Search

Introduction: This study aims to compare the efficacy of ropivacaine and lidocaine in the treatment of temporomandibular joint (TMJ) disorders, with the goal of exploring a more effective treatment for TMJ disorders., Methods: Patients with Wilkes stage III and IV unilateral TMJ disorders were enrolled in the study. 0.5% ropivacaine was used for local anesthesia in group A, 2% lidocaine was used in group B. Sodium hyaluronate was injected after supra-articular lavage in both groups. The patients' general conditions, pain scores, and maximum opening before and after treatment were collected, the time of onset and maintenance of anesthesia, and the levels of inflammatory factors IL-1β and IL-6 in the joint lavage fluid were detected., Results: Study showed that the onset of anesthesia was faster and longer maintained in group A. The decrease in IL-1β was more pronounced in group A (16.08 ± 3.10) than in group B (18.03 ± 2.84), p < 0.05. At 2 months after treatment, the joint clicking rate was higher in group A (75%) compared to group B (35%), p < 0.05. At 3 months after treatment, the joint clicking rate was higher in group A (76.69%) compared to group B (40%) and the maximum mouth opening was greater in group A (45.00 ± 2.38) compared to group B (41.73 ± 4.18), p < 0.05. There were no statistically significant differences in VAS score and lateral excursion in group A compared with group B at 2 months and 3 months after treatment., Conclusions: Compared with lidocaine, the application of ropivacaine combined with sodium hyaluronate supra-articular lavage for the treatment of temporomandibular joint disorder is more clinically effective., Clinical Trials Registration Number: ChiCTR2300075241 (30/08/2023)., (© 2024. The Author(s).)

The proficient handling of diabetic wounds, a rising issue coinciding with the global escalation of diabetes cases, poses significant clinical difficulties. A range of biofunctional dressings have been engineered and produced to expedite the healing process of diabetic wounds. This study proposes a multifunctional hydrogel dressing for diabetic wound healing, which is composed of Polyvinyl Alcohol (PVA) and N 1 -(4-boronobenzyl)-N 3 -(4-boronophenyl)-N 1 , N 1 , N 3 , N 3 -teramethylpropane-1, 3-diaminium (TSPBA), and a dual-drug loaded Gelatin methacryloyl (GM) microgel. The GM microgel is loaded with sodium fusidate (SF) and nanoliposomes (LP) that contain metformin hydrochloride (MH). Notably, adhesive and self-healing properties the hydrogel enhance their therapeutic potential and ease of application. In vitro assessments indicate that SF-infused hydrogel can eliminate more than 98% of bacteria within 24 h and maintain a sustained release over 15 days. Additionally, MH incorporated within the hydrogel has demonstrated effective glucose level regulation for a duration exceeding 15 days. The hydrogel demonstrates a sustained ability to neutralize ROS throughout the entire healing process, predominantly by electron donation and sequestration. This multifunctional hydrogel dressing, which integrated biological functions of efficient bactericidal activity against both MSSA and MRSA strains, blood glucose modulation, and control of active oxygen levels, has successfully promoted the healing of diabetic wounds in rats in 14 days. The hydrogel dressing exhibited significant effectiveness in facilitating the healing process of diabetic wounds, highlighting its considerable promise for clinical translation., (© 2024. The Author(s).)

Background: Diabetic wounds present significant challenges, specifically in terms of bacterial infection and delayed healing. Therefore, it is crucial to address local bacterial issues and promote accelerated wound healing. In this investigation, we utilized electrospinning to fabricate microgel/nanofiber membranes encapsulating MXene-encapsulated microgels and chitosan/gelatin polymers., Results: The film dressing facilitates programmed photothermal therapy (PPT) and mild photothermal therapy (MPTT) under near-infrared (NIR), showcasing swift and extensive antibacterial and biofilm-disrupting capabilities. The PPT effect achieves prompt sterilization within 5 min at 52 °C and disperses mature biofilm within 10 min. Concurrently, by adjusting the NIR power to induce local mild heating (42 °C), the dressing stimulates fibroblast proliferation and migration, significantly enhancing vascularization. Moreover, in vivo experimentation successfully validates the film dressing, underscoring its immense potential in addressing the intricacies of diabetic wounds., Conclusions: The MXene microgel-loaded nanofiber dressing employs temperature-coordinated photothermal therapy, effectively amalgamating the advantageous features of high-temperature sterilization and low-temperature promotion of wound healing. It exhibits rapid, broad-spectrum antibacterial and biofilm-disrupting capabilities, exceptional biocompatibility, and noteworthy effects on promoting cell proliferation and vascularization. These results affirm the efficacy of our nanofiber dressing, highlighting its significant potential in addressing the challenge of diabetic wounds struggling to heal due to infection., (© 2024. The Author(s).)

Diabetic wounds pose a challenge to healing due to increased bacterial susceptibility and poor vascularization. Effective healing requires simultaneous bacterial and biofilm elimination and angiogenesis stimulation. In this study, we incorporated polyaniline (PANI) and S-Nitrosoglutathione (GSNO) into a polyvinyl alcohol, chitosan, and hydroxypropyltrimethyl ammonium chloride chitosan (PVA/CS/HTCC) matrix, creating a versatile wound dressing membrane through electrospinning. The dressing combines the advantages of photothermal antibacterial therapy and nitric oxide gas therapy, exhibiting enduring and effective bactericidal activity and biofilm disruption against methicillin-sensitive Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, and Escherichia coli. Furthermore, the membrane's PTT effect and NO release exhibit significant synergistic activation, enabling a nanodetonator-like burst release of NO through NIR irradiation to disintegrate biofilms. Importantly, the nanofiber sustained a uniform release of nitric oxide, thereby catalyzing angiogenesis and advancing cellular migration. Ultimately, the employment of this membrane dressing culminated in the efficacious amelioration of diabetic-infected wounds in Sprague-Dawley rats, achieving wound closure within a concise duration of 14 days. Upon applying NIR irradiation to the PVA-CS-HTCC-PANI-GSNO nanofiber membrane, it swiftly eradicates bacteria and biofilm within 5 min, enhancing its inherent antibacterial and anti-biofilm properties through the powerful synergistic action of PTT and NO therapy. It also promotes angiogenesis, exhibits excellent biocompatibility, and is easy to use, highlighting its potential in treating diabetic wounds., (© 2024. The Author(s).)

Background: The early Cambrian arthropod clade Megacheira, also referred to as great appendage arthropods, comprised a group of diminutive and elongated predators during the early Palaeozoic era, around 518 million years ago. In addition to those identified in the mid-Cambrian Burgess Shale biota, numerous species are documented in the renowned 518-million-year-old Chengjiang biota of South China. Notably, one species, Tanglangia longicaudata, has remained inadequately understood due to limited available material and technological constraints. In this study, we, for the first time, examined eight fossil specimens (six individuals) utilizing state-of-the-art μCT and computer-based 3D rendering techniques to unveil the hitherto hidden ventral and appendicular morphology of this species., Results: We have identified a set of slender endopodites gradually narrowing distally, along with a leaf-shaped exopodite adorned with fringed setae along its margins, and a small putative exite attached to the basipodite. Our techniques have further revealed the presence of four pairs of biramous appendages in the head, aligning with the recently reported six-segmented head in other early euarthropods. Additionally, we have discerned two peduncle elements for the great appendage. These findings underscore that, despite the morphological diversity observed in early euarthropods, there exists similarity in appendicular morphology across various groups. In addition, we critically examine the existing literature on this taxon, disentangling previous mislabelings, mentions, descriptions, and, most importantly, illustrations., Conclusions: The μCT-based investigation of fossil material of Tanglangia longicaudata, a distinctive early Cambrian euarthropod from the renowned Chengjiang biota, enhances our comprehensive understanding of the evolutionary morphology of the Megacheira. Its overall morphological features, including large cup-shaped eyes, raptorial great appendages, and a remarkably elongated telson, suggest its potential ecological role as a crepuscular predator and adept swimmer in turbid waters., (© 2024. The Author(s).)

Background: Central nervous system leukemia (CNSL) is one of the major causes of the poor prognosis of childhood leukemia. We aimed to compare the sensitivity of cytomorphology (CM) and flow cytometry (FCM) in diagnosing CNSL, emphasizing the importance of FCM in the diagnosis process., Methods: One-hundred-sixty-five children with newly diagnosed B-cell Acute Lymphoblastic Leukemia (B-cell ALL) were included in this study. Cerebrospinal fluid (CSF) samples were taken for routine CSF analysis, CM analysis, and FCM examination. Computed tomography scans and/or magnetic resonance imaging were performed at diagnosis. Patients with CNS2, CNS3, and traumatic lumbar puncture (TLP) at diagnosis received two additional courses of triple intrathecal injections during induction treatment. We compared the sensitivity of FCM and CM in the diagnosis of children with CNSL., Results: One hundred and twenty-eight (77.58%) CSF samples were negative by either CM or FCM (CM - /FCM - ), four (2.42%) were positive by both CM and FCM (CM + /FCM + ), and thirty-three (20%) displayed a single positive finding by FCM (CM - /FCM + ) (p = 0.044). By adding two intrathecal injections in the induction treatment, ten children with TLP + had no CNS relapse, like those with TLP - . However, compared to CNS1 and TLP, the event-free survival (EFS) did not significantly improve in patients with CNS2 and CNS3. Moreover, CNSL status was associated with worse 3-year EFS (p < 0.05)., Conclusions: We have validated that FCM is more accurate in stratifying the status of the CNS compared to CM analysis. However, to improve the EFS rate of childhood leukemia, it is necessary to combine CM examination, FCM, and cranial imaging for the early diagnosis of CNSL., (© 2024. The Author(s).)

Background: Prompt response to induction chemotherapy is a prognostic factor in pediatric acute myeloid leukemia. In this study, we aimed to evaluate the prognostic significance of multiparametric flow cytometry-minimal residual disease (MFC-MRD), assessed at the end of the first and second induction courses., Methods: MFC-MRD was performed at the end of the first induction (TP1) in 524 patients and second induction (TP2) in 467 patients who were treated according to the modified Medical Research Council (UK) acute myeloid leukemia 15 protocol., Results: Using a 0.1% cutoff level, patients with MFC-MRD at the two time points had lower event-free survival and overall survival. Only the TP2 MFC-MRD level could predict the outcome in a separate analysis of high and intermediate risks based on European LeukemiaNet risk stratification and KMT2A rearrangement. The TP2 MFC-MRD level could further differentiate the prognosis of patients into complete remission or non-complete remission based on morphological evaluation. Multivariate analysis indicated the TP2 MFC-MRD level as an independent adverse prognostic factor for event-free survival and overall survival. When comparing patients with MFC-MRD ≥ 0.1%, those who underwent hematopoietic stem cell transplant during the first complete remission had significantly higher 5-year event-free survival and overall survival and lower cumulative incidence of relapse than those who only received consolidation chemotherapy., Conclusions: The TP2 MFC-MRD level can predict the outcomes in pediatric patients with acute myeloid leukemia and help stratify post-remission treatment., (© 2024. The Author(s).)

Background: Osteoarthritis (OA) is a degenerative disease related to cholesterol metabolism disorders. However, current therapies for OA are insufficient and no convincing disease-modifying OA drugs exist. Therefore, we aimed to elucidate the mechanism by which borojoa iridoid glycoside (BIG) inhibits chondrocyte apoptosis in OA., Methods: Borojoa pulp was heated to 70 °C, and the main active substance in borojoa, BIG, was extracted by fractionation at an ultraviolet 254-nm absorption peak. Chondrocytes were identified by immunohistochemistry and visualized by immunofluorescence confocal microscopy. The proliferation of chondrocytes cultured with BIG was determined by MTS assay. The apoptosis of chondrocytes cultured with BIG was tested by Annexin V-FITC/PI, and the cytokine, protein, and cholesterol levels in chondrocytes were detected by ELISA, RT‒qPCR, Western blot, and biochemistry analyses. Protein‒protein interactions were verified by a coimmunoprecipitation (Co-IP) assay., Results: BIG promoted chondrocyte proliferation and reduced apoptosis in vitro. BIG induced an alteration of the total RNA profiles in chondrocytes, and bioinformatic analysis showed that BIG inhibited chondrocyte apoptosis by promoting c-MYC expression; KEGG analysis confirmed that BIG-inhibited apoptosis was enriched in the cell cycle pathway. Flow cell cycle experiments confirmed that BIG promoted chondrocyte proliferation by significantly increasing the S phase cell number. The c-MYC inhibitor 10058-F4 stimulated the increased expression of IL-1β, IL-6, TNF-α, and AGEs and suppressed the cholesterol metabolism, which promoted chondrocyte apoptosis and autophagy. Co-IP analysis showed that BIG promoted the interaction of c-MYC and CH25H, Bcl-2, which suggests that BIG could inhibit chondrocyte apoptosis in part by enhancing c-MYC-mediated cholesterol metabolism., Conclusions: This study confirmed that BIG promotes chondrocyte proliferation and inhibits apoptosis and autophagy, and BIG improving OA is associated with cholesterol metabolism. The results identify a potential mechanism by which BIG enhances c-MYC-mediated CH25H regulation of cholesterol metabolism in vitro and suggest that BIG might be a promising new drug against OA., (© 2023. The Author(s).)

Background: Semen quality significantly influences conception, and its preservation is crucial for couples seeking pregnancy. We investigated dietary and lifestyle risk factors impacting semen quality., Methods: A total of 466 males from the Guangzhou Women and Children's Medical Center's pre-pregnancy consultation clinic were recruited between January 2021 and March 2023 for inclusion. Semen analysis was performed, and diet and lifestyle data were gathered via questionnaire. Logistic regression was utilized to examine the link between diet, lifestyle variables, and semen quality., Results: Smoking worsened progressive sperm motility (38.0% vs. 36.0%, t = 2.262; P = 0.049). Alcohol consumption impaired progressive motility (40.5 ± 17.8% vs. 34.7 ± 16.1%, t = 3.396; P < 0.001) and total motility (56.0% vs. 64.0%; P = 0.001). Using plastic beverage bottles for oil or seasonings lowered sperm concentrations (40.4% vs. 59.0% vs. 65.5%; P = 0.032). A sweet diet correlated with higher total sperm motility (55.0% vs. 60.0%, 62.0% vs. 63.2%; P = 0.017). Higher milk product intake improved sperm concentration (41.610 6 vs. 63.710 6 vs. 66.1*10 6 ; P = 0.021) and motility (54.5% vs. 56.0% vs. 63.0%; P = 0.033). More frequent egg consumption increased semen volume (3.1 mL vs. 3.8 mL vs. 4.0 mL; P = 0.038). Roughage intake enhanced sperm concentration (160.810 6 vs. 224.610 6 ; P = 0.027), and adequate sleep improved progressive sperm motility rate (35.4% ± 18.2% vs. 40.2 ± 16.3%, F = 3.747; P = 0.024) and total motility (52.7% vs. 61.5%; P = 0.013). The regression model showed that using plastic containers for condiments was a protective factor for semen volume (OR: 0.12; CI 0.03-0.55; P = 0.006), sperm concentration (OR: 0.001, CI 0.00-0.30; P = 0.012), and count (OR: 0.12, CI 0.03-0.48; P = 0.003). Milk and egg consumption were also protective for semen volume (OR: 0.18, CI 0.06-0.51; P = 0.001 and OR: 0.11, CI 0.03-0.55; P = 0.006, respectively), while sufficient sleep benefitted total sperm motility (OR: 0.47, CI 0.24-0.95; P = 0.034)., Conclusions: Smoking and drinking, type of condiment container, diet preference, sleep duration, and milk, roughage, and egg consumption may reduce semen quality., (© 2023. The Author(s).)

Background: It is not clear what the most effective implementation strategies are for supporting the enactment and sustainment of depression care services in primary care settings. This type-II Hybrid Implementation-Effectiveness study will compare the effectiveness of three system-level strategies for implementing depression care programs at 36 community health stations (CHSs) across 2 provinces in Vietnam., Methods: In this cluster-randomized controlled trial, CHSs will be randomly assigned to one of three implementation conditions: (1) Usual Implementation (UI), which consists of training workshops and toolkits; (2) Enhanced Supervision (ES), which includes UI combined with bi-weekly/monthly supervision; and (3) Community-Engaged Learning Collaborative (CELC), which includes all components of ES, combined with bi-monthly province-wide learning collaborative meetings, during which cross-site learning and continuous quality improvement (QI) strategies are implemented to achieve better implementation outcomes. The primary outcome will be measured based on the RE-AIM framework (Reach, Effectiveness, Adoption, Implementation quality, and Maintenance) using indicators on implementation, provider, and client factors. The secondary outcome examines factors associated with barriers and facilitators of quality implementation, while the tertiary outcome evaluates the incremental cost-effectiveness ratio of services provided in the ES and CELC conditions, relative to UI condition for depression care. A total of 1,296 clients receiving depression care at CHSs will be surveyed at baseline and 6-month follow-up to assess mental health and psychosocial outcomes (e.g., depression and anxiety severity, health function, quality of life). Additionally, 180 CHS staff and 180 non-CHS staff will complete pre- and post-training evaluation and surveys at baseline, 6, 12, and 24 months., Discussion: We hypothesize that the additional implementation supports will make mental health service implementation superior in the ES and CELC arms compared to the UI arm. The findings of this project could identify effective implementation models and assess the added value of specific QI strategies for implementing depression care in primary care settings in Vietnam, with implications and recommendations for other low- and middle-income settings. More importantly, this study will provide evidence for key stakeholders and policymakers to consider policies that disseminate, scale up, and advance quality mental health care in Vietnam., Trial Registration: NCT04491045 on Clinicaltrials.gov. Registered July 29, 2020., (© 2023. The Author(s).)

Background: Influenza A viruses have undergone rapid evolution with virulent; however, complete and comprehensive data on gene evolution and amino acid variation of HA and NA in immunosuppressed patients was few. In this study, we analysed molecular epidemiology and evolution of influenza A viruses in immunosuppressed population, and immunocompetent population were used as controls., Methods: Full sequences of HA and NA of A(H1N1)pdm09 and A(H3N2) were acquired through reverse transcription-polymerase chain reaction (RT-PCR). HA and NA genes were sequenced using the Sanger method and phylogenetically analysed using ClustalW 2.10 and MEGA software version 11.0., Results: During the 2018-2020 influenza seasons, 54 immunosuppressed and 46 immunocompetent inpatients screened positive for influenza A viruses by using the quantitative real-time PCR (qRT-PCR) were enrolled. 27 immunosuppressed and 23 immunocompetent nasal swab or bronchoalveolar lavage fluid samples were randomly selected and sequenced using the Sanger method. A(H1N1)pdm09 were detected in 15 samples and the remaining 35 samples were A(H3N2) positive. By analyzing the HA and NA gene sequences of these virus strains, we found that all A(H1N1)pdm09 viruses shared high similarities to each other and the HA and NA genes of these viruses exclusively belonged to subclade 6B.1A.1. Some NA genes of A(H3N2) viruses were not in the same clade as those of A/Singapore/INFIMH-16-0019/2016 and A/Kansas/14/2017, which may have led to A(H3N2) being the dominant strain in the 2019-2020 influenza season. Both A(H1N1)pdm09 and A(H3N2) viruses showed similar evolutionary lineages patterns of HA and NA between immunosuppressed and immunocompetent patients. Compared with the vaccine strains, there were no statistically significant of HA and NA genes and amino acid sequences of influenza A viruses in immunosuppressed and immunocompetent patients. However, the oseltamivir resistance substitution of NA-H275Y and R292K have been observed in immunosuppressed patients., Conclusions: A(H1N1)pdm09 and A(H3N2) viruses showed similar evolutionary lineages patterns of HA and NA between immunosuppressed and immunocompetent patients. Both immunocompetent and immunosuppressed patients have some key substitutions, which should be of note monitored, especially those with potential to affect the viral antigen., (© 2023. The Author(s).)

Background: Sepsis is a life-threatening organ dysfunction caused by the infection-related host response disorder. Adequate mean arterial pressure is an important prerequisite of tissue and organ perfusion, which runs through the treatment of sepsis patients, and an appropriate mean arterial pressure titration in the early-stage correlates to the positive outcome of the treatment. Therefore, in the present study, we aimed to elucidate the relationship between early mean arterial pressure levels and short-term mortality in sepsis patients., Methods: We included all suspected sepsis patients from MIMIC-III database with average mean arterial pressure ≥ 60 mmHg on the first day of intensive care unit stay. Those patients were then divided into a permissive low-mean arterial pressure group (60-65 mmHg) and a high-mean arterial pressure group (> 65 mmHg). Multivariate Cox regression analysis was conducted to analyze the relationship between MAP level and 30-day, 60-day, and 100-day mortality of suspected sepsis patients in the two groups. Propensity score matching, inverse probability of treatment weighing, standardized mortality ratio weighting, PA weighting, overlap weighting, and doubly robust analysis were used to verify our results., Results: A total of 14,031 suspected sepsis patients were eligible for inclusion in our study, among which 1305 (9.3%) had an average first-day mean arterial pressure of 60-65 mmHg, and the remaining 12,726 patients had an average first-day mean arterial pressure of more than 65 mmHg. The risk of 30-day mortality was reduced in the high mean arterial pressure group compared with the permissive low-mean arterial pressure group (HR 0.67 (95% CI 0.60-0.75; p < 0.001)). The higher mean arterial pressure was also associated with lower 60-day and 100-day in-hospital mortality as well as with shorter duration of intensive care unit stay. Patients in the high-mean arterial pressure group also had more urine output on the first and second days of intensive care unit admission., Conclusions: After risk adjustment, the initial mean arterial pressure of above 65 mmHg was associated with reduced short-term mortality, shorter intensive care unit stay, and higher urine volume in the first two days among patients with sepsis., (© 2023. The Author(s).)

For social insects such as ants, the internal organs are likely important in understanding their eusocial behavior and evolution. Such organs, however, are rarely preserved on fossils. In each of the few cases reporting exceptionally fossilized soft tissues in arthropods, the nervous, muscular and cardiovascular systems have been described individually, but never in combination. Here, we report a female specimen (gyne) of the extinct ant group- † Zigrasimecia-included in a Cretaceous amber piece from Kachin, Myanmar, with an almost complete system formed by various internal organs. These include the brain, the main exocrine system, part of the digestive tract, and several muscle clusters. This research expands our knowledge of internal anatomy in stem group ants. As the gyne bears a morphologically unique labrum, our specimen's internal and external features support the notion that the early ant may have special ecological habits during the Cretaceous period., (© 2022. The Author(s).)

Background: Brain volume has been widely studied in the neuroimaging field, since it is an important and heritable trait associated with brain development, aging and various neurological and psychiatric disorders. Genome-wide association studies (GWAS) have successfully identified numerous associations between genetic variants such as single nucleotide polymorphisms and complex traits like brain volume. However, it is unclear how these genetic variations influence regional gene expression levels, which may subsequently lead to phenotypic changes. S-PrediXcan is a tissue-specific transcriptomic data analysis method that can be applied to bridge this gap. In this work, we perform an S-PrediXcan analysis on GWAS summary data from two large imaging genetics initiatives, the UK Biobank and Enhancing Neuroimaging Genetics through Meta Analysis, to identify tissue-specific transcriptomic effects on two closely related brain volume measures: total brain volume (TBV) and intracranial volume (ICV)., Results: As a result of the analysis, we identified 10 genes that are highly associated with both TBV and ICV. Nine out of 10 genes were found to be associated with TBV in another study using a different gene-based association analysis. Moreover, most of our discovered genes were also found to be correlated with multiple cognitive and behavioral traits. Further analyses revealed the protein-protein interactions, associated molecular pathways and biological functions that offer insight into how these genes function and interact with others., Conclusions: These results confirm that S-PrediXcan can identify genes with tissue-specific transcriptomic effects on complex traits. The analysis also suggested novel genes whose expression levels are related to brain volumetric traits. This provides important insights into the genetic mechanisms of the human brain., (© 2022. The Author(s).)

Cerebellar dysfunction is commonly observed following traumatic brain injury (TBI). While direct impact to the cerebellum by TBI is rare, cerebellar pathology may be caused by indirect injury via cortico-cerebellar pathways. To address the hypothesis that degeneration of Purkinje cells (PCs), which constitute the sole output from the cerebellum, is linked to long-range axonal injury and demyelination, we used the central fluid percussion injury (cFPI) model of widespread traumatic axonal injury in mice. Compared to controls, TBI resulted in early PC loss accompanied by alterations in the size of pinceau synapses and levels of non-phosphorylated neurofilament in PCs. A combination of vDISCO tissue clearing technique and immunohistochemistry for vesicular glutamate transporter type 2 show that diffuse TBI decreased mossy and climbing fiber synapses on PCs. At 2 days post-injury, numerous axonal varicosities were found in the cerebellum supported by fractional anisotropy measurements using 9.4 T MRI. The disruption and demyelination of the cortico-cerebellar circuits was associated with poor performance of brain-injured mice in the beam-walk test. Despite a lack of direct input from the injury site to the cerebellum, these findings argue for novel long-range mechanisms causing Purkinje cell injury that likely contribute to cerebellar dysfunction after TBI., (© 2022. The Author(s).)

Doxorubicin (Dox) is the standard treatment approach for osteosarcoma (OS), while acquired drug resistance seriously attenuates its treatment efficiency. The present study aimed to investigate the potential roles of metabolic reprogramming and the related regulatory mechanism in Dox-resistant OS cells. The results showed that the ATP levels, lactate generation, glucose consumption and oxygen consumption rate were significantly increased in Dox-resistant OS cells compared with parental cells. Furthermore, the results revealed that the increased expression of estrogen-related receptor alpha (ERRα) was involved in metabolic reprogramming in chemotherapy resistant OS cells, since targeted inhibition of ERRα restored the shifting of metabolic profiles. Mechanistic analysis indicated that the mRNA stability, rather than ERRα transcription was markedly increased in chemoresistant OS cells. Therefore, it was hypothesized that the 3'-untranslated region of ERRα mRNA was methylated by N 6 -methyladenine, which could further recruit insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1) to suppress mRNA decay and increase mRNA stability. IGF2BP1 knockdown downregulated ERRα and reversed the metabolic alteration of resistant OS cells. Additionally, the oncogenic effect of the IGF2BP1/ERRα axis on Dox-resistant OS cells was verified by in vitro and in vivo experiments. Clinical analysis also revealed that the expression levels of IGF2BP1 and ERRα were associated with the clinical progression of OS. Collectively, the current study suggested that the IGF2BP1/ERRα axis could regulate metabolic reprogramming to contribute to the chemoresistance of OS cells., (© 2022. The Author(s).)

Background: Recent guidelines recommended a systolic blood pressure (SBP) target of < 130 mmHg for patients with or without diabetes but without providing a lower bound. Our study aimed to explore whether additional clinical benefits remain at achieved blood pressure (BP) levels below the recommended target., Methods: We performed a secondary analysis of the Systolic Blood Pressure Intervention Trial (SPRINT) among the non-diabetic population and the Action to Control Cardiovascular Risk in Diabetes BP (ACCORD-BP) trial among diabetic subjects. We used the propensity score method to match patients from the intensive BP group to those from the standard group in each trial. Individuals with different achieved BP levels from the intensive BP group were used as "reference." For each stratum, the trial-specific primary outcome (i.e., composite outcome of myocardial infarction (MI), acute coronary syndrome not resulting in MI, stroke, acute decompensated heart failure (HF), or cardiovascular death for SPRINT; non-fatal MI, non-fatal stroke, or cardiovascular death for ACCORD-BP) was compared by Cox regression., Results: A non-linear association was observed between the mean achieved BP and incidence of composite cardiovascular events, regardless of treatment allocation. The significant treatment benefit for primary outcome remained at SBP 110-120 mmHg (hazard ratio, 0.59 [95% CI, 0.46, 0.76] for SPRINT; 0.67 [0.52, 0.88] for ACCORD-BP) and SBP 120-130 mmHg for SPRINT (0.47 [0.34, 0.63]) but not for ACCORD-BP (0.93 [0.70, 1.23]). The results were similar for the secondary outcomes including all-cause mortality, cardiovascular mortality, MI, stroke, and HF. Intensive BP treatment benefits existed among patients maintaining a diastolic BP of 60-70 mmHg but were less distinct., Conclusions: The treatment benefit persists at as low as SBP 110-120 mmHg irrespective of diabetes status. Achieved very low BP levels appeared to increase cardiovascular events and all-cause mortality., (© 2022. The Author(s).)

Background: To determine the incidence, clinical and MRI features of sacral insufficiency fracture (SIF) after radiotherapy (RT) in patients with cervical cancer., Methods: Our study included 167 patients with cervical cancer after radiotherapy that underwent pelvic MRI for follow-up. MRIs included pre-enhanced T1-weighted, coronal fat-Suppressed T2-weighted (FS-T2W) and enhanced T1-weighted imaging. The clinical and MRI dates were reviewed. The gold standard of SIF was based on radiologic findings, clinical data and follow-up at least 12 months., Results: 28 patients (10.8%) with 47 sites were diagnosed with SIFs, including 9 patients with unilateral SIF and 19 patients with bilateral SIFs. The median age was 60 years (range 41-72 years), and 89.3% (25/28) of patients were postmenopausal. 64.3% (18/28) of patients were symptomatic, and 53.6% of patients (15/28) had concomitant pelvic fractures. The median interval time from RT to SIFs was 10 months (range 3-34 months). For the lesion-wise analysis based on all MR images, all lesions were detected by visualizing bone marrow edema patterns, and fracture lines were detected in 64.6% (31/47) of SIFs. No soft-tissue tumors were founded. For each MRI sequence analysis, coronal FS-T2WI detected the most bone marrow edema pattern and fracture line than T1WI or enhanced T1WI., Conclusion: SIF is a common complication in cervical cancer after radiotherapy, which has some certain clinical and MRI features. Coronal FS-T2WI may be more useful to detect and characterize these fractures than other imaging sequences., (© 2022. The Author(s).)

Background: Both mild and conventional controlled ovarian stimulation are the frequently used protocols for poor ovarian responders. However, there are some debates about which treatment is better. Moreover, little is known about the follicular physiology after the two ovarian stimulation protocols. This study was intended to investigate the features in granulosa cells and follicular fluid micro-environment after the two different ovarian stimulation protocols in poor responders., Methods: Granulosa cells RNA were sequenced using Illumina Hiseq technology. Specific differently expressed genes and proteins were verified by real-time quantitative PCR and Western blot analysis. Moreover, hormone and cytokine concentrations in the follicular fluid were measured by electrochemiluminescence immunoassay and enzyme-linked immunoabsorbent assay. The correlation between the results of molecular experiments and the laboratory outcomes were analyzed by Spearman correlation analysis., Results: The differentially expressed genes between the two groups were involved in 4 signaling pathways related to the follicular development; three proteins pertinent to the TGF-β signaling pathway were expressed differently in granulosa cells between the two, and the constituents in the follicular fluid were also different. Further, a correlation between the TGF-β signaling pathway and the good-quality embryo was observed., Conclusions: The present study made a comparison for the first time in the transcriptome of human granulosa cells and the follicular fluid micro-environment between poor responders with the conventional controlled ovarian stimulation or the mild ovarian stimulation, showing that the TGF-β signaling pathway may correlate with the good-quality of embryos in the mild group, which may be instrumental to the choice of optimal management for IVF patients., (© 2022. The Author(s).)

Background: Compared with immunocompetent patients, immunosuppressed patients have higher morbidity and mortality, a longer duration of viral shedding, more frequent complications, and more antiviral resistance during influenza infections. However, few data on this population in China have been reported. We analysed the clinical characteristics, effects of antiviral therapy, and risk factors for admission to the intensive care unit (ICU) and death in this population after influenza infections and explored the influenza vaccination situation for this population., Methods: We analysed 111 immunosuppressed inpatients who were infected with influenza virus during the 2015-2020 influenza seasons. Medical data were collected through the electronic medical record system and analysed. Univariate analysis and multivariate logistics analysis were used to identify risk factors., Results: The most common cause of immunosuppression was malignancies being treated with chemotherapy (64.0%, 71/111), followed by haematopoietic stem cell transplantation (HSCT) (23.4%, 26/111). The most common presenting symptoms were fever and cough. Dyspnoea, gastrointestinal symptoms and altered mental status were more common in HSCT patients than in patients with immunosuppression due to other causes. Approximately 14.4% (16/111) of patients were admitted to the ICU, and 9.9% (11/111) of patients died. Combined and double doses of neuraminidase inhibitors did not significantly reduce the risk of admission to the ICU or death. Risk factors for admission to the ICU were dyspnoea, coinfection with other pathogens and no antiviral treatment within 48 h. The presence of dyspnoea and altered mental status were independently associated with death. Only 2.7% (3/111) of patients less than 12 months old had received a seasonal influenza vaccine., Conclusion: Fever and other classic symptoms of influenza may be absent in immunosuppressed recipients, especially in HSCT patients. Conducting influenza virus detection at the first presentation seems to be a good choice for early diagnosis. Clinicians should pay extra attention to immunosuppressed patients with dyspnoea, altered mental status, coinfection with other pathogens and no antiviral treatment within 48 h because these patients have a high risk of severe illness. Inactivated influenza vaccines are recommended for immunosuppressed patients., (© 2022. The Author(s).)

Background: The neuroimaging manifestations of eclampsia and preeclampsia often overlap, mainly presenting as posterior reversible encephalopathy syndrome (PRES). The purpose of this retrospective study was to compare the extent and nature of brain edema in eclampsia and preeclampsia patients with PRES based on MRI characteristics., Methods: One hundred fifty women diagnosed with preeclampsia-eclampsia and undergoing cranial MRI were enrolled; 24 of these were diagnosed as having eclampsia. According to clinicoradiologic diagnosis of PRES, eligible patients were classified as having eclampsia with PRES (group E-PRES) and preeclampsia with PRES (group P-PRES). A scale on T2W FLAIR-SPIR images was established to evaluate the extent of brain edema, and the score of brain edema (SBE) of both groups was compared. In patients of the two groups who also underwent DWI sequence, the presence or absence of hyperintensity on DWI and hypointensity on ADC maps were determined to compare the nature of brain edema. Furthermore, clinical and biochemical data of the two groups were compared., Results: The incidence of PRES in eclampsia patients was significantly higher than that in preeclampsia patients (87.50% vs. 46.03%, P<0.001). The SBE of all regions and typical regions in group E-PRES patients were significantly higher than those in group P-PRES patients (15.88±8.72 vs. 10.90±10.21, P=0.021; 8.52±3.87 vs. 5.01±4.19, P=0.002; respectively). The presence of hyperintensity on DWI was determined more frequently in group E-PRES patients than group P-PRES patients (71.43% vs. 32.00%, P=0.024). Age, systolic blood pressure, white blood cell count, neutrophil count and percentage of neutrophils were significantly different between the two groups (P<0.05)., Conclusions: Certain MRI characteristics that reflect the extent and nature of brain edema were different between eclampsia and preeclampsia patients with PRES. Additional prospective studies are still required to explore whether these MRI characteristics of brain edema may further become a potential predictor for eclamptic seizures in preeclampsia patients with PRES., (© 2021. The Author(s).)

Background: The Chengjiang biota from southwest China (518-million-years old, early Cambrian) has yielded nearly 300 species, of which more than 80 species represent early chelicerates, crustaceans and relatives. The application of µCT-techniques combined with 3D software (e.g., Drishti), has been shown to be a powerful tool in revealing and analyzing 3D features of the Chengjiang euarthropods. In order to address several open questions that remained from previous studies on the morphology of the xandarellid euarthropod Sinoburius lunaris, we reinvestigated the µCT data with Amira to obtain a different approach of visualization and to generate new volume-rendered models. Furthermore, we used Blender to design 3D models showing aspects of intraspecific variation., Results: New findings are: (1) antennulae consist of additional proximal articles that have not been detected before; (2) compared to other appendages, the second post-antennular appendage has a unique shape, and its endopod is comprised of only five articles (instead of seven); (3) the pygidium bears four pairs of appendages which are observed in all specimens. On the other hand, differences between specimens also have been detected. These include the presence/absence of diplotergites resulting in different numbers of post-antennular appendages and tergites and different distances between the tip of the hypostome and the anterior margin of the head shield., Conclusions: Those new observations reveal intraspecific variation among Chengjiang euarthropods not observed before and encourage considerations about possible sexual dimorphic pairs or ontogenetic stages. Sinoburius lunaris is a variable species with respect to its morphological characters, cautioning that taxon-specific variabilities need to be considered when exploring new species.

Background: Non-mass enhancement (NME) is a diagnostic dilemma and highly reliant on the experience of the radiologists. Texture analysis (TA) could serve as an objective method to quantify lesion characteristics. However, it remains unclear what role TA plays in a predictive model based on routine MRI characteristics. The purpose of this study was to explore the value of TA in distinguishing between benign and malignant NME in premenopausal women., Methods: Women in whom NME was histologically proven (n = 147) were enrolled (benign: 58; malignant: 89) was retrospective. Then, 102 and 45 patients were classified as the training and validation groups, respectively. Scanning sequences included Fat-suppressed T2-weighted and fat-suppressed contrast-enhanced T1-weighted which were acquired on a 1.5T MRI system. Clinical and routine MR characteristics (CRMC) were evaluated by two radiologists according to the Breast Imaging and Reporting and Data system (2013). Texture features were extracted from all post-contrast sequences in the training group. The combination model was built and then assessed in the validation group. Pearson's chi-square test and Mann-Whitney U test were used to compare categorical variables and continuous variables, respectively. Logistic regression analysis and receiver operating characteristic curve were employed to assess the diagnostic performance of CRMC, TA, and their combination model in NME diagnosis., Results: The combination model showed superior diagnostic performance in differentiating between benign and malignant NME compared to that of CRMC or TA alone (AUC, 0.887 vs 0.832 vs 0.74). Moreover, compared to CRMC, the model showed high specificity (72.5% vs 80%). The results obtained in the validation group confirmed the model was promising., Conclusions: With the combined use of TA and CRMC could afford an improved diagnostic performance in differentiating between benign and malignant NME.

Background: The Chengjiang biota is one of the most species-rich Cambrian Konservat-Lagerstätten, and preserves a community dominated by non-biomineralized euarthropods. However, several Chengjiang euarthropods have an unfamiliar morphology, are extremely rare, or incompletely preserved., Results: We employed micro-computed tomography to restudy the enigmatic euarthropod Jianshania furcatus. We reveal new morphological details, and demonstrate that the specimens assigned to this species represent two different taxa. The holotype of J. furcatus features a head shield with paired anterolateral notches, stalked lateral eyes, and an articulated tailspine with a bifurcate termination. The other specimen is formally redescribed as Xiaocaris luoi gen. et sp. nov., and is characterized by stalked eyes connected to an anterior sclerite, a subtrapezoidal head shield covering three small segments with reduced tergites, a trunk with 15 overlapping tergites with a well-developed dorsal keel, and paired tail flukes., Conclusions: The presence of antennae, biramous appendages with endopods composed of 15 articles, and multiple appendage pairs associated with the trunk tergites identify X. luoi nov. as a representative of Fuxianhuiida, an early branching group of stem-group euarthropods endemic to the early Cambrian of Southwest China. X. luoi nov. represents the fifth fuxianhuiid species described from the Chengjiang biota, and its functional morphology illuminates the ecological diversity of this important clade for understanding the early evolutionary history of euarthropods.

Background: OTUB1 (ovarian tumor domain protease domain-containing ubiquitin aldehyde-binding proteins)-mediated deubiquitination of FOXM1 (Forkhead box M1) participates in carcinogenesis of various tumors. We aim to investigate the effect and mechanism of OTUB1/FOXM1 on RCC (renal cell carcinoma) progression. Expression levels of OTUB1 in RCC tissues and cell lines were examined by qRT-PCR (quantitative real-time polymerase chain reaction) and immunohistochemistry. Cell proliferation was measured with CCK8 (Cell Counting Kit-8) and colony formation assays. Wound healing and transwell assays were used to determine cell migration and invasion, respectively. The effect of OTUB1 on FOXM1 ubiquitination was examined by Immunoprecipitation. Western blot was used to uncover the underlying mechanism. In vivo subcutaneous xenotransplanted tumor model combined with immunohistochemistry and western blot were used to examine the tumorigenic function of OTUB1., Results: OTUB1 was up-regulated in RCC tissues and cell lines, and was associated with poor prognosis of RCC patients. Knockdown of OTUB1 inhibited cell viability and proliferation, as well as migration and invasion of RCC cells. Mechanistically, knockdown of OTUB1 down-regulated FOXM1 expression by promoting its ubiquitination. Down-regulation of FOXM1 inhibited ECT2 (epithelial cell transforming 2)-mediated Rho signaling. Moreover, the inhibition of RCC progression caused by OTUB1 knockdown was reversed by FOXM1 over-expression. In vivo subcutaneous xenotransplanted tumor model also revealed that knockdown of OTUB1 could suppress in vivo RCC growth via down-regulation of FOXM1-mediated ECT2 expression., Conclusions: OTUB1-mediated deubiquitination of FOXM1 up-regulates ECT-2 to promote tumor progression in RCC, providing a new potential therapeutic target for RCC treatment., Competing Interests: Competing interestsThe authors declare that they have no competing interests, and all authors should confirm its accuracy., (© The Author(s) 2020.)

Background: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease and has become a public health concern worldwide. The hallmark of NAFLD is hepatic steatosis. Therefore, there is an urgent need to develop new therapeutic strategies that are efficacious and have minimal side effects in hepatic steatosis and NAFLD treatment. The present study aimed to investigate the effect of dietary supplement of curcumin on high-fat diet (HFD)-induced hepatic steatosis and the underlying mechanism., Methods: ApoE -/- mice were fed a normal diet, high-fat diet (HFD) or HFD supplemented with curcumin (0.1% w/w) for 16 weeks. Body and liver weight, blood biochemical.parameters, and liver lipids were measured. Intestinal permeability, hepatic steatosis and mRNA and protein expressions of TLR4-related inflammatory signaling molecule were analyzed., Results: The administration of curcumin significantly prevented HFD-induced body weight gain and reduced liver weight. Curcumin attenuated hepatic steatosis along with improved serum lipid profile. Moreover, curcumin up-regulated the expression of intestinal tight junction protein zonula occluden-1 and occludin, which further improved gut barrier dysfunction and reduced circulating lipopolysaccharide levels. Curcumin also markedly down-regulated the protein expression of hepatic TLR4 and myeloid differentiation factor 88 (MyD88), inhibited p65 nuclear translocation and DNA binding activity of nuclear factor-κB (NF-κB) in the liver. In addition, the mRNA expression of hepatic tumour necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) as well as the plasma levels of TNF-α and IL-1β were also lowered by curcumin treatment., Conclusion: These results indicated that curcumin protects against HFD-induced hepatic steatosis by improving intestinal barrier function and reducing endotoxin and liver TLR4/NF-κB inflammation. The ability of curcumin to inhibit hepatic steatosis portrayed its potential as effective dietry intervention for NAFLD prevention., Competing Interests: Competing interestsConflict of interest On behalf of all authors, the corresponding author states. that there is no conflict of interest., (© The Author(s). 2019.)

Background: Treatment with metformin, the biguanide of hepatic insulin sensitizer, in patients with non-alcoholic fatty liver disease (NAFLD) has been reported with contradictory findings regarding the effectiveness on blood lipids and liver histology. In this study, we aimed to explore the preventive effects of metformin on NAFLD in Zucker diabetic fatty (ZDF) rats., Methods: Male ZDF rats and Zucker lean rats aged 4-8 weeks were subjected to vehicle or metformin treatment for 6 months. Liver cDNA microarray assay, and protein semiquantitative and histological examinations were performed., Results: Data demonstrated that ZDF rats developed hyperglycemia, hyperlipidemia, liver deficiency and hepatocyte degeneration. The metformin treatment significantly reduced post-load blood glucose levels, but not blood lipid profiles or liver enzyme levels. Hepatocyte degeneration was not attenuated after the treatment. The metformin-treated ZDF rats showed activation of AMP-activated protein kinase by Western blot and overexpression of cytochrome c oxidase by immunofluorescent microscopy. Gene expression microarray assay demonstrated that a panel of genes participating in glucose and lipid metabolisms were changed in the ZDF rats, and most of the altered genes involved in glucose and cholesterol metabolisms, but not those in fatty acid metabolisms, were corrected by the metformin treatment. No genes associated with inflammation, apoptosis, fibrosis, or cell death were overexpressed in the metformin-treated ZDF rats., Conclusions: These results suggest that long-term metformin treatment presents no preventive effect for NAFLD in ZDF rats., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2019.)

Background: Artiopodan euarthropods represent common and abundant faunal components in sites with exceptional preservation during the Cambrian. The Chengjiang biota in South China contains numerous taxa that are exclusively known from this deposit, and thus offer a unique perspective on euarthropod diversity during the early Cambrian. One such endemic taxon is the non-trilobite artiopodan Sinoburius lunaris, which has been known for approximately three decades, but few details of its anatomy are well understood due to its rarity within the Chengjiang, as well as technical limitations for the study of these fossils. Furthermore, the available material does not provide clear information on the ventral organization of this animal, obscuring our understanding of phylogenetically significant details such as the appendages., Results: We employed X-ray computed tomography to study the non-biomineralized morphology of Sinoburius lunaris. Due to the replacement of the delicate anatomy with pyrite typical of Chengjiang fossils, computed tomography reveals substantial details of the ventral anatomy of Sinoburius lunaris, and allow us to observe in detail the three-dimensionally preserved appendicular organization of this taxon for the first time. The dorsal exoskeleton consists of a crescent-shaped head shield with well-developed genal spines, a thorax with seven freely articulating tergites, and a fused pygidium with lateral and median spines. The head bears a pair of ventral stalked eyes that are accommodated by dorsal exoskeletal bulges, and an oval elongate ventral hypostome. The appendicular organization of the head is unique among Artiopoda. The deutocerebral antennae are reduced, consisting of only five podomeres, and bear an antennal scale on the second podomere that most likely represents an exite rather than a true ramus. The head includes four post-antennal biramous limb pairs. The first two biramous appendages are differentiated from the rest. The first appendage pair consists of a greatly reduced endopod coupled with a greatly elongated exopod with a potentially sensorial function. The second appendage pair carries a more conventionally sized endopod, but also has an enlarged exopod. The remaining biramous appendages are homonomous in their construction, but decrease in size towards the posterior end of the body. They consist of a basipodite with ridge-like crescentic endites, an endopod with seven podomeres and a terminal claw, and a lamellae-bearing exopod with a slender shaft. Contrary to previous reports, we confirm the presence of segmental mismatch in Sinoburius lunaris, expressed as diplotergites in the thorax. Maximum parsimony and Bayesian phylogenetic analyses support the monophyly of Xandarellida within Artiopoda, and illuminate the internal relationships within this enigmatic clade. Our results allow us to propose a transformation series explaining the origin of archetypical xandarellid characters, such as the evolution of eye slits in Xandarella spectaculum and Phytophilaspis pergamena as derivates from the anterolateral notches in the head shield observed in Cindarella eucalla and Luohuilinella species. In this context, Sinoburius lunaris is found to feature several derived characters within the group, such as the secondary loss of eye slits and a high degree of appendicular tagmosis. Contrary to previous findings, our analyses strongly support close affinities between Sinoburius lunaris, Xandarella spectaculum and Phytophilaspis pergamena, although the precise relationships between these taxa are sensitive to different methodologies., Conclusions: The revised morphology of Sinoburius lunaris, made possible through the use of computed tomography to resolve details of its three-dimensionally preserved appendicular anatomy, contributes towards an improved understanding of the morphology of this taxon and the evolution of Xandarellida more broadly. Our results indicate that Sinoburius lunaris possesses an unprecedented degree of appendicular tagmosis otherwise unknown within Artiopoda, with the implication that this iconic group of Palaeozoic euarthropods likely had a more complex ecology and functional morphology than previously considered. The application of computer tomographic techniques to the study of Chengjiang euarthropods holds exceptional promise for understanding the morphological diversity of these organisms, and also better reconstructing their phylogenetic relationships and evolutionary history.

Background: Although the prognosis of chronic myeloid leukemia (CML) has dramatically improved, the pathogenesis of CML remains elusive. Studies have shown that sustained phosphorylation of AKT1 plays a crucial role in the proliferation of CML cells. Evidence indicates that in tongue cancer cells, FAM168A, also known as tongue cancer resistance-associated protein (TCRP1), can directly bind to AKT1 and regulate AKT1/NFκB signaling pathways. This study aimed to investigate the role of FAM168A in regulation of AKT1/NFκB signaling pathway and cell cycle in CML., Methods: FAM168A interference was performed, and the expression and phosphorylation of FAM168A downstream proteins were measured in K562 CML cell line. The possible roles of FAM168A in the proliferation of CML cells were investigated using in vitro cell culture, in vivo animal models and clinical specimens., Results: We found that the expression of FAM168A significantly increased in the peripheral blood mononuclear cells of CML patients, compared with normal healthy controls. FAM168A interference did not change AKT1 protein expression, but significantly decreased AKT1 phosphorylation, significantly increased IκB-α protein level, and significantly reduced nuclear NFκB protein level. Moreover, there was a significant increase of G2/M phase cells and Cyclin B1 level. Immunoprecipitation results showed that FAM168A interacts with breakpoint cluster region (BCR) -Abelson murine leukemia (ABL1) fusion protein and AKT1, respectively. Animal experiments confirmed that FAM168A interference prolonged the survival and reduced the tumor formation in mice inoculated with K562 cells. The results of clinical specimens showed that FAM168A expression and AKT1 phosphorylation were significantly elevated in CML patients., Conclusion: This study demonstrates that FAM168A may act as a linker protein that binds to BCR-ABL1 and AKT1, which further mediates the downstream signaling pathways in CML. Our findings demonstrate that FAM168A may be involved in the regulation of AKT1/NFκB signaling pathway and cell cycle in CML.

Hepatocellular carcinoma (HCC) is one of the most notable lethal malignancies worldwide. However, the molecular mechanisms involved in the initiation and progression of this disease remain poorly understood. Over the past decade, many studies have demonstrated the important regulatory roles of long non-coding RNAs (lncRNAs) in HCC. Here, we comprehensively review recent discoveries regarding HCC-associated lncRNA functions, which we have classified and described according to their mechanism models.

Background: The recent advancement of whole genome alignment software has made it possible to align two genomes very efficiently and with only a small sacrifice in sensitivity. Yet it becomes very slow if the extra sensitivity is needed. This paper proposes a simple but effective method to improve the sensitivity of existing whole-genome alignment software without paying much extra running time., Results and Conclusions: We have applied our method to a popular whole genome alignment tool LAST, and we called the resulting tool LASTM. Experimental results showed that LASTM could find more high quality alignments with a little extra running time. For example, when comparing human and mouse genomes, to produce the similar number of alignments with similar average length and similarity, LASTM was about three times faster than LAST. We conclude that our method can be used to improve the sensitivity, and the extra time it takes is small, and thus it is worthwhile to be implemented in existing tools.

Background: China experiencing an increasing HIV epidemic among men who have sex with men (MSM), and unprotected anal intercourse (UAI) has played a key role in this process. The aims of this study were to examine the trend of UAI and to explore the factors correlated with UAI among MSM in Guangzhou, China., Methods: Data from 2008 to 2013 were retrieved from the annual serological and behavioral surveys system. We collected information on demographic, HIV related sexual behavior with men and women, access to HIV prevention services, and symptoms of sexually transmitted infections. Chi-square test was used to examine the similarity of the participants during the study period. Univariate and multivariate logistic regression were conducted to test the factors associated with UAI. Trend test was used to check the change of UAI in different characteristic stratums during the study period., Results: In total, 58.4% (range from 54.5% to 62.0%) of the participants reported that they engaged in UAI in the past six months. Participants who aged less than 20 [Adjusted Odds Ratio (AOR): 2.22, 95% Confidential Interval (CI): 1.07-4.61], only attended elementary school (or less) (AOR: 1.41, 95% CI: 1.04-1.90), cohabiting with male partner (AOR: 2.15, 95% CI: 1.66-2.79), divorced or widowed (AOR: 2.80, 95% CI: 1.54-5.07), did not test for HIV in the past year (AOR: 1.36, 95% CI: 1.12-1.65), and had 10 or more partners in the past six months (AOR: 1.85, 95% CI: 1.18-2.91) had higher odds of UAI. However, the proportions of UAI were stable in different stratums during the study period., Conclusions: The proportion of MSM engaged in UAI was consistently high during the study period. Effective intervention strategies, which include but not limit to risk reduction counseling and testing services, are urgently needed to bring down the risk behaviors of the MSM in Guangzhou, in order to control HIV/STIs epidemic in this specific population.