral E2 glycoprotein. Reverse genetics experiments confirmed that the E2-G55R mutation alone was sufficient to reduce virus production in vitro and virulence in mice. Conclusions: These findings highlight the attenuating effects of the E2-G55R mutation on CHIKV pathogenicity and neurovirulence and emphasize the importance of monitoring this mutation in natural infections. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to investigate the effect factors associated with the postoperative dissatisfaction of patients undergoing open-door laminoplasty for cervical OPLL. Methods: In this study, 194 patients, who underwent open-door laminoplasty for cervical OPLL from January 2009 to January 2016, were retrospectively reviewed. The Patient Satisfaction Index (PSI) was collected at discharge, 6 months, 1 year, and the last follow-up. According to the PSI, patients were divided into satisfied group and dissatisfied group. The possible effect factors included demographic variables and surgery-related variables. Results: At discharge, 42 (21.6%) patients were in the dissatisfied group, as compared to the satisfied group, the hospitalization cost, hospital stay, postoperative depression, the axial neck pain, delayed wound healing, and VAS-neck had significant statistical differences. At 6-month follow-up, 25 (12.9%) patients were in the dissatisfied group. The axial neck pain and JOA score had significant statistical differences between the two groups, and no significant differences were found between the two groups in other items. At 1 year with 18 (9.3%) dissatisfied patients and last follow-up with 14 (7.2%) dissatisfied patients, the JOA score and symptom recurrence had significant statistical differences. For further analysis, the dissatisfied patients with axial neck pain at 6 months were significantly higher than that at other terms and the JOA score of the two groups increased gradually with prolonging of restoration years but compared with the dissatisfied group, the JOA scores were obviously better in the satisfied group at the last follow-up. Conclusions: Overall, to patients undergoing open-door laminoplasty for cervical OPLL, hospitalization cost and neck pain might be mainly associated with patient dissatisfaction at the early and middle recovery. Patient dissatisfaction at the long-term treatment outcome might be mainly associated with the low improvement rate of JOA score and symptom recurrence. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to explore the prevalence and risk factors for axial neck pain in patients undergoing multilevel anterior cervical decompression with fusion surgery. Methods: In this study, 88 patients, who underwent multilevel anterior cervical decompression with fusion surgery from January 2012 to January 2017, were retrospectively reviewed. Based on the postoperative axial neck pain, the patients were classified into two groups: axial pain group and no axial pain group. The patients were followed up 3 weeks, 3 months, and 1 year after cervical anterior surgery for the early- and long-term clinical evaluation. The possible effect factors included demographic variables (age, sex, BMI, smoking, drinking, heart disease, hypertension, diabetes, preoperative kyphosis, preoperative axial neck pain, preoperative JOA scores, and ODI) and surgery-related variables (surgical option, vertebral lesions, spinal canal stenosis rate, superior fusion segment, presence of intramedullary high signal intensity). Results: The prevalence of axial neck pain was 27.3% (24 cases of 88). Our results showed that preoperative axial neck pain (62% vs 23%, P < 0.001) and preoperative kyphosis (42% vs 21.9%, P < 0.001) were risk factors for axial pain after multilevel anterior cervical surgery. Additionally, for patients with preoperative cervical kyphosis, compared to no axial pain group, the axial neck group was significantly more likely to exist a higher preoperative angle of C2–7 (13.31 ± 2.33 vs 7.33 ± 2.56, P < 0.001) and a higher correction range for kyphosis (20.24 ± 4.12 vs 12.34 ± 3.12, P < 0.001). However, for all the patients with postoperative axial symptoms, the improvement rate of axial pain was significantly higher for patients without cervical kyphosis at the early-term follow-up (3 weeks) (P = 0.032), no significant differences were found at the medium-term (P = 0.554) and long-term follow-up (P = 0.902), and improvements of clinical symptom have no obvious difference at the last follow-up. Conclusions: Overall, preoperative axial neck pain and kyphosis could predict axial neck pain for patients undergoing multilevel anterior cervical decompression with fusion surgery, and recovery of cervical kyphosis may contribute to the long-term recovery of neural function, but may also suffer from risk of short-term axial pain, which could be reduced through moderate cervical curvature recovery. [ABSTRACT FROM AUTHOR]

Background: The long chain non-coding RNA HOXA11-OS was recently identified. Increasing studies have shown that HOXA11-OS has regulatory effects on genes in gastric cancer, prostate cancer, and various kidney diseases, but research on its role in systemic lupus erythematosus is still lacking. The present study aimed to investigate the role of HOXA11-OS in the regulation of podocyte autophagy in the development of lupus nephritis (LN) and its potential molecular mechanism. Methods: mRNA and protein expression of the target gene (i.e., Cyr61) was detected by quantitative real-time polymerase chain reaction, western blotting, and immunofluorescence. Mouse podocytes were induced using serum immunoglobulin G (IgG) from patients with lupus and their viability was detected using the cell counting kit-8 assay. The interaction of miR-124-3p with HOXA11-OS and Cyr61 was analyzed by double luciferase reporter gene assay. Serum autoantibody levels were detected by enzyme-linked immunosorbent assay. Pathological lesions in the kidney tissue were detected by hematoxylin–eosin and periodate-Schiff staining. The independent samples t-test was used for comparing two groups, and one-way analysis of variance for comparing multiple groups. Results: HOXA11-OS was highly expressed in LN tissues, serum, and cells, and the expression of some key autophagy factors and Cyr61 was significantly increased, while miR-124-3p expression was significantly decreased. In vitro, LN-IgG inhibited podocyte activity, increased autophagy and Cyr61 expression, and aggravated podocyte injury in a time- and dose-dependent manner. As a competitive endogenous RNA of miR-124-3p, HOXA11-OS promoted the expression of Cyr61, thus enhancing the autophagy increase induced by LN-IgG and aggravating podocyte injury. Knockdown of HOXA11-OS had the opposite effect. miR-124-3p mimic or Cyr61 knockdown restored the high expression of autophagy factors and Cyr61 induced by HOXA11-OS overexpression and alleviated podocyte injury. Further in vivo experiments showed that injection of sh-HOXA11-OS adeno-associated virus downregulated HOXA11-OS and significantly alleviated renal damage in lupus mice. Conclusions: HOXA11-OS is involved in the occurrence and development of LN by regulating podocyte autophagy through miR-124-3p/Cyr61 sponging, which may provide a good potential therapeutic target for LN. [ABSTRACT FROM AUTHOR]

Background: Lung cancer is a kind of malignancy with high morbidity and mortality worldwide. Paclitaxel (PTX) is the main treatment for non-small cell lung cancer (NSCLC), and resistance to PTX seriously affects the survival of patients. However, the underlying mechanism and potential reversing strategy need to be further explored. Methods: We identified ALDH2 as a PTX resistance-related gene using gene microarray analysis. Subsequently, a series of functional analysis in cell lines, patient samples and xenograft models were performed to explore the functional role, clinical significance and the aberrant regulation mechanism of ALDH2 in PTX resistance of NSCLC. Furthermore, the pharmacological agents targeting ALDH2 and epigenetic enzyme were used to investigate the diverse reversing strategy against PTX resistance. Results: Upregulation of ALDH2 expression is highly associated with resistance to PTX using in vitro and in vivo analyses of NSCLC cells along with clinicopathological analyses of NSCLC patients. ALDH2-overexpressing NSCLC cells exhibited significantly reduced PTX sensitivity and increased biological characteristics of malignancy in vitro and tumor growth and metastasis in vivo. EHMT2 (euchromatic histone lysine methyltransferase 2) inhibition and NFYA (nuclear transcription factor Y subunit alpha) overexpression had a cooperative effect on the regulation of ALDH2. Mechanistically, ALDH2 overexpression activated the RAS/RAF oncogenic pathway. NSCLC/PTX cells re-acquired sensitivity to PTX in vivo and in vitro when ALDH2 was inhibited by pharmacological agents, including the ALDH2 inhibitors Daidzin (DZN)/Disulfiram (DSF) and JIB04, which reverses the effect of EHMT2. Conclusion: Our findings suggest that ALDH2 status can help predict patient response to PTX therapy and ALDH2 inhibition may be a promising strategy to overcome PTX resistance in the clinic. [ABSTRACT FROM AUTHOR]

Introduction: Adult non-degenerative scoliosis accounts for 90% of spinal deformities in young adults. However, perioperative complications and related risk factors of long posterior instrumentation and fusion for the treatment of adult non-degenerative scoliosis have not been adequately studied.Methods: We evaluated clinical and radiographical results from 146 patients with adult non-degenerative scoliosis who underwent long posterior instrumentation and fusion. Preoperative clinical data, intraoperative variables, and perioperative radiographic parameters were collected to analyze the risk factors for perioperative complications. Potential and independent risk factors for perioperative complications were evaluated by univariate analysis and logistic regression analysis.Results: One hundred forty-six adult non-degenerative scoliosis patients were included in our study. There were 23 perioperative complications for 21 (14.4%) patients, eight of which were cardiopulmonary complications, two of which were infection, six of which were neurological complications, three of which were gastrointestinal complications, and four of which were incision-related complication. The independent risk factors for development of total perioperative complications included change in Cobb angle (odds ratio [OR] = 1.085, 95% CI = 1.035 ~ 1.137, P = 0.001) and spinal osteotomy (OR = 3.565, 95% CI = 1.039 ~ 12.236, P = 0.043). The independent risk factor for minor perioperative complications is change in Cobb angle (OR = 1.092, 95% CI = 1.023 ~ 1.165, P = 0.008). The independent risk factors for major perioperative complications are spinal osteotomy (OR = 4.475, 95% CI = 1.960 ~ 20.861, P = 0.036) and change in Cobb angle (OR = 1.106, 95% CI = 1.035 ~ 1.182, P = 0.003).Conclusions: Our study indicate that change in Cobb angle and spinal osteotomy are independent risk factors for total perioperative complications after long-segment posterior instrumentation and fusion in adult non-degenerative scoliosis patients. Change in Cobb angle is an independent risk factor for minor perioperative complications. Change in Cobb angle and spinal osteotomy are independent risk factors for major perioperative complications. [ABSTRACT FROM AUTHOR]

Background: Adrenal vein sampling (AVS) is the preferred method for subtyping patients with primary aldosteronism, while the procedure is technically challenging. This study evaluated the feasibility and effectiveness of a single-catheter approach for AVS. Methods: A retrospective analysis of 106 consecutive patients who underwent AVS was performed to determine the procedural success and complication rates. Bilateral AVS procedures were performed using a single 5-Fr Tiger catheter with repeated manual reshaping. Results: We successfully advanced the catheter into the bilateral adrenal veins of all patients and reached a 90.6% procedural success rate of AVS. The procedural period was 33.0 ± 8.2 min, the fluoroscopy period was 5.8 ± 1.7 min, and the diagnostic contrast used was 17.3 ± 5.5 ml. Only one patient (0.9%) had a hematoma at the femoral puncture site. No other complications were observed. The operation period gradually shortened as the cumulative number of operations increased. The number of procedures required to overcome the learning curve was about 33 cases. Conclusions: The single-catheter approach is feasible and effective for AVS. Moreover, this approach required a relatively short learning curve for an inexperienced trainee. [ABSTRACT FROM AUTHOR]

Background: Influenza is an infectious respiratory disease that can cause serious public health hazard. Due to its huge threat to the society, precise real-time forecasting of influenza outbreaks is of great value to our public. Results: In this paper, we propose a new deep neural network structure that forecasts a real-time influenza-like illness rate (ILI%) in Guangzhou, China. Long short-term memory (LSTM) neural networks is applied to precisely forecast accurateness due to the long-term attribute and diversity of influenza epidemic data. We devise a multi-channel LSTM neural network that can draw multiple information from different types of inputs. We also add attention mechanism to improve forecasting accuracy. By using this structure, we are able to deal with relationships between multiple inputs more appropriately. Our model fully consider the information in the data set, targetedly solving practical problems of the Guangzhou influenza epidemic forecasting. Conclusion: We assess the performance of our model by comparing it with different neural network structures and other state-of-the-art methods. The experimental results indicate that our model has strong competitiveness and can provide effective real-time influenza epidemic forecasting. [ABSTRACT FROM AUTHOR]

Background: Collective cell migration is a significant and complex phenomenon that affects many basic biological processes. The coordination between leader cell and follower cell affects the rate of collective cell migration. However, there are still very few papers on the impacts of the stimulus signal released by the leader on the follower. Tracking cell movement using 3D time-lapse microscopy images provides an unprecedented opportunity to systematically study and analyze collective cell migration. Results: Recently, deep reinforcement learning algorithms have become very popular. In our paper, we also use this method to train the number of cells and control signals. By experimenting with single-follower cell and multi-follower cells, it is concluded that the number of stimulation signals is proportional to the rate of collective movement of the cells. Such research provides a more diverse approach and approach to studying biological problems. Conclusion: Traditional research methods are always based on real-life scenarios, but as the number of cells grows exponentially, the research process is too time consuming. Agent-based modeling is a robust framework that approximates cells to isotropic, elastic, and sticky objects. In this paper, an agent-based modeling framework is used to establish a simulation platform for simulating collective cell migration. The goal of the platform is to build a biomimetic environment to demonstrate the importance of stimuli between the leading and following cells. [ABSTRACT FROM AUTHOR]

Background: Although the sensory drive hypothesis can explain the geographic variation in echolocation frequencies of some bat species, the molecular mechanisms underlying this phenomenon are still unclear. The three lineages of greater horseshoe bat (Rhinolophus ferrumequinum) in China (northeast, central-east, and southwest) have significant geographic variation in resting frequencies (RF) of echolocation calls. Because their cochleae have an acoustic fovea that is highly sensitive to a narrow range of frequencies, we reported the transcriptomes of cochleae collected from three genetic lineages of R. ferrumequinum, which is an ideal organism for studying geographic variation in echolocation signals, and tried to understand the mechanisms behind this bat phenomenon by analyzing gene expression and sequence variation. Results: A total of 8190 differentially expressed genes (DEGs) were identified. We identified five modules from all DEGs that were significantly related to RF or forearm length (FL). DEGs in the RF-related modules were significantly enriched in the gene categories involved in neural activity, learning, and response to sound. DEGs in the FL-related modules were significantly enriched in the pathways related to muscle and actin functions. Using 21,945 single nucleotide polymorphisms, we identified 18 candidate unigenes associated with hearing, five of which were differentially expressed among the three populations. Additionally, the gene ERBB4, which regulates diverse cellular processes in the inner ear such as cell proliferation and differentiation, was in the largest module. We also found 49 unigenes that were under positive selection from 4105 one-to-one orthologous gene pairs between the three R. ferrumequinum lineages and three other Chiroptera species. Conclusions: The variability of gene expression and sequence divergence at the molecular level might provide evidence that can help elucidate the genetic basis of geographic variation in echolocation signals of greater horseshoe bats. [ABSTRACT FROM AUTHOR]