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Circulating metabolites have been implicated in stroke pathogenesis, but their genetic determinants are understudied. Using a Mendelian randomization approach, our aim was to provide evidence for the relationship of circulating metabolites and the risk of stroke and its subtypes.Genetic instruments of 102 circulating metabolites were obtained from a genome-wide association study, including 24,925 European individuals. Stroke was extracted from the MEGASTROKE dataset (67,162 cases; 454,450 controls) and a lacunar stroke dataset (7338 cases; 254,798 controls). The magnetic resonance imaging markers of cerebral small vessel disease and microstructural injury were evaluated by a genome-wide association study of white matter hyperintensities (N = 18,381), fractional anisotropy (N = 17,663), mean diffusivity (N = 17,467) and brain microbleeds (N = 25,862). The inverse-variance weighted method Mendelian randomization was used as the primary analytical method, and directional pleiotropy and heterogeneity were examined in sensitivity analyses.A genetic predisposition to a higher level of cholesterol in small and low-density lipoprotein (LDL) was associated with risk of stroke (odds ratio [OR] 1.14, 95% confidence interval [CI] 1.08-1.21, p = 5.98 × 10Genetically determined levels of lipids in small LDL were associated with the risk of stroke, suggesting that a therapeutic strategy targeting small LDL levels may be crucial for stroke prevention. HDL-C was positively associated with the risk of intracerebral haemorrhage.

Inter-fraction organ variations cause deviations between planned and delivered doses in patients receiving radiotherapy for prostate cancer. This study compared planned (DP) vs accumulated doses (DA) obtained from daily cone-beam computed tomography (CBCT) scans in high-risk- prostate cancer with pelvic lymph nodes irradiation. An intensity-based deformable image registration algorithm used to estimate contours for DA was validated using geometrical agreement between radiation oncologist's and deformable image registration algorithm propagated contours. Spearman rank correlations (rs) between geometric measures and changes in organ volumes were evaluated for 20 cases. Dose-volume (DV) differences between DA and DP were compared (Wilcoxon rank test, p < 0.05). A novel region-of-interest (ROI) method was developed and mean doses were analyzed. Geometrical measures for the prostate and organ-at-risk contours were within clinically acceptable criteria. Inter-group mean (± SD) CBCT volumes for the rectum were larger compared to planning CT (pCT) (51.1 ± 11.3 cm3vs 46.6 ± 16.1 cm3), and were moderately correlated with variations in pCT volumes, rs = 0.663, p < 0.01. Mean rectum DV for DA was higher at V30-40 Gy and lower at V70-75 Gy, p < 0.05. Mean bladder CBCT volumes were smaller compared to pCT (198.8 ± 55 cm3vs 211.5 ± 89.1 cm3), and was moderately correlated with pCT volumes, rs = 0.789, p < 0.01. Bladder DA was higher at V30-65 Gy and lower at V70-75 Gy (p < 0.05). For the ROI method, rectum and bladder DA were lower at 5 to 10 mm (p < 0.01) as compared to DP, whilst bladder DA was higher than DP at 20 to 50 mm (p < 0.01). Generated DA demonstrated significant differences in organ-at-risk doses as compared to DP. A well-constructed workflow incorporating a ROI DV-extraction method has been validated in terms of efficiency and accuracy designed for seamless integration in the clinic to guide future plan adaptation.

AimsHeart failure (HF) remains a major public health problem with increasing prevalence in China. This study evaluated the clinical performance and quality measures for HF management to identify gaps in the standardization of care for patients hospitalized for HF in China.Methods and resultsFollowing the results of China-HF stage I (2012-2015), the second stage of the China-HF was launched in 2017. Among 113 hospitals with ≥100 cases, the China-HF Stage II assessed the quality of care measures for HF and compared results with previous data in China and the US-based Get with The Guidelines-Heart Failure (GWTG-HF) registries. In total, 34938 patients hospitalized with HF were enrolled from January 2017 to October 2020. Echocardiographic left ventricular function and natriuretic peptide test were performed in 93.7% and 93.0% of the cases, respectively. Adherence to standardized guidelines in China-HF stage II was higher than that in the China-HF stage I, but generally lower than GWTG-HF registry with 78.2% of eligible patients was prescribed oral diuretics, 78.7% renin-angiotensin-system inhibitors, and 82.2% beta-blockers. Implantable cardioverter-defibrillators and cardiac resynchronization devices were implanted in 3.9% and 14.6%, respectively. In contrast, the proportion of eligible patients discharged with spironolactone (87.8%) was higher than GWTG-HF. The median length of hospitalization was 9 (6, 12) days, and 938 (2.8%) patients died or withdrew from treatment during hospitalization.ConclusionsDespite significant improvements in the use of guideline-recommended testing and therapy, there remain major gaps in quality of care for patients hospitalized for HF in China that are generally larger than gaps observed in the United States.

To evaluate binocular visual function after unilateral and bilateral implantation of segmented refractive multifocal intraocular lenses (MIOLs). This prospective comparative pilot study included patients who underwent SBL-3 (Lenstec; + 3.00 D) implantation at Peking University Third Hospital. Patients were divided into two groups (monocular or binocular surgery). Thirty-two patients with emmetropic presbyopic contralateral eyes and 49 patients with bilateral SBL-3 implantation within a week between eyes were included in the unilateral SBL-3 and bilateral groups, respectively. At 3-month follow-up, the main outcomes were binocular uncorrected distant, intermediate, and near visual acuity (UDVA, UIVA, and UNVA). Secondary outcomes included binocular best-corrected visual acuity at all distances, defocus curve, contrast sensitivity, photic phenomena, spectacle independence, patient satisfaction, and National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) score. The essential perceptual phenomena constituting binocular vision, simultaneous perception, fusion, and stereopsis were also evaluated. Both groups showed similar binocular UDVA and UIVA, but UNVA was significantly better in the bilateral group (0.07 ± 0.07 versus 0.12 ± 0.07, P = 0.008). Better binocular defocus curve at intermediate to near focal points, higher percentage of spectacle independence at near distance, and NEI-VFQ-25 near activity scores were observed in the bilateral group. No significant differences in contrast sensitivity, photic phenomena, overall satisfaction, other NEI-VFQ-25 subscales, fusional amplitude, and stereoacuity were found between groups. Unilateral implantation of segmented refractive MIOL provided desirable distant visual acuity and high patient satisfaction, but inferior intermediate and near visual outcomes compared with bilateral implantation.

The limit of dynamic endurance during repetitive contractions has been referred to as the point of muscle fatigue, which can be measured by mechanical and electrophysiological parameters combined with subjective estimates of load tolerance for revealing the human real-world capacity required to work continuously. In this study, an isotonic muscular endurance (IME) testing protocol under a psychophysiological fatigue criterion was developed for measuring the retentive capacity of the power output of lower limb muscles. Additionally, to guide the development of electrophysiological evaluation methods, linear and non-linear techniques for creating surface electromyography (sEMG) models were compared in terms of their ability to estimate muscle fatigue. Forty healthy college-aged males performed three trials of an isometric peak torque test and one trial of an IME test for the plantar flexors and knee and hip extensors. Meanwhile, sEMG activity was recorded from the medial gastrocnemius, lateral gastrocnemius, vastus medialis, rectus femoris, vastus lateralis, gluteus maximus, and biceps femoris of the right leg muscles. Linear techniques (amplitude-based parameters, spectral parameters, and instantaneous frequency parameters) and non-linear techniques (a multi-layer perception neural network) were used to predict the time-dependent power output during dynamic contractions. Two mechanical manifestations of muscle fatigue were observed in the IME tests, including power output reduction between the beginning and end of the test and time-dependent progressive power loss. Compared with linear mapping (linear regression) alone or a combination of sEMG variables, non-linear mapping of power loss during dynamic contractions showed significantly higher signal-to-noise ratios and correlation coefficients between the actual and estimated power output. Muscular endurance required in real-world activities can be measured by considering the amount of work produced or the activity duration via the recommended IME testing protocol under a psychophysiological termination criterion. Non-linear mapping techniques provide more powerful mapping of power loss compared with linear mapping in the IME testing protocol.

This study aims to conduct a comprehensive clinical and genetic investigation on a large family with members having various phenotypes, including acromesomelic dysplasia, type Maroteaux (AMDM), idiopathic short stature (ISS), Crouzon syndrome (CS). Prenatal diagnosis was performed on the high-risk fetus. We performed the whole-exome sequencing on three members with AMDM, ISS, or CS. Detailed genotypes and phenotypes were investigated on members of this 4-generation family. Genetic analysis identified three variants, which were designated as p.Val548del, p.Arg989Gln in natriuretic peptide receptor B/guanylate cyclase B (

Background To assess and compare the efficacy, safety, accuracy, predictability and visual quality of a diffractive trifocal intraocular lens (IOL) and a refractive rotationally asymmetric bifocal IOL in eyes with axial myopia. Methods This prospective cohort study enrolled patients with implantation of the diffractive trifocal IOL or the refractive bifocal IOL. Eyes were divided into four groups according to the IOL implanted and axial length. Manifest refraction, uncorrected and corrected visual acuity at far, intermediate and near distances, prediction error of spherical equivalent (SE), contrast sensitivity and aberrations were evaluated three months after surgery. Results In total, 80 eyes of 80 patients were included: 20 eyes in each group. Three months postoperatively, the corrected distance visual acuity of two trifocal groups were significantly better than the axial myopia bifocal group (P = 0.007 and 0.043). There was no significant difference of postoperative SE (P = 0.478), but the SE predictability of the trifocal IOL was better, whether in axial myopia groups (P = 0.015) or in control groups (P = 0.027). The contrast sensitivity was similar among four groups. The total aberration, higher order aberration and trefoil aberration of bifocal groups were significantly higher (all P Conclusions The diffractive trifocal IOL and the refractive bifocal IOL both provided good efficacy, accuracy, predictability and safety for eyes with axial myopia. By contrast, the trifocal IOL had a better performance in corrected distance visual acuity and visual quality. Trial registration The study was retrospectively registered and posted on clinicaltrials.gov at 12/02/2020 (NCT04265846).

This study aimed to assess morphological changes in the retinal microvasculature and foveal avascular zone (FAZ) in patients with ischemic stroke and its different subtypes.Thirty-three patients with ischemic stroke (14 with nonlacunar infarction and 19 with lacunar infarction) and 27 control participants were enrolled in this study. Based on optical coherence tomography angiography (OCTA), three vascular parameters, including vascular area density, vascular fractal dimension (VFD), and vascular orientation distribution (VOD), and four FAZ-related parameters, including FAZ area, FAZ axis ratio (FAR), FAZ circularity (FC), and FAZ roundness, in the superficial capillary plexus (SCP) and deep capillary plexus (DCP) were extracted and analyzed.Logistic regression results showed that worse best-corrected visual acuity (odds ratio [OR], 0.21), higher FAR (OR, 2.77) and lower FC (OR, 0.36) of the DCP were associated with ischemic stroke. Furthermore, lower VOD of the SCP was significantly associated with lacunar infarction compared with nonlacunar infarction.Our study shows that the FAR and FC of the DCP may be potential biomarkers of ischemic stroke. Moreover, we demonstrated that OCT showed specific damage patterns in retinal microvascular and macular morphology in different subtypes of ischemic stroke.This work lays the foundation for the pathophysiological characteristics of cerebrovascular diseases assisted by retinal imaging and artificial intelligence.

Background:. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder associated with loss of motor neurons. Our objective was to explore the epidemiology, clinical features, and survival factors of 1809 patients with ALS. Methods:. We analyzed 1809 ALS patients, who were recruited from the Peking University Third Hospital from January 2005 to December 2015. Demographic data and disease-related parameters were collected. Kaplan-Meier curves were used to compare survival time. Cox proportional hazards function and the hazard ratio were used to identify adjusted prognostic predictors. Results:. The results showed that the average annual incidence in Beijing alone was 0.38 cases/100,000 person-years and the mean age of onset was 48.88 ± 11.35 (95% confidence interval [CI]: 48.17–49.85) years. The median survival time from onset to death/tracheostomy was 58.89 ± 33.03 (95% CI: 51.46–63.84) months. In the adjusted Cox proportional hazard model, age of onset, diagnosis delay, rate of disease progression (Amyotrophic Lateral Sclerosis Functional Rating Scale Revised decline [points/month]), and body mass index all had an independent effect on survival in ALS. Conclusions:. Our study provides information on epidemiology, clinical features, and survival factors of patients with ALS in China. These results can be helpful in clinical practice, clinical trial design, and validation of new tools to predict disease progression.

Correlative imaging and quantification of intracellular nanoparticles with the underlying ultrastructure is crucial for understanding cell-nanoparticle interactions in biological research. However, correlative nanoscale imaging of whole cells still remains a daunting challenge. Here, we report a straightforward nanoscopic approach for whole-cell correlative imaging, by simultaneous ionoluminescence and ultrastructure mapping implemented with a highly focused beam of alpha particles. We demonstrate that fluorescent nanodiamonds exhibit fast, ultrabright and stable emission upon excitation by alpha particles. Thus, by using fluorescent nanodiamonds as imaging probes, our approach enables quantification and correlative localization of single nanodiamonds within a whole cell at sub-30 nm resolution. As an application example, we show that our approach, together with Monte Carlo simulations and radiobiological experiments, can be employed to provide unique insights into the mechanisms of nanodiamond radiosensitization at the single whole-cell level. These findings may benefit clinical studies of radio-enhancement effects by nanoparticles in charged-particle cancer therapy., The authors demonstrate efficient excitation of nanodiamonds by a focused beam of helium ions, resulting in ionoluminescence. They use this for quantification and correlative localization of single particles within a whole cell at sub-30 nm resolution, and investigate nanodiamond radiosensitisation effects.

Graphic abstract Paeonol, derived from natural plants (Moutan Cortex), has a wide range of biological effects, including anti-inflammatory and antitumor effects as well as favorable effects against cardiovascular and neurodegenerative diseases. The anti-inflammatory action is the main pharmacological activity of paeonol and has the greatest clinical relevance. However, the anti-inflammatory mechanism of paeonol has not been reported in sufficient detail. We systematically analyzed the anti-inflammatory mechanism of paeonol using network pharmacological databases and platforms, including TCMSP, Swiss TargetPrediction, OMIM, DrugBank, TTD, Jevnn, STRING11.0, and Metascape. Furthermore, we used high-throughput molecular docking method to prove the results of the above analyses, providing a reference for exploring the mechanism of paeonol and developing targeted drugs.

Background Appropriate sizing of the implantable collamer lens (ICL) and accurate prediction of the vault are crucial prior to surgery. However, sometimes, the vault value is higher or lower than predicted, necessitating reoperation. The present study aimed to develop neural networks for improving predictions of vault values following ICL implantation based on preoperative biometric data. Methods This retrospective study included 137 eyes of 74 patients with ICLs. Linear regression and neural network analyses were used to examine the relationship between vault values at the 6-month follow-up and preoperative parameters (e.g., ICL characteristics and biometrics). Results Linear regression analysis revealed that vault values were correlated with five variables: ICL size, anterior chamber depth (ACD), angle-to-angle (ATA), white-to-white (WTW), and lens thickness (LT) (adjusted R2 = 0.411). Inclusion of more input variables was associated with better performance in the neural network analysis. The degree of fit when all 11 variables were included in the neural network model was close to 1 (R2 = 0.98). R2 values for the quaternary neural network model enrolling four input variables (ICL size, ATA, ACD, and LT) reached 0.90. Conclusions A neural network equation including the ICL size and biometric parameters of the anterior segment (ATA, ACD, and LT) can be used to predict the postoperative vault, aiding in the selection of an appropriate ICL size and reducing the need for reoperation after surgery.

As an autoimmune disease affecting women of reproductive age, systemic lupus erythematosus (SLE) is linked to adverse fetal and maternal outcomes. However, the status of peripheral lymphocytes in SLE patients with different pregnancy outcomes is unclear. This retrospective cross-sectional study explored the relationship between lymphocyte subpopulations and pregnancy outcomes in married SLE female patients.The absolute numbers of peripheral T, helper T (Th)1, Th2, Th17, regulatory T (Treg), B, and natural killer (NK) cell subpopulations from 585 female SLE patients and 91 female healthy controls (HCs) were assessed. We compared the lymphocyte subpopulations in SLE patients with HCs and analyzed the absolute number and ratio of Treg cells according to pregnancy outcome in SLE patients.SLE patients had decreased numbers of T, B, NK, Th1, Th2, Th17, and Treg cells and an imbalance in pro- and anti-inflammatory cells (p .05), as well as adverse pregnancy outcomes. In abortion patients, the number of Treg cells (p = .008) decreased, leading to an imbalance in effector T and Treg cells. The ratio of Treg cells was higher in SLE patients with nulliparity than in those with one or two parities.The absolute numbers of lymphocyte subpopulations in SLE patients decreased, which was associated with abortion and parity (p .05). These results suggest that a loss of immune tolerance mediated by Tregs triggers pregnancy loss.

A direct evaluation of insulin sensitivity on pituitary response to gonadotropin relasing hormone (GnRH) has not been shown in congenital hypogonadotropic hypogonadism (CHH), despite a growing body of evidence in the association of testosterone concentrations with insulin sensitiviy. The objective of the study was to explore whether increased testosterone concentrations in men with CHH improve insulin sensitivity, or vice versa.A retrospective study at a tertiary centre.Series of male CHH patients were included from Jannuary 2014 to December 2019.Insulin sensitivity indices calculated from oral glucose tolerance test and steroid hormone levels were examined in 52 patients with newly diagnosed CHH and 22 healthy controls. Thirty-two of the 52 CHH patients received pulsatile GnRH therapy with follow-up every 3-6 months.Compared to healthy controls, CHH patients had elevated 2 h post-load glucose, HbA1c, fasting insulin, HOMA of insulin resistance (HOMA-IR) and decreased Matsuda index and testosterone (p ≤ .01). The median follow-up for patients (n = 32) who received pulsatile GnRH therapy was 13.5 (11.3-24) months (432 person-months in total). GnRH therapy increased testosterone and Matsuda index (p ≤ .0001), whilst decreased platelet count (p = .04), leptin (p = .04), fasting glucose (p = .01) and HOMA-IR (p lt; .0001) compared with baseline. The median treatment duration first time to reach the lower limit of normal testosterone concentrations of patients with high and low baseline insulin sensitivity was 15 (95% CI: 8.1-21.9) and 30 months (21.2-38.8), respectively. Correspondingly, after GnRH therapy, luteinizing hormone responsiveness to GnRH provocative test was more vigorous in patients with high insulin sensitivity than those with low insulin sensitivity [17.0 (9.5-25.9) vs. 8.2 (3.3-13.0), p = .01].Pulsatile GnRH therapy elevated testosterone levels in male CHH patients, ameliorated impaired insulin sensitivity and attenuated subclinical inflammatory response, increased insulin sensitivity, in turn, may benefit the efficacy of pulsatile GnRH therapy.

Background Many surgical options have been described to manage post-tubercular kyphosis, but the standard approach for treating severe post-tubercular angular kyphosis in children has not been established yet. The present study was performed to evaluate the safety and efficacy of deformed complex vertebral osteotomy (DCVO) for the treatment of severe thoracic post-tubercular angular kyphosis (> 70°) in children. Methods Deformed complex vertebrae indicated that multiple deformed and fused vertebrae were usually involved with two or more vertebral bodies and the partial or total fusion of many segments' facet joints and intervertebral discs. Thus, DCVO indicated that a wider posterior wedge-shaped and three-column osteotomy was performed within deformed complex vertebrae to correct a more extensive range of angles. From 2010 to 2017, 15 children who suffered from severe thoracic post-tubercular angular kyphosis underwent DCVO. Deformed complex vertebrae involved two vertebral bodies in 9 patients and three vertebral bodies in 6 patients. The Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI) were assessed preoperatively and at the final follow up. This was a retrospective study analysing the outcome after grade 4/5 spinal osteotomies in deformed complex vertebrae. Results The mean duration of surgery was 239 ± 37.81 min. The average period of follow-up was 31.6 ± 6.98 months. The preoperative mean kyphosis of deformed complex vertebrae was 83.39° ± 9.04°; the mean thoracic kyphosis (TK) and lumbar lordosis (LL) were 81.09° ± 8.51° and 80.51° ± 7.64°, respectively; the mean sagittal vertical axis (SVA) was 3.83 cm ± 1.43 cm. The postoperative mean kyphosis of deformed complex vertebrae was reduced to 19.98° ± 2.47° (P P P p = 0.982, p = 0.604, p = 0.754). Complicated with neural dysfunction preoperatively, 5 Frankel's grade D cases showed complete neurological recovery at final follow up. VAS score reduced from 3.6 ± 1.18 to 0.87 ± 0.64 (P P Conclusions DCVO was an individualized osteotomy for treating severe thoracic post-tubercular angular kyphosis in children and could be safe and effective in reducing the incidence of complications and significantly improving kyphosis correction.

Background Pyogenic vertebral osteomyelitis (PVO), which is a potentially life-threatening condition and is associated with significant morbidity and mortality, is a cause of back pain that can lead to neurologic deficits if not diagnosed in time and effectively treated. The objective of this study is to compare the efficacy of posterior single-segment and short-segment fixation combined with one-stage posterior debridement and fusion for the treatment of mono-segmental lumbar or lumbosacral PVO. Methods Charts of all patients with mono-segmental lumbar or lumbosacral PVO were treated by single-stage posterior debridement, bone graft fusion, and pedicle screw fixation from April 2012 to January 2016. All patients were divided into two groups: sinlge-segment fixation (Group A, n = 31) and short-segment fixation (Group B, n = 36). These patients were followed up for a minimum of five years. The clinical efficacy was evaluated and compared on average operation time, blood loss, visual analog scale (VAS), erythrocyte sedimentation rate (ESR), C-Reactive protein (CRP), neurological function recovery and local lordotic angle. Results All 67 patients were completely cured during the follow-up. All patients had significant improvement of neurological condition and pain relief at the final follow-up. The VAS was 7.1 ± 0.7 in group A and 7.2 ± 0.6 in group B pre-operatively, which decreased to 2.1 ± 0.6 and 2.0 ± 0.7, respectively, at three months after surgery, then reduced to 0.4 ± 0.5 and 0.5 ± 0.5, respectively, at the final follow-up. ESR, CRP returned to normal limits in all patients 3 months after surgery. The mean blood loss and operation time in group A were less than that in group B (P P P P Conclusion Posterior-only debridement, interbody graft using titanium mesh cage, posterior single-segment instrumentation and fusion represent a safe and effective treatment option for selected patients with mono-segmental lumbar and lumbosacral PVO. This approach may preserve more lumbar normal motor units with less blood loss and operation time when compared with that of short-segment fixation. But short-segment fixation was superior to the single-segment fixation in the correction of kyphosis.

Cervicothoracic scoliosis will cause severe deformities in the early stage, and its structure is complex and the surgical methods are varied. The purpose of this research is to explore the indication and analyze the corrective effect of the two different posterior approach surgical strategies, including correction with fusion and hemivertebra osteotomy, for congenital cervicothoracic scoliosis deformities in children and adolescents.This was a retrospective study of 21 patients with cervicothoracic scoliosis who received surgical treatment from January 2010 to June 2020, including nine cases of posterior hemivertebra osteotomy and fusion surgery and 12 cases of posterior correction and fusion alone. The Cobb angle, T1 tilt angle, clavicular angle, neck tilt angle, radiographic shoulder height, sagittal vertical axis, coronal balance distance, and local kyphosis angle were measured preoperatively, postoperatively, and at the last follow-up. Posterior approach hemivertebra resection or correction with fusion surgery was adopted based on the different individual characteristics of deformity such as main curve Cobb angle, growth potential, and flexibility. Patients were divided into two groups (osteotomy group and nonosteotomy group) according to whether a hemivertebra osteotomy was performed, and the corrective results in the two groups were compared. Paired-sample t tests or independent-sample t tests were used.The median follow-up after surgery of the 21 patients was 36 months (range, 18-72 months). The Cobb angle was corrected from 45.81° ± 14.23° preoperatively to 10.48° ± 5.56° postoperatively (correction rate, 77.78% ± 8.93%). The T1 tilt angle decreased from 15.26° ± 7.08° preoperatively to 3.33° ± 2.14° postoperatively (correction rate,73.42% ± 21.86%). The radiographic shoulder height was corrected from 1.13 ± 0.74 cm preoperatively to 0.52 ± 0.42 cm postoperatively (correction rate, 39.51% ± 35.65%). The clavicular angle improved from 2.52° ± 1.55° preoperatively to 1.16° ± 0.96° postoperatively (correction rate, 47.18% ± 35.84%). No significant differences were found at the last follow-up (p 0.05). The Cobb angle of the main curve, T1 tilt angle, clavicular angle, cervical tilt angle, and shoulder height difference were similar in the two groups (p 0.05).Posterior approach hemivertebra resection or correction with fusion surgery can be used in the treatment of congenital cervicothoracic scoliosis with satisfactory results, and the surgeon can make an individualized surgical plan according to individual characteristics of deformity.

The aggressive nature and poor prognosis of lung cancer led us to explore the mechanisms driving disease progression. Utilizing our invasive cell-based model, we identified methylthioadenosine phosphorylase (MTAP) and confirmed its suppressive effects on tumorigenesis and metastasis. Patients with low MTAP expression display worse overall and progression-free survival. Mechanistically, accumulation of methylthioadenosine substrate in MTAP-deficient cells reduce the level of protein arginine methyltransferase 5 (PRMT5)-mediated symmetric dimethylarginine (sDMA) modification on proteins. We identify vimentin as a dimethyl-protein whose dimethylation levels drop in response to MTAP deficiency. The sDMA modification on vimentin reduces its protein abundance but trivially affects its filamentous structure. In MTAP-deficient cells, lower sDMA modification prevents ubiquitination-mediated vimentin degradation, thereby stabilizing vimentin and contributing to cell invasion. MTAP and PRMT5 negatively correlate with vimentin in lung cancer samples. Taken together, we propose a mechanism for metastasis involving vimentin post-translational regulation.

Objective. This research is aimed at investigating the relationship between liver fibrosis in viral hepatitis and macrophage colony-stimulating factor (M-CSF), tissue inhibitor of matrix metalloproteinase (TIMP-1), and ceruloplasmin (CER) in serum level. Methods. Patients were randomly selected among those admitted to our hospital, and 60 healthy volunteers were chosen to serve as control participants. The levels of serum M-CSF, CER, and TIMP-1 were compared. According to the severity of their liver fibrosis, patients with CHB were separated into four groups: S1, S2, S3, and S4. Serum levels of M-CSF, CER, and TIMP-1 were correlated with liver fibrosis and hepatitis markers, and the diagnostic usefulness of the three indices was assessed with liver cirrhosis patients. Results. Increases in M-CSF and TIMP-1 in the CHB group but decreases in CER were statistically significant ( P < 0.05 ). Serum levels of M-CSF, CER, TIMP-1, HA, PC-III, C-IV, and LN differed significantly across the four study groups ( P < 0.05 ). Over time, as liver fibrosis worsened, we observed a progressive uptick in M-CSF, TIMP-1, LN, HA, C-IV, and PC-III levels and a progressive downtick in CER levels, with significant ( P < 0.05 ) differences between the groups. There was a significant positive correlation between liver fibrosis and serum M-CSF, PC-III, TIMP-1, HA, LN, and C-IV levels in the CHB group ( P < 0.05 ) and a significant negative correlation between serum CER and these same factors ( P < 0.05 ). The AUC of 0.956 for diagnosing the S4 stage was greater than that of 0.857, 0.851, and 0.817 for M-CSF, CER, and TIMP-1, respectively. Conclusions. In CHB patients, the liver fibrosis degree is associated with the M-CSF, CER, and TIMP-1 levels, and the combined clinical detection of these three markers has better diagnostic significance.

The design and synthesis of water-soluble phototherapeutic agents with near-infrared (NIR) fluorescence emission is highly desirable for cancer diagnosis and treatment. Here, we report the construction of an amphiphilic perylene-derived photosensitizer, AP. AP shows NIR emission with large Stokes shift (130 nm) and high

Purpose To investigate the expression of pigment epithelium-derived factor (PEDF) in ocular surface in dry eye disease (DED) and its anti-inflammatory roles and mechanisms, clinically and by experiments in vivo and in vitro. Methods A cross-sectional study was conducted to detect the expression of PEDF in tears of dry eye patients by enzyme-linked immunosorbent assay (ELISA). Using dry eye mouse model and human corneal epithelial cells (hCECs) stimulated by hyperosmolarity or inflammatory cytokines, expression of PEDF in corneal epithelial cells, stroma and conjunctiva was quantified by real-time polymerase chain reaction, ELISA and Western blot. Next, either dry eye mice or hyperosmotic hCECs were treated with recombinant PEDF or neutralizing antibodies, and the expressions of inflammatory cytokines and immune cells were detected. Finally, Western blot was performed on MAPK and NF-κB to investigate the signaling pathways by which PEDF played its roles. Results Concentrations of PEDF were increased in tears of dry eye patients. Increased PEDF was observed in corneal epithelial cells (CECs) rather than corneal stroma or conjunctiva in dry eye mice. Furthermore, hCECs exposed to hyperosmolarity showed upregulation of PEDF. In vivo and in vitro studies showed that PEDF suppressed the expression of inflammatory cytokines including IL-1β, IL-6, TNF-α and IL-17A, as well as the percentage of Th17 cells in DED. Further investigation showed that PEDF inhibited the phosphorylation of MAPK p38 and JNK in hyperosmotic hCECs. Conclusions CECs derived PEDF is increased in DED. PEDF plays anti-inflammatory and immunoregulatory roles in the pathogenesis of DED.

We investigated the expression and functions of circular RNA (circRNA) circNINL and miR-921 in breast cancer (BC) in this study. We found that the expression of circNINL increased while the expression of miR-921 decreased in BC tissues and cell lines, and their anomalous expressions were associated with malignant features and poor prognostic of BC. Then, we demonstrated that circNINL could interact with miR-921 and facilitate BC cells malignant process including proliferation acceleration, migration enhancement and apoptosis evasion via sponging miR-921 in vitro. Further investigations revealed that circNINL/miR-921 axis could mediate the expression of ADAM9 which was a direct target of miR-921. In addition, we exhibited that ADAM9 may activate β-catenin signaling by interacting with E-cadherin. We presented the vital roles of circNINL/miR-921/ADAM9/β-catenin signaling in the progression of BC.

There remains a significant gap in our quantitative understanding of crosstalk between apoptosis and necroptosis pathways. By employing the SWATH-MS technique, we quantified absolute amounts of up to thousands of proteins in dynamic assembling/de-assembling of TNF signaling complexes. Combining SWATH-MS-based network modeling and experimental validation, we found that when RIP1 level is below ~1000 molecules/cell (mpc), the cell solely undergoes TRADD-dependent apoptosis. When RIP1 is above ~1000 mpc, pro-caspase-8 and RIP3 are recruited to necrosome respectively with linear and nonlinear dependence on RIP1 amount, which well explains the co-occurrence of apoptosis and necroptosis and the paradoxical observations that RIP1 is required for necroptosis but its increase down-regulates necroptosis. Higher amount of RIP1 (>~46,000 mpc) suppresses apoptosis, leading to necroptosis alone. The relation between RIP1 level and occurrence of necroptosis or total cell death is biphasic. Our study provides a resource for encoding the complexity of TNF signaling and a quantitative picture how distinct dynamic interplay among proteins function as basis sets in signaling complexes, enabling RIP1 to play diverse roles in governing cell fate decisions. Electronic supplementary material The online version of this article (10.1007/s13238-020-00810-x) contains supplementary material, which is available to authorized users.

Background Congenital scoliosis (CS) is a congenital deformity of the spine resulting from abnormal and asymmetrical development of vertebral bodies during pregnancy. However, the etiology and mechanism of CS remain unclear. Epigenetics is the study of heritable variations in gene expression outside of changes in nucleotide sequence. Among these, DNA methylation was described first and is the most characteristic and most stable epigenetic mechanism. Therefore, in this study, we aim to explore the association between genome methylation and CS which are not been studied before. Methods Two pairs of monozygotic twins were included, with each pair involving one individual with and one without CS. Agilent SureSelect XT Human Methyl-Sequencing was used for genome methylation sequencing. MethylTarget was used to detect methylation levels in target regions. Immunohistochemistry was performed to visualize expression of associated genes in candidate regions. Results A total of 75 differentially methylated regions were identified, including 24 with an increased methylation level and 51 with a decreased methylation level in the CS group. Nine of the differentially methylated regions were selected (TNS3, SEMAC3, GPR124, MEST, DLK1, SNTG1, PPIB, DEF8, and GRHL2). The results showed that the methylation level of the promoter region of TNS3 was 0.72 ± 0.08 in the CS group and 0.43 ± 0.06 in the control group (p = 0.00070 SEMAC3, GPR124, MEST, DLK1, SNTG1, PPIB, DEF8, or GRHL2 between the two groups. Immunohistochemistry showed significantly decreased TNS3 expression in the cartilage of the articular process in CS (CS: 0.011 ± 0.002; control: 0.018 ± 0.006, P = 0.003 Conclusion Compared with the control group, high-level methylation of the TNS3 promoter region and low TNS3 expression in the cartilage layer of the articular process characterize CS. Thus, DNA methylation and TNS3 may play important roles in the pathogenesis of CS.

Objectives We aimed to assess the clinical value of multimodal photoacoustic/ultrasound (PA/US) articular imaging scores, a novel imaging method which can reflect the micro-vessels and oxygenation level of inflamed joints of rheumatoid arthritis (RA). Methods Seven small joints were examined by the PA/US imaging system. A 0–3 scoring system was used to semi-quantify the PA and power-Doppler (PD) signals, and the sums of PA and PD scores (PA-sum and PD-sum scores) of the seven joints were calculated. The relative oxygen saturation (SO2) values of the inflamed joints were measured and classified into 3 PA+SO2 patterns. The correlations between the PA/US imaging scores and the disease activity scores were assessed. Results Thirty-one patients of RA and a total of 217 joints were examined using the PA/US system. The PA-sum had high positive correlations with the standard clinical scores of RA (DAS28 [ESR] ρ = 0.754, DAS28 [CRP] ρ = 0.796, SDAI ρ = 0.836, CDAI ρ = 0.837, p < 0.001), which were superior to the PD-sum (DAS28 [ESR] ρ = 0.651, DAS28 [CRP] ρ = 0.676, SDAI ρ = 0.716, CDAI ρ = 0.709, p < 0.001). For the patients with high PA-sum scores, significant differences between hypoxia and hyperoxia were identified in pain visual analog score (p = 0.020) and patient’s global assessment (p = 0.026). The PA+SO2 patterns presented moderate and high correlation with PGA (ρ = 0.477, p = 0.0077) and VAS pain score (ρ = 0.717, p < 0.001). Conclusion The PA scores have significant correlations with standard clinical scores for RA, and the PA+SO2 patterns are also related with clinical scores that reflect pain severity. PA may have clinical potential in evaluating RA. Key Points • Multimodal photoacoustic/ultrasound imaging is a novel method to assess micro-vessels and oxygenation of local lesions. • Significant correlations between multimodal imaging parameters and clinical scores of RA patients were verified. • The multimodal PA/US system can provide objective imaging parameters, including PA scores of micro-vessels and relative SO2value, as a supplementary to disease activity evaluation.

Background: Hypometabolism detected by fluorodeoxyglucose F18 positron emission tomography ([18F] FDG PET) is an early neuropathologic changes in Alzheimer’s disease (AD) and provides important pathologic staging information. Objective: This study aimed to discover genetic interactions that regulate longitudinal glucose metabolic decline in AD-related brain regions. Methods: A total of 586 non-Hispanic white individuals from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) 1/GO/2 cohorts that met all quality control criteria were included in this study. Genome-wide association study of glucose metabolic decline in regions of interest (ROIs) was performed with linear regression under the additive genetic model. Results: We identified two novel variants that had a strong association with longitudinal metabolic decline in different ROI. Rs4819351-A in gene 1-acylglycerol-3-phosphate O-acyltransferase 3 (AGPAT3) demonstrated reduced metabolic decline in right temporal gyrus (p = 3.97×10–8, β= –0.016), while rs13387360-T in gene LOC101928196 demonstrated reduced metabolic decline in left angular gyrus (p = 1.69×10–8, β= –0.027). Conclusion: Our results suggest two genome-wide significant SNPs (rs4819351, rs13387360) in AGPAT3 and LOC101928196 as protective loci that modulate glucose metabolic decline. These two genes should be further investigated as potential therapeutic target for neurodegeneration diseases.

Hypertensive retinopathy refers to the retinal vascular changes associated with systemic arterial hypertension. Hypertensive retinopathy can be divided into chronic and acute phases. A cross‐sectional study was performed to explore a method of measurement in the diameters of retinal vessels for diagnosis of chronic hypertensive retinopathy based on spectral domain optical coherence tomography (SD‐OCT). The central retinal artery diameter (CRAD), the central retinal vein diameter (CRVD), and the artery‐to‐vein ratio (AVR) were measured. A total of 119 subjects with 119 eyes were included in this study, in which 56 subjects with 56 eyes were included in hypertensive group and 63 subjects with 63 eyes were included in normotensive group. There were significant differences between the two groups in the CRAD (t = −2.14, P = .04) and the AVR (t = −2.59, P = .01). The cutoff point of 0.75 was determined by receiver operating characteristic (ROC) curve (area under the curve, AUC 0.786; 95% confidence interval, 95% CI 0.70‐0.87). Multivariate logistic regression analysis showed the probability of AVR below to 0.75 was more in patients with high systolic blood pressure (odds ratio OR 4.39; P = .048), more in male (OR 4.15; P = .004) and more in smokers (OR 5.80; P = .01). Bland‐Altman plots showed small mean bias between the measurements of the two technicians in the CRAD, the CRVD, and the AVR. In summary, application of SD‐OCT is an accurate, reproducible, convenient method for measuring the diameters of retinal vessels. It is valuable for the diagnosis of chronic stage of hypertensive retinopathy.

The up‐regulation of EMT regulator Twist1 has been implicated in vasculogenic mimicry (VM) formation in human triple‐negative breast cancer (TNBC). Twist1 targets the Claudin15 promoter in hepatocellular carcinoma cells. Claudin family members are related with TNBC. However, the relationship between Claudin15 and VM formation is not clear. In this study, we first found that Claudin15 expression was frequently down‐regulated in human TNBC, and Claudin15 down‐regulation was significantly associated with VM and Twist1 nuclear expression. Claudin15 down‐regulation correlated with shorter survival compared with high levels. Claudin15 silence significantly enhanced cell motility, invasiveness and VM formation in the non‐TNBC MCF‐7 cells. Conversely, an up‐regulation of Claudin15 remarkably reduced TNBC MDA‐MB‐231 cell migration, invasion and VM formation. We also showed that down‐regulation of Claudin15 was Twist1‐dependent, and Twist1 repressed Claudin15 promoter activity. Furthermore, GeneChip analyses of mammary glands of Claudin15‐deficient mice indicated that Claudin18 and Jun might be downstream factors of Twist1‐Claudin15. Our results suggest that Twist1 induced VM through Claudin15 suppression in TNBC, and Twist1 inhibition of Claudin15 might involve Claudin18 and Jun expression.

Background The National Institute on Aging and Alzheimer's Association proposed an ATN classification system which divided Alzheimer's disease biomarkers into three binary classes: amyloid deposition (A), tauopathy (T), and neurodegeneration or neuronal injury (N). Objective To estimate the prevalence of each profile and to describe the demographic characteristics of each group in Chinese cognitively intact older adults. Methods In this cross-sectional study, 561 cognitively intact participants from the Chinese Alzheimer's Biomarker and LifestylE (CABLE) study were classified into eight groups using cerebrospinal fluid amyloid-β 42/40 as A, phosphorylated tau as T, and total tau as N. Multinomial models were used to determine the estimated prevalence of the eight groups. Results The number and proportion of 561 participants in each ATN profile were 254 A-T-N- (45.3%), 28 A-T+N- (5.0%), 21 A-T-N+ (3.7%), 71 A-T+N+ (12.7%), 78 A + T-N- (13.9%), 14 A + T+N- (2.5%), 21 A + T-N+ (3.7%), and 74 A + T+N+ (13.2%). Individuals in N+ groups tend to be older than N- groups. A+ groups included more female individuals. The prevalence of A-T-N- profile declined with age, while that of A + T+N+ increased continuously. Conclusion This is the first work to estimate the prevalence of each ATN profile and describe the demographic characteristics of ATN profiles based on a Chinese cohort. The clinical implications of our findings need to be scrutinized further in longitudinal studies of the ATN classification system.

BACKGROUND The role of cerebral microbleeds (CMBs) in cognitive impairment remains controversial. OBJECTIVE To investigate the possible links between the presence, progression, number, and location of CMBs and cognition. METHODS We assessed 792 subjects from the Alzheimer's Disease Neuroimaging Initiative who underwent both brain 3 Tesla MRI scans and cognitive testing. The association between CMBs and cognitive change was explored using linear mixed-effects models (LME). RESULTS Presence and number of CMBs were associated with memory (β= -0.03, p = 0.015; β= -0.01, p = 0.003), executive function (β= -0.04, p = 0.010; β= -0.01, p = 0.014), and global cognitive function (β= -0.06, p = 0.025; β= -0.03, p

Neurodegenerative diseases have become a major global health concern, posing a huge disease burden on patients and their families. Although there has been rapid progress in the development of therapies, a lack of accurate disease models and efficient drug screening platforms have made achieving a breakthrough difficult. The technology of human-induced pluripotent stem cells (iPSCs) shows better recapitulation of disease pathophysiology and provides a more accessible supply of patient-specific samples compared to other modeling methods. It has been a powerful tool for mechanism exploration and drug development.This review describes the recent use of human iPSC-derived cells for modeling neurodegenerative disorders and discovering potential drugs.Model systems based on iPSC-derived cells have created a paradigm shift in drug discovery. Accuracy, consistency, translatability, and cost-effectiveness are the four major focuses of academic and industrial communities to fulfill the potential of iPSC technology for their purposes. It is the art of balance between these four factors to generate efficacious outputs with maximum efficiency. Future studies should persist in refining this technology and promote its application in this field to benefit all the disease-affected population eventually.

Accumulating data suggest cerebrospinal fluid (CSF) neurogranin (Ng) as a potential biomarker for cognitive decline and neurodegeneration in Alzheimer disease (AD). To investigate whether the CSF Ng can be used for diagnosis, prognosis, and monitoring of AD, we examined 111 cognitively normal (CN) controls, 193 mild cognitive impairment (MCI) patients and 95 AD patients in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort. Correlations were tested between baseline CSF Ng levels and baseline core AD biomarkers and longitudinal glucose metabolism, brain atrophy and cognitive decline. We detected that CSF Ng levels increased with disease severity, and correlated with phosphorylated tau and total tau levels within each diagnostic group. High baseline CSF Ng levels correlated with longitudinal reductions in cortical glucose metabolism within each diagnostic group and hippocampal volume within MCI group during follow-up. In addition, high baseline CSF Ng levels correlated with cognitive decline as reflected by decreased cognitive scale scores. The CSF Ng levels predicted future cognitive impairment (adjusted hazard ratio:3.66, 95%CI: 1.74-7.70, P = 0.001) in CN controls. These data demonstrate that CSF Ng offers diagnostic utility for AD and predicts future cognitive impairment in CN individuals and, therefore, may be a useful addition to the current AD biomarkers.

Background We investigated the clinical value of accurate sublobectomy of pulmonary nodules using video‐assisted thoracoscopy (VATS). In June 2017 to June 2019, single lung nodule patients who accepted thoracoscopic resection were included. Palpation and intraoperative ultrasound (IU) were used to localize lung nodules, and the success rate, location time and safety compared. Performance of lung nodule ultrasound was assessed. The success rate of IU localization of pulmonary nodules with different properties was studied. Results A total of 33 cases with single pulmonary nodules were included in the study, and 32 cases (97%) were successfully located by IU as opposed to 16 cases (48.5%) located by palpation (P

Postoperative cognitive dysfunction (POCD) is a common sequela following surgery and hospitalization. The prevention and management of POCD are important during clinical practice. POCD more commonly affects elderly patients who have undergone major surgery and can result in major decline in quality of life for both patients and their families. Acupuncture has been suggested as an effective intervention for many neurological disorders. In recent years, there are increasing interest in the use of acupuncture to prevent and treat POCD. In this review, we summarized the clinical and preclinical evidence of acupuncture on POCD using a narrative approach and discussed the potential mechanisms involved. The experimental details and findings of studies were summarized in tables and analyzed. Most of the clinical studies suggested that acupuncture before surgery could reduce the incidence of POCD and reduce the levels of systematic inflammatory markers. However, their reliability is limited by methodological flaws. Animal studies showed that acupuncture reduced cognitive impairment and the associated pathology after various types of surgery. It is possible that acupuncture modulates inflammation, oxidative stress, synaptic changes, and other cellular events to mitigate POCD. In conclusion, acupuncture is a potential intervention for POCD. More clinical studies with good research design are required to confirm its effectiveness. At the same time, findings from animal studies will help reveal the protective mechanisms, in which systematic inflammation is likely to play a major role.

Background The lack of interaction and communication in pharmacology courses, especially since the onset of the coronavirus disease 2019 (COVID-19) pandemic, which required a fast shift to remote learning at medical schools, leads to an unsatisfactory learning outcome. New interactive teaching approaches are required to improve pharmacology learning attention and interaction in remote education and traditional classrooms. Methods We introduced bullet screens to pharmacology teaching. Then, a survey was distributed to first-, second- and third-year pre-clinical undergraduate medical and nursing students at the Shanghai Jiao Tong University School of Medicine from November 2020 to March 2022. We evaluated the essential features, instructional effectiveness, and entertainment value of bullet screens. Responses to structured and open-ended questions about the strengths and weaknesses of the bullet screen and overall thoughts were coded and compared between medical and nursing students. Results In terms of essential features, bullet screens have a high degree of acceptability among students, and this novel instructional style conveniently increased classroom interaction. Considering instructional effectiveness, bullet screen may stimulate students’ in-depth thinking. Meanwhile, students tended to use bullet-screen comments as a way to express their support rather than to make additional comments or to express their different viewpoints. The entertainment value of bullet screen was noteworthy. The lack of ideas might lead to relative differences between medical and nursing students, indicating that guiding the appropriate use of bullet screen is necessary. Conclusions The bullet screen may be popularized as an auxiliary teaching approach to promote interaction between teachers and students in the classroom as well as during remote education. It is an interesting and beneficial tool in pharmacology courses, yet there are several aspects of this device that should be improved for popularization.

Backgrounds: Respiratory gating is one of the motion management techniques that is used to deliver radiation dose to a tumor at a specific position under free breathing. However, due to the dynamic feedback process of this approach, regular equipment quality assurance (QA) and patient-specific QA checks need to be performed. This work proposes a new QA methodology using electronic portal imaging detector (EPID) to determine the target localization accuracy of phase gating. Methods: QA tools comprising 3D printed spherical tumor phantoms, programmable stages, and an EPID detector are characterized and assembled. Algorithms for predicting portal dose (PD) through moving phantoms are developed and verified using gamma analysis for two spherical tumor phantoms (2 cm and 4 cm), two different 6 MV volumetric modulated arc therapy plans, and two different gating windows (30%–70% and 40%–60%). Comparison between the two gating windows is then performed using the Wilcoxon signed-rank test. An optimizer routine, which is used to determine the optimal window, based on maximal gamma passing rate (GPR), was applied to an actual breathing curve and breathing plan. This was done to ascertain if our method yielded a similar result with the actual gating window. Results: High GPRs of more than 97% and 91% were observed when comparing the predicted PD with the measured PD in moving phantom at 2 mm/2% and1 mm/1% levels, respectively. Analysis of gamma heatmaps shows an excellent agreement with the tumor phantom. The GPR of 40%–60% PD was significantly lower than that of the 30%–70%PD at the 1 mm/1% level (p=0.0064). At the 2 mm/2% level, no significant differences were observed. The optimizer routine could accurately predict the center of the gating window to within a 10% range. Conclusion: We have successfully performed and verified a new method for QA with the use of a moving phantom with EPID for phase gating with real-time position management. Published version This work was supported by SingHealth Duke-NUS Academic Medicine and National Health Innovation Centre Singapore Joint MedTech grant (AM-NHIC/JMT006/2020) and Duke-NUS Oncology Aca-demic Clinical Programme Proton Research Fund(08/FY2021/EX(SL)/92-A146, 08/FY2020/EX(SL)/76-A152) grants.

Background During open-door laminoplasty, the position of the bone gutter is not fixed, and when the gutter migrates inward, the outer end of the titanium plate must be fixed on the lamina edge. It is unclear whether this will affect the clinical efficacy. This study aimed to observe the influence of the titanium plate fixation position on the effectiveness of open-door laminoplasty for cervical spondylotic myelopathy (CSM). Methods A total of 98 patients with CSM who underwent open-door laminoplasty from August 2016 to October 2019 were included in this retrospective study. Fifty-five patients had the titanium plate fixed on the lateral mass (lateral mass group), and 43 patients had the titanium plate fixed on the lamina edge (lamina group). The opening angle, opening width, occurrence of hinge fracture, spinal cord drift distance, cervical curvature index (CCI), neurological function recovery (JOA score), neck function (NDI), C5 palsy and severity of axial symptoms were observed and compared between the two groups. Results The opening angle in the lamina group was significantly larger than that in the lateral mass group, while the opening width and the spinal cord drift distance were significantly smaller than those in the lateral mass group (P P P > 0.05), and there was no significant difference between the groups (P > 0.05). After surgery, the JOA score significantly increased in both groups (P P P P P Conclusions In open-door laminoplasty, it is feasible to fix the titanium plate on the lateral mass or to the lamina due to the same neurological function recovery. However, fixing it to the lamina will increase the opening angle and decrease the opening width, making the hinge prone to fracture and increasing the severity of postoperative axial symptoms.

Azvudine (FNC) is a nucleoside analog that inhibits HIV-1 RNA-dependent RNA polymerase (RdRp). Recently, we discovered FNC an agent against SARS-CoV-2, and have taken it into Phase III trial for COVID-19 patients. FNC monophosphate analog inhibited SARS-CoV-2 and HCoV-OC43 coronavirus with an EC50 between 1.2 and 4.3 μM, depending on viruses or cells, and selective index (SI) in 15–83 range. Oral administration of FNC in rats revealed a substantial thymus-homing feature, with FNC triphosphate (the active form) concentrated in the thymus and peripheral blood mononuclear cells (PBMC). Treating SARS-CoV-2 infected rhesus macaques with FNC (0.07 mg/kg, qd, orally) reduced viral load, recuperated the thymus, improved lymphocyte profiles, alleviated inflammation and organ damage, and lessened ground-glass opacities in chest X-ray. Single-cell sequencing suggested the promotion of thymus function by FNC. A randomized, single-arm clinical trial of FNC on compassionate use (n = 31) showed that oral FNC (5 mg, qd) cured all COVID-19 patients, with 100% viral ribonucleic acid negative conversion in 3.29 ± 2.22 days (range: 1–9 days) and 100% hospital discharge rate in 9.00 ± 4.93 days (range: 2–25 days). The side-effect of FNC is minor and transient dizziness and nausea in 16.12% (5/31) patients. Thus, FNC might cure COVID-19 through its anti-SARS-CoV-2 activity concentrated in the thymus, followed by promoted immunity.

At the local and regional climate scale, one of the most studied environmental issues is urban heat island (UHI). UHI is a thermal anomaly caused by temperature differences between urban and rural settings, which adds heat to the atmosphere and makes people feel uncomfortable. This study explores the influence of new land-cover data on UHI simulations using the high-resolution Weather Research and Forecasting (WRF) model coupled with the single-layer urban canopy model (SLUCM) in the city of Harbin. A comparison was performed between the new Tsinghua University (TU) land cover dataset with the default United States Geological Survey (USGS) and Moderate Resolution Imaging Spectroradiometer (MODIS) land cover datasets. The results of this study revealed that the new TU land cover data had better representation and more realistic land cover changes than the default datasets. The diurnal, seasonal, and long-term nighttime UHIs of air and surface temperatures were higher than the daytime UHIs for both downtown Harbin and the satellite towns. We discovered that coal-burning during winter had a significant influence on UHI in Harbin. Moreover, the results from our buffer revealed a rapid increase in the UHIs of satellite towns, thus revealing the need to focus on the effects of UHI in satellite towns in the future. Therefore, the timely updating of land cover datasets in the WRF model and implementing mitigation strategies will help improve the urban climatic comfort.

Recently, increasing attention has been paid to the role of Squalene epoxidase (SQLE) in several types of cancers. However, its functional role in tumor progression of head and neck squamous cell carcinoma (HNSCC) is still unclear. We performed bioinformatic analyses and relative experiments to assess the potential mechanism of SQLE-mediated HNSCC malignancy. And the results showed that SQLE was significantly upregulated in tumor samples compared with peritumor samples. Mechanistically, miR-584-5p downregulation may lead to the upregulation of SQLE in HNSCC. Moreover, high SQLE expression in HNSCC was associated with TNM stage, distant metastasis, and poor survival, indicating that SQLE be involved in the progression of HNSCC. Furtherly, SQLE boosted proliferation, migration, invasion of HNSCC cells

LINC00184 has been suggested to be associated with cancer prognosis and has been implicated in cancer glycolysis; however, its role in oesophageal squamous cell carcinoma (ESCC) remains poorly understood. Herein, to understand the expression and the biological roles of LINC00184 in ESCC, in situ hybridization (ISH) and quantitative PCR (qPCR) were performed to detect the expression of LINC00184 in tissue blocks and in fresh tissues, respectively. Furthermore, with an in vitro cell culture system, LINC00184 was stably knocked down in ESCC cell lines KYSE-150 and Eca109, followed by determining alterations in their proliferation and motility relative to control. To gain insight into the regulation of LINC00184, STAT3 was bioinformatically identified as a transcription factor of LINC00184, which was further corroborated by chromatin-immunoprecipitation (CHIP) assay. The dephosphorylation of STAT3 with NSC74859 was shown to be unable to suppress the expression of LINC00184 in vivo in a xenograft mouse model. Moreover, STAT3, once phosphorylated at serine 727, tended to translocate into the mitochondria to promote LINC00184 expression in ESCC cells. Together, these data strongly support the oncogenic role of LINC00184 in ESCC.

A 9-year-old girl with remarkable hyponatremia was diagnosed with SIADH that was likely secondary to varicella. Under appropriate treatment, her serum sodium returned to the normal level. There was no evidence of hyponatremia at a 3-month follow-up. We propose that medical professionals need to consider the existence of that SIADH when treating patients with varicella who present with severe hyponatremia.

Progressive loss of neurons in a specific brain area is one of the manifestations of Alzheimer’s disease (AD). Much effort has been devoted to investigating brain atrophy and AD. However, the causal relationship between cortical structure and AD is not clear. We conducted a bidirectional two-sample Mendelian randomization analysis to investigate the causal relationship between cortical structure (surface area and thickness of the whole cortex and 34 cortical regions) and AD risk. Genetic variants used as instruments came from a large genome-wide association meta-analysis of cortical structure (33,992 participants of European ancestry) and AD (AD and AD-by-proxy, 71,880 cases, 383,378 controls). We found suggestive associations of the decreased surface area of the temporal pole (OR (95% CI): 0.95 (0.9, 0.997), p = 0.04), and decreased thickness of cuneus (OR (95% CI): 0.93 (0.89, 0.98), p = 0.006) with higher AD risk. We also found a suggestive association of vulnerability to AD with the decreased surface area of precentral (β (SE): –43.4 (21.3), p = 0.042) and isthmus cingulate (β (SE): –18.5 (7.3), p = 0.011). However, none of the Bonferroni-corrected p values of the causal relationship between cortical structure and AD met the threshold. We show suggestive evidence of an association of the atrophy of the temporal pole and cuneus with higher AD risk. In the other direction, there was a suggestive causal relationship between vulnerability to AD and the decreased surface area of the precentral and isthmus cingulate. Our findings shed light on the associations of cortical structure with the occurrence of AD.

Background:Neoadjuvant chemotherapy (NAC) plays an important role in the management of locally advanced breast cancer. It allows for downstaging of tumours, potentially allowing for breast conservation. NAC also allows for in-vivo testing of the tumours’ response to chemotherapy and provides important prognostic information. There are currently no clearly defined clinical models that incorporate imaging with clinical data to predict response to NAC. Thus, the aim of this work is to develop a predictive AI model based on routine CT imaging and clinical parameters to predict response to NAC. Methods:The CT scans of 324 patients with NAC from multiple centers in Singapore were used in this study. Four different radiomics models were built for predicting pathological complete response (pCR): first two were based on textural features extracted from peri-tumoral and tumoral regions, the third model based on novel space-resolved radiomics which extract feature maps using voxel-based radiomics and the fourth model based on Deep Learning (DL). Clinical parameters were included to build a final prognostic model. Results:The best performing models were based on space-resolved and deep learning approaches. Space-resolved radiomics improves the clinical AUCs of pCR prediction from 0.743 (0.650 to 0.831) to 0.775 (0.685 to 0.860) and our DL model improved it from 0.743 (0.650 to 0.831) to 0.772 (0.685 to 0.853). The tumoral radiomics model performs the worst with no improvement of the AUC from the clinical model. The peri-tumoral combined model gives moderate performance with an AUC of 0.765 (0.671 to 0.855). Conclusions:Radiomics features extracted from diagnostic CT augments the predictive ability of pathological complete response when combined with clinical features. The novel space-resolved radiomics and deep learning radiomics approaches outperformed conventional radiomics techniques.

High-performance liquid chromatography-size exclusion chromatography and excitation-emission matrix (EEM) fluorescence spectroscopy were used to analyze the seasonal variations and potential sources of molecular weight (MW) separated light-absorbing chromophores and fluorophores of water-soluble organic compounds (WSOC) and methanol-soluble organic compounds (MSOC) in PM