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PURPOSE: To propose MCUR1 gene as a potential biomarker for ovarian cancer prognosis. METHODS: The ovarian cancer patient specimen from TCGA database were analyzed using survival analysis. The immune cell infiltration ratio and checkpoints had also been investigated for different expression group of MCUR1. The function of MCUR1 as a ovarian cancer prognosis biomarker was verified in clinic. RESULTS: The low expression of MCUR1 was associated with the poor prognosis of ovarian cancer patients. The expressions of majority of immune cells and 6 checkpoints in low expression group of MCUR1 were significantly lower than that in high expression group of MCUR1 (P< 0.05). The MCUR1 could be utilized as a prognostic biomarker for ovarian cancer patients in clinic. CONCLUSION: This study has proposed a potential prognostic biomarker for ovarian cancer patients, which offers a beneficial reference for future ovarian cancer administration.

Graphical abstract, Introduction The COVID-19 global pandemic is far from ending. There is an urgent need to identify applicable biomarkers for early predicting the outcome of COVID-19. Growing evidences have revealed that SARS-CoV-2 specific antibodies evolved with disease progression and severity in COIVD-19 patients. Objectives We assumed that antibodies may serve as biomarkers for predicting the clinical outcome of hospitalized COVID-19 patients on admission. Methods By taking advantage of a newly developed SARS-CoV-2 proteome microarray, we surveyed IgG responses against 20 proteins of SARS-CoV-2 in 1,034 hospitalized COVID-19 patients on admission and followed till 66 days. The microarray results were further correlated with clinical information, laboratory test results and patient outcomes. Cox proportional hazards model was used to explore the association between SARS-CoV-2 specific antibodies and COVID-19 mortality. Results Nonsurvivors (n=955) induced higher levels of IgG responses against most of non-structural proteins than survivors (n=79) on admission. In particular, the magnitude of IgG antibodies against 8 non-structural proteins (NSP1, NSP4, NSP7, NSP8, NSP9, NSP10, RdRp, and NSP14) and 2 accessory proteins (ORF3b and ORF9b) possessed significant predictive power for patient death, even after further adjustments for demographics, comorbidities, and common laboratory biomarkers for disease severity (all with p trend < 0.05). Additionally, IgG responses to all of these 10 non-structural/accessory proteins were also associated with the severity of disease, and differential kinetics and serum positive rate of these IgG responses were confirmed in COVID-19 patients of varying severities within 20 days after symptoms onset. The area under curves (AUCs) for these IgG responses, determined by computational cross-validations, were between 0.62 and 0.71. Conclusions Our findings might have important implications for improving clinical management of COVID-19 patients.

Background The diagnosis of subclinical depression (SD) currently relies exclusively on subjective clinical scores and structured interviews, which shares great similarities with major depression (MD) and increases the risk of misdiagnosis of SD and MD. This study aimed to develop a method of disease classification for SD and MD by resting-state functional features using radiomics strategy. Methods Twenty-six SD, 36 MD subjects and 33 well-matched healthy controls (HC) were recruited and underwent resting-state functional magnetic resonance imaging (rs-fMRI). A novel radiomics analysis was proposed to discriminate SD from MD. Multi-scale brain functional features were extracted to explore a comprehensive representation of functional characteristics. A two-level feature selection strategy and support vector machine (SVM) were employed for classification. Results The overall classification accuracy among SD, MD and HC groups was 84.21%. Particularly, the model excellently distinguished SD from MD with 96.77% accuracy, 100% sensitivity, and 92.31% specificity. Moreover, features with high discriminative power to distinguish SD from MD showed a strong association with default mode network, frontoparietal network, affective network, and visual network regions. Limitation The sample size was relatively small, which may limit the application in clinical translation to some extent. Conclusion These findings demonstrated that a valid radiomics approach based on functional measures can discriminate SD from MD with a high classification performance, facilitating an objective and reliable diagnosis individually in clinical practice. Features with high discriminative power may provide insight into a profound understanding of the brain functional impairments and pathophysiology of SD and MD.

Aging is frequently accompanied by various types of physiological deterioration, which increases the risk of human pathologies. Global public health efforts to increase human lifespan has been increasingly focusing on lowering the risk of incidences of aging-related disease, such as diabetes, neurodegenerative diseases, cardiovascular disease and cancers. Dietary interventions is a promising approach to maintain human health during aging. Lactoferrin (LF) is known for its physiologically pleiotropic properties. Anti-aging interventions of LF have proven to be safe and effective for various pharmacological activities such as antioxidants, anti-cellular senescence, anti-inflammation, and anti-carcinogenic. As well as the pivotal role of LF on the modulating of major signaling pathways that influence longevity of organisms. Thus, LF is expected to be able to attenuate the process of aging and greatly ameliorate its effects.

Lulu Song,1 Xiaomu Kong,2 Zhaojun Yang,1 Jinping Zhang,1 Wenying Yang,1 Bo Zhang,1 Xiaoping Chen,1 Xin Wang1 1Department of Endocrinology, China-Japan Friendship Hospital, Beijing, People’s Republic of China; 2Clinical Laboratory, China-Japan Friendship Hospital, Beijing, People’s Republic of ChinaCorrespondence: Xin WangDepartment of Endocrinology, China-Japan Friendship Hospital, 2 Yinghua East Road, Beijing, 100029, People’s Republic of ChinaTel +86 1084205254Email xiangpian11@163.comPurpose: To assess the effect of acarbose in lowering low-grade albuminuria compared to metformin in newly diagnosed Chinese type 2 diabetes (T2DM) patients.Patients and Methods: The Metformin and AcaRbose Clinical Trial was a randomized, open-label trial in newly diagnosed T2DM patients. Participants received 48 weeks of monotherapy with acarbose (100 mg three times a day) or metformin (1500 mg once a day). As the hypoglycemic effect of acarbose and metformin has been evaluated in previous reports. This analysis studied the effect of the two antidiabetic drugs on reducing urinary albumin. The percent change in the urinary albumin/creatinine ratio (uACR) from baseline to week 48 was analyzed, and ANCOVA was employed to establish whether the effect in decreasing uACR was mediated by metabolic improvement.Results: Acarbose reduced the adjusted mean percent uACR by − 31.5% (95% confidence interval [CI] − 48.4 to − 7.5) compared with metformin. When adjusting for changes in glycated hemoglobin, body weight, systolic blood pressure and triglycerides or changes in area under the curve of glucagon-like peptide 1 (AUCGLP-1) in the standard meal test, the uACR-lowering effect was not attenuated. If stratified by eGFR, blood glucose level, sex or uACR level, the effect of acarbose versus metformin was consistent across subgroups. The proportion of patients with a reduction in uACR of at least 70% was 48.6% in the acarbose group and 34.1% in the metformin group.Conclusion: Acarbose lowered the uACR compared to metformin in newly diagnosed T2DM patients independent of improvements in hyperglycemia, blood pressure, body weight and triglycerides.Keywords: diabetes mellitus, type 2, diabetic nephropathies, hypoglycemic agents

To investigate the optimal blood pressure (BP) levels and relative importance of BP and BP variability in the early phase of acute ischemic stroke (AIS) for hypertensive patients with carotid artery stenosis (CAS). A single‐center cohort study included 750 AIS patients with hypertension and tests were performed for CAS. Participants were categorized to Group 1 (SBP

Objectives Postmenopausal osteoporosis (PMO) and osteoporotic fracture seriously impair human health in developed countries. The present study aims to explore whether sensory nerves, calcitonin gene-related peptide (CGRP), and brain-derived serotonin are related to bone loss in ovariectomized (OVX) rats. Methods Female rats were grouped into the ovariectomized (OVX) and sham surgery (SHAM) groups. Immunocytochemistry, western blotting, and qPCR were performed to detect CGRP expression in the femurs. The expression levels of serotonin and CGRP in the spinal cord and brainstem were estimated using western blotting, immunofluorescence, and qPCR. ELISA was used to evaluate the serum biomarkers of bone formation and resorption. Bone mineral density was measured using dual-energy X-ray (DXA) analysis. Femur microstructure was imaged by Micro CT. P values less than 0.05 were considered statistically significant. Results ELISA showed that serum bone alkaline phosphatase (BALP), tartrate-resistant acid phosphatase (TRAP), β-crosslaps, and β-ctx were increased in the OVX group. In the OVX group, in vivo bone mineral density, trabecular bone mineral density, bone volume fraction (BV/TV), and trabecular number (Tb. N) were significantly decreased, while trabecular spacing (Tb. Sp) and trabecular bone pattern factor (Tb. Pf) were markedly increased. In the OVX group, the expression levels of CGRP of the femur were significantly downregulated. In contrast, CGRP and serotonin expression was increased in the spinal cord of the OVX group. Serotonin expression was increased in the brainstem, brainstem nucleus raphe magnus (RMG), and nucleus raphe dorsalis (DRN). Conclusion Our results indicated that the activation of osteoclast triggered the release of CGRP from nociceptive sensory nerve fibers and transmitted this painful stimulus to the dorsal horn of the spinal cord to release increased CGRP. The descending serotonergic inhibitory system was activated by increased CGRP levels of the spinal cord and promoted serotonin release in the brainstem RMG, DRN, and the spinal cord, contributing to the decreased CGRP level in bone tissue, which revealed a novel mechanism of bone loss in PMO.

Hepatectomy with tumor thrombectomy is the preferred treatment option for hepatocellular carcinoma (HCC) patients with bile duct tumor thrombus (BDTT); however, the impact of BDTT on their prognosis is unclear. We aimed to investigate the long-term surgical outcomes of HCC patients with BDTT. The data of HCC patients with and without BDTT who underwent hepatectomy were retrospectively reviewed and the long-term outcomes were compared. For propensity score matching (PSM) analysis, patients were matched in a 1:1 ratio. Subgroup analysis was conducted according to the American Joint Committee on Cancer (AJCC) staging system. Before PSM, HCC patients with BDTT had more advanced tumor stages and adverse clinicopathological features. Recurrence-free survival (RFS) and overall survival (OS) were significantly higher in the non-BDTT group before PSM (RFS, p

To determine the most effective and safest treatment mode for locally advanced resectable esophageal squamous cell carcinoma through a network meta-analysis. A Bayesian model was used for a network meta-analysis comparing the efficacy and safety of surgery alone, neoadjuvant therapy, and adjuvant therapy. Thirty clinical studies, including thirty-one articles, 4866 patients, were analyzed. Overall survival rate: Adjuvant chemoradiotherapy and neoadjuvant chemoradiotherapy were significantly advantageous over surgery alone [hazard ratio (HR) 0.73, 95% confidence interval (CI) 0.57–0.93; HR 0.75, 95%CI 0.65–0.86]. There was no statistically significant difference between adjuvant chemoradiotherapy and neoadjuvant chemoradiotherapy [HR 0.97, 95%CI 0.75–1.28]. Disease-free survival rate: Compared with surgery alone, neoadjuvant chemoradiotherapy had significant benefits [HR 0.65, 95%CI 0.53–0.78]; adjuvant chemoradiotherapy had similar, but not significant benefits [HR 0.7, 0.95%CI 0.45–1.06]. The difference between neoadjuvant chemoradiotherapy and adjuvant chemoradiotherapy was also not statistically significant [HR 0.94, 0.95%CI 0.61–1.43]. Surgery after neoadjuvant chemoradiotherapy: The R0 resection rate was significantly improved [relative risk (RR) 0.25, 95%CI 0.07–0.86], but the overall postoperative morbidity rate and 30-day postoperative mortality rate tended to increase [RR 1.27, 95%CI 0.8–2.01; RR 1.59, 95%CI 0.7–3.22]. Neither neoadjuvant chemotherapy nor neoadjuvant radiotherapy significantly altered the surgical safety or R0 resection rate. Both neoadjuvant chemoradiotherapy and adjuvant chemoradiotherapy appear to be the best supplements to surgery for locally advanced resectable esophageal squamous cell carcinoma.

Purpose To compare differences in visual, refractive, and ablating outcomes between corneal topography-guided laser in situ keratomileusis (LASIK) by SCHWIND AMARIS and WaveLight Contoura for myopia and myopic astigmatism correction. Setting Department of Refractive Surgery, Guangzhou Aier Eye Hospital, Guangzhou, China. Design Prospective nonrandomized study. Methods Patients treated with LASIK to correct ametropia and corneal higher-order aberrations (HOAs) with 6.5 mm of plan optical zone were recruited. In the AMARIS platform, there were 2 centration strategies: the symmetric (AA) and asymmetric (AS) offset modes. In the WaveLight platform, there was only symmetric offset (ES) mode. HOAs, contrast sensitivity, effective optical zone (EOZ), ablation depth, and ablating center were evaluated 3 months after the operation. Results The study included 138 eyes. At 3 months after operation, the postoperative manifest refractive spherical equivalent was 0.04 ± 0.34 diopters (D), 0.06 ± 0.25 D, and -0.09 ± 0.21 D in AS, AA, and ES groups, respectively (P = .018). The EOZs of the AS and AA groups were 5.01 mm and 4.96 mm, and both were larger than 4.88 mm in the ES group (P = .04 and .03, respectively). The ablation depth of the AS group was 103.6 μm, which were larger than 86.6 μm in the AA group and 91.2 μm in the ES group. Conclusions The SCHWIND AMARIS and WaveLight EX500 corneal topography-guided LASIK achieved comparable and excellent visual and refractive outcomes. The EX500 Contoura LASIK ablated less corneal tissue because of the smaller EOZ compared with the AMARIS, with a similar plan optical zone.

Study design Retrospective. Objective The purpose of this study was to assess trends in utilization rates of adult spinal deformity (ASD) surgery, as well as perioperative surgical metrics between black and white patients undergoing operative treatment for ASD in the United States. Summary of background data Racial disparities in access to care, complications, and surgical selection have been shown to exist in the field of spine surgery. However, there is a paucity of data concerning racial disparities in the management of ASD patients. Methods Adult patients undergoing ASD surgery from 2004 to 2014 were identified in the Nationwide Inpatient Sample (NIS). Utilization rates, major complications rates, and length of stay (LOS) for black patients and white patients were trended over time. Utilization rates were reported per 1,000,000 people and determined using annual census data among subpopulations stratified by race. All reported complication rates and prolonged hospital stay rates are adjusted for Elixhauser Comorbidity Index, income quartile by zip code, and insurance payer status. Results From 2004 to 2014, ASD utilization for black patients increased from 24.0 to 50.9 per 1,000,000 people, whereas ASD utilization for white patients increased from 29.9 to 73.1 per 1,000,000 people, indicating a significant increase in racial disparities in ASD utilization (p-trend 0.05 for both). Conclusion Although black and white patients undergoing ASD surgery do not differ significantly in terms of postoperative complications and length of hospital stay, there is a growing disparity in utilization of ASD surgery between white and black patients from 2004 to 2014 in the United States. There is need for continued focus on identifying ways to reduce racial disparities in surgical selection and perioperative management in spine deformity surgery.Level of Evidence: 3.

Unconventional surgical procedures may be utilized in treating complicated middle aortic syndrome (MAS), the outcome and prognosis of which remain largely undetermined due to limited numbers and significant heterogeneity of this population. Using computational fluid dynamics (CFD) analysis, this study aimed to assess the dynamic changes of postoperative aortic flow in seeking to unveil the relationship between hemodynamics and vascular remodeling and thrombotic events. One patient with middle aortic syndrome complicated with aortic rupture was treated with hybrid repair of extra-anatomic bypass and fenestrated endovascular aortic repair. The patient was followed-up for 8 months by computational tomography angiography and Doppler ultrasound. Thoracoabdominal aortic blood flow and locations with ongoing thrombosis at 1, 3, and 6 months postoperatively were simulated and analyzed. Remodeling processes, including low wall shear-mediated constrictive remodeling of non-stented aorta, neointimal hyperplasia at suture lines, and minimal thrombosis at various locations, were evident. Meanwhile, abdominal blood flow was tri-phasic at 1 month after surgery, and was reversed and stabilized at 6 months. The distribution of newly formed thrombus vary at different follow-up stages, which were in line with the numerical simulation of thrombosis from different postoperative time points. CFD-based sequential monitoring is of promising value in capturing dynamic changes of vascular outcome.

The myxomycete life-cycle mainly consists of cellular uninucleate amoeboflagellates, stationary spore-bearing sporophores, and acellular multinucleate plasmodia. The plasmodium is able to regulate complex behavior, but no differentiated signaling structures have been detected. As a basal lineage eukaryote, research on any neuron-like substances may contribute to our understanding of the origin of the nervous system in complex organisms. We examined the expression and localization of the neuropeptide adreno-cortico-tropic-hormone (ACTH) and the neuroprokaryotic protein (NeuN) in two species of Physarum under different culture conditions were studied by immunofluorescence and western blotting. ACTH was expressed in the cytoplasm of the plasmodium of Physarum flavicomum, and NeuN was expressed in the nuclear membrane of the plasmodium of P. polycephalum and in the cytoplasm of that of P. flavicomum. This demonstrates the occurrence of neuropeptides in the myxomycete plasmodium for the first time and contributes to the understanding of intercellular communication in Myxomycetes.

Background CD4+ T cell counts in certain human immunodeficiency virus (HIV)-infected patients called immunological non-responders (INRs) could not return to a normal level even with sustained antiretroviral therapy (ART) because of persistent immune activation, which is associated with pro-inflammatory cytokines production and an altered intestinal microbiome profile. Changes in gut bacterial composition have been linked to low CD4+ T cell counts in HIV-infected individuals. However, the association between CD4+ T cell counts and gut microbiota community composition and cytokines levels in INRs (CD4+ T cell counts Methods To address this issue, we carried out a cross-sectional study of 34 HIV-infected INRs. The patients were divided into CD4 count > 200 cells/μL group and CD4 count 16S rRNA gene sequencing. We also compared CD8+ T cell counts, pro-inflammatory cytokines levels, and nutritional status between the two groups. Results Compared to INRs with CD4 count > 200 cells/μL, those with CD4 count Ruminococcaceae was less abundant in the CD4 count 200 cells/μL group, and difference in alpha diversity was observed between the two groups. Moreover, CD4+ T cell counts were negatively associated with TNF-α and IL-1α levels and positively associated with the relative abundance of Ruminococcaceae. Conclusions Our study demonstrated that lower CD4+ T cell counts in INRs are associated with a reduced abundance of Ruminococcaceae in the gut and elevated serum pro-inflammatory cytokines levels. Thus, interventions targeting gut microbiota to increase CD4+ T cell counts are a potential strategy for promoting immune reconstitution in HIV-infected INRs.

Objective: To establish a new classification of biliary tumor thrombus (BTT). Methods: Overall survival of patients with BTT was first used to determine whether it correlated with current hepatocellular carcinoma staging systems. Univariate and multivariate analyses were used to determine factors affecting the overall survival (OS) to form the basis of our new classification for BTT. Results: All 6 international staging systems showed overlapping survival curves. Univariate followed by multivariate analyses showed that total bilirubin and intrahepatic/extrahepatic BTT were significant risk factors of OS. Based on these data, a new BTT classification was defined as: Type I: intrahepatic BTT; and Type II: extrahepatic BTT involving a common bile duct or common hepatic duct. Type I was further subdivided into type Ia: BTT involving a second-order intrahepatic duct or above, and type Ib: BTT involving a first-order intrahepatic duct. Type II was further subdivided into type IIa and type IIb using a cut-off total bilirubin (TB) > 300 μmol/L. The numbers (percentages) of patients with types I and II BTT were 69 (34.2%) and 133 (65.8%), respectively. The median OS of type I patients was significantly higher than that of type II patients (37.5 months vs. 23.2 months; P = 0.002). Using subgroup analyses, OS outcomes were significantly different between the subgroups of type IIb and type IIa, although there was no significant difference between the type Ia and type Ib subgroups (P = 0.07). Conclusions: A new BTT classification was established to predict prognoses of HCC patients with BTT who underwent liver resection.

BACKGROUND AND OBJECTIVES This study aimed to characterize the efficacy of neoadjuvant imatinib in rectal gastrointestinal stromal tumors (GISTs) and the prognostic characteristics of patients after surgery. METHODS Patients with rectal GISTs who received neoadjuvant imatinib between 2000 and 2019 were selected from 11 large-scale tertiary hospitals in China. The best response to neoadjuvant imatinib was assessed. Propensity score matching (PSM) was conducted to reduce confounders. Recurrence free survival (RFS) and overall survival (OS) were estimated using Kaplan-Meier method. RESULTS Of the 100 patients, 75, 18, and 7 had a partial response (PR), stable disease (SD), and progressive disease (PD), respectively. The median tumor size decreased from 5 cm before treatment to 4 cm after treatment (p

To the best of our knowledge, this is the largest clinical retrospective study in AN‐SAH patients, and is the first time to establish accurate predictive models paired with bleeding pattern. Background Angiogram‐negative subarachnoid hemorrhage (AN‐SAH) has a definite incidence of delayed cerebral ischemia (DCI) and poor clinical outcomes. The purpose is to screen independent factors and establish a nomogram to guide the clinical therapy and assess post‐discharge prognosis. Methods We identified 273 consecutive patients referred to our institute from 2013 to 2018 for AN‐SAH. A nomogram to predict poor outcomes was formulated based on the multivariable models of independent risk factors. The accuracy and discrimination of nomograms were determined in training and internal validation cohorts. Results The overall poor outcome rates of AN‐SAH were 14.3% and 8.7% at 3 months and 12 months, respectively. In addition, perimesencephalic AN‐SAH (PAN‐SAH) presented with a more unfavorable prognosis compared with non‐perimesencephalic AN‐SAH (NPAN‐SAH). The clinical prognosis was associated with the World Federation of Neurosurgical Societies scale (WFNS) (odds ratio, 3.82 [95% CI, 1.15‐12.67] for 3‐month outcome; and odds ratio, 31.69 [95% CI, 3.65‐275.43] for 12‐month outcome), Subarachnoid hemorrhage Early Brain Edema Score (SEBES) (odds ratio, 10.39 [95% CI, 1.98‐54.64] for 3‐month outcome; odds ratio, 10.01 [95% CI, 1.87‐53.73] for 12‐month outcome), and symptomatic vasospasm (odds ratio, 3.16 [95% CI, 1.03‐9.70] for 3‐month outcome; odds ratio, 5.15 [95% CI, 1.34‐19.85] for 12‐month outcome). The nomogram was constructed based on the above features, which represented great predictive value in clinical outcomes. Conclusions Symptomatic vasospasm, high WFNS, cerebral edema, and NPAN‐SAH after hemorrhage were associated with poor outcome of AN‐SAH. The nomogram with WFNS (3‐5), SEBES (3‐4), vasospasm, and NPAN‐SAH represented a practical approach to provide individualized risk assessment for AN‐SAH patients., To the best of our knowledge, this is the largest clinical retrospective study in AN‐SAH, and is the first time to establish accurate predictive models paired with bleeding pattern.

Objective This study was undertaken to describe long-term clinical and developmental outcomes in pediatric refractory status epilepticus (RSE) and identify factors associated with new neurological deficits after RSE. Methods We performed retrospective analyses of prospectively collected observational data from June 2011 to March 2020 on pediatric patients with RSE. We analyzed clinical outcomes from at least 30 days after RSE and, in a subanalysis, we assessed developmental outcomes and evaluated risk factors in previously normally developed patients. Results Follow-up data on outcomes were available in 276 patients (56.5% males). The median (interquartile range [IQR]) follow-up duration was 1.6 (.9-2.7) years. The in-hospital mortality rate was 4% (16/403 patients), and 15 (5.4%) patients had died after hospital discharge. One hundred sixty-six (62.9%) patients had subsequent unprovoked seizures, and 44 (16.9%) patients had a repeated RSE episode. Among 116 patients with normal development before RSE, 42 of 107 (39.3%) patients with available data had new neurological deficits (cognitive, behavioral, or motor). Patients with new deficits had longer median (IQR) electroclinical RSE duration than patients without new deficits (10.3 [2.1-134.5] h vs. 4 [1.6-16] h, p = .011, adjusted odds ratio = 1.003, 95% confidence interval = 1.0008-1.0069, p = .027). The proportion of patients with an unfavorable functional outcome (Glasgow Outcome Scale-Extended score ≥ 4) was 22 of 90 (24.4%), and they were more likely to have received a continuous infusion. Significance About one third of patients without prior epilepsy developed recurrent unprovoked seizures after the RSE episode. In previously normally developing patients, 39% presented with new deficits during follow-up, with longer electroclinical RSE duration as a predictor.

Background Endoscopic thyroidectomy is widely performed as it does not result in neck scar. However, there is a paucity of reports pertaining to completely endoscopic lateral neck dissection (LND). In this study, we introduce our step-wise approach for performing endoscopic selective LND via the chest–breast approach. We refer to this approach as Qin’s seven steps. Methods The Qin’s seven steps are: (1) establishment of working space range; (2) dissection of lymph nodes between the SCM and the sternohyoid muscle (level IV) and exposure of omohyoid; (3) dissection of lymph nodes at level IV; (4) dissection of lymph nodes at level III; (5) dissection of lymph nodes at carotid triangle (level III); (6) exposure of accessory nerve and dissection of lymph nodes at level II a; (7) dissection of lymph nodes at level II b. We reviewed the clinical data of 35 patients with papillary thyroid cancer (PTC) who were operated using the Qin’s seven steps. Results All 35 patients successfully underwent LND; bilateral LND was performed in 5 patients. The mean tumor size was 1.8 ± 1.0 cm; seven patients had multiple lesions. The mean number of retrieved lymph nodes in level II, III and IV were 8.8 ± 5.6, 6.1 ± 4.0 and 9.3 ± 5.1, respectively. As for complications, there were 3 cases of accessory nerve injury and 1 case of hypoglossal nerve injury. Internal jugular vein injury, cervical plexus injury and lymphatic leakage occurred in 2, 7, and 1 patients, respectively. Conclusion The Qin’s seven steps for performing endoscopic selective LND could be safely used in PTC patients with lateral lymph node metastasis. Satisfactory results were achieved in the short-term follow-up period. We recommend the use of Qin’s seven steps for PTC patients who are not desirous of neck scar.

Purpose To investigate the associations of sociodemographic characteristics and PROMIS domain scores with patient activation among patients presenting for spine surgery at a university-affiliated spine center. Methods Patients completed a survey collecting demographic and social information. Patients also completed the Patient-Reported Outcomes Measurement Information System (PROMIS) and Patient Activation Measure questionnaires. The associations of PROMIS scores and sociodemographic characteristics with patient activation were assessed using linear and ordinal logistic regression (patient activation stage as ordinal). Results A total of 1018 patients were included. Most respondents were white (84%), married (73%), and female (52%). Patients were distributed among the 4 activation stages as follows: stage I, 7.7%; stage II, 12%; stage III, 26%; and stage IV, 55%. Mean (±standard deviation) patient activation score was 70 ± 17 points. Female sex (adjusted coefficient [AC] = 4.3; 95% confidence interval [CI] 2.1, 6.4) and annual household income >$80,000 (OR = 3.7; 95% CI 0.54, 6.9) were associated with higher patient activation scores. Lower patient activation scores were associated with worse PROMIS Depression (AC = −0.31; 95% CI −0.48, −0.14), Fatigue (OR = −0.19; 95% CI −0.33, −0.05), Pain (OR = 0.22; 95% CI 0.01, 0.43), and Social Satisfaction (OR = 0.33; 95% CI 0.14, 0.51) scores. Conclusion Depression and socioeconomic status, along with PROMIS Pain, Fatigue, and Social Satisfaction domains, were associated with patient activation. Patients with a greater burden of depressive symptoms had lower patient activation; conversely, women and those with higher income had greater patient activation. Level of evidence Level 1.

The surgical approaches and resection extent for rectal gastrointestinal stromal tumors (GISTs) are controversial due to the low incidence of this disease. A multicenter retrospective cohort study was conducted to compare the postoperative and oncologic outcomes of local excision (LE) and radical resection (RR) in patients with low rectal GIST.The medical records of rectal GIST patients from 11 large-scale medical centers in China (January 2000-December 2019) were reviewed. All patients were divided into either the LE group or the RR group. Propensity score matching (PSM) was conducted to reduce confounders.A total of 280 patients with low rectal GIST were enrolled. After PSM, 144 patients were included (72 in each group). The LE group showed a higher anal preservation rate (100.0% vs. 76.4%, P 0.001), shorter operation time (77.1 ± 68.4 min vs. 159.1 ± 83.6 min, P 0.001), fewer complications (8.3% vs. 22.2%, P = 0.021) and shorter postoperative hospital stay (4.9 ± 4.1 d vs. 10.7 ± 8.1 d, P 0.001) than the RR group. There was no significant difference in recurrence-free survival (RFS) between the RR and LE groups among patients with tumors ≤2 cm (P = 0.220), and the RR group had a superior RFS than the LE group in patients with tumors2 cm (P = 0.046).LE resulted in improved postoperative outcomes and comparable oncological safety with a low rectal GIST of ≤2 cm. However, for patients with a low rectal GIST of2 cm, RR might be a more appropriate option with better RFS.

Objective: The objective of this study is to investigate the association between the serum sclerostin, the coronary artery calcification (CAC), and patient outcomes in maintenance dialysis patients. Methods: We performed a prospective cohort study of 65 maintenance dialysis patients in 2014, including 39 patients on peritoneal dialysis and 26 on hemodialysis, and followed up for 5 years. Parameters of mineral metabolism including bone-specific alkaline phosphatase, fibroblast growth factor 23, sclerostin, and other biochemical factors were determined at the baseline. Meanwhile, the CAC score was analyzed by cardiac computed tomography. Results: Serum sclerostin in hemodialysis patients was significantly higher than that in peritoneal dialysis patients (632.35 ± 369.18 vs. 228.85 ± 188.92, p < 0.001). The patients with CAC were older, receiving hemodialysis, lower Kt/V, and had longer dialysis vintage, as well as higher levels of serum 25-(OH)-vit D and sclerostin. In multivariate logistic regression analysis, older age and lower Kt/V were risk factors for CAC. The area under the receiver operating characteristic curves for prediction of CAC by sclerostin was 0.74 (95% confidence interval 0.605–0.878, p = 0.03), and the cutoff value of sclerostin is 217.55 pg/mL with the sensitivity 0.829 and specificity 0.619. After 5 years of follow-up, 51 patients survived. The patients in the survival group had significantly lower age, sclerostin levels, and low CAC scores than the nonsurvival group. Old age (≥60 years, p < 0.001) and high CAC score (≥50 Agatston unit, p = 0.031) were significant risk factors for the patient survival. Conclusions: Sclerostin is significantly elevated in dialysis patients with CAC. But sclerostin is not a risk factor for CAC. After 5 years of follow-up, patients in the survival group are younger and have lower sclerostin levels and CAC scores. But sclerostin levels are not independent risk factors for high mortality in dialysis patients.

Lead (Pb) exposure can cause central nervous system (CNS) damage. The process of Pb neurotoxicity is accompanied by the microglia activation. In addition, microglia activation was observed under the intervention of high-fat diets (HFD). This study was designed to investigate the effect of Pb on the cognitive function of mice with HFD, with focus on the microglia activation in brain. Male C57BL/6J mice, 8 weeks of age, were randomly divided into control, HFD, Pb, and HFD + Pb groups. The results showed that HFD following Pb exposure could exacerbate the learning and memory impairment in mice. Pb exposure could promote microglia activation and increase the expression of M1 microglia marker and decrease the expression of M2 microglia marker in the hippocampus of mice with HFD. Our finding suggested that Pb exposure may aggravate CNS damage by promoting M1 polarization and inhibiting M2 polarization of hippocampal microglia in HFD mice.

The current study aimed to assess the dietary salt intake in patients with CKD in Jiangsu province and investigate the relationship of urinary sodium excretion with blood pressure. A total of 800 patients with CKD stages 1–4 were recruited. All enrolled patients were asked to collect complete 24‐h urine specimen. At the same time, patient's demographic and laboratory data were recorded. The mean age was 47.45 ± 15.25 years old, including 423 men and 377 women. There was no significant difference in urinary sodium excretion among different stages of CKD (p = .748). This study revealed that the median urinary sodium excretion of all patients was 127.20 mmol/d (IQR 91.03–172.06), corresponding to a salt intake of 7.4 g/d. Among them, only 167 (20.9%) cases had salt intake

Background. To assess the association of metformin monotherapy with the risk of all-cause deaths and cardiovascular deaths and events in type 2 diabetes patients in real clinical practice. Methods. This retrospective, observational study comprised patients with type 2 diabetes initially treated with metformin or nonmetformin monotherapy over 2011-2016. Data were extracted from the National Healthcare Big Data database in Fuzhou, China. Propensity score matching (PSM) was performed, matching each patient on metformin to one on nonmetformin in terms of a set of covariates. The primary endpoint was all-cause death, and secondary endpoints were cardiovascular death, heart failure, and heart failure hospitalization. Covariate-adjusted associations of metformin use with all the endpoints were assessed by Cox proportional hazards models. Results. Among 24,099 patients, 5491 were initially treated with metformin and 18,608 with nonmetformin. PSM yielded 5482 patients in each cohort. During a median follow-up of 2.02 years, we observed 110 and 211 deaths in the metformin and nonmetformin groups, respectively. Metformin was significantly associated with reduced risk of all-cause death (adjusted hazard ratio (aHR) 0.52, 95% confidence interval (CI) 0.39-0.69), cardiovascular death (aHR 0.63, 95% CI 0.43-0.91), and heart failure (aHR 0.61, 95% CI 0.52-0.73), whereas the reduced risk in heart failure hospitalization was not statistically significant (aHR 0.70, 95% CI 0.47-1.02). Conclusions. In this analysis of electronic health record data from a large database in China, metformin as first-line monotherapy greatly reduced the risk of all-cause death, cardiovascular death, and heart failure in diabetes patients as compared with nonmetformin medications.

Heavy ion therapy is currently recognized as the most advanced cancer radiotherapy approach in the world. This article introduces a high-precision and non-contact measurement method based on close-...

Objective To identify spine patients' barriers to appropriate postoperative opioid use, comfort with naloxone, knowledge of safe opioid disposal practices, and associated factors. Methods We preoperatively surveyed 174 spine patients about psychobehavioral barriers to appropriate opioid use, comfort with naloxone, and knowledge about opioid disposal. Multivariable logistic regression identified factors associated with barriers and knowledge (α = 0.05). Results Common barriers were fear of addiction (71%) and concern about disease progression (43%). Most patients (78%) had neutral/low confidence in the ability of nonopioid medications to control pain; most (57%) felt neutral or uncomfortable with using naloxone; and most (86%) were familiar with safe disposal. Anxiety was associated with fear of distracting the physician (adjusted odds ratio [aOR], 3.8; 95% confidence interval [CI], 1.1–14) and with lower odds of knowing safe disposal methods (aOR, 0.18; 95% CI, 0.04–0.72). Opioid use during the preceding month was associated with comfort with naloxone (aOR, 4.9; 95% CI, 2.1–12). Patients with a higher educational level had lower odds of reporting fear of distracting the physician (aOR, 0.30; 95% CI, 0.09–0.97), and those with previous postoperative opioid use had lower odds of concern about disease progression (aOR, 0.25; 95% CI, 0.09–0.63) and with a belief in tolerating pain (aOR, 0.34; 95% CI, 0.12–0.95). Conclusions Many spine patients report barriers to appropriate postoperative opioid use and are neutral or uncomfortable with naloxone. Some are unfamiliar with safe disposal. Associated factors include anxiety, lack of recent opioid use, and no previous postoperative use.

Coronary artery bypass graft (CABG) surgery is the most widely performed cardiac surgery in the United States. Transesophageal echocardiography (TEE) is frequently used in a variety of cardiac surgical procedures, but its clinical benefit in isolated CABG surgery is unclear, and guidelines remain indeterminate. The aim of this study was to compare clinical outcomes among patients undergoing isolated CABG surgery with versus without TEE in order to test the hypothesis that TEE would be associated with improved clinical outcomes after CABG surgery.A matched retrospective cohort study was conducted among Medicare beneficiaries undergoing isolated CABG surgery with versus without intraoperative monitoring using TEE in the United States. The primary analysis was a near/far instrumental variable match that paired hospitals with similar characteristics and patient populations but with opposing probabilities for using TEE in CABG surgery. Outcomes included 30-day mortality, a composite outcome of stroke or 30-day mortality, length of hospitalization, and incidence of esophageal perforation.Of 114,871 patients undergoing isolated CABG surgery, 65,471 (57%) underwent TEE and 49,400 (43%) did not. Hospital-level instrumental variable matched analysis demonstrated that among the subset of 968 matched hospitals, TEE receipt was associated with lower 30-day mortality (3.7% vs 4.9%, P .001), a lower incidence of the composite outcome of stroke or 30-day mortality (4.5% vs 5.6%, P .001), no difference in length of hospitalization (10.32 vs 10.52 days, P = .26), and no difference in the incidence of esophageal perforation (0.01% vs 0.01%, P = .63). These results were replicated in surgeon-level and patient-level matched-pair instrumental variable analyses, and all analyses were robust to sensitivity analyses that tested for biases introduced by unmeasured confounding.The findings from this study suggest that TEE may offer a clinical benefit to cardiac surgical patients undergoing isolated CABG surgery.

Background This study aimed to evaluate the feasibility and safety of the trans-oral endoscopic thyroidectomy vestibular approach (TOETVA) with neuroprotection techniques for the surgical management of papillary thyroid carcinoma (PTC). Methods Patients with PTC who underwent TOETVA between December 2016 and July 2020 were included in this study, and their relevant clinical characteristics, operational details, and surgical outcomes were reviewed and extracted from their medical records for further analysis. Results A total of 75 patients successfully underwent TOETVA with zero conversions. Unilateral lobectomy with isthmectomy and total thyroidectomy were completed for 58 and 17 patients, respectively, all using our unique neuroprotective procedure and ipsilateral central neck dissection (CND). The mean number of retrieved lymph nodes versus positive lymph nodes was 6.8 ± 3.7 vs. 1.5 ± 2.3. Postoperative complications included three cases of transient superior laryngeal nerve (SLN) palsy (4.0%), five cases of transient recurrent laryngeal nerve (RLN) palsy (6.7%), 14 cases of transient hypoparathyroidism (18.7%), two cases of numb chin (2.7%) and two cases of flap perforation (2.7%). The follow-up period for patients with PTC lasted for 15.6 ± 10.9 months, during which no other complications or tumor recurrence were observed. Conclusion TOETVA can be safely performed for patients with PTC with satisfactory results during the short-term follow-up period. Our neuroprotection techniques can be integrated into TOETVA, which is worth recommending for PTC patients who desire better cosmetic surgical outcomes.

Calcific myonecrosis (CM) is a rare benign long-term complication secondary to trauma, especially when trauma is combined with neurovascular injury or osteofascial compartment syndrome. CM frequently manifests as an asymptomatic mass and the anterior tibial area is the most common site, which is apt to be misdiagnosed as a bone tumor. In addition, even if the diagnosis is clear, the therapy is controversial because some authors suggested regular follow-up could replace surgery. However, patients with CM are prone to infection. Under such conditions, infection is hard to be controlled and non-surgical therapy will provide the limited effect. Here we reported a rare and interesting case about a patient diagnosed with calcific myonecrosis in our hospital. Imaging presented typical and impressive features of CM in his left leg. Besides, the patient suffered severe infection and antibiotics played a limited role. Subsequently, the abscess formed and the incision is unhealed after abscess incision drainage with the lasting outflow of pus and sequestrum. Finally, surgery was conducted and we found his anterior tibial muscle was replaced by osteoid and necrotic tissues. Postoperative pathology identified traumatic tumoral calcinosis. This patient now has no evidence of recurrence, with a follow-up of 22 months.

Reconstruction of complete bilateral maxillary defects (CBMDs) can be challenging due to the extensive loss of bone and soft tissues. This is a retrospective case series of 46 consecutive patients with CBMDs that were reconstructed with different microvascular free flaps. The authors aimed to evaluate the surgical outcomes and discuss the different reconstruction options in this case series. Thirty-six patients underwent reconstruction following ablation surgery for malignant tumors, 6 for benign tumors, 3 patients were treated for osteomyelitis, and 1 patient underwent free flap reconstruction for posttraumatic defects. Free fibula flap (n = 26) is the most commonly used reconstruction method in this case series, which was used in all defect types. This is followed by anterolateral thigh flap (n = 10), 5 rectus abdominis myocutaneous free flap, 3 radial forearm free flaps, and 2 composite free flaps. In this series, 44 free flaps survived, whereas only 2 flaps were lost. All patients could resume a soft diet postoperatively. Reconstruction of CBMDs with vascularized free flaps is a safe and reliable procedure.

Background The majority of clinical trials of first-line systemic treatments for hepatocellular carcinoma (HCC) used placebo or sorafenib as comparators, and there are limited data providing a cross comparison of treatments in this setting, especially for newly-approved immune checkpoint inhibitor and vascular endothelial growth factor inhibitor combination treatments. Aim To systematically review and compare response rates, survival outcomes, and safety of first-line systemic therapies for advanced hepatocellular carcinoma. Methods We searched PubMed, Science Direct, the Cochrane Database, Excerpta Medica Database, and abstracts from the American Society of Clinical Oncology 2020 annual congress. Eligible studies were randomized controlled trials of systemic therapy enrolling adults with advanced/unresectable HCC. Risk of bias was assessed with the Cochrane risk of bias tool for randomized controlled trials. A network meta-analysis was used to synthesize data and perform direct and indirect comparisons between treatments. P value, a frequentist analog to the surface under the cumulative ranking curve, was used to rank treatments. Results In total, 1398 articles were screened and 27 included. Treatments compared were atezolizumab plus bevacizumab, brivanib, donafenib, dovitinib, FOLFOX4, lenvatinib, linifanib, nintedanib, nivolumab, sorafenib, sunitinib, vandetanib, 11 sorafenib combination therapies, and three other combination therapies. For overall response rate, lenvatinib ranked 1/19, followed by atezolizumab plus bevacizumab and nivolumab. For progression-free survival (PFS), atezolizumab + bevacizumab was ranked 1/15, followed by lenvatinib. With the exception of atezolizumab + bevacizumab [hazard ratios (HR)PFS = 0.90; 95% confidence interval (CI): 0.64-1.25], the estimated HRs for PFS for all included treatments vs lenvatinib were > 1; however, the associated 95%CI passed through unity for bevacizumab plus erlotinib, linifanib, and FOLFOX4. For overall survival, atezolizumab plus bevacizumab was ranked 1/25, followed by vandetanib 100 mg/d and donafinib, with lenvatinib ranked 6/25. Atezolizumab + bevacizumab was associated with a lower risk of death vs lenvatinib (HRos = 0.63; 95%CI: 0.44-0.89), while the HR for overall survival for most other treatments vs lenvatinib had associated 95%CIs that passed through unity. Vandetanib 300 mg/d and 100 mg/d were ranked 1/13 and 2/13, respectively, for the lowest incidence of treatment terminations due to adverse events, followed by sorafenib (5/13), lenvatinib (10/13), and atezolizumab + bevacizumab (13/13). Conclusion There is not one single first-line treatment for advanced HCC associated with superior outcomes across all outcome measurements. Therefore, first-line systemic treatment should be selected based on individualized treatment goals.

Diabetes mellitus (DM) is defined as a group of metabolic diseases characterized by hyperglycemia, which results from a deficiency in insulin secretion and/or insulin action. In diabetic patients, type 2 diabetes mellitus (T2DM) is in the majority. We explored the effects of circANKRD36 on streptozotocin (STZ)-induced insulin resistance and inflammation in diabetic rats with the aim of uncovering the underlying mechanism. STZ was used to induce the in vivo T2DM rat model. After circANKRD36 interference, blood glucose, insulin and adiponectin were respectively detected. Hematoxylin and eosin (H&E), enzyme-linked immunosorbent assay (ELISA) and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL) were conducted to examine inflammation and apoptosis in T2DM rats, and western blot was used for detecting apoptosis-related proteins. The binding relationships among circANKRD36, miR-145 and XBP1 were examined by luciferase reporter assay. Results showed that circANKRD36 was expressed at a high level in T2DM rats, while silencing circANKRD36 led to decreased blood glucose and insulin, accompanied by increased adiponectin level, and ameliorating insulin resistance. Silencing circANKRD36 alleviated the inflammation and suppressed cell apoptosis in the pancreatic tissues of T2DM rats, which was abated by miR-145 inhibitor. The binding of miR-145 to XBP1 was then confirmed. Additionally, miR-145 inhibitor increased the level of XBP1 in T2DM rats, which was decreased in the presence of circANKRD36 silencing. This study is the first to prove that silencing circANKRD36 inhibits STZ-induced insulin resistance and inflammation in diabetic rats by targeting miR- 145 via XBP1. The results warrant the importance of circRNAs as drug target and thereby pave way for the development of newer therapeutic measures for T2DM.

Purpose Numerous studies have applied a variety of methods to assess paraspinal muscle degeneration. However, the methodological differences in imaging evaluation may lead to imprecise or inconsistent results. This article aimed to provide a pragmatic summary review of the current imaging modalities, measurement protocols, and imaging parameters in the evaluation of paraspinal muscle fat infiltration (FI) in MRI studies. Methods Web of Science, EMBASE, and PubMed were searched from January 2005 to March 2020 to identify studies that examined the FI of paraspinal muscles on MRI among patients with lumbar degenerative diseases. Results Intramyocellular lipids measured by magnetic resonance spectroscopy and FI measured by chemical‐shift MRI were both correlated to low back pain and several degenerative lumbar diseases, whereas results on the relationship between FI and degenerative lumbar pathologies using conventional MRI were conflicting. Multi‐segment measurement of FI at the lesion segment and adjacent segments could be a prognostic indicator for lumbar surgery. Most studies adopted the center of the intervertebral disc or endplate as the level of slice to evaluate the FI. Compared with visual semiquantitative assessment, quantitative parameters appeared to be precise for eliminating individual or modality differences. It has been demonstrated that fat CSA/total CSA (based on area) and muscle–fat index (based on signal intensity) as quantitative FI parameters are associated with multiple lumbar diseases and clinical outcomes after surgery. Conclusion Having a good command of the methodology of paraspinal muscle FI on MRI was effective for diagnosis and prognosis in clinical practice., Heterogeneity in assessing the paraspinal muscle fat infiltration exists in imaging modalities, measurement protocols (including measured level and slices, region of interest definition, and fat detection methods), and imaging parameters (semiquantitative and quantitative parameters).

Background Bipolar disorder (BD) is predominantly treated with medication, and previous studies have shown that psychotropic drugs have an effect on the neuroendocrine system. And the objectives of this study were: 1) to assess changes in neuroendocrine hormones of HPA axis and HPT axis in patients with BD after psychotropic drug treatment; 2) to determine differences in the above neuroendocrine hormones between psychotropic drug monotherapy and polytherapy treated patients. Methods This study was a retrospective study that included 188 subjects. Results After psychotropic drugs treatment, TSH levels increased significantly from baseline (p Conclusion Although the incidence of significant HPT axis and HPA axis dysfunction after psychotropic drug treatment is low in patients with BD who have normal baseline neuroendocrine hormone levels, psychotropic drug treatment does suppress HPT axis and HPA axis function irrespective of the use of psychotropic drugs alone or in combination, and duration of psychotropic drug treatment. Therefore, even patients with BD who have normal baseline levels of neuroendocrine hormones should have their neuroendocrine hormone levels regularly monitored after psychotropic drug medication. But, the interval of monitoring can be slightly longer, which can be once every six months after taking psychotropic drugs.

Objective Deep brain stimulation (DBS) of the globus pallidus internus (GPi) has been shown to be a safe and effective alternative therapy for ameliorating medically refractory primary Meige syndrome. However, the associations between DBS target position and surrounding electrophysiological properties as well as patients’ clinical outcomes remains largely unknown. In a large number of patients, we investigated electrophysiological features around stimulation targets and explored their roles in predicting clinical outcomes following bilateral GPi-DBS. Methods The locations of DBS active contacts along the long axis of the GPi in a standard space were calculated and compared among three groups with different clinical outcomes. The firing rates of individual neurons within the GPi were calculated for each patient and compared across the three groups. Results Compared with the bad group (poor clinical outcome), active contacts in the good group (good clinical outcome) and the best group (best clinical outcome) were located in the more posterior GPi. The average firing rates in the good and best groups were significantly higher than in the bad group, and this difference was pronounced within the ventral GPi. For the bad group, the average firing rates were significantly lower in the ventral than in the dorsal GPi. Conclusions This study suggests that DBS of the posterior GPi may produce better clinical outcomes during primary Meige syndrome treatment and that higher GPi neuronal activity, particularly within the ventral part, can be used as a biomarker to guide DBS electrode implantation during surgery.

There is now a relatively large body of evidence suggesting a relationship between dysfunction of myelin and oligodendrocytes and the etiology of several neuropsychiatric disorders, including depression and schizophrenia, and also suggesting that ultrasound methods may alleviate some of the symptoms of depression. We have applied low-intensity pulsed ultrasound (LIPUS) to the brains of mice treated with the demyelinating drug cuprizone, a drug that has been used as the basis for a rodent model relevant to a number of psychiatric and neurologic disorders including depression, schizophrenia, and multiple sclerosis. Prior to conducting the studies in mice, preliminary studies were carried out on the effects of LIPUS in vitro in neuron-like SH-SY5Y cells and primary glial cells. In subsequent studies in mice, female C57BL/6 mice were restrained in plastic tubes for 20 min daily with the ultrasound transducer near the end of the tube directly above the mouse's head. LIPUS was used at an intensity of 25 mW/cm2 once daily for 22 days in control mice and in mice undergoing daily repetitive restraint stress (RRS). Behavioral or neurochemical studies were done on the mice or the brain tissue obtained from them. The studies in vitro indicated that LIPUS stimulation at an intensity of 15 mW/cm2 delivered for 5 min daily for 3 days in an enclosed sterile cell culture plate in an incubator increased the viability of SH-SY5Y and primary glial cells. In the studies in mice, LIPUS elevated levels of doublecortin, a marker for neurogenesis, in the cortex compared to levels in the RRS mice and caused a trend in elevation of brain levels of brain-derived neurotrophic factor in the hippocampus relative to control levels. LIPUS also increased sucrose preference (a measure of the attenuation of anhedonia, a common symptom of several psychiatric disorders) in the RRS model in mice. The ability of LIPUS administered daily to rescue damaged myelin and oligodendrocytes was studied in mice treated chronically with cuprizone for 35 days. LIPUS increased cortex and corpus callosum levels of myelin basic protein, a protein marker for mature oligodendrocytes, and neural/glial antigen 2, a protein marker for oligodendrocyte precursor cells, relative to levels in the cuprizone + sham animals. These results of this exploratory study suggest that future comprehensive time-related studies with LIPUS on brain chemistry and behavior related to neuropsychiatric disorders are warranted. Exploratory Study on Neurochemical Effects of Low Intensity Pulsed Ultrasound in Brains of Mice. Upper part of figure: LIPUS device and in-vitro cell experimental set-up. The center image is the LIPUS generating box; the image in the upper left shows the cell experiment set-up; the image in the upper right shows a zoomed-in sketch for the cell experiment; the image in the lower left shows the set-up of repetitive restraint stress (RRS) with a mouse; the image in the lower middle shows the set-up of LIPUS treatment of a mouse; the image in the lower right shows a zoomed-in sketch for the LIPUS treatment of a mouse.

Cerebellar hemangioblastomas with pregnancy is rare, but coexistence of pregnancy and recurrent cerebellar hemangioblastomas is rather rare. And coexistence of other diseases during pregnancy usually leads to misdiagnosis because of pregnancy reaction. A 29-year-old woman, at the 8th week of pregnancy, complained of nausea, vomiting, and episodic posterior occipital pain and was misdiagnosed pregnancy reaction without any special treatment during her several visits to local hospital. The patient was diagnosed cerebellar hemangioblastomas 14 years ago, after surgery, she received regular re-examination without recurrence. At the 15th week of pregnancy, the situation of the patient got worse, and she was admitted to our hospital. Brain magnetic resonance imaging showed a lesion in cerebellum. It was considered to be cerebellar hemangioblastomas and was confirmed finally by postoperative pathological examination. In clinical practice, differential diagnosis is of great importance during pregnancy because many other diseases can mimic pregnancy reaction. In this patient, the intracranial hypertension caused by recurrent cerebellar hemangioblastomas was misdiagnosed as pregnancy reaction and it was suggested that the change of hormones, neuroendocrine, and cardiovascular function promoted the recurrence of cerebellar hemangioblastomas.

Objective The aim of this study was to determine the clinical outcomes and long-term stability of individualized titanium mesh combined with free flap for orbital floor reconstruction after maxillectomy and to identify the risk factors for titanium mesh exposure. Material and methods The data of 66 patients who underwent maxillectomy and orbital floor defect reconstruction by individualized titanium mesh in Peking University School and Hospital of Stomatology between 2011 and 2019 were retrospectively reviewed. Postoperative ophthalmic function and success of aesthetic restoration were assessed. Titanium mesh exposure was recorded and the risk factors were identified. Results Mean follow-up was for 24.8 months (range, 6-92 months). Ophthalmic function was successfully restored in 63/66 patients. Aesthetic restoration was not considered satisfactory by 10 patients. Titanium mesh exposure occurred in six patients (exposure rate, 9.1%). Preoperative radiotherapy was identified as an independent risk factor for mesh exposure (OR = 28.8, P = 0.006). Previous surgery, postoperative radiotherapy, pathological type of the primary lesion, the type of tissue flap applied, and the use of intraoperative navigation were not significant risk factors. Six patients with titanium mesh exposure underwent second surgery, but mesh exposure recurred in two patients due to insufficient soft tissue coverage. Conclusion Individualized titanium mesh with free flap can effectively restore maxilla-orbital defects. Preoperative radiotherapy is an independent predictor of postoperative titanium mesh exposure. Adequate soft tissue coverage of the mesh may reduce the risk of mesh exposure. Level of evidence Level 4 (case-control study) Laryngoscope, 2021.

The ongoing coronavirus disease 2019 (COVID-19) pandemic caused more than 96 million infections and over 2 million deaths worldwide so far. However, there is no approved vaccine available for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the disease causative agent. Vaccine is the most effective approach to eradicate a pathogen. The tests of safety and efficacy in animals are pivotal for developing a vaccine and before the vaccine is applied to human populations. Here we evaluated the safety, immunogenicity, and efficacy of an inactivated vaccine based on the whole viral particles in human ACE2 transgenic mouse and in non-human primates. Our data showed that the inactivated vaccine successfully induced SARS-CoV-2-specific neutralizing antibodies in mice and non-human primates, and subsequently provided partial (in low dose) or full (in high dose) protection of challenge in the tested animals. In addition, passive serum transferred from vaccine-immunized mice could also provide full protection from SARS-CoV-2 infection in mice. These results warranted positive outcomes in future clinical trials in humans. Supplementary Information The online version contains supplementary material available at 10.1007/s12250-021-00376-w.

BACKGROUND Mechanical thrombectomy (MT) has been demonstrated to be useful for the treatment of ischemic stroke in patients with large vessel occlusions. However, recanalization by MT is not recommended for distal vessels such as second-order branches of the middle cerebral artery and posterior inferior cerebellar artery (PICA). Because of the small size and tortuosity of these arteries, the risks of using the available endovascular devices outweigh the benefits of treatment. However, MT appears to be effective in patients with primary distal vessel occlusion in eloquent areas, those with a high National Institutes of Health Stroke Scale score, and those ineligible for recombinant tissue plasminogen activator therapy. Here, we report the use of MT for treating acute occlusion of the PICA using a direct-aspiration first-pass technique (ADAPT). CASE SUMMARY In this case, the patient received acute occlusion of the PICA with ADAPT when right internal carotid artery stenting was performed. CONCLUSION With the introduction of advanced endovascular devices, MT may now be a feasible treatment for acute occlusion of the PICA.

INTRODUCTION Impaired esophageal and gastric motilities are known to contribute to symptoms of gastroesophageal reflux disease (GERD). However, there is a lack of GERD therapy, targeting both gastric and esophageal functions. This study was designed to investigate the effects of transcutaneous electrical acustimulation (TEA) on symptoms of GERD and gastroesophageal functions and possible mechanisms in patients with GERD. METHODS Thirty patients with GERD with ineffective esophageal motility were equally divided and randomized into a 4-week sham-TEA or 4-week TEA treatment. The GERD questionnaire (GerdQ), GERD health-related quality-of-life questionnaire, high-resolution esophageal manometry, a nutrient drink test, the electrogastrogram, and ECG were performed to assess the severity of reflux symptoms, low esophageal sphincter (LES) pressure, distal contractile integral (DCI), gastric accommodation, gastric slow waves (GSW), and autonomic functions, respectively. RESULTS Compared with sham-TEA, the 4-week TEA treatment significantly decreased the GerdQ score (P = 0.011) and GERD health-related quality of life (P = 0.028) and improved nutrient drink-induced fullness (P < 0.001) and belching (P < 0.001) in patients with GERD. Although only acute TEA significantly enhanced LES pressure (P < 0.05), both acute and chronic TEA remarkedly increased DCI (P < 0.05) and reduced the incidence of ineffective esophageal contractions during wet swallows (P = 0.02). In addition, chronic TEA significantly increased gastric accommodation and the percentage of postprandial normal GSW compared with sham-TEA and baseline. Concurrently, TEA-enhanced vagal activity (P = 0.02) and the vagal activity positively correlated with LES pressure (r = 0.528; P = 0.003) and DCI (r = 0.522; P = 0.003). DISCUSSION The TEA treatment performed in this study improves reflux-related symptoms, increases DCI, reduces the incidence of ineffective esophageal contractions during wet swallows, and improves gastric accommodation and slow waves. The improvement in GERD symptoms might be attributed to the integrative effects of TEA on these gastroesophageal functions mediated via the vagal mechanism.

Objective:. This study conducted inverse probability of treatment weighting (IPTW) survival analysis to examine survival in pancreatic adenocarcinoma patients. Methods:. In this population-based study, data from the Surveillance, Epidemiology, and End Results program of the United States were analyzed to identify patients diagnosed with adenocarcinoma of the pancreas 2004 to 2014. Differences in survival rates were examined among patients who underwent pancreatectomy alone, radiotherapy alone, and those who had pancreatectomy plus adjuvant radiotherapy. Kaplan–Meier estimates and Cox proportional hazards models with the IPTW were performed to determine the effect of different treatments on overall and cancer-specific survival. This study was approved by the Ethics Review Board of Weifang Medical University. Results:. A total of 8191 patients were included, with 3409 taking pancreatectomy only, 2865 taking radiotherapy only, and 1917 taking pancreatectomy plus adjuvant radiotherapy. Patients who received surgery plus adjuvant radiotherapy had statistically a higher survival rate than those who received the other 2 treatments. Survival analysis with the IPTW for the 3 different groups showed that the difference in median overall survival time among these patient groups was significant. Conclusion:. Using IPTW survival analysis, the present study shows that surgery with adjuvant radiotherapy is significantly associated with improved overall and cancer-specific survival among patients with pancreatic adenocarcinoma.

Background Previous studies have suggested that sensory loss is linked to depression. However, most of these studies have been conducted in developed countries and the results are mixed. Objectives The current study aims to examine the longitudinal relationship between hearing loss, vision loss, dual sensory loss, and depression among Chinese older adults over four years. Methods The data were obtained from the China Health and Retirement Longitudinal Survey (CHARLS). In total, 6353 Chinese older adults aged 60 years and over were included at baseline in this study. Self-reported hearing and vision status was used, and dual sensory loss was a combined variable of hearing loss and vision loss. Depressive symptoms were assessed by The Center for Epidemiologic Studies Depression Scale (CESD-10). The baseline relationship between sensory loss and depression was explored by logistic regression analyses. A logistic mixed model was used to assess whether baseline sensory loss was associated with incident depression for older adults with no depressive symptoms at baseline over four years. Results At baseline, vision loss (OR=1.46, 95%CI: 1.19-1.79) and dual sensory loss (OR=2.14, 95%CI: 1.77-2.58) were associated with depression, while hearing loss was not. After four years, vision loss (OR=1.60, 95%CI: 1.16-2.22) and dual sensory loss (OR=1.78, 95%CI: 1.32-2.41) were associated with incident depression. Limitations Not all potential confounding factors are measured and adjusted in the analysis. Apart from that, all measurements of interest are self-reported scales. Conclusion Vision loss and dual sensory loss are significantly associated with both onset and increased depressive symptoms over time, while hearing loss is not associated with depression. Interactions between all types of sensory loss and social activities are not significant. Our results suggest that target mental health intervention programs should be delivered to vision loss or dual sensory loss populations.

Aims/Introduction To investigate the differential effects of maternal versus paternal history of diabetes on the risks for diabetes and prediabetes, as well as on insulin secretion and resistance in Chinese individuals. Materials and Methods From the 2007 to 2008 China National Diabetes and Metabolism Disorders Study, 39,244 participants were included and divided into four categories: negative parental history, paternal history only (PH), maternal history only (MH), and both paternal and maternal history. Results The age‐ and sex‐standardized prevalence rates of diabetes in the negative parental history, PH, MH, and both paternal and maternal history groups were 8.59, 12.56, 15.86 and 29.81%, respectively. The prevalence rates of impaired glucose metabolism were 24.13, 25.41, 31.13 and 50.80%, with the prevalence in the MH group being significantly higher than that in the PH group. Compared with that in the FH0 group, the risks of diabetes in the PH, MH, and both paternal and maternal history groups were 2.01‐, 2.67‐ and 6.37‐fold greater, and the risks of impaired glucose metabolism were 1.28‐, 1.65‐ and 3.45‐fold greater. In addition, MH had a significantly greater impact on impaired glucose metabolism than PH (P MHvsPH = 0.0292). Regression analyses suggested MH was associated with homeostatic model assessment for β‐cell function (β[SE] = −0.0910[0.0334], P = 0.0065), insulinogenic index (−0.1866[0.0550], P = 0.0007), homeostatic model assessment for insulin resistance (0.0662[0.0227], P = 0.0036) and Matsuda Index [−0.0716(0.0203), P = 0.0004]. PH was specifically associated with homeostatic model assessment for insulin resistance (0.1343[0.0267], P, Impaired glucose metabolism was significantly more prevalent among participants with a maternal history of diabetes than among those with a paternal history. Maternal history had significantly greater influences on the elevated disease risk for impaired glucose metabolism than paternal history. Maternal history could contribute to the diseases through its impact on both insulin secretion impairment and insulin resistance, whereas the contribution of paternal history could rely on its specific impact on insulin resistance.

Introduction Pediatric myasthenia encompasses juvenile myasthenia gravis (JMG) and congenital myasthenic syndrome (CMS), which are chronic disorders with fluctuating symptoms amenable to medical therapy. Disease activity and treatment response may be difficult to assess, but, unlike adults, outcome measures have not been developed in children. Methods The study was performed in children (0-18 years of age) at the neuromuscular center of a pediatric hospital over a 3-year period. Patients were recruited prospectively as part of their routine clinical care. Demographic data, diagnosis (JMG/CMS), and the following scales were recorded at each visit: Myasthenia Gravis Foundation of America (MGFA) class, Myasthenia Gravis Composite (MGC), and Pediatric Myasthenia-Quality of Life 15 (PM-QOL15). Results Thirty-three patients (24 JMG, 9 CMS) were included in the study, 22 had two or more visits. We established known-groups validity of the MGC and PM-QOL15 scores as compared with the MGFA class. To establish concurrent validity, we constructed a receiver-operating characteristic curve and calculated threshold values of MGC and PM-QOL15 with optimal sensitivity and specificity for identifying a patient with more severe (MGFA III or higher) disease. Finally, we demonstrated the concordance between the MGC and PM-QOL15 by their statistically significant positive Pearson and Spearman correlations. Discussion Our study suggests that MGC and PM-QOL15 are important disease outcome measures in pediatric myasthenia that are easy to administer and provide reliable assessment of disease activity in the clinic setting. Further studies are needed to validate their use for pediatric clinical research trials.

We aimed to determine associations of regression to normal glucose tolerance (NGT), maintaining impaired glucose tolerance (IGT) or progression to diabetes with subsequent risks of CVD and microvascular disease among Chinese adults with IGT. We conducted an observational study among 540 participants in the Da Qing Diabetes Prevention Study, a 6 year lifestyle intervention trial in people with IGT, defined by 1985 WHO criteria as fasting plasma glucose

To investigate the grade of endolymphatic hydrops in patients with "probable" and "definite" Ménière's disease via magnetic resonance imaging (MRI) and to determine whether MRI could assist clinicians in differential diagnosis between probable and definite Ménière's disease.Prospective study.Three-dimensional FLAIR MRI (fluid-attenuated inversion recovery) to examine endolymphatic hydrops in Ménière's disease.A total of 51 patients diagnosed with probable (n = 20) or definite (n = 31) unilateral Ménière's disease were enrolled. Three-dimensional FLAIR MRI was performed to evaluate the grade of endolymphatic hydrops. The differences in endolymphatic hydrops between the probable and definite groups were analyzed.The grade of endolymphatic hydrops was more severe in the definite group than in the probable group (MRI revealed a higher grade of endolymphatic hydrops in patients with definite Ménière's disease than in patients with probable Ménière's disease. As a result, it may be clinically useful and an effective tool in the differentiation between definite and probable Ménière's disease.

The benefit of removing the splenic lymph nodes in patients with proximal gastric cancer has been controversial. The purpose of our study was to investigate the importance of performing a splenic hilar lymph node dissection without splenectomy in patients undergoing total gastrectomy for gastric cancer.From January 2006 to December 2015, we retrospectively reviewed patients who underwent a curative total gastrectomy for gastric cancer. Propensity score matching was used to balance any potential discrepancy of the other covariates between patients with and without splenic hilar lymph node dissection. Survival analysis, Cox univariate and multivariate analysis, and subgroups analysis were conducted to determine the value of splenic hilar lymph node dissection. After matching, 2 nomograms among patients with and without splenic hilar lymph node dissection were established respectively, the C-index, calibration curve and decision curve analysis were used to further evaluate the value of splenic hilar lymph node dissection.The rate of metastatic splenic hilar lymph nodes in the 274 patients undergoing splenic hilar lymph node dissection was 16.4% (45/274). Patients undergoing splenic hilar lymph node dissection had better survival outcomes than those not undergoing splenic hilar lymph node dissection before (P = .003) and after (P = .003) propensity score matching. Cox multivariate analysis also confirmed that splenic hilar lymph node dissection was an independent prognostic factor both before (hazard ratio 1.284, 95% confidence interval 1.042-1.583, P = .019) and after (hazard ratio 1.480, 95% confidence interval 1.156-1.894, P = .002) propensity score matching. Subgroup analysis indicted that splenic hilar lymph node dissection offered better survival outcomes for esophagogastric junctional adenocarcinoma (P.001, P for interaction = .018). After propensity score matching, the nomogram of patients with splenic hilar lymph node dissection (C-index 0.735, 95% confidence interval 0.695-0.774) also indicated a statistically significant advantage compared with that without splenic hilar lymph node dissection (C-index 0.708, 95% confidence interval 0.668-0.748, P.001).Our study suggests that spleen-preserving splenic hilar lymph node dissection should be an essential procedure among patients undergoing total gastrectomy.