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Background: Stroke frequently results in upper limb motor dysfunction, with traditional therapies often failing to yield sufficient improvements. Emerging technologies such as virtual reality (VR) and noninvasive brain stimulation (NIBS) present promising new rehabilitation possibilities., Objectives: This study systematically reviews and meta-analyses the effectiveness of VR and NIBS in improving upper limb motor function in stroke patients., Methods: Registered with PROSPERO (CRD42023494220) and adhering to the PRISMA guidelines, this study conducted a thorough search of databases including PubMed, MEDLINE, PEDro, REHABDATA, EMBASE, Web of Science, Cochrane, CNKI, Wanfang, and VIP from 2000 to December 1, 2023, to identify relevant studies. The inclusion criterion was stroke patients receiving combined VR and NIBS treatment, while exclusion criteria were studies with incomplete articles and data. The risk of bias was assessed using the Cochrane Collaboration tool. Statistical analysis was performed using Stata SE 15.0, employing either a fixed-effects model or a random-effects model based on the level of heterogeneity., Results: A total of 11 studies involving 493 participants were included, showing a significant improvement in Fugl-Meyer Assessment Upper Extremity (FMA-UE) scores in the combined treatment group compared to the control group (SMD = 0.85, 95% CI [0.40, 1.31], p = 0.017). The Modified Ashworth Scale (MAS) scores significantly decreased (SMD = - 0.51, 95% CI [- 0.83, - 0.20], p = 0.032), the Modified Barthel Index (MBI) scores significantly increased (SMD = 0.97, 95% CI [0.76, 1.17], p = 0.004), and the Wolf Motor Function Test (WMFT) scores also significantly increased (SMD = 0.36, 95% CI [0.08, 0.64], p = 0.021). Subgroup analysis indicated that the duration of treatment influenced the outcomes in daily living activities., Conclusions: The combination of VR and NIBS demonstrates significant improvements in upper limb motor function in stroke patients. The duration of treatment plays a critical role in influencing the outcomes, particularly in activities of daily living. This systematic review has limitations, including language bias, unclear randomization descriptions, potential study omissions, and insufficient follow-up periods. Future studies should focus on exploring long-term effects and optimizing treatment duration to maximize the benefits of combined VR and NIBS therapy., (© 2024. The Author(s).)

A transition metal coordination polymer (CP), [Cd(Hdpcp)] n (Cd-CP) was prepared based on 3-(2,4-dicarboxyphenyl)-6-carboxypyridine ligand (H 3 dpcp), and then its composite Eu@Cd-CP was synthesized by the post-modification through loading Eu 3+ ions on Cd-CP. Eu@Cd-CP has outstanding fluorescence stability in aqueous solution with a wide range of pH. Furthermore, Eu@Cd-CP can distinguish sodium salicylate (SS) and sodium dehydroacetate (SA) in some food additives by quenching the characteristic fluorescence of Eu 3+ ion. Eu@Cd-CP is the first known CP-based fluorescent probe for selective detection of SS and SA. In addition, the fluorescence mechanisms of discerning above analytes by Eu@Cd-CP have been thoroughly evaluated. It has found that synergistic effect of the dynamic process, photoinduced electron transfer (PET) process, energy absorption competition, and formation of Eu-O bonding interactions in sensing SA lead to the fluorescence quenching of Eu@Cd-CP. The fluorescence response mechanism of Eu@Cd-CP with SA is ascribed to the combination of the dynamic process, PET process, and energy absorption competition. A series of portable devices based on Eu@Cd-CP including fluorescence test strips, lamp beads, and composite films were developed to discern SS and SA via visual changes in luminescence color. This composite material can be potentially used as a multifunctional fluorescent probe for practical applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Solid tumours often endure nutrient insufficiency during progression. How tumour cells adapt to temporal and spatial nutrient insufficiency remains unclear. We previously identified STC2 as one of the most upregulated genes in cells exposed to nutrient insufficiency by transcriptome screening, indicating the potential of STC2 in cellular adaptation to nutrient insufficiency. However, the molecular mechanisms underlying STC2 induction by nutrient insufficiency and subsequent adaptation remain elusive. Here, we report that STC2 protein is dramatically increased and secreted into the culture media by Gln-/Glc- deprivation. STC2 promoter contains cis-elements that are activated by ATF4 and p65/RelA, two transcription factors activated by a variety of cellular stress. Biologically, STC2 induction and secretion promote cell survival but attenuate cell proliferation during nutrient insufficiency, thus switching the priority of cancer cells from proliferation to survival. Loss of STC2 impairs tumour growth by inducing both apoptosis and necrosis in mouse xenografts. Mechanistically, under nutrient insufficient conditions, cells have increased levels of reactive oxygen species (ROS), and lack of STC2 further elevates ROS levels that lead to increased apoptosis. RNA-Seq analyses reveal STC2 induction suppresses the expression of monoamine oxidase B (MAOB), a mitochondrial membrane enzyme that produces ROS. Moreover, a negative correlation between STC2 and MAOB levels is also identified in human tumour samples. Importantly, the administration of recombinant STC2 to the culture media effectively suppresses MAOB expression as well as apoptosis, suggesting STC2 functions in an autocrine/paracrine manner. Taken together, our findings indicate that nutrient insufficiency induces STC2 expression, which in turn governs the adaptation of cancer cells to nutrient insufficiency through the maintenance of redox homoeostasis, highlighting the potential of STC2 as a therapeutic target for cancer treatment., (© 2024. The Author(s).)

Background: Parkinson's disease (PD) is a prevalent neurodegenerative disorder that significantly benefits from early diagnosis for effective disease management and intervention. Despite advancements in medical technology, there remains a critical gap in the early and non-invasive detection of PD. Current diagnostic methods are often invasive, expensive, or late in identifying the disease, leading to missed opportunities for early intervention., Objective: The goal of this study is to explore the efficiency and accuracy of combining fNIRS technology with machine learning algorithms in diagnosing early-stage PD patients and to evaluate the feasibility of this approach in clinical practice., Methods: Using an ETG-4000 type near-infrared brain function imaging instrument, data was collected from 120 PD patients and 60 healthy controls. This cross-sectional study employed a multi-channel mode to monitor cerebral blood oxygen changes. The collected data were processed using a general linear model and β values were extracted. Subsequently, four types of machine learning models were developed for analysis: Support vector machine (SVM), K-nearest neighbors (K-NN), random forest (RF), and logistic regression (LR). Additionally, SHapley Additive exPlanations (SHAP) technology was applied to enhance model interpretability., Results: The SVM model demonstrated higher accuracy in differentiating between PD patients and control group (accuracy of 85%, f1 score of 0.85, and an area under the ROC curve of 0.95). SHAP analysis identified the four most contributory channels (CH) as CH01, CH04, CH05, and CH08., Conclusion: The model based on the SVM algorithm exhibited good diagnostic performance in the early detection of PD patients. Future early diagnosis of PD should focus on the Frontopolar Cortex (FPC) region., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Hui, Jiang, Wang, Wang, Li, Fang, Wang, Wang and Qie.)

Background: A large number of literatures show that rhythmic auditory stimulation (RAS) can effectively improve Parkinson's disease (PD) patients' gait speed, frequency and speed. Its application and curative effect on upper limb motor function is relatively few., Objective: By studying the immediate effect of RAS with different rhythms on the prefrontal cortex (PFC) blood oxygen response during upper limb movement in PD patients, this study discusses the potential neurophysiological mechanism of RAS on upper limb movement in PD patients, which is expected to provide guidance for patients with upper limb dysfunction such as Parkinson's disease., Methods: In this study, 31 PD patients with upper limb static tremors were recruited to complete the nail board task on the healthy upper limb under the baseline rhythm, slow rhythm and fast rhythm provided by the therapist. At the same time, fNIRS was used to observe the blood oxygen response of PFC., Results: There was no significant main effect onsidein all brain regions ( p  > 0.05), and there was no interaction between rhythm and side ( p  > 0.05); Except lPFC, the main effect of rhythm in other brain regions was significant ( p  < 0.05), and ΔHbO increased with the change of rhythm. Paired analysis showed that there were significant differences in ΔHbO between slow rhythm and baseline rhythm, between fast rhythm and baseline rhythm, and between slow rhythm and fast rhythm ( p  < 0.05); The ΔHbO of rPFC, lDLPFC and rDLPFC were significantly different between slow rhythm and fast rhythm ( p  < 0.05); there were significant differences in the ΔHbO of BA8 between slow rhythm and baseline rhythm, and between slow rhythm and fast rhythm ( p  < 0.05)., Conclusion: RAS may be a useful upper limb rehabilitation strategy for PD patients with upper limb dysfunction. At the same time, RAS with different rhythms also have different responses to PFC blood oxygen during upper limb movement in PD patients, so that we can design interventions for this kind of cortical mechanism. Identifying the neurophysiological mechanism of RAS on upper limb movement in PD patients may help clinicians customize rehabilitation methods for patients according to clues, so as to highly personalize upper limb training and optimize its effect., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Li, Wang, Wang, Qie, Jin and Du.)

African swine fever (ASF) caused by the African swine fever virus (ASFV) is a fatal and highly contagious disease of domestic pigs characterized by rapid disease progression and death within 2 weeks. How the immune cells respond to acute ASFV infection and contribute to the immunopathogenesis of ASFV has not been completely understood. In this study, we examined the activation, apoptosis, and functional changes of distinct immune cells in domestic pigs following acute infection with the ASFV CADC&#95;HN09 strain using multicolor flow cytometry. We found that ASFV infection induced broad apoptosis of DCs, monocytes, neutrophils, and lymphocytes in the peripheral blood of pigs over time. The expression of MHC class II molecule (SLA-DR/DQ) on monocytes and conventional DCs as well as CD21 expression on B cells were downregulated after ASFV infection, implying a potential impairment of antigen presentation and humoral response. Further examination of CD69 and ex vivo expression of IFN-γ on immune cells showed that T cells were transiently activated and expressed IFN-γ as early as 5 days post-infection. However, the capability of T cells to produce cytokines was significantly impaired in the infected pigs when stimulated with mitogen. These results suggest that the adaptive cellular immunity to ASFV might be initiated but later overridden by ASFV-induced immunosuppression. Our study clarified the cell types that were affected by ASFV infection and contributed to lymphopenia, improving our understanding of the immunopathogenesis of ASFV., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Tian, Wang, He, Cao, Li, Jiang, Shi, Hao, Wei, Wang, Qie, Wang, Li, Hao, Zhu, Wu, Shang and Zhai.)

Objectives: The purpose of this study is to evaluate the potential of the flattening filter free (FFF) mode of a linear accelerator for patients with hippocampal avoidance whole-brain radiotherapy (HA-WBRT) by comparison with flattened beams (FF) technique in the application of volumetric modulated arc therapy (VMAT) and intensity modulated radiation therapy (IMRT) using dosimetric and radiobiological indexes based on the volume of hippocampus and target., Methods: 2 VMAT- and 2 IMRT- plans were optimized in Eclipse planning system with 2 different delivery modes (6 MV standard vs. 6 MV FFF) for each of 25 patients. Dose distributions of the target and organs at risk (OARs), normal tissue complication probability (NTCP) of the hippocampus, monitor units, treatment time and quality assurance results were evaluated to compare the normal and FFF beam characteristics by Wilcoxon matched-pair signed-rank test with a significance level of 0.05., Results: VMAT-FFF provided the significantly best homogeneity and conformity of the target, delivered the lowest dose to hippocampus and the other OARs, and led to the lowest NTCP of the hippocampus among all modalities, which has the potential to alleviate neurocognitive decline after WBRT. IMRT-FFF reduced the dose to the lens with similar dose distributions of the target compared with IMRT-FF, whereas the lower dose to the hippocampus was achieved using the conventional beams. The monitor units were obviously increased by 19.2% for VMAT and 33.8% for IMRT, when FFF beams w ere used. The removal of flattening filter for IMRT resulted in a 26% reduction in treatment time, but VMAT had the similar treatment time for the two modes owing to the limitation of gantry rotation speed. Gamma analysis showed an excellent agreement for all plans at 3%/2 mm, and no statistical differences were found between FF and FFF., Conclusion: In conclusion, this study suggests that FFF mode is feasible and advantageous in HA-WBRT and VMAT-FFF is the optimal solution in terms of dose distribution of the target, OARs sparing, NTCP of the hippocampus and delivery efficiency compared to the other three techniques. Additionally, the advantages of the FFF technique for VMAT are more prominent in cases with small hippocampal volumes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Liu, Peng, Li, Zhang, Shi, Qie and Zhang.)

Tumour cells mainly generate energy from glycolysis, which is commonly coupled with lactate production even under normoxic conditions. As a critical lactate transporter, monocarboxylate transporter 4 (MCT4) is highly expressed in glycolytic tissues, such as muscles and tumours. Overexpression of MCT4 is associated with poor prognosis for patients with various tumours. However, how MCT4 function is post-translationally regulated remains largely unknown. Taking advantage of human lung adenocarcinoma (LUAD) cells, this study revealed that MCT4 can be polyubiquitylated in a nonproteolytic manner by SYVN1 E3 ubiquitin ligase. The polyubiquitylation facilitates the localization of MCT4 into the plasma membrane, which improves lactate export by MCT4; in accordance, metabolism characterized by reduced glycolysis and lactate production is effectively reprogrammed by SYVN1 knockdown, which can be reversed by MCT4 overexpression. Biologically, SYVN1 knockdown successfully compromises cell proliferation and tumour xenograft growth in mouse models that can be partially rescued by overexpression of MCT4. Clinicopathologically, overexpression of SYVN1 is associated with poor prognosis in patients with LUAD, highlighting the importance of the SYVN1-MCT4 axis, which performs metabolic reprogramming during the progression of LUAD., (© 2023. The Author(s).)

The effective discrimination and determination of the chiral antimalarial drugs quinine (QN) and quinidine (QD) are extremely important for human health. Herein, a 2D achiral Sm-based metal-organic framework (IMU-MOF 1 = [Sm(tpba)(L)] n , where Htpba = 4-(2,2':6″,2'-terpyridin)-4'-ylbenzioc acid and H 2 L = 2,2'-biquinoline-4,4'-dicarboxylic acid) was successfully prepared by the solvothermal method. More importantly, IMU-MOF 1 was designed as an ultrasensitive fluorescent probe for the identification of chiral enantiomer drugs. The limits of detection for QN and QD are 4.24 × 10 -11 and 7.54 × 10 -12 M, respectively. Furthermore, it was demonstrated that the stronger hydrogen-bonding interactions between IMU-MOF 1 and quinine furnish a more efficient energy transfer to the ligands in the sensing process, resulting in a significant fluorescence enhancement of IMU-MOF 1 .

The aim of this was to investigate the efficacy of physical exercise (leg swing and quadriceps strengthening exercises) versus platelet-rich plasma (PRP) and hyaluronic acid (HA) combination therapy. From January 2020 to August 2021, 106 patients with Kellgren-Lawrence Grade I-III knee osteoarthritis were divided into leg swing and quadriceps strengthening exercises (Group A) and intra-articular combination injections of PRP and HA (Group B) according to the treatment strategies. Patients in Group A received regular leg swing and quadriceps strengthening exercises for 3 months. Patients in Group B received 2 intra-articular combination injections of PRP (2 mL) and HA (2 mL) every 2 weeks. The primary outcome measures were the Visual Analogue Scale (VAS) and the Western Ontario and McMaster Universities (WOMAC) score. Secondary outcomes included single leg stance test and functional activity by 2-minute walk test and time up and go test. All outcomes were evaluated at baseline and again 1, 3, 6, and 12 months. The VAS and WOMAC scores were similar in both groups at 1 and 3 months after treatment (P > .05); however, Group A patients had significantly superior VAS and WOMAC scores than Group B patients at 6 and 12 months after treatment. For the single leg stance test, 2-minute walk test, and time up and go test, Group A patients were significantly superior to Group B throughout follow-up (P < .001). The leg swing and quadriceps strengthening exercises resulted in a significantly better clinical outcomes than the combined PRP and HA therapy, with a sustained lower pain score and improved quality of life, balance ability, and functional activity within 12 months., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: Solid tumor cells utilize amino acid transporters (AATs) to increase amino acid uptake in response to nutrient-insufficiency. The upregulation of AATs is therefore critical for tumor development and progression. This study identifies the upregulated AATs under amino acid deprived conditions, and further determines the clinicopathological importance of these AATs in evaluating the prognosis of patients with cancers., Materials and Methods: In this experimental study, the Gene Expression Omnibus (GEO) datasets (GSE62673, GSE26370, GSE125782 and GSE150874) were downloaded from the NCBI website and utilized for integrated differential expression and pathway analysis v0.96, Gene Set Enrichment Analysis (GSEA), and REACTOME analyses to identify the AATs upregulated in response to amino acid deprivation. In addition, The Cancer Genome Atlas (TCGA) datasets with prognostic information were assessed and employed to evaluate the association of identified AATs with patients' prognoses using SurvExpress analysis., Results: Using analysis of NCBI GEO data, this study shows that amino acid deprivation leads to the upregulation of six AAT genes; SLC3A2, SLC7A5, SLC7A1, SLC1A4, SLC7A11 and SLC1A5. GSEA and REACTOME analyses identified altered signaling in cells exposed to amino acid deprivation, such as pathways related to stress responses, the cell cycle and apoptosis. In addition, Principal Component Analysis showed these six AAT genes to be well divided into two distinct clusters in relation to TCGA tumor tissues versus normal counterparts. Finally, Log-Rank analysis confirmed the upregulation of this panel of six AAT genes is correlated with poor prognosis in patients with colorectal, esophageal, kidney and lung cancers., Conclusion: The upregulation of a panel of six AATs is common in several human cancers and may provide a valuable diagnostic tool to evaluate the prognosis of patients with colorectal, esophageal, kidney and lung cancers.

As a key 5G technology, massive multiple-input multiple-output (MIMO) can effectively improve system capacity and reduce latency. This paper proposes a user scheduling and spectrum allocation method based on combinatorial multi-armed bandit (CMAB) for a massive MIMO system. Compared with traditional methods, the proposed CMAB-based method can avoid channel estimation for all users, significantly reduce pilot overhead, and improve spectral efficiency. Specifically, the proposed method is a two-stage method; in the first stage, we transform the user scheduling problem into a CMAB problem, with each user being referred to as a base arm and the energy of the channel being considered a reward. A linear upper confidence bound (UCB) arm selection algorithm is proposed. It is proved that the proposed user scheduling algorithm experiences logarithmic regret over time. In the second stage, by grouping the statistical channel state information (CSI), such that the statistical CSI of the users in the angular domain in different groups is approximately orthogonal, we are able to select one user in each group and allocate a subcarrier to the selected users, so that the channels of users on each subcarrier are approximately orthogonal, which can reduce the inter-user interference and improve the spectral efficiency. The simulation results validate that the proposed method has a high spectral efficiency.

Objective: To evaluate the efficacy and safety of 0.01% atropine alone and in combination with orthokeratology for myopia control using a meta-analysis., Methods: PubMed, Cochrane Library, and EMBASE were searched. We included eligible randomized controlled trials (RCTs), non-RCTs, and retrospective cohort studies, published up to August 1, 2022. We calculated the weighted mean difference (WMD) and 95% confidence interval (CI) for all outcomes and plotted them in forest plots., Results: Fourteen studies were included; 4 and 11 in the 0.01% atropine monotherapy and atropine-orthokeratology (AOK) groups, respectively. Compared with orthokeratology (OK) alone, 0.01% atropine alone had similar effects on slowing the axial elongation (WMD: -0.00 mm; 95% CI: -0.05-0.04, p<0.31), while AOK significantly lowered axial growth. Moreover, the baseline myopic degree and duration of treatment were influential for the change in axial elongation (WMD: -0.12 mm; 95% CI: -0.17--0.07, p = 0.00001 and WMD: -0.11 mm; 95% CI: -0.15--0.108, p<0.00001, respectively). Additionally, the AOK may reduce the change rate of the spherical equivalent refraction and the accommodation amplitude (WMD: -0.13 D; 95% CI: 0.07-0.19, p<0.001 and WMD: -1.08 mm; 95% CI: -1.73--0.43, p<0.0001, respectively), and cause a slight increase in the diameter of the pupil (WMD: 0.56 mm; 95% CI: 0.43-0.70, p = 0.007). No significant differences in the uncorrected distant visual acuity, best corrected visual acuity, intraocular pressure, tear film break-up time, lipid layer thickness, and corneal endothelial cell density were found between the OK and AOK groups., Conclusion: In slowing the axial elongation, 0.01% atropine alone and OK alone have similar effects, while AOK is more effective than OK alone in slowing down the axial elongation. Furthermore, the baseline degree of myopia and treatment duration may affect changes in axial elongation., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: Unilateral spatial neglect (USN) is an impaired contralesional stimulus detection, response, or action, causing functional disability. After a stroke, the right hemisphere experiences USN more noticeably, severely, and persistently than the left. However, few studies using fNIRS have been reported in cases of USN. This study aimed to confirm weaker RSFC in USN and investigate the potential inherent features in hemodynamic fluctuations that may be associated with USN. Furthermore, these features were combined into a mathematical model for more accurate classification., Methods: A total of 33 stroke patients with right-sided brain damage were chosen, of whom 12 had non-USN after stroke, and 21 had USN after stroke (the USN group). Graph theory was used to evaluate the hemodynamic signals of the brain's right cerebral cortex during rest. Furthermore, a support vector machine model was built to categorize the subjects into two groups based on the chosen network properties., Results: First, mean functional connectivity was lower in the USN group (0.745 ± 0.239) than in the non-USN group (0.843 ± 0.254) ( t = -4.300, p < 0.001). Second, compared with the non-USN group, USN patients had a larger clustering coefficient (C) ( t = 3.145, p < 0.001), local efficiency (LE) ( t = 3.189, p < 0.001), and smaller global efficiency (GE) ( t = 3.047, p < 0.001). Notably, there were differences in characteristic path length (L) and small worldness (σ) values between the two groups at certain thresholds, mainly as higher L ( t = 3.074, p < 0.001) and lower small worldness (σ) values ( t = 2.998, p < 0.001) in USN patients compared with non-USN patients. Finally, the classification accuracy of the SVM model based on AUC aC ( t = -2.259, p = 0.031) and AUC aLE ( t = -2.063, p = 0.048) was 85%, the sensitivity was 75%, and the specificity was 89%., Conclusion: The functional network architecture of the right cerebral cortex exhibits significant topological alterations in individuals with USN following stroke, and the sensitivity index based on the small-world property AUC may be utilized to identify these patients accurately., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Shi, Qie, Wang, Wang and Liu.)

Objective: This study aimed to investigate the muscle activation of patients with lumbar disc herniation (LDH) during walking by surface electromyography (SEMG) and establish a diagnostic model based on SEMG parameters using random forest (RF) algorithm for localization diagnosis of compressed nerve root in LDH patients., Methods: Fifty-eight patients with LDH and thirty healthy subjects were recruited. The SEMG of tibialis anterior (TA) and lateral gastrocnemius (LG) were collected bilaterally during walking. The peak root mean square (RMS-peak), RMS-peak time, mean power frequency (MPF), and median frequency (MF) were analyzed. A diagnostic model based on SEMG parameters using RF algorithm was established to locate compressed nerve root, and repeated reservation experiments were conducted for verification. The study evaluated the diagnostic efficiency of the model using accuracy, precision, recall rate, F1-score, Kappa value, and area under the receiver operating characteristic (ROC) curve., Results: The results showed that delayed activation of TA and decreased activation of LG were observed in the L5 group, while decreased activation of LG and earlier activation of LG were observed in the S1 group. The RF model based on eight SEMG parameters showed an average accuracy of 84%, with an area under the ROC curve of 0.93. The RMS peak time of TA was identified as the most important SEMG parameter., Conclusion: These findings suggest that the RF model can assist in the localization diagnosis of compressed nerve roots in LDH patients, and the SEMG parameters can provide further references for optimizing the diagnosis model in the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wang, Wang, Li, Wang and Qie.)

Background: Studies have found that toxic heavy metals exposure could induce the generation of reactive oxygen species (ROS), and is of epigenetic effect, which might be associated with the occurrence of Autistic Disorder (ASD). This systematic review and meta-analysis aims to elucidate the association between exposure to 4 heavy metals, cadmium (Cd), lead (Pb), arsenic(As), and mercury (Hg), and the occurrence of ASD in children., Methods: We searched PubMed, Web of Science, Embase, and Cochrane Library, from their inception to October 2022, for epidemiological investigations that explore the association between exposure to Cd, Pb, As, or Hg and the occurrence of child ASD., Results: A total of 53 studies were included, involving 5,054 individuals aged less than 18 (2,533 ASD patients and 2,521 healthy controls). Compared with the healthy controls, in hair and blood tests, concentrations of the 4 heavy metals were significantly higher in the ASD group than in the healthy control group, and the differences in Pb, arsenic and Hg were statistically significant ( P  < 0.05). In the urine test, concentrations of arsenic and Hg were significantly higher in the ASD group than in the healthy control group ( P  < 0.05), while the results of Cd and Pb were opposite to those of arsenic and Hg ( P  > 0.05). Subgroup analysis for geographic regions showed that ASD patients in Asia and Europe had higher concentrations of the 4 heavy metals, compared with the healthy controls, in which the differences in Pb, arsenic, and Hg were statistically significant ( P  < 0.05), while in North America, the healthy controls had higher Cd, arsenic, and Hg concentrations ( P  > 0.05)., Conclusion: Compared with the healthy control group, the ASD group had higher concentrations of Cd, Pb, arsenic, and Hg. These 4 heavy metals play different roles in the occurrence and progression of ASD. Moreover, there is significant heterogeneity among the included studies due to controversies about the study results among different countries and regions and different sources of detection materials. The results of this study firmly support the policies to limit heavy metals exposure, especially among pregnant women and young children, so as to help reduce the incidence of ASD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Ding, Shi, Qie, Li and Xi.)

Objectives: We investigated the impact of traumatic spinal cord injury (TSCI) on daily living activities and motor function of TSCI patients. Methods: A total of 88 TSCI patients were randomly divided into Group A (N=44) and Group B (N=44). Group A received rehabilitation treatment 7 days after the stabilization of vital signs, and Group B received rehabilitation treatment 30 days after hospitalization. Results: The compliance rate of Group A (93.18%) was higher than that of Group B (72.73%) ( χ 2 =6.510, p<.05); The scores of American Spinal Injury Association (ASIA) and Activities of Daily Living (ADL) in Group A were higher than those in Group B. The self-rating score of anxiety and depression was lower than that of Group B (p<.05). Conclusion: For the rehabilitation treatment of TSCI patients, it is better to choose the intervention after the vital signs are stable to improve patients' ability for daily living activities and motor function.

Background: To evaluate the effect of repetitive transcranial magnetic stimulation (rTMS) combined with task-oriented training (TOT) on upper limb function in stroke patients with hemiplegia., Methods: A systematic review and meta-analysis was performed using PRISMA guidelines. Computer searches of PubMed, Cochrane Library, Embase, Web of science, China Knowledge Network, Wanfang, and Wipu databases were conducted from the time of database creation to October 27, 2022. Clinical trials meeting the inclusion criteria were screened, with rTMS combined with TOT in the test group and other therapies in the control group. Literature screening and data extraction were performed independently by 2 investigators, and meta-analysis was performed using Stata software after quality evaluation of the literature., Results: Meta-analysis results showed that repeated transcranial magnetic stimulation combined with TOT was more effective in box and block test (I2 = 0%, P = .820, 95% confidence interval [CI] [-0.20, 0.88]), Fugl-Meyer Assessment (I2 = 0%, P = .569, 95% CI [0.88, 1.26]), and modified Barthel Index (I2 = 39.9%, P = .189, 95% CI [0.45, 1.03]) were not significantly different from controls, and the efficacy was significantly better in motor evoked potentials (I2 = 86.5%, P < .001, 95% CI [-1.38, -0.83])., Conclusions: Data analysis clarified the efficacy of rTMS) combined with TOT on upper extremity motor function disorders after stroke, but there was no significant difference between the efficacy in box and block test, Fugl-Meyer Assessment, and modified Barthel Index and the efficacy in motor evoked potentials between rTMS and the control group, suggesting that the neuro plasticizing effect of rTMS may translate into functional improvement by promoting neuro electrical signaling., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Importance: Double-agent intravenous chemotherapy concurrent with radiotherapy is the standard of care for patients with inoperable esophageal cancer. However, patients tend to tolerate intravenous chemotherapy less well with age and comorbidities. It is essential to find a better treatment modality that improves survival outcomes without reducing the quality of life., Objective: To evaluate the effectiveness of simultaneous integrated boost radiotherapy (SIB-RT) with concurrent and consolidated oral S-1 chemotherapy for patients aged 70 years and older with inoperable esophageal squamous cell carcinoma (ESCC)., Design, Setting, and Participants: This multicenter, phase III randomized clinical trial was conducted between March 2017 and April 2020 in 10 centers in China. Patients with inoperable, locally advanced, clinical stage II to IV ESCC were enrolled and randomized to receive SIB-RT concurrent with and followed by oral S-1 chemotherapy (CRTCT group) or SIB-RT alone (RT group). Data analysis was completed on March 22, 2022., Interventions: In both groups, the planning gross tumor volume was administered with radiation dose of 59.92 Gy and the planning target volume was administered with radiation dose of 50.4 Gy, in 28 fractions each. In the CRTCT group, concurrent S-1 was administered on radiotherapy days, and consolidated S-1 was administered at 4 to 8 weeks after SIB-RT., Main Outcomes and Measures: The primary end point was overall survival (OS) of the intent-to-treat population. Secondary end points were progression-free survival (PFS) and toxicity profile., Results: A total of 330 patients (median [IQR] age, 75.5 [72-79] years; 220 [66.7%] male patients) were included, with 146 patients randomized to the RT group and 184 randomized to the CRTCT group. A total of 107 patients (73.3%) in the RT group and 121 patients (67.9%) in the CRTCT group were clinically diagnosed with stage III to IV disease. At the time of analysis of the 330 patients in the intent-to treat-population (March 22, 2022), OS was improved in the CRTCT group compared with the RT group at 1 year (72.2% vs 62.3%) and 3 years (46.2% vs 33.9%; log-rank P = .02). PFS was similarly improved in the CRTCT group compared with the RT group at 1 year (60.8% vs 49.3%) and 3 years (37.3% vs 27.9%; log-rank P = .04). There was no significant difference in the incidence of treatment-related toxic effects higher than grade 3 between the 2 groups. Grade 5 toxic effects occurred in each group, including 1 patient who experienced myelosuppression and 4 patients with pneumonitis in the RT group and 3 patients with pneumonitis and 2 patients with fever in the CRTCT group., Conclusions and Relevance: These findings suggest that oral S-1 chemotherapy administered with SIB-RT should be considered as an alternative treatment option for patients aged 70 years and older with inoperable ESCC, since it improved survival outcomes without additional treatment-related toxic effects compared with SIB-RT alone., Trial Registration: ClinicalTrials.gov Identifier: NCT02979691.

Background: Anterior cruciate ligament reconstruction (ACLR) is a common treatment for anterior cruciate ligament (ACL) injury. However, after ACLR, a significant proportion of patients do not return to pre-injury levels. Research on muscle function during movement has important implications in rehabilitation. Methods: Sixty patients with unilateral ACL injury were recruited for this study and assigned into three groups: group A, individuals with an ACL injury before 6 months; group B, individuals with ACLR from 6 months to 1 year; and group C, individuals with ACLR 1 year later. Surface electromyography (SEMG) signals were collected from the bilateral rectus femoris (RF), vastus medialis (VM), vastus lateralis (VL), biceps femoris (BF), and semitendinosus (ST). The tasks performed during the experiment included straight leg raising (SLR) training at 30°, SLR training at 60°, ankle dorsiflexion, walking, and fast walking. Results: In the maximum muscle strength test, the affected side of the BF in group A (199.4 ± 177.12) was significantly larger than in group B (53.91 ± 36.61, p = 0.02) and group C (75.08 ± 59.7, p = 0.023). In the walking test, the contralateral side of the RF in group B (347.53 ± 518.88) was significantly greater than that in group C (139.28 ± 173.78, p = 0.029). In the SLR training (60°) test, the contralateral side of the RF in group C (165.37 ± 183.06) was significantly larger than that in group A (115.09 ± 62.47, p = 0.023) and smaller than that in group B (226.21 ± 237.17, p = 0.046); In the ankle dorsiflexion training test, the contralateral side of the RF in group B (80.37 ± 87.9) was significantly larger than that in group C (45.61 ± 37.93, p = 0.046). Conclusion: This study showed the EMG characteristics of patients with ACL injury helped to determine which muscle requires more training and which exercise model would be best suited for intervention., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Cui, Cao, Wang, Zhang, Chen, Wu, Zhao, Qie and Li.)

The etiology of adolescent myopia involves genetic and environmental factors. The pathological mechanism of modern medicine includes blood perfusion, changes in blood molecules, neurotransmitters, and sclera remodeling. Chinese medicine believes that myopia is mainly related to the deficiency of liver blood and spleen and stomach disorders. The prevention and treatment of myopia in adolescents are very important, but in terms of the current incidence of myopia in adolescents and the level of clinical diagnosis and treatment, its prevention and treatment are insufficient. Modern medicine and traditional Chinese medicine both pay attention to integrity, so adolescent myopia should not only pay attention to eye changes but also pay attention to other body systems and other aspects of change. Intestinal flora has become a research hotspot in recent years, and it has been found that it is closely associated with multi-system and multi-type diseases. No studies have directly investigated the link between Intestinal flora and myopia in adolescents. Therefore, by summarizing the pathological mechanism of adolescent myopia and the connection between intestinal flora and the pathological mechanism of adolescent myopia, this paper analyzes the possible pathological mechanism of the influence of intestinal flora on adolescent myopia, providing a theoretical basis for future studies on the correlation between changes of intestinal flora and its metabolites and the incidence of adolescent myopia, which is of great significance for the study on the risk prediction of adolescent myopia., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Stroke causes varying degrees of neurological deficits, leading to corresponding dysfunctions. There are different therapeutic principles for each stage of pathological development. Neuroprotection is the main treatment in the acute phase, and functional recovery becomes primary in the subacute and chronic phases. Neuroplasticity is considered the basis of functional restoration and neurological rehabilitation after stroke, including the remodeling of dendrites and dendritic spines, axonal sprouting, myelin regeneration, synapse shaping, and neurogenesis. Spatiotemporal development affects the spontaneous rewiring of neural circuits and brain networks. Microglia are resident immune cells in the brain that contribute to homeostasis under physiological conditions. Microglia are activated immediately after stroke, and phenotypic polarization changes and phagocytic function are crucial for regulating focal and global brain inflammation and neurological recovery. We have previously shown that the development of neuroplasticity is spatiotemporally consistent with microglial activation, suggesting that microglia may have a profound impact on neuroplasticity after stroke and may be a key therapeutic target for post-stroke rehabilitation. In this review, we explore the impact of neuroplasticity on post-stroke restoration as well as the functions and mechanisms of microglial activation, polarization, and phagocytosis. This is followed by a summary of microglia-targeted rehabilitative interventions that influence neuroplasticity and promote stroke recovery.

Background: Music therapy has been shown to improve communication in children with autism spectrum disorders (ASD), but little is known about how different types of music and images affect hemodynamic changes in the frontal lobe of the brain in children with ASD. This study aims to use functional near infrared spectroscopy (fNIRS) to explore the effects of different types of visual music on different brain regions of oxyhemoglobin (HbO) in the prefrontal lobe of children with ASD and children with typical development (TD), so as to provide evidence for better application of different types of visual music in the treatment of children with ASD., Methods: Seven children with ASD and nine matched children with TD were selected. Changes in HbO in their prefrontal lobes were determined by fNIRS after resting states and 12 different types of visual music tasks., Results: (I) Intra-group comparison: the influence of different types of light and music on ∆HbO in ROI (zone F) of ASD children is different, the activation degree shows that red light & positive music is less than green light & neutral music, red light & positive music is less than blue light & negative music, and there is no difference between green light & neutral music and blue light & negative music. (II) Comparison between groups: Visual musical tasks 1, 2, 3, 4, and 8 positively activated HbO in the prefrontal B and E regions of the brain in children with ASD and negatively activated HbO in TD children. Visual musical tasks 5, 9, 10, and 12 negatively activated HbO in the prefrontal F regions of the brain in children with ASD and positively activated HbO in TD children., Conclusions: When the two groups of children received the same visual music task, the changes of HbO in different regions of the prefrontal lobe were different; The effects of different types of visual music on the frontal lobe of the brain in children with ASD are inconsistent., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-22-693/coif). The authors have no conflicts of interest to declare., (2023 Translational Pediatrics. All rights reserved.)

Background: Treatment failure is the main cause of death from papillary thyroid carcinoma (PTC). It is urgent to look for new intervention targets and to develop new therapies for treating PTC. Aurora-A kinase (AURKA) functionally regulates cell mitosis and is closely related to the occurrence and development of a variety of tumours. However, the expression and potential functions of AURKA in PTC remain largely elusive., Results: Clinicopathologically, AURKA is highly expressed in PTC tissues compared to normal tissues and is correlated with lymph node metastasis, TNM stage and patient prognosis. Biologically, AURKA functions as an oncoprotein to promote the proliferation and migration of PTC cells. Mechanistically, AURKA directly binds to SIN1 and compromises CUL4B-based E3 ligase-mediated ubiquitination and subsequent degradation of SIN1, leading to hyperactivation of the mTORC2-AKT pathway in PTC cells., Conclusions: We found that AURKA plays critical roles in regulating the progression of PTC by activating the mTORC2-AKT pathway, highlighting the potential of targeting AURKA to treat PTC., (© 2022. The Author(s).)

Odonate is a new, intelligent three-dimensional gait analysis system based on binocular depth cameras and neural networks, but its accuracy has not been validated. Twenty-six healthy subjects and sixteen patients with post-stroke were recruited to investigate the validity and reliability of Odonate for gait analysis and examine its ability to discriminate abnormal gait patterns. The repeatability tests of different raters and different days showed great consistency. Compared with the results measured by Vicon, gait velocity, cadence, step length, cycle time, and sagittal hip and knee joint angles measured by Odonate showed high consistency, while the consistency of the gait phase division and the sagittal ankle joint angle was slightly lower. In addition, the stages with statistical differences between healthy subjects and patients during a gait cycle measured by the two systems were consistent. In conclusion, Odonate has excellent inter/intra-rater reliability, and has strong validity in measuring some spatiotemporal parameters and the sagittal joint angles, except the gait phase division and the ankle joint angle. Odonate is comparable to Vicon in its ability to identify abnormal gait patterns in patients with post-stroke. Therefore, Odonate has the potential to provide accessible and objective measurements for clinical gait assessment.

Heterogeneous Nuclear Ribonucleoprotein K (hnRNPK) is a multifunctional RNA binding protein (RBP) localized in the nucleus and the cytoplasm. Abnormal cytoplasmic enrichment observed in solid tumors often correlates with poor clinical outcome. The mechanism of cytoplasmic redistribution and ensuing functional role of cytoplasmic hnRNPK remain unclear. Here we demonstrate that the SCF Fbxo4 E3 ubiquitin ligase restricts the pro-oncogenic activity of hnRNPK via K63 linked polyubiquitylation, thus limiting its ability to bind target mRNA. We identify SCF Fbxo4 -hnRNPK responsive mRNAs whose products regulate cellular processes including proliferation, migration, and invasion. Loss of SCF Fbxo4 leads to enhanced cell invasion, migration, and tumor metastasis. C-Myc was identified as one target of SCF Fbxo4 -hnRNPK. Fbxo4 loss triggers hnRNPK-dependent increase in c-Myc translation, thereby contributing to tumorigenesis. Increased c-Myc positions SCF Fbxo4 -hnRNPK dysregulated cancers for potential therapeutic interventions that target c-Myc-dependence. This work demonstrates an essential role for limiting cytoplasmic hnRNPK function in order to maintain translational and cellular homeostasis., (© 2022. The Author(s).)

Distant metastases of small-cell lung cancer (DM-SCLC) is an important factor in the selection of treatment strategies. In this study, we established a nomogram to predict DM-SCLC and determine the benefit of radiotherapy (RT) for DM-SCLC. We analyzed DM-SCLC prognosis based on surveillance, epidemiology, and end result database (SEER) data. A comprehensive and practical nomogram that predicts the overall survival (OS) of DM-SCLC was constructed and the results were compared with the 7th edition of the American Joint Committee on Cancer (AJCC) TNM stage system. A concordance index (C-index) and receiver operating characteristic plot were generated to evaluate the nomogram discrimination. The calibration was evaluated with a calibration plot, and its effectiveness was evaluated by a decision curve analysis (DCA). A score was assigned to each variable, and a total score was established for the risk stratification model. A total of 13,403 DM-SCLC patients were included. Eight characteristic variables were identified as independent prognostic variables. The C-index of the validation and training cohorts was 0.716 and 0.734, respectively. The area under the receiver operating characteristic curve (AUC) values of the nomogram used to predict 1-, 2-, and 3-year OS were 0.751, 0.744, and 0.786 in the validation cohorts (0.761, 0.777, 0.787 in the training cohorts), respectively. The calibration curve of 1-, 2-, 3-year survival rates showed that the prediction of the nomogram was in good agreement with the actual observation. The nomogram exhibited higher clinical utility after evaluation with the 1-, 2-, 3-year DCA compared with the AJCC stage system. A predictive nomogram and risk stratification model have been constructed to evaluate the prognosis of DM-SCLC effectively and accurately. This nomogram may provide a reference for prognosis stratification and treatment decisions., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The purpose of this study was to analyze the clinical characteristics and prognosis of EPEC and to construct a prediction model based on the SEER database., Methods: All EPECs from the SEER database were retrospectively analyzed. A comprehensive and practical nomogram that predicts the overall survival (OS) of EPEC was constructed. Univariate and multivariate Cox regression analysis was performed to explore the clinical factors influencing the prognosis of EPEC, and finally, the 1 -, 3 - and 5-year OS were predicted by establishing the nomogram. The discriminant and predictive ability of the nomogram was evaluated by consistency index (C-index), calibration plot, area under the curve (AUC), and receiver operating characteristic (ROC) curve. Decision curve analysis (DCA) was used to evaluate the clinical value of the nomogram., Results: A total of 3478 patients diagnosed with EPEC were extracted from the SEER database, and the data were randomly divided into the training group (n=2436) and the validation group (n=1402). T stage, N stage, M stage, surgery, chemotherapy, radiotherapy, age, grade, and tumor size were independent risk factors for 1 -, 3 - and 5-year OS of EPEC (P< 0.05), and these factors were used to construct the nomogram prediction mode. The C-index of the validation and training cohorts was 0.718 and 0.739, respectively, which were higher than those of the TNM stage system. The AUC values of the nomogram used to predict 1-, 2-, and 3-year OS were 0.751, 0.744, and 0.786 in the validation cohorts (0.761, 0.777, 0.787 in the training cohorts), respectively. The calibration curve of 1-, 2-, and 3-year OS showed that the prediction of the nomogram was in good agreement with the actual observation. The nomogram exhibited higher clinical utility after evaluation with the 1-, 2-, and 3-year DCA compared with the AJCC stage system., Conclusions: This study shows that the nomogram prediction model for EPEC based on the SEER database has high accuracy and its prediction performance is significantly better than the TNM staging system, which can accurately and individually predict the OS of patients and help clinicians to formulate more accurate and personalized treatment plans., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Qie, Shi, Wang, Liu, Gu, Liu, Li and Sun.)

Due to extensive tumor spread, systemic chemotherapy is the main treatment for distant metastatic small-cell lung cancer (DM-SCLC). It is still unclear whether adding local radiotherapy (RT) on the basis of chemotherapy can improve the long-term survival of patients with DM-SCLC. This study aims to explore the population with DM-SCLC who can benefit from RT. Patients with metastatic SCLC with complete data were collected from the Surveillance, Epidemiology, and End Results database and divided into 2 groups according to whether RT was given or not. The propensity score matching method was used to balance the covariate differences between the RT group and the non-RT group. Lasso Cox regression model and Cox proportional hazards regression analyses were used to identifying independent risk factors affecting survival. Kaplan-Meier method was used to calculate the survival rate. P < .05 was considered statistically significant. After matching, there were 3150 patients in both groups. Sex, tumor size, N stage, RT, chemotherapy, brain metastasis, liver metastasis, age, and site metastasis were independent factors of survival in DM-SCLC. The 1- and 2-year survival rates were 24.5% and 5.8% in the RT group and 14.8% and 2.3% in the non-RT group (P < .001). The median survival time of the RT group was 9 months, and that of the non-RT group was 7 months, and the difference was statistically significant (P < .001). RT improved survival in all sex subgroups, any N stage subgroup, any tumor size subgroup, no brain metastases subgroup, no liver metastases subgroup, any age subgroup, and 1-2 organ metastases subgroup. RT improves 1- and 2-year survival in DM-SCLC., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Aims: Considering individual variability in regards to the effects of orthokeratology (ortho-k) on myopia progression and controversies regarding the precise underlying mechanism, the aim of this study was to investigate several ocular measurements associated with axial length (AL) growth in children wearing ortho-k lenses., Methods: In this retrospective chart review, medical records of 53 Chinese children who wore ortho-k lenses over the course of 12 months were reviewed. Baseline variables included age at initiation of ortho-k wear, refractive error (spherical equivalent, SE), central corneal thickness (CCT), and flat and steep keratometry of corneal principal meridians. The change of anterior chamber depth (ACD) and the change of crystalline lens thickness (CLT) between baseline and the 12-month follow-up were also analyzed. The contributions of all analyzed variables to AL change were assessed using univariate and multivariate regression analyses., Results: Initially, the results of paired t-test showed that CLT and AL were significantly increased after 12 months of ortho-k wear compared with that at baseline (P = 0.001 and < 0.001). The ACD did not change significantly after 12 months compared with that at baseline (P = 0.491). Subsequently, univariate analyses showed that a reduced rate of AL elongation was found in children who were older age at initiation of ortho-k wear (P = 0.028), had greater SE (higher degree of myopia) at baseline (p = 0.006), had thicker CCT at baseline (P = 0.04), and had greater increase of CLT (P = 0.001) in 12 months. At last, only greater SE (higher degree of myopia) and greater increase of CLT were associated with smaller increases of AL in multivariable analyses, (P = 0.003 and 0.001)., Conclusions: Both CLT and AL were significantly increased in children with overnight ortho-k wear after 12 months of follow-up. Greater baseline SE and greater increase of CLT were associated with less increase in AL during ortho-k wear in children with myopia., (Copyright © 2021 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.)

Stanniocalcin 2 (STC2) is a glycoprotein which is expressed in a broad spectrum of tumour cells and tumour tissues derived from human breast, colorectum, stomach, esophagus, prostate, kidney, liver, bone, ovary, lung and so forth. The expression of STC2 is regulated at both transcriptional and post-transcriptional levels; particularly, STC2 is significantly stimulated under various stress conditions like ER stress, hypoxia and nutrient deprivation. Biologically, STC2 facilitates cells dealing with stress conditions and prevents apoptosis. Importantly, STC2 also promotes the development of acquired resistance to chemo- and radio- therapies. In addition, multiple groups have reported that STC2 overexpression promotes cell proliferation, migration and immune response. Therefore, the overexpression of STC2 is positively correlated with tumour growth, invasion, metastasis and patients' prognosis, highlighting its potential as a biomarker and a therapeutic target. This review focuses on discussing the regulation, biological functions and clinical importance of STC2 in human cancers. Future perspectives in this field will also be discussed., (© 2022. The Author(s).)

Fbxo4, also known as Fbx4, belongs to the F-box protein family with a conserved F-box domain. Fbxo4 can form a complex with S-phase kinase-associated protein 1 and Cullin1 to perform its biological functions. Several proteins are identified as Fbxo4 substrates, including cyclin D1, Trf1/Pin2, p53, Fxr1, Mcl-1, ICAM-1, and PPARγ. Those factors can regulate cell cycle progression, cell proliferation, survival/apoptosis, and migration/invasion, highlighting their oncogenic or oncogene-like activities. Therefore, Fbxo4 is defined as a tumor suppressor. The biological functions of Fbxo4 make it a potential candidate for developing new targeted therapies. This review summarizes the gene and protein structure of Fbxo4, the mechanisms of how its expression and activity are regulated, and its substrates, biological functions, and clinicopathological importance in human cancers.

Precise identification of deficient intersegmental coordination patterns and functional limitations is conducive to the evaluation of surgical outcomes after total knee arthroplasty (TKA) and the design of optimal personalized rehabilitation protocols. However, it is still not clear how and when intersegmental coordination patterns change during walking, and what functional limitations are in patients with TKA. This study was designed to investigate lower limb intersegmental coordination patterns in patients with knee osteoarthritis before and after TKA and identify how intersegmental coordination of patients is altered during walking before and after TKA. It was hypothesized that 6-month after TKA, intersegmental coordination patterns of patients are improved compared with that before TKA, but still do not recover to the level of healthy subjects. Gait analysis was performed on 36 patients before and 6-month after TKA and on 34 healthy subjects. Continuous relative phase (CRP) derived from the angle-velocity phase portrait was used to measure the coordination between interacting segments throughout the gait cycle. Thigh-shank CRP and shank-foot CRP were calculated for each subject. Statistical parametric mapping (SPM), a one-dimensional analysis of the entire gait cycle curve, was performed directly to determine which periods of the gait cycle were different in patients and healthy subjects. Six-month after TKA, thigh-shank CRP was significantly higher during 5-12% of the gait cycle ( p = 0.041) and lower during 44-95% of the gait cycle ( p < 0.001) compared with healthy subjects, and was significantly higher during 62-91% of the gait cycle ( p = 0.002) compared with pre-operation. Shank-foot CRP was significantly lower during 0-28% of the gait cycle ( p < 0.001) and higher during 58-94% of the gait cycle ( p < 0.001) compared with healthy subjects, and was significantly lower during 3-18% of the gait cycle ( p = 0.005) compared with pre-operation. This study found that patients exhibited altered intersegmental coordination during the loading response and swing phase both before and after TKA. Six-month after TKA, the thigh-shank coordination was partially improved compared with pre-operation, but still did not recover to the level of healthy subjects, while there was no improvement in the shank-foot coordination pattern after TKA compared with pre-operation. CRP combined with SPM methods can provide insights into the evaluation of surgical outcomes and the design of rehabilitation strategy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Qie, Li, Yan, Zeng and Zhang.)

Background: Peritoneal dialysis (PD) patients have a high incidence of poor clinical outcomes, which is related to the inflammatory and nutritional status of this population. Platelet-to-albumin ratio (PAR), recently identified as a useful biomarker to monitor inflammation and nutrition, can predict a poor prognosis in various diseases. The aim of this study was to investigate the association between PAR and technique failure and mortality in PD patients., Methods: This single-center retrospective study enrolled 405 PD patients from 1 January 2011 to 31 December 2019 and collected complete demographic characteristics, clinical laboratory baseline data. The outcomes were technique failure and mortality. The associations between PAR and technique failure, death were analyzed by Cox proportional hazard models and competing risk regression models with kidney transplantation as a competing event. The areas under the curve (AUC) of receiver-operating characteristic analysis were used to determine the predictive values of PAR for technique failure and mortality., Results: During a median follow-up period of 24.0 (range, 4.0-91.0) months, 139 (34.3%) PD patients experienced technique failure, 61 (15.1%) PD patients died. The patients with higher PAR levels had increased risk of technique failure and mortality. After adjustment for confounding factors, we found that high PAR levels were risk factor for both technique failure (subdistribution hazard ratio [ SHR ] 1.775; 95%CI , 1.157-2.720; p  = 0.033] and mortality [ SHR 3.710; 95%CI , 1.870-7.360; p  < 0.001]. The predictive ability of PAR was superior to platelet and albumin based on AUC calculations for technique failure and mortality., Conclusions: PAR was a risk factor associated with technique failure and mortality in PD patients.

Background: The efficacy of traditional rehabilitation, proprioceptive training, and neuromuscular training after anterior cruciate ligament (ACL) reconstruction is also controversial. In order to help medical staff better choose the rehabilitation treatment plan after ACL reconstruction, we conducted this network meta-analysis., Methods: Chinese and English databases such as Wanfang, Weipu, China Zhiwang, and PubMed, Cochrane Library, Embase were retrieved. We collected clinical controlled trial papers on traditional rehabilitation therapy, proprioceptive training and neuromuscular training after ACL reconstruction for meta-analysis., Results: In this meta-analysis, 12 studies were included, including 486 patients who received rehabilitation treatment after ACL reconstruction. Based on network meta-analysis, it was found that 4 groups of direct comparison and 6 groups of indirect comparison were formed for 5 rehabilitation treatment schemes after ACL reconstruction. The curative effect of traditional rehabilitation training combined with proprioception training is better than that of traditional rehabilitation training (mean difference value of traditional rehabilitation training combined with proprioception training vs traditional rehabilitation training was 8.00, 95% confidence interval: 2.61,13.39). The efficacy of proprioceptive training is better than that of traditional rehabilitation training (mean difference value of proprioceptive training vs traditional rehabilitation training is 11.01, 95% confidence interval: 0.62,21.39). There was no statistical significance between the other rehabilitation trainings. According to the surface under cumulative ranking curve, the therapeutic effects of the 5 rehabilitation treatment programs after ACL reconstruction were ranked as follows: proprioceptive training (72%) > traditional rehabilitation training combined with neuromuscular training (70.8%) > traditional rehabilitation training combined with proprioception training (57.1%) > neuromuscular training (45.5%) > traditional rehabilitation training (4.6%). No publication bias was found in the funnel plot., Conclusion: Combined with the results of meta-analysis and surface under cumulative ranking efficacy sequence diagram, it can be seen that traditional rehabilitation training combined with proprioceptive training and traditional rehabilitation training combined with neuromuscular training have significant efficacy. Due to the limitations of this study, the conclusions of this network meta-analysis still need to be further confirmed by a large sample size and well-designed randomized controlled trials., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Microglial polarization mediated neuroinflammation plays an important role in the pathological process of stroke. The aim of this study is to determine whether baicalein indirectly ameliorates neuronal injury through modulating microglial polarization after stroke and if so, then by what mechanism. The effects of baicalein on microglial polarization were revealed through the middle cerebral artery occlusion mouse model (MCAO, n = 6), the lipopolysaccharide (LPS) + interferon-γ (IFN-γ) and oxygen-glucose deprivation (OGD) induced neuroinflammatory microglia model (BV2, n = 3), respectively. Mice were treated with baicalein (100 mg/kg, i.g.) after reperfusion, and followed by daily administrations for 3 days. Results showed that the infarct volumes at 3 d in vehicle and baicalein-treated MCAO mice were 91.18 ± 4.02% and 55.36 ± 4.10%. Baicalein improved sensorimotor functions (p < 0.01) after MCAO. Real-time PCR revealed that baicalein decreased proinflammatory markers expression (p < 0.05), while elevated the anti-inflammatory markers (p < 0.05) in vivo and in vitro. Both western blot and immunofluorescent staining further confirmed that baicalein reduced proinflammatory marker CD16 levels (p < 0.01) and enhanced anti-inflammatory marker CD206 or Arg-1 levels (p < 0.05). Notably, baicalein suppressed the release of proinflammatory cytokines (p < 0.05) and nitric oxide (NO, p < 0.001). Mechanistically, baicalein prevented increases in TLR4 protein levels (p < 0.001), the phosphorylation of IKBα and p65 (p < 0.01), and the nuclear translocation of NF-κB p65 (p < 0.05). The NF-κB inhibitor, BAY 11-7085, enhanced the inhibitory effect of baicalein on the proinflammatory microglial polarization. Baicalein also inhibited the phosphorylation of signal transducer and activator of transcription 1 (STAT1, p < 0.001). A microglia-neuron co-culture system revealed that baicalein driven neuroprotection against OGD induced neuronal damage through modulating microglial polarization (p < 0.05). Baicalein indirectly ameliorates neuronal injury after stroke by polarizing microglia toward the anti-inflammatory phenotype via inhibition of the TLR4/NF-κB pathway and down-regulation of phosphorylated STAT1, suggesting that baicalein might serve a potential therapy for stroke., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: To analyze the survival benefits and treatment related toxic effects of simultaneous integrated boost intensity-modulated radiotherapy (SIB-RT) for non-operative esophageal squamous cell carcinoma patients. Methods: The data of 2 132 ESCC patients who were not suitable for surgery or rejected operation, and underwent radical radiotherapy from 2002 to 2016 in 10 hospitals of Jing-Jin-Ji Esophageal and Esophagogastric Cancer Radiotherapy Oncology Group (3JECROG) were analyzed. Among them, 518 (24.3%) cases underwent SIB (SIB group) and 1 614 (75.7%) cases did not receive SIB (No-SIB group). The two groups were matched with 1∶2 according to propensity score matching (PSM) method (caliper value=0.02). After PSM, 515 patients in SIB group and 977 patients in No-SIB group were enrolled. Prognosis and treatment related adverse effects of these two groups were compared and the independent prognostic factor were analyzed. Results: The median follow-up time was 61.7 months. Prior to PSM, the 1-, 3-, and 5-years overall survival (OS) rates of SIB group were 72.2%, 42.8%, 35.5%, while of No-SIB group were 74.3%, 41.4%, 31.9%, respectively ( P =0.549). After PSM, the 1-, 3-, and 5-years OS rates of the two groups were 72.5%, 43.4%, 36.4% and 75.3%, 41.7%, 31.6%, respectively ( P =0.690). The univariate survival analysis of samples after PSM showed that the lesion location, length, T stage, N stage, TNM stage, simultaneous chemoradiotherapy, gross tumor volume (GTV) and underwent SIB-RT or not were significantly associated with the prognosis of advanced esophageal carcinoma patients who underwent radical radiotherapy ( P <0.05). Cox model multivariate regression analysis showed lesion location, TNM stage, GTV and simultaneous chemoradiotherapy were independent prognostic factors of advanced esophageal carcinoma patients who underwent radical radiotherapy ( P <0.05). Stratified analysis showed that, in the patients whose GTV volume≤50 cm(3), the median survival time of SIB and No-SIB group was 34.7 and 30.3 months ( P =0.155), respectively. In the patients whose GTV volume>50 cm(3), the median survival time of SIB and No-SIB group was 16.1 and 20.1 months ( P =0.218). The incidence of radiation esophagitis and radiation pneumonitis above Grade 3 in SIB group were 4.3% and 2.5%, significantly lower than 13.1% and 11% of No-SIB group ( P <0.001). Conclusions: The survival benefit of SIB-RT in patients with locally advanced esophageal carcinoma is not inferior to non-SIB-RT, but without more adverse reactions, and shortens the treatment time. SIB-RT can be used as one option of the radical radiotherapy for locally advanced esophageal cancer.

Background: Anemia is a common complication for patients with kidney disease. Roxadustat is an oral hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor (PHI), which is a newly approved oral drug for anemia. We performed this study to build evidence regarding efficacy and safety of roxadustat in kidney disease patients with or without dialysis., Methods: We searched the databases of PubMed, Embase, Cochrane library and clinicaltrials.gov from the inception to July 20, 2020. The randomized controlled trials (RCTs) which compared roxadustat with placebo or other therapies in the treatment of anemia in kidney disease patients were included. Data were extracted from eligible studies and pooled in a meta-analysis model using RevMan5.3 and stata13.0 software., Results: Eight RCTs with 1010 patients were included in our analysis. We found that roxadustat significantly increased hemoglobin (Hb) level (1.10 g/dL, 95% CI [0.52 g/dL, 1.67 g/dL], p = 0.0002), total iron-binding capacity (TIBC) (58.71 µg/dL, 95% CI [44.10 µg/dL, 73.32 µg/dL], p < 0.00001), iron level (9.28 µg/dL, 95% CI [0.11 µg/dL, 18.45 µg/dL], p = 0.05) compared with control group in kidney disease patients. In addition, our result showed that a significant reduction in hepcidin level (- 31.96 ng/mL, 95% CI [- 35.05 ng/mL, - 28.87 ng/mL], p < 0.00001), ferritin (- 44.82 ng/mL, 95% CI [- 64.42 ng/mL, - 25.23 ng/mL], p < 0.00001) was associated with roxadustat. No difference was found between roxadustat and control group in terms of oral iron supplementation, adverse events (AEs), serious adverse events (SAEs), infection, myocardial infraction, stroke, heart failure and death., Conclusions: Roxadustat has higher mean Hb level than placebo or EPO. Due to the short follow-up period and the lack of critical data, more RCTs are needed to prove long-term safety and effectiveness of roxadustat in the future.

Abstract: This study aims to establish an effective prognostic nomogram for small cell carcinoma of the esophagus (SCCE).A total of 552 patients with SCCE from 1975 to 2016 were extracted from the surveillance, epidemiology, and end results (SEER) database. A Cox proportional hazard regression model was used to analyze the prognostic factors of patients, and a nomogram was constructed. The nomogram was then validated internally by using a consistency index (C-index) and a correction curve to evaluate its predictive value.The Cox proportional hazard regression model showed that age, stage, surgery, primary site, radiotherapy, and chemotherapy were the prognostic factors of SCCE (P < .1), and they were used to construct the nomogram. The C-index of the nomogram for predicting survival was 0.749 (95% confidence interval [CI] = 0.722-0.776). The data were randomly divided into a modeling group and a validation group based on 7:3 for internal validation. The C-indices of the modeling and validation groups were 0.753 and 0.725, respectively, and they were close to 0.749. The calibration curves exhibited good consistency between the predicted and actual survival rates.The nomogram of the survival and prognosis of patients with SCCE in this study had a good predictive value and could provide clinicians with accurate and practical predictive tools. It could also be used to facilitate a rapid and accurate assessment of patients' survival and prognosis on an individual basis., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Abstract: Birth defects have been linked to administration of alkylating agents during pregnancy. The anti-tumor efficacy of alkylating agents correlate with their ability to induce DNA lesions, especially interstrand crosslinks (ICLs). Yet the role of DNA damages in birth defects remains to be clarified, owing, in part, to a lack of cell models. Here we generate DNA lesions in NIH/3T3 cells to mimic defects in fetus triggered by 3-Bis(2-chloroethyl)-1-nitrosourea (BCNU, carmustine). CCK-8 assay suggests that BCNU-induced cell death was dose-dependent. Alkaline comet tests and γ-H2AX staining confirm DNA ICLs and other forms of DNA damages caused by BCNUs. The cell cycle analysis shows cells arrest in G2/M phase until crosslinks repair is complete. Taken together, all these experiments demonstrate we have successfully established normal cell models for birth defects caused by BCNU-mediated DNA damages. The model can not only guide the development of effective and low-toxicity anticancer drugs, but also be of great significance for the study of neonatal malformation triggered by BCNUs., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2020 by Mutaz B. Habal, MD.)