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The Coma Recovery Scale-Revised (CRS-R) is the gold standard behavioral assessment scale for diagnosis of patients with disorders of consciousness (DOC). The reliability of CRS-R in monitoring the state of consciousness is well established. It is widely used by experts working in the fields of DOC. However, it is complex, time-consuming and difficult to use by non-professionals. Hence, it is imperative to simplify the evaluation to ease clinical workflow and increase work efficiency. In this study we evaluated the accuracy of a simplified scale using only 8 most commonly observed behaviors from the standard 29-item CRS-R scale. To assess the diagnostic accuracy of the simplified evaluation process of CRS-R compared to the standard CRS-R, a total of 150 patients with DOC who were admitted to the Hospital of Zhejiang People's Armed Police between February 2020 and September 2021 were screened in a prospective, observational study. Two trained clinicians used the CRS-R and the simplified CRS-R to evaluate the consciousness level of the enrolled patients, respectively. SPSS 23 was used for statistical analysis. Weighted kappa was used to demonstrate the level of agreement between the two methods. A p-value 0.01 was considered to be statistically significant. Kappa coefficient was 0.952 (95 % CI: 0.905-0.999, p 0.01), which indicated that the difference was statistically significant, thereby suggesting satisfactory level of agreement between the diagnostic outcomes of the CRS-R and simplified CRS-R. The simplified CRS-R could determine the state of consciousness of patients with ease and high accuracy.

Job burnout is related to both environmental and genetic factors. However, previous studies on job burnout in teachers have mainly focused on potential stressors in the environment, while ignoring genetic factors. Brain-derived neurotrophic factor (BNDF) may be a pathogenic factor involved in burnout symptoms. Therefore, this study further investigated the relationship between the BNDF gene polymorphism, job stress and job burnout in Chinese university teachers.Using a cross-sectional design, 361 faculty and staff members from a university in Beijing were enrolled. Job stress was measured with the Work Stress Scale. Job burnout was measured by the Chinese version of the Maslach Burnout Inventory which has three dimensions, namely emotional exhaustion (EE), cynicism (CY), and reduced personal accomplishment (PA). The BDNF gene rs16917237 polymorphism was genotyped in all participants.CY score was associated with education level (p 0.01), and PA score was associated with age (p 0.05). Job stress was positively correlated with EE (r = 0.776), CY (r = 0.457), and PA (r = 0.163) (all p 0.01). After controlling for gender, age and education level, the BDNF gene rs16917237 polymorphism did not affect job burnout, but it interacted with job stress to influence EE and CY (both p 0.05), indicating that individuals with TT genotype were more susceptible to higher levels of job stress, resulting in job burnout symptoms.Our results suggest that the BDNF gene rs16917237 TT genotype may be a risk factor for job burnout in Chinese university teachers.

Chronic occupational manganese (Mn) exposure is characterized by motor and cognitive dysfunction. This study aimed to investigate structural abnormalities in Mn-exposed welders compared to healthy controls (HCs).Thirty-five HCs and forty Mn-exposed welders underwent magnetic resonance imaging (MRI) scans in this study. Based on T1-weighted MRI, the voxel-based morphometry (VBM), structural covariance, and receiver operating characteristic (ROC) curve were applied to examine whole-brain structural changes in Mn-exposed welders.Compared to HCs, Mn-exposed welders had altered gray matter volume (GMV) mainly in the medial prefrontal cortex, lentiform nucleus, hippocampus, and parahippocampus. ROC analysis indicated the potential highest classification power of the hippocampus/parahippocampus. Moreover, distinct structural covariance patterns in the two groups were associated with regions, mainly including the thalamus, insula, amygdala, sensorimotor area, and middle temporal gyrus. No significant relationships were found between the findings and clinical characteristics.Our findings showed Mn-exposed welders had changed GMV and structural covariance patterns in some regions, which implicated in motivative response, cognitive control, and emotional regulation. These results might provide preliminary evidence for understanding the pathophysiology of Mn overexposure.• Chronic Mn exposure might be related to abnormal brain structural neural mechanisms. • Mn-exposed welders had morphological changes in brain regions implicated in emotional modulation, cognitive control, and motor-related response. • Altered gray matter volume in the hippocampus/parahippocampus and putamen might serve as potential biomarkers for Mn overexposure.

Genomic instability (GIN) plays a key role in cancer progression. The disorders of polymerase theta (POLQ) were reported to contribute to GIN and progression in many cancers. Here, we found that POLQ over-expression was related to salivary adenoid cystic carcinoma (SACC) progression and poor prognosis. Then, we investigated the role and mechanism of POLQ in the GIN in SACC. GIN was assessed by chromosome staining with DAPI and Giemsa, as well as qRT-PCR of the mitosis-related gene expression. Meanwhile, PCR-SSCP was used to evaluate microsatellite instability. Modulation of POLQ expression increased chromosomal instability and enhanced the sensitivity to etoposide without impacting microsatellite stability. Mechanistically, POLQ regulated genome stability by promoting the expression of the error-prone alt-NHEJ-related protein PARP1, and down-regulating c-NHEJ- and HR-related proteins KU70 and RAD51. In vitro CCK, Transwell assays and in vivo murine xenograft models indicated that the PARP inhibitor olaparib suppressed SACC growth in the case of etoposide-induced DNA damage. Bioinformatic analysis identified CEBPB as a potential POLQ-regulating transcription factor. In summary, our research provides new insights into the mechanisms of SACC chromosomal instability and identifies new potential targets for SACC treatment.

Stimulator of interferon genes (STING) is a pivotal innate immune adaptor, and its functions during DNA virus infections have been extensively documented. However, its homeostatic regulation is not well understood. Our study demonstrates that Unc-93 homolog B1 (UNC93B1) is a crucial checker for STING to prevent hyperactivation. Ectopic expression of UNC93B1 attenuates IFN-β promoter activity and the transcriptions of IFN-β, ISG54, and ISG56 genes. Moreover, UNC93B1 also blocks the IRF3 nuclear translocation induced by ectopic expression of both cyclic GMP-AMP synthase (cGAS) and STING and reduces the stability of STING by facilitating its autophagy-lysosome degradation, which can be reversed by lysosome inhibitors. Mechanistically, UNC93B1 interacts with STING and suppresses STING-activated downstream signaling by delivering STING to the lysosomes for degradation, depending on its trafficking capability. UNC93B1 knockout in human embryonic kidney 293T cells facilitates IFN-β promoter activity, IFN-β, ISG54, and ISG56 transcriptions, and IRF3 nuclear translocation induced by ectopic expression of cGAS and STING. Infected with herpes simplex virus-1 (HSV-1), UNC93B1 knockdown BJ cells or primary peritoneal macrophages from Unc93b1-deficient (Unc93b1

Objective. To explore the interhemispheric functional coordination following traumatic brain injury (TBI) and its association with posttraumatic anxiety and depressive symptoms. Methods. This was a combination of a retrospective cohort study and a cross-sectional observational study. We investigated the functional coordination between hemispheres by voxel-mirrored homotopic connectivity (VMHC). Grey matter volumes were examined by voxel-based morphometry (VBM), and microstructural integrity of the corpus callosum (CC) was assessed by diffusion tension imaging (DTI). The anxiety and depressive symptoms were evaluated with the Hospital Anxiety and Depression Scale. Results. The VMHC values of the bilateral middle temporal gyrus (MTG) and orbital middle frontal gyrus (MFG) were significantly decreased in TBI patients versus the healthy controls. Weakened homotopic functional connectivity (FC) in the bilateral orbital MFG is moderate positively correlated with anxiety and depressive symptoms. The white matter integrity in the CC was extensively reduced in TBI patients. In the receiver operating characteristic analysis, the VMHC value of the orbital MFG could distinguish TBI from HC with an area under the curve of 0.939 (sensitivity of 1 and specificity of 0.867). Conclusion. TBI disrupts the interhemispheric functional and structural connection, which is correlated with posttraumatic mood disorders. These findings may serve as a clinical indicator for diagnosis.

Many studies have been conducted over the last few decades to understand better the functions of IRF3 and IRF7 in antiviral immune responses. However, the precise underlying molecular mechanism of IRF1-mediated immune response remains largely unknown. Recent studies indicate that IRF1 exerts strong antiviral activities against several viral infections through diverse mechanisms, both in IFN-dependent and IFN-independent manners. Nevertheless, the efficacy and kinetics of inducing IFNs and ISGs remain unknown. Here we summarize the recent advances in IRF1 research and highlight its potential roles in initiating IFN immune responses and subsequent IRF1-triggering antiviral responses. Challenges regarding the IFN positive feedback mediated by IRF7 during infection will be discussed; this classical loop may also be mediated in part by IRF1. Therefore, we propose a revised model that may help decipher the functional roles of IRF1 in antiviral immunity.

The simple and accurate determination of pathogenic infectious diseases is very beneficial to public health prevention and control. For this purpose, we designed a colorimetric sensor for label-free avian influenza A (H7N9) virus gene sequence detection based on gold@platinum core-shell bimetallic-nanoparticle-decorated molybdenum disulfide (MoS

Currently, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide as an Omicron variant. This variant is a heavily mutated virus and designated as a variant of concern by the World Health Organization (WHO). WHO cautioned that the Omicron variant of SARS-CoV-2 held a very high risk of infection, reigniting anxieties about the economy's recovery from the 2-year pandemic. The extensively mutated Omicron variant is likely to spread internationally, posing a high risk of infection surges with serious repercussions in some areas. According to preliminary data, the Omicron variant of SARS-CoV-2 has a higher risk of reinfection. On the other hand, whether the current COVID-19 vaccines could effectively resist the new strain is still under investigation. However, there is very limited information on the current situation of the Omicron variant, such as genomics, transmissibility, efficacy of vaccines, treatment, and management. This review focused on the genomics, transmission, and effectiveness of vaccines against the Omicron variant, which will be helpful for further investigation of a new variant of SARS-CoV-2.

This study aims to introduce a new sagittal cephalometric measurement, the sagittal G-triangle analysis, to accurately and reproducibly assess the sagittal jaw relationship. Sagittal G-triangle analysis, which consists of angles AXK and BXK, is based on an equilateral triangle (Bo-X-K) constructed using 5 cephalometric landmarks (Ba, Bo, Po, Or, and G). To test the diagnostic efficiency of this analysis, pretreatment cephalometric radiographs of 120 female and 120 male Chinese patients were randomly selected. For each enlisted subject, angles SNA and SNB as well as angles AXK and BXK were measured and recorded. On the basis of the SNA and SNB results, subjects were categorized into 6 groups: maxillary retrognathism, normal maxilla, maxillary prognathism, mandibular retrognathism, normal mandible, and mandibular prognathism. The diagnostic efficiency of angles AXK and BXK were evaluated using various statistical tests. A high correlation was detected between angles SNA and AXK as well as between angles SNB and BXK. Female patients with angle AXK between -2.255° and 2.860° and male patients with angle AXK between -2.615° and 2.120° were considered to have a normal maxilla position. Female patients with angle BXK between -2.61° and 2.93° and male patients with angle BXK between -2.275° and 0.610° were considered to have a normal mandible position. In conclusion, sagittal G-triangle analysis could be used as an alternative method for the evaluation of the sagittal position of the maxilla and mandible in cephalometric analysis.

More than 20 members of the human cyclin-dependent kinases (CDKs) family share the feature of being activated by cyclins. CDKs have been involved in diverse biological processes, such as cell cycle, transcription, DNA damage response, and apoptosis. If CDKs are not properly regulated, they can cause diseases like cancer. CDKs are Ser/Thr kinases that work with cyclins to control cell cycle progression. Various CDK-cyclin complexes phosphorylate particular target proteins and drive different cell cycle stages. Accumulating evidence demonstrated that CDKs play an essential role in the cell cycle; however, their roles in antiviral innate immunity are just emerging. This minireview summarizes how CDKs play their roles in antiviral innate immunity. Our goal is to draw attention to the involvement of CDKs in antiviral innate immunity, whether as separate entities or as components of CDK/cyclin complexes that have gotten less attention in the past.

Rapid pathogen screening holds the key against certain viral infections, especially in an overwhelming pandemic. Herein, a CRISPR-empowered electrochemical biosensor was designed for the ultrasensitive detection of the avian influenza A (H7N9) virus gene sequence. Combining the CRISPR/Cas system, a signal-amplification strategy and a high-conductivity sensing substrate, the developed biosensor showed an ultrawide dynamic range, an ultralow detection limit, and excellent selectivity for H7N9 detection, providing a potential sensing platform for the simple, fast, sensitive, and on-site detection of infectious diseases.

CXCL12 expression was significantly lower in tumor samples than in corresponding normal samples. CXCL12 expression was significantly positively related to the infiltration levels of T cells, dendritic cells (DCs), immature DCs, cytotoxic cells, Tfh cells, mast cells, B cells, Th1 cells, natural killer (NK) cells, pDCs, neutrophils, and T helper cells (Spearman correlation coefficient > 0.5, P < 0.001) and negatively correlated with the infiltration level of NK CD56bright cells. In addition, pancreatic hTERT-HPNE cells treated with three diverse CXCL12 isoforms exhibited changes mainly in the regulation of the epithelial-mesenchymal transition activation pathway.

Cancer stemness represents a major source of development and progression of colorectal cancer (CRC). c-Met critically contributes to CRC stemness, but how c-Met is activated in CRC remains elusive. We previously identified the lipolytic factor ABHD5 as an important tumour suppressor gene in CRC. Here, we show that loss of ABHD5 promotes c-Met activation to sustain CRC stemness in a non-canonical manner. Mechanistically, we demonstrate that ABHD5 interacts in the cytoplasm with the core subunit of the SET1A methyltransferase complex, DPY30, thereby inhibiting the nuclear translocation of DPY30 and activity of SET1A. In the absence of ABHD5, DPY30 translocates to the nucleus and supports SET1A-mediated methylation of YAP and histone H3, which sequesters YAP in the nucleus and increases chromatin accessibility to synergistically promote YAP-induced transcription of c-Met, thus promoting the stemness of CRC cells. This study reveals a novel role of ABHD5 in regulating histone/non-histone methylation and CRC stemness., This study reveals an unrecognized role of ABHD5 in regulating colon cancer stemness via controlling YAP methylation and nuclear localization, further explaining the molecular mechanism through which ABHD5 functions as a tumour suppressor gene in colon cancer.

Objective To explore the applications of 3-dimensional digital subtraction angiography (3D-DSA) double-volume reconstruction technique (DVRT) in endovascular embolization for the treatment of intracranial aneurysm. Methods A cohort of 112 patients with a total of 127 intracranial aneurysms admitted to the neurosurgery department from June 2018 to October 2019 were selected. Cerebrovascular angiographies were performed after admission. Patients were divided into observation group (56 of 112) and control group (56 of 112) randomly when endovascular embolization was performed. Individuals in the control group were treated with 2D-DSA technique, and patients in the observation group were treated with 3D-DSA DVRT. The Raymond method was used to determine the degree of embolism. Results There was no significant difference in sex, blood pressure, cerebral atherosclerosis, aneurysm site or size, contrast agent dosage, x-ray dose, or surgical cost between the 2 groups. There was no postoperative recurrence in the observation group. However, the recurrence rate in the control group is 10.7% (6 of 56). Postoperative thrombosis occurred in 1 case (1 of 56, 1.8%) in the observation group and 7 cases (7 of 56, 12.5%) in the control group. No postoperative cerebral infarction was recorded in the observation group, while 5 cases (8.9%, 5 of 56) in the control group presented with postoperative cerebral infarction. Conclusions 3D-DVRT for intracranial aneurysm embolization provides the best working angle, clearly shows the process of aneurysm embolization and its relationship with peripheral vessels, and reduces the occurrence of surgical complications including postoperative recurrence, thrombosis, and cerebral infarction.

Little is known about the damage to the important peripheral immune organ spleen caused by Streptococcus suis infection. In this study, we found that S. suis induced splenomegaly and lymphocyte disruption in spleens of mice. To explore the mechanism of splenic lesions induced by S. suis, we conducted further studies. The results showed that S. suis induced apoptosis in B cells, which is related to the cleavage of caspase-3 and caspase-8, but not the release of apoptosis-inducing factor (AIF). Thus, S. suis induced apoptosis in the spleen through caspase-dependent and AIF-independent pathways. Inflammation lesions induced in the spleen of infected mice were also investigated; we found macrophages increased in histopathological lesions of infected spleens from 12 h postinoculation to 7 days postinoculation (dpi), and the type of increased macrophages was M1 type by confocal microscopy, which can secrete proinflammatory cytokines. Meanwhile, inflammasome NLRP3 and caspase-1 were activated, and gasdermin D (GSDMD) was cleaved, which causes pyroptosis that may result in the release of numerous proinflammatory cytokines. What's more, the increase of p-JNK and p-p38 indicated that the MAPK pathway was also involved in the proinflammatory responses during S. suis infection, whereas anti-inflammatory responses in spleen were suppressed, with regulatory T cells (Tregs) upregulating at 1 dpi. Taken together, proinflammatory immune responses dominate in early infection, which induce splenomegaly and splenocyte apoptosis. This is the first report of mechanisms associated with S. suis-induced splenic lesions.

The pathogenesis of preeclampsia (PE) is associated with inflammation and endothelial damage. Ulinastatin (UTI) mainly inhibits proteolytic activity and significantly reduces the release of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) from macrophages. It also ameliorates vascular endothelial damage in pathological conditions. Hence, we investigated the effects of UTI in a rat model of PE induced using N(gamma)-nitro-l-arginine methyl ester (L-NAME).Although inducing PE in a rat model, 5000 U/kg of UTI were injected daily. Systolic blood pressure (SBP) and protein levels in the urine were measured. Renal function, and serum concentrations of TNF-α, IL-6, placental growth factor (PLGF), and von Willebrand factor (vWF) were evaluated. The number and weight of live fetuses as well as the weight of placentas were measured. Placentas were collected for western blot and pathological analysis.UTI slightly ameliorated proteinuria and the increases in SBP, blood urea nitrogen (BUN), and serum creatinine. Furthermore, UTI improved serum and placental protein expression levels of TNF-α, IL-6, vWF, and PLGF. Pathological analysis revealed that vascular density and blood flow perfusion was enhanced, vessel wall thickening and neutrophil infiltration were diminished, and the weight and number of live fetuses as well as the weight of the placentas were improved with UTI.Preventive use of UTI in the PE rat model induced by L-NAME partially alleviated hypertension, proteinuria, and impaired renal function; improved fetal growth restriction; diminished vascular endothelial injury; and ameliorated placental vasculogenesis abnormality and malperfusion by inhibiting the systemic and placental inflammatory response, suggesting that UTI is a potential drug for PE prevention or treatment.

Background Malignant peritoneal mesothelioma (MPM) is a rare malignant tumor with a high mortality rate and extremely poor prognosis. In-depth pathological analysis is essential to assess tumor biological behaviors and explore potential therapeutic targets of MPM. Nucleoplasmin 2 (NPM2) is a molecular chaperone that binds histones and may play a key role in the development and progression of tumors. This study aimed to analyze the correlation between the expression level of NPM2 and the main clinicopathological characteristics and prognosis of MPM. Methods Ninety-two postoperative specimens from MPM patients following cytoreductive surgery were collected. Postoperative specimens were stained with immunohistochemistry. The expression level of NPM2 was quantitatively analyzed by QuPath-0.3.2 software. Univariate and multivariate analyses were conducted to investigate the correlation between NPM2 expression and other conventional clinicopathological characteristics. Results Among the 92 MPM patients, there were 47 males (48.9%) and 45 females (51.1%), with a median age of 56 (range: 24–73). There were 70 (76.0%) cases with loss of NPM2 protein expression, 11 (12.0%) cases with low expression, and 11 (12.0%) cases with high expression. Univariate analysis showed that NPM2 protein expression level (negative vs. low expression vs. high expression) was negatively correlated with the following three clinicopathological factors: completeness of cytoreduction (CC) score, vascular tumor emboli, and serious adverse events (SAEs) (all P < 0.05). Multivariate analysis showed that NPM2 protein expression level (negative vs. low expression vs. high expression) was independently negatively correlated with the following two clinicopathological factors: CC score [odds ratio (OR) = 0.317, 95% CI: 0.317–0.959, P = 0.042] and vascular tumor emboli (OR = 0.092, 95% CI = 0.011–0.770, P = 0.028). Survival analysis showed that loss of NPM2 protein expression (negative vs. positive) was associated with poor prognosis of MPM. Conclusions Loss of NPM2 expression is a potential immunohistochemical marker for MPM.

Background: The present study aimed to investigate the prevalence of peri-implant disease and identify potential disease risk factors in western China. Methods: The present retrospective study was conducted in 131 consecutive patients receiving 248 dental implants treated with implant-supported prostheses with a mean follow-up of 2.52 years. Several patient-related, implant-related, and oral hygiene maintenance factors were analyzed. Results: Peri-implant disease developed in 68 (51.91%) patients and 110 (44.35%) implants. The prevalence of peri-implant mucositis and peri-implantitis were 45.80% and 7.63%, respectively, at the subject level, and 36.69% and 7.66%, respectively, at the implant level. Multivariate analysis exhibited that male [odds ratio (OR) = 1.91; 95% confidence interval (CI): 1.02–3.57; p = 0.04], implant length < 10mm (OR = 7.87; 95% CI:1.62–38.46; p = 0.01), poor proximal contact of the prosthesis (OR = 1.90; 95% CI: 1.06–3.42; p = 0.03), tooth brushing once a day (OR = 3.11; 95% CI: 1.26–7.68; p = 0.04) and moderate periodontitis (OR = 13.00; 95% CI: 4.38–38.60; p < 0.01) were independent risk factors for peri-implant disease.

Background and objectives This study aimed to compare outcomes between neoadjuvant imatinib and upfront surgery in patients with localized rectal gastrointestinal stromal tumors (GIST) patients. Methods Eighty-five patients with localized rectal GIST were divided into two groups: upfront surgery ± adjuvant imatinib (Group A, n = 33) and the neoadjuvant imatinib + surgery + adjuvant imatinib (Group B, n = 52). Baseline characteristics between groups were controlled for with inverse probability of treatment weighting (IPTW) adjusted analysis. Results The response rate to neoadjuvant imatinib was 65.9%. After the IPTW-adjusted analysis, patients who underwent neoadjuvant therapy had better distant recurrence-free survival (DRFS) and disease-specific survival (DSS) compared with those who underwent upfront surgery (5-year DRFS 97.8 vs. 71.9%, hazard ratio [HR], 0.15; 95% CI, 0.03-0.87; p = 0.03; 5-year DSS 100 vs. 77.1%; HR, 0.11; 95% CI, 0.01-0.92; p = 0.04). While no significant association was found between overall survival (OS) and treatment groups (p = 0.07), 5-year OS was higher for the neoadjuvant group than upfront surgery group (97.8% vs. 71.9%; HR, 0.2; 95% CI, 0.03-1.15). Conclusions In patients with localized rectal GIST, neoadjuvant imatinib not only shrunk the tumor size but also decreased the risk of metastasis and tumor-related deaths when compared to upfront surgery and adjuvant imatinib alone.

Introduction Subcutaneous galcanezumab was an effective, well-tolerated preventive treatment for adults with episodic (EM) or chronic migraine (CM) in 4 phase 3 randomized controlled trials: EVOLVE-1, EVOLVE-2, REGAIN, and CONQUER. Number needed to treat (NNT) and to harm (NNH) are metrics of effect size used to evaluate benefit–risk profiles. This study evaluated NNT, NNH, and benefit–risk profiles (measured as likelihood to be helped or harmed, LHH) of galcanezumab 120 mg versus placebo in patients with EM or CM. Methods Primary efficacy outcomes were responses defined as ≥ 30%, ≥ 50%, and ≥ 75% reductions from baseline in number of monthly migraine headache days in patients with EM (EVOLVE-1; EVOLVE-2; CONQUER) and CM (REGAIN; CONQUER); corresponding NNTs to achieve respective responses; and corresponding NNHs for discontinuations due to adverse events (DCAEs) among the safety population. Secondary efficacy outcomes were responses for patients with ≥ 2 failed prior preventive treatments due to lack of efficacy and/or for tolerability reasons. All LHHs were based on ≥ 50% response and DCAEs. Results During double-blind treatment periods with galcanezumab 120 mg, NNT to achieve ≥ 30% and ≥ 50% responses ranged from 4 to 10 and NNT to achieve ≥ 75% responses ranged from 5 to 23 in individual trials. NNH ranged from 93 to 1000, while LHH ranged from 18.6 to 104.6. NNTs were generally more robust among patients with EM than with CM; however, in patients with failure of ≥ 2 prior preventive treatments, NNTs to achieve ≥ 30% and ≥ 50% responses were similar between patients with CM and EM. NNHs were imputed as 1000 for both migraine types. Resulting LHHs were 178.8 (EM) and 127 (CM). Conclusion Across 4 trials, galcanezumab 120 mg demonstrated a favorable benefit–risk profile versus placebo, based on low NNTs to achieve response and high NNHs associated with DCAEs. LHH values consistently far exceeded 1. Trial Registration Numbers EVOLVE-1: ClinicalTrials.gov identifier, NCT02614183; EVOLVE-2: ClinicalTrials.gov identifier, NCT02614196; REGAIN: ClinicalTrials.gov identifier, NCT02614261; CONQUER: ClinicalTrials.gov identifier, NCT03559257. Supplementary Information The online version contains supplementary material available at 10.1007/s12325-021-01848-x.

MicroRNAs (miRNAs), useful biomarkers for cancer diagnosis, play an important role in tumorigenesis and progression, but many of the current analysis methods can suffer from excessive protease dependence, being time-consuming and unsatisfactory performance. Therefore, a reliable sensing strategy for the protein-free, ultrasensitive analysis of tumor-associated miRNAs is desired. The proposed dual-walker biosensing strategy based on an entropy-driven catalytic (EDC) walker coupled with a smart-responsive DNAzyme walker was demonstrated for the dual-amplification detection of miRNA-21. Namely, the target miRNA-21 initiates the three-stranded substrate complex of the traditional EDC circuit to release the input trigger of the Dz walker, which recognizes the circular binding domain to restore the cleavage activity of the DzS-AuNP walker. The fluorescence signal continuously released from the AuNPs was recorded by a fluorescence reader for miRNA-21 sensing. The optimized dual-walker exhibited appreciable sensitivity with a detection limit of 70 fM, satisfactory flexibility, fine specificity and ideal stability for clinical serum sample assays. The proposed strategy may open a new avenue for the development of powerful DNA molecular tools for cancer diagnosis.

Ubiquitination is a highly conserved and fundamental posttranslational modification (PTM) in all eukaryotes regulating thousands of proteins. The RING (really interesting new gene) finger (RNF) protein, containing the RING domain, exerts E3 ubiquitin ligase that mediates the covalent attachment of ubiquitin (Ub) to target proteins. Multiple reviews have summarized the critical roles of the tripartite-motif (TRIM) protein family, a subgroup of RNF proteins, in various diseases, including cancer, inflammatory, infectious, and neuropsychiatric disorders. Except for TRIMs, since numerous studies over the past decades have delineated that other RNF proteins also exert widespread involvement in several diseases, their importance should not be underestimated. This review summarizes the potential contribution of dysregulated RNF proteins, except for TRIMs, to the pathogenesis of some diseases, including cancer, autoimmune diseases, and neurodegenerative disorder. Since viral infection is broadly involved in the induction and development of those diseases, this manuscript also highlights the regulatory roles of RNF proteins, excluding TRIMs, in the antiviral immune responses. In addition, we further discuss the potential intervention strategies targeting other RNF proteins for the prevention and therapeutics of those human diseases.

Revealing the mechanisms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry and cell-to-cell spread might provide insights for understanding the underlying mechanisms of viral pathogenesis, tropism, and virulence. The signaling pathways involved in SARS-CoV-2 entry and viral spike-mediated cell-to-cell fusion remain elusive. In the current study, we found that macropinocytosis inhibitors significantly suppressed SARS-CoV-2 infection at both the entry and viral spike-mediated cell-to-cell fusion steps. We demonstrated that SARS-CoV-2 entry required the small GTPase Rac1 and its effector kinase p21-activated kinase 1 by dominant-negative and RNAi assays in human embryonic kidney 293T-angiotensin-converting enzyme 2 cells and that the serine protease transmembrane serine protease 2 reversed the decrease in SARS-CoV-2 entry caused by the macropinocytosis inhibitors. Moreover, in the cell-to-cell fusion assay, we confirmed that macropinocytosis inhibitors significantly decreased viral spike-mediated cell-to-cell fusion. Overall, we provided evidence that SARS-CoV-2 utilizes a macropinocytosis pathway to enter target cells and to efficiently promote viral spike-mediated cell-to-cell fusion.

ObjectiveTo analyse the prevalence and heart rate variability (HRV) characteristics of premature ventricular contraction (PVC) detected by 24-hour Holter among Chinese outpatients with palpitations.DesignA cross-sectional study.SettingThis study was conducted in a tertiary hospital.ParticipantsA total of 4754 outpatients who received 24-hour Holter for palpitations.Main outcome measuresPrevalence, HRV time-domain and frequency-domain analyses of 24-hour Holter, and echocardiographic parameters were assessed. Propensity score matching (PSM) was applied to balance baseline variables (age, gender) to decrease the bias between comparison groups.ResultsThe prevalence of PVC was 67.7% (3220/4754), and was higher in men than women (69.9% vs 66.0%, p=0.004); the prevalence of frequent PVCs (PVC burden≥5%) was 7.7% (368/4754). Older patients had the highest frequency of PVC among all patients. However, among 3220 patients with PVC, younger patients’ PVC burden was much higher. Matched 1:1 by age and gender, the HRV time-domain parameters in patients with PVC were all lower than those in patients without PVC (all pConclusionsThe prevalence of PVC and frequent PVCs were 67.7% and 7.7%, respectively, detected by 24-hour Holter among Chinese outpatients with palpitations. Decreased HRV time-domain parameters suggested the occurrence of PVC, and increased LF/HF ratio represented the imbalance of autonomic nervous system in patients with frequent PVCs. Further studies are needed to understand the HRV indexes in PVC patients.

Coronavirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic and has severely affected socio-economic conditions and people’s life. The lung is the major target organ infected and (seriously) damaged by SARS-CoV-2, so a comprehensive understanding of the virus and the mechanism of infection are the first choices to overcome COVID-19. Recent studies have demonstrated the enormous value of human organoids as platforms for virological research, making them an ideal tool for researching host–pathogen interactions. In this study, the various existing lung organoids and their identification biomarkers and applications are summarized. At the same time, the seven coronaviruses currently capable of infecting humans are outlined. Finally, a detailed summary of existing studies on SARS-CoV-2 using lung organoids is provided and includes pathogenesis, drug development, and precision treatment. This review highlights the value of lung organoids in studying SARS-CoV-2 infection, bringing hope that research will alleviate COVID-19-associated lung infections.

Background Cancer metabolism is largely altered compared to normal cells. This study aims to explore critical metabolism pathways in colon adenocarcinoma (COAD), and reveal the possible mechanism of their role in cancer progression. Methods Expression data and sequencing data of COAD samples were obtained from The Cancer Genome Atlas and Gene Expression Omnibus databases. The expression profiles between tumor and normal samples were compared to identify differential metabolism pathways through single sample gene set enrichment analysis. Results Fatty acid synthesis was identified as a key metabolism pathway in COAD. Based on fatty acid-related lncRNAs, two molecular subtypes (C1 and C2) were defined. C2 subtype with worse prognosis had higher immune infiltration and higher expression of immune checkpoints. Five transcription factors (TFs) including FOS, JUN, HIF1A, STAT3 and STAT2 were highly expressed in C2 subtype. Five fatty acid-related lncRNAs were identified to be biomarkers for predicting COAD prognosis. Finally, further experients showed that knockdown of lncRNA PAXIP1-AS1 decreased the triglyceride content and the fatty acid synthase and acetyl-CoA carboxylase 1 expressions, which suggested that lncRNA PAXIP1-AS1 plays an important role in fatty acid metabolism of COAD. Conclusions This study demonstrated that fatty acid synthesis was greatly altered in COAD. Fatty acid-related lncRNAs were speculated to be involved in cancer progression through associating with TFs. The five screened TFs may serve as new drug targets for treating COAD.

Antiphospholipid syndrome (APS) is an autoimmune disease characterized by thrombotic events and/or pregnancy morbidity (≥3 recurrent early miscarriage or fetal death or a prematurity34 weeks of gestation) with persistently positive antiphospholipid antibodies (aPLs). It is reported that aPLs damage the placental tissue by binding to β2-glycoprotein I (β2GPI) on the surface of trophoblast and endothelial cells. Hydroxychloroquine (HCQ) is considered to be beneficial in the treatment of obstetrical APS and shown to restore the aPL-inhibited invasion and differentiation of trophoblast. However, not enough evidence exists regarding the effect of HCQ on endometrial angiogenesis. The aim of our study was to assess whether HCQ has an effect on aPL-inhibited endothelial angiogenesis.In this research, to explore the effect of HCQ for angiogenesis, we investigated: (1) Human umbilical vein endothelial cells (HUVECs) viability by CCK-8; (2) HUVECs migration by wound healing; (3) HUVEC angiogenesis by Matrigel assayWe found that HCQ treatment significantly restored the expression of aPL-inhibitedIn conclusion, aPLs inhibit HUVECs angiogenesis, however, HCQ can restore the effect of aPL-inhibited HUVECs migration and angiogenesis

Prostate cancer susceptibility is a polygenic trait. We aimed to examine the controversial diagnostic utility of single-nucleotide polymorphisms (SNP) for prostate cancer. We analyzed two datasets collected from Europeans and one from Africans. These datasets were generated by the genome-wide association studies, that is, CGEMS, BPC3, and MEC-Africans, respectively. About 540,000 SNPs, including 61 risk markers that constitute a panel termed MK-61, were commonly genotyped. For each dataset, we augmented the MK-61 panel to generate an MK-61+ one by adding several thousands of SNPs that were moderately associated with prostate cancer occurrence in external dataset(s). We assessed the diagnostic utility of both panels by measuring their predictive strength for prostate cancer occurrence with AUC statistics. We calculated the theoretical AUCs using quantitative genetics model-based formulae and obtained the empirical estimates via 10-fold cross-validation using statistical and machine learning techniques. For the MK-61 panel, the 95% confidence intervals of the theoretical AUCs (AUC-CI.95) were 0.578–0.655, 0.596–0.656, and 0.539–0.596 in the CGEMS, BPC3, and MEC-Africans cohorts, respectively. For the MK-61+ panels, the corresponding AUC-CI.95 were 0.617–0.663, 0.527–0.736, and 0.547–0.565. The empirical AUCs largely fell within the theoretical interval. A promising result (AUC = 0.703, FNR = 0.354, FPR = 0.353) was obtained in the BPC3 cohort when the MK-61+ panel was used. In the CGEMS cohort, the MK-61+ panel complemented PSA in predicting the disease status of PSA ≥ 2.0 ng/mL samples. This study demonstrates that augmented risk SNP panels can enhance prostate cancer prediction for males of European ancestry, especially those with {\rm{PSA}} \ge 2.0\ $ng/mL. Prevention Relevance: This study demonstrates that augmented risk SNP panels can enhance prostate cancer prediction for males of European ancestry, especially those with PSA ≥ 2 ng/mL.

Upregulation of androgen receptor splice variants (AR-Vs), especially AR-V7, is associated with castration resistance of prostate cancer. At the RNA level, AR-V7 upregulation is generally coupled with increased full-length AR (AR-FL); consequently, AR-V7 and AR-Vs collectively constitute a minority of the AR population. However, Western blotting showed that the relative abundance of AR-V proteins is much higher in many castration-resistant prostate cancers (CRPCs). To address the mechanism underlying this discrepancy, we analyzed RNA-seq data from ~350 CRPC samples and found a positive correlation between all canonical and alternative AR splicing. This indicates that increased alternative splicing is not at the expense of canonical splicing. Instead, androgen deprivation releases AR-FL from repressing the transcription of the AR gene to induce coordinated increase of AR-FL and AR-V mRNAs. At the protein level, however, androgen deprivation induces AR-FL, but not AR-V, degradation. Moreover, AR-V7 is translated much faster than AR-FL. Thus, androgen-deprivation-induced AR-gene transcription and AR-FL protein decay, together with efficient AR-V7 translation, explain the discrepancy between the relative AR-V mRNA and protein abundances in many CRPCs, highlighting the inevitability of AR-V induction after endocrine therapy.

Extensive evidence has explored the involvement of microRNAs (miRNAs) in osteosarcoma (OS). Limitedly, the concrete function of microRNA-18b-5p (miR-18b-5p) in OS remains unexplored and largely elusive. Here, we validated that miR-18b-5p significantly elevated in OS via analyzing the data from GEO database. The results showed that miR-18b-5p was overexpressed in human OS tissues and cell lines. The clinical evidence suggested that high level of miR-18b-5p was negatively correlated with the poor prognosis of OS. Meanwhile, miR-18b-5p upregulation facilitated the proliferation and metastasis of OS cells in vitro and in vivo. The mechanism exploration demonstrated that miR-18b-5p acted as a potential inhibitor of PHF2, a tumor suppressor gene, at post-transcriptional level. Moreover, hypoxia induced gene expression of miR-18b-5p was clarified to be transcriptionally mediated by HIF-1α. The clinicopathological analysis in samples of OS patients further supported that miR-18b-5p had a positive correlation with HIF-1α expression, and negative correlation with PHF2. Collectively, the present study uncovered a new molecular mechanism of OS tumorigenesis and development and miR-18b-5p might be a prognostic biomarker and potential therapeutic target for OS treatment.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), since its outbreak in December 2019, has been capable of continuing the pandemic by mutating itself into different variants. Mass vaccinations, antibiotic treatment therapy, herd immunity, and preventive measures have reduced the disease's severity from the emerging variants. However, the virus is undergoing recombination among the current two variants: Delta and Omicron, resulting in a new variant, informally known as "Deltacron," which was controversial as it might be a product of lab contamination between Omicron and Delta samples. However, the proclamation was proved wrong, and the experts are putting more effort into better understanding the variant's epidemiological characteristics to control potential outbreaks. This review has discussed the potential mutations in the novel variant and prospective risk factors and therapeutic options in the context of this new variant. This study could be used as a guide for implementing appropriate controls in a sudden outbreak of this new variant.

To investigate the influence of peripheral hemoglobin (Hb)-to-red cell distribution width (RDW) ratio (HRR) on the prognosis of patients with diffuse large B-cell lymphoma (DLBCL).Data of 265 patients with diffuse large B-cell lymphoma (DLBCL) at the Affiliated Hospital of Xuzhou Medical University from January 2014 to December 2019 were retrospectively analyzed. 132 healthy people in the same period were used as normal control group. The best cut-off points of HRR was determined by receiver operating characteristics (ROC) curve; the chi-square test was used to analyze the correlation of clinical characteristics with HRR; the Kaplan-Meier method was used to compare the overall survival (OS) and progression-free survival (PFS) of HRR patients in different groups; the Cox proportional risk model was used for univariate and multivariate analysis.The best cut-off value of HRR was 0.936, which was divided into low HRR group and high HRR group. The low HRR group had a higher ECOG score, higher incidence of advanced Ann Arbor stage, higher NCCN-IPI score, and elevated LDH level. K-M survival analysis showed that OS (P0.001) and PFS (P0.001) in the low HRR group were significantly shorter than that in the higher HRR group. The multivariate analysis revealed that HRR was an independent predictor of OS（HR＝0.379，95％CI：0.237-0.605，P0.001） and PFS （HR＝0.384，95％CI：0.241－0.614，P0.001） in DLBCL patients.Low HRR（0.936） in patients with DLBCL indicates a poor prognosis, which is an independent prognosis risk factor.外周血红蛋白/红细胞分布宽度比值对弥漫大B细胞淋巴瘤患者预后的影响.探讨外周血红蛋白/红细胞分布宽度比值（HRR）对弥漫大B细胞淋巴瘤（DLBCL）患者预后的影响.回顾性分析2014年1月至2019年12月徐州医科大学附属医院收治的265例初诊DLBCL患者的临床资料，以同期132名健康体检者作为正常对照。采用受试者工作特征（ROC）曲线确定HRR最佳截断值；应用卡方检验分析HRR与DLBCL患者临床特征的相关性；采用Kaplan-Meier法比较不同分组HRR患者的总生存（OS）率和无进展生存（PFS）率；采用Cox比例风险模型进行单因素、多因素分析.HRR最佳截断值为0.936，以此为界分为低HRR组（0.936）和高HRR组（≥0.936）。低HRR组患者ECOG评分较高、Ann Arbor分期较晚、LDH水平高于正常值、NCCN-IPI评分较高。K-M生存分析显示，低HRR组的OS（P0.001）和PFS（P0.001）时间均较高HRR组显著缩短。多因素Cox分析结果显示，HRR是影响DLBCL患者OS（HR＝0.377，95％CI：0.236-0603，P0.001）和PFS（HR＝0.383，95％CI：0.240-0.612，P0.001）的独立危险因素.初诊DLBCL患者低HRR（0.936）提示预后不良，是影响预后的独立危险因素.

Background CGAR, a Phase 3b open-label study, evaluated the long-term safety of galcanezumab in patients with cluster headache who completed one of two Phase 3 double-blind studies in chronic or episodic cluster headache. Methods Patients (N = 164) received galcanezumab 300 mg subcutaneously up to once a month. Primary endpoint was safety, as assessed by treatment-emergent adverse events, serious adverse events, and suicidality. Other endpoints included discontinuation rates, immunogenicity, efficacy as assessed by the Patient Global Impression of Improvement, and health values. Results At baseline, mean (standard deviation) age was 48.3 (9.8) years, 75.0% were men, and 85.4% were white. Treatment-emergent adverse events (n = 119 [72.6%]) were mostly mild-to-moderate, with nasopharyngitis the most commonly reported (22.0%). One of 18 serious adverse events was judged as treatment related (constipation). Two patients (1.2%) reported suicidal ideation. Five patients (3.1%) discontinued due to an adverse event. Eight patients were treatment-emergent anti-drug antibody positive, two of whom were not treatment-emergent anti-drug antibody positive in the parent studies. On the Patient Global Impression of Improvement, ≥81% reported their cluster headache status as very much, much, or a little better at Months 1, 6, and 12. Health value scores generally improved from baseline. Conclusions In this open-label study, galcanezumab was generally well tolerated and improved patient-reported cluster headache status. Trial registration number: NCT02797951; https://clinicaltrials.gov/ct2/show/NCT02797951

In controlled clinical trials, compared with placebo, a significantly greater proportion of participants using lasmiditan to treat a migraine attack achieved 2-h pain freedom (PF) and experienced ≥ 1 treatment-emergent adverse event (TEAE).To better inform clinicians about treatment expectations by evaluating the association between TEAEs and efficacy outcomes after lasmiditan treatment.Pooled data from SAMURAI, SPARTAN, MONONOFU, and CENTURION were analyzed. A common TEAE (CTEAE) was defined as occurring in ≥ 2% in the overall population. Central nervous system (CNS)-CTEAEs were based on Medical Dictionary for Regulatory Activities.At 2 h, a significantly higher percentage of lasmiditan 200 mg-treated participants who achieved PF experienced ≥ 1 CTEAE than non-responders who continued to experience moderate/severe pain (48.2% vs. 28.7%, respectively). Correspondingly, a significantly higher percentage of lasmiditan 200 mg-treated participants who experienced ≥ 1 CTEAE achieved PF at 2 h than those who did not (39.0% vs. 30.2%, respectively). Similar results were generally observed with individual CNS-CTEAEs, but for non-CNS-CTEAEs, this pattern was less evident or in the opposite direction. No consistent differences were observed for migraine-related functional disability freedom. The percentage of participants with improved patient global impression of change (PGIC) was greater with a CNS-CTEAE versus no CNS-CTEAE.Those who had PF at 2 h were more likely to experience a CNS-CTEAE, and those with CNS-CTEAEs were more likely to experience PF. The occurrence of CTEAEs did not seem to negatively affect disability freedom or PGIC.SAMURAI (NCT02439320), SPARTAN (NCT02605174), MONONOFU (NCT03962738), CENTURION (NCT03670810), ClinicalTrials.gov: NCT02439320, NCT02605174, NCT03962738, NCT03670810.

To investigate independent factors for the efficacy and safety of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of diffuse malignant peritoneal mesothelioma (DMPM).The clinical database of 110 DMPM patients treated with CRS + HIPEC at our hospital was retrospectively analyzed. Independent prognostic factors were screened using univariate and multivariate analyses and the safety of the perioperative period was evaluated based on adverse events.Among the 110 patients with DMPM, 34 (30.9%) had a peritoneal cancer index (PCI)20 and 76 (69.1%) had PCI ≥20; 59 (53.6%) patients achieved completeness of cytoreduction (CC) 0/1 and 51 (46.4%) cases achieved CC 2/3. At the median follow-up of 43.3 (95%CI: 37.3-49.4) months, 48 (43.6%) patients were still alive and 62 (56.4%) patients died. The median overall survival was 32.6 months. Serious adverse events (SAEs) occurred in 41 patients (37.3%) and the perioperative mortality rate was 2.7%. Univariate analysis identified nine prognostic factors: Karnofsky performance status score, perioperative tumor markers, PCI, red blood cell infusion, pathological type, vascular tumor emboli, lymphatic metastasis, Ki-67 index, and perioperative SAEs (allCRS + HIPEC for DMPM treatment resulted in prolonged survival with acceptable safety. Tumor pathology and SAEs are key factors for successful CRS + HIPEC.

Self-control is a well-known inhibitor of aggression, but the effect of self-control on different kinds of aggression (such as reactive-proactive aggression) and the underlying mediating mechanisms of these effects are unclear. We developed a mediation model to address these issues. A three-wave study was conducted with a sample of 1203 qualifying Chinese undergraduates to test the model. The results showed that self-control at Wave 1 negatively predicted reactive aggression at Wave 3 through mediating effects of hostile rumination and moral disengagement at Wave 2 at the same time, while self-control at Wave 1 negatively predicted proactive aggression at Wave 3 only through moral disengagement at Wave 2. Furthermore, the longitudinal relationship between hostile rumination and moral disengagement is mutual. The current findings support our hypotheses regarding the mediation model of self-control inhibiting reactive-proactive aggression and suggest that moral disengagement should be a common and basic variable to predict most kinds of aggression; further, hostile rumination only has a particular effect on reactive aggression. The present study used motivation theory to explain its mediation model, which develops aggressive theory regarding varied common influencing factors and underlying mediating mechanisms of reactive and proactive aggression.

To analyze the clinical characteristics and genetic basis of two children patients with CHARGE syndrome.The clinical features of the two patients were analyzed, and potential variants were detected by Trio whole exome sequencing (trio-WES) of the probands and their parents.Child 1 has manifested cerebellar vermis dysplasia, enlargement of cerebral ventricles, whereas child 2 manifested with infantile spasm and congenital hip dysplasia. Both children were found to harbor de novo heterozygous variants of the CHD7 gene, namely c.4015CT (exon 17) and c.5050GA (exon 22). Based on the guidelines of the American College of Medical Genetics and Genomics, the two variants were rated as pathogenic variants, and the related disease was CHARGE syndrome. Furthermore, child 2 was also found to harbor a novel heterozygous c.6161AC (p.Gln2054Pro) missense variant of COL12A1 gene, which was rated as possibly pathogenic, and the associated disease was Bethlem myopathy type 2, which is partially matched with the patient' s clinical phenotype.The special clinical phenotypes shown by the two children harboring novel CHD7 variants have further expanded the phenotypic spectrum of CHARGE syndrome.

Background Oral squamous cell carcinoma (OSCC) is one of the common cancers worldwide. The lack of specific biomarkers and therapeutic targets leads to delayed diagnosis and hence the poor prognosis of OSCC patients. Thus, it is urgent to identify effective biomarkers and therapeutic targets for OSCC. Methods We established the golden hamster carcinogenic model of OSCC induced by 7,12-dimethylbenz(a) anthrancene (DMBA) and used mRNA microarrays to detect the differentially expressed genes (DEGs). DEGs were validated in OSCC clinical tissue microarrays using immunohistochemistry method. Whole transcriptome sequencing was performed to obtain an overview of biological functions of Lsm12. PCR assay and sequencing were employed to investigate the alternative splicing of genes regulated by Lsm12. Cell proliferation, colony formation, Transwell migration and invasion assay and in vivo tumor formation assay were performed to investigate the roles of Lsm12 and two transcript variants of USO1 in OSCC cells. Results Lsm12 was identified to be significantly up-regulated in the animal model of OSCC tumorigenesis, which was validated in the clinical OSCC samples. In the paired normal tissues, Lsm12 staining was negative (91%, 92/101) or weak, while in OSCC tissues, positive rate is 100% and strong staining spread over the whole tissues in 93 (93/101, 92%) cases. Lsm12 overexpression significantly promoted OSCC cell growth, colony formation, migration and invasion abilities, while Lsm12 knockdown showed the opposite trends on these phenotypes and obviously inhibited the tumor formation in vivo. Furthermore, Lsm12 overexpression caused the inclusion of USO1 exon 15 and Lsm12 knockdown induced exon 15 skipping. Exon 15-retained USO1 significantly promoted the malignant phenotypes of OSCC cells when compared with the exon 15-deleted USO1. Conclusions We identified Lsm12, a novel tumorigenesis-related gene, as an important regulator involved in OSCC tumorigenesis. Lsm12 is a novel RNA-splicing related gene and can regulate the alternative splicing of USO1 exon 15 which was associated closely with OSCC carcinogenesis. Our findings thus provide that Lsm12 might be a potent biomarker and potential therapeutic target for OSCC.

ObjectiveTo investigate injury trends, injury distribution, and disease burden from three surveillance hospitals in Urumqi from 2006 to 2018.MethodInjury data from the National Injury Surveillance System (NISS) from three hospitals in Urumqi (2006 to 2018) were collected to analyze changes in the characteristics of outpatient injury cases. Years of potential life lost (YPLL) were calculated to determine the disease burden of the injury cases.ResultsA total of 161,400 injury cases were recorded over 13 years, and the average age of the patient seeking medical attention was 32.4 years old. Male patients outnumbered female patients with a ratio of 1.6:1, but the proportion of female patients was greater after 45 years of age. The highest number of cases occurred in patients 15–29 years of age, accounting for 26.8% of all injury cases. Injury in females occurred most frequently in the home. A total of 41.4% of injury cases occurred while doing housework. The top three causes of injury were falls (49.7%), blunt force of an object, (13.7%), and motor vehicle accidents (MVA) (13.5%). Years of potential life lost from injury accounted for 7.39% of the total YPLL in the three hospitals.ConclusionMales should be targeted for injury prevention and intervention in Urumqi. The prevention of falls, blunt force of objects, and MVA should be made a priority. Injury prevention strategies and targeted projects should be developed to reduce the disease burden of injury.

Exosomes have been widely used in early cancer diagnosis as promising cancer biomarkers due to their abundant tumor-specific molecular information. In this study, we developed a sensitive and straightforward surface-enhanced Raman scattering (SERS) aptasensor to detect exosomes based on gold nanostars-decorated molybdenum disulfide (MoS

Background Nephrotic syndrome (NS) is a common glomerular disease in children. Nursing during hospitalization alone cannot solve the psychological, physiological and social health problems of children. Continuing care models may provide patients with more continuous and efficient care services. Therefore, the present study aimed to provide theoretical support for the implementation and development of children's primary nephrotic syndrome (PNS) and children's chronic disease continuing nursing through the construction of a children's PNS continuing nursing model. Methods Each item of the transitional care model for children with PNS was demonstrated using the Delphi method for two rounds of correspondence. The main items included four components: the composition of personnel, the responsibilities of each member, the content of work, and the evaluation indicators. Results A transitional care model for children with PNS was formed. The expert judgment coefficient of two rounds of correspondence was 0.84, the familiarity degree coefficient was 0.76, the authority degree coefficient was 0.80, the coefficient of variation was between 0.02 and 0.23, and the coordination coefficient was 0.458 and 0.327, respectively (P Conclusions The experts in the present research were highly motivated, had a high degree of authority, and presented consistent opinions. Hence, the construction of a transitional care model for children with PNS is scientifically feasible.

Background Galcanezumab is a monoclonal antibody (mAb) that binds calcitonin gene-related peptide (CGRP) and is indicated for the preventive treatment of migraine. Galcanezumab demonstrated early onset of effect in patients with migraine but it is unknown whether the same holds true for patients who have not benefited from multiple prior migraine preventives. Methods Patients with episodic or chronic migraine from a 3-month, randomized, double-blind, placebo-controlled, phase 3b study (CONQUER) who had 2 to 4 migraine preventive medication category failures in the past 10 years were randomized 1:1 to placebo (N = 230) or galcanezumab 120 mg/month (240 mg loading dose; N = 232). In this post-hoc analysis, change from baseline in number of monthly and weekly migraine headache days was assessed. Monthly onset of effect was the earliest month at which significant improvement with galcanezumab compared to placebo was achieved and maintained at all subsequent months. Weekly onset was the initial week at which statistical separation was achieved and maintained at all subsequent weeks during that month. Proportion of patients with migraine headache days in the first week of treatment, and patients achieving ≥50%, ≥75%, and 100% response by month and week were also assessed. Results Galcanezumab-treated patients had a significantly greater reduction in monthly migraine headache days starting at month 1, which remained significant for all subsequent months compared to placebo (all p ≤ 0.0001, month 1 mean change from baseline: placebo − 0.7; galcanezumab − 4.0). Weekly migraine headache days was significantly reduced in galcanezumab-treated patients starting at week 1 and continued for each subsequent week of month 1 compared to placebo (all p p p p Conclusion Galcanezumab showed early onset of effect beginning the day after treatment initiation in patients who had not previously benefited from migraine preventive treatments. Trial registration ClinicalTrials.gov, NCT03559257. Registered 18 June 2018.

The abnormal self-assembly of amyloid-β protein (Aβ) into toxic aggregates is a major pathological hallmark of Alzheimer's disease (AD). Modulation of Aβ fibrillization with pharmacological modalities has become an active field of research, which aims to mitigate Aβ-induced neurotoxicity and ameliorate impaired recognition. Among the various strategies for AD treatment, phototherapy, including photothermal therapy (PTT), photodynamic therapy (PDT), and photoresponsive release systems have attracted increased attention because of the spatiotemporal controllability. Under the irradiation of light, the heat or reactive oxygen species generated by photothermal or photodynamic processes significantly enhances the efficacy of the inhibitor or modulator, and the "caged" drug can be accurately released at the intended site, thus avoiding adverse effects. This review, from a viewpoint of materials, focuses on the recent advances in modulating Aβ aggregation by light that irradiates on the materials that function on modulating Aβ aggregation. Representative examples of PTT, PDT, and photoresponsive drug release systems are discussed in terms of inhibitory mechanism, the unique properties of materials, and the design of modulators. The major challenges of phototherapy against AD are addressed and the promising prospects are proposed. It is concluded that the noninvasive light-assisted approaches will become a promising strategy for intensifying the modulation of Aβ aggregation and thus facilitating AD treatment. STATEMENT OF SIGNIFICANCE: Alzheimer's disease (AD) with the hallmark of amyloid-β protein (Aβ) deposition is affecting more than 50 million people globally. It is urgent to explore intelligent materials to modulate Aβ aggregation. This review summarizes the intensified modulation of Aβ aggregation by a variety of photoresponsive materials including photothermal, photosensitizing and photoresponsive release materials, focusing on their characteristics and functionalities. We believe this review would arouse more interest in the research field of stimuli-responsive materials and promote their clinical applications in AD therapy.

Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) are associated with mild cognitive impairment (MCI). However, this association is unclear. This study aimed to assess the prevalence of MCI in patients with overlap syndrome, determine whether OSA increases the risk of MCI in patients with COPD, and investigate the potential mechanisms for this association.Participants with stable Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 2-4 COPD and complaints of snoring in 2016-2018 were enrolled in this cross-sectional observational study. All were free of asthma, acute left-sided congestive heart failure, unstable coronary heart disease, uncontrolled hypertension, diabetes, encephalitis, and epilepsy. They underwent pulmonary function tests and overnight polysomnography and completed the Montreal Cognitive Assessment (MoCA). MCI was defined by an MoCA score of23, while OSA was defined by an apnea-hypopnea index (AHI) of ≥15 per hour. The association between MCI, demographics, and comorbidities was tested by logistic regression analysis with adjustment for confounders. Sleep-disordered breathing measures were investigated as potential mechanisms underlying this relationship.MCI was significantly more common in patients with overlap syndrome than in those with COPD (40.6% [43/106] vs 24.6% [42/171]). After adjustment, severe OSA was an independent contributor to MCI (odds ratio, OR 2.27; 95% confidence interval, CI 1.12-4.62). Increased percent of night-time spent with oxygen saturation90% (TSatMCI is more prevalent in overlap syndrome than in COPD. OSA may contribute to MCI in COPD. The mechanism may involve TSat

In recent years, narcissism has been attracting considerable interest by researchers because of its enigmatic constructs. To enhance our understanding of narcissists' psychosocial functioning, considering the relationship between narcissism and interpersonal trust is crucial. This study aimed to investigate how narcissistic admiration and rivalry are associated with interpersonal trust. To gain a more nuanced understanding, a cross-lagged design was conducted at two time points that were six months apart. In total, 357 adolescents (Mage = 16.33 years) completed the Narcissistic Admiration and Rivalry Questionnaire (NARQ) and the Interpersonal Trust Scale. The results showed that narcissistic admiration positively predicted interpersonal trust while narcissistic rivalry negatively predicted interpersonal trust at the second time point. However, interpersonal trust did not predict subsequent levels of narcissistic admiration and rivalry. These findings enhanced our understanding by showing that narcissistic admiration and rivalry have different effects on interpersonal trust, and that they remain relatively stable during a six-month period.

We investigated changes in the intestinal flora of children withBetween September 2019 and November 2019, stool samples from 14 children with MPP from The Fourth Hospital of Baotou city, Inner Mongolia Autonomous Region, were collected and divided into general treatment (AF) and probiotic (AFY) groups, according to the treatment of "combinedIntestinal flora abundance and diversity in children with MPP were decreased. Both Shannon and Simpson indices were lower in the AF group when compared with healthy controls (The intestinal flora of children with MPP is disturbed, manifested as decreased abundance and diversity, and decreased