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Background: Unhealthy lifestyles, which include unhealthy diet and unhealthy sleep duration, have been widely recognized as modifiable risk factors for depressive symptoms. This study aims to explore the associations between dietary quality, sleep duration, and depression symptoms, as well as their combined effects., Methods: The NHANES 2007 to 2014 cycles provided the data for this study, in which 19,134 adults aged 20 years and older were included. Unhealthy diet, measured using an average Healthy Eating Index (HEI)-2015 score below the 60th percentile, and unhealthy sleep duration, measured as sleep duration at night less than 7 h or greater than/equal to 9 h, were the primary exposures. Then participants were divided into four different lifestyles. A weighted-multivariable logistic regression was employed, controlling for relevant variables. Furthermore, stratified analyses were conducted to assess the robustness of the findings and identify potential high-risk groups., Results: The overall prevalence of depressive symptoms among all participants was 8.44%. Among the participants, 56.58% met the criteria for healthy sleep duration, and 24.83% scored at or above the 60th percentile on the HEI-2015. Unhealthy diet (OR: 1.40, 95% CI: 1.18-1.67, p < 0.001) and unhealthy sleep duration (OR: 1.94, 95% CI: 1.63-2.31, p < 0.001) exhibited positive associations with depression symptoms. Individuals who maintained an unhealthy diet but healthy sleep duration (OR: 1.60, 95% CI: 1.20-2.13, p = 0.002), healthy diet but unhealthy sleep duration (OR: 2.50, 95% CI: 1.64-3.80, p < 0.001), or an unhealthy diet and unhealthy sleep duration (OR: 2.91, 95% CI: 2.16-3.92, p < 0.001) were significantly associated with depressive symptoms compared to those with a healthy diet and healthy sleep duration, respectively. In stratified analyses, females, middle-aged individuals, those with a college degree or higher education, and individuals who do not meet the recommended level of physical activity exhibit heightened susceptibility to depressive symptoms when exposed to unhealthy diet and unhealthy sleep duration., Conclusion: In summary, our study suggests that individuals affected by the individual and synergistic effect of an unhealthy diet and unhealthy sleep duration are more susceptible to experiencing depressive symptoms., (© 2024. The Author(s).)

Background: In recent years, deep learning (DL) technology has been increasingly used for the diagnosis and treatment of lumbar intervertebral disc (IVD) degeneration. This study aims to evaluate the performance of DL technology for IVD segmentation in magnetic resonance (MR) images and explore improvement strategies., Methods: We developed a PRISMA systematic review protocol and systematically reviewed studies that used DL algorithm frameworks to perform IVD segmentation based on MR images published up to April 10, 2024. The Quality Assessment of Diagnostic Accuracy Studies-2 tool was used to assess methodological quality, and the pooled dice similarity coefficient (DSC) score and Intersection over Union (IoU) were calculated to evaluate segmentation performance., Results: 45 studies were included in this systematic review, of which 16 provided complete segmentation performance data and were included in the quantitative meta-analysis. The results indicated that DL models showed satisfactory IVD segmentation performance, with a pooled DSC of 0.900 (95% confidence interval [CI]: 0.887-0.914) and IoU of 0.863 (95% CI: 0.730-0.995). However, the subgroup analysis did not show significant effects of factors on IVD segmentation performance, including network dimensionality, algorithm type, publication year, number of patients, scanning direction, data augmentation, and cross-validation., Conclusions: This study highlights the potential of DL technology in IVD segmentation and its further applications. However, due to the heterogeneity in algorithm frameworks and result reporting of the included studies, the conclusions should be interpreted with caution. Future research should focus on training generalized models on large-scale datasets to enhance their clinical application., (© 2024. The Author(s).)

Background: Prostate cancer is one of the most common malignant tumors in middle-aged and elderly men and carries significant prognostic implications, and recent studies suggest that dual-energy computed tomography (DECT) utilizing new virtual monoenergetic images can enhance cancer detection rates. This study aimed to assess the impact of virtual monoenergetic images reconstructed from DECT arterial phase scans on the image quality of prostate lesions and their diagnostic performance for prostate cancer., Methods: We conducted a retrospective analysis of 83 patients with prostate cancer or prostatic hyperplasia who underwent DECT scans at Meizhou People's Hospital between July 2019 and December 2023. The variables analyzed included age, tumor diameter and serum prostate-specific antigen (PSA) levels, among others. We also compared CT values, signal-to-noise ratio (SNR), subjective image quality ratings, and contrast-to-noise ratio (CNR) between virtual monoenergetic images (40-100 keV) and conventional linear blending images. Receiver operating characteristic (ROC) curve analyses were performed to evaluate the diagnostic efficacy of virtual monoenergetic images (40 keV and 50 keV) compared to conventional images., Results: Virtual monoenergetic images at 40 keV showed significantly higher CT values (168.19 ± 57.14) compared to conventional linear blending images (66.66 ± 15.5) for prostate cancer (P < 0.001). The 50 keV images also demonstrated elevated CT values (121.73 ± 39.21) compared to conventional images (P < 0.001). CNR values for the 40 keV (3.81 ± 2.13) and 50 keV (2.95 ± 1.50) groups were significantly higher than the conventional blending group (P < 0.001). Subjective evaluations indicated markedly better image quality scores for 40 keV (median score of 5) and 50 keV (median score of 5) images compared to conventional images (P < 0.05). ROC curve analysis revealed superior diagnostic accuracy for 40 keV (AUC: 0.910) and 50 keV (AUC: 0.910) images based on CT values compared to conventional images (AUC: 0.849)., Conclusions: Virtual monoenergetic images reconstructed at 40 keV and 50 keV from DECT arterial phase scans substantially enhance the image quality of prostate lesions and improve diagnostic efficacy for prostate cancer., (© 2024. The Author(s).)

Background: The molecular mechanisms underlying nonalcoholic fatty liver disease (NAFLD) remain to be fully elucidated. Ubiquitin specific protease 13 (USP13) is a critical participant in inflammation-related signaling pathways, which are linked to NAFLD. Herein, the roles of USP13 in NAFLD and the underlying mechanisms were investigated., Methods: L02 cells and mouse primary hepatocytes were subjected to free fatty acid (FFA) to establish an in vitro model reflective of NAFLD. To prepare in vivo model of NAFLD, mice fed a high-fat diet (HFD) for 16 weeks and leptin-deficient (ob/ob) mice were used. USP13 overexpression and knockout (KO) strategies were employed to study the function of USP13 in NAFLD in mice., Results: The expression of USP13 was markedly decreased in both in vitro and in vivo models of NAFLD. USP13 overexpression evidently inhibited lipid accumulation and inflammation in FFA-treated L02 cells in vitro. Consistently, the in vivo experiments showed that USP13 overexpression ameliorated hepatic steatosis and metabolic disorders in HFD-fed mice, while its deficiency led to contrary outcomes. Additionally, inflammation was similarly attenuated by USP13 overexpression and aggravated by its deficiency in HFD-fed mice. Notably, overexpressing of USP13 also markedly alleviated hepatic steatosis and inflammation in ob/ob mice. Mechanistically, USP13 bound to transforming growth factor β-activated kinase 1 (TAK1) and inhibited K63 ubiquitination and phosphorylation of TAK1, thereby dampening downstream inflammatory pathways and promoting insulin signaling pathways. Inhibition of TAK1 activation reversed the exacerbation of NAFLD caused by USP13 deficiency in mice., Conclusions: Our findings indicate the protective role of USP13 in NAFLD progression through its interaction with TAK1 and inhibition the ubiquitination and phosphorylation of TAK1. Targeting the USP13-TAK1 axis emerges as a promising therapeutic strategy for NAFLD treatment., (© 2024. The Author(s).)

Background: Upper lumbar disc herniation (ULDH) accounts for 1-10% of all lumbar disc herniations (LDH). This study aimed to evaluate the clinical characteristics and outcomes of patients with ULDH who underwent percutaneous transforaminal endoscopic discectomy (PTED) compared with those with lower LDH., Methods: 60 patients with ULDH or L4-L5 LDH treated with PTED between May 2016 and October 2021. MacNab criteria, visual analog scale (VAS) of back pain and leg pain, and Japanese Orthopedic Association (JOA) were evaluated before and after surgery., Results: In the L1-L3 group, 59.1% of the patients had a positive femoral nerve tension test, and 81.8% of the patients had a sensory deficit. Both groups showed significant improvements in VAS scores for low back and leg pain, and JOA scores postoperatively. No significant differences in the degree of improvement were observed between the two groups. The excellent/good rate was 81.8% in the L1-L3 group and 84.2% in the L4-L5 group, showing no significant difference., Conclusion: PTED has comparable efficacy in treating ULDH as it does in treating lower LDH, it is a safe and effective treatment method for ULDH., (© 2024. The Author(s).)

Background: Chronic Lateral Ankle Instability (CLAI) is a common condition treated using either Anterior Talofibular and Calcaneofibular Ligament (ATFL and CFL) reconstruction or Modified Brostrom Procedure (MBP). However, the comparative efficacy of these approaches is not well-studied., Methods: In this study, clinical data were retrospectively collected from 101 patients diagnosed with CLAI who underwent either ATFL and CFL reconstruction (n = 51) or the MBP (n = 50). Patients were comparable in terms of age, sex, Body Mass Index (BMI), post-injury duration, preoperative American Orthopedic Foot and Ankle Society (AOFAS) score, Karlsson score, Visual Analog Score (VAS), Anterior Talar Translation, and Talar Tilt Angle., Results: The post-operative measures showed no significant differences in AOFAS Score, Karlsson Score, and VAS between both treatment groups. However, patients who underwent ATFL and CFL reconstruction showed significantly lower follow-up Anterior Talar Translation (mean = 4.1667 ± 1.3991 mm) and Talar Tilt Angle (mean = 5.0549 ± 1.6173°) compared to those who underwent MBP. Further, patients treated with ATFL and CFL reconstruction experienced a significantly longer postoperative recovery time (median = 6 weeks) compared to MBP (median = 3 weeks)., Conclusions: Although both therapeutic techniques were generally effective in treating CLAI, the ATFL and CFL reconstruction approach delivered superior control of Anterior Talar Translation and Talar Tilt Angle. However, its longer recovery time merits further study to optimize the balance between therapeutic efficacy and recovery speed., (© 2024. The Author(s).)

Background: The specific pathogenesis of UC is still unclear, but it has been clear that defects in intestinal barrier function play an important role in it. There is a temporary lack of specific drugs for clinical treatment. Astragaloside IV (AS-IV) is one of the main active ingredients extracted from Astragalus root and is a common Chinese herbal medicine for the treatment of gastrointestinal diseases. This study aimed to determine whether AS-IV has therapeutic value for DSS or LPS-induced intestinal epithelial barrier dysfunction in vivo and in vitro and its potential molecular mechanisms., Methods: The intestinal tissues from UC patients and colitis mice were collected, intestinal inflammation was observed by colonoscopy, and mucosal barrier function was measured by immunofluorescence staining. PI3K/AKT signaling pathway activator YS-49 and inhibitor LY-29 were administered to colitic mice to uncover the effect of this pathway on gut mucosal barrier modulation. Then, network pharmacology was used to screen Astragaloside IV (AS-IV), a core active component of the traditional Chinese medicine Astragalus membranaceus. The potential of AS-IV for intestinal barrier function repairment and UC treatment through blockade of the PI3K/AKT pathway was further confirmed by histopathological staining, FITC-dextran, transmission electron microscopy, ELISA, immunofluorescence, qRT-PCR, and western blotting. Finally, 16 S rRNA sequencing was performed to uncover whether AS-IV can ameliorate UC by regulating gut microbiota homeostasis., Results: Mucosal barrier function was significantly damaged in UC patients and murine colitis, and the activated PI3K/AKT signaling pathway was extensively involved. Both in vivo and vitro showed that the AS-IV-treated group significantly relieved inflammation and improved intestinal epithelial permeability by inhibiting the activation of the PI3K/AKT signaling pathway. In addition, microbiome data found that gut microbiota participates in AS-IV-mediated intestinal barrier recovery as well., Conclusions: Our study highlights that AS-IV exerts a protective effect on the integrality of the mucosal barrier in UC based on the PI3K/AKT pathway, and AS-IV may serve as a novel AKT inhibitor to provide a potential therapy for UC., (© 2024. The Author(s).)

Background: Few studies have focused on functional impairment in depressed patients during symptomatic remission. The exact relationship between cognitive performance and functional outcomes of patients with Major depressive disorder (MDD) remains unclear., Methods: Participants diagnosed with MDD were included and interviewed at both baseline and follow-up. Cognitive function was assessed during acute episodes using the Cambridge Neuropsychological Test Automated Battery (CANTAB), which targeted attention (Rapid Visual Processing - RVP), visual memory (Pattern Recognition Memory - PRM), and executive function (Intra-Extra Dimensional Set Shift - IED). The 17-item Hamilton Depression Scale (HAMD) was used for symptom assessment. Participants were divided into two groups based on their SDSS (Social Disability Screening Schedule) scores, and the differences between their demographic information, HAMD scores, and baseline CANTAB test results were compared. Logistic regression analysis was used to identify cognitive predictors of social function during symptomatic remission., Results: According to the SDSS score at follow-up, 103 patients were divided into the normal social function group (n = 81,78.6%) and the poor social function group (n = 22, 21.4%) during clinical remission. Participants with poorer social function performed worse in the visual memory (PRM) and executive function tests (IED) at the baseline. Logistic regression analysis suggested that performance on the PRM (95%CI = 0.31-0.93, p = 0.030) and IED (95%CI = 1.01-1.13, p = 0.014) tests, instead of less severe symptoms, significantly contributed to functional outcomes., Conclusion: Better performance in visual memory and executive function during acute episodes may predict better social functional outcomes in individuals with MDD. A potential early intervention to improve social function in individuals with MDD could include the treatments for executive function and visual memory., (© 2024. The Author(s).)

Background: Small extracellular vesicles (sEV) are closely associated with the development and metastasis of many types of mammalian cancer. Glycoconjugates are highly expressed on sEV and play important roles in sEV biogenesis and their interaction with other cells. However, the study on vesicular glycoconjugates are far behind proteins and nucleic acids. Especially, the functions of sialic acids which are the terminal components of glycoconjugates, are poorly understood in sEV., Methods: Sialic acid levels on sEV from plasma and bladder cancer cells were determined by ELISA and lectin blotting. Effects of sialylation on sEV uptake were determined by flow cytometry. Vesicular glycoproteins bearing sialic acids responsible for sEV uptake was identified by proteomics and density gradient centrifugation, and their site-specific sialylation functions were assayed by N-glycosylation site mutation. Effects of integrin β1 bearing sialic acids on the pro-metastatic function of sEV in vivo were explored using Balb/c nu/nu mice., Results: (1) Increased sialic acid levels were observed in sEV from malignant bladder cancer cells. (2) Elimination of sialic acids on sEV impaired sEV uptake by recipient cells. (3) Vesicular integrin β1 bearing sialic acids was identified to play a key role in sEV uptake. (4) Desialylation of the hybrid domain of vesicular integrin β1 inhibited its binding to matrix fibronectin, and reduced sEV entry into recipient cells. (5) Sialylation on integrin β1 affected pro-metastatic function of sEV in Balb/c nu/nu mice., Conclusions: Taken together, our findings indicate important functional roles of sialic acids in sEV uptake and reprogramming plasticity of surrounding normal epithelial cells., (© 2024. The Author(s).)

Background: Cognitive and emotional impairment are among the core features of schizophrenia; assessment of vocal emotion recognition may facilitate the detection of schizophrenia. We explored the differences between cognitive and social aspects of emotion using vocal emotion recognition and detailed clinical characterization., Methods: Clinical symptoms and social and cognitive functioning were assessed by trained clinical psychiatrists. A vocal emotion perception test, including an assessment of emotion recognition and emotional intensity, was conducted. One-hundred-six patients with schizophrenia (SCZ) and 230 healthy controls (HCs) were recruited., Results: Considering emotion recognition, scores for all emotion categories were significantly lower in SCZ compared to HC. Considering emotional intensity, scores for anger, calmness, sadness, and surprise were significantly lower in the SCZs. Vocal recognition patterns showed a trend of unification and simplification in SCZs. A direct correlation was confirmed between vocal recognition impairment and cognition. In diagnostic tests, only the total score of vocal emotion recognition was a reliable index for the presence of schizophrenia., Conclusions: This study shows that patients with schizophrenia are characterized by impaired vocal emotion perception. Furthermore, explicit and implicit vocal emotion perception processing in individuals with schizophrenia are viewed as distinct entities. This study provides a voice recognition tool to facilitate and improve the diagnosis of schizophrenia., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Aberrant ubiquitin-proteasome system (UPS) triggers various disorders of biological events and contributes to progression of tumorigenesis. The tripartite motif containing 22 (TRIM22) was demonstrated to participate in the progression of multiple malignancies. Nevertheless, the role of TRIM22 in melanoma is still indefinite. This project aims to investigate the biological function of TRIM22 in melanoma and provide novel therapeutical targets., Methods: Bioinformatic algorithms were used to investigate prognostic significance of TRIM22. The in vitro or in vivo assays were used to explore the functions of TRIM22 in melanoma. The Co-Immunoprecipitation (Co-IP) and in vivo ubiquitination assays were used to assess regulations of TRIM22 on lysine acetyltransferase 2 A (KAT2A). The Chromatin immunoprecipitation (ChIP) assays and luciferase reporter assay were utilized to explore epigenetic regulations of KAT2A on Notch1., Results: Here, we utilized the bioinformatic methods to confirm that TRIM22 is decreased in melanoma than normal tissues. Patients with low TRIM22 levels had shorter survival months than those with high TRIM22 levels. Targeting TRIM22 favors melanoma cell migration, proliferation, and tumor development in vitro and in vivo. Mechanistically, TRIM22 interacts with KAT2A and promotes its degradation in a ubiquitination-dependent manner. Melanoma cells with TRIM22 deficiency depended on KAT2A to enhance malignant progression, including proliferation, migration, and in vivo growth. KEGG analysis determined the positive correlation between KAT2A and Notch signaling. Chromatin Immunoprecipitation (ChIP) assays implicated that KAT2A directly binds to the promoter region of Notch1 and mediates the enrichment of H3K9ac modification. KAT2A activates Notch1 transcriptional levels and sustains the stemness feature of melanoma cells. Nocth1 inhibitor (IMR-1) effectively suppresses the growth of TRIM22 low melanoma in vitro and in vivo but fails to inhibit TRIM22 high melanoma., Conclusion: Together, our study illustrates the mechanism by which the TRIM22-KAT2A-Notch1 axis promotes melanoma progression, and demonstrates that KAT2A/Nocth1 confers an epigenetic vulnerability in TRIM22 low melanoma., (© 2023. The Author(s).)

Background: Regorafenib is an oral multikinase inhibitor and became the first second-line systemic treatment for hepatocellular carcinoma (HCC) following the phase III RESORCE trial. This single-center study retrospectively analyzed the clinical data and follow-up results of patients with recurrent HCC treated with regorafenib and discussed the prognostic factors to provide guidance for clinical treatment., Methods: Ninety-three recurrent HCC patients were enrolled in the research and follow up from December 2017 to December 2020. Clinical and pathological data were collected. SPSS software v26.0 was used (Chicago, IL, USA) for statistical analysis. A two-sided P < 0.05 was considered statistically significant., Results: The patients included 81 males and 12 females with a median age of 57 years. Eighty-seven patients had hepatitis B virus (HBV) infection. The objective response rate (ORR) was 14.0%, and the disease control rate (DCR) was 62.4%. The median overall survival (mOS) and median time to progression (mTTP) were 15.9 and 5.0 months. Multivariate analysis showed that Child-Pugh classification, the Eastern Cooperative Oncology Group performance status (ECOG PS), the neutrophil-to-lymphocyte ratio (NLR), combined treatment, and the time from first diagnosis of HCC to second-line treatment were independent factors affecting the prognosis of recurrent HCC patients., Conclusions: This real-world study demonstrated similar findings to those of the RESORCE trial. Regorafenib could effectively improve the prognosis of patients after first-line treatment failure. Combination therapy under multidisciplinary treatment (MDT) team guidance could be effective in impeding tumor progression and improving the prognosis of recurrent HCC patients., (© 2023. The Author(s).)

Background: Liver transplantation is one of the most effective treatments for end-stage liver disease. Split liver transplantation (SLT) can effectively improve the utilization efficiency of grafts. However, split liver transplantation still faces shortcomings and is not widely used in surgery. How to improve the effective transplantation volume of split liver transplantation and promote the postoperative recovery of patients has important clinical significance., Methods: In our study, the donor's liver was split into the extended right graft and left lateral sector, and the IV segment occur ischemia. To guarantee the functional graft size, and avoid complications, we reconstructed the IV segment portal vein and left portal vein. And we analyzed the operation time, intraoperative bleeding, liver function, and postoperative complications., Results: In our research, 14 patients underwent IV segment portal vein reconstruction, and 8 patients did not undergo vascular reconstruction. We found that the ischemic area of the IV segment decreased significantly after IV segment portal vein reconstruction. We found that there was no significant difference in operation time and postoperative complications between the patients of the groups. There were significant differences in ALT on the 1st day and albumin on the 6th day after the operation., Conclusion: It indicates that IV segment reconstruction in SLT surgery can alleviate the graft ischemic and promote the recovery of liver function after the operation. And, IV segment reconstruction as a novel operating procedure may be widely used in SLT., (© 2022. The Author(s).)

Background: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. The fat mass and obesity-associated protein (FTO) has been shown to be involved in obesity; however, its role in NAFLD and the underlying molecular mechanisms remain largely unknown., Methods: FTO expression was first examined in the livers of patients with NAFLD and animal and cellular models of NAFLD by real-time PCR and Western blotting. Next, its role in lipid accumulation in hepatocytes was assessed both in vitro and in vivo via gene overexpression and knockdown studies., Results: FTO expression was obviously elevated in the livers of mice and humans with hepatic steatosis, probably due to its decreased ubiquitination. FTO overexpression in HepG2 cells induced triglyceride accumulation, whereas FTO knockdown exerted an opposing effect. Consistent with the findings of in vitro studies, adeno-associated viruses 8 (AAV8)-mediated FTO overexpression in the liver promoted hepatic steatosis in C57BL/6J mice. Mechanistically, FTO inhibited the mRNA of peroxisome proliferator-activated receptor α (PPARα) in hepatocytes. Activation of PPARα by its agonist GW7647 reversed lipid accumulation in hepatocytes induced by FTO overexpression., Conclusions: Overall, FTO expression is increased in NAFLD, and it promotes hepatic steatosis by targeting PPARα., (© 2022. The Author(s).)

Background: With the advancements in surgical methods, optical designs, and surgical instruments, percutaneous endoscopic transforaminal discectomy (PETD) has become an effective and minimally invasive procedure to treat lumbar spinal stenosis (LSS) in recent years. Few studies have focused on the complications associated with the treatment of LSS using percutaneous endoscopic lumbar discectomy (PELD). This study aimed to summarize the complications of PETD and identify the associated risk factors., Methods: Complications in a total of 738 consecutive LSS patients who underwent single-level PETD were retrospectively recorded and analyzed between January 2016 and July 2020. In addition, a matched case-control study was designed, and according to the date of operation, the control group was matched with patients without complications, with a matching ratio of 1:3. Demographic parameters included age, sex, BMI, smoking and drinking status, comorbidity, and surgical level. The radiological parameters included grade of surgical-level disc degeneration, number of degenerative lumbar discs, grade of lumbar spinal stenosis, degenerative lumbar scoliosis, lumbar lordosis, disc angle, and disc height index. Univariate analysis was performed using independent samples t-test and chi-squared test., Results: The incidence of different types of complications was 9.76% (72/738). The complications and occurrence rates were as follows: recurrence of LSS (rLSS), 2.30% (17/738); persistent lumbosacral or lower extremity pain, 3.79% (28/738); dural tear, 1.90% (14/738); incomplete decompression, 0.81% (6/738); surgical site infection, 0.41% (3/738); epidural hematoma, 0.27% (2/738); and intraoperative posterior neck pain, 0.27% (2/738). Univariate analysis demonstrated that age, the grade of surgical-level disc degeneration (P < 0.001) and the number of disc degeneration levels (P = 0.004) were significantly related to the complications., Conclusion: Complications in the treatment of LSS using PELD included rLSS, persistent pain of the lumbosacral or lower extremity, dural tear, incomplete decompression, surgical site infection, epidural hematoma, and intraoperative posterior neck pain. In addition, old age, severe grade of surgical-level disc degeneration and more disc degeneration levels significantly increased the incidence of complications., (© 2021. The Author(s).)

Background: Asf1 is a well-conserved histone chaperone that regulates multiple cellular processes in different species. Two paralogous genes, Asf1a and Asf1b exist in mammals, but their role during fertilization and early embryogenesis remains to be investigated further., Methods: We analyzed the dynamics of histone chaperone Asf1a and Asf1b in oocytes and pre-implantation embryos in mice by immunofluorescence and real-time quantitative PCR, and further investigated the role of Asf1a and Asf1b during fertilization and pre-implantation development by specific Morpholino oligos-mediated knock down approach., Results: Immunofluorescence with specific antibodies revealed that both Asf1a and Asf1b were deposited in the nuclei of fully grown oocytes, accumulated abundantly in zygote and 2-cell embryonic nuclei, but turned low at 4-cell stage embryos. In contrast to the weak but definite nuclear deposition of Asf1a, Asf1b disappeared from embryonic nuclei at morula and blastocyst stages. The knockdown of Asf1a and Asf1b by specific Morpholino oligos revealed that Asf1a but not Asf1b was required for the histone H3.3 assembly in paternal pronucleus. However, knockdown of either Asf1a or Asf1b expression decreased developmental potential of pre-implantation embryos. Furthermore, while Asf1a KD severely reduced H3K56 acetylation level and the expression of Oct4 in blastocyst stage embryos, Asf1b KD almost eliminated nuclear accumulation of proliferating cell marker-PCNA in morula stage embryos. These results suggested that histone chaperone Asf1a and Asf1b play distinct roles during fertilization and pre-implantation development in mice., Conclusions: Our data suggested that both Asf1a and Asf1b are required for pre-implantation embryonic development. Asf1a regulates H3K56ac levels and Oct4 expression, while Asf1b safeguards pre-implantation embryo development by regulating cell proliferation. We also showed that Asf1a, but not Asf1b, was necessary for the assembly of histone H3.3 in paternal pronuclei after fertilization., (© 2021. The Author(s).)

Background: Although recent studies have investigated the risk factors for PSI, few studies have focused on the impact of scoliotic correction on postoperative shoulder imbalance (PSI), especially in severe and rigid scoliosis (SRS). The purpose of the study was to study the effect of scoliotic correction on PSI in SRS., Methods: The preoperative, postoperative, and minimum 2-year follow-up radiographs of 48 consecutive patients with SRS who underwent posterior spinal fusion surgery were evaluated. We regarded radiographic shoulder height (RSH) as a shoulder balance parameter and divided the patients into improved and aggravated groups of PSI from pre- to post-operation and from post-operation to last follow-up, respectively. In addition, patients were divided into nine groups based on the observed changes in PSI after surgery and at follow-up, and the correction rate ratios were calculated among the groups. Independent samples T test and Chi-squared test were performed between the improved and aggravated groups of PSI., Results: After surgery, the proximal thoracic curve (PTC) flexibility (P = 0.040), correction rate of the main thoracic curve (MTC) (P = 0.010), and Cobb angle of the lumbar curve (LC) (P = 0.037) were significantly higher, while the ratio of the correction rate of the PTC to the MTC (P = 0.042) was smaller in the aggravated group. At follow-up, the improved group had significantly larger PTC flexibility (P = 0.006), larger ratio of the correction rate of PTC to MTC (P = 0.046), a larger ratio correction rate of PTC to LC (P = 0.027), and a smaller correction rate of LC (P = 0.030). The correction rate ratios of the groups after surgery were as follows: negative to negative (N-N) (1.08) > negative to balance (N-B) (0.96) > negative to positive (N-P) (0.67), B-N (1.26) > B-B (0.94) > B-P (0.89), and P-N (0.34) > P-P (0.83). The order of the correction rate ratio at follow-up was as follows: N-N (0.96) > N-B (0.51), B-B (0.97) > B-P (0.90), and P-B (0.87) > P-P (0.84)., Conclusion: Harmonizing the correction rate ratio of the PTC, MTC, and LC should be recommended for intraoperative correction and postoperative compensation of PSI. In addition, greater PTC flexibility plays an important role in the spontaneous correction and compensation of PSI in SRS., (© 2021. The Author(s).)

Background: The goal of this study is to disclose the clinically significant genomic alterations in the Chinese and Western patients with intrahepatic cholangiocarcinoma., Methods: A total of 86 Chinese patients were enrolled in this study. A panel of 579 pan-cancer genes was sequenced for the qualified samples from these patients. Driver genes, actionability, and tumor mutational burden were inferred and compared to a cohort of Western patients., Results: Totally, 36 and 12 driver genes were identified in the Chinese and Western cohorts, respectively. Of them, seven driver genes (IDH1, KRAS, TP53, BAP1, PBRM1, ARID1A, and NRAS) were shared by the two cohorts. Four driver genes (SPTA1, ARID2, TP53, and GATA1) were found significantly correlated with the tumor mutational burden. For both cohorts, half of the patients had actionable mutations. The two cohorts shared the most actionable genes but differed much in their frequency. Though KRAS mutations were at the first and second actionable rank respectively for the Chinese and Western populations, they were still at a relatively low level of actionable evidence., Conclusions: The study on the clinical significance of genomic alterations directs the future development of precision medicine for intrahepatic cholangiocarcinoma treatment.

Background: Several studies on the relationship between morphological parameters and traumatic diseases of the knee have already been conducted. However, few studies focused on the association between knee morphology and posterior cruciate ligament (PCL) avulsion fracture in adults. The objective of this study was to evaluate the impact of knee morphology on PCL avulsion fracture., Methods: 76 patients (comprised 40 men and 36 women) with PCL avulsion fracture and 76 age- and sex-matched controls without PCL avulsion fracture were studied from 2012 to 2020. MRI measurements of the knee were acquired in the sagittal, coronal, and axial planes. The assessed measurements including intercondylar notch width index, coronal tibial slope, and medial/lateral posterior tibial slopes were compared between men and women, and between case and control groups respectively using independent sample t-tests. In addition, binary logistic regression analyses were used to identify independent risk factors of PCL avulsion fracture., Results: Except notch width index (coronal) (p = 0.003) in the case groups, there was no statistical difference in the assessed measurements including notch width index (axial), coronal tibial slope, medial posterior tibial slope, and lateral posterior tibial slope between men and women in the case and control groups (p > 0.05). When female patients were analyzed, the notch width index (coronal) was significantly smaller (p = 0.0004), the medial posterior tibial slope (p = 0.018) and the lateral posterior tibial slope (p = 0.033) were significantly higher in the case group. The binary logistic regression analysis showed that the notch width index (coronal) (B = -0.347, OR = 0.707, p = 0.003) was found to be an independent factor of PCL avulsion fracture. However, none of the assessed measurements was found to have a statistical difference between the case and control groups in men (p > 0.05)., Conclusions: Notch width index (coronal), medial posterior tibial slope, and lateral posterior tibial slope were found to affect PCL avulsion fracture in women, but no such measurements affected the PCL avulsion fracture in men. Furthermore, a smaller notch width index (coronal) in women was found to be a risk factor in PCL avulsion fracture.

Background: Anxiety, an important factor that affects the therapeutic effect and preservation rate of methadone maintenance treatment, has a high prevalence among MMT patients. This study aims to investigate the effects of treatment status and life quality on anxiety in MMT patients., Methods: One hundred and Seventy-seven methadone maintenance treatment users in Guangzhou, China were evaluated. The socio-demographic, duration and MMT-related characteristics were documented. Anxiety level and quality of life were evaluated by Beck Anxiety inventory (BAI) and the Quality of Life-Drug Addiction (QOL-DA) respectively. The correlation between different factors and BAI score was also analyzed., Results: The BAI total score and the QOL-DA score were 7.1±8.2, 163.5±21.4 respectively. 30.5% of the subjects showed mild to severe anxiety. Treatment interruption and QOL-DA score had strong correlations with the score of BAI, with correlation coefficients of 0.17 and - 0.08 respectively., Conclusions: Anxiety symptoms were commonly presented in MMT patients. Treatment interruption and quality of life are two major factors affecting anxiety of MMT patients.

Background: Infection is one of the important causes of death in patients with severe acute pancreatitis (SAP), but the bacterial spectrum and antibiotic resistance are constantly changing. Making good use of antibiotics and controlling multi-drug-resistant (MDR) bacterial infections are of vital importance in improving the cure rate of SAP. We conducted a retrospective study in the hope of providing references for antibiotic selection and control of drug-resistant bacteria., Methods: Retrospective analysis was performed on the data of patients hospitalized in our hospital due to acute pancreatitis (AP) in the past 5 years. General data were classified and statistically analyzed. Subsequently, the bacterial spectrum characteristics and the data related to drug-resistant bacterial infection of 569 AP patients were analyzed. Finally, unconditional logistic regression analysis was conducted to analyze the risk factors of MDR infection., Results: A total of 398 patients were enrolled in this study and the hospitalization data and associated results were analyzed. A total of 461 strains of pathogenic bacteria were detected, including 223 (48.4%) gram-negative bacterial strains, 190 (41.2%) gram-positive bacterial strains and 48 (10.4%) fungal strains. The detection rates of resistance in gram-negative and gram-positive bacterial strains were 48.0% (107/223) and 25.3% (48/190), respectively. There were significant differences between the MDR group and the non-MDR group for the factors of precautionary antibiotic use, kinds of antibiotics used, receipt of carbapenem, tracheal intubation, hemofiltration and number of hospitalization days in the intensive care unit. Unconditional logistic regression revealed 2 risk factors for MDR bacterial infection., Conclusions: Our results illustrate that gram-negative bacteria were the most common pathogens in SAP infection, and the proportion of gram-positive bacteria increased notably. The rate of antibiotic resistance was higher than previously reported. Unconditional logistic regression analysis showed that using more types of antibiotics and the number of hospitalization days in the ICU were the risk factors associated with MDR bacterial infection.

Background: Transforaminal percutaneous endoscopic lumbar surgeries (PELS) for lumbar disc herniation and spinal stenosis are growing in popularity. However, there are some problems in the establishment of the working channel and foraminoplasty such as nerve and blood vessel injuries, more radiation exposure, and steeper learning curve. Rapid technological advancements have allowed robotic technology to assist surgeons in improving the accuracy and safety of surgeries. Therefore, the purpose of this study is to develop a robot-assisted system for transforaminal PELS, which can provide navigation and foraminoplasty., Methods: The robot-assisted system consists of three systems: preoperative planning system, navigation system, and foraminoplasty system. In the preoperative planning system, 3D visualization of the surgical segment and surrounding tissues are realized using the multimodal image fusion technique of computed tomography and magnetic resonance imaging, and the working channel planning is carried out to reduce the risk for injury to vital blood vessels and nerves. In the navigation system, the robot can obtain visual perception ability from a visual receptor and automatically adjust the robotic platform and robot arm to the appropriate positions according to the patient's position and preoperative plan. In addition, the robot can automatically register the surgical levels through intraoperative fluoroscopy. After that, the robot will provide navigation using the 6 degree-of-freedom (DOF) robot arm according to the preoperative planning system and guide the surgeon to complete the establishment of the working channel. In the foraminoplasty system, according to the foraminoplasty planning in the preoperative planning system, the robot performs foraminoplasty automatically using the high speed burr at the end of the robot arm. The system can provide real-time feedback on the working status of the bur through multi-mode sensors such as multidimensional force, position, and acceleration. Finally, a prototype of the system is constructed and performance tests are conducted., Discussion: Our study will develop a robot-assisted system to perform transforaminal PELS, and this robot-assisted system can also be used for other percutaneous endoscopic spinal surgeries such as interlaminar PELS and percutaneous endoscopic cervical and thoracic surgeries through further research. The development of this robot-assisted system can be of great significance. First, the robot can improve the accuracy and efficiency of endoscopic spinal surgeries. In addition, it can avoid multiple intraoperative fluoroscopies, minimize exposure to both patients and the surgical staff, shorten the operative time, and improve the learning curve of beginners, which is beneficial to the popularization of percutaneous endoscopic spinal surgeries.

Background: Many studies indicate that gallstone formation has genetic components. The abnormal expression of lipid-related genes could be the basis for particular forms of cholesterol gallstone disease. The aim of this study was to obtain insight into lipid metabolism disorder during cholesterol gallstone formation and to evaluate the effect of ursodeoxycholic acid (UDCA) on the improvement of bile lithogenicity and its potential influence on the transcription of lipid-related genes., Methods: Gallstone-susceptible mouse models were induced by feeding with a lithogenic diet (LD) for 8 weeks. Bile and liver tissues were obtained from these mouse models after 0, 4 and 8 weeks. Bile lipids were measured enzymatically, and the cholesterol saturation index (CSI) was calculated to evaluate the bile lithogenicity by using Carey's critical tables. Real-time polymerase chain reaction (RT-PCR) was used to detect the mRNA expression levels of farnesoid X receptor (FXR), liver X receptor (LXR), adenosine triphosphate-binding cassette subfamily G member 5/8 (ABCG5/8), cholesterol 7-α hydroxylase (CYP7A1), oxysterol 7-α hydroxylase (CYP7B1), sterol 27-α hydroxylase (CYP27A1), peroxisome proliferator-activated receptor alpha (PPAR-α) and adenosine triphosphate-binding cassette subfamily B member 11 (ABCB11)., Results: The rate of gallstone formation was 100% in the 4-week group but only 30% in the UDCA-treated group. The UDCA-treated group had a significantly lower CSI compared with other groups. Of special note, the data on the effects of UDCA showed higher expression levels of ABCG8, ABCB11 and CYP27A1, as well as lower expression levels of LXR and PPAR-α, compared to the model control group., Conclusions: UDCA exhibits tremendously potent activity in restraining lipid accumulation, thus reversing the lithogenic effect and protecting hepatocytes from serious pathological damage. The abnormal expression of ABCG8, CYP7A1, CYP27A1, LXR and PPAR-α might lead to high lithogenicity of bile. These results are helpful in exploring new lipid metabolism pathways and potential targets for the treatment of cholesterol stones and for providing some basis for the study of the pathogenesis and genetic characteristics of cholelithiasis. Research on the mechanism of UDCA in improving lipid metabolism and bile lithogenicity may be helpful for clinical treatment and for reducing the incidence of gallstones.

Background: Triglycerides (TG) to high-density lipoprotein cholesterol (HDL-C) ratio (TG/HDL-C) has been recommended as a surrogate marker for insulin resistance. In the present study, we aimed to investigate the relationship between TG/HDL-C and NAFLD in an apparently healthy population., Methods: A total of 18,061 subjects who participated in a health checkup program were included. NAFLD was diagnosed by ultrasonography., Results: The prevalence rate of NAFLD was 24.8% in the whole population, and progressively increased across the quartiles of TG/HDL-C (4.9, 14.1, 26.8 and 53.5%, respectively, P <  0.001). After adjustment for confounding factors, TG/HDL-C was independently associated with the risk of NAFLD. Compared with the first quartile of TG/HDL-C (Q1), the odds ratios (95% confidence intervals) for NAFLD in the increasing quartiles (Q2-Q4) were 2.1(1.8-2.6), 3.6 (3.0-4.3) and 9.2(7.6-11.1), respectively. In addition, the area under receiver operator characteristic curve (95% confidence interval) of TG/HDL-C for NAFLD was 0.85 (0.84-0.86) in women and 0.79 (0.78-0.80) in men, significantly higher than that of TG, TC, LDL-C, HDL-C, ALT and AST (P <  0.05). The optimal cutoff point of TG/HDL-C for detection of NAFLD was 0.9 in women (sensitivity = 78.8%, specificity = 77.3%) and 1.4 in men (sensitivity = 70.7%, specificity = 73.5%)., Conclusions: TG/HDL-C is independently associated with NAFLD in apparently healthy individuals and may be used as a surrogate for NAFLD.

Objective: To study the clinicopathological characteristics and genetic features of melanin-producing medullary thyroid carcinoma (MP-MTC)., Methods: The immunophenotype of MP-MTC was studied using the immunohistochemical method, and its genetic features were assayed using an amplification refractory mutation system or PCR method., Results: A 71-year-old man presented with a slowly growing 5-cm mass on the left side of the neck for approximately two months. The cut surface of the neoplasm was brown and black. Melanin was found in the cytoplasm of tumor cells or the extracellular matrix. The tumor cells were positive for AE1/AE3, S-100 protein, melan A, HMB-45, synaptophysin, calcitonin, chromogranin A, melanoma, and thyroid transcription factor-1 (TTF-1) and negative for thyroglobulin. No typical genetic features were observed in this case. The patient showed no symptoms and recurrence at 12 months after the operation., Conclusions: The tumor cells of MP-MTC were positive for melanin biomarkers, TTF-1 and exhibited no genetic features. Histopathology and immunohistochemistry of the tumor cells will aid accurate diagnosis.

Background: The increasing prevalence of non-alcoholic fatty liver disease (NAFLD) has followed the international rise in obesity rates. Multiple mechanisms are involved in NAFLD, including endoplasmic reticulum stress and oxidative stress. Heat shock protein 70 (HSP70), which is abundant in most organisms, is sensitive to stress. However, the role of HSP70 in NAFLD has not been investigated. Here, we investigated the possible role of HSP70 in lipid synthesis., Methods: C57BL/6 mice were fed a high-fat diet, and HepG2 cells were treated with 0.5 mM palmitic acid (PA). HSP70 expression was detected by qPCR, Western blot and immunohistochemistry. Total cholesterol (TC) and triglyceride (TG) levels were detected by enzyme-linked immunosorbent assay (ELISA). After Hsp70 overexpression and knockdown, TC and TG levels and FAS, SCD, and ACC expression were detected., Results: HSP70 expression was significantly increased in the livers of obese mice. In vitro, HSP70 expression was markedly induced by PA in HepG2 cells. Notably, HSP70 overexpression in HepG2 cells enhanced TC and TG synthesis, in parallel with the upregulation of lipogenic genes, including FAS, SCD and ACC. By contrast, HSP70 knockdown decreased the levels of cellular lipids and the expression of FAS, SCD, and ACC in HepG2 cells. Together, our results suggest that HSP70 may promote lipogenesis in HepG2 cells., Conclusions: Heat shock protein 70 promotes lipogenesis in HepG2 cells.

Background: Plant height (PH) and ear height (EH) are two important agronomic traits in maize selection breeding. F 1 hybrid exhibit significant heterosis for PH and EH as compared to their parental inbred lines. To understand the genetic basis of heterosis controlling PH and EH, we conducted quantitative trait locus (QTL) analysis using a recombinant inbreed line (RIL) based design III population derived from the elite maize hybrid Zhengdan 958 in five environments., Results: A total of 14 environmentally stable QTLs were identified, and the number of QTLs for Z 1 and Z 2 populations was six and eight, respectively. Notably, all the eight environmentally stable QTLs for Z 2 were characterized by overdominance effect (OD), suggesting that overdominant QTLs were the most important contributors to heterosis for PH and EH. Furthermore, 14 environmentally stable QTLs were anchored on six genomic regions, among which four are trait-specific QTLs, suggesting that the genetic basis for PH and EH is partially different. Additionally, qPH.A-1.3, modifying about 10 centimeters of PH, was further validated in backcross populations., Conclusions: The genetic basis for PH and EH is partially different, and overdominant QTLs are important factors for heterosis of PH and EH. A major QTL qPH.A-1.3 may be a desired target for genetic improvement of maize plant height.

Background: TAR DNA-binding protein 43 (TDP-43) is a nuclear protein, but it is redistributed in the neuronal cytoplasm in both amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Because small transgenic animal models often lack cytoplasmic TDP-43, how the cytoplasmic accumulation of TDP-43 contributes to these diseases remains unclear. The current study is aimed at studying the mechanism of cytoplasmic pathology of TDP-43., Results: We established transgenic pigs expressing mutant TDP-43 (M337V). This pig model shows severe phenotypes and early death. We found that transgenic TDP-43 is also distributed in the cytoplasm of neuronal cells in the spinal cord and brain. Transgenic TDP-43 interacts with PSF, an RNA splicing factor that associates with NeuN to regulate neuronal RNA splicing. The interaction of TDP-43, PSF and NeuN causes PSF and NeuN mislocalize into the neuronal cytoplasm in transgenic pigs. Consistently, abnormal PSF-related neuronal RNA splicing is seen in TDP-43 transgenic pigs. The cytoplasmic localization of PSF and NeuN as well as abnormal PSF-related neuronal RNA splicing was also found in ALS patient brains., Conclusion: Our findings from a large mammalian model suggest that cytoplasmic mutant TDP-43 could reduce the nuclear function of RNA splicing factors, contributing to neuropathology.

Background: Lung cancer has been considered as one of the most important causes of cancer-related mortality worldwide. To predict lung cancer, researchers identified several molecular markers. However, many underlying markers of lung cancer remain unclear. One of these markers is Rab GDP dissociation inhibitor beta (GDIβ), which is related to tumorigenicity, development and invasion. This study was designed to analyze the biological characteristics of Rab GDIβ and to detect the mRNA and protein expressions of Rab GDIβ in lung cancer cells; this study also aimed to investigate the functions of this protein in lung cancer., Method: Using online software from the websites of NCBI, ProtParam and so on, we analyzed the biological characteristics of Rab GDIβ. RT-PCR was performed to detect gene expressions in A549 and 16HBE cell lines and immunohistochemistry (IHC) staining was conducted to detect Rab GDIβ protein expression in 57 cases of human lung cancer tissues and 19 cases of normal lung tissues. The association of protein expression with patient clinical and pathological characteristics was assessed in each dataset., Results: Bioinformatic analysis on Rab GDIβ: The mRNA of human Rab GDIβ contains two transcript variants; the common structural elements of the two proteins are mainly α-helix, random coil, β-turn and extended strand. Three and four transmembrane domains could be found in the entire polypeptide chain of protein variants 1 and 2, respectively; both transcript variants are hydrophilic and soluble proteins. The RT-PCR result: The mRNA expression of Rab GDIβ was down-regulation in A549 cells compared with that in 16HBE cells. The IHC result: The protein expression of Rab GDIβ in lung cancer cells was significantly lower than that in normal lung tissues (P <0.05) but was not correlated with patients' age, gender, tumor size, pathological type, differentiation, lymph node metastasis, distant metastasis and TNM stage., Conclusion: The expression of Rab GDIβ was low in non-small cell lung cancer (NSCLC). Hence, Rab GDIβ may be a tumor suppressor and could function as an indicator of tumorigenesis in NSCLC; nevertheless, this result should be further studied., Virtual Slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000&#95;2014&#95;201.

Purpose: Stigma towards people with mental illness is believed to be widespread in low and middle income countries., Methods: This study assessed the attitudes towards people with mental illness among psychiatrists, psychiatric nurses, involved family members of patients in a psychiatric facility and the general public using a standard 43-item survey (N = 535). Exploratory factor analysis identified four distinctive attitudes which were then compared using Analysis of Covariance (ANCOVA) among the four groups, all with ties to the largest psychiatric facility in Guangzhou, China, adjusting for sociodemographic differences., Results: Four uncorrelated factors expressed preferences for 1) community-based treatment, social integration and a biopsychosocial model of causation, 2) direct personal relationships with people with mental illness, 3) a lack of fear and positive views of personal interactions with people with mental illness, 4) disbelief in superstitious explanations of mental illness. Statistically significant differences favored community-based treatment and biopsychosocial causation (factor 1) among professional groups (psychiatrists and nurses) as compared with family members and the general public (p < 0.001); while family members, unexpectedly, showed far weaker personal preferences for direct personal relationships with people with mental illness than all three other groups (p < 0.001)., Conclusion: Both psychiatrists and nurses showed greater support for social integration and biopsychosocial understandings of mental illness than the lay public, most likely because of their training and experience, while family members showed the least positive attitudes towards direct personal relationships with people with mental illness. These findings suggest support for a more extensive, formal system of care that gives family members some distance from the problems of their relatives and support in their care.